Engineering in situ cross-linkable and neurocompatible hydrogels

Physical injuries of the central nervous system (CNS) are prevalent and very severe because the CNS has limited capacity to replace neuronal loss from the injury. A growing body of evidence has suggested that exogenous cell transplantation is one promising strategy to promote CNS regeneration. Direct injection of neural stem cells (NSCs) to the lesion site, however, may not be an optimal therapeutic strategy because of poor viability and functionality of transplanted cells resulting from the local hostile tissue environment. The overall objective of this study is to engineer an injectable and biocompatible hydrogel system as a supportive niche to provide a regeneration permissive microenvironment for transplanted NSCs to survive, functionally differentiate, and integrate with host tissues for CNS regeneration. A highly biocompatible hydrogel, based on thiol functionalized hyaluronic acid and thiol functionalized gelatin (Gtn-SH), which can be cross-linked by poly(ethylene glycol) diacrylate (PEGDA), was used. By controlling the cross-linking density via varying the amount of cross-linker (PEGDA) and the concentration of the adhesive component gelatin, an optimal microenvironment for the survival, proliferation, and neuronal differentiation of NSCs was created in vitro. The soft hydrogel of less than 10 Pa with Gtn-SH content (50%) is one of the optimal conditions to support NSCs growth and neuronal differentiation in vitro. The optimized hydrogel holds great potential as a carrier of stem cells to treat CNS injuries and diseases in which cell therapies may be essential.