Thermoreversible Hyaluronic Acid-PNIPAAm Hydrogel Systems for 3D Stem Cell Culture

Barbara L. Ekerdt, Christina M. Fuentes, Yuguo Lei, Maroof M. Adil, Anusuya Ramasubramanian, Rachel A. Segalman, David V. Schaffer

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


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.

Original languageEnglish (US)
Article number1800225
JournalAdvanced Healthcare Materials
Issue number12
StatePublished - Jun 20 2018


  • hyaluronic acid
  • poly(N-isopropylacrylamide)
  • stem cell cultures
  • thermoresponsive hydrogels

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science


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