A multifunctional MOF-mineralized conductive hydrogel coating on zinc implants orchestrates neuro-osteogenic coupling for enhanced bone defect repair

Zinc (Zn)-based implants face critical challenges in clinical orthopedic applications due to rapid corrosion, localized Zn 2+ -induced cytotoxicity, and inadequate osteogenic activity. Herein, we report a metal-organic framework (MOF)-mediated mineralization strategy to engineer a multifunctional conductive hydrogel coating on pure zinc substrates, integrated with polypyrrole nanoparticles (Ppy NPs). This hierarchical coating design significantly enhances interfacial adhesion and reduces the in vitro corrosion volume ratio of zinc substrates by approximately 53.23% after 14 days of immersion, effectively mitigating excessive degradation-associated ion release. The MOF- mediated mineralized layer provides controlled Zn 2+ /Cu 2+ release and stabilizes the implant interface, while Ppy NPs establish an intrinsic electroactive microenvironment. These synergistic ionic and electrical cues promote Schwann cell functional activity, enhance neurotrophic factor secretion, and subsequently facilitate mesenchymal stem cell (MSC) osteogenic differentiation through neuro-osteogenic communication. Notably, co-culture of MSCs with Schwann cells on the Zn/H@MP coating surface results in a 257% increase in alkaline phosphatase activity and a 222% enhancement in mineralized nodule formation compared to MSC mono-culture, accompanied by significant upregulation of key osteogenic markers, demonstrating the neuro-osteogenic coupling effect. In vivo evaluation in a rat bone defect model reveals that the coated implants achieve 79.46% new bone volume fraction at 8 weeks post-implantation, with accelerated osseointegration, mature bone formation, and enhanced peri-implant innervation. By integrating corrosion regulation, bioactive ion delivery, and electroactive neuro-osteogenic modulation, this multifunctional coating provides a promising strategy for next-generation biodegradable orthopedic implants.