Responses of Rat Mesenchymal Stromal Cells to Nanocellulose with Different Functional GroupsClick to copy article linkArticle link copied!
- Ahmad Rashad*Ahmad Rashad*Email: [email protected]. Tel: +47 55586575.Center of Translational Oral Research (TOR), Department of Clinical Dentistry, University of Bergen, Bergen 5009, NorwayMore by Ahmad Rashad
- Martha GrøndahlMartha GrøndahlDepartment of Biotechnology and Food Science, Norwegian University of Science and Technology, Trondheim 7491, NorwayMore by Martha Grøndahl
- Ellinor Bævre Heggset
- Kamal MustafaKamal MustafaCenter of Translational Oral Research (TOR), Department of Clinical Dentistry, University of Bergen, Bergen 5009, NorwayMore by Kamal Mustafa
- Kristin SyverudKristin SyverudRISE PFI, Trondheim 7491, NorwayDepartment of Chemical Engineering, Norwegian University of Science and Technology (NTNU), Trondheim 7491, NorwayMore by Kristin Syverud
Abstract
Cellulose nanofibrils (CNFs) are multiscale hydrophilic biocompatible polysaccharide materials derived from wood and plants. TEMPO-mediated oxidation of CNFs (TO-CNF) turns some of the primary hydroxyl groups to carboxylate and aldehyde groups. Unlike carboxylic functional groups, there is little or no information about the biological role of the aldehyde groups on the surface of wood-based CNFs. In this work, we replaced the aldehyde groups in the TO-CNF samples with carboxyl groups by another oxidation treatment (TO-O-CNF) or with primary alcohols with terminal hydroxyl groups by a reduction reaction (TO-R-CNF). Rat mesenchymal stem/stromal cells (MSCs) derived from bone marrow were seeded on polystyrene tissue culture plates (TCP) coated with CNFs with and without aldehyde groups. TCP and TCP coated with bacterial nanocellulose (BNC) were used as control groups. Protein adsorption measurements demonstrated that more proteins were adsorbed from cell culture media on all CNF surfaces compared to BNC. Live/dead and lactate dehydrogenase assays confirmed that all nanocellulose biomaterials supported excellent cell viability. Interestingly, TO-R-CNF samples, which have no aldehyde groups, showed better cell spreading than BNC and comparable results to TCP. Unlike TO-O-CNF surfaces, which have no aldehyde groups either, TO-R-CNF stimulated cells, in osteogenic medium, to have higher alkaline phosphatase activity and to form more biomineralization than TCP and TO-CNF groups. These findings indicate that the presence of aldehyde groups (280 ± 14 μmol/g) on the surface of TEMPO-oxidized CNFs might have little or no effect on attachment, proliferation, and osteogenic differentiation of MSCs.
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You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
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Introduction
Experimental Section
Preparation of CNFs with Different Functional Groups
Carboxylate and Aldehyde Contents
Viscosity and Structural Characterization
ζ-Potential, Contact Angle, and Protein Adsorption
Cell Culture
Cytotoxicity and Morphological Assessments
Cell Proliferation and Differentiation
Statistical Analysis
Results and Discussion
Structure, Chemistry, and Viscosity of CNFs
Figure 1
Figure 1. Preparation and characterization of nanocellulose hydrogels. (A) Macroscopic images of different CNF materials and BNC. (B) Aldehyde content of nanocellulose materials in reference to glucose concentrations (0 to 0.04% in water). (C) Change in viscosity of CNF suspensions as a function of shear rate (spindle speed).
nanocellulose | aldehyde (μmol/g) | carboxyl (μmol/g) | roughness (Ra) nm | contact angle | ζ-potential in medium (mV) |
---|---|---|---|---|---|
TO-CNF | 280 ± 14 | 804 ± 3 | 46.1 | 48.6 ± 7.1 | –10.0 ± 0.6 |
TO-O-CNF | 992 ± 24 | 180.0 | 63.0 ± 6.6 | –10.7 ± 0.5 | |
TO-R-CNF | 675 ± 14 | 43.0 | 63.8 ± 7.5 | –9.7 ± 0.7 | |
BNC | 31.3 | 27.6 ± 7.9 | –10.7 ± 0.6 |
Morphological Assessment of CNFs
Figure 2
Figure 2. Morphological assessment and fiber analysis. (A) macroscopic (top) and microscopic images of nanocellulose before (middle) and after (bottom) staining with crystal violet. (B–E) Fiber analysis of CNF samples (n = 3). All values are expressed as mean ± SD (## p ≤ 0.001).
Figure 3
Figure 3. AFM images showing different nanoscale morphologies of CNFs and BNC materials.
Wettability, Surface Charges, and Protein Adsorption
Figure 4
Figure 4. Water contact angle and ζ-potential measurements of different nanocellulose materials. (A) Water contact angle on 2D coated samples (n = 12). (B) ζ-Potential in growth medium with 10% FBS (n = 15). All values are expressed as mean ± SD. * Significant difference between BNC and any CNF groups (*, p ≤ 0.05; ***, p ≤ 0.001). # Significant difference between CNF groups (#, p ≤ 0.05; ##, p ≤ 0.01).
Protein Adsorption
Figure 5
Figure 5. Protein adsorption onto different nanocellulose surfaces in (A) BSA solution, (B) FBS solution, (C) and 10% FBS solution. All values are expressed as mean ± SD (n = 5). * Significant difference between BNC and any CNF group (***, p ≤ 0.001). # Significant difference between CNF groups (#, p ≤ 0.05; ###, p ≤ 0.001).
Indirect and Direct Cytotoxicity
Figure 6
Figure 6. Indirect cytotoxicity assessment of rat MSCs treated with extracts of nanocelluloses. (A–E) Fluorescence images of live/dead stain. Calcein AM (green) represents live cells, and ethidium homodimer (red) represents dead cells. (F) Mitochondrial activity by the Alamar Blue assay. All values are expressed as mean ± SD (n = 4).
Figure 7
Figure 7. Direct cytotoxicity assessment of rat MSCs cultured on TCP, CNF, and BNC surfaces. (A–E) Fluorescence images of live/dead stain. (F) LDH assay. All values are expressed as mean ± SD (n = 4).
Cell Adhesion and Morphology
Figure 8
Figure 8. Cytoskeleton analysis of rat MSCs cultured on TCP, CNF, and BNC surfaces. Fluorescence microscopy images of the F-actin (green) and nuclei (blue). All values are expressed as mean ± SD (n = 20 cells). * Significant difference between TCP and other groups (**, p ≤ 0.01; ***, p ≤ 0.001). # Significant difference between CNF and BNC groups (##, p ≤ 0.01; ###, p ≤ 0.001). & Significant difference between CNF groups (&&, p ≤ 0.01).
Cell Proliferation and Differentiation
Figure 9
Figure 9. Cell proliferation and ALP activity of BMSCs cultured on TCP, CNFs, and BNC in (A, B) growth and (C, D) osteogenic media. All values are expressed as mean ± SD (n = 5). * Significant difference between TCP and other groups (*, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001). # Significant difference between CNF and BNC groups (##, p ≤ 0.01; ###, p ≤ 0.001). & Significant difference between CNF groups (&&, p ≤ 0.01).
Figure 10
Figure 10. Mineralization assay by Alizarin red S at day 21. All values are expressed as mean ± SD (n = 5). * Significant difference between TCP and other groups (**, p ≤ 0.01). # Significant difference between CNF and BNC groups (##, p ≤ 0.01).
Conclusions
Acknowledgments
This work has been funded by the Research Council of Norway through the projects of NORCEL Project (Grant No. 228147) and 3DPRENT (Grant No. 302043) and by Trond Mohn Foundation (BFS2018TMT10). The authors would like to thank Dr. Shuntaro Yamada for cell isolation and characterization.
References
This article references 56 other publications.
- 1Patil, T. V.; Patel, D. K.; Dutta, S. D.; Ganguly, K.; Santra, T. S.; Lim, K. T. Nanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applications. Bioact. Mater. 2022, 9, 566– 589, DOI: 10.1016/j.bioactmat.2021.07.006Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlGhsbfE&md5=7d9fd3032a9676053303368c2162d5deNanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applicationsPatil, Tejal V.; Patel, Dinesh K.; Dutta, Sayan Deb; Ganguly, Keya; Santra, Tuhin Subhra; Lim, Ki-TaekBioactive Materials (2022), 9 (), 566-589CODEN: BMIAD4; ISSN:2452-199X. (Elsevier B.V.)A review. Nanocellulose, a biopolymer, has received wide attention from researchers owing to its superior physicochem. properties, such as high mech. strength, low d., biodegradability, and biocompatibility. Nanocellulose can be extd. from wide range of sources, including plants, bacteria, and algae. Depending on the extn. process and dimensions (diam. and length), they are categorized into three main types: cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). CNCs are a highly cryst. and needle-like structure, whereas CNFs have both amorphous and cryst. regions in their network. BNC is the purest form of nanocellulose. The nanocellulose properties can be tuned by chem. functionalization, which increases its applicability in biomedical applications. This review highlights the fabrication of different surface-modified nanocellulose to deliver active mols., such as drugs, proteins, and plasmids. Nanocellulose-mediated delivery of active mols. is profoundly affected by its topog. structure and the interaction between the loaded mols. and nanocellulose. The applications of nanocellulose and its composites in tissue engineering have been discussed. Finally, the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active mols.
- 2Luo, H.; Cha, R.; Li, J.; Hao, W.; Zhang, Y.; Zhou, F. Advances in tissue engineering of nanocellulose-based scaffolds: A review. Carbohydr. Polym. 2019, 224, 115144 DOI: 10.1016/j.carbpol.2019.115144Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFChsrjE&md5=ee968a0fc0776be4e69f5f558fc01d49Advances in tissue engineering of nanocellulose-based scaffolds: A reviewLuo, Huize; Cha, Ruitao; Li, Juanjuan; Hao, Wenshuai; Zhang, Yan; Zhou, FengshanCarbohydrate Polymers (2019), 224 (), 115144CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)A review, with refs. Scaffolds based on nanocellulose (NC) have crucial applications in tissue engineering (TE) owing to the biocompatibility, water absorption, water retention, optical transparency, and chemo-mech. properties. In this review, we summarize the scaffolds based on nanocellulose, including nanocryst. cellulose and nanofibrillated cellulose. We compare four representative methods to prep. NC-based scaffolds, contg. electrospinning, freeze-drying, 3D printing, and solvent casting. We outline the characteristics of scaffolds obtained by different methods. Our focus is on the applications of NC-based scaffolds to repair, improve or replace damaged tissues and organs, including skin, blood vessel, nerve, skeletal muscle, heart, liver, and ophthalmol. NC-based scaffolds are attractive materials for regeneration of different tissues and organs due to the remarkable features. Finally, we propose the challenges and potentials of NC-based TE scaffolds.
- 3Du, H.; Liu, W.; Zhang, M.; Si, C.; Zhang, X.; Li, B. Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applications. Carbohydr. Polym. 2019, 209, 130– 144, DOI: 10.1016/j.carbpol.2019.01.020Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFSit7g%253D&md5=beff516f2d4c0225823d8539b74d0947Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applicationsDu, Haishun; Liu, Wei; Zhang, Miaomiao; Si, Chuanling; Zhang, Xinyu; Li, BinCarbohydrate Polymers (2019), 209 (), 130-144CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The prodn. of cellulose nanomaterials from lignocellulosic biomass opens an opportunity for the development and application of new materials in nanotechnol. Over the last decade, cellulose nanomaterials based hydrogels have emerged as promising materials in the field of biomedical applications due to their low toxicity, biocompatibility, biodegradability, as well as excellent mech. stability. In this review, recent progress on the prepn. of cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs) based hydrogels and their biomedical applications is summarized and discussed based on the analyses of the latest studies (esp. for the reports in the past five years). We begin with a brief introduction of the differences in prepn. methods and properties of two main types of cellulose nanomaterials: CNCs and CNFs isolated from lignocellulosic biomass. Then, various processes for the fabrication of CNCs based hydrogels and CNFs based hydrogels were elaborated, resp., with the focus on some new methods (e.g. 3D printing). Furthermore, a no. of biomedical applications of CNCs and CNFs based hydrogels, including drug delivery, wound dressings and tissue engineering scaffolds were highlighted. Finally, the prospects and ongoing challenges of CNCs and CNFs based hydrogels for biomedical applications were summarized. This work demonstrated that the CNCs and CNFs based hydrogels have great promise in a wide range of biomedical applications in the future.
- 4Ferreira, F. V.; Otoni, C. G.; De France, K. J.; Barud, H. S.; Lona, L. M. F.; Cranston, E. D.; Rojas, O. J. Porous nanocellulose gels and foams: Breakthrough status in the development of scaffolds for tissue engineering. Mater. Today 2020, 37, 126– 141, DOI: 10.1016/j.mattod.2020.03.003Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXltlCgurs%253D&md5=2263926615ac0a2c95a727485a349c9bPorous nanocellulose gels and foams: Breakthrough status in the development of scaffolds for tissue engineeringFerreira, Filipe V.; Otoni, Caio G.; De France, Kevin J.; Barud, Hernane S.; Lona, Liliane M. F.; Cranston, Emily D.; Rojas, Orlando J.Materials Today (Oxford, United Kingdom) (2020), 37 (), 126-141CODEN: MTOUAN; ISSN:1369-7021. (Elsevier Ltd.)A review. We report on the latest scientific advances related to the use of porous foams and gels prepd. with cellulose nanofibrils (CNF) and nanocrystals (CNC) as well as bacterial nanocellulose (BNC) collectively nanocelluloses as biomedical materials for application in tissue regeneration. Interest in such applications stems from the lightwt. and strong structures that can be efficiently produced from these nanocelluloses. Dried nanocellulose foams and gels, including xerogels, cryogels, and aerogels have been synthesized effortlessly using green, scalable, and cost-effective techniques. Methods to control structural features (e.g., porosity, morphol., and mech. performance) and biol. interactions (e.g., biocompatibility and biodegradability) are discussed in light of specific tissues of interest. The state-of-the-art in the field of nanocellulose-based scaffolds for tissue engineering is presented, covering physicochem. and biol. properties relevant to these porous systems that promise groundbreaking advances. Specifically, these materials show excellent performance for in vitro cell culturing and in vivo implantation. We report on recent efforts related to BNC scaffolds used in animal and human implants, which furthermore support the viability of CNF and CNC based scaffolds in next-generation biomedical materials.
- 5Chen, C.; Ding, W.; Zhang, H.; Zhang, L.; Huang, Y.; Fan, M.; Yang, J.; Sun, D. Bacterial cellulose-based biomaterials: From fabrication to application. Carbohydr. Polym. 2022, 278, 118995 DOI: 10.1016/j.carbpol.2021.118995Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXivVSnt7bK&md5=b1a9d3571cb35bc0779bbc64fb9e3c8fBacterial cellulose-based biomaterials: From fabrication to applicationChen, Chuntao; Ding, Weixiao; Zhang, Heng; Zhang, Lei; Huang, Yang; Fan, Mengmeng; Yang, Jiazhi; Sun, DongpingCarbohydrate Polymers (2022), 278 (), 118995CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)A review. Driven by its excellent phys. and chem. properties, BC (bacterial cellulose) has achieved significant progress in the last decade, rendering with many novel applications. Due to its resemblance to the structure of extracellular matrix, BC-based biomaterials have been widely explored for biomedical applications such as tissue engineering and drug delivery. The recent advances in nanotechnol. endow further modifications on BC and generate BC-based composites for different applications. This article presents a review on the research advancement on BC-based biomaterials from fabrication methods to biomedical applications, including wound dressing, artificial skin, vascular tissue engineering, bone tissue regeneration, drug delivery, and other applications. The prepn. of these materials and their potential applications are reviewed and summarized. Important factors for the applications of BC in biomedical applications including degrdn. and pore structure characteristic are discussed in detail. Finally, the challenges in future development and potential advances of these materials are also discussed.
- 6Sharma, C.; Bhardwaj, N. K. Bacterial nanocellulose: Present status, biomedical applications and future perspectives. Mater. Sci. Eng. C 2019, 104, 109963 DOI: 10.1016/j.msec.2019.109963Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVSqu73N&md5=92ca03a674a50307fc27f1625887d399Bacterial nanocellulose: Present status, biomedical applications and future perspectivesSharma, Chhavi; Bhardwaj, Nishi K.Materials Science & Engineering, C: Materials for Biological Applications (2019), 104 (), 109963CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A review. Bacterial nanocellulose (BNC) has emerged as a natural biopolymer of significant importance in diverse technol. areas due to its incredible physicochem. and biol. characteristics. However, the high capital investments, prodn. cost and lack of well-organized scale-up processes resulting in low BNC prodn. are the major impediments need to be resolved. This review enfolds the three different and important portions of BNC. Firstly, advancement in prodn. technologies of BNC like cell-free ext. technol., static intermittent fed batch technol. and novel cost-effective substrates that might surmount the barriers assocd. with BNC prodn. at industrial level. Secondly, as BNC and its composites (with other polymers/nanoparticles) represents the utmost material of preference in current regenerative and diagnostic medicine, therefore recently reported biomedical applications of BNC and functionalized BNC in drug delivery, tissue engineering, antimicrobial wound healing and biosensing are widely been focused here. The third and the most important aspect of this review is an in-depth discussion of various pitfalls assocd. with BNC prodn. Recent trends in BNC research to overcome the existing snags that might pave a way for industrial scale prodn. of BNC thereby facilitating its feasible application in various fields are highlighted.
- 7Vielreicher, M.; Kralisch, D.; Volkl, S.; Sternal, F.; Arkudas, A.; Friedrich, O. Bacterial nanocellulose stimulates mesenchymal stem cell expansion and formation of stable collagen-I networks as a novel biomaterial in tissue engineering. Sci. Rep. 2018, 8, 9401 DOI: 10.1038/s41598-018-27760-zGoogle Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mbps1Kisw%253D%253D&md5=84ad96177c751228796f02ad34b14365Bacterial nanocellulose stimulates mesenchymal stem cell expansion and formation of stable collagen-I networks as a novel biomaterial in tissue engineeringVielreicher Martin; Sternal Fabian; Friedrich Oliver; Kralisch Dana; Volkl Simon; Arkudas AndreasScientific reports (2018), 8 (1), 9401 ISSN:.Biomimetic scaffolds are of great interest to tissue engineering (TE) and tissue repair as they support important cell functions. Scaffold coating with soluble collagen-I has been used to achieve better tissue integration in orthopaedy, however, as collagen persistence was only temporary such efforts were limited. Adequate coverage with cell-derived ECM collagen-I would promise great success, in particular for TE of mechanically challenged tissues. Here, we have used label-free, non-invasive multiphoton microscopy (MPM) to characterise bacterial nanocellulose (BNC) - a promising biomaterial for bone TE - and their potency to stimulate collagen-I formation by mesenchymal stem cells (MSCs). BNC fleeces were investigated by Second Harmonic Generation (SHG) imaging and by their characteristic autofluorescence (AF) pattern, here described for the first time. Seeded MSCs adhered fast, tight and very stable, grew to multilayers and formed characteristic, wide-spread and long-lasting collagen-I. MSCs used micron-sized lacunae and cracks on the BNC surface as cell niches. Detailed analysis using a collagen-I specific binding protein revealed a highly ordered collagen network structure at the cell-material interface. In addition, we have evidence that BNC is able to stimulate MSCs towards osteogenic differentiation. These findings offer new options for the development of engineered tissue constructs based on BNC.
- 8Zhang, W.; Wang, X. C.; Li, X. Y.; Zhang, L. L.; Jiang, F. A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineering. Carbohydr. Polym. 2020, 236, 116043 DOI: 10.1016/j.carbpol.2020.116043Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvFGru7s%253D&md5=74b7391f28a6d93d42a99e18c941a920A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineeringZhang, Wen; Wang, Xue-chuan; Li, Xi-yue; Zhang, Le-le; Jiang, FeiCarbohydrate Polymers (2020), 236 (), 116043CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)Collagen (COL) and bacterial cellulose (BC) were chem. recombined by Malaprade and Schiff-base reactions. A three-dimensional (3D) porous microsphere of COL/BC/Bone morphogenetic protein 2 (BMP-2) with multistage structure and components were prepd. by the template method combined with reverse-phase suspension regeneration. The microspheres were full of pores and had a rough surface. The particle size ranged from 8 to 12μ, the sp. surface area (SBET) was 123.4 m2/g, the pore vol. (VPore) was 0.59 cm3/g, and the av. pore diam. (DBJH) was 198.5 nm. The adsorption isotherm of the microspheres on the N2 mol. belongs to that of mesoporous materials. The microspheres showed good biocompatibility, and the 3D porous microspheres with multiple structures and components effectively promoted the adhesion, proliferation, and osteogenic differentiation of mice MC3T3-E1 cells. The study can provide a theor. basis for the application of COL/BC porous microspheres in the field of bone tissue engineering.
- 9Rashad, A.; Mustafa, K.; Heggset, E. B.; Syverud, K. Cytocompatibility of Wood-Derived Cellulose Nanofibril Hydrogels with Different Surface Chemistry. Biomacromolecules 2017, 18, 1238– 1248, DOI: 10.1021/acs.biomac.6b01911Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjs12ns7Y%253D&md5=7f3c218a92c40e563cbd846a3f001363Cytocompatibility of Wood-Derived Cellulose Nanofibril Hydrogels with Different Surface ChemistryRashad, Ahmad; Mustafa, Kamal; Heggset, Ellinor Baevre; Syverud, KristinBiomacromolecules (2017), 18 (4), 1238-1248CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)The current study aims to demonstrate the influence of the surface chem. of wood-derived cellulose nanofibril (CNF) hydrogels on fibroblasts for tissue engineering applications. TEMPO-mediated oxidn. or carboxymethylation pretreatments were employed to produce hydrogels with different surface chem. This study demonstrates the following: first, the gelation of CNF with cell culture medium and formation of stable hydrogels with improved rheol. properties; second, the response of mouse fibroblasts cultured on the surface of the hydrogels or sandwiched within the materials with respect to cytotoxicity, cell attachment, proliferation, morphol., and migration. Indirect cytotoxicity tests showed no toxic effect of either hydrogel. The direct contact with the carboxymethylated hydrogel adversely influenced the morphol. of the cells and limited their spreading, while typical morphol. and spreading of cells were obsd. with the TEMPO-oxidized hydrogel. The porous fibrous structure may be a key to cell proliferation and migration in the hydrogels.
- 10Bhattacharya, M.; Malinen, M. M.; Lauren, P.; Lou, Y. R.; Kuisma, S. W.; Kanninen, L.; Lille, M.; Corlu, A.; GuGuen-Guillouzo, C.; Ikkala, O.; Laukkanen, A.; Urtti, A.; Yliperttula, M. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. J. Controlled Release 2012, 164, 291– 298, DOI: 10.1016/j.jconrel.2012.06.039Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVOltr7E&md5=414ada6021acb8ab4ea21c664c26347fNanofibrillar cellulose hydrogel promotes three-dimensional liver cell cultureBhattacharya, Madhushree; Malinen, Melina M.; Lauren, Patrick; Lou, Yan-Ru; Kuisma, Saara W.; Kanninen, Liisa; Lille, Martina; Corlu, Anne; GuGuen-Guillouzo, Christiane; Ikkala, Olli; Laukkanen, Antti; Urtti, Arto; Yliperttula, MarjoJournal of Controlled Release (2012), 164 (3), 291-298CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)Over the recent years, various materials were introduced as potential 3D cell culture scaffolds. These include protein exts., peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunol. point of view. Here the authors demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. The authors show (1) rheol. properties that allow formation of a 3D scaffold in-situ after facile injection, (2) cellular biocompatibility without added growth factors, (3) cellular polarization, and (4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aq. NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, the authors conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chem. testing, tissue engineering, and cell therapy.
- 11Lou, Y. R.; Kanninen, L.; Kuisma, T.; Niklander, J.; Noon, L. A.; Burks, D.; Urtti, A.; Yliperttula, M. The Use of Nanofibrillar Cellulose Hydrogel As a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem Cells. Stem Cells Dev. 2014, 23, 380– 392, DOI: 10.1089/scd.2013.0314Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFChtr0%253D&md5=49970e1e82647e2bee47b86777f0529eThe Use of Nanofibrillar Cellulose Hydrogel As a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem CellsLou, Yan-Ru; Kanninen, Liisa; Kuisma, Tytti; Niklander, Johanna; Noon, Luke A.; Burks, Deborah; Urtti, Arto; Yliperttula, MarjoStem Cells and Development (2014), 23 (4), 380-392CODEN: SCDTAE; ISSN:1547-3287. (Mary Ann Liebert, Inc.)Human embryonic stem cells and induced pluripotent stem cells have great potential in research and therapies. The current in vitro culture systems for human pluripotent stem cells (hPSCs) do not mimic the three-dimensional (3D) in vivo stem cell niche that transiently supports stem cell proliferation and is subject to changes which facilitate subsequent differentiation during development. Here, we demonstrate, for the first time, that a novel plant-derived nanofibrillar cellulose (NFC) hydrogel creates a flexible 3D environment for hPSC culture. The pluripotency of hPSCs cultured in the NFC hydrogel was maintained for 26 days as evidenced by the expression of OCT4, NANOG, and SSEA-4, in vitro embryoid body formation and in vivo teratoma formation. The use of a cellulose enzyme, cellulase, enables easy cell propagation in 3D culture as well as a shift between 3D and two-dimensional cultures. More importantly, the removal of the NFC hydrogel facilitates differentiation while retaining 3D cell organization. Thus, the NFC hydrogel represents a flexible, xeno-free 3D culture system that supports pluripotency and will be useful in hPSC-based drug research and regenerative medicine.
