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

• Published in: Advanced functional materials 2022-07, Vol.32 (27), p.n/a
• Main Authors: Yuan, Zhang, Wu, Jianshuang, Fu, Zhenxiang, Meng, Siyu, Dai, Liangliang, Cai, Kaiyong
• Format: Article
• Language: English
• Subjects: Aspartic acid; Biomedical materials; bone repair; Carbon monoxide; CO gas therapies; Differentiation (biology); Glycine; implant‐associated infections; Infections; Kinases; macrophage polarization; Macrophages; Materials science; Nanogenerators; photo‐activatable antibiosis; Polarization; Polypeptides; Transplants & implants
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202200374

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. The development of a multifunctional interface is described by integrating a carbon monoxide gas (CO) nanogenerator onto titanium implant, which displays light‐activatable antibiosis, CO‐mediated anti‐inflammation, and macrophage M2 polarization. It provides valuable information to understand the importance of macrophage phenotype reprogramming in bone repair under abnormal inflammatory conditions, but also provides new insights for biomedical application of CO gas therapy.