TiO₂ Nanotube Implants Modified with Silk Fibroin and Mesoporous Silica Nanocomposite Coatings Enable Efficient Drug Release to Promote Osteogenesis

Enhanced bone healing within 1 week after post-titanium (Ti) dental implant surgery especially contributes to the subsequent long-term osseointegration, and the commonly used drug-loaded TiO₂ nanotubes (TNTs) can promote osteogenesis yet still face the challenge of burst drug release that makes it difficult to maintain long-term effective drug concentrations and good osseointegration. Here, we prepared a double drug loading/release system of silk fibroin/mesoporous silica nanoparticles (SF/MSN) nanocomposite coating modified TNTs (TAMA) with AZD2858 (Wnt/β-catenin pathway agonist for promoting osteogenesis) as the therapeutic drug, realizing a long-term stable drug release and better osteogenesis. The increased β-sheet content of SF reduced the degradation rate of the SF/MSN coating, thus avoiding the AZD2858 burst release. The adsorption of MSN maintained the effective drug concentration more than 1 week that was especially critical for early bone healing. Under the protection of SF/MSN coating, the TAMA implant showed a well-organized spatial release of AZD2858, well enabling the osteogenic differentiation and mineralization at cellular level for up to 21 days. Animal experiments further demonstrated that the slow release of AZD2858 in the TAMA implant effectively activated the Wnt/β-catenin pathway, enabling rapid bone healing in the early stage of implantation and finally achieving the best osseointegration efficacy. Thus, this study proposed an efficient strategy for developing high-performance dental implants via the construction of a biodegradable SF/MSN coating.