ROS-responsive puerarin-loaded MOF hydrogel coating: Reprogramming the pathological microenvironment for enhanced...

The impaired osseointegration of titanium implants in diabetic bone defects is critically challenged by the synergistic interference of oxidative stress, chronic inflammation, and compromised angiogenesis. To address this, this study developed a reactive oxygen species (ROS)-responsive hydrogel coating, termed CS-PA/Mg-GA@P. This coating was constructed by dynamically integrating puerarin-loaded Mg-GA-MOF (Magnesium-Gallic acid metal-organic frameworks) into a CS-PA (chondroitin sulfate, CS; polyvinyl alcohol, PA) network via boronate ester bonds, which enabled a precise response to high-ROS microenvironments and the time-controlled release of multiple components. In vitro experiments demonstrated that the coating effectively scavenged excess ROS and stabilized mitochondrial membrane potential, primarily attributed to the antioxidant action of gallic acid (GA). Furthermore, the released Mg²⁺ synergistically promoted macrophage polarization toward the anti-inflammatory M2 phenotype, thereby modulating the local inflammatory microenvironment. Simultaneously, the sustained release of puerarin (P) continuously activated osteogenic signaling pathways, enhancing bone matrix deposition and mineralization. The coating also exhibited excellent pro-angiogenic activity. These multifunctional effects were further validated in vivo using subcutaneous implantation and critical-sized femoral defect models in type 1 diabetic rats. The CS-PA/Mg-GA@P coating significantly exerted combined anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteogenic actions, effectively promoting the osseointegration of titanium implants under diabetic conditions. In conclusion, the CS-PA/Mg-GA@P coating achieves intelligent microenvironmental response and synergistic regulation at diabetic bone defect sites, providing an innovative strategy for the functionalization of titanium implant surfaces.