- 12Maharjan, B.; Park, J.; Kaliannagounder, V. K.; Awasthi, G. P.; Joshi, M. K.; Park, C. H.; Kim, C. S. Regenerated cellulose nanofiber reinforced chitosan hydrogel scaffolds for bone tissue engineering. Carbohydr. Polym. 2021, 251, 117023 DOI: 10.1016/j.carbpol.2020.117023Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVajsbfN&md5=19920aa35e4d9b770eb9f0bc407ca432Regenerated cellulose nanofiber reinforced chitosan hydrogel scaffolds for bone tissue engineeringMaharjan, Bikendra; Park, Jeesoo; Kaliannagounder, Vignesh Krishnamoorthi; Awasthi, Ganesh Prasad; Joshi, Mahesh Kumar; Park, Chan Hee; Kim, Cheol SangCarbohydrate Polymers (2021), 251 (), 117023CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)Natural hydrogel scaffolds usually exhibit insufficient mech. strength which remains a major challenge in bone tissue engineering. In this study, the limitation was addressed by incorporating regenerated cellulose (rCL) nanofibers into chitosan (CS) hydrogel. The rCL nanofibers were regenerated from deacetylation of electrospun cellulose acetate (CA) nanofibers. As-prepd. rCL/CS composite scaffold showed unique porous morphol. with rCL nanofibers imbibed CS matrix. The compressive strength test exhibited that the rCL/CS scaffold have higher compressive strength compared to pure CS. The rCL/CS scaffold showed increased biomineralization and enhanced pre-osteoblast cell (MC3T3-E1) viability, attachment, and proliferation. The alk. phosphatase (ALP) and alizarin red (ARS) staining results suggested that the osteogenic differentiation ability was improved in rCL/CS composite scaffold. Hence, the novel fabrication idea and the obtained results suggested that the rCL/CS composite hydrogel scaffolds could be a promising three-dimensional bio-scaffold for bone tissue engineering.
- 13Ojansivu, M.; Rashad, A.; Ahlinder, A.; Massera, J.; Mishra, A.; Syverud, K.; Finne-Wistrand, A.; Miettinen, S.; Mustafa, K. Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabrication 2019, 11, 035010 DOI: 10.1088/1758-5090/ab0692Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFCht7k%253D&md5=58b3c3fe4f31f418d316fa7b8d2d46fdWood-based nanocellulose and bioactive glass modified gelatin- alginate bioinks for 3D bioprinting of bone cellsOjansivu, Miina; Rashad, Ahmad; Ahlinder, Astrid; Massera, Jonathan; Mishra, Ayush; Syverud, Kristin; Finne-Wistrand, Anna; Miettinen, Susanna; Mustafa, KamalBiofabrication (2019), 11 (3), 035010CODEN: BIOFFN; ISSN:1758-5090. (IOP Publishing Ltd.)A challenge in the extrusion-based bioprinting is to find a bioink with optimal biol. and physicochem. properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils(CNF) and bioactive glass(BaG) on the rheol. properties of gelatin-alginate bioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chem. characterization by SEM-EDX and ion release anal. confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells(Saos2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-contg. gels and crosslinked with CaCl2. Viability, proliferation and alk. phosphatase activity (ALP)were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a const. increase in the ALP activity in all the hydrogels. Further bioprinting expts. were conducted using human bone marrow-derived mesenchymal stem cells(hBMSCs), a clin. relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addn. of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications.
- 14Shavandi, A.; Hosseini, S.; Okoro, O. V.; Nie, L.; Eghbali Babadi, F.; Melchels, F. 3D Bioprinting of Lignocellulosic Biomaterials. Adv. Healthcare Mater. 2020, 9, 2001472 DOI: 10.1002/adhm.202001472Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFeqs7fO&md5=0abd32a8ed29dcbd00770e360205d0b6Bioprinting of Lignocellulosic BiomaterialsShavandi, Amin; Hosseini, Soraya; Okoro, Oseweuba Valentine; Nie, Lei; Eghbali Babadi, Farahnaz; Melchels, FerryAdvanced Healthcare Materials (2020), 9 (24), 2001472CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The interest in bioprinting of sustainable biomaterials is rapidly growing, and lignocellulosic biomaterials have a unique role in this development. Lignocellulosic materials are biocompatible and possess tunable mech. properties, and therefore promising for use in the field of 3D-printed biomaterials. This review aims to spotlight the recent progress on the application of different lignocellulosic materials (cellulose, hemicellulose, and lignin) from various sources (wood, bacteria, and fungi) in different forms (including nanocrystals and nanofibers in 3D bioprinting). Their crystallinity, leading to water insoly. and the presence of suspended nanostructures, makes these polymers stand out among hydrogel-forming biomaterials. These unique structures give rise to favorable properties such as high ink viscosity and strength and toughness of the final hydrogel, even when used at low concns. In this review, the application of lignocellulosic polymers with other components in inks is reported for 3D bioprinting and identified supercrit. CO2 as a potential sterilization method for 3D-printed cellulosic materials. This review also focuses on the areas of potential development by highlighting the opportunities and unmet challenges such as the need for standardization of the prodn., biocompatibility, and biodegradability of the cellulosic materials that underscore the direction of future research into the 3D biofabrication of cellulose-based biomaterials.
- 15Lin, L.; Jiang, S.; Yang, J.; Qiu, J.; Jiao, X.; Yue, X.; Ke, X.; Yang, G.; Zhang, L. Application of 3D-bioprinted nanocellulose and cellulose derivative-based bio-inks in bone and cartilage tissue engineering. Int. J. Bioprint. 2022, 9, 637 DOI: 10.18063/ijb.v9i1.637Google ScholarThere is no corresponding record for this reference.
- 16Onyianta, A. J.; Dorris, M.; Williams, R. L. Aqueous morpholine pre-treatment in cellulose nanofibril (CNF) production: comparison with carboxymethylation and TEMPO oxidisation pre-treatment methods. Cellulose 2018, 25, 1047– 1064, DOI: 10.1007/s10570-017-1631-0Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1el&md5=09bf8e13fb7ef11f5a97fafc1c92d4f6Aqueous morpholine pre-treatment in cellulose nanofibril (CNF) production: comparison with carboxymethylation and TEMPO oxidization pre-treatment methodsOnyianta, Amaka J.; Dorris, Mark; Williams, Rhodri L.Cellulose (Dordrecht, Netherlands) (2018), 25 (2), 1047-1064CODEN: CELLE8; ISSN:0969-0239. (Springer)In this study, pulped cellulose fibers were pre-treated with aq. morpholine prior to mech. disruption in the prodn. of cellulose nanofibrils (CNF). The properties of the morpholine pre-treated CNF (MCNF) were closely compared with CNF obtained from carboxymethylation (CMCNF) and TEMPO-oxidn. (TCNF) pre-treatment methods. An investigation of the swelling behaviors of cellulose in varying concns. of morpholine revealed that there is a synergistic behavior between morpholine and water in its ability to swell cellulose. As a result, cellulose pulp dispersed in 1:1 mol ratio of morpholine to water was well swollen and readily fibrillated by mech. shear. Surface chem. analyses indicated that the surface of the MCNF remained unmodified, compared to the CMCNF and TCNF which were modified with anionic groups. This resulted in only a slight decrease in crystallinity index and a minimal effect on the thermal stability of MCNF, compared to CMCNF and TCNF which showed marked decreases in crystallinity indexes and thermal stabilities. The av. widths of MCNF, CMCNF and TCNF, as measured from electron microscopic images, were broadly similar. The higher polydispersity of MCNF widths however led to a differential sedimentation and subsequent lower aspect ratio in comparison with CMCNF and TCNF as estd. using the sedimentation approach. Also, the presence of electrostatic repulsive forces, phys. interactions/entanglements and lower rigidity threshold of the CMCNF and TCNF resulted in higher storage moduli compared to the MCNF, whose elasticity is controlled by phys. interactions and entanglements. Aq. morpholine pre-treatment can potentially be regarded as an ecol. sustainable process for unmodified CNF prodn., since the chem. reagent is not consumed and can be recovered and reused.
- 17Amani, H.; Arzaghi, H.; Bayandori, M.; Dezfuli, A. S.; Pazoki-Toroudi, H.; Shafiee, A.; Moradi, L. Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques. Adv. Mater. Interfaces 2019, 6, 1900572 DOI: 10.1002/admi.201900572Google ScholarThere is no corresponding record for this reference.
- 18Cao, B.; Peng, Y.; Liu, X.; Ding, J. Effects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned Surfaces. ACS Appl. Mater. Interfaces 2017, 9, 23574– 23585, DOI: 10.1021/acsami.7b08339Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpvFOlsr4%253D&md5=3d54edf5c491d9158f1444a6c3e4a50dEffects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned SurfacesCao, Bin; Peng, Yuanmeng; Liu, Xiangnan; Ding, JiandongACS Applied Materials & Interfaces (2017), 9 (28), 23574-23585CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Functional groups of materials are known to affect cell behaviors, yet the corresponding effect on stem cell differentiation is always coupled with that of cell spreading; it is thus unclear whether the chem. groups influence cell differentiation directly or via cell spreading indirectly. Herein we used a unique surface patterning technique to decouple the corresponding effects. Mesenchymal stem cells (MSCs) derived from bone marrow were seeded on surfaces coated with alkanethiols with one of four functional end groups (-CH3, -OH, -COOH, and -NH2) and underwent 9 days of chondrogenic induction. The measurements of quartz crystal microbalance with dissipation confirmed less proteins adsorbed from the cell culture media on the neutral -CH3 and -OH surfaces than on the charged -COOH and -NH2 surfaces. The neutral surfaces exhibited less cell spreading and higher extents of chondrogenic differentiation than the charged surfaces, according to the characterizations of immunofluorescence staining and quant. real-time polymerase chain reaction. We further used a transfer lithog. technique to prep. patterned surfaces on nonfouling poly(ethylene glycol) hydrogels to localize single MSCs on microislands with self-assembly monolayers of different alkanethiols, under given microisland areas and thus well-defined spreading areas of cells. While small microislands were always beneficial for chondrogenic induction, we found that the type of functional groups had no significant effect on chondrogenic induction under the given cell spreading areas, implying that the chem. groups influence cell differentiation only indirectly. Our results hence illustrate that functional groups regulate stem cell differentiation via tuning protein adsorption and then nonspecific cell adhesion and thus cell spreading.
- 19Hasan, A.; Pattanayek, S. K.; Pandey, L. M. Effect of Functional Groups of Self-Assembled Monolayers on Protein Adsorption and Initial Cell Adhesion. ACS Biomater. Sci. Eng. 2018, 4, 3224– 3233, DOI: 10.1021/acsbiomaterials.8b00795Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOltrzP&md5=45da8f0712f6f1e949bb23be0f823e1cEffect of Functional Groups of Self-Assembled Monolayers on Protein Adsorption and Initial Cell AdhesionHasan, Abshar; Pattanayek, Sudip K.; Pandey, Lalit M.ACS Biomaterials Science & Engineering (2018), 4 (9), 3224-3233CODEN: ABSEBA; ISSN:2373-9878. (American Chemical Society)Surface modification plays a vital role in regulating protein adsorption and subsequently cell adhesion. In the present work, we prepd. nanoscaled modified surfaces using silanization and characterized them using Fourier-transform IR spectroscopy (FTIR), water contact angle (WCA), and at. force microscopy (AFM). Five different (amine, octyl, mixed, hybrid, and COOH) surfaces were prepd. based on their functionality and varying wettability and their effect on protein adsorption and initial cell adhesion was investigated. AFM anal. revealed nanoscale roughness on all modified surfaces. Fetal bovine serum (FBS) was used for protein adsorption expt. and effect of FBS was analyzed on initial cell adhesion kinetics (up to 6 h) under three different exptl. conditions: (a) with FBS in media, (b) with preadsorbed FBS on surfaces, and (c) incomplete media, i.e., without FBS. Various cell features such as cell morphol./circularity, cell area and nuclei size were also studied for the above stated conditions at different time intervals. The cell adhesion rate as well as cell spread area were highest in the case of surfaces with preadsorbed FBS. We obsd. higher surface coverage rate by adhering cells on hybrid (rate, 0.073 h-1) and amine (0.072 h-1) surfaces followed by COOH (0.062 h-1) and other surfaces under preadsorbed FBS condition. Surface treated with cells in incomplete media exhibited least adhesion rate, poor cell spreading and improper morphol. Furthermore, we found that initial cell adhesion rate and Δadhered cells (%) linearly increased with the change in α-helix content of adsorbed FBS on surfaces. Among all the modified surfaces and under all three exptl. conditions, hybrid surface exhibited excellent properties for supporting cell adhesion and growth and hence can be potentially used as surface modifiers in biomedical applications to design biocompatible surfaces.
- 20Arima, Y.; Iwata, H. Effect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayers. Biomaterials 2007, 28, 3074– 3082, DOI: 10.1016/j.biomaterials.2007.03.013Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXksVersrs%253D&md5=53f7ae424002f4e144950a2db5ab9f7bEffect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayersArima, Yusuke; Iwata, HirooBiomaterials (2007), 28 (20), 3074-3082CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Self-assembled monolayers (SAMs) of alkanethiols, which can provide flat and chem. well-defined surfaces, were employed as model surfaces to understand cellular interaction with artificial materials. SAMs presenting a wide range of wettabilities were prepd. by mixing 2 kinds of alkanethiols carrying terminal Me (CH3), hydroxyl (OH), carboxylic acid (COOH), or amino (NH2) groups. Adhesion behavior of human umbilical vein endothelial cells (HUVECs) and HeLa cells on these mixed SAMs were examd. The no. of adhered HUVECs reached a max. on CH3/OH mixed SAMs with a water contact angle of 40°, while cell adhesion increased with decreasing water contact angle up to 60-70° and then leveled off on CH3/COOH and CH3/NH2 mixed SAMs. Nos. of adhered HeLa cells showed a max. on CH3/OH and CH3/COOH mixed SAMs with a water contact angle of 50°. These facts suggest that cell adhesion is mainly detd. by surface wettability, but is also affected by the surface functional group, its surface d., and the kinds of cells. The effect of exchange of adsorbed proteins on cell adhesion was also examd. HUVECs were cultured on the mixed SAMs preadsorbed with albumin. Cell adhesion was effectively prohibited on hydrophobic SAMs pretreated with albumin. Albumin strongly adsorbed and resisted replacement by cell adhesive proteins on hydrophobic SAMs. On the other hand, cells adhered to albumin-adsorbed hydrophilic SAMs. Displacement of preadsorbed albumin with cell adhesive proteins effectively occurs on these hydrophilic SAMs. This effect contributes to induce SAMs with moderate wettability to give suitable surfaces for cell adhesion.
- 21Viswanathan, P.; Ondeck, M. G.; Chirasatitsin, S.; Ngamkham, K.; Reilly, G. C.; Engler, A. J.; Battaglia, G. 3D surface topology guides stem cell adhesion and differentiation. Biomaterials 2015, 52, 140– 147, DOI: 10.1016/j.biomaterials.2015.01.034Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXisleqsLs%253D&md5=60ca8932a525ea93079ed2ef809d6ceb3D surface topology guides stem cell adhesion and differentiationViswanathan, Priyalakshmi; Ondeck, Matthew G.; Chirasatitsin, Somyot; Ngamkham, Kamolchanok; Reilly, Gwendolen C.; Engler, Adam J.; Battaglia, GiuseppeBiomaterials (2015), 52 (), 140-147CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Polymd. high internal phase emulsion (polyHIPE) foams are extremely versatile materials for investigating cell-substrate interactions in vitro. Foam morphologies can be controlled by polymn. conditions to result in either open or closed pore structures with different levels of connectivity, consequently enabling the comparison between 2D and 3D matrixes using the same substrate with identical surface chem. conditions. Addnl., here we achieve the control of pore surface topol. (i.e. how different ligands are clustered together) using amphiphilic block copolymers as emulsion stabilizers. We demonstrate that adhesion of human mesenchymal progenitor (hES-MP) cells cultured on polyHIPE foams is dependent on foam surface topol. and chem. but is independent of porosity and interconnectivity. We also demonstrate that the interconnectivity, architecture and surface topol. of the foams has an effect on the osteogenic differentiation potential of hES-MP cells. Together these data demonstrate that the adhesive heterogeneity of a 3D scaffold could regulate not only mesenchymal stem cell attachment but also cell behavior in the absence of sol. growth factors.
- 22Griffin, M. F.; Ibrahim, A.; Seifalian, A. M.; Butler, P. E. M.; Kalaskar, D. M.; Ferretti, P. Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages. Acta Biomater. 2017, 50, 450– 461, DOI: 10.1016/j.actbio.2016.12.016Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmslantA%253D%253D&md5=9778c83eccae321e91e54dff5ad3ccddChemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineagesGriffin, M. F.; Ibrahim, A.; Seifalian, A. M.; Butler, P. E. M.; Kalaskar, D. M.; Ferretti, P.Acta Biomaterialia (2017), 50 (), 450-461CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomech. properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chem. groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14 days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymn. at 24 h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alk. phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chem. groups through plasma surface polymn. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects. Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chem. groups using plasma surface polymn. techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds resp. Plasma polymn. can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.
- 23Keselowsky, B. G.; Collard, D. M.; Garcia, A. J. Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 5953– 5957, DOI: 10.1073/pnas.0407356102Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXkt1Cmur0%253D&md5=d75346b1d9b03787be65ca704cfcda90Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiationKeselowsky, Benjamin G.; Collard, David M.; Garcia, Andres J.Proceedings of the National Academy of Sciences of the United States of America (2005), 102 (17), 5953-5957CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Biomaterial surface chem. has profound consequences on cellular and host responses, but the underlying mol. mechanisms remain poorly understood. Using self-assembled monolayers as model biomaterial surfaces presenting well defined chemistries, we demonstrate that surface chem. modulates osteoblastic differentiation and matrix mineralization independently from alterations in cell proliferation. Surfaces were precoated with equal densities of fibronectin (FN), and surface chem. modulated FN structure to alter integrin adhesion receptor binding. OH- and NH2-terminated surfaces up-regulated osteoblast-specific gene expression, alk. phosphatase enzymic activity, and matrix mineralization compared with surfaces presenting COOH and CH3 groups. These surface chem.-dependent differences in cell differentiation were controlled by binding of specific integrins to adsorbed FN. Function-perturbing antibodies against the central cell binding domain of FN completely inhibited matrix mineralization. Furthermore, blocking antibodies against β1 integrin inhibited matrix mineralization on the OH and NH2 surfaces, whereas function-perturbing antibodies specific for β3 integrin increased mineralization on the COOH substrate. These results establish surface-dependent differences in integrin binding as a mechanism regulating differential cellular responses to biomaterial surfaces. This mechanism could be exploited to engineer materials that control integrin binding specificity to elicit desired cellular activities to enhance the integration of biomaterials and improve the performance of biotechnol. culture supports.
- 24Saito, T.; Isogai, A. Introduction of aldehyde groups on surfaces of native cellulose fibers by TEMPO-mediated oxidation. Colloids Surf., A 2006, 289, 219– 225, DOI: 10.1016/j.colsurfa.2006.04.038Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtVagt7nK&md5=22f81c4a66f6848ac99c355b9aaacbc4Introduction of aldehyde groups on surfaces of native cellulose fibers by TEMPO-mediated oxidationSaito, Tsuguyuki; Isogai, AkiraColloids and Surfaces, A: Physicochemical and Engineering Aspects (2006), 289 (1-3), 219-225CODEN: CPEAEH; ISSN:0927-7757. (Elsevier B.V.)Native cellulose fibers were suspended in water and oxidized to various degrees with sodium hypochlorite and catalytic amts. of 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) and sodium bromide at pH 10.5. The oxidn. was accomplished within 30 min at room temp. The TEMPO-oxidized cellulose fibers were then converted to sheets like paper. Tensile strength of the sheets soaked in water, i.e. wet strength, showed a max. value, when 0.3 mmol NaClO per g cellulose was used in the TEMPO-mediated oxidn. Aldehyde groups up to 0.225 mmol/g were introduced in native cellulose fibers by the TEMPO-mediated oxidn., and were stably present in there. However, only surface aldehyde groups in the TEMPO-oxidized cellulose fibers contributed to the wet strength development of the sheets. Carboxylate groups were also formed not only on the surfaces but also insides of cellulose fibers by the TEMPO-mediated oxidn., although they had nearly no contribution to wet strength development of the sheets. These surface aldehyde groups forms hemiacetal linkages with cellulose hydroxyl groups at the inter-fiber bonds, resulting in the clear wet strength development of the sheets prepd. thereof. The TEMPO-mediated oxidn. is, therefore, applicable to introduction of not only carboxylate groups but also aldehyde groups to native cellulose surfaces as an efficient chem. modification under aq. conditions.
- 25Saito, T.; Okita, Y.; Nge, T. T.; Sugiyama, J.; Isogai, A. TEMPO-mediated oxidation of native cellulose: Microscopic analysis of fibrous fractions in the oxidized products. Carbohydr. Polym. 2006, 65, 435– 440, DOI: 10.1016/j.carbpol.2006.01.034Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XotlWmtrY%253D&md5=b83d8519f579cbf20702df05b0b1dd8cTEMPO-mediated oxidation of native cellulose: Microscopic analysis of fibrous fractions in the oxidized productsSaito, T.; Okita, Y.; Nge, T. T.; Sugiyama, J.; Isogai, A.Carbohydrate Polymers (2006), 65 (4), 435-440CODEN: CAPOD8; ISSN:0144-8617. (Elsevier B.V.)The 2,2,6,6-tetramethylpiperidine-1-oxy radial (TEMPO)-mediated oxidn. was applied to aq. suspensions of cotton linters, ramie and spruce holocellulose at pH 10.5, and water-insol. fractions of the TEMPO-oxidized celluloses collected by filtration with water were analyzed by optical and transmission electron microscopy and others. The results showed that both fibrous forms and microfibrillar nature of the original native celluloses were maintained after the TEMPO-mediated oxidn., even though carboxylate and aldehyde groups of 0.67-1.16 and 0.09-0.21 mmol/g, resp., were introduced into the water-insol. fractions. Neither crystallinity nor crystal size of cellulose I of the original native celluloses was changed under the conditions adopted in this study. Carboxylate groups in the TEMPO-oxidized ramie were mapped by labeling with lead ions as their counter ions. The transmission electron micrographs indicated that some heterogeneous distribution of carboxylate groups along each cellulose microfibril or each bundle of cellulose microfibrils seemed to be present in the TEMPO-oxidized celluloses.
- 26Yamada, S.; Yassin, M. A.; Weigel, T.; Schmitz, T.; Hansmann, J.; Mustafa, K. Surface activation with oxygen plasma promotes osteogenesis with enhanced extracellular matrix formation in three-dimensional microporous scaffolds. J. Biomed. Mater. Res. A 2021, 109, 1560– 1574, DOI: 10.1002/jbm.a.37151Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlslSqsbk%253D&md5=6b6f8af23889ec892a037dfdfa1803e0Surface activation with oxygen plasma promotes osteogenesis with enhanced extracellular matrix formation in three-dimensional microporous scaffoldsYamada, Shuntaro; Yassin, Mohammed A.; Weigel, Tobias; Schmitz, Tobias; Hansmann, Jan; Mustafa, KamalJournal of Biomedical Materials Research, Part A (2021), 109 (9), 1560-1574CODEN: JBMRCH; ISSN:1549-3296. (John Wiley & Sons, Inc.)Various types of synthetic polyesters have been developed as biomaterials for tissue engineering. These materials commonly possess biodegradability, biocompatibility, and formability, which are preferable properties for bone regeneration. The major challenge of using synthetic polyesters is the result of low cell affinity due to their hydrophobic nature, which hinders efficient cell seeding and active cell dynamics. To improve wettability, plasma treatment is widely used in industry. Here, we performed surface activation with oxygen plasma to hydrophobic copolymers, poly(L-lactide-co-trimethylene carbonate), which were shaped in 2D films and 3D microporous scaffolds, and then we evaluated the resulting surface properties and the cellular responses of rat bone marrow stem cells (rBMSC) to the material. Using SEM and Fourier-transform IR spectroscopy, we demonstrated that short-term plasma treatment increased nanotopog. surface roughness and wettability with minimal change in surface chem. On treated surfaces, initial cell adhesion and elongation were significantly promoted, and seeding efficiency was improved. In an osteoinductive environment, rBMSC on plasma-treated scaffolds exhibited accelerated osteogenic differentiation with osteogenic markers including RUNX2, osterix, bone sialoprotein, and osteocalcin upregulated, and a greater amt. of collagen matrix and mineral deposition were found. This study shows the utility of plasma surface activation for polymeric scaffolds in bone tissue engineering.
- 27Jaušovec, D.; Vogrinčič, R.; Kokol, V. Introduction of aldehyde vs. carboxylic groups to cellulose nanofibers using laccase/TEMPO mediated oxidation. Carbohydr. Polym. 2015, 116, 74– 85, DOI: 10.1016/j.carbpol.2014.03.014Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlt1Wgtbc%253D&md5=e4cba0de540350945e489cdba07ced6cIntroduction of aldehyde vs. carboxylic groups to cellulose nanofibers using laccase/TEMPO mediated oxidationJausovec, Darja; Vogrincic, Robert; Kokol, VanjaCarbohydrate Polymers (2015), 116 (), 74-85CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The chemo-enzymic modification of cellulose nanofibers (CNFs) using laccase as biocatalysts and TEMPO or 4-Amino-TEMPO as mediators under mild aq. conditions (pH 5, 30 °C) has been investigated to introduce surface active aldehyde groups. 4-Amino TEMPO turned out to be kinetically 0.5-times (50%) more active mediator, resulting to oxoammonium cation intermediacy generated and its in situ regeneration during the modification of CNFs. Accordingly, beside of around 750 mmol/kg terminally-located aldehydes, originated during CNFs isolation, the reaction resulted to about 140% increase of C6-located aldehydes at optimal conditions, without reducing CNFs crystallinity. While only the C6-aldehydes were wholly transformed into the carboxyls after addnl. post-treatment using NaOH according to the Cannizzaro reaction, the post-oxidn. with air-oxygen in EtOH/water medium or NaClO2 resulted to no- or very small amts. of carboxyls created, resp., at a simultaneous loss of all C6- and some terminal-aldehydes in the latter due to the formation of highly-resistant hemiacetal covalent linkages with available cellulose hydroxyls. The results indicated a new way of prepg. and stabilizing highly reactive C6-aldehydes on cellulose, and their exploitation in the development of new nanocellulose-based materials.
