Programmed Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 and Inorganic Ion Composite Hydrogel as Artificial Periosteum.

ABSTRACT

Recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioceramic are the widely used bioactive factors in treatment of bone defects, but these easily cause side effects because of uncontrollable local concentration. In this study, rhBMP-2 was grafted on the surface of mesoporous bioglass nanoparticles (MBGNs) with an amide bond and then photo-cross-linked together with methacrylate gelatin (GelMA); in this way, a GelMA/MBGNs-rhBMP-2 hydrogel membrane was fabricated to release rhBMP-2 in a controllable program during the early bone regeneration period and then release calcium and silicon ions to keep promoting osteogenesis instead of rhBMP-2 in a long term. In this way, rhBMP-2 can keep releasing for 4 weeks and then the ions keep releasing after 4 weeks; this process is matched to early and late osteogenesis procedures. In vitro study demonstrated that the early release of rhBMP-2 can effectively promote local cell osteogenic differentiation in a short period, and then, the inorganic ions can promote cell adhesion not only in the early stage but also keep promoting osteogenic differentiation for a long period. Finally, the GelMA/MBGNs-rhBMP-2 hydrogel shows a superior capacity in long-term osteogenesis and promoting bone tissue regeneration in rat calvarial critical size defect. This GelMA/MBGNs-rhBMP-2 hydrogel demonstrated a promising strategy for the controllable and safer use of bioactive factors such as rhBMP-2 in artificial periosteum to accelerate bone repairing.