Thiol-Epoxy “Click” Chemistry to Engineer Cytocompatible PEG-Based Hydrogel for siRNA-Mediated Osteogenesis of hMSCs

Thiol-epoxy “click” chemistry is employed for the first time to engineer a new cytocompatible PEG-based hydrogel system in aqueous media with the ability to encapsulate human mesenchymal stem cells (hMSCs) and control their fate for tissue regeneration. Cells were easily encapsulated into the hydrogels and exhibited high cell viability over 4 weeks of culture regardless of the presence of siRNA, complexed with polyethylenimine (PEI) in the form of siRNA/PEI nanocomplexes, indicating the biocompatibility of the developed hydrogel. Loading pro-osteogenic siNoggin in the hydrogel significantly enhanced the osteogenesis of encapsulated hMSCs, demonstrating the potential application of this system in tissue engineering