Peptide-based Self-adaptive Implant Coating Sequentially Regulates Bone Regeneration to Enhance Interfacial Osseointegration

Aseptic loosening is the primary cause of orthopaedic implant failure. Previous designs for implant coatings failed to follow the physiological process of bone regeneration, leading to inadequate osseointegration at the bone–implant interface. We engineered a novel self-adaptive titanium-based coating (DOPA-P1@P2) by combining a mussel-inspired biomimetic strategy with bioorthogonal click chemistry techniques. Both in vitro and in vivo results confirmed that DOPA-P1@P2 exhibited excellent biocompatibility and effectively enhanced osseointegration. Specifically, the outermost K23 layer of DOPA-P1@P2 promotes M2 macrophage polarization in the first stage of bone regeneration, creating a favourable immune microenvironment. Following the release of K23, the sequential exposure of the K15 and Y5 layers promoted angiogenesis and osteogenesis during the second stage of bone regeneration. In the third stage of bone regeneration, the DOPA-P1@P2 group exhibited a 161% increase in maximal push-out force, a 207% increase in BV/TV, and a remarkable 1409% increase in BIC, compared to the TiO ₂ control group. In summary, DOPA-P1@P2 effectively promoted bone regeneration through sequential regulation, thus enhancing osseointegration at the bone–implant interface.