Microenvironment-responsive nanoparticles functionalized titanium implants mediate redox balance and immunomodulation for enhanced osseointegration

Various pathological conditions ( e.g. , diabetes, osteoporosis) are accompanied by persistent oxidative stress, which compromises the immune microenvironment and poses substantial challenges for osseointegration. Reactive oxygen species (ROS) play a “double-edged sword” role in bone tissue. Therefore, developing responsive biomaterials to maintain redox balance dynamically is crucial for enhanced osseointegration. Herein, the microenvironment-responsive coordination nanoparticles (C-Ca-SalB NPs) composed of salvianolic acid B (SalB), catechol-conjugated chitosan (CS-C), and Ca 2+ are constructed and further covalently immobilized onto titanium implant surfaces. The resulting implants achieve on-demand antioxidant and immunomodulatory effects in a microenvironment-responsive manner, thus facilitating bone regeneration under both normal and oxidative conditions. Under physiological conditions, the functionalized implants display modest immunomodulatory properties without affecting oxidative balance, while C-Ca-SalB NPs remain relatively stable. However, the modified implants enable rapid decomposition of C-Ca-SalB NPs under acidic oxidative conditions, displaying robust ROS-scavenging, anti-inflammatory, and osteoinductive capacities, ultimately remodeling the pathological microenvironment into a regenerative one. Overall, smart implants with controlled bioactive agent release in this study present a comprehensive solution for enhancing bone-implant integration, particularly in the challenging context of oxidative stress. In the present study, the coordination nanoparticles (C-Ca-SalB NPs) are designed and further covalently immobilized onto titanium implant surfaces. The resulting novel implants can facilitate osseointegration under various conditions, including normal conditions and challenging oxidative stress conditions, by achieving on-demand antioxidant and immunomodulatory effects in a microenvironment-responsive manner.