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

Various pathological conditions (<i>e.g.</i>, 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 Ca²⁺ 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.