A Novel Hydrogel Surface Grafted With Dual Functional Peptides for Sustaining Long‐Term Self‐Renewal of Human Induced Pluripotent Stem Cells and Manipulating Their Osteoblastic Maturation

Abstract Realizing the clinical potential of human induced pluripotent stem cells (hiPSCs) in bone regenerative medicine requires the development of safe and chemically defined biomaterials for expansion of hiPSCs followed by directing their lineage commitment to osteoblasts. In this study, novel multipurpose peptide‐presenting hydrogel surfaces are prepared on common tissue culture plates via carboxymethyl chitosan grafting and subsequent immobilization of two functional peptides allowing for in vitro feeder‐free culture, long‐term self‐renewal, and osteogenic induction of hiPSCs. After vitronectin (VN) peptide modification, the engineered surfaces facilitate adhesion, proliferation, colony formation, and the maintenance of pluripotency of hiPSCs up to passage 10 under fully defined conditions without Matrigel or protein coating. Further, this synthetic niche exhibits an appealing regulatory effect on the osteogenic conversion of hiPSCs to osteoblastic phenotype without an embryoid body formation step by co‐decoration of different ratios of VN and bone‐forming peptide. Such a well‐defined, xeno‐free 2D engineered microenvironment not only helps to accelerate the clinical development of hiPSCs, but also provides a safe and robust platform for the generation of osteoblast‐like cells or bone‐like tissues at different maturation levels. Thus, the strategy may hold great potential for application in cell therapy and bone tissue engineering.