The initial stability of orthopedic implants in osteoporotic bone matrix is reduced, coupled with excessive M1 macrophage polarization at the bone-implant interface, which disrupts bone immune homeostasis and vascularization, ultimately leading to implant loosening or failure. Inspired by the foot protein (Mefp) of the marine mussel Mytilus edulis, a pH-responsive multifunctional bone glue (YDC-Gel-Zn) with broad-spectrum adhesion ability was developed for osteoporotic bone-implant integration. This pseudo Mefp bio-glue achieves dual interface adhesion through sequences rich in catechol, mediates stable metal-phenolic coordination with the metal implant, and hydrogen bond/michael addition-driven interactions with the bone matrix, thereby improving the initial implant fixation. In the osteoporotic inflammatory microenvironment, the sequential dissociation of borate ester bonds and metal-phenolic coordination promotes the controlled release of Zn2⁺ and pro-angiogenic/osteogenic peptides (YDC). The released Zn2⁺ is regulated by glutathione S-transferase (GST)-mediated glutathione (GSH) levels to reshape glutathione metabolism, inhibits JAK1/STAT1/NLRP3 inflammatory body activation, inhibits the release of pro-inflammatory cytokines by senescent M1 macrophages, and recalibrates the bone-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the biomimetic bone bio-glue improves the fixation strength by 194% in osteoporotic rat models and achieves 93% stable bone implantation in healthy bone. Overall, this study provides a clinically translational strategy for stable implantation under osteoporotic conditions through synergistic mechanical adaptation, bioactivity regulation, and intelligent environmental responsiveness. This research was published in Advanced Materials under the title "A Pseudo-Mytilus Edulis Foot Protein-Based Hydrogel Adhesive with Osteo-Vascular-Immune Coupling Effects for Osteoporotic Bone-Implant Integration".
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DOI: 10.1002/adma.202511840