- 28Nechyporchuk, O.; Belgacem, M. N.; Pignon, F. Current Progress in Rheology of Cellulose Nanofibril Suspensions. Biomacromolecules 2016, 17, 2311– 2320, DOI: 10.1021/acs.biomac.6b00668Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XpvVWktrc%253D&md5=9375c07b97738e73c1aebcf458ad2170Current Progress in Rheology of Cellulose Nanofibril SuspensionsNechyporchuk, Oleksandr; Belgacem, Mohamed Naceur; Pignon, FredericBiomacromolecules (2016), 17 (7), 2311-2320CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Cellulose nanofibrils (CNFs) are produced and commonly used in the form of aq. suspensions or gels. A no. of studies have focused lately on rheol. properties of CNF suspensions, which gives insight into properties of such materials and can reflect their behavior during handling. This Review summarizes the recent progress in rheol. studies on CNF aq. suspensions using rotational rheometry. Here, we discuss linear viscoelastic properties, i.e., frequency-dependent storage and loss moduli; shear flow behavior, i.e., apparent viscosity and shear stress as a function of shear rate; local flow characteristics, etc. In this Review, we point out that the rheol. behavior of at least two types of CNF suspensions should be distinguished: (i) ones produced using mech. fibrillation with or without enzymic pretreatment (no surface chem. modification), which possess highly flocculated structure, and (ii) ones produced involving chem. modification pretreatments, e.g., carboxylation, carboxymethylation, quaternization, or sulfonation, which possess better colloidal stability and do not evidently flocculate.
- 29Wang, R. F.; Rosen, T.; Zhan, C. B.; Chodankar, S.; Chen, J. H.; Sharma, P. R.; Sharma, S. K.; Liu, T. B.; Hsiao, B. S. Morphology and Flow Behavior of Cellulose Nanofibers Dispersed in Glycols. Macromolecules 2019, 52, 5499– 5509, DOI: 10.1021/acs.macromol.9b01036Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKjt7jJ&md5=961304ac9dacf1cf5e696c3edee46395Morphology and Flow Behavior of Cellulose Nanofibers Dispersed in GlycolsWang, Ruifu; Rosen, Tomas; Zhan, Chengbo; Chodankar, Shirish; Chen, Jiahui; Sharma, Priyanka R.; Sharma, Sunil K.; Liu, Tianbo; Hsiao, Benjamin S.Macromolecules (Washington, DC, United States) (2019), 52 (15), 5499-5509CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Understanding the morphol. and flow behavior of cellulose nanofibers (CNFs) dispersed in org. solvents can improve the process of fabricating new cellulose-based nanocomposites. In this study, jute-based 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized CNFs with two different charge densities (0.64 and 1.03 mmol/g) were dispersed in ethylene glycol (EG) and propylene glycol (PG) using the solvent exchange method. The morphol. and dimensions of CNFs in dry and suspension states were characterized using TEM, at. force microscopy, and small-angle x-ray scattering techniques. The cross-sectional dimensions remained the same in different solvents. Rheol. measurements revealed that CNF suspensions in water or glycol (EG and PG) behaved similar to typical polymer solns. with a solvent-independent overlap concn. corresponding to the crowding factor of about 14. Furthermore, a thixotropic behavior was found in the concd. CNF/glycol systems as obsd. in typical CNF aq. suspensions. The fact that TEMPO-oxidized CNFs can be well dispersed in org. solvents opens up new possibilities to improve the CNF-polymer matrix blending, where the use of a viscous solvent can delay the transition to turbulence in processing and improve the control of fiber orientation because of a slower Brownian diffusive motion.
- 30Osong, S. H.; Norgren, S.; Engstrand, P. Processing of wood-based microfibrillated cellulose and nanofibrillated cellulose, and applications relating to papermaking: a review. Cellulose 2016, 23, 93– 123, DOI: 10.1007/s10570-015-0798-5Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGltL7K&md5=797786edf044c38994c3950c934193ccProcessing of wood-based microfibrillated cellulose and nanofibrillated cellulose, and applications relating to papermaking: a reviewOsong, Sinke H.; Norgren, Sven; Engstrand, PerCellulose (Dordrecht, Netherlands) (2016), 23 (1), 93-123CODEN: CELLE8; ISSN:0969-0239. (Springer)A review. As an emerging cellulosic nanomaterial, microfibrillated cellulose (MFC) and nanofibrillated cellulose (NFC) have shown enormous potential in the forest products industry. The forest products industry and academia are working together to realize the possibilities of commercializing MFC and NFC. However, there are still needs to improve the processing, characterization and material properties of nanocellulose in order to realize its full potential. The annual no. of research publications and patents on nanocellulose with respect to manufg., properties and applications is now up in the thousands, so it is of the utmost importance to review articles that endeavour to research on this explosive topic of cellulose nanomaterials. This review examines the past and current situation of wood-based MFC and NFC in relation to its processing and applications relating to papermaking.
- 31Wang, L.; Li, K.; Copenhaver, K.; Mackay, S.; Lamm, M. E.; Zhao, X.; Dixon, B.; Wang, J.; Han, Y.; Neivandt, D.; Johnson, D. A.; Walker, C. C.; Ozcan, S.; Gardner, D. J. Review on Nonconventional Fibrillation Methods of Producing Cellulose Nanofibrils and Their Applications. Biomacromolecules 2021, 22, 4037– 4059, DOI: 10.1021/acs.biomac.1c00640Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvFymtLzM&md5=3d36dd87639eeeb9b481e961239535ecReview on Nonconventional Fibrillation Methods of Producing Cellulose Nanofibrils and Their ApplicationsWang, Lu; Li, Kai; Copenhaver, Katie; Mackay, Susan; Lamm, Meghan E.; Zhao, Xianhui; Dixon, Brandon; Wang, Jinwu; Han, Yousoo; Neivandt, David; Johnson, Donna A.; Walker, Colleen C.; Ozcan, Soydan; Gardner, Douglas J.Biomacromolecules (2021), 22 (10), 4037-4059CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)A review. The prodn. of cellulose nanofibrils (CNFs) continues to receive considerable attention because of their desirable material characteristics for a variety of consumer applications. There are, however, challenges that remain in transitioning CNFs from research to widespread adoption in the industrial sectors, including prodn. cost and material performance. This Review covers CNFs produced from nonconventional fibrillation methods as a potential alternative soln. Pretreating biomass by biol., chem., mech., or phys. means can render plant feedstocks more facile for processing and thus lower energy requirements to produce CNFs. CNFs from nonconventional fibrillation methods have been investigated for various applications, including films, composites, aerogels, and Pickering emulsifiers. Continued research is needed to develop protocols to standardize the characterization (e.g., degree of fibrillation) of the lignocellulosic fibrillation processes and resulting CNF products to make them more attractive to the industry for specific product applications.
- 32Wu, C. N.; Saito, T.; Yang, Q. L.; Fukuzumi, H.; Isogai, A. Increase in the Water Contact Angle of Composite Film Surfaces Caused by the Assembly of Hydrophilic Nanocellulose Fibrils and Nanoclay Platelets. ACS Appl. Mater. Interfaces 2014, 6, 12707– 12712, DOI: 10.1021/am502701eGoogle Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOjtL%252FP&md5=1c03e11b05db02364cffb4957541affcIncrease in the Water Contact Angle of Composite Film Surfaces Caused by the Assembly of Hydrophilic Nanocellulose Fibrils and Nanoclay PlateletsWu, Chun-Nan; Saito, Tsuguyuki; Yang, Quanling; Fukuzumi, Hayaka; Isogai, AkiraACS Applied Materials & Interfaces (2014), 6 (15), 12707-12712CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A procedure for increasing water contact angles (CAs) of composite film surfaces via the assembly of two different hydrophilic components, nanocellulose fibrils and nanoclay platelets, is reported. The nanocellulose fibrils and nanoclay platelets have ionic groups on their surfaces in high densities (∼1 mmol g-1) and have no hydrophobic surface. The increase in the CA of the nanocellulose/nanoclay composite films was thus analyzed on the basis of the air area fractions of their nanostructured surfaces following Cassie's law. The air area fractions were geog. estd. from the at. force microscopy height profiles of the composite film surfaces. The CAs of the composite film surfaces were found to be well described by Cassie's law. The composite films consisting of two hydrophilic nanoelements with different shapes exhibited CAs larger than those of the individual neat films.
- 33Lopes, V. R.; Stromme, M.; Ferraz, N. In Vitro Biological Impact of Nanocellulose Fibers on Human Gut Bacteria and Gastrointestinal Cells. Nanomaterials 2020, 10, 1159 DOI: 10.3390/nano10061159Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVOhtL3F&md5=50a79b4d6af794e0ba7e1354204bc696In vitro biological impact of nanocellulose fibers on human gut bacteria and gastrointestinal cellsLopes, Viviana R.; Stromme, Maria; Ferraz, NataliaNanomaterials (2020), 10 (6), 1159CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Wood-derived nanofibrillated cellulose (NFC) has long been recognized as a valuable nanomaterial for food-related applications. However, the safety of NFC cannot be predicted just from the chem. nature of cellulose, and there is a need to establish the effect of the nanofibers on the gastrointestinal tract, to reassure the safe use of NFC in food-related products. The present work selected the intestinal cells Caco-2 and the gut bacteria Escherichia coli and Lactobacillus reuteri to evaluate the in vitro biol. response to NFC. NFC materials with different surface modifications(carboxymethylation, hydroxypropyl tri-Me ammonium-substitution, phosphorylation, and sulfoethylation) and unmodified NFC were investigated. The materials were characterized in terms of surface functional group content, fiber morphol., zeta potential and degree of crystallinity. The Caco-2 cell response to the materials was evaluated by assessing metabolic activity and cell membrane integrity. The effects of the NFC materials on the model bacteria were evaluated by measuring bacterial growth (optical d. at 600 nm) and by detg. colony forming units counts after NFC exposure. Results showed no sign of cytotoxicity in Caco-2 cells exposed to the NFC materials, and NFC surface functionalization did not impact the cell response. Interestingly, a bacteriostatic effect on E. coli was obsd. while the materials did not affect the growth of L. reuteri. The present findings are foreseen to contribute to increase the knowledge about the potential oral toxicity of NFC and, in turn, add to the development of safe NFC-based food products.
- 34Pajorova, J.; Skogberg, A.; Hadraba, D.; Broz, A.; Travnickova, M.; Zikmundova, M.; Honkanen, M.; Hannula, M.; Lahtinen, P.; Tomkova, M.; Bacakova, L.; Kallio, P. Cellulose Mesh with Charged Nanocellulose Coatings as a Promising Carrier of Skin and Stem Cells for Regenerative Applications. Biomacromolecules 2020, 21, 4857– 4870, DOI: 10.1021/acs.biomac.0c01097Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1SgtbnL&md5=43ce36c938b77a631813a56b49a00892Cellulose Mesh with Charged Nanocellulose Coatings as a Promising Carrier of Skin and Stem Cells for Regenerative ApplicationsPajorova, Julia; Skogberg, Anne; Hadraba, Daniel; Broz, Antonin; Travnickova, Martina; Zikmundova, Marketa; Honkanen, Mari; Hannula, Markus; Lahtinen, Panu; Tomkova, Maria; Bacakova, Lucie; Kallio, PasiBiomacromolecules (2020), 21 (12), 4857-4870CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Engineering artificial skin constructs is an ongoing challenge. An ideal material for hosting skin cells is still to be discovered. A promising candidate is low-cost cellulose, which is commonly fabricated in the form of a mesh and is applied as a wound dressing. Unfortunately, the structure and the topog. of current cellulose meshes are not optimal for cell growth. To enhance the surface structure and the physicochem. properties of a com. available mesh, we coated the mesh with wood-derived cellulose nanofibrils (CNFs). Three different types of mesh coatings are proposed in this study as a skin cell carrier: pos. charged cationic cellulose nanofibrils (cCNFs), neg. charged anionic cellulose nanofibrils (aCNFs), and a combination of these two materials (c+aCNFs). These cell carriers were seeded with normal human dermal fibroblasts (NHDFs) or with human adipose-derived stem cells (ADSCs) to investigate cell adhesion, spreading, morphol., and proliferation. The neg. charged aCNF coating significantly improved the proliferation of both cell types. The pos. charged cCNF coating significantly enhanced the adhesion of ADSCs only. The no. of NHDFs was similar on the cCNF coatings and on the noncoated pristine cellulose mesh. However, the three-dimensional (3D) structure of the cCNF coating promoted cell survival. The c+aCNF construct proved to combine benefits from both types of CNFs, which means that the c+aCNF cell carrier is a promising candidate for further application in skin tissue engineering.
- 35Hoven, V.; Tangpasuthadol, V.; Angkitpaiboon, Y.; Vallapa, N.; Kiatkamjornwong, S. Surface-charged chitosan: Preparation and protein adsorption. Carbohydr. Polym. 2007, 68, 44– 53, DOI: 10.1016/j.carbpol.2006.07.008Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsF2itb8%253D&md5=e6fa60f2a4623548a07f168463bd1472Surface-charged chitosan: Preparation and protein adsorptionHoven, Voravee P.; Tangpasuthadol, Varawut; Angkitpaiboon, Yaowamand; Vallapa, Napanporn; Kiatkamjornwong, SudaCarbohydrate Polymers (2007), 68 (1), 44-53CODEN: CAPOD8; ISSN:0144-8617. (Elsevier B.V.)Pos. and neg. charges were introduced to chitosan surfaces via methylation using Me iodide (MeI) and reductive alkylation using 5-formyl-2-furan sulfonic acid (FFSA). Attenuated total reflectance-Fourier transform IR (ATR-FTIR) spectroscopy, XPS and zeta potential measurement confirmed the presence of the desired functional groups on the surface-modified chitosan films. The chitosan films having neg. charges of N-sulfofurfuryl groups on their surface (SFC films) exhibited selective protein adsorption against both neg. charged proteins (albumin and fibrinogen) and pos. charged proteins (RNase, lysozyme). Its adsorption can be explained in terms of electrostatic attraction and repulsion. In contrast, the adsorption behavior of chitosan films having pos. charges of quaternary ammonium groups on their surface (QAC films) was anomalous. The quantity of the adsorbed protein tended to increase as a function of the swelling ratio of the QAC film regardless of the charge characteristics of the protein.
- 36Shalumon, K. T.; Anulekha, K. H.; Chennazhi, K. P.; Tamura, H.; Nair, S. V.; Jayakumar, R. Fabrication of chitosan/poly(caprolactone) nanofibrous scaffold for bone and skin tissue engineering. Int. J. Biol. Macromol. 2011, 48, 571– 576, DOI: 10.1016/j.ijbiomac.2011.01.020Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXksFynu78%253D&md5=f8e045c72389b6c801e3c426ecbeffdbFabrication of chitosan/poly(caprolactone) nanofibrous scaffold for bone and skin tissue engineeringShalumon, K. T.; Anulekha, K. H.; Chennazhi, K. P.; Tamura, H.; Nair, S. V.; Jayakumar, R.International Journal of Biological Macromolecules (2011), 48 (4), 571-576CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Chitosan/poly(caprolactone) (CS/PCL) nanofibrous scaffold was prepd. by a single step electrospinning technique. The presence of CS in CS/PCL scaffold aided a significant improvement in the hydrophilicity of the scaffold as confirmed by a decrease in contact angle, which thereby enhanced bioactivity and protein adsorption on the scaffold. The cytocompatibility of the CS/PCL scaffold was examd. using human osteoscarcoma cells (MG63) and found to be non toxic. Moreover, CS/PCL scaffold was found to support the attachment and proliferation of various cell lines such as mouse embryo fibroblasts (NIH3T3), murine aneuploid fibrosarcoma (L929), and MG63 cells. Cell attachment and proliferation was further confirmed by nuclear staining using 4',6-diamidino-2-phenylindole (DAPI). All these results indicate that CS/PCL nanofibrous scaffold would be an excellent system for bone and skin tissue engineering.
- 37Yang, D. Y.; Lu, X. Y.; Hong, Y.; Xi, T. F.; Zhang, D. Y. The molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterials. Biomaterials 2013, 34, 5747– 5758, DOI: 10.1016/j.biomaterials.2013.04.028Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnt1Sgtb0%253D&md5=d3e3604c0d0a388bfcfe05f1fd4079bdThe molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterialsYang, Dayun; Lu, Xiaoying; Hong, Ying; Xi, Tingfei; Zhang, DeyuanBiomaterials (2013), 34 (23), 5747-5758CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)To explore mol. mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examd. endothelial cell adhesion, morphol. and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amt. of serum proteins adsorbed on the three surfaces by proteomic technol. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and mol. biol. expts. Results showed that the type and amt. of adsorbed serum proteins assocd. with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence contg. proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addn., the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization.
- 38Giamblanco, N.; Yaseen, M.; Zhavnerko, G.; Lu, J. R.; Marletta, G. Fibronectin conformation switch induced by coadsorption with human serum albumin. Langmuir 2011, 27, 312– 319, DOI: 10.1021/la104127qGoogle Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCltb7N&md5=a47aea98fe19f4a09d0100b2916dd668Fibronectin Conformation Switch Induced by Coadsorption with Human Serum AlbuminGiamblanco, Nicoletta; Yaseen, Mohammed; Zhavnerko, Genady; Lu, Jian R.; Marletta, GiovanniLangmuir (2011), 27 (1), 312-319CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)The dynamic adsorption of human serum albumin (HSA) and plasma fibronectin (Fn) onto hydrophobic poly(hydroxymethylsiloxane) (PHMS) and the structures of adsorbed protein layers from single and binary protein solns. were studied. Spectroscopic ellipsometry (SE) and quartz crystal microbalance with dissipation monitoring (QCM-D) together with at. force microscopy (AFM) were used to measure the effective mass, thickness, viscoelastic properties, and morphol. of the adsorbed protein films. Adsorbed HSA formed a rigid, tightly bound monolayer of deformed protein, and Fn adsorption yielded a thick, very viscoelastic layer that was firmly bound to the substrate. The mixed protein layers obtained from the coadsorption of binary equimol. HSA-Fn solns. are almost exclusively dominated by Fn mols. Further sequential adsorption expts. showed little evidence of HSA adsorbed onto the predeposited Fn layer (denoted as Fn » HSA), and Fn was not adsorbed onto predeposited HSA (HSA » Fn). The conformational arrangement of the adsorbed Fn was analyzed in terms of the relative availability of two Fn domains. In particular, 4F1·5F1 binding domains in the Hep I fragment, close to the amino terminal of Fn, were targeted using a polyclonal antifibronectin antibody (anti-Fn), and the RGD sequence in the 10th segment, in the central region of the mol., was tested by cell culture expts. The results suggested that coadsorption with HSA induced the Fn switch from an open conformation, with the amino terminal subunit oriented toward the soln., to a close conformation, with the Fn central region oriented toward the soln.
- 39Othman, Z.; Pastor, B. C.; van Rijt, S.; Habibovic, P. Understanding interactions between biomaterials and biological systems using proteomics. Biomaterials 2018, 167, 191– 204, DOI: 10.1016/j.biomaterials.2018.03.020Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlt1Sqt7k%253D&md5=2d7ffb5dd7410eaf7255a71bb7b53218Understanding interactions between biomaterials and biological systems using proteomicsOthman, Ziryan; Cillero Pastor, Berta; van Rijt, Sabine; Habibovic, PamelaBiomaterials (2018), 167 (), 191-204CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)A review. The role that biomaterials play in the clin. treatment of damaged organs and tissues is changing. While biomaterials used in permanent medical devices were required to passively take over the function of a damaged tissue in the long term, current biomaterials are expected to trigger and harness the self-regenerative potential of the body in situ and then to degrade, the foundation of regenerative medicine. To meet these different requirements, it is imperative to fully understand the interactions biomaterials have with biol. systems, in space and in time. This knowledge will lead to a better understanding of the regenerative capabilities of biomaterials aiding their design with improved functionalities (e.g. biocompatibility, bioactivity). Proteins play a pivotal role in the interaction between biomaterials and cells or tissues. Protein adsorption on the material surface is the very first event of this interaction, which is determinant for the subsequent processes of cell growth, differentiation, and extracellular matrix formation. Against this background, the aim of the current review is to provide insight in the current knowledge of the role of proteins in cell-biomaterial and tissue-biomaterial interactions. In particular, the focus is on proteomics studies, mainly using mass spectrometry, and the knowledge they have generated on protein adsorption of biomaterials, protein prodn. by cells cultured on materials, safety and efficacy of new materials based on nanoparticles and the anal. of extracellular matrixes and extracellular matrix-derived products. In the outlook, the potential and limitations of this approach are discussed and mass spectrometry imaging is presented as a powerful technique that complements existing mass spectrometry techniques by providing spatial mol. information about the material-biol. system interactions.
- 40Hua, K.; Carlsson, D. O.; Ålander, E.; Lindström, T.; Strømme, M.; Mihranyan, A.; Ferraz, N. Translational study between structure and biological response of nanocellulose from wood and green algae. RSC Adv. 2014, 4, 2892– 2903, DOI: 10.1039/c3ra45553jGoogle Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFCrtLvP&md5=b3b456f8cd45b55624e25ceaeda022adTranslational study between structure and biological response of nanocellulose from wood and green algaeHua, Kai; Carlsson, Daniel O.; Aalander, Eva; Lindstroem, Tom; Stromme, Maria; Mihranyan, Albert; Ferraz, NataliaRSC Advances (2014), 4 (6), 2892-2903CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The influence of nanostructure on the cytocompatibility of cellulose films is analyzed providing insight into how physicochem. properties of surface modified microfibrillated cellulose (MFC) and Cladophora nanocellulose (CC) affect the materials cytocompatibility. CC is modified through TEMPO-mediated oxidn. and glycidyltrimethylammonium chloride (EPTMAC) condensation to obtain anionic and cationic nanocellulose samples resp., while anionic and cationic MFC samples are obtained by carboxymethylation and EPTMAC condensation resp. Films of unmodified, anionic and cationic MFC and CC are prepd. by vacuum filtration and characterized in terms of sp. surface area, pore size distribution, degree of crystallinity, surface charge and water content. Human dermal fibroblasts are exposed to culture medium exts. of the films in an indirect contact cytotoxicity test. Moreover, cell adhesion and viability are evaluated in a direct contact assay and the effects of the physicochem. properties on cell behavior are discussed. In the indirect cytotoxicity test no toxic leachables are detected, evidencing that the CC and MFC materials are non-cytotoxic, independently of the chem. treatment that they have been subjected to. The direct contact tests show that carboxymethylated-MFC presents a more cytocompatible profile than unmodified and trimethylammonium-MFC. TEMPO-CC promotes fibroblast adhesion and presents cell viability comparable to the results obtained with the tissue culture material Thermanox. We hypothesize that the distinct aligned nanofiber structure present in the TEMPO-CC films is responsible for the improved cell adhesion. Thus, by controlling the surface properties of cellulose nanofibers, such as chem., charge, and orientation, cell adhesion properties can be promoted.
- 41Alexandrescu, L.; Syverud, K.; Gatti, A.; Chinga-Carrasco, G. Cytotoxicity tests of cellulose nanofibril-based structures. Cellulose 2013, 20, 1765– 1775, DOI: 10.1007/s10570-013-9948-9Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1WqtLfE&md5=97d3c3ab35c74ca86888f72f2cbb8248Cytotoxicity tests of cellulose nanofibril-based structuresAlexandrescu, Laura; Syverud, Kristin; Gatti, Antonietta; Chinga-Carrasco, GaryCellulose (Dordrecht, Netherlands) (2013), 20 (4), 1765-1775CODEN: CELLE8; ISSN:0969-0239. (Springer)Cellulose nanofibrils based on wood pulp fibers are most promising for biomedical applications. Bacterial cellulose has been suggested for some medical applications and is presently used as wound dressing. However, cost-efficient processes for mass prodn. of bacterial cellulose are lacking. Hence, fibrillation of cellulose wood fibers is most interesting, as the cellulose nanofibrils can efficiently be produced in large quantities. However, the utilization of cellulose nanofibrils from wood requires a thorough verification of its biocompatibility, esp. with fibroblast cells which are important in regenerative tissue and particularly in wound healing. The cellulose nanofibril structures used in this study were based on Eucalyptus and Pinus radiata pulp fibers. The nanofibrillated materials were manufd. using a homogenizer without pre-treatment and with 2,2,6,6-tetramethylpiperidine-1-oxy radical as pre-treatment, thus yielding nanofibrils low and high level of anionic charge, resp. From these materials, two types of nanofibril-based structures were formed; (1) thin and dense structures and (2) open and porous structures. Cytotoxicity tests were applied on the samples, which demonstrated that the nanofibrils do not exert acute toxic phenomena on the tested fibroblast cells (3T3 cells). The cell membrane, cell mitochondrial activity and the DNA proliferation remained unchanged during the tests, which involved direct and indirect contact between the nano-structured materials and the 3T3 cells. Some samples were modified using the crosslinking agent polyethyleneimine (PEI) or the surfactant cetyl trimethylammonium bromide (CTAB). The sample modified with CTAB showed a clear toxic behavior, having neg. effects on cell survival, viability and proliferation. CTAB is an antimicrobial component, and thus this result was as expected. The sample crosslinked with PEI also had a significant redn. in cell viability indicating a redn. in DNA proliferation. We conclude that the neat cellulose nanostructured materials tested in this study are not toxic against fibroblasts cells. This is most important as nano-structured materials based on nanofibrils from wood pulp fibers are promising as substrate for regenerative medicine and wound healing.
