Adhesive hydrogel barriers synergistically promote bone regeneration by self-constructing microstress and mineralization microenvironment

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 <i>via</i> polyethyleneimine/polyacrylic acid (PEI/PAA) and generates micro-stress through the volume deformation of poly(<i>N</i>-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. <i>In vivo</i>, 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.