A Pseudo-Mytilus Edulis Foot Protein-Based Hydrogel Adhesive with Osteo-Vascular-Immune Coupling Effects for Osteoporotic Bone-Implant Integration

The reduced initial stability of orthopedic implants in osteoporotic bone matrices, coupled with excessive M1 macrophage polarization at bone-implant interfaces, disrupt 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 glue (YDC-Gel-Zn) with broad-spectrum adhesion capabilities is developed for osteoporotic bone-implant integration. This pseudo-Mefp bioglue enables dual-interface adhesion via catechol-rich sequences that mediate stable metal-phenolic coordination with metallic implants and hydrogen-bonded/Michael addition-driven interactions with the bone matrix, thereby improving initial implant fixation. Under osteoporotic inflammatory microenvironments, sequential dissociation of borate ester bonds and metal‒phenolic coordination facilitates the controlled release of Zn 2 ⁺ and proangiogenic/osteogenic peptides (YDC). The released Zn 2 ⁺ remodels glutathione metabolism through glutathione S-transferase (GST)-mediated regulation of glutathione (GSH) levels, inhibits JAK1/STAT1/NLRP3 inflammasome activation, and suppresses the release of proinflammatory cytokines from senescent M1 macrophages, recalibrating the osteo-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the bioinspired bone bioglue demonstrated a 194% increase in fixation strength in osteoporotic rat models, 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 smart environmental responsiveness.