Thermoresponsive Hydrogels as Microniches for Growth and Controlled Release of Induced Pluripotent Stem Cells

Abstract

The recently emerging stem-cell artificial niche engineering in induced pluripotent stem cell (iPSCs) 3D cultures has provided enormous opportunities to fully utilize the potential of these cells in biomedical applications. Although a fully chemically defined niche environment can supply cells with desirable safety for clinical use, establishing an artificial degradable niche environment for the controlled release of proliferated cells under mild conditions is still a big challenge. Here, an advanced controlled releasable iPSC 3D artificial niche is reported based on dendritic polyglycerol and poly(N-isopropylacrylamide)-co-polyethylene glycol polymers via a physical–chemical cogelation strategy. Benefiting from the chemically defined synthetic materials and their precise cooperation by covalent cross-linking and physical phase transition, the cogelation-based artificial niche system can be adjusted with optimal parameters and owns high cell biocompatibility to support the robust production of high quality iPSCs with an excellent expansion efficiency. Moreover, the expanded cells can be released out of their niche environment controllably only by adjusting the temperature. Overall, this controlled release hydrogel scaffold shows great promise in iPSC 3D culture for downstream applications.