Photo-mediated zwitterionic hydrogel as “blocked” platform for expansion and maintaining stemness of stem cells

Abstract

Three-dimensional cell culture based on hydrogels has been a promising method for offering sufficient and effective seed cells for clinical stem cell therapy. However, the development of a required platform is always a great challenge for large expansion and stemness maintenance of stem cells. In this study, a photoresponsive zwitterionic copolymer (PSC)-based hydrogel is designed and prepared, comprising of sulfobetaine methacrylate (SBMA) and coumarin derivative (CMA) segments. By incorporating CMA segments, the PSC hydrogel possesses a comfortable gelation process and rapid photocleavage behavior under different UV radiation for cell encapsulation and harvesting. The SBMA segments provide a clean microenvironment for the stemness maintenance of stem cells via protein resistance. In addition, the cellular recognition peptide CGRGDS immobilized to hydrogel also improves the specific adhesion and proliferative capacity of stem cells. Finally, the well-defined zwitterionic hydrogel can act as a “blocked” platform for cell expansion. Both L929 cells and adipose-derived stem cells (ADSCs) encapsulated in the hydrogel show high viability and expansion. More importantly, zwitterionic hydrogels can maintain the stemness expression of ADSCs regardless of differentiation mediums. Overall, the novel “blocked” platform provided in this work has promising prospects in the large-scale expansion of stem cells.