Calcium Phosphate Cement with Minocycline Hydrochloride-loaded Gelatine Microspheres for Peri-implantitis Treatment

Objectives: This study aimed to fabricate an antibacterial calcium phosphate cement (CPC) with minocycline hydrochloride (MINO)-loaded gelatine microspheres (GMs) as a local drug delivery system for the treatment of peri‑implantitis.

Methods: CPC/GMs(MINO), incorporating MINO-loaded GMs into CPC, was developed and characterised using scanning electron microscopy (SEM), X-ray diffraction (XRD), and drug release profiling. The antibacterial activity against Porphyromonas gingivalis and Fusobacterium nucleatum was evaluated. Bone mesenchymal stem cells (BMSCs) were cultured in the extracts of the developed cements to evaluate osteoinductivity in vitro. Furthermore, a rabbit femoral model was established to evaluate osteogenic ability in vivo.

Results: SEM and XRD confirmed the porous structure and chemical stability of CPC/GMs(MINO). The release profile showed a sustained release of MINO from CPC/GMs(MINO), reaching an equilibrium state on the 14th day with a cumulative release ratio of approximately 84%. For antibacterial assays, the inhibition zone of CPC/GMs(MINO) was 3.67 ± 0.31 cm for P. gingivalis and 7.47 ± 0.50 cm for F. nucleatum. Most bacteria seeded on CPC/GMs(MINO) died after 24 h of culture. In addition, CPC/GMs(MINO) significantly enhanced alkaline phosphatase activity, osteogenic gene expression, and BMSC mineralisation compared with CPC/GMs and the control group (P < 0.05). The in vivo results showed that CPC/GMs(MINO) possessed a higher quality and quantity of bone formation and maturation than CPC/GMs and CPC.

Conclusions: CPC/GMs(MINO) showed excellent antibacterial activity against pathogens associated with peri‑implantitis and demonstrated good osteoinductivity and osteogenic ability.

Clinical Significance: Peri-implantitis is among the most common and challenging biological complications associated with dental implants. In this study, MINO-loaded GMs were incorporated into CPC, which endowed the composite cement with excellent antibacterial and osteogenic abilities, demonstrating its potential as a bone graft substitute for treating peri‑implantitis.