부산대학교 도서관

Titanium and its alloys are widely used materials for biomedical devices including orthopedic/dental implants. However, peri-implantitis is associated with recurrent surgeries and remains problematic and therefore a biocompatible approach is required to reduce instances of infection. Herein, we report on the antimicrobial potential (against key oral pathogens) and biocompatibility of a novel metronidazole-loaded chitosan formulation (coating titanium surfaces) and compare the findings with those obtained for metronidazole-loaded poly-(lactide-co-glycolide) (PLGA) coatings. Titanium disc surfaces were coated with defined metronidazole-loaded polymer-based formulations and physicochemically characterized using scanning electron microscopy (SEM), Raman spectroscopy, X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). Metronidazole released at each time point was measured using high-pressure liquid chromatography (HPLC). Antimicrobial activity of the coatings was assessed using agar disk diffusion method. