Cell-derived extracellular matrix coating on β‑zirconium alloy for enhanced osteogenic and angiogenic responses with pH-responsive antibacterial activity

Zirconium-based alloys, especially β‑zirconium alloys, are promising biomaterials due to low stiffness and bone compatibility. However, infection and insufficient bioactivity remain major challenges limiting their long-term clinical performance. Herein, we developed a multifunctional cell-derived extracellular matrix (ECM)-based coating that integrates osteogenic and angiogenic responses with pH-responsive antibacterial activity. A native ECM layer was generated on the porous hydroxyapatite-coated alloy surface through mesenchymal stem cell induction and subsequently functionalized with vancomycin via EDC/NHS-mediated covalent coupling, enabling pH-responsive vancomycin release under acidic conditions. The ECM-derived interface provides a protein-rich biomimetic microenvironment that facilitates rapid cell adhesion and proliferation. Moreover, the aligned ECM fibers directed cell alignment toward an elongated spindle-shaped morphology and promoted osteogenic differentiation. The vancomycin-functionalized ECM (optimized at 5 mg/mL loading) preserved these biological properties while exhibiting effective antibacterial activity in vitro through pH-responsive vancomycin release and a potential coating-interface effect. In vivo, implants modified with the ECM-vancomycin coating exhibited significantly enhanced osseointegration, characterized by increased new bone formation, improved collagen matrix maturation, and enhanced angiogenic responses at the implant-bone interface. This study presents a multifunctional implant surface strategy that combines cell-derived ECM-mediated regeneration with in vitro pH-responsive antibacterial functionality, providing a promising strategy for improving the biological performance of orthopedic implants.