Preparation of Simvastatin-Reduced TiO ₂ Nanotube-Hydrogel System for Exogenous Dynamic Immune Regulation

Titanium (Ti) is one of the most widely used implant materials; however, postoperative failures still frequently occur due to its poor osseointegration and limited antibacterial performance. The key to accelerating bone healing and improving implantation success lies in modulating immune responses through the regulation of immune cell behaviors. In this work, simvastatin, which is reported to have the immune regulation function, was loaded into photothermal TiO 2 nanotubes (diameter 60–65[Formula: see text]nm) formed on the Ti surface and subsequently covered with an intelligent thermosensitive chitosan hydrogel (phase transition temperature 38.95[Formula: see text]C) to construct a light-controlled drug release system (SCTH@rNT). The release of simvastatin from TiO 2 nanotubes was precisely regulated under Near-Infrared (NIR) irradiation. In vitro, the SCTH@rNT [Formula: see text] NIR system exhibited remarkable antibacterial activity, reducing the viable colonies of Staphylococcus aureus and Escherichia coli by 98.6% and 97.4%, respectively, and significantly promoting osteogenic differentiation, with Alkaline Phosphatase (ALP) activity 1.8-fold higher than that of the control on day 14. The controlled release further enabled immunomodulation by up-regulating Interleukin-10 (IL-10) expression 2.3-fold and down-regulating Tumor Necrosis Factor-alpha (TNF-[Formula: see text] by 48%, thereby alleviating inflammation. In vivo, the system reduced inflammatory cell infiltration by 62.7% and markedly enhanced new bone formation. Overall, this light-controlled drug delivery platform effectively creates a favorable immune microenvironment by dynamically regulating the macrophages behaviors, showing great potential for clinical translation in improving the integration and longevity of Ti-based implants.