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Tropoelastin-Coated Tendon Biomimetic Scaffolds Promote Stem Cell Tenogenic Commitment and Deposition of Elastin-Rich Matrix

  • Helena Almeida
    Helena Almeida
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
  • Rui M. A. Domingues
    Rui M. A. Domingues
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
    The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Barco, 4805-017 Guimarães, Portugal
  • Suzanne M. Mithieux
    Suzanne M. Mithieux
    School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia
  • Ricardo A. Pires
    Ricardo A. Pires
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
    The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Barco, 4805-017 Guimarães, Portugal
  • Ana I. Gonçalves
    Ana I. Gonçalves
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
  • Manuel Gómez-Florit*
    Manuel Gómez-Florit
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
    *E-mail: [email protected] (M.G-F.).
  • Rui L. Reis
    Rui L. Reis
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
    The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Barco, 4805-017 Guimarães, Portugal
    More by Rui L. Reis
  • Anthony S. Weiss
    Anthony S. Weiss
    School of Life and Environmental Sciences, Charles Perkins Centre, Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
  • , and 
  • Manuela E. Gomes*
    Manuela E. Gomes
    3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
    ICVS/3B’s−PT Government Associate Laboratory, Braga/Guimarães, Portugal
    The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Barco, 4805-017 Guimarães, Portugal
    *E-mail: [email protected] (M.E.G.).
Cite this: ACS Appl. Mater. Interfaces 2019, 11, 22, 19830–19840
Publication Date (Web):May 15, 2019
https://doi.org/10.1021/acsami.9b04616
Copyright © 2019 American Chemical Society
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Abstract

Abstract Image

Tendon tissue engineering strategies that recreate the biophysical and biochemical native microenvironment have a greater potential to achieve regeneration. Here, we developed tendon biomimetic scaffolds using mechanically competent yarns of poly-ε-caprolactone, chitosan, and cellulose nanocrystals to recreate the inherent tendon hierarchy from a nano-to-macro scale. These were then coated with tropoelastin (TROPO) through polydopamine (PDA) linking, to mimic the native extracellular matrix (ECM) composition and elasticity. Both PDA and TROPO coatings decreased surface stiffness without masking the underlying substrate. We found that human adipose-derived stem cells (hASCs) seeded onto these TROPO biomimetic scaffolds more rapidly acquired their spindle-shape morphology and high aspect ratio characteristic of tenocytes. Immunocytochemistry shows that the PDA and TROPO-coated surfaces boosted differentiation of hASCs toward the tenogenic lineage, with sustained expression of the tendon-related markers scleraxis and tenomodulin up to 21 days of culture. Furthermore, these surfaces enabled the deposition of a tendon-like ECM, supported by the expression of collagens type I and III, tenascin, and decorin. Gene expression analysis revealed a downregulation of osteogenic and fibrosis markers in the presence of TROPO when compared with the control groups, suggesting proper ECM deposition. Remarkably, differentiated cells exposed to TROPO acquired an elastogenic profile due to the evident elastin synthesis and deposition, contributing to the formation of a more mimetic matrix in comparison with the PDA-coated and uncoated conditions. In summary, our biomimetic substrates combining biophysical and biological cues modulate stem cell behavior potentiating their long-term tenogenic commitment and the production of an elastin-rich ECM.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.9b04616.

  • Synthesis of CNCs and characterization; chitosan purification; surface characterization of the coatings; directionality analysis; real-time PCR primers and SCX mRNA levels; tropoelastin release from the yarns (PDF)

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Cited By


This article is cited by 12 publications.

