Microenvironment-responsive coating with bio-functional switching from infection clearance to adaptive osteogenesis.

Abstract

Successful long-term bone repair requires implant interfaces to precisely regulate the competitive recruitment between pathogens and host cells. However, coordinating the transition from potent pathogen clearance to refined osteogenic induction remains challenging, as the high-affinity synergies required for rapid bactericidal action often hinder the spatiotemporal signaling necessary for later cell differentiation. Herein, a microenvironment-responsive implant coating (Ti-TF-R) is developed to orchestrate this critical spatiotemporal transition from infection eradication to tissue repair. The platform encapsulates a photothermal metal-phenolic network (TA/Fe) within a biomimetic red blood cell membrane (RBCM) shell. During the acidic infection phase, near-infrared (NIR) irradiation enhances RBCM fluidity, opening "lipid valves" that promote the dissociation and release of the inner TA/Fe layer. TA reduces Fe³⁺ to Fe²⁺, triggering a strong Fenton-like reaction in the infectious environment with high H₂O₂ concentration. This reaction, together with the RBCM-enhanced local photothermal efficiency, induces a bacterial metabolic collapse and ferroptosis. As the infection subsides, the gradually shedding of the RBCM exposes the underlying bioactive TA/Fe layer, which maintains a sustained low-dose iron supply, creating a favorable microenvironment for osteoblast adhesion and differentiation. This spatiotemporally coordinated strategy effectively addresses recalcitrant implant-associated infections while accelerating bone-implant integration, providing a generalizable paradigm for time-programmed therapeutic biomaterials.