Continuous local minocycline delivery from PLA nanosphere-coated dental implants with long-term antibacterial...

Peri-implant infections remain a major cause of dental implant failure and are often associated with bacterial colonization and biofilm formation on implant surfaces. This study aimed to develop and evaluate minocycline (MC)-coated dental implants for local antibiotic delivery and infection prevention. Drug-free poly(d,l-lactic acid) (PLA) nanospheres and free MC were co-deposited onto the implant surface. The coated implants were evaluated for drug release, antibacterial activity, biocompatibility, and osseointegration. In vitro drug release studies demonstrated continuous MC release for at least 12 weeks, with concentrations remaining above the minimum inhibitory concentration (MIC) of Porphyromonas gingivalis. Antibacterial activity was confirmed by bacterial immersion and agar diffusion assays, showing inhibition of P. gingivalis growth for up to 12 weeks. Hemocompatibility and cytocompatibility evaluations revealed negligible hemolysis and high cell viability, indicating good in vitro biocompatibility. In vivo intracutaneous irritation and skin sensitization studies performed according to ISO 10993 standards demonstrated no evidence of irritation or delayed hypersensitivity reactions. Furthermore, a 12-week implantation study in rabbits demonstrated no adverse clinical signs, inflammatory responses, foreign body reactions, or tissue necrosis. Histological examination revealed direct bone-to-implant contact, normal bone marrow architecture, and the absence of fibrous encapsulation in both uncoated and MC-coated implants, indicating successful osseointegration. Collectively, the results demonstrate that MC-coated dental implants provided prolonged local antibiotic delivery and long-term antibacterial activity while maintaining biocompatibility and osseointegration. The PLA nanosphere coating approach may facilitate the development of drug-eluting dental implants for localized delivery of therapeutic agents to support peri-implant tissue health and reduce the risk of implant-associated infections.