ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Biomater. Sci. Eng. 2015, 1, 3, 157-165
RETURN TO ISSUEPREVArticleNEXT

Microfluidic Synthesis of Biodegradable Polyethylene-Glycol Microspheres for Controlled Delivery of Proteins and DNA Nanoparticles

View Author Information
† Department of Bioengineering, Stanford University 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California 94305, United States
‡ MSTP Program, School of Medicine, Stanford University 300 Pasteur Drive, Stanford, California 94305, United States
§ Department of Biological Sciences, San Jose State University One Washington Square, San Jose, California 95192, United States
⊥ Department of Orthopaedic Surgery, Stanford University, 300 Pasteur Drive, Stanford, California 94305, United States
*E-mail: [email protected]
Cite this: ACS Biomater. Sci. Eng. 2015, 1, 3, 157–165
Publication Date (Web):February 10, 2015
https://doi.org/10.1021/ab500051v
Copyright © 2015 American Chemical Society
Request reuse permissions

    Article Views

    1468

    Altmetric

    -

    Citations

    30
    LEARN ABOUT THESE METRICS
    Read OnlinePDF (2 MB)
    Get e-Alerts
    Supporting Info (1)»
    SUBJECTS:

    Abstract

    Abstract Image

    Polymeric microspheres represent an injectable platform for controlling the release of a variety of biologics; microspheres may be combined in a modular fashion to achieve temporal release of two or more biomolecules. Microfluidics offers a versatile platform for synthesizing uniform polymeric microspheres harboring a variety of biologics under relatively mild conditions. Poly(ethylene glycol) (PEG) is a bioinert polymer that can be easily tailored to encapsulate and control the release of biologics. In this study, we report the microfluidic synthesis of biodegradable PEG-based microparticles for controlled release of growth factors or DNA nanoparticles. Simple changes in microfluidic design increased the rate of microparticle formation and controlled the size of the microspheres. Mesh size and degradation rate were controlled by varying the PEG polymer weight percent from 7.5 to 15% (w/v), thus tuning the release of growth factors and DNA nanoparticles, which retained their bioactivity in assays of cell proliferation and DNA transfection, respectively. This platform may provide a useful tool for synthesizing microspheres for use as injectable carriers to achieve coordinated growth-factor or DNA nanoparticle release in therapeutic applications.

    KEYWORDS:

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The following file is available free of charge on the ACS Publications website at DOI: 10.1021/ab500051v.

    • bFGF encapsulation efficiency (Figure S1) and microsphere formation rate (Table S1) (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 30 publications.

