Protean bio-heterojunction nanoparticle coating for dynamically modulating diabetic microenvironment

Due to the increased risk of tooth loss associated with diabetes mellitus, patients exhibit a markedly higher demand for dental implant restoration. However, hyperglycemia and the accumulation of advanced glycation end-products (AGEs) induce oxidative stress, increase the risk of peri-implantitis, and impair osseointegration, posing significant challenges to the long-term success of implants. Moreover, the incorporation of antibacterial agents, while enhancing antibacterial efficacy, often elevates oxidative stress and compromises osteogenic capacity and cytocompatibility. Herein, a single-step fabricated bioactive protean TiO₂/ZnO bio-heterojunction (BJ) system was developed on carbon-fiber-reinforced polyetheretherketone (CFRPEEK) implants to dynamically modulate diabetic microenvironment through multi-functional synergy (antibacterial/osteogenic/antioxidant). The CFRPEEK was firstly titanium plasma immersion ion implanted (PIIID-Ti) to obtain a micro-nanoscaled titanium dioxide (TiO₂) interface. Sequentially, enhanced functionalities were attained by incorporating zinc oxide nanoparticles (ZnO NPs) to form TiO₂/ZnO BJ through polydopamine (PDA) assisted π-π covalent immobilization. The results reveal that the TiO₂/ZnO BJ effectively modulates reactive oxygen species (ROS) levels. The BJ PIIID-Ti surface exhibits excellent biocompatibility, osteo-inductive potential, and antibacterial efficacy during the early stage, while featuring a ROS scavenging function facilitated by PDA@ZnO NPs during the later stage. In vivo assessments further confirmed that the modified implants possess excellent biosafety, antibacterial ability and osseointegration capacity in the diabetic rat femoral defect model over six weeks. Moreover, the modified implants alleviated oxidative stress and improved the local regenerative microenvironment through activation of the Keap1/Nrf2 pathway. The BJ PIIID-Ti modified CFRPEEK implants demonstrate potential for combating diabetic infection and self-regulating oxidative stress for tissue protection, offering a theoretical basis for future clinical application.