Click-based injectable bioactive PEG-hydrogels guide rapid craniomaxillofacial bone regeneration by the spatiotemporal delivery of rhBMP-2

Craniomaxillofacial bone defects result in physical and psychological dual injuries making the promotion or acceleration of bone regeneration imperative. In this work, a fully biodegradable hydrogel is facilely prepared via thiol-ene click reactions under human physiological conditions using multifunctional poly(ethylene glycol) (PEG) derivatives as precursors. This hydrogel shows excellent biological compatibility, enough mechanical strength, a low swelling rate and an appropriate degradation rate. Rat bone marrow mesenchymal stem cells (rBMSCs) can survive and proliferate on/in the PEG hydrogel and differentiate into osteogenic cells. The PEG hydrogel can also effectively load rhBMP-2 through the above click reaction. Under the physical barrier of the chemically crosslinked hydrogel network, the spatiotemporal release of rhBMP-2 effectively promotes the proliferation and osteogenic differentiation of rBMSCs at a loading concentration of 1 mu g ml(-1). Finally, based on a rat calvarial critical-size defect model, the rhBMP-2 immobilized hydrogel loaded with rBMSCs basically accomplishes the repair and regeneration within 4 weeks featured by remarkably enhanced osteogenesis and angiogenesis. The click-based injectable bioactive PEG hydrogel developed in the present study is a new type of bone substitute with great expectations in future clinical applications.

Automated summary

In this study, a fully biodegradable hydrogel, with excellent biological compatibility and mechanical properties, was prepared via thiol-ene click reactions using multifunctional poly(ethylene glycol) (PEG) derivatives. Rat bone marrow mesenchymal stem cells (rBMSCs) could survive, proliferate, and differentiate into osteogenic cells on/in the hydrogel. The hydrogel also effectively loaded rhBMP-2, promoting the proliferation and osteogenic differentiation of rBMSCs. Furthermore, in a rat calvarial critical-size defect model, the hydrogel loaded with rhBMP-2 and rBMSCs achieved successful repair and regeneration within 4 weeks.