    1. Bin Wang, Dong Liu, Yuting Liao, Yanjie Huang, Miao Ni, Mengchen Wang, Zhanpeng Ma, Zijian Wu, Yuan Lu. Spatiotemporally Actuated Hydrogel by Magnetic Swarm Nanorobotics. ACS Nano 2022, 16 (12) , 20985-21001. https://doi.org/10.1021/acsnano.2c08626
    2. Sébastien Sart, Gustave Ronteix, Shreyansh Jain, Gabriel Amselem, Charles N. Baroud. Cell Culture in Microfluidic Droplets. Chemical Reviews 2022, 122 (7) , 7061-7096. https://doi.org/10.1021/acs.chemrev.1c00666
    3. Bruna G. Carvalho, Franciele F. Vit, Hernandes F. Carvalho, Sang W. Han, Lucimara G. de la Torre. Layer-by-Layer Biomimetic Microgels for 3D Cell Culture and Nonviral Gene Delivery. Biomacromolecules 2022, 23 (4) , 1545-1556. https://doi.org/10.1021/acs.biomac.1c01130
    4. Weiling Song, Pan Song, Yujie Sun, Zhonghui Zhang, Hong Zhou, Xiaoru Zhang, Peng He. Self-Assembly of Multifunctional DNA Nanohydrogels with Tumor Microenvironment-Responsive Cascade Reactions for Cooperative Cancer Therapy. ACS Biomaterials Science & Engineering 2021, 7 (11) , 5165-5174. https://doi.org/10.1021/acsbiomaterials.1c00959
    5. Saahil Sheth, Samuel Stealey, Nicole Y. Morgan, Silviya P. Zustiak. Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition. Langmuir 2021, 37 (40) , 11793-11803. https://doi.org/10.1021/acs.langmuir.1c01739
    6. Alex J. Anderson, Emerson Grey, Nicholas J. Bongiardina, Christopher N. Bowman, Stephanie J. Bryant. Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications. Biomacromolecules 2021, 22 (3) , 1127-1136. https://doi.org/10.1021/acs.biomac.0c01563
    7. Haijun Qu, Mengchao Yu, Wenbin Du, Lei Xu, Weiyuan Lyu, Feng Shen. Slip Molding for Precision Fabrication of Microparts. Langmuir 2020, 36 (2) , 585-590. https://doi.org/10.1021/acs.langmuir.9b03156
    8. Haoran Zhao, Xuexia Yuan, Jiantao Yu, Yishun Huang, Chen Shao, Fan Xiao, Li Lin, Yan Li, Leilei Tian. Magnesium-Stabilized Multifunctional DNA Nanoparticles for Tumor-Targeted and pH-Responsive Drug Delivery. ACS Applied Materials & Interfaces 2018, 10 (18) , 15418-15427. https://doi.org/10.1021/acsami.8b01932
    9. Nima Beheshtizadeh, Maliheh Gharibshahian, Mohammad Bayati, Reza Maleki, Hannah Strachan, Sarah Doughty, Lobat Tayebi. Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine. Biomedicine & Pharmacotherapy 2023, 166 , 115301. https://doi.org/10.1016/j.biopha.2023.115301
    10. Jingyan Guan, Jingwei Feng, Feng Lu, . Recent Advances in the Hydrogel-Based Biomolecule Delivery System for Cartilage Tissue Engineering. Advances in Materials Science and Engineering 2022, 2022 , 1-16. https://doi.org/10.1155/2022/1899400
    11. Xiaoyu Ma, Mengjie Wang, Yuanyuan Ran, Yusi Wu, Jin Wang, Fuhai Gao, Zongjian Liu, Jianing Xi, Lin Ye, Zengguo Feng. Design and Fabrication of Polymeric Hydrogel Carrier for Nerve Repair. Polymers 2022, 14 (8) , 1549. https://doi.org/10.3390/polym14081549
    12. Bruna G. Carvalho, Bruno T. Ceccato, Mariano Michelon, Sang W. Han, Lucimara G. de la Torre. Advanced Microfluidic Technologies for Lipid Nano-Microsystems from Synthesis to Biological Application. Pharmaceutics 2022, 14 (1) , 141. https://doi.org/10.3390/pharmaceutics14010141
    13. Reyhaneh Sadat Hayaei Tehrani, Mohammad Amin Hajari, Zeynab Ghorbaninejad, Fereshteh Esfandiari. Droplet microfluidic devices for organized stem cell differentiation into germ cells: capabilities and challenges. Biophysical Reviews 2021, 13 (6) , 1245-1271. https://doi.org/10.1007/s12551-021-00907-5
    14. Marie Hébert, Carolyn L. Ren. Droplet microfluidics for biomedical devices. 2021, 163-204. https://doi.org/10.1016/B978-0-12-819971-8.00001-9
    15. Nan Shi, Md Moniruzzaman, Christopher J. Easley. Tissue Engineering and Analysis in Droplet Microfluidics. 2020, 223-260. https://doi.org/10.1039/9781839162855-00223
    16. Jielai Yang, Yuan Zhu, Fei Wang, Liangfu Deng, Xiangyang Xu, Wenguo Cui. Microfluidic liposomes-anchored microgels as extended delivery platform for treatment of osteoarthritis. Chemical Engineering Journal 2020, 400 , 126004. https://doi.org/10.1016/j.cej.2020.126004
