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The initial stability of orthopedic implants in osteoporotic bone matrix is reduced, and excessive M1 macrophage polarization at the bone-implant interface disrupts bone immune homeostasis and vascularization, ultimately leading to implant loosening or failure. Inspired by the marine mussel Mytilus edulis foot protein (Mefp), a pH-responsive multifunctional bone gel (YDC-Gel-Zn) with broad-spectrum adhesive ability was developed for osteoporotic bone-implant integration. This pseudo-Mefp bioadhesive achieves dual-interface adhesion through catechol-rich sequences, mediating stable metal-phenol coordination with metallic implants and hydrogen bond/Michael addition-driven interactions with bone matrix, thereby improving initial implant fixation. In the osteoporotic inflammatory microenvironment, the sequential dissociation of boronate ester bonds and metal-phenol coordination promotes the controlled release of Zn²⁺ and pro-angiogenic/osteogenic peptides (YDC).The released Zn2⁺ remodels glutathione metabolism by regulating glutathione (GSH) levels mediated by glutathione S-transferase (GST), inhibits JAK1/STAT1/NLRP3 inflammasome activation, suppresses pro-inflammatory cytokine release from senescent M1 macrophages, and recalibrates the bone-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the biomimetic bone hydrogel increased fixation strength by 194% in an osteoporotic rat model, achieving 93% healthy bone implant stability. Overall, this study provides a clinically translatable strategy for stable implantation under osteoporotic conditions through synergistic mechanical adaptation, bioactivity regulation, and intelligent environmental responsiveness.
