Polydopamine-Mediated Interfacial Functionalization of Implants for Accelerating Infected Bone Repair through Light-Activatable Antibiosis and Carbon Monoxide Gas Regulated Macrophage Polarization

Current treatments for implant-associated infection remain unsatisfactory due to secondary infection and excessive inflammation, which impairs osseointegration. Herein, an interfacial functionalization strategy is proposed by the integration of a carbon monoxide gas (CO) nanogenerator on titanium implants, followed by covalently grafting arginine-glycine-aspartic acid (RGD) polypeptide. Under near-infrared light (NIR) irradiation, the designed surface displays great light-activatable antibiosis through CO-potentiated mild photothermal therapy. Interestingly, the functionalized surface exerts a CO-mediated anti-inflammatory effect by activating the expression of heme oxygenase (HO-1), and inducing the down-regulation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) (p50/p65). More importantly, the combination of CO delivery and RGD immobilization drives the polarization of lipopolysaccharide (LPS)-stimulated M1-phenotype macrophages towards anti-inflammatory M2-phenotype through a potential Janus kinase 1/signal transducer and activator of transcription 6 (JAK1/STAT6) pathway, thereby remodeling the damaged microenvironment into a pro-regenerative microenvironment. In a rat model of implant-associated infection, the designed surface effectively eliminates the residual bacteria, alleviates the accompanying inflammation and mediates macrophage-mediated immunomodulation, resulting in good osteogenesis. Together, these findings are a first report on the therapeutic potential of CO signal in the cascade of immunomodulation-osteogenic differentiation. The functionalized implant may serve as a promising candidate in implant replacement surgeries.