Microsphere-Coated Drug Reservoirs in Titanium Implants with pH-Responsive and Osmolality-Adaptive Drug Release for Enhanced Antibacterial Efficacy and Biocompatibility

The clinical mandibular implant surgery disrupts the semiopen oral environment, posing risks of postoperative infection and inadequate osseointegration. Unfortunately, the conventional mandibular implants with local drug reservoirs typically follow predetermined release profiles, which limit their adaptability to the complex and variable oral environment. To solve this problem, this paper proposes a microsphere-coated drug reservoir with pH-responsive/osmolality-adaptive drug release, aiming to achieve closed-loop drug delivery. First, the drug reservoir was designed in a funnel shape. Its inner wall was modified using a combination of silicone oil treatment and laser etching to create a surface suitable for microsphere anchoring. Second, Staphylococcus aureus is a common oral pathogen whose metabolic products can lower local pH levels. Inspired by this, the pH-responsive characteristics of drug-loaded microspheres were analyzed through comparative studies. The osmotic pressure regulation mechanism was elucidated through U-tube experiments. Finally, adaptive antimicrobial and biocompatibility evaluations were conducted. The results show that the cumulative release of CIP-gelatin microspheres in a severe inflammation model (pH 5.5) reaches 55.17% after 120 h, significantly higher than the 29.18% in a mild inflammation model (pH 6.5). Consequently, the antimicrobial efficacy of the drug reservoir equipped with CIP-gelatin microspheres is markedly enhanced. Moreover, the number of chondrosarcoma cells adhering to the surface of the modified reservoir increased by 60%, indicating its excellent biocompatibility. Therefore, the proposed microsphere-coated drug reservoir provides both theoretical insight and practical guidance for developing adaptive (closed-loop) drug delivery mandibular implants.