  1. Mari Carmen Echave, Rui M. A. Domingues, Manuel Gómez-Florit, José Luis Pedraz, Rui L. Reis, Gorka Orive, Manuela E. Gomes. Biphasic Hydrogels Integrating Mineralized and Anisotropic Features for Interfacial Tissue Engineering. ACS Applied Materials & Interfaces 2019, 11 (51) , 47771-47784. https://doi.org/10.1021/acsami.9b17826
  2. Francisco R. Almeida-González, Arlyng González-Vázquez, Suzanne M. Mithieux, Fergal J. O'Brien, Anthony S. Weiss, Claire M. Brougham. A step closer to elastogenesis on demand; Inducing mature elastic fibre deposition in a natural biomaterial scaffold. Materials Science and Engineering: C 2021, 120 , 111788. https://doi.org/10.1016/j.msec.2020.111788
  3. Simão P. B. Teixeira, Rui M. A. Domingues, Pedro S. Babo, Dominika Berdecka, Margarida S. Miranda, Manuela E. Gomes, Nicholas A. Peppas, Rui L. Reis. Epitope‐Imprinted Nanoparticles as Transforming Growth Factor‐β3 Sequestering Ligands to Modulate Stem Cell Fate. Advanced Functional Materials 2020, 3 , 2003934. https://doi.org/10.1002/adfm.202003934
  4. Maria Rita Citeroni, Maria Camilla Ciardulli, Valentina Russo, Giovanna Della Porta, Annunziata Mauro, Mohammad El Khatib, Miriam Di Mattia, Devis Galesso, Carlo Barbera, Nicholas R. Forsyth, Nicola Maffulli, Barbara Barboni. In Vitro Innovation of Tendon Tissue Engineering Strategies. International Journal of Molecular Sciences 2020, 21 (18) , 6726. https://doi.org/10.3390/ijms21186726
  5. Liren Wang, Yuhao Kang, Hexin Yan, Xuejing Zhu, Tonghe Zhu, Jia Jiang, Jinzhong Zhao. Tendon regeneration induced by umbilical cord graft in a rabbit tendon defect model. Journal of Tissue Engineering and Regenerative Medicine 2020, 14 (8) , 1009-1018. https://doi.org/10.1002/term.3052
  6. Yongjie Jiao, Chaojing Li, Laijun Liu, Fujun Wang, Xingxing Liu, Jifu Mao, Lu Wang. Construction and application of textile-based tissue engineering scaffolds: a review. Biomaterials Science 2020, 8 (13) , 3574-3600. https://doi.org/10.1039/D0BM00157K
  7. Yuzhen Wang, Ubaldo Armato, Jun Wu. Targeting Tunable Physical Properties of Materials for Chronic Wound Care. Frontiers in Bioengineering and Biotechnology 2020, 8 https://doi.org/10.3389/fbioe.2020.00584
  8. Sadhana P. Mutalik, Abhijeet Pandey, Srinivas Mutalik. Nanoarchitectronics: A versatile tool for deciphering nanoparticle interaction with cellular proteins, nucleic acids and phospholipids at biological interfaces. International Journal of Biological Macromolecules 2020, 151 , 136-158. https://doi.org/10.1016/j.ijbiomac.2020.02.150
  9. Abhirup Mandal, John R. Clegg, Aaron C. Anselmo, Samir Mitragotri. Hydrogels in the clinic. Bioengineering & Translational Medicine 2020, 5 (2) https://doi.org/10.1002/btm2.10158
  10. Sara Tabatabaee, Mohammed Najafi-Ashtiani, Ali Mousavi, Nafiseh Baheiraei. Nanobiomaterials in musculoskeletal regeneration. 2020,,, 43-76. https://doi.org/10.1016/B978-0-12-820262-3.00002-5
  11. Ana I. Gonçalves, Márcia T. Rodrigues, Ana M. Matos, Helena Almeida, Manuel Gómez-Florit, Rui M. A. Domingues, Manuela E. Gomes. Multiscale Multifactorial Approaches for Engineering Tendon Substitutes. 2020,,, 1-24. https://doi.org/10.1007/978-3-030-18512-1_8-1
  12. Azizeh Rahmani Del Bakhshayesh, Nahideh Asadi, Alireza Alihemmati, Hamid Tayefi Nasrabadi, Azadeh Montaseri, Soodabeh Davaran, Sepideh Saghati, Abolfazl Akbarzadeh, Ali Abedelahi. An overview of advanced biocompatible and biomimetic materials for creation of replacement structures in the musculoskeletal systems: focusing on cartilage tissue engineering. Journal of Biological Engineering 2019, 13 (1) https://doi.org/10.1186/s13036-019-0209-9

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