Adhesive Hydrogel Barriers Synergistically Promote Bone Regeneration by Self-Constructing Microstress and Mineralization Microenvironment

Abstract

Mechanical loading is a key factor in bone growth and regeneration. In bone defect repair, combining micro-stress stimulation with an excellent inorganic microenvironment offers a more effective strategy for promoting bone regeneration. In this study, guided by the strategy to create both micro-stress and a mineralization microenvironment in the bone defect area, a membrane-like hydrogel barrier (PN-GEL@BP-PE) was designed. The hydrogel barrier adheres tightly to the bone surface via polyethyleneimine/polyacrylic acid (PEI/PAA) and generates micro-stress through the volume deformation of poly(N-isopropylacrylamide) at body temperature. Meanwhile, the inorganic microenvironment that promotes bone mineralization is induced by the calcium recruitment properties of black phosphorus nanosheets (BPNs). This membrane activates the cellular micro-stress response in mesenchymal cells, working synergistically with the calcium recruitment effect of BPNs to enhance osteogenic mineralization. In vivo, the bone regeneration effect of the hydrogel membrane is approximately 50% higher than that of conventional treatments, indicating that PN-GEL@BP-PE exhibits strong osteogenic efficacy. This synergistic strategy, combining osteogenic physical and chemical microenvironments, represents a promising direction for future research.