- 42Čolić, M.; Mihajlovićic, D.; Mathew, A.; Naseri, N.; Kokol, V. Cytocompatibility and immunomodulatory properties of wood based nanofibrillated cellulose. Cellulose 2015, 22, 763– 778, DOI: 10.1007/s10570-014-0524-8Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVyhurrL&md5=1617ee8867d141689d686c89cfa083c9Cytocompatibility and immunomodulatory properties of wood based nanofibrillated celluloseColic, Miodrag; Mihajlovic, Dusan; Mathew, Aji; Naseri, Narges; Kokol, VanjaCellulose (Dordrecht, Netherlands) (2015), 22 (1), 763-778CODEN: CELLE8; ISSN:0969-0239. (Springer)Cellulose nanofibrils (CNFs), unique and promising natural materials have gained significant attention recently for biomedical applications, due to their special biomech. characteristics, surface chem., good biocompatibility and low toxicity. However, their long bio-persistence in the organism may provoke immune reactions and this aspect of CNFs has not been studied to date. Therefore, the aim of this work was to examine and compare the cytocompatibility and immunomodulatory properties of CNFs in vitro. CNFs (diams. of 10-70 nm; lengths of a few microns) were prepd. from Norway spruce (Picea abies) by mech. fibrillation and high pressure homogenization. L929 cells, rat thymocytes or human peripheral blood mononuclear cells (PBMNCs) were cultivated with CNFs. None of the six concns. of CNFs (31.25 μg/mL-1 mg/mL) induced cytotoxicity and oxidative stress in the L929 cells, nor induced necrosis and apoptosis of thymocytes and PBMNCs. Higher concns. (250 μg/mL-1 mg/mL) slightly inhibited the metabolic activities of the L929 cells as a consequence of inhibited proliferation. The same concns. of CNFs suppressed the proliferation of PBMNCs to phytohemaglutinine, a T-cell mitogen, and the process was followed by down-regulation of interleukin-2 (IL-2) and interferon-γ prodn. The highest concn. of CNFs inhibited IL-17A, but increased IL-10 and IL-6 prodn. The secretion of pro-inflammatory cytokines, IL-1β and tumor necrosis factor-α as well as Th2 cytokine (IL-4), remained unaltered. In conclusion, the results suggest that these CNFs are cytocompatible nanomaterial, according to current ISO criteria, with non-inflammatory and non-immunogenic properties. Higher concns. seem to be tolerogenic to the immune system, a characteristic very desirable for implantable biomaterials.
- 43Hua, K.; Rocha, I.; Zhang, P.; Gustafsson, S.; Ning, Y.; Stromme, M.; Mihranyan, A.; Ferraz, N. Transition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated Nanocellulose. Biomacromolecules 2016, 17, 1224– 1233, DOI: 10.1021/acs.biomac.6b00053Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xis1amsbs%253D&md5=b02c030f76e1352c796009e5a74d59bcTransition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated NanocelluloseHua, Kai; Rocha, Igor; Zhang, Peng; Gustafsson, Simon; Ning, Yi; Stroemme, Maria; Mihranyan, Albert; Ferraz, NataliaBiomacromolecules (2016), 17 (3), 1224-1233CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)This work presents an insight into the relationship between cell response and physicochem. properties of Cladophora cellulose (CC) by investigating the effect of CC functional group d. on the response of model cell lines. CC was carboxylated by electrochem. TEMPO-mediated oxidn. By varying the amt. of charge passed through the electrolysis setup, CC materials with different degrees of oxidn. were obtained. The effect of carboxyl group d. on the material's physicochem. properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased sp. surface area and smaller total pore vol. compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore vol., and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group d. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidn. increased. It was found that a threshold value in carboxyl group d. needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to com. tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the d. of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials.
- 44Loh, E. Y. X.; Fauzi, M. B.; Ng, M. H.; Ng, P. Y.; Ng, S. F.; Ariffin, H.; Amin, M. C. I. M. Cellular and Molecular Interaction of Human Dermal Fibroblasts with Bacterial Nanocellulose Composite Hydrogel for Tissue Regeneration. ACS Appl. Mater. Interfaces 2018, 10, 39532– 39543, DOI: 10.1021/acsami.8b16645Google ScholarThere is no corresponding record for this reference.
- 45Arima, Y.; Iwata, H. Preferential adsorption of cell adhesive proteins from complex media on self-assembled monolayers and its effect on subsequent cell adhesion. Acta Biomater. 2015, 26, 72– 81, DOI: 10.1016/j.actbio.2015.08.033Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVyis7jJ&md5=baaadbe4f5b6140dbd6d4d21a570bd56Preferential adsorption of cell adhesive proteins from complex media on self-assembled monolayers and its effect on subsequent cell adhesionArima, Yusuke; Iwata, HirooActa Biomaterialia (2015), 26 (), 72-81CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)We examd. the effect of surface chem. on adsorption of fibronectin (Fn) and vitronectin (Vn) and subsequent cell adhesion, employing self-assembled monolayers (SAMs) of alkanethiols carrying terminal Me (CH3), hydroxyl groups (OH), carboxylic acid (COOH), and amine (NH2). More Fn and Vn adsorbed to COOH- and NH2-SAMs than to CH3- and OH-SAMs from a mixt. with bovine serum albumin (BSA) and from 2% fetal bovine serum. Adhesion of human umbilical vein endothelial cells (HUVECs) on CH3- and OH-SAMs preadsorbed with Fn and BSA decreased with decreasing adsorbed Fn; however, HUVECs adhered to COOH- and NH2-SAMs even in the presence of BSA at 1000-fold more than Fn in a mixt. because of the preferential adsorption of Fn and/or displacement of preadsorbed BSA with Fn and Vn in a serum-contg. medium. SAMs coated with a mixt. of Vn and BSA exhibited adhesion of HUVECs regardless of surface functional groups. A well-organized focal adhesion complex and actin stress fibers were obsd. only for COOH- and NH2-SAMs when SAMs were preadsorbed with Vn and BSA. These results suggest that COOH- and NH2-SAMs allow for both cell adhesion and cell spreading because of the high d. of cell-binding domains derived from adsorbed Vn. Adsorption of cell adhesive proteins including fibronectin (Fn) and vitronectin (Vn) plays an important role in cell adhesion to artificial materials. However, for the development of biomaterials that contact with biol. fluids, it is important to understand adsorption of Fn and Vn in complex media contg. many kinds of proteins. Here, we focused on adsorption of Fn and Vn from complex media including mixed soln. with albumin and fetal bovine serum, and its role on cell adhesion using self-assembled monolayers (SAMs). Our result demonstrates that SAMs carrying carboxylic acid or amine allow for both cell adhesion and cell spreading because of preferentially adsorbed Vn. The result provides insights into surface design of cell culture substrates and tissue engineering scaffolds.
- 46Rashad, A.; Mohamed-Ahmed, S.; Ojansivu, M.; Berstad, K.; Yassin, M. A.; Kivijarvi, T.; Heggset, E. B.; Syverud, K.; Mustafa, K. Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem Cells. Biomacromolecules 2018, 19, 4307– 4319, DOI: 10.1021/acs.biomac.8b01194Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKgtLbL&md5=e94e0f19f7568a7f9caa2d5a01f2eb1eCoating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem CellsRashad, Ahmad; Mohamed-Ahmed, Samih; Ojansivu, Miina; Berstad, Kaia; Yassin, Mohammed A.; Kivijarvi, Tove; Heggset, Ellinor Baevre; Syverud, Kristin; Mustafa, KamalBiomacromolecules (2018), 19 (11), 4307-4319CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue engineering, but the hydrophobic surface may hinder optimal cell responses. The surface properties can be improved by coating the scaffold with cellulose nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial derived from wood. In this study, human bone marrow-derived mesenchymal stem cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds coated with CNF. Cellular responses to the surfaces (viability, attachment, proliferation, and osteogenic differentiation) were documented. CNF significantly enhanced the hydrophilic properties of PCL scaffolds and promoted protein adsorption. Live/dead staining and lactate dehydrogenase release assays confirmed that CNF did not inhibit cellular viability. The CNF between the 3D printed PCL strands and pores acted as a hydrophilic barrier, enhancing cell seeding efficiency, and proliferation. CNF supported the formation of a well-organized actin cytoskeleton and cellular prodn. of vinculin protein on the surfaces of TCP and PCL scaffolds. Moreover, CNF-coated surfaces enhanced not only alk. phosphatase activity, but also collagen Type-I and mineral formation. It is concluded that CNF coating enhances cell attachment, proliferation, and osteogenic differentiation and has the potential to improve the performance of 3D printed PCL scaffolds for bone tissue engineering.
- 47Nguyen, A. T.; Sathe, S. R.; Yim, E. K. F. From nano to micro: topographical scale and its impact on cell adhesion, morphology and contact guidance. J. Phys.: Condens. Matter 2016, 28, 183001 DOI: 10.1088/0953-8984/28/18/183001Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFehtbnE&md5=6ced494d4edd5b047fdbb4bd5e754b6cFrom nano to micro: topographical scale and its impact on cell adhesion, morphology and contact guidanceNguyen, Anh Tuan; Sathe, Sharvari R.; Yim, Evelyn K. F.Journal of Physics: Condensed Matter (2016), 28 (18), 183001/1-183001/16CODEN: JCOMEL; ISSN:0953-8984. (IOP Publishing Ltd.)Topog., among other phys. factors such as substrate stiffness and extracellular forces, is known to have a great influence on cell behaviors. Optimization of topog. features, in particular topog. dimensions ranging from nanoscale to microscale, is the key strategy to obtain the best cellular performance for various applications in tissue engineering and regenerative medicine. In this review, we provide a comprehensive survey on the significance of sizes of topog. and their impacts on cell adhesion, morphol. and alignment, and neurite guidance. Also recent works mimicking the hierarchical structure of natural extracellular matrix by combining both nanoscale and microscale topogs. are highlighted.
- 48Cao, X.; Ban, E.; Baker, B. M.; Lin, Y.; Burdick, J. A.; Chen, C. S.; Shenoy, V. B. Multiscale model predicts increasing focal adhesion size with decreasing stiffness in fibrous matrices. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, E4549– E4555, DOI: 10.1073/pnas.1620486114Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntVKjsL8%253D&md5=ad3f15c02a77a8b9253ff06b732cd26eMultiscale model predicts increasing focal adhesion size with decreasing stiffness in fibrous matricesCao, Xuan; Ban, Ehsan; Baker, Brendon M.; Lin, Yuan; Burdick, Jason A.; Chen, Christopher S.; Shenoy, Vivek B.Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (23), E4549-E4555CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We describe a multiscale model that incorporates force-dependent mech. plasticity induced by interfiber cross-link breakage and stiffness-dependent cellular contractility to predict focal adhesion (FA) growth and mechanosensing in fibrous extracellular matrixes (ECMs). The model predicts that FA size depends on both the stiffness of ECM and the d. of ligands available to form adhesions. Although these two quantities are independent in commonly used hydrogels, contractile cells break cross-links in soft fibrous matrixes leading to recruitment of fibers, which increases the ligand d. in the vicinity of cells. Consequently, although the size of focal adhesions increases with ECM stiffness in nonfibrous and elastic hydrogels, plasticity of fibrous networks leads to a departure from the well-described pos. correlation between stiffness and FA size. We predict a phase diagram that describes nonmonotonic behavior of FA in the space spanned by ECM stiffness and recruitment index, which describes the ability of cells to break cross-links and recruit fibers. The predicted decrease in FA size with increasing ECM stiffness is in excellent agreement with recent observations of cell spreading on electrospun fiber networks with tunable cross-link strengths and mechanics. Our model provides a framework to analyze cell mechanosensing in nonlinear and inelastic ECMs.
- 49Kumar, G.; Waters, M. S.; Farooque, T. M.; Young, M. F.; Simon, C. G., Jr. Freeform fabricated scaffolds with roughened struts that enhance both stem cell proliferation and differentiation by controlling cell shape. Biomaterials 2012, 33, 4022– 4030, DOI: 10.1016/j.biomaterials.2012.02.048Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xjs1Gmur0%253D&md5=d9cfb6e656d7fecfa109e74862816825Freeform fabricated scaffolds with roughened struts that enhance both stem cell proliferation and differentiation by controlling cell shapeKumar, Girish; Waters, Michael S.; Farooque, Tanya M.; Young, Marian F.; Simon, Carl G.Biomaterials (2012), 33 (16), 4022-4030CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)We demonstrate that freeform fabricated (FFF) scaffolds with a roughened surface topog. can support hBMSC proliferation, while also inducing osteogenic differentiation, for maximized generation of calcified, bone-like tissue. Previously, hBMSCs rapidly proliferated, without osteogenic differentiation, during culture in FFF scaffolds. In contrast, hBMSCs underwent osteogenic differentiation, with slow proliferation, during culture in nanofiber scaffolds. Anal. of cell morphol. showed that the topog. presented by the nanofiber scaffolds drove hBMSC differentiation by guiding them into a morphol. that induced osteogenic differentiation. Herein, we hypothesized that using the high-surface area architecture of FFF scaffolds to present a surface roughness that drives hBMSCs into a morphol. that induces osteogenic differentiation would yield a max. amt. differentiated hBMSCs and bone-like tissue. Thus, a solvent etching method was developed that imparted a 5-fold increase in roughness to the surface of the struts of poly(ε-caprolactone) (PCL) FFF scaffolds. The etched scaffolds induced osteogenic differentiation of the hBMSCs while un-etched scaffolds did not. The etched scaffolds also supported the same high levels of hBMSC proliferation that un-etched scaffolds supported. Finally, hBMSCs on un-etched scaffolds had a large spread area, while hBMSCs on etched scaffolds has a smaller area and were more rounded, indicating that the surface roughness from the etched scaffolds dictated the morphol. of the hBMSCs. The results demonstrate that FFF scaffolds with surface roughness can support hBMSC proliferation, while also inducing osteogenic differentiation, to maximize generation of calcified tissue. This work validates a rational approach to scaffold fabrication where the structure of the scaffold was designed to optimize stem cell function by controlling cell morphol.
- 50Frith, J. E.; Mills, R. J.; Hudson, J. E.; Cooper-White, J. J. Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell Differentiation. Stem Cells Dev. 2012, 21, 2442– 2456, DOI: 10.1089/scd.2011.0615Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1yntr7E&md5=a005b0679bcde2deb41cb76edb7a3237Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell DifferentiationFrith, Jessica Ellen; Mills, Richard James; Hudson, James Edward; Cooper-White, Justin JohnStem Cells and Development (2012), 21 (13), 2442-2456CODEN: SCDTAE; ISSN:1547-3287. (Mary Ann Liebert, Inc.)Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM mols. or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be detd. how specific integrin-ECM interactions may alter this or how they change during differentiation. We detd. that human bone marrow-derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of α5 integrin on day 7 of osteogenesis and an increase in α6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin-ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conductive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Addnl., we also detd. that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin-ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies.
- 51Curran, J. M.; Chen, R.; Hunt, J. A. The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials 2006, 27, 4783– 4793, DOI: 10.1016/j.biomaterials.2006.05.001Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlsFCrur0%253D&md5=37af274df0c066f91666bfb98d1b5b28The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrateCurran, Judith M.; Chen, Rui; Hunt, John A.Biomaterials (2006), 27 (27), 4783-4793CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Material-driven control of bone-marrow-derived mesenchymal stem cell (MSC) behavior and differentiation is a very exciting possibility. The aim of this study was to use silane-modified surfaces to control MSC adhesion and differentiation in vitro and evaluate the use of such techniques to control MSC behavior both in basal and stimulated conditions. A range of characterized clean glass silane-modified surfaces, Me (-CH3), amino (-NH2), silane (-SH), hydroxyl (-OH) and carboxyl (-COOH), were produced and cultured in contact with human MSC, in conjunction with a clean glass (TAAB) control, for time periods up to 28 days in basal, chondrogenic and osteogenic stimulated media. The samples were analyzed for levels of viable cell adhesion, morphol. and the prodn. of various differentiation and transcription markers using both fluorescent immunohistochem. (collagen I, II, osteocalcin, CBFA1) and real-time polymerase chain reaction (PCR) (collagen I, II, osteocalcin, osteopontin, osteonectin, CBFA1 and Sox 9). Anal. of the results demonstrated that the range of materials could be broken down into three distinct categories. Firstly, the -TAAB control and -CH3 surfaces maintained the MSC phenotype; secondly, the -NH2 and -SH-modified surfaces promoted and maintained osteogenesis both in the presence and absence of biol. stimuli. These surfaces did not support long-term chondrogenesis under any test conditions. Finally, the -OH and -COOH-modified surfaces promoted and maintained chondrogenesis under both basal and chondrogenic stimulated conditions, but did not support osteogenesis. These results demonstrate that intricate material properties such as surface chem. and energy can influence MSC behavior in vitro. These results have implications not only in promoting the efficiency of tissue-engineered constructs, but also to the wider field of MSC isolation, maintenance and expansion.
- 52Khang, D.; Choi, J.; Im, Y. M.; Kim, Y. J.; Jang, J. H.; Kang, S. S.; Nam, T. H.; Song, J.; Park, J. W. Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cells. Biomaterials 2012, 33, 5997– 6007, DOI: 10.1016/j.biomaterials.2012.05.005Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFyisLk%253D&md5=b228f1c03a57b3c149677f61973ee063Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cellsKhang, Dongwoo; Choi, Jungil; Im, Yeon-Min; Kim, Youn-Jeong; Jang, Je-Hee; Kang, Sang Soo; Nam, Tae-Hyun; Song, Jonghan; Park, Jin-WooBiomaterials (2012), 33 (26), 5997-6007CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Subnano, nano and sub-micron surface features can selectively activate integrin receptors and induce osteoblast differentiation of bone marrow mesenchymal stem cells. Although it is widely accepted that nanoscale titanium surface roughness may promote differentiation of various osteoblast lineages, there has been no clear report on the threshold dimension of surface features and the optimized dimensions of surface features for triggering integrin activation and stem cell differentiation. This study systematically controlled titanium surface features from the sub-nano to sub-micron scales and investigated the corresponding effects on stem cell responses, such as integrin activation, cyclins, key transcriptional genes of osteoblast differentiation and osteoblastic phenotype genes. Surface features with sub-nano surface dimensions were insufficient to increase integrin activation compared to pure nanoscale titanium surface features. Although both pure nanoscale and nano-submicron hybrid scales of titanium surface features were sufficient for activating integrin-ligand proteins interactions through the α integrin subunits, only nano-submicron hybrid titanium surface features significantly accelerated subsequent osteoblast differentiation of primary mouse bone marrow stromal cells after 2 wk. In addn., live cell anal. of human bone marrow mesenchymal stem cells on transparent titanium demonstrated rapid cytoskeletal re-organization on the nanoscale surface features, which ultimately induced higher expression of osteoblast phenotype genes after 3 wk.
- 53Faia-Torres, A. B.; Guimond-Lischer, S.; Rottmar, M.; Charnley, M.; Goren, T.; Maniura-Weber, K.; Spencer, N. D.; Reis, R. L.; Textor, M.; Neves, N. M. Differential regulation of osteogenic differentiation of stem cells on surface roughness gradients. Biomaterials 2014, 35, 9023– 9032, DOI: 10.1016/j.biomaterials.2014.07.015Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1ekt7bK&md5=3edaf61bc00e1b563a627fb569705f6dDifferential regulation of osteogenic differentiation of stem cells on surface roughness gradientsFaia-Torres, Ana B.; Guimond-Lischer, Stefanie; Rottmar, Markus; Charnley, Mirren; Goren, Tolga; Maniura-Weber, Katharina; Spencer, Nicholas D.; Reis, Rui L.; Textor, Marcus; Neves, Nuno M.Biomaterials (2014), 35 (33), 9023-9032CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Tissue engineering using scaffold-cell constructs holds the potential to develop functional strategies to regenerate bone. The interface of orthopedic implants with the host tissues is of great importance for its later performance. Thus, the optimization of the implant surface in a way that could stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) is of significant therapeutic interest. The effect of surface roughness of polycaprolactone (PCL) on the osteogenic differentiation of human bone-marrow MSCs was investigated. We prepd. surface roughness gradients of av. roughness (Ra) varying from the sub-micron to the micrometer range (∼0.5-4.7 μm), and mean distance between peaks (RSm) gradually varying from ∼214 μm to 33 μm. We analyzed the degree of cytoskeleton spreading, expression of alk. phosphatase, collagen type 1 and mineralization. The response of cells to roughness divided the gradient into three groups of elicited stem cell behavior: 1) faster osteogenic commitment and strongest osteogenic expression; 2) slower osteogenic commitment but strong osteogenic expression, and 3) similar or inferior osteogenic potential in comparison to the control material. The stem-cell modulation by specific PCL roughness surfaces highlights the potential for creating effective solns. for orthopedic applications featuring a clin. relevant biodegradable material.
- 54Tew, L. S.; Ching, J. Y.; Ngalim, S. H.; Khung, Y. L. Driving mesenchymal stem cell differentiation from self-assembled monolayers. RSC Adv. 2018, 8, 6551– 6564, DOI: 10.1039/c7ra12234aGoogle Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisFeqsb0%253D&md5=7ee77db049237861fee91811ef941b6cDriving mesenchymal stem cell differentiation from self-assembled monolayersTew, L. S.; Ching, J. Y.; Ngalim, S. H.; Khung, Y. L.RSC Advances (2018), 8 (12), 6551-6564CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The utilization of self-assembled monolayer (SAM) systems to direct Mesenchymal Stem Cell (MSC) differentiation has been covered in the literature for years, but finding a general consensus pertaining to its exact role over the differentiation of stem cells had been rather challenging. Although there are numerous reports on surface functional moieties activating and inducing differentiation, the results are often different between reports due to the varying surface conditions, such as topog. or surface tension. Herein, in view of the complexity of the subject matter, we have sought to catalog the recent developments around some of the more common functional groups on predominantly hard surfaces and how these chem. groups may influence the overall outcome of the mesenchymal stem cells (MSC) differentiation so as to better establish a clearer underlying relationship between stem cells and their base substratum interactions.
- 55Moursi, A. M.; Globus, R. K.; Damsky, C. H. Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitro. J. Cell Sci. 1997, 110, 2187– 2196, DOI: 10.1242/jcs.110.18.2187Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsFamtbo%253D&md5=eb2adeab7c8ea9f35cc047598a05a411Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitroMoursi, Amr M.; Globus, Ruth K.; Damsky, Caroline H.Journal of Cell Science (1997), 110 (18), 2187-2196CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists)We previously showed that anti-fibronectin antibodies or sol. fibronectin fragments contg. the central cell-binding domain inhibit formation of mineralized nodules by fetal calvarial osteoblasts in vitro. These findings suggest a crit. role for fibronectin in osteoblast differentiation and morphogenesis. In this study we tested the hypothesis that fibronectin's effects on osteogenesis are mediated via direct interactions with integrin receptors for fibronectin on osteoblasts. Immunocytochem. anal. identified the integrin fibronectin receptor α5β1 in fetal rat calvarial tissue and in cultured osteoblasts at all stages of differentiation. Three other integrins, α3β1, α8β1 and αvβ3, which can bind fibronectin, as well as other matrix components, were also identified in tissue and at all stages of cell culture. Immunopptn. data showed that α5β1 levels are const. throughout osteoblast differentiation whereas levels of α3β1 and α8β1 decline in mature mineralized cultures. To det. whether integrin fibronectin receptors are required for osteoblast formation of mineralized nodules, we examd. the extent of nodule formation in the presence and absence of function-perturbing anti-integrin antibodies. The antibodies were present continuously in cultures beginning at confluence (day 3), and nodule formation was measured at days 10 and 20. An anti-α5 integrin subunit antibody reduced nodule formation to less than 5% of control values at both time points. Inhibition of nodule formation was reversible and did not affect cell attachment and viability. Function-perturbing antibodies against α3β1 and α8β1 also reduced nodule formation, to less than 20% of control values. In contrast, function-perturbing antibodies to αvβ3 and αvβ5 did not affect nodule formation, indicating that the inhibitions noted were indeed specific. To det. the effect of antibody treatment on gene expression, steady-state mRNA expression was examd. and found to be suppressed for osteoblast markers alk. phosphatase and osteocalcin. Together, these results indicate that direct osteoblast interactions with the extracellular matrix are mediated by a select group of integrin receptors that includes α5β1, α3β1 and α8β1. We further conclude that the specific α5β1 fibronectin receptor mediates crit. interactions between osteoblasts and fibronectin required for both bone morphogenesis and osteoblast differentiation.
