Current natural polymer-based cell-laden hydrogel scaffolds exhibit poor mechanical properties, fast degradation and cytotoxicity. We therefore designed natural protein-based hydrogel scaffolds with tunable physical and biological properties to accelerate tissue regeneration by enabling cells to ‘mechanosense’ their microenvironments. We demonstrated that by modulating the hydrogel microstructure, we changed the materials’ mechanical properties, degradation profile, biocompatibility, and drug release kinetics, thereby regulating the adhesion, proliferation, migration and differentiation of stem cells seeded onto or encapsulated within such scaffolds. Utilizing various forms like injectable gels, microspheres, micro/nanofibers enabled both hard and soft tissue regeneration. For example, bone mesenchymal stem cell (BMSC)-loaded hydrogel microspheres accelerated bone regeneration by enhancing cell viability and proliferation. Also, improved cell infiltration and scaffold vascularization generated functional skins displaying high electrical resistance and good water retention. This work enables future research into microenvironment design for rapid tissue regeneration and creation of 3D in vitro tissue models (organ on chips).

These projects generated publications in Adv Funct Mater (2016, 26, 2809; 2017, 27, 1604617; both selected as journal cover and reported by MaterialsViews),Biomaterials (2014, 35, 7308), Acta Biomater (2017, 49, 66, reported by China Science Daily, etc); Adv Healthc Mater (2015, 5, 108, 2015 hot paper), J Mater Chem B (2014, 2, 6660; 2015, 3, 6368; 2016, 4, 3770).