Thermoreversible Hyaluronic Acid‐PNIPAAm Hydrogel Systems for 3D Stem Cell Culture
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Human pluripotent stem cells (hPSCs) offer considerable potential for biomedical applications including drug screening and cell replacement therapies. Clinical translation of hPSCs requires large quantities of high quality cells, so scalable methods for cell culture are needed. However, current methods are limited by scalability, the use of animal‐derived components, and/or low expansion rates. A thermoresponsive 3D hydrogel for scalable hPSC expansion and differentiation into several defined lineages is recently reported. This system would benefit from increased control over material properties to further tune hPSC behavior, and here a scalable 3D biomaterial with the capacity to tune both the chemical and the mechanical properties is demonstrated to promote hPSC expansion under defined conditions. This 3D biomaterial, comprised of hyaluronic acid and poly( N ‐isopropolyacrylamide), has thermoresponsive properties that readily enable mixing with cells at low temperatures, physical encapsulation within the hydrogel upon elevation at 37 °C, and cell recovery upon cooling and reliquefaction. After optimization, the resulting biomaterial supports hPSC expansion over long cell culture periods while maintaining cell pluripotency. The capacity to modulate the mechanical and chemical properties of the hydrogel provides a new avenue to expand hPSCs for future therapeutic application.
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A thermoreversible hyaluronic acid-poly(N-isopropylacrylamide) (PNIPAAm) based hydrogel that solidifies at 37 °C and re-liquefies upon cooling enabled culture and recovery of human pluripotent stem cells without enzymatically digesting the matrix.
“For example, a thermoreversible hyaluronic acid- poly(N-isopropylacrylamide) (PNIPAAm) based hydrogel that solidifies at 37 oC and re-liquefies upon cooling enabled culture and recovery of human pluripotent stem cells without enzymatically digesting the matrix133.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [133]
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- Authors
- Ekerdt, B. L., Fuentes, C. M., Lei, Y., Adil, M. M., Ramasubramanian, A., Segalman, R. A., & Schaffer, D. V.
- Affiliations
- University of California, Berkeley (US)
- University of Nebraska–Lincoln (US)
- University of California, Santa Barbara (US)
- Corresponding author
- Schaffer, David V.
- Venue
- Advanced Healthcare Materials
- Publisher
- Wiley
- Published
- 2018-05-02
- Volume
- 7
- Issue
- 12
- Pages
- e1800225-e1800225
- ISSN
- 2192-2640 (ISSN-L)
- 2192-2659
- PMC
- PMC6289514
- OpenAlex
- W2801492698
- Cited by
- 117
- References
- 70
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 7 · 2023: 19 · 2022: 12 · 2021: 18 · 2020: 21 · 2019: 9 · 2018: 4
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Healthcare Materials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- California Institute of Regenerative Medicine (DISC2‐08982, RT3‐07800)
- National Institutes of Health (R01 NS074831, R01 NS083856)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- thermosensitive hydrogel, hyaluronic acid, poly(N-isopropylacrylamide), human pluripotent stem cells, cell encapsulation, hydrogel mechanical properties, cell differentiation, cell replacement therapy
- MeSH terms
- Acrylic Resins, Cell Line, Hot Temperature, Humans, Hyaluronic Acid, Cell Culture Techniques, Hydrogels, Pluripotent Stem Cells
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