- 56Besbes, I.; Alila, S.; Boufi, S. Nanofibrillated cellulose from TEMPO-oxidized eucalyptus fibres: Effect of the carboxyl content. Carbohyd. Polym. 2011, 84 (3), 975– 983, DOI: 10.1016/j.carbpol.2010.12.052Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXitVShurY%253D&md5=ae9da05b1bf12dda17ef09624e3bcc05Nanofibrillated cellulose from TEMPO-oxidized eucalyptus fibres: Effect of the carboxyl contentBesbes, Iskander; Alila, Sabrine; Boufi, SamiCarbohydrate Polymers (2011), 84 (3), 975-983CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The effect of the carboxyl content on the high pressure defibrillation of oxidized eucalyptus from micro to nanoscale size was investigated. It has been shown that TEMPO-mediated oxidn. of dried softwood pulp not only facilitates the defibrillation process, but also reduces the no. of passes necessary to get the gel, as well as preventing the clogging of the homogenizer. In fact, these effects became apparent up to a carboxyl content about 300 μmol/g, and over 500 μmol/g, the yield in the nanofibrillated cellulose exceeded 90%, at a defibrillation pressure of 600 bar. The morphol. of the ensuing nanofibrillated cellulose (NFC) and its cryst. degree were characterized by FE-SEM and DRX measurement, resp. The evolution of the transparency degree and the viscosity according to the oxidn. degree and defibrillation pressure were also analyzed by UV-vis transmittance and rheol. measurement. The reinforcing potential of the ensuing NFC was explored by means of dynamic mech. anal. (DMA) carried on nanocomposite film prepd. from a suspension of NFC as the reinforcing phase and an acrylic latex dispersion as the matrix.
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Abstract
Figure 1
Figure 1. Preparation and characterization of nanocellulose hydrogels. (A) Macroscopic images of different CNF materials and BNC. (B) Aldehyde content of nanocellulose materials in reference to glucose concentrations (0 to 0.04% in water). (C) Change in viscosity of CNF suspensions as a function of shear rate (spindle speed).
Figure 2
Figure 2. Morphological assessment and fiber analysis. (A) macroscopic (top) and microscopic images of nanocellulose before (middle) and after (bottom) staining with crystal violet. (B–E) Fiber analysis of CNF samples (n = 3). All values are expressed as mean ± SD (## p ≤ 0.001).
Figure 3
Figure 3. AFM images showing different nanoscale morphologies of CNFs and BNC materials.
Figure 4
Figure 4. Water contact angle and ζ-potential measurements of different nanocellulose materials. (A) Water contact angle on 2D coated samples (n = 12). (B) ζ-Potential in growth medium with 10% FBS (n = 15). All values are expressed as mean ± SD. * Significant difference between BNC and any CNF groups (*, p ≤ 0.05; ***, p ≤ 0.001). # Significant difference between CNF groups (#, p ≤ 0.05; ##, p ≤ 0.01).
Figure 5
Figure 5. Protein adsorption onto different nanocellulose surfaces in (A) BSA solution, (B) FBS solution, (C) and 10% FBS solution. All values are expressed as mean ± SD (n = 5). * Significant difference between BNC and any CNF group (***, p ≤ 0.001). # Significant difference between CNF groups (#, p ≤ 0.05; ###, p ≤ 0.001).
Figure 6
Figure 6. Indirect cytotoxicity assessment of rat MSCs treated with extracts of nanocelluloses. (A–E) Fluorescence images of live/dead stain. Calcein AM (green) represents live cells, and ethidium homodimer (red) represents dead cells. (F) Mitochondrial activity by the Alamar Blue assay. All values are expressed as mean ± SD (n = 4).
Figure 7
Figure 7. Direct cytotoxicity assessment of rat MSCs cultured on TCP, CNF, and BNC surfaces. (A–E) Fluorescence images of live/dead stain. (F) LDH assay. All values are expressed as mean ± SD (n = 4).
Figure 8
Figure 8. Cytoskeleton analysis of rat MSCs cultured on TCP, CNF, and BNC surfaces. Fluorescence microscopy images of the F-actin (green) and nuclei (blue). All values are expressed as mean ± SD (n = 20 cells). * Significant difference between TCP and other groups (**, p ≤ 0.01; ***, p ≤ 0.001). # Significant difference between CNF and BNC groups (##, p ≤ 0.01; ###, p ≤ 0.001). & Significant difference between CNF groups (&&, p ≤ 0.01).
Figure 9
Figure 9. Cell proliferation and ALP activity of BMSCs cultured on TCP, CNFs, and BNC in (A, B) growth and (C, D) osteogenic media. All values are expressed as mean ± SD (n = 5). * Significant difference between TCP and other groups (*, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001). # Significant difference between CNF and BNC groups (##, p ≤ 0.01; ###, p ≤ 0.001). & Significant difference between CNF groups (&&, p ≤ 0.01).
Figure 10
Figure 10. Mineralization assay by Alizarin red S at day 21. All values are expressed as mean ± SD (n = 5). * Significant difference between TCP and other groups (**, p ≤ 0.01). # Significant difference between CNF and BNC groups (##, p ≤ 0.01).
References
This article references 56 other publications.
- 1Patil, T. V.; Patel, D. K.; Dutta, S. D.; Ganguly, K.; Santra, T. S.; Lim, K. T. Nanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applications. Bioact. Mater. 2022, 9, 566– 589, DOI: 10.1016/j.bioactmat.2021.07.0061https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlGhsbfE&md5=7d9fd3032a9676053303368c2162d5deNanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applicationsPatil, Tejal V.; Patel, Dinesh K.; Dutta, Sayan Deb; Ganguly, Keya; Santra, Tuhin Subhra; Lim, Ki-TaekBioactive Materials (2022), 9 (), 566-589CODEN: BMIAD4; ISSN:2452-199X. (Elsevier B.V.)A review. Nanocellulose, a biopolymer, has received wide attention from researchers owing to its superior physicochem. properties, such as high mech. strength, low d., biodegradability, and biocompatibility. Nanocellulose can be extd. from wide range of sources, including plants, bacteria, and algae. Depending on the extn. process and dimensions (diam. and length), they are categorized into three main types: cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). CNCs are a highly cryst. and needle-like structure, whereas CNFs have both amorphous and cryst. regions in their network. BNC is the purest form of nanocellulose. The nanocellulose properties can be tuned by chem. functionalization, which increases its applicability in biomedical applications. This review highlights the fabrication of different surface-modified nanocellulose to deliver active mols., such as drugs, proteins, and plasmids. Nanocellulose-mediated delivery of active mols. is profoundly affected by its topog. structure and the interaction between the loaded mols. and nanocellulose. The applications of nanocellulose and its composites in tissue engineering have been discussed. Finally, the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active mols.
- 2Luo, H.; Cha, R.; Li, J.; Hao, W.; Zhang, Y.; Zhou, F. Advances in tissue engineering of nanocellulose-based scaffolds: A review. Carbohydr. Polym. 2019, 224, 115144 DOI: 10.1016/j.carbpol.2019.1151442https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFChsrjE&md5=ee968a0fc0776be4e69f5f558fc01d49Advances in tissue engineering of nanocellulose-based scaffolds: A reviewLuo, Huize; Cha, Ruitao; Li, Juanjuan; Hao, Wenshuai; Zhang, Yan; Zhou, FengshanCarbohydrate Polymers (2019), 224 (), 115144CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)A review, with refs. Scaffolds based on nanocellulose (NC) have crucial applications in tissue engineering (TE) owing to the biocompatibility, water absorption, water retention, optical transparency, and chemo-mech. properties. In this review, we summarize the scaffolds based on nanocellulose, including nanocryst. cellulose and nanofibrillated cellulose. We compare four representative methods to prep. NC-based scaffolds, contg. electrospinning, freeze-drying, 3D printing, and solvent casting. We outline the characteristics of scaffolds obtained by different methods. Our focus is on the applications of NC-based scaffolds to repair, improve or replace damaged tissues and organs, including skin, blood vessel, nerve, skeletal muscle, heart, liver, and ophthalmol. NC-based scaffolds are attractive materials for regeneration of different tissues and organs due to the remarkable features. Finally, we propose the challenges and potentials of NC-based TE scaffolds.
- 3Du, H.; Liu, W.; Zhang, M.; Si, C.; Zhang, X.; Li, B. Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applications. Carbohydr. Polym. 2019, 209, 130– 144, DOI: 10.1016/j.carbpol.2019.01.0203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtFSit7g%253D&md5=beff516f2d4c0225823d8539b74d0947Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applicationsDu, Haishun; Liu, Wei; Zhang, Miaomiao; Si, Chuanling; Zhang, Xinyu; Li, BinCarbohydrate Polymers (2019), 209 (), 130-144CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The prodn. of cellulose nanomaterials from lignocellulosic biomass opens an opportunity for the development and application of new materials in nanotechnol. Over the last decade, cellulose nanomaterials based hydrogels have emerged as promising materials in the field of biomedical applications due to their low toxicity, biocompatibility, biodegradability, as well as excellent mech. stability. In this review, recent progress on the prepn. of cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs) based hydrogels and their biomedical applications is summarized and discussed based on the analyses of the latest studies (esp. for the reports in the past five years). We begin with a brief introduction of the differences in prepn. methods and properties of two main types of cellulose nanomaterials: CNCs and CNFs isolated from lignocellulosic biomass. Then, various processes for the fabrication of CNCs based hydrogels and CNFs based hydrogels were elaborated, resp., with the focus on some new methods (e.g. 3D printing). Furthermore, a no. of biomedical applications of CNCs and CNFs based hydrogels, including drug delivery, wound dressings and tissue engineering scaffolds were highlighted. Finally, the prospects and ongoing challenges of CNCs and CNFs based hydrogels for biomedical applications were summarized. This work demonstrated that the CNCs and CNFs based hydrogels have great promise in a wide range of biomedical applications in the future.
- 4Ferreira, F. V.; Otoni, C. G.; De France, K. J.; Barud, H. S.; Lona, L. M. F.; Cranston, E. D.; Rojas, O. J. Porous nanocellulose gels and foams: Breakthrough status in the development of scaffolds for tissue engineering. Mater. Today 2020, 37, 126– 141, DOI: 10.1016/j.mattod.2020.03.0034https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXltlCgurs%253D&md5=2263926615ac0a2c95a727485a349c9bPorous nanocellulose gels and foams: Breakthrough status in the development of scaffolds for tissue engineeringFerreira, Filipe V.; Otoni, Caio G.; De France, Kevin J.; Barud, Hernane S.; Lona, Liliane M. F.; Cranston, Emily D.; Rojas, Orlando J.Materials Today (Oxford, United Kingdom) (2020), 37 (), 126-141CODEN: MTOUAN; ISSN:1369-7021. (Elsevier Ltd.)A review. We report on the latest scientific advances related to the use of porous foams and gels prepd. with cellulose nanofibrils (CNF) and nanocrystals (CNC) as well as bacterial nanocellulose (BNC) collectively nanocelluloses as biomedical materials for application in tissue regeneration. Interest in such applications stems from the lightwt. and strong structures that can be efficiently produced from these nanocelluloses. Dried nanocellulose foams and gels, including xerogels, cryogels, and aerogels have been synthesized effortlessly using green, scalable, and cost-effective techniques. Methods to control structural features (e.g., porosity, morphol., and mech. performance) and biol. interactions (e.g., biocompatibility and biodegradability) are discussed in light of specific tissues of interest. The state-of-the-art in the field of nanocellulose-based scaffolds for tissue engineering is presented, covering physicochem. and biol. properties relevant to these porous systems that promise groundbreaking advances. Specifically, these materials show excellent performance for in vitro cell culturing and in vivo implantation. We report on recent efforts related to BNC scaffolds used in animal and human implants, which furthermore support the viability of CNF and CNC based scaffolds in next-generation biomedical materials.
- 5Chen, C.; Ding, W.; Zhang, H.; Zhang, L.; Huang, Y.; Fan, M.; Yang, J.; Sun, D. Bacterial cellulose-based biomaterials: From fabrication to application. Carbohydr. Polym. 2022, 278, 118995 DOI: 10.1016/j.carbpol.2021.1189955https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXivVSnt7bK&md5=b1a9d3571cb35bc0779bbc64fb9e3c8fBacterial cellulose-based biomaterials: From fabrication to applicationChen, Chuntao; Ding, Weixiao; Zhang, Heng; Zhang, Lei; Huang, Yang; Fan, Mengmeng; Yang, Jiazhi; Sun, DongpingCarbohydrate Polymers (2022), 278 (), 118995CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)A review. Driven by its excellent phys. and chem. properties, BC (bacterial cellulose) has achieved significant progress in the last decade, rendering with many novel applications. Due to its resemblance to the structure of extracellular matrix, BC-based biomaterials have been widely explored for biomedical applications such as tissue engineering and drug delivery. The recent advances in nanotechnol. endow further modifications on BC and generate BC-based composites for different applications. This article presents a review on the research advancement on BC-based biomaterials from fabrication methods to biomedical applications, including wound dressing, artificial skin, vascular tissue engineering, bone tissue regeneration, drug delivery, and other applications. The prepn. of these materials and their potential applications are reviewed and summarized. Important factors for the applications of BC in biomedical applications including degrdn. and pore structure characteristic are discussed in detail. Finally, the challenges in future development and potential advances of these materials are also discussed.
- 6Sharma, C.; Bhardwaj, N. K. Bacterial nanocellulose: Present status, biomedical applications and future perspectives. Mater. Sci. Eng. C 2019, 104, 109963 DOI: 10.1016/j.msec.2019.1099636https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVSqu73N&md5=92ca03a674a50307fc27f1625887d399Bacterial nanocellulose: Present status, biomedical applications and future perspectivesSharma, Chhavi; Bhardwaj, Nishi K.Materials Science & Engineering, C: Materials for Biological Applications (2019), 104 (), 109963CODEN: MSCEEE; ISSN:0928-4931. (Elsevier B.V.)A review. Bacterial nanocellulose (BNC) has emerged as a natural biopolymer of significant importance in diverse technol. areas due to its incredible physicochem. and biol. characteristics. However, the high capital investments, prodn. cost and lack of well-organized scale-up processes resulting in low BNC prodn. are the major impediments need to be resolved. This review enfolds the three different and important portions of BNC. Firstly, advancement in prodn. technologies of BNC like cell-free ext. technol., static intermittent fed batch technol. and novel cost-effective substrates that might surmount the barriers assocd. with BNC prodn. at industrial level. Secondly, as BNC and its composites (with other polymers/nanoparticles) represents the utmost material of preference in current regenerative and diagnostic medicine, therefore recently reported biomedical applications of BNC and functionalized BNC in drug delivery, tissue engineering, antimicrobial wound healing and biosensing are widely been focused here. The third and the most important aspect of this review is an in-depth discussion of various pitfalls assocd. with BNC prodn. Recent trends in BNC research to overcome the existing snags that might pave a way for industrial scale prodn. of BNC thereby facilitating its feasible application in various fields are highlighted.
- 7Vielreicher, M.; Kralisch, D.; Volkl, S.; Sternal, F.; Arkudas, A.; Friedrich, O. Bacterial nanocellulose stimulates mesenchymal stem cell expansion and formation of stable collagen-I networks as a novel biomaterial in tissue engineering. Sci. Rep. 2018, 8, 9401 DOI: 10.1038/s41598-018-27760-z7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mbps1Kisw%253D%253D&md5=84ad96177c751228796f02ad34b14365Bacterial nanocellulose stimulates mesenchymal stem cell expansion and formation of stable collagen-I networks as a novel biomaterial in tissue engineeringVielreicher Martin; Sternal Fabian; Friedrich Oliver; Kralisch Dana; Volkl Simon; Arkudas AndreasScientific reports (2018), 8 (1), 9401 ISSN:.Biomimetic scaffolds are of great interest to tissue engineering (TE) and tissue repair as they support important cell functions. Scaffold coating with soluble collagen-I has been used to achieve better tissue integration in orthopaedy, however, as collagen persistence was only temporary such efforts were limited. Adequate coverage with cell-derived ECM collagen-I would promise great success, in particular for TE of mechanically challenged tissues. Here, we have used label-free, non-invasive multiphoton microscopy (MPM) to characterise bacterial nanocellulose (BNC) - a promising biomaterial for bone TE - and their potency to stimulate collagen-I formation by mesenchymal stem cells (MSCs). BNC fleeces were investigated by Second Harmonic Generation (SHG) imaging and by their characteristic autofluorescence (AF) pattern, here described for the first time. Seeded MSCs adhered fast, tight and very stable, grew to multilayers and formed characteristic, wide-spread and long-lasting collagen-I. MSCs used micron-sized lacunae and cracks on the BNC surface as cell niches. Detailed analysis using a collagen-I specific binding protein revealed a highly ordered collagen network structure at the cell-material interface. In addition, we have evidence that BNC is able to stimulate MSCs towards osteogenic differentiation. These findings offer new options for the development of engineered tissue constructs based on BNC.
- 8Zhang, W.; Wang, X. C.; Li, X. Y.; Zhang, L. L.; Jiang, F. A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineering. Carbohydr. Polym. 2020, 236, 116043 DOI: 10.1016/j.carbpol.2020.1160438https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjvFGru7s%253D&md5=74b7391f28a6d93d42a99e18c941a920A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineeringZhang, Wen; Wang, Xue-chuan; Li, Xi-yue; Zhang, Le-le; Jiang, FeiCarbohydrate Polymers (2020), 236 (), 116043CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)Collagen (COL) and bacterial cellulose (BC) were chem. recombined by Malaprade and Schiff-base reactions. A three-dimensional (3D) porous microsphere of COL/BC/Bone morphogenetic protein 2 (BMP-2) with multistage structure and components were prepd. by the template method combined with reverse-phase suspension regeneration. The microspheres were full of pores and had a rough surface. The particle size ranged from 8 to 12μ, the sp. surface area (SBET) was 123.4 m2/g, the pore vol. (VPore) was 0.59 cm3/g, and the av. pore diam. (DBJH) was 198.5 nm. The adsorption isotherm of the microspheres on the N2 mol. belongs to that of mesoporous materials. The microspheres showed good biocompatibility, and the 3D porous microspheres with multiple structures and components effectively promoted the adhesion, proliferation, and osteogenic differentiation of mice MC3T3-E1 cells. The study can provide a theor. basis for the application of COL/BC porous microspheres in the field of bone tissue engineering.
- 9Rashad, A.; Mustafa, K.; Heggset, E. B.; Syverud, K. Cytocompatibility of Wood-Derived Cellulose Nanofibril Hydrogels with Different Surface Chemistry. Biomacromolecules 2017, 18, 1238– 1248, DOI: 10.1021/acs.biomac.6b019119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjs12ns7Y%253D&md5=7f3c218a92c40e563cbd846a3f001363Cytocompatibility of Wood-Derived Cellulose Nanofibril Hydrogels with Different Surface ChemistryRashad, Ahmad; Mustafa, Kamal; Heggset, Ellinor Baevre; Syverud, KristinBiomacromolecules (2017), 18 (4), 1238-1248CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)The current study aims to demonstrate the influence of the surface chem. of wood-derived cellulose nanofibril (CNF) hydrogels on fibroblasts for tissue engineering applications. TEMPO-mediated oxidn. or carboxymethylation pretreatments were employed to produce hydrogels with different surface chem. This study demonstrates the following: first, the gelation of CNF with cell culture medium and formation of stable hydrogels with improved rheol. properties; second, the response of mouse fibroblasts cultured on the surface of the hydrogels or sandwiched within the materials with respect to cytotoxicity, cell attachment, proliferation, morphol., and migration. Indirect cytotoxicity tests showed no toxic effect of either hydrogel. The direct contact with the carboxymethylated hydrogel adversely influenced the morphol. of the cells and limited their spreading, while typical morphol. and spreading of cells were obsd. with the TEMPO-oxidized hydrogel. The porous fibrous structure may be a key to cell proliferation and migration in the hydrogels.
- 10Bhattacharya, M.; Malinen, M. M.; Lauren, P.; Lou, Y. R.; Kuisma, S. W.; Kanninen, L.; Lille, M.; Corlu, A.; GuGuen-Guillouzo, C.; Ikkala, O.; Laukkanen, A.; Urtti, A.; Yliperttula, M. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. J. Controlled Release 2012, 164, 291– 298, DOI: 10.1016/j.jconrel.2012.06.03910https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVOltr7E&md5=414ada6021acb8ab4ea21c664c26347fNanofibrillar cellulose hydrogel promotes three-dimensional liver cell cultureBhattacharya, Madhushree; Malinen, Melina M.; Lauren, Patrick; Lou, Yan-Ru; Kuisma, Saara W.; Kanninen, Liisa; Lille, Martina; Corlu, Anne; GuGuen-Guillouzo, Christiane; Ikkala, Olli; Laukkanen, Antti; Urtti, Arto; Yliperttula, MarjoJournal of Controlled Release (2012), 164 (3), 291-298CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)Over the recent years, various materials were introduced as potential 3D cell culture scaffolds. These include protein exts., peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunol. point of view. Here the authors demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. The authors show (1) rheol. properties that allow formation of a 3D scaffold in-situ after facile injection, (2) cellular biocompatibility without added growth factors, (3) cellular polarization, and (4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aq. NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, the authors conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chem. testing, tissue engineering, and cell therapy.
- 11Lou, Y. R.; Kanninen, L.; Kuisma, T.; Niklander, J.; Noon, L. A.; Burks, D.; Urtti, A.; Yliperttula, M. The Use of Nanofibrillar Cellulose Hydrogel As a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem Cells. Stem Cells Dev. 2014, 23, 380– 392, DOI: 10.1089/scd.2013.031411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFChtr0%253D&md5=49970e1e82647e2bee47b86777f0529eThe Use of Nanofibrillar Cellulose Hydrogel As a Flexible Three-Dimensional Model to Culture Human Pluripotent Stem CellsLou, Yan-Ru; Kanninen, Liisa; Kuisma, Tytti; Niklander, Johanna; Noon, Luke A.; Burks, Deborah; Urtti, Arto; Yliperttula, MarjoStem Cells and Development (2014), 23 (4), 380-392CODEN: SCDTAE; ISSN:1547-3287. (Mary Ann Liebert, Inc.)Human embryonic stem cells and induced pluripotent stem cells have great potential in research and therapies. The current in vitro culture systems for human pluripotent stem cells (hPSCs) do not mimic the three-dimensional (3D) in vivo stem cell niche that transiently supports stem cell proliferation and is subject to changes which facilitate subsequent differentiation during development. Here, we demonstrate, for the first time, that a novel plant-derived nanofibrillar cellulose (NFC) hydrogel creates a flexible 3D environment for hPSC culture. The pluripotency of hPSCs cultured in the NFC hydrogel was maintained for 26 days as evidenced by the expression of OCT4, NANOG, and SSEA-4, in vitro embryoid body formation and in vivo teratoma formation. The use of a cellulose enzyme, cellulase, enables easy cell propagation in 3D culture as well as a shift between 3D and two-dimensional cultures. More importantly, the removal of the NFC hydrogel facilitates differentiation while retaining 3D cell organization. Thus, the NFC hydrogel represents a flexible, xeno-free 3D culture system that supports pluripotency and will be useful in hPSC-based drug research and regenerative medicine.
- 12Maharjan, B.; Park, J.; Kaliannagounder, V. K.; Awasthi, G. P.; Joshi, M. K.; Park, C. H.; Kim, C. S. Regenerated cellulose nanofiber reinforced chitosan hydrogel scaffolds for bone tissue engineering. Carbohydr. Polym. 2021, 251, 117023 DOI: 10.1016/j.carbpol.2020.11702312https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVajsbfN&md5=19920aa35e4d9b770eb9f0bc407ca432Regenerated cellulose nanofiber reinforced chitosan hydrogel scaffolds for bone tissue engineeringMaharjan, Bikendra; Park, Jeesoo; Kaliannagounder, Vignesh Krishnamoorthi; Awasthi, Ganesh Prasad; Joshi, Mahesh Kumar; Park, Chan Hee; Kim, Cheol SangCarbohydrate Polymers (2021), 251 (), 117023CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)Natural hydrogel scaffolds usually exhibit insufficient mech. strength which remains a major challenge in bone tissue engineering. In this study, the limitation was addressed by incorporating regenerated cellulose (rCL) nanofibers into chitosan (CS) hydrogel. The rCL nanofibers were regenerated from deacetylation of electrospun cellulose acetate (CA) nanofibers. As-prepd. rCL/CS composite scaffold showed unique porous morphol. with rCL nanofibers imbibed CS matrix. The compressive strength test exhibited that the rCL/CS scaffold have higher compressive strength compared to pure CS. The rCL/CS scaffold showed increased biomineralization and enhanced pre-osteoblast cell (MC3T3-E1) viability, attachment, and proliferation. The alk. phosphatase (ALP) and alizarin red (ARS) staining results suggested that the osteogenic differentiation ability was improved in rCL/CS composite scaffold. Hence, the novel fabrication idea and the obtained results suggested that the rCL/CS composite hydrogel scaffolds could be a promising three-dimensional bio-scaffold for bone tissue engineering.
- 13Ojansivu, M.; Rashad, A.; Ahlinder, A.; Massera, J.; Mishra, A.; Syverud, K.; Finne-Wistrand, A.; Miettinen, S.; Mustafa, K. Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabrication 2019, 11, 035010 DOI: 10.1088/1758-5090/ab069213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFCht7k%253D&md5=58b3c3fe4f31f418d316fa7b8d2d46fdWood-based nanocellulose and bioactive glass modified gelatin- alginate bioinks for 3D bioprinting of bone cellsOjansivu, Miina; Rashad, Ahmad; Ahlinder, Astrid; Massera, Jonathan; Mishra, Ayush; Syverud, Kristin; Finne-Wistrand, Anna; Miettinen, Susanna; Mustafa, KamalBiofabrication (2019), 11 (3), 035010CODEN: BIOFFN; ISSN:1758-5090. (IOP Publishing Ltd.)A challenge in the extrusion-based bioprinting is to find a bioink with optimal biol. and physicochem. properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils(CNF) and bioactive glass(BaG) on the rheol. properties of gelatin-alginate bioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chem. characterization by SEM-EDX and ion release anal. confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells(Saos2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-contg. gels and crosslinked with CaCl2. Viability, proliferation and alk. phosphatase activity (ALP)were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a const. increase in the ALP activity in all the hydrogels. Further bioprinting expts. were conducted using human bone marrow-derived mesenchymal stem cells(hBMSCs), a clin. relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addn. of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications.