    17. Miran Hannah Choi, Alexandra Blanco, Samuel Stealey, Xin Duan, Natasha Case, Scott Allen Sell, Muhammad Farooq Rai, Silviya Petrova Zustiak. Micro-Clotting of Platelet-Rich Plasma Upon Loading in Hydrogel Microspheres Leads to Prolonged Protein Release and Slower Microsphere Degradation. Polymers 2020, 12 (8) , 1712. https://doi.org/10.3390/polym12081712
    18. Zhongliang Jiang, Rajib Shaha, Ralph McBride, Kun Jiang, Mingchen Tang, Bang Xu, Alexander K Goroncy, Carl Frick, John Oakey. Crosslinker length dictates step-growth hydrogel network formation dynamics and allows rapid on-chip photoencapsulation. Biofabrication 2020, 12 (3) , 035006. https://doi.org/10.1088/1758-5090/ab7ef4
    19. Chul Min Kim, Hye Jin Choi, Eun Ju Park, Gyu Man Kim. Repeated geometrical T-junction breakup microfluidic filter device by injection of premixed emulsion for microdroplet production. Journal of Industrial and Engineering Chemistry 2020, 81 , 81-87. https://doi.org/10.1016/j.jiec.2019.08.055
    20. Andrew C. Daly, Lindsay Riley, Tatiana Segura, Jason A. Burdick. Hydrogel microparticles for biomedical applications. Nature Reviews Materials 2020, 5 (1) , 20-43. https://doi.org/10.1038/s41578-019-0148-6
    21. Xuan Luo, Peng Su, Wei Zhang, Colin L. Raston. Microfluidic Devices in Fabricating Nano or Micromaterials for Biomedical Applications. Advanced Materials Technologies 2019, 4 (12) https://doi.org/10.1002/admt.201900488
    22. Zhongliang Jiang, Kun Jiang, Ralph McBride, John S Oakey. Comparative cytocompatibility of multiple candidate cell types to photoencapsulation in PEGNB/PEGDA macroscale or microscale hydrogels. Biomedical Materials 2018, 13 (6) , 065012. https://doi.org/10.1088/1748-605X/aadf9a
    23. L.P. Ferreira, V.M. Gaspar, J.F. Mano. Design of spherically structured 3D in vitro tumor models -Advances and prospects. Acta Biomaterialia 2018, 75 , 11-34. https://doi.org/10.1016/j.actbio.2018.05.034
    24. Gabriel Jaime Colmenares Roldán, Liliana María Agudelo Gomez, Jesús Antonio Carlos Cornelio, Luis Fernando Rodriguez, Rodolfo Pinal, Lina Marcela Hoyos Palacio. Production of polycaprolactone nanoparticles with low polydispersity index in a tubular recirculating system by using a multifactorial design of experiments. Journal of Nanoparticle Research 2018, 20 (3) https://doi.org/10.1007/s11051-018-4168-8
    25. Wen Li, Liyuan Zhang, Xuehui Ge, Biyi Xu, Weixia Zhang, Liangliang Qu, Chang-Hyung Choi, Jianhong Xu, Afang Zhang, Hyomin Lee, David A. Weitz. Microfluidic fabrication of microparticles for biomedical applications. Chemical Society Reviews 2018, 47 (15) , 5646-5683. https://doi.org/10.1039/C7CS00263G
    26. Caroline C. Ahrens, Ziye Dong, Wei Li. Engineering cell aggregates through incorporated polymeric microparticles. Acta Biomaterialia 2017, 62 , 64-81. https://doi.org/10.1016/j.actbio.2017.08.003
    27. Torri E. Rinker, Brandon D. Philbrick, Johnna S. Temenoff. Core-shell microparticles for protein sequestration and controlled release of a protein-laden core. Acta Biomaterialia 2017, 56 , 91-101. https://doi.org/10.1016/j.actbio.2016.12.042
    28. Jyoti Boken, Sarvesh K. Soni, Dinesh Kumar. Microfluidic Synthesis of Nanoparticles and their Biosensing Applications. Critical Reviews in Analytical Chemistry 2016, 46 (6) , 538-561. https://doi.org/10.1080/10408347.2016.1169912
    29. Amjed Javid, Manish Kumar, Long Wen, Seokyoung Yoon, Su B. Jin, Jung Heon Lee, Jeon Geon Han. Surface energy and wettability control in bio-inspired PEG like thin films. Materials & Design 2016, 92 , 405-413. https://doi.org/10.1016/j.matdes.2015.12.046
    30. Weiqian Jiang, Mingqiang Li, Zaozao Chen, Kam W. Leong. Cell-laden microfluidic microgels for tissue regeneration. Lab on a Chip 2016, 16 (23) , 4482-4506. https://doi.org/10.1039/C6LC01193D
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect