Mn-TA nanoparticle-reinforced hydrogel coating on TiO2 nanotube implants for enhanced osseointegration via antioxidant, anti-inflammatory, and osteogenic activities

Excessive oxidative stress and associated inflammation significantly impair bone regeneration around implants. To address this, we developed a novel therapeutic strategy based on metal-polyphenol nanoparticles self-assembled from tannic acid (TA) and manganese ions (Mn 2+ ). These Mn-TA nanoparticles (Mn-TA NPs) were subsequently incorporated into a gelatin methacryloyl (GelMA) hydrogel, which was then applied as a coating onto TiO 2 nanotube (TNT) surfaces by spin coating. The resulting modified titanium was designated as TNT-GelMA@NPs. Surface and interfacial characterization using scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, spectroscopic ellipsometry and nanoindentation confirmed the successful fabrication of a uniform, adherent hydrogel coating on the TNT surfaces. The coating reduced surface roughness while maintaining hydrophilicity, and achieved sustained Mn 2+ release, as verified via inductively coupled plasma atomic emission spectroscopy (ICP-AES). TNT-GelMA@NPs exhibited potent ROS scavenging capacity, protected mitochondrial membrane potential, and upregulated antioxidant genes. Moreover, it promoted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, thereby creating a favorable osteoimmune microenvironment. Additionally, it promoted osteogenic differentiation by increasing ALP activity, mineralization, and the expression of osteogenic genes. In a rat femoral defect model, TNT-GelMA@NPs implants reduced oxidative damage and inflammation, while enhancing bone formation, as evidenced by histological staining and micro-CT analysis. This study demonstrates that the Mn-TA NP-reinforced hydrogel coating acts as a multifunctional biointerface with excellent potential for advanced implant surface engineering.