- 14Shavandi, A.; Hosseini, S.; Okoro, O. V.; Nie, L.; Eghbali Babadi, F.; Melchels, F. 3D Bioprinting of Lignocellulosic Biomaterials. Adv. Healthcare Mater. 2020, 9, 2001472 DOI: 10.1002/adhm.20200147214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFeqs7fO&md5=0abd32a8ed29dcbd00770e360205d0b6Bioprinting of Lignocellulosic BiomaterialsShavandi, Amin; Hosseini, Soraya; Okoro, Oseweuba Valentine; Nie, Lei; Eghbali Babadi, Farahnaz; Melchels, FerryAdvanced Healthcare Materials (2020), 9 (24), 2001472CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The interest in bioprinting of sustainable biomaterials is rapidly growing, and lignocellulosic biomaterials have a unique role in this development. Lignocellulosic materials are biocompatible and possess tunable mech. properties, and therefore promising for use in the field of 3D-printed biomaterials. This review aims to spotlight the recent progress on the application of different lignocellulosic materials (cellulose, hemicellulose, and lignin) from various sources (wood, bacteria, and fungi) in different forms (including nanocrystals and nanofibers in 3D bioprinting). Their crystallinity, leading to water insoly. and the presence of suspended nanostructures, makes these polymers stand out among hydrogel-forming biomaterials. These unique structures give rise to favorable properties such as high ink viscosity and strength and toughness of the final hydrogel, even when used at low concns. In this review, the application of lignocellulosic polymers with other components in inks is reported for 3D bioprinting and identified supercrit. CO2 as a potential sterilization method for 3D-printed cellulosic materials. This review also focuses on the areas of potential development by highlighting the opportunities and unmet challenges such as the need for standardization of the prodn., biocompatibility, and biodegradability of the cellulosic materials that underscore the direction of future research into the 3D biofabrication of cellulose-based biomaterials.
- 15Lin, L.; Jiang, S.; Yang, J.; Qiu, J.; Jiao, X.; Yue, X.; Ke, X.; Yang, G.; Zhang, L. Application of 3D-bioprinted nanocellulose and cellulose derivative-based bio-inks in bone and cartilage tissue engineering. Int. J. Bioprint. 2022, 9, 637 DOI: 10.18063/ijb.v9i1.637There is no corresponding record for this reference.
- 16Onyianta, A. J.; Dorris, M.; Williams, R. L. Aqueous morpholine pre-treatment in cellulose nanofibril (CNF) production: comparison with carboxymethylation and TEMPO oxidisation pre-treatment methods. Cellulose 2018, 25, 1047– 1064, DOI: 10.1007/s10570-017-1631-016https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1el&md5=09bf8e13fb7ef11f5a97fafc1c92d4f6Aqueous morpholine pre-treatment in cellulose nanofibril (CNF) production: comparison with carboxymethylation and TEMPO oxidization pre-treatment methodsOnyianta, Amaka J.; Dorris, Mark; Williams, Rhodri L.Cellulose (Dordrecht, Netherlands) (2018), 25 (2), 1047-1064CODEN: CELLE8; ISSN:0969-0239. (Springer)In this study, pulped cellulose fibers were pre-treated with aq. morpholine prior to mech. disruption in the prodn. of cellulose nanofibrils (CNF). The properties of the morpholine pre-treated CNF (MCNF) were closely compared with CNF obtained from carboxymethylation (CMCNF) and TEMPO-oxidn. (TCNF) pre-treatment methods. An investigation of the swelling behaviors of cellulose in varying concns. of morpholine revealed that there is a synergistic behavior between morpholine and water in its ability to swell cellulose. As a result, cellulose pulp dispersed in 1:1 mol ratio of morpholine to water was well swollen and readily fibrillated by mech. shear. Surface chem. analyses indicated that the surface of the MCNF remained unmodified, compared to the CMCNF and TCNF which were modified with anionic groups. This resulted in only a slight decrease in crystallinity index and a minimal effect on the thermal stability of MCNF, compared to CMCNF and TCNF which showed marked decreases in crystallinity indexes and thermal stabilities. The av. widths of MCNF, CMCNF and TCNF, as measured from electron microscopic images, were broadly similar. The higher polydispersity of MCNF widths however led to a differential sedimentation and subsequent lower aspect ratio in comparison with CMCNF and TCNF as estd. using the sedimentation approach. Also, the presence of electrostatic repulsive forces, phys. interactions/entanglements and lower rigidity threshold of the CMCNF and TCNF resulted in higher storage moduli compared to the MCNF, whose elasticity is controlled by phys. interactions and entanglements. Aq. morpholine pre-treatment can potentially be regarded as an ecol. sustainable process for unmodified CNF prodn., since the chem. reagent is not consumed and can be recovered and reused.
- 17Amani, H.; Arzaghi, H.; Bayandori, M.; Dezfuli, A. S.; Pazoki-Toroudi, H.; Shafiee, A.; Moradi, L. Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques. Adv. Mater. Interfaces 2019, 6, 1900572 DOI: 10.1002/admi.201900572There is no corresponding record for this reference.
- 18Cao, B.; Peng, Y.; Liu, X.; Ding, J. Effects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned Surfaces. ACS Appl. Mater. Interfaces 2017, 9, 23574– 23585, DOI: 10.1021/acsami.7b0833918https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXpvFOlsr4%253D&md5=3d54edf5c491d9158f1444a6c3e4a50dEffects of Functional Groups of Materials on Nonspecific Adhesion and Chondrogenic Induction of Mesenchymal Stem Cells on Free and Micropatterned SurfacesCao, Bin; Peng, Yuanmeng; Liu, Xiangnan; Ding, JiandongACS Applied Materials & Interfaces (2017), 9 (28), 23574-23585CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Functional groups of materials are known to affect cell behaviors, yet the corresponding effect on stem cell differentiation is always coupled with that of cell spreading; it is thus unclear whether the chem. groups influence cell differentiation directly or via cell spreading indirectly. Herein we used a unique surface patterning technique to decouple the corresponding effects. Mesenchymal stem cells (MSCs) derived from bone marrow were seeded on surfaces coated with alkanethiols with one of four functional end groups (-CH3, -OH, -COOH, and -NH2) and underwent 9 days of chondrogenic induction. The measurements of quartz crystal microbalance with dissipation confirmed less proteins adsorbed from the cell culture media on the neutral -CH3 and -OH surfaces than on the charged -COOH and -NH2 surfaces. The neutral surfaces exhibited less cell spreading and higher extents of chondrogenic differentiation than the charged surfaces, according to the characterizations of immunofluorescence staining and quant. real-time polymerase chain reaction. We further used a transfer lithog. technique to prep. patterned surfaces on nonfouling poly(ethylene glycol) hydrogels to localize single MSCs on microislands with self-assembly monolayers of different alkanethiols, under given microisland areas and thus well-defined spreading areas of cells. While small microislands were always beneficial for chondrogenic induction, we found that the type of functional groups had no significant effect on chondrogenic induction under the given cell spreading areas, implying that the chem. groups influence cell differentiation only indirectly. Our results hence illustrate that functional groups regulate stem cell differentiation via tuning protein adsorption and then nonspecific cell adhesion and thus cell spreading.
- 19Hasan, A.; Pattanayek, S. K.; Pandey, L. M. Effect of Functional Groups of Self-Assembled Monolayers on Protein Adsorption and Initial Cell Adhesion. ACS Biomater. Sci. Eng. 2018, 4, 3224– 3233, DOI: 10.1021/acsbiomaterials.8b0079519https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVOltrzP&md5=45da8f0712f6f1e949bb23be0f823e1cEffect of Functional Groups of Self-Assembled Monolayers on Protein Adsorption and Initial Cell AdhesionHasan, Abshar; Pattanayek, Sudip K.; Pandey, Lalit M.ACS Biomaterials Science & Engineering (2018), 4 (9), 3224-3233CODEN: ABSEBA; ISSN:2373-9878. (American Chemical Society)Surface modification plays a vital role in regulating protein adsorption and subsequently cell adhesion. In the present work, we prepd. nanoscaled modified surfaces using silanization and characterized them using Fourier-transform IR spectroscopy (FTIR), water contact angle (WCA), and at. force microscopy (AFM). Five different (amine, octyl, mixed, hybrid, and COOH) surfaces were prepd. based on their functionality and varying wettability and their effect on protein adsorption and initial cell adhesion was investigated. AFM anal. revealed nanoscale roughness on all modified surfaces. Fetal bovine serum (FBS) was used for protein adsorption expt. and effect of FBS was analyzed on initial cell adhesion kinetics (up to 6 h) under three different exptl. conditions: (a) with FBS in media, (b) with preadsorbed FBS on surfaces, and (c) incomplete media, i.e., without FBS. Various cell features such as cell morphol./circularity, cell area and nuclei size were also studied for the above stated conditions at different time intervals. The cell adhesion rate as well as cell spread area were highest in the case of surfaces with preadsorbed FBS. We obsd. higher surface coverage rate by adhering cells on hybrid (rate, 0.073 h-1) and amine (0.072 h-1) surfaces followed by COOH (0.062 h-1) and other surfaces under preadsorbed FBS condition. Surface treated with cells in incomplete media exhibited least adhesion rate, poor cell spreading and improper morphol. Furthermore, we found that initial cell adhesion rate and Δadhered cells (%) linearly increased with the change in α-helix content of adsorbed FBS on surfaces. Among all the modified surfaces and under all three exptl. conditions, hybrid surface exhibited excellent properties for supporting cell adhesion and growth and hence can be potentially used as surface modifiers in biomedical applications to design biocompatible surfaces.
- 20Arima, Y.; Iwata, H. Effect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayers. Biomaterials 2007, 28, 3074– 3082, DOI: 10.1016/j.biomaterials.2007.03.01320https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXksVersrs%253D&md5=53f7ae424002f4e144950a2db5ab9f7bEffect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayersArima, Yusuke; Iwata, HirooBiomaterials (2007), 28 (20), 3074-3082CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Self-assembled monolayers (SAMs) of alkanethiols, which can provide flat and chem. well-defined surfaces, were employed as model surfaces to understand cellular interaction with artificial materials. SAMs presenting a wide range of wettabilities were prepd. by mixing 2 kinds of alkanethiols carrying terminal Me (CH3), hydroxyl (OH), carboxylic acid (COOH), or amino (NH2) groups. Adhesion behavior of human umbilical vein endothelial cells (HUVECs) and HeLa cells on these mixed SAMs were examd. The no. of adhered HUVECs reached a max. on CH3/OH mixed SAMs with a water contact angle of 40°, while cell adhesion increased with decreasing water contact angle up to 60-70° and then leveled off on CH3/COOH and CH3/NH2 mixed SAMs. Nos. of adhered HeLa cells showed a max. on CH3/OH and CH3/COOH mixed SAMs with a water contact angle of 50°. These facts suggest that cell adhesion is mainly detd. by surface wettability, but is also affected by the surface functional group, its surface d., and the kinds of cells. The effect of exchange of adsorbed proteins on cell adhesion was also examd. HUVECs were cultured on the mixed SAMs preadsorbed with albumin. Cell adhesion was effectively prohibited on hydrophobic SAMs pretreated with albumin. Albumin strongly adsorbed and resisted replacement by cell adhesive proteins on hydrophobic SAMs. On the other hand, cells adhered to albumin-adsorbed hydrophilic SAMs. Displacement of preadsorbed albumin with cell adhesive proteins effectively occurs on these hydrophilic SAMs. This effect contributes to induce SAMs with moderate wettability to give suitable surfaces for cell adhesion.
- 21Viswanathan, P.; Ondeck, M. G.; Chirasatitsin, S.; Ngamkham, K.; Reilly, G. C.; Engler, A. J.; Battaglia, G. 3D surface topology guides stem cell adhesion and differentiation. Biomaterials 2015, 52, 140– 147, DOI: 10.1016/j.biomaterials.2015.01.03421https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXisleqsLs%253D&md5=60ca8932a525ea93079ed2ef809d6ceb3D surface topology guides stem cell adhesion and differentiationViswanathan, Priyalakshmi; Ondeck, Matthew G.; Chirasatitsin, Somyot; Ngamkham, Kamolchanok; Reilly, Gwendolen C.; Engler, Adam J.; Battaglia, GiuseppeBiomaterials (2015), 52 (), 140-147CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Polymd. high internal phase emulsion (polyHIPE) foams are extremely versatile materials for investigating cell-substrate interactions in vitro. Foam morphologies can be controlled by polymn. conditions to result in either open or closed pore structures with different levels of connectivity, consequently enabling the comparison between 2D and 3D matrixes using the same substrate with identical surface chem. conditions. Addnl., here we achieve the control of pore surface topol. (i.e. how different ligands are clustered together) using amphiphilic block copolymers as emulsion stabilizers. We demonstrate that adhesion of human mesenchymal progenitor (hES-MP) cells cultured on polyHIPE foams is dependent on foam surface topol. and chem. but is independent of porosity and interconnectivity. We also demonstrate that the interconnectivity, architecture and surface topol. of the foams has an effect on the osteogenic differentiation potential of hES-MP cells. Together these data demonstrate that the adhesive heterogeneity of a 3D scaffold could regulate not only mesenchymal stem cell attachment but also cell behavior in the absence of sol. growth factors.
- 22Griffin, M. F.; Ibrahim, A.; Seifalian, A. M.; Butler, P. E. M.; Kalaskar, D. M.; Ferretti, P. Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages. Acta Biomater. 2017, 50, 450– 461, DOI: 10.1016/j.actbio.2016.12.01622https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmslantA%253D%253D&md5=9778c83eccae321e91e54dff5ad3ccddChemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineagesGriffin, M. F.; Ibrahim, A.; Seifalian, A. M.; Butler, P. E. M.; Kalaskar, D. M.; Ferretti, P.Acta Biomaterialia (2017), 50 (), 450-461CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomech. properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chem. groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14 days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymn. at 24 h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alk. phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chem. groups through plasma surface polymn. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects. Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chem. groups using plasma surface polymn. techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds resp. Plasma polymn. can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.
- 23Keselowsky, B. G.; Collard, D. M.; Garcia, A. J. Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 5953– 5957, DOI: 10.1073/pnas.040735610223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXkt1Cmur0%253D&md5=d75346b1d9b03787be65ca704cfcda90Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiationKeselowsky, Benjamin G.; Collard, David M.; Garcia, Andres J.Proceedings of the National Academy of Sciences of the United States of America (2005), 102 (17), 5953-5957CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Biomaterial surface chem. has profound consequences on cellular and host responses, but the underlying mol. mechanisms remain poorly understood. Using self-assembled monolayers as model biomaterial surfaces presenting well defined chemistries, we demonstrate that surface chem. modulates osteoblastic differentiation and matrix mineralization independently from alterations in cell proliferation. Surfaces were precoated with equal densities of fibronectin (FN), and surface chem. modulated FN structure to alter integrin adhesion receptor binding. OH- and NH2-terminated surfaces up-regulated osteoblast-specific gene expression, alk. phosphatase enzymic activity, and matrix mineralization compared with surfaces presenting COOH and CH3 groups. These surface chem.-dependent differences in cell differentiation were controlled by binding of specific integrins to adsorbed FN. Function-perturbing antibodies against the central cell binding domain of FN completely inhibited matrix mineralization. Furthermore, blocking antibodies against β1 integrin inhibited matrix mineralization on the OH and NH2 surfaces, whereas function-perturbing antibodies specific for β3 integrin increased mineralization on the COOH substrate. These results establish surface-dependent differences in integrin binding as a mechanism regulating differential cellular responses to biomaterial surfaces. This mechanism could be exploited to engineer materials that control integrin binding specificity to elicit desired cellular activities to enhance the integration of biomaterials and improve the performance of biotechnol. culture supports.
- 24Saito, T.; Isogai, A. Introduction of aldehyde groups on surfaces of native cellulose fibers by TEMPO-mediated oxidation. Colloids Surf., A 2006, 289, 219– 225, DOI: 10.1016/j.colsurfa.2006.04.03824https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtVagt7nK&md5=22f81c4a66f6848ac99c355b9aaacbc4Introduction of aldehyde groups on surfaces of native cellulose fibers by TEMPO-mediated oxidationSaito, Tsuguyuki; Isogai, AkiraColloids and Surfaces, A: Physicochemical and Engineering Aspects (2006), 289 (1-3), 219-225CODEN: CPEAEH; ISSN:0927-7757. (Elsevier B.V.)Native cellulose fibers were suspended in water and oxidized to various degrees with sodium hypochlorite and catalytic amts. of 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) and sodium bromide at pH 10.5. The oxidn. was accomplished within 30 min at room temp. The TEMPO-oxidized cellulose fibers were then converted to sheets like paper. Tensile strength of the sheets soaked in water, i.e. wet strength, showed a max. value, when 0.3 mmol NaClO per g cellulose was used in the TEMPO-mediated oxidn. Aldehyde groups up to 0.225 mmol/g were introduced in native cellulose fibers by the TEMPO-mediated oxidn., and were stably present in there. However, only surface aldehyde groups in the TEMPO-oxidized cellulose fibers contributed to the wet strength development of the sheets. Carboxylate groups were also formed not only on the surfaces but also insides of cellulose fibers by the TEMPO-mediated oxidn., although they had nearly no contribution to wet strength development of the sheets. These surface aldehyde groups forms hemiacetal linkages with cellulose hydroxyl groups at the inter-fiber bonds, resulting in the clear wet strength development of the sheets prepd. thereof. The TEMPO-mediated oxidn. is, therefore, applicable to introduction of not only carboxylate groups but also aldehyde groups to native cellulose surfaces as an efficient chem. modification under aq. conditions.
- 25Saito, T.; Okita, Y.; Nge, T. T.; Sugiyama, J.; Isogai, A. TEMPO-mediated oxidation of native cellulose: Microscopic analysis of fibrous fractions in the oxidized products. Carbohydr. Polym. 2006, 65, 435– 440, DOI: 10.1016/j.carbpol.2006.01.03425https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XotlWmtrY%253D&md5=b83d8519f579cbf20702df05b0b1dd8cTEMPO-mediated oxidation of native cellulose: Microscopic analysis of fibrous fractions in the oxidized productsSaito, T.; Okita, Y.; Nge, T. T.; Sugiyama, J.; Isogai, A.Carbohydrate Polymers (2006), 65 (4), 435-440CODEN: CAPOD8; ISSN:0144-8617. (Elsevier B.V.)The 2,2,6,6-tetramethylpiperidine-1-oxy radial (TEMPO)-mediated oxidn. was applied to aq. suspensions of cotton linters, ramie and spruce holocellulose at pH 10.5, and water-insol. fractions of the TEMPO-oxidized celluloses collected by filtration with water were analyzed by optical and transmission electron microscopy and others. The results showed that both fibrous forms and microfibrillar nature of the original native celluloses were maintained after the TEMPO-mediated oxidn., even though carboxylate and aldehyde groups of 0.67-1.16 and 0.09-0.21 mmol/g, resp., were introduced into the water-insol. fractions. Neither crystallinity nor crystal size of cellulose I of the original native celluloses was changed under the conditions adopted in this study. Carboxylate groups in the TEMPO-oxidized ramie were mapped by labeling with lead ions as their counter ions. The transmission electron micrographs indicated that some heterogeneous distribution of carboxylate groups along each cellulose microfibril or each bundle of cellulose microfibrils seemed to be present in the TEMPO-oxidized celluloses.
- 26Yamada, S.; Yassin, M. A.; Weigel, T.; Schmitz, T.; Hansmann, J.; Mustafa, K. Surface activation with oxygen plasma promotes osteogenesis with enhanced extracellular matrix formation in three-dimensional microporous scaffolds. J. Biomed. Mater. Res. A 2021, 109, 1560– 1574, DOI: 10.1002/jbm.a.3715126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlslSqsbk%253D&md5=6b6f8af23889ec892a037dfdfa1803e0Surface activation with oxygen plasma promotes osteogenesis with enhanced extracellular matrix formation in three-dimensional microporous scaffoldsYamada, Shuntaro; Yassin, Mohammed A.; Weigel, Tobias; Schmitz, Tobias; Hansmann, Jan; Mustafa, KamalJournal of Biomedical Materials Research, Part A (2021), 109 (9), 1560-1574CODEN: JBMRCH; ISSN:1549-3296. (John Wiley & Sons, Inc.)Various types of synthetic polyesters have been developed as biomaterials for tissue engineering. These materials commonly possess biodegradability, biocompatibility, and formability, which are preferable properties for bone regeneration. The major challenge of using synthetic polyesters is the result of low cell affinity due to their hydrophobic nature, which hinders efficient cell seeding and active cell dynamics. To improve wettability, plasma treatment is widely used in industry. Here, we performed surface activation with oxygen plasma to hydrophobic copolymers, poly(L-lactide-co-trimethylene carbonate), which were shaped in 2D films and 3D microporous scaffolds, and then we evaluated the resulting surface properties and the cellular responses of rat bone marrow stem cells (rBMSC) to the material. Using SEM and Fourier-transform IR spectroscopy, we demonstrated that short-term plasma treatment increased nanotopog. surface roughness and wettability with minimal change in surface chem. On treated surfaces, initial cell adhesion and elongation were significantly promoted, and seeding efficiency was improved. In an osteoinductive environment, rBMSC on plasma-treated scaffolds exhibited accelerated osteogenic differentiation with osteogenic markers including RUNX2, osterix, bone sialoprotein, and osteocalcin upregulated, and a greater amt. of collagen matrix and mineral deposition were found. This study shows the utility of plasma surface activation for polymeric scaffolds in bone tissue engineering.
- 27Jaušovec, D.; Vogrinčič, R.; Kokol, V. Introduction of aldehyde vs. carboxylic groups to cellulose nanofibers using laccase/TEMPO mediated oxidation. Carbohydr. Polym. 2015, 116, 74– 85, DOI: 10.1016/j.carbpol.2014.03.01427https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlt1Wgtbc%253D&md5=e4cba0de540350945e489cdba07ced6cIntroduction of aldehyde vs. carboxylic groups to cellulose nanofibers using laccase/TEMPO mediated oxidationJausovec, Darja; Vogrincic, Robert; Kokol, VanjaCarbohydrate Polymers (2015), 116 (), 74-85CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The chemo-enzymic modification of cellulose nanofibers (CNFs) using laccase as biocatalysts and TEMPO or 4-Amino-TEMPO as mediators under mild aq. conditions (pH 5, 30 °C) has been investigated to introduce surface active aldehyde groups. 4-Amino TEMPO turned out to be kinetically 0.5-times (50%) more active mediator, resulting to oxoammonium cation intermediacy generated and its in situ regeneration during the modification of CNFs. Accordingly, beside of around 750 mmol/kg terminally-located aldehydes, originated during CNFs isolation, the reaction resulted to about 140% increase of C6-located aldehydes at optimal conditions, without reducing CNFs crystallinity. While only the C6-aldehydes were wholly transformed into the carboxyls after addnl. post-treatment using NaOH according to the Cannizzaro reaction, the post-oxidn. with air-oxygen in EtOH/water medium or NaClO2 resulted to no- or very small amts. of carboxyls created, resp., at a simultaneous loss of all C6- and some terminal-aldehydes in the latter due to the formation of highly-resistant hemiacetal covalent linkages with available cellulose hydroxyls. The results indicated a new way of prepg. and stabilizing highly reactive C6-aldehydes on cellulose, and their exploitation in the development of new nanocellulose-based materials.
- 28Nechyporchuk, O.; Belgacem, M. N.; Pignon, F. Current Progress in Rheology of Cellulose Nanofibril Suspensions. Biomacromolecules 2016, 17, 2311– 2320, DOI: 10.1021/acs.biomac.6b0066828https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XpvVWktrc%253D&md5=9375c07b97738e73c1aebcf458ad2170Current Progress in Rheology of Cellulose Nanofibril SuspensionsNechyporchuk, Oleksandr; Belgacem, Mohamed Naceur; Pignon, FredericBiomacromolecules (2016), 17 (7), 2311-2320CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Cellulose nanofibrils (CNFs) are produced and commonly used in the form of aq. suspensions or gels. A no. of studies have focused lately on rheol. properties of CNF suspensions, which gives insight into properties of such materials and can reflect their behavior during handling. This Review summarizes the recent progress in rheol. studies on CNF aq. suspensions using rotational rheometry. Here, we discuss linear viscoelastic properties, i.e., frequency-dependent storage and loss moduli; shear flow behavior, i.e., apparent viscosity and shear stress as a function of shear rate; local flow characteristics, etc. In this Review, we point out that the rheol. behavior of at least two types of CNF suspensions should be distinguished: (i) ones produced using mech. fibrillation with or without enzymic pretreatment (no surface chem. modification), which possess highly flocculated structure, and (ii) ones produced involving chem. modification pretreatments, e.g., carboxylation, carboxymethylation, quaternization, or sulfonation, which possess better colloidal stability and do not evidently flocculate.
- 29Wang, R. F.; Rosen, T.; Zhan, C. B.; Chodankar, S.; Chen, J. H.; Sharma, P. R.; Sharma, S. K.; Liu, T. B.; Hsiao, B. S. Morphology and Flow Behavior of Cellulose Nanofibers Dispersed in Glycols. Macromolecules 2019, 52, 5499– 5509, DOI: 10.1021/acs.macromol.9b0103629https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKjt7jJ&md5=961304ac9dacf1cf5e696c3edee46395Morphology and Flow Behavior of Cellulose Nanofibers Dispersed in GlycolsWang, Ruifu; Rosen, Tomas; Zhan, Chengbo; Chodankar, Shirish; Chen, Jiahui; Sharma, Priyanka R.; Sharma, Sunil K.; Liu, Tianbo; Hsiao, Benjamin S.Macromolecules (Washington, DC, United States) (2019), 52 (15), 5499-5509CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)Understanding the morphol. and flow behavior of cellulose nanofibers (CNFs) dispersed in org. solvents can improve the process of fabricating new cellulose-based nanocomposites. In this study, jute-based 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized CNFs with two different charge densities (0.64 and 1.03 mmol/g) were dispersed in ethylene glycol (EG) and propylene glycol (PG) using the solvent exchange method. The morphol. and dimensions of CNFs in dry and suspension states were characterized using TEM, at. force microscopy, and small-angle x-ray scattering techniques. The cross-sectional dimensions remained the same in different solvents. Rheol. measurements revealed that CNF suspensions in water or glycol (EG and PG) behaved similar to typical polymer solns. with a solvent-independent overlap concn. corresponding to the crowding factor of about 14. Furthermore, a thixotropic behavior was found in the concd. CNF/glycol systems as obsd. in typical CNF aq. suspensions. The fact that TEMPO-oxidized CNFs can be well dispersed in org. solvents opens up new possibilities to improve the CNF-polymer matrix blending, where the use of a viscous solvent can delay the transition to turbulence in processing and improve the control of fiber orientation because of a slower Brownian diffusive motion.
- 30Osong, S. H.; Norgren, S.; Engstrand, P. Processing of wood-based microfibrillated cellulose and nanofibrillated cellulose, and applications relating to papermaking: a review. Cellulose 2016, 23, 93– 123, DOI: 10.1007/s10570-015-0798-530https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGltL7K&md5=797786edf044c38994c3950c934193ccProcessing of wood-based microfibrillated cellulose and nanofibrillated cellulose, and applications relating to papermaking: a reviewOsong, Sinke H.; Norgren, Sven; Engstrand, PerCellulose (Dordrecht, Netherlands) (2016), 23 (1), 93-123CODEN: CELLE8; ISSN:0969-0239. (Springer)A review. As an emerging cellulosic nanomaterial, microfibrillated cellulose (MFC) and nanofibrillated cellulose (NFC) have shown enormous potential in the forest products industry. The forest products industry and academia are working together to realize the possibilities of commercializing MFC and NFC. However, there are still needs to improve the processing, characterization and material properties of nanocellulose in order to realize its full potential. The annual no. of research publications and patents on nanocellulose with respect to manufg., properties and applications is now up in the thousands, so it is of the utmost importance to review articles that endeavour to research on this explosive topic of cellulose nanomaterials. This review examines the past and current situation of wood-based MFC and NFC in relation to its processing and applications relating to papermaking.
- 31Wang, L.; Li, K.; Copenhaver, K.; Mackay, S.; Lamm, M. E.; Zhao, X.; Dixon, B.; Wang, J.; Han, Y.; Neivandt, D.; Johnson, D. A.; Walker, C. C.; Ozcan, S.; Gardner, D. J. Review on Nonconventional Fibrillation Methods of Producing Cellulose Nanofibrils and Their Applications. Biomacromolecules 2021, 22, 4037– 4059, DOI: 10.1021/acs.biomac.1c0064031https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvFymtLzM&md5=3d36dd87639eeeb9b481e961239535ecReview on Nonconventional Fibrillation Methods of Producing Cellulose Nanofibrils and Their ApplicationsWang, Lu; Li, Kai; Copenhaver, Katie; Mackay, Susan; Lamm, Meghan E.; Zhao, Xianhui; Dixon, Brandon; Wang, Jinwu; Han, Yousoo; Neivandt, David; Johnson, Donna A.; Walker, Colleen C.; Ozcan, Soydan; Gardner, Douglas J.Biomacromolecules (2021), 22 (10), 4037-4059CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)A review. The prodn. of cellulose nanofibrils (CNFs) continues to receive considerable attention because of their desirable material characteristics for a variety of consumer applications. There are, however, challenges that remain in transitioning CNFs from research to widespread adoption in the industrial sectors, including prodn. cost and material performance. This Review covers CNFs produced from nonconventional fibrillation methods as a potential alternative soln. Pretreating biomass by biol., chem., mech., or phys. means can render plant feedstocks more facile for processing and thus lower energy requirements to produce CNFs. CNFs from nonconventional fibrillation methods have been investigated for various applications, including films, composites, aerogels, and Pickering emulsifiers. Continued research is needed to develop protocols to standardize the characterization (e.g., degree of fibrillation) of the lignocellulosic fibrillation processes and resulting CNF products to make them more attractive to the industry for specific product applications.
- 32Wu, C. N.; Saito, T.; Yang, Q. L.; Fukuzumi, H.; Isogai, A. Increase in the Water Contact Angle of Composite Film Surfaces Caused by the Assembly of Hydrophilic Nanocellulose Fibrils and Nanoclay Platelets. ACS Appl. Mater. Interfaces 2014, 6, 12707– 12712, DOI: 10.1021/am502701e32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtVOjtL%252FP&md5=1c03e11b05db02364cffb4957541affcIncrease in the Water Contact Angle of Composite Film Surfaces Caused by the Assembly of Hydrophilic Nanocellulose Fibrils and Nanoclay PlateletsWu, Chun-Nan; Saito, Tsuguyuki; Yang, Quanling; Fukuzumi, Hayaka; Isogai, AkiraACS Applied Materials & Interfaces (2014), 6 (15), 12707-12712CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A procedure for increasing water contact angles (CAs) of composite film surfaces via the assembly of two different hydrophilic components, nanocellulose fibrils and nanoclay platelets, is reported. The nanocellulose fibrils and nanoclay platelets have ionic groups on their surfaces in high densities (∼1 mmol g-1) and have no hydrophobic surface. The increase in the CA of the nanocellulose/nanoclay composite films was thus analyzed on the basis of the air area fractions of their nanostructured surfaces following Cassie's law. The air area fractions were geog. estd. from the at. force microscopy height profiles of the composite film surfaces. The CAs of the composite film surfaces were found to be well described by Cassie's law. The composite films consisting of two hydrophilic nanoelements with different shapes exhibited CAs larger than those of the individual neat films.
- 33Lopes, V. R.; Stromme, M.; Ferraz, N. In Vitro Biological Impact of Nanocellulose Fibers on Human Gut Bacteria and Gastrointestinal Cells. Nanomaterials 2020, 10, 1159 DOI: 10.3390/nano1006115933https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVOhtL3F&md5=50a79b4d6af794e0ba7e1354204bc696In vitro biological impact of nanocellulose fibers on human gut bacteria and gastrointestinal cellsLopes, Viviana R.; Stromme, Maria; Ferraz, NataliaNanomaterials (2020), 10 (6), 1159CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Wood-derived nanofibrillated cellulose (NFC) has long been recognized as a valuable nanomaterial for food-related applications. However, the safety of NFC cannot be predicted just from the chem. nature of cellulose, and there is a need to establish the effect of the nanofibers on the gastrointestinal tract, to reassure the safe use of NFC in food-related products. The present work selected the intestinal cells Caco-2 and the gut bacteria Escherichia coli and Lactobacillus reuteri to evaluate the in vitro biol. response to NFC. NFC materials with different surface modifications(carboxymethylation, hydroxypropyl tri-Me ammonium-substitution, phosphorylation, and sulfoethylation) and unmodified NFC were investigated. The materials were characterized in terms of surface functional group content, fiber morphol., zeta potential and degree of crystallinity. The Caco-2 cell response to the materials was evaluated by assessing metabolic activity and cell membrane integrity. The effects of the NFC materials on the model bacteria were evaluated by measuring bacterial growth (optical d. at 600 nm) and by detg. colony forming units counts after NFC exposure. Results showed no sign of cytotoxicity in Caco-2 cells exposed to the NFC materials, and NFC surface functionalization did not impact the cell response. Interestingly, a bacteriostatic effect on E. coli was obsd. while the materials did not affect the growth of L. reuteri. The present findings are foreseen to contribute to increase the knowledge about the potential oral toxicity of NFC and, in turn, add to the development of safe NFC-based food products.
- 34Pajorova, J.; Skogberg, A.; Hadraba, D.; Broz, A.; Travnickova, M.; Zikmundova, M.; Honkanen, M.; Hannula, M.; Lahtinen, P.; Tomkova, M.; Bacakova, L.; Kallio, P. Cellulose Mesh with Charged Nanocellulose Coatings as a Promising Carrier of Skin and Stem Cells for Regenerative Applications. Biomacromolecules 2020, 21, 4857– 4870, DOI: 10.1021/acs.biomac.0c0109734https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1SgtbnL&md5=43ce36c938b77a631813a56b49a00892Cellulose Mesh with Charged Nanocellulose Coatings as a Promising Carrier of Skin and Stem Cells for Regenerative ApplicationsPajorova, Julia; Skogberg, Anne; Hadraba, Daniel; Broz, Antonin; Travnickova, Martina; Zikmundova, Marketa; Honkanen, Mari; Hannula, Markus; Lahtinen, Panu; Tomkova, Maria; Bacakova, Lucie; Kallio, PasiBiomacromolecules (2020), 21 (12), 4857-4870CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)Engineering artificial skin constructs is an ongoing challenge. An ideal material for hosting skin cells is still to be discovered. A promising candidate is low-cost cellulose, which is commonly fabricated in the form of a mesh and is applied as a wound dressing. Unfortunately, the structure and the topog. of current cellulose meshes are not optimal for cell growth. To enhance the surface structure and the physicochem. properties of a com. available mesh, we coated the mesh with wood-derived cellulose nanofibrils (CNFs). Three different types of mesh coatings are proposed in this study as a skin cell carrier: pos. charged cationic cellulose nanofibrils (cCNFs), neg. charged anionic cellulose nanofibrils (aCNFs), and a combination of these two materials (c+aCNFs). These cell carriers were seeded with normal human dermal fibroblasts (NHDFs) or with human adipose-derived stem cells (ADSCs) to investigate cell adhesion, spreading, morphol., and proliferation. The neg. charged aCNF coating significantly improved the proliferation of both cell types. The pos. charged cCNF coating significantly enhanced the adhesion of ADSCs only. The no. of NHDFs was similar on the cCNF coatings and on the noncoated pristine cellulose mesh. However, the three-dimensional (3D) structure of the cCNF coating promoted cell survival. The c+aCNF construct proved to combine benefits from both types of CNFs, which means that the c+aCNF cell carrier is a promising candidate for further application in skin tissue engineering.
- 35Hoven, V.; Tangpasuthadol, V.; Angkitpaiboon, Y.; Vallapa, N.; Kiatkamjornwong, S. Surface-charged chitosan: Preparation and protein adsorption. Carbohydr. Polym. 2007, 68, 44– 53, DOI: 10.1016/j.carbpol.2006.07.00835https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsF2itb8%253D&md5=e6fa60f2a4623548a07f168463bd1472Surface-charged chitosan: Preparation and protein adsorptionHoven, Voravee P.; Tangpasuthadol, Varawut; Angkitpaiboon, Yaowamand; Vallapa, Napanporn; Kiatkamjornwong, SudaCarbohydrate Polymers (2007), 68 (1), 44-53CODEN: CAPOD8; ISSN:0144-8617. (Elsevier B.V.)Pos. and neg. charges were introduced to chitosan surfaces via methylation using Me iodide (MeI) and reductive alkylation using 5-formyl-2-furan sulfonic acid (FFSA). Attenuated total reflectance-Fourier transform IR (ATR-FTIR) spectroscopy, XPS and zeta potential measurement confirmed the presence of the desired functional groups on the surface-modified chitosan films. The chitosan films having neg. charges of N-sulfofurfuryl groups on their surface (SFC films) exhibited selective protein adsorption against both neg. charged proteins (albumin and fibrinogen) and pos. charged proteins (RNase, lysozyme). Its adsorption can be explained in terms of electrostatic attraction and repulsion. In contrast, the adsorption behavior of chitosan films having pos. charges of quaternary ammonium groups on their surface (QAC films) was anomalous. The quantity of the adsorbed protein tended to increase as a function of the swelling ratio of the QAC film regardless of the charge characteristics of the protein.
- 36Shalumon, K. T.; Anulekha, K. H.; Chennazhi, K. P.; Tamura, H.; Nair, S. V.; Jayakumar, R. Fabrication of chitosan/poly(caprolactone) nanofibrous scaffold for bone and skin tissue engineering. Int. J. Biol. Macromol. 2011, 48, 571– 576, DOI: 10.1016/j.ijbiomac.2011.01.02036https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXksFynu78%253D&md5=f8e045c72389b6c801e3c426ecbeffdbFabrication of chitosan/poly(caprolactone) nanofibrous scaffold for bone and skin tissue engineeringShalumon, K. T.; Anulekha, K. H.; Chennazhi, K. P.; Tamura, H.; Nair, S. V.; Jayakumar, R.International Journal of Biological Macromolecules (2011), 48 (4), 571-576CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)Chitosan/poly(caprolactone) (CS/PCL) nanofibrous scaffold was prepd. by a single step electrospinning technique. The presence of CS in CS/PCL scaffold aided a significant improvement in the hydrophilicity of the scaffold as confirmed by a decrease in contact angle, which thereby enhanced bioactivity and protein adsorption on the scaffold. The cytocompatibility of the CS/PCL scaffold was examd. using human osteoscarcoma cells (MG63) and found to be non toxic. Moreover, CS/PCL scaffold was found to support the attachment and proliferation of various cell lines such as mouse embryo fibroblasts (NIH3T3), murine aneuploid fibrosarcoma (L929), and MG63 cells. Cell attachment and proliferation was further confirmed by nuclear staining using 4',6-diamidino-2-phenylindole (DAPI). All these results indicate that CS/PCL nanofibrous scaffold would be an excellent system for bone and skin tissue engineering.
- 37Yang, D. Y.; Lu, X. Y.; Hong, Y.; Xi, T. F.; Zhang, D. Y. The molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterials. Biomaterials 2013, 34, 5747– 5758, DOI: 10.1016/j.biomaterials.2013.04.02837https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnt1Sgtb0%253D&md5=d3e3604c0d0a388bfcfe05f1fd4079bdThe molecular mechanism of mediation of adsorbed serum proteins to endothelial cells adhesion and growth on biomaterialsYang, Dayun; Lu, Xiaoying; Hong, Ying; Xi, Tingfei; Zhang, DeyuanBiomaterials (2013), 34 (23), 5747-5758CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)To explore mol. mechanism of mediation of adsorbed proteins to cell adhesion and growth on biomaterials, this study examd. endothelial cell adhesion, morphol. and viability on bare and titanium nitride (TiN) coated nickel titanium (NiTi) alloys and chitosan film firstly, and then identified the type and amt. of serum proteins adsorbed on the three surfaces by proteomic technol. Subsequently, the mediation role of the identified proteins to cell adhesion and growth was investigated with bioinformatics analyses, and further confirmed by a series of cellular and mol. biol. expts. Results showed that the type and amt. of adsorbed serum proteins assocd. with cell adhesion and growth was obviously higher on the alloys than on the chitosan film, and these proteins mediated endothelial cell adhesion and growth on the alloys via four ways. First, proteins such as adiponectin in the adsorbed protein layer bound with cell surface receptors to generate signal transduction, which activated cell surface integrins through increasing intracellular calcium level. Another way, thrombospondin 1 in the adsorbed protein layer promoted TGF-β signaling pathway activation and enhanced integrins expression. The third, RGD sequence contg. proteins such as fibronectin 1, vitronectin and thrombospondin 1 in the adsorbed protein layer bound with activated integrins to activate focal adhesion pathway, increased focal adhesion formation and actin cytoskeleton organization and mediated cell adhesion and spreading. In addn., the activated focal adhesion pathway promoted the expression of cell growth related genes and resulted in cell proliferation. The fourth route, coagulation factor II (F2) and fibronectin 1 in the adsorbed protein layer bound with cell surface F2 receptor and integrin, activated regulation of actin cytoskeleton pathway and regulated actin cytoskeleton organization.
- 38Giamblanco, N.; Yaseen, M.; Zhavnerko, G.; Lu, J. R.; Marletta, G. Fibronectin conformation switch induced by coadsorption with human serum albumin. Langmuir 2011, 27, 312– 319, DOI: 10.1021/la104127q38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCltb7N&md5=a47aea98fe19f4a09d0100b2916dd668Fibronectin Conformation Switch Induced by Coadsorption with Human Serum AlbuminGiamblanco, Nicoletta; Yaseen, Mohammed; Zhavnerko, Genady; Lu, Jian R.; Marletta, GiovanniLangmuir (2011), 27 (1), 312-319CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)The dynamic adsorption of human serum albumin (HSA) and plasma fibronectin (Fn) onto hydrophobic poly(hydroxymethylsiloxane) (PHMS) and the structures of adsorbed protein layers from single and binary protein solns. were studied. Spectroscopic ellipsometry (SE) and quartz crystal microbalance with dissipation monitoring (QCM-D) together with at. force microscopy (AFM) were used to measure the effective mass, thickness, viscoelastic properties, and morphol. of the adsorbed protein films. Adsorbed HSA formed a rigid, tightly bound monolayer of deformed protein, and Fn adsorption yielded a thick, very viscoelastic layer that was firmly bound to the substrate. The mixed protein layers obtained from the coadsorption of binary equimol. HSA-Fn solns. are almost exclusively dominated by Fn mols. Further sequential adsorption expts. showed little evidence of HSA adsorbed onto the predeposited Fn layer (denoted as Fn » HSA), and Fn was not adsorbed onto predeposited HSA (HSA » Fn). The conformational arrangement of the adsorbed Fn was analyzed in terms of the relative availability of two Fn domains. In particular, 4F1·5F1 binding domains in the Hep I fragment, close to the amino terminal of Fn, were targeted using a polyclonal antifibronectin antibody (anti-Fn), and the RGD sequence in the 10th segment, in the central region of the mol., was tested by cell culture expts. The results suggested that coadsorption with HSA induced the Fn switch from an open conformation, with the amino terminal subunit oriented toward the soln., to a close conformation, with the Fn central region oriented toward the soln.
- 39Othman, Z.; Pastor, B. C.; van Rijt, S.; Habibovic, P. Understanding interactions between biomaterials and biological systems using proteomics. Biomaterials 2018, 167, 191– 204, DOI: 10.1016/j.biomaterials.2018.03.02039https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlt1Sqt7k%253D&md5=2d7ffb5dd7410eaf7255a71bb7b53218Understanding interactions between biomaterials and biological systems using proteomicsOthman, Ziryan; Cillero Pastor, Berta; van Rijt, Sabine; Habibovic, PamelaBiomaterials (2018), 167 (), 191-204CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)A review. The role that biomaterials play in the clin. treatment of damaged organs and tissues is changing. While biomaterials used in permanent medical devices were required to passively take over the function of a damaged tissue in the long term, current biomaterials are expected to trigger and harness the self-regenerative potential of the body in situ and then to degrade, the foundation of regenerative medicine. To meet these different requirements, it is imperative to fully understand the interactions biomaterials have with biol. systems, in space and in time. This knowledge will lead to a better understanding of the regenerative capabilities of biomaterials aiding their design with improved functionalities (e.g. biocompatibility, bioactivity). Proteins play a pivotal role in the interaction between biomaterials and cells or tissues. Protein adsorption on the material surface is the very first event of this interaction, which is determinant for the subsequent processes of cell growth, differentiation, and extracellular matrix formation. Against this background, the aim of the current review is to provide insight in the current knowledge of the role of proteins in cell-biomaterial and tissue-biomaterial interactions. In particular, the focus is on proteomics studies, mainly using mass spectrometry, and the knowledge they have generated on protein adsorption of biomaterials, protein prodn. by cells cultured on materials, safety and efficacy of new materials based on nanoparticles and the anal. of extracellular matrixes and extracellular matrix-derived products. In the outlook, the potential and limitations of this approach are discussed and mass spectrometry imaging is presented as a powerful technique that complements existing mass spectrometry techniques by providing spatial mol. information about the material-biol. system interactions.
- 40Hua, K.; Carlsson, D. O.; Ålander, E.; Lindström, T.; Strømme, M.; Mihranyan, A.; Ferraz, N. Translational study between structure and biological response of nanocellulose from wood and green algae. RSC Adv. 2014, 4, 2892– 2903, DOI: 10.1039/c3ra45553j40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFCrtLvP&md5=b3b456f8cd45b55624e25ceaeda022adTranslational study between structure and biological response of nanocellulose from wood and green algaeHua, Kai; Carlsson, Daniel O.; Aalander, Eva; Lindstroem, Tom; Stromme, Maria; Mihranyan, Albert; Ferraz, NataliaRSC Advances (2014), 4 (6), 2892-2903CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The influence of nanostructure on the cytocompatibility of cellulose films is analyzed providing insight into how physicochem. properties of surface modified microfibrillated cellulose (MFC) and Cladophora nanocellulose (CC) affect the materials cytocompatibility. CC is modified through TEMPO-mediated oxidn. and glycidyltrimethylammonium chloride (EPTMAC) condensation to obtain anionic and cationic nanocellulose samples resp., while anionic and cationic MFC samples are obtained by carboxymethylation and EPTMAC condensation resp. Films of unmodified, anionic and cationic MFC and CC are prepd. by vacuum filtration and characterized in terms of sp. surface area, pore size distribution, degree of crystallinity, surface charge and water content. Human dermal fibroblasts are exposed to culture medium exts. of the films in an indirect contact cytotoxicity test. Moreover, cell adhesion and viability are evaluated in a direct contact assay and the effects of the physicochem. properties on cell behavior are discussed. In the indirect cytotoxicity test no toxic leachables are detected, evidencing that the CC and MFC materials are non-cytotoxic, independently of the chem. treatment that they have been subjected to. The direct contact tests show that carboxymethylated-MFC presents a more cytocompatible profile than unmodified and trimethylammonium-MFC. TEMPO-CC promotes fibroblast adhesion and presents cell viability comparable to the results obtained with the tissue culture material Thermanox. We hypothesize that the distinct aligned nanofiber structure present in the TEMPO-CC films is responsible for the improved cell adhesion. Thus, by controlling the surface properties of cellulose nanofibers, such as chem., charge, and orientation, cell adhesion properties can be promoted.
- 41Alexandrescu, L.; Syverud, K.; Gatti, A.; Chinga-Carrasco, G. Cytotoxicity tests of cellulose nanofibril-based structures. Cellulose 2013, 20, 1765– 1775, DOI: 10.1007/s10570-013-9948-941https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1WqtLfE&md5=97d3c3ab35c74ca86888f72f2cbb8248Cytotoxicity tests of cellulose nanofibril-based structuresAlexandrescu, Laura; Syverud, Kristin; Gatti, Antonietta; Chinga-Carrasco, GaryCellulose (Dordrecht, Netherlands) (2013), 20 (4), 1765-1775CODEN: CELLE8; ISSN:0969-0239. (Springer)Cellulose nanofibrils based on wood pulp fibers are most promising for biomedical applications. Bacterial cellulose has been suggested for some medical applications and is presently used as wound dressing. However, cost-efficient processes for mass prodn. of bacterial cellulose are lacking. Hence, fibrillation of cellulose wood fibers is most interesting, as the cellulose nanofibrils can efficiently be produced in large quantities. However, the utilization of cellulose nanofibrils from wood requires a thorough verification of its biocompatibility, esp. with fibroblast cells which are important in regenerative tissue and particularly in wound healing. The cellulose nanofibril structures used in this study were based on Eucalyptus and Pinus radiata pulp fibers. The nanofibrillated materials were manufd. using a homogenizer without pre-treatment and with 2,2,6,6-tetramethylpiperidine-1-oxy radical as pre-treatment, thus yielding nanofibrils low and high level of anionic charge, resp. From these materials, two types of nanofibril-based structures were formed; (1) thin and dense structures and (2) open and porous structures. Cytotoxicity tests were applied on the samples, which demonstrated that the nanofibrils do not exert acute toxic phenomena on the tested fibroblast cells (3T3 cells). The cell membrane, cell mitochondrial activity and the DNA proliferation remained unchanged during the tests, which involved direct and indirect contact between the nano-structured materials and the 3T3 cells. Some samples were modified using the crosslinking agent polyethyleneimine (PEI) or the surfactant cetyl trimethylammonium bromide (CTAB). The sample modified with CTAB showed a clear toxic behavior, having neg. effects on cell survival, viability and proliferation. CTAB is an antimicrobial component, and thus this result was as expected. The sample crosslinked with PEI also had a significant redn. in cell viability indicating a redn. in DNA proliferation. We conclude that the neat cellulose nanostructured materials tested in this study are not toxic against fibroblasts cells. This is most important as nano-structured materials based on nanofibrils from wood pulp fibers are promising as substrate for regenerative medicine and wound healing.
- 42Čolić, M.; Mihajlovićic, D.; Mathew, A.; Naseri, N.; Kokol, V. Cytocompatibility and immunomodulatory properties of wood based nanofibrillated cellulose. Cellulose 2015, 22, 763– 778, DOI: 10.1007/s10570-014-0524-842https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVyhurrL&md5=1617ee8867d141689d686c89cfa083c9Cytocompatibility and immunomodulatory properties of wood based nanofibrillated celluloseColic, Miodrag; Mihajlovic, Dusan; Mathew, Aji; Naseri, Narges; Kokol, VanjaCellulose (Dordrecht, Netherlands) (2015), 22 (1), 763-778CODEN: CELLE8; ISSN:0969-0239. (Springer)Cellulose nanofibrils (CNFs), unique and promising natural materials have gained significant attention recently for biomedical applications, due to their special biomech. characteristics, surface chem., good biocompatibility and low toxicity. However, their long bio-persistence in the organism may provoke immune reactions and this aspect of CNFs has not been studied to date. Therefore, the aim of this work was to examine and compare the cytocompatibility and immunomodulatory properties of CNFs in vitro. CNFs (diams. of 10-70 nm; lengths of a few microns) were prepd. from Norway spruce (Picea abies) by mech. fibrillation and high pressure homogenization. L929 cells, rat thymocytes or human peripheral blood mononuclear cells (PBMNCs) were cultivated with CNFs. None of the six concns. of CNFs (31.25 μg/mL-1 mg/mL) induced cytotoxicity and oxidative stress in the L929 cells, nor induced necrosis and apoptosis of thymocytes and PBMNCs. Higher concns. (250 μg/mL-1 mg/mL) slightly inhibited the metabolic activities of the L929 cells as a consequence of inhibited proliferation. The same concns. of CNFs suppressed the proliferation of PBMNCs to phytohemaglutinine, a T-cell mitogen, and the process was followed by down-regulation of interleukin-2 (IL-2) and interferon-γ prodn. The highest concn. of CNFs inhibited IL-17A, but increased IL-10 and IL-6 prodn. The secretion of pro-inflammatory cytokines, IL-1β and tumor necrosis factor-α as well as Th2 cytokine (IL-4), remained unaltered. In conclusion, the results suggest that these CNFs are cytocompatible nanomaterial, according to current ISO criteria, with non-inflammatory and non-immunogenic properties. Higher concns. seem to be tolerogenic to the immune system, a characteristic very desirable for implantable biomaterials.
- 43Hua, K.; Rocha, I.; Zhang, P.; Gustafsson, S.; Ning, Y.; Stromme, M.; Mihranyan, A.; Ferraz, N. Transition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated Nanocellulose. Biomacromolecules 2016, 17, 1224– 1233, DOI: 10.1021/acs.biomac.6b0005343https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xis1amsbs%253D&md5=b02c030f76e1352c796009e5a74d59bcTransition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated NanocelluloseHua, Kai; Rocha, Igor; Zhang, Peng; Gustafsson, Simon; Ning, Yi; Stroemme, Maria; Mihranyan, Albert; Ferraz, NataliaBiomacromolecules (2016), 17 (3), 1224-1233CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)This work presents an insight into the relationship between cell response and physicochem. properties of Cladophora cellulose (CC) by investigating the effect of CC functional group d. on the response of model cell lines. CC was carboxylated by electrochem. TEMPO-mediated oxidn. By varying the amt. of charge passed through the electrolysis setup, CC materials with different degrees of oxidn. were obtained. The effect of carboxyl group d. on the material's physicochem. properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased sp. surface area and smaller total pore vol. compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore vol., and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group d. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidn. increased. It was found that a threshold value in carboxyl group d. needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to com. tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the d. of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials.
- 44Loh, E. Y. X.; Fauzi, M. B.; Ng, M. H.; Ng, P. Y.; Ng, S. F.; Ariffin, H.; Amin, M. C. I. M. Cellular and Molecular Interaction of Human Dermal Fibroblasts with Bacterial Nanocellulose Composite Hydrogel for Tissue Regeneration. ACS Appl. Mater. Interfaces 2018, 10, 39532– 39543, DOI: 10.1021/acsami.8b16645There is no corresponding record for this reference.
- 45Arima, Y.; Iwata, H. Preferential adsorption of cell adhesive proteins from complex media on self-assembled monolayers and its effect on subsequent cell adhesion. Acta Biomater. 2015, 26, 72– 81, DOI: 10.1016/j.actbio.2015.08.03345https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVyis7jJ&md5=baaadbe4f5b6140dbd6d4d21a570bd56Preferential adsorption of cell adhesive proteins from complex media on self-assembled monolayers and its effect on subsequent cell adhesionArima, Yusuke; Iwata, HirooActa Biomaterialia (2015), 26 (), 72-81CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)We examd. the effect of surface chem. on adsorption of fibronectin (Fn) and vitronectin (Vn) and subsequent cell adhesion, employing self-assembled monolayers (SAMs) of alkanethiols carrying terminal Me (CH3), hydroxyl groups (OH), carboxylic acid (COOH), and amine (NH2). More Fn and Vn adsorbed to COOH- and NH2-SAMs than to CH3- and OH-SAMs from a mixt. with bovine serum albumin (BSA) and from 2% fetal bovine serum. Adhesion of human umbilical vein endothelial cells (HUVECs) on CH3- and OH-SAMs preadsorbed with Fn and BSA decreased with decreasing adsorbed Fn; however, HUVECs adhered to COOH- and NH2-SAMs even in the presence of BSA at 1000-fold more than Fn in a mixt. because of the preferential adsorption of Fn and/or displacement of preadsorbed BSA with Fn and Vn in a serum-contg. medium. SAMs coated with a mixt. of Vn and BSA exhibited adhesion of HUVECs regardless of surface functional groups. A well-organized focal adhesion complex and actin stress fibers were obsd. only for COOH- and NH2-SAMs when SAMs were preadsorbed with Vn and BSA. These results suggest that COOH- and NH2-SAMs allow for both cell adhesion and cell spreading because of the high d. of cell-binding domains derived from adsorbed Vn. Adsorption of cell adhesive proteins including fibronectin (Fn) and vitronectin (Vn) plays an important role in cell adhesion to artificial materials. However, for the development of biomaterials that contact with biol. fluids, it is important to understand adsorption of Fn and Vn in complex media contg. many kinds of proteins. Here, we focused on adsorption of Fn and Vn from complex media including mixed soln. with albumin and fetal bovine serum, and its role on cell adhesion using self-assembled monolayers (SAMs). Our result demonstrates that SAMs carrying carboxylic acid or amine allow for both cell adhesion and cell spreading because of preferentially adsorbed Vn. The result provides insights into surface design of cell culture substrates and tissue engineering scaffolds.
- 46Rashad, A.; Mohamed-Ahmed, S.; Ojansivu, M.; Berstad, K.; Yassin, M. A.; Kivijarvi, T.; Heggset, E. B.; Syverud, K.; Mustafa, K. Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem Cells. Biomacromolecules 2018, 19, 4307– 4319, DOI: 10.1021/acs.biomac.8b0119446https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvVKgtLbL&md5=e94e0f19f7568a7f9caa2d5a01f2eb1eCoating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem CellsRashad, Ahmad; Mohamed-Ahmed, Samih; Ojansivu, Miina; Berstad, Kaia; Yassin, Mohammed A.; Kivijarvi, Tove; Heggset, Ellinor Baevre; Syverud, Kristin; Mustafa, KamalBiomacromolecules (2018), 19 (11), 4307-4319CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue engineering, but the hydrophobic surface may hinder optimal cell responses. The surface properties can be improved by coating the scaffold with cellulose nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial derived from wood. In this study, human bone marrow-derived mesenchymal stem cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds coated with CNF. Cellular responses to the surfaces (viability, attachment, proliferation, and osteogenic differentiation) were documented. CNF significantly enhanced the hydrophilic properties of PCL scaffolds and promoted protein adsorption. Live/dead staining and lactate dehydrogenase release assays confirmed that CNF did not inhibit cellular viability. The CNF between the 3D printed PCL strands and pores acted as a hydrophilic barrier, enhancing cell seeding efficiency, and proliferation. CNF supported the formation of a well-organized actin cytoskeleton and cellular prodn. of vinculin protein on the surfaces of TCP and PCL scaffolds. Moreover, CNF-coated surfaces enhanced not only alk. phosphatase activity, but also collagen Type-I and mineral formation. It is concluded that CNF coating enhances cell attachment, proliferation, and osteogenic differentiation and has the potential to improve the performance of 3D printed PCL scaffolds for bone tissue engineering.
- 47Nguyen, A. T.; Sathe, S. R.; Yim, E. K. F. From nano to micro: topographical scale and its impact on cell adhesion, morphology and contact guidance. J. Phys.: Condens. Matter 2016, 28, 183001 DOI: 10.1088/0953-8984/28/18/18300147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFehtbnE&md5=6ced494d4edd5b047fdbb4bd5e754b6cFrom nano to micro: topographical scale and its impact on cell adhesion, morphology and contact guidanceNguyen, Anh Tuan; Sathe, Sharvari R.; Yim, Evelyn K. F.Journal of Physics: Condensed Matter (2016), 28 (18), 183001/1-183001/16CODEN: JCOMEL; ISSN:0953-8984. (IOP Publishing Ltd.)Topog., among other phys. factors such as substrate stiffness and extracellular forces, is known to have a great influence on cell behaviors. Optimization of topog. features, in particular topog. dimensions ranging from nanoscale to microscale, is the key strategy to obtain the best cellular performance for various applications in tissue engineering and regenerative medicine. In this review, we provide a comprehensive survey on the significance of sizes of topog. and their impacts on cell adhesion, morphol. and alignment, and neurite guidance. Also recent works mimicking the hierarchical structure of natural extracellular matrix by combining both nanoscale and microscale topogs. are highlighted.
- 48Cao, X.; Ban, E.; Baker, B. M.; Lin, Y.; Burdick, J. A.; Chen, C. S.; Shenoy, V. B. Multiscale model predicts increasing focal adhesion size with decreasing stiffness in fibrous matrices. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, E4549– E4555, DOI: 10.1073/pnas.162048611448https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntVKjsL8%253D&md5=ad3f15c02a77a8b9253ff06b732cd26eMultiscale model predicts increasing focal adhesion size with decreasing stiffness in fibrous matricesCao, Xuan; Ban, Ehsan; Baker, Brendon M.; Lin, Yuan; Burdick, Jason A.; Chen, Christopher S.; Shenoy, Vivek B.Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (23), E4549-E4555CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)We describe a multiscale model that incorporates force-dependent mech. plasticity induced by interfiber cross-link breakage and stiffness-dependent cellular contractility to predict focal adhesion (FA) growth and mechanosensing in fibrous extracellular matrixes (ECMs). The model predicts that FA size depends on both the stiffness of ECM and the d. of ligands available to form adhesions. Although these two quantities are independent in commonly used hydrogels, contractile cells break cross-links in soft fibrous matrixes leading to recruitment of fibers, which increases the ligand d. in the vicinity of cells. Consequently, although the size of focal adhesions increases with ECM stiffness in nonfibrous and elastic hydrogels, plasticity of fibrous networks leads to a departure from the well-described pos. correlation between stiffness and FA size. We predict a phase diagram that describes nonmonotonic behavior of FA in the space spanned by ECM stiffness and recruitment index, which describes the ability of cells to break cross-links and recruit fibers. The predicted decrease in FA size with increasing ECM stiffness is in excellent agreement with recent observations of cell spreading on electrospun fiber networks with tunable cross-link strengths and mechanics. Our model provides a framework to analyze cell mechanosensing in nonlinear and inelastic ECMs.
- 49Kumar, G.; Waters, M. S.; Farooque, T. M.; Young, M. F.; Simon, C. G., Jr. Freeform fabricated scaffolds with roughened struts that enhance both stem cell proliferation and differentiation by controlling cell shape. Biomaterials 2012, 33, 4022– 4030, DOI: 10.1016/j.biomaterials.2012.02.04849https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xjs1Gmur0%253D&md5=d9cfb6e656d7fecfa109e74862816825Freeform fabricated scaffolds with roughened struts that enhance both stem cell proliferation and differentiation by controlling cell shapeKumar, Girish; Waters, Michael S.; Farooque, Tanya M.; Young, Marian F.; Simon, Carl G.Biomaterials (2012), 33 (16), 4022-4030CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)We demonstrate that freeform fabricated (FFF) scaffolds with a roughened surface topog. can support hBMSC proliferation, while also inducing osteogenic differentiation, for maximized generation of calcified, bone-like tissue. Previously, hBMSCs rapidly proliferated, without osteogenic differentiation, during culture in FFF scaffolds. In contrast, hBMSCs underwent osteogenic differentiation, with slow proliferation, during culture in nanofiber scaffolds. Anal. of cell morphol. showed that the topog. presented by the nanofiber scaffolds drove hBMSC differentiation by guiding them into a morphol. that induced osteogenic differentiation. Herein, we hypothesized that using the high-surface area architecture of FFF scaffolds to present a surface roughness that drives hBMSCs into a morphol. that induces osteogenic differentiation would yield a max. amt. differentiated hBMSCs and bone-like tissue. Thus, a solvent etching method was developed that imparted a 5-fold increase in roughness to the surface of the struts of poly(ε-caprolactone) (PCL) FFF scaffolds. The etched scaffolds induced osteogenic differentiation of the hBMSCs while un-etched scaffolds did not. The etched scaffolds also supported the same high levels of hBMSC proliferation that un-etched scaffolds supported. Finally, hBMSCs on un-etched scaffolds had a large spread area, while hBMSCs on etched scaffolds has a smaller area and were more rounded, indicating that the surface roughness from the etched scaffolds dictated the morphol. of the hBMSCs. The results demonstrate that FFF scaffolds with surface roughness can support hBMSC proliferation, while also inducing osteogenic differentiation, to maximize generation of calcified tissue. This work validates a rational approach to scaffold fabrication where the structure of the scaffold was designed to optimize stem cell function by controlling cell morphol.
- 50Frith, J. E.; Mills, R. J.; Hudson, J. E.; Cooper-White, J. J. Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell Differentiation. Stem Cells Dev. 2012, 21, 2442– 2456, DOI: 10.1089/scd.2011.061550https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1yntr7E&md5=a005b0679bcde2deb41cb76edb7a3237Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell DifferentiationFrith, Jessica Ellen; Mills, Richard James; Hudson, James Edward; Cooper-White, Justin JohnStem Cells and Development (2012), 21 (13), 2442-2456CODEN: SCDTAE; ISSN:1547-3287. (Mary Ann Liebert, Inc.)Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM mols. or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be detd. how specific integrin-ECM interactions may alter this or how they change during differentiation. We detd. that human bone marrow-derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of α5 integrin on day 7 of osteogenesis and an increase in α6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin-ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conductive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Addnl., we also detd. that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin-ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies.
- 51Curran, J. M.; Chen, R.; Hunt, J. A. The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials 2006, 27, 4783– 4793, DOI: 10.1016/j.biomaterials.2006.05.00151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlsFCrur0%253D&md5=37af274df0c066f91666bfb98d1b5b28The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrateCurran, Judith M.; Chen, Rui; Hunt, John A.Biomaterials (2006), 27 (27), 4783-4793CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Material-driven control of bone-marrow-derived mesenchymal stem cell (MSC) behavior and differentiation is a very exciting possibility. The aim of this study was to use silane-modified surfaces to control MSC adhesion and differentiation in vitro and evaluate the use of such techniques to control MSC behavior both in basal and stimulated conditions. A range of characterized clean glass silane-modified surfaces, Me (-CH3), amino (-NH2), silane (-SH), hydroxyl (-OH) and carboxyl (-COOH), were produced and cultured in contact with human MSC, in conjunction with a clean glass (TAAB) control, for time periods up to 28 days in basal, chondrogenic and osteogenic stimulated media. The samples were analyzed for levels of viable cell adhesion, morphol. and the prodn. of various differentiation and transcription markers using both fluorescent immunohistochem. (collagen I, II, osteocalcin, CBFA1) and real-time polymerase chain reaction (PCR) (collagen I, II, osteocalcin, osteopontin, osteonectin, CBFA1 and Sox 9). Anal. of the results demonstrated that the range of materials could be broken down into three distinct categories. Firstly, the -TAAB control and -CH3 surfaces maintained the MSC phenotype; secondly, the -NH2 and -SH-modified surfaces promoted and maintained osteogenesis both in the presence and absence of biol. stimuli. These surfaces did not support long-term chondrogenesis under any test conditions. Finally, the -OH and -COOH-modified surfaces promoted and maintained chondrogenesis under both basal and chondrogenic stimulated conditions, but did not support osteogenesis. These results demonstrate that intricate material properties such as surface chem. and energy can influence MSC behavior in vitro. These results have implications not only in promoting the efficiency of tissue-engineered constructs, but also to the wider field of MSC isolation, maintenance and expansion.
- 52Khang, D.; Choi, J.; Im, Y. M.; Kim, Y. J.; Jang, J. H.; Kang, S. S.; Nam, T. H.; Song, J.; Park, J. W. Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cells. Biomaterials 2012, 33, 5997– 6007, DOI: 10.1016/j.biomaterials.2012.05.00552https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnsFyisLk%253D&md5=b228f1c03a57b3c149677f61973ee063Role of subnano-, nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cellsKhang, Dongwoo; Choi, Jungil; Im, Yeon-Min; Kim, Youn-Jeong; Jang, Je-Hee; Kang, Sang Soo; Nam, Tae-Hyun; Song, Jonghan; Park, Jin-WooBiomaterials (2012), 33 (26), 5997-6007CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Subnano, nano and sub-micron surface features can selectively activate integrin receptors and induce osteoblast differentiation of bone marrow mesenchymal stem cells. Although it is widely accepted that nanoscale titanium surface roughness may promote differentiation of various osteoblast lineages, there has been no clear report on the threshold dimension of surface features and the optimized dimensions of surface features for triggering integrin activation and stem cell differentiation. This study systematically controlled titanium surface features from the sub-nano to sub-micron scales and investigated the corresponding effects on stem cell responses, such as integrin activation, cyclins, key transcriptional genes of osteoblast differentiation and osteoblastic phenotype genes. Surface features with sub-nano surface dimensions were insufficient to increase integrin activation compared to pure nanoscale titanium surface features. Although both pure nanoscale and nano-submicron hybrid scales of titanium surface features were sufficient for activating integrin-ligand proteins interactions through the α integrin subunits, only nano-submicron hybrid titanium surface features significantly accelerated subsequent osteoblast differentiation of primary mouse bone marrow stromal cells after 2 wk. In addn., live cell anal. of human bone marrow mesenchymal stem cells on transparent titanium demonstrated rapid cytoskeletal re-organization on the nanoscale surface features, which ultimately induced higher expression of osteoblast phenotype genes after 3 wk.
- 53Faia-Torres, A. B.; Guimond-Lischer, S.; Rottmar, M.; Charnley, M.; Goren, T.; Maniura-Weber, K.; Spencer, N. D.; Reis, R. L.; Textor, M.; Neves, N. M. Differential regulation of osteogenic differentiation of stem cells on surface roughness gradients. Biomaterials 2014, 35, 9023– 9032, DOI: 10.1016/j.biomaterials.2014.07.01553https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1ekt7bK&md5=3edaf61bc00e1b563a627fb569705f6dDifferential regulation of osteogenic differentiation of stem cells on surface roughness gradientsFaia-Torres, Ana B.; Guimond-Lischer, Stefanie; Rottmar, Markus; Charnley, Mirren; Goren, Tolga; Maniura-Weber, Katharina; Spencer, Nicholas D.; Reis, Rui L.; Textor, Marcus; Neves, Nuno M.Biomaterials (2014), 35 (33), 9023-9032CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Tissue engineering using scaffold-cell constructs holds the potential to develop functional strategies to regenerate bone. The interface of orthopedic implants with the host tissues is of great importance for its later performance. Thus, the optimization of the implant surface in a way that could stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) is of significant therapeutic interest. The effect of surface roughness of polycaprolactone (PCL) on the osteogenic differentiation of human bone-marrow MSCs was investigated. We prepd. surface roughness gradients of av. roughness (Ra) varying from the sub-micron to the micrometer range (∼0.5-4.7 μm), and mean distance between peaks (RSm) gradually varying from ∼214 μm to 33 μm. We analyzed the degree of cytoskeleton spreading, expression of alk. phosphatase, collagen type 1 and mineralization. The response of cells to roughness divided the gradient into three groups of elicited stem cell behavior: 1) faster osteogenic commitment and strongest osteogenic expression; 2) slower osteogenic commitment but strong osteogenic expression, and 3) similar or inferior osteogenic potential in comparison to the control material. The stem-cell modulation by specific PCL roughness surfaces highlights the potential for creating effective solns. for orthopedic applications featuring a clin. relevant biodegradable material.
- 54Tew, L. S.; Ching, J. Y.; Ngalim, S. H.; Khung, Y. L. Driving mesenchymal stem cell differentiation from self-assembled monolayers. RSC Adv. 2018, 8, 6551– 6564, DOI: 10.1039/c7ra12234a54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisFeqsb0%253D&md5=7ee77db049237861fee91811ef941b6cDriving mesenchymal stem cell differentiation from self-assembled monolayersTew, L. S.; Ching, J. Y.; Ngalim, S. H.; Khung, Y. L.RSC Advances (2018), 8 (12), 6551-6564CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The utilization of self-assembled monolayer (SAM) systems to direct Mesenchymal Stem Cell (MSC) differentiation has been covered in the literature for years, but finding a general consensus pertaining to its exact role over the differentiation of stem cells had been rather challenging. Although there are numerous reports on surface functional moieties activating and inducing differentiation, the results are often different between reports due to the varying surface conditions, such as topog. or surface tension. Herein, in view of the complexity of the subject matter, we have sought to catalog the recent developments around some of the more common functional groups on predominantly hard surfaces and how these chem. groups may influence the overall outcome of the mesenchymal stem cells (MSC) differentiation so as to better establish a clearer underlying relationship between stem cells and their base substratum interactions.
- 55Moursi, A. M.; Globus, R. K.; Damsky, C. H. Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitro. J. Cell Sci. 1997, 110, 2187– 2196, DOI: 10.1242/jcs.110.18.218755https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmsFamtbo%253D&md5=eb2adeab7c8ea9f35cc047598a05a411Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitroMoursi, Amr M.; Globus, Ruth K.; Damsky, Caroline H.Journal of Cell Science (1997), 110 (18), 2187-2196CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists)We previously showed that anti-fibronectin antibodies or sol. fibronectin fragments contg. the central cell-binding domain inhibit formation of mineralized nodules by fetal calvarial osteoblasts in vitro. These findings suggest a crit. role for fibronectin in osteoblast differentiation and morphogenesis. In this study we tested the hypothesis that fibronectin's effects on osteogenesis are mediated via direct interactions with integrin receptors for fibronectin on osteoblasts. Immunocytochem. anal. identified the integrin fibronectin receptor α5β1 in fetal rat calvarial tissue and in cultured osteoblasts at all stages of differentiation. Three other integrins, α3β1, α8β1 and αvβ3, which can bind fibronectin, as well as other matrix components, were also identified in tissue and at all stages of cell culture. Immunopptn. data showed that α5β1 levels are const. throughout osteoblast differentiation whereas levels of α3β1 and α8β1 decline in mature mineralized cultures. To det. whether integrin fibronectin receptors are required for osteoblast formation of mineralized nodules, we examd. the extent of nodule formation in the presence and absence of function-perturbing anti-integrin antibodies. The antibodies were present continuously in cultures beginning at confluence (day 3), and nodule formation was measured at days 10 and 20. An anti-α5 integrin subunit antibody reduced nodule formation to less than 5% of control values at both time points. Inhibition of nodule formation was reversible and did not affect cell attachment and viability. Function-perturbing antibodies against α3β1 and α8β1 also reduced nodule formation, to less than 20% of control values. In contrast, function-perturbing antibodies to αvβ3 and αvβ5 did not affect nodule formation, indicating that the inhibitions noted were indeed specific. To det. the effect of antibody treatment on gene expression, steady-state mRNA expression was examd. and found to be suppressed for osteoblast markers alk. phosphatase and osteocalcin. Together, these results indicate that direct osteoblast interactions with the extracellular matrix are mediated by a select group of integrin receptors that includes α5β1, α3β1 and α8β1. We further conclude that the specific α5β1 fibronectin receptor mediates crit. interactions between osteoblasts and fibronectin required for both bone morphogenesis and osteoblast differentiation.
- 56Besbes, I.; Alila, S.; Boufi, S. Nanofibrillated cellulose from TEMPO-oxidized eucalyptus fibres: Effect of the carboxyl content. Carbohyd. Polym. 2011, 84 (3), 975– 983, DOI: 10.1016/j.carbpol.2010.12.05256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXitVShurY%253D&md5=ae9da05b1bf12dda17ef09624e3bcc05Nanofibrillated cellulose from TEMPO-oxidized eucalyptus fibres: Effect of the carboxyl contentBesbes, Iskander; Alila, Sabrine; Boufi, SamiCarbohydrate Polymers (2011), 84 (3), 975-983CODEN: CAPOD8; ISSN:0144-8617. (Elsevier Ltd.)The effect of the carboxyl content on the high pressure defibrillation of oxidized eucalyptus from micro to nanoscale size was investigated. It has been shown that TEMPO-mediated oxidn. of dried softwood pulp not only facilitates the defibrillation process, but also reduces the no. of passes necessary to get the gel, as well as preventing the clogging of the homogenizer. In fact, these effects became apparent up to a carboxyl content about 300 μmol/g, and over 500 μmol/g, the yield in the nanofibrillated cellulose exceeded 90%, at a defibrillation pressure of 600 bar. The morphol. of the ensuing nanofibrillated cellulose (NFC) and its cryst. degree were characterized by FE-SEM and DRX measurement, resp. The evolution of the transparency degree and the viscosity according to the oxidn. degree and defibrillation pressure were also analyzed by UV-vis transmittance and rheol. measurement. The reinforcing potential of the ensuing NFC was explored by means of dynamic mech. anal. (DMA) carried on nanocomposite film prepd. from a suspension of NFC as the reinforcing phase and an acrylic latex dispersion as the matrix.