Bioactive materials play vital roles in the repair of critical bone defects. However, bone tissue engineering and regenerative medicine are still challenged by the need to repair bone defects evenly and completely. In this study, we functionally simulated the natural creeping substitution process of autologous bone repair by constructing an injectable, hierarchically degradable bioactive scaffold with a composite hydrogel, decalcified bone matrix (DBM) particles, and bone morphogenetic protein 2. This composite scaffold exhibited superior mechanical properties. The scaffold promoted cell proliferation and osteogenic differentiation through multiple signaling pathways. The hierarchical degradation rates of the crosslinked hydrogel and DBM particles accelerated tissue ingrowth and bone formation with a naturally woven bone-like structure in vivo. In the rat calvarial critical defect repair model, the composite scaffold provided even and complete repair of the entire defect area while also integrating the new and host bone effectively. Our results indicate that this injectable, hierarchically degradable bioactive scaffold promotes bone regeneration and provides a promising strategy for evenly and completely repairing the bone defects.
Keywords: BMP2; DBM particles; bone regeneration; hierarchical degradation; hydrogel; tissue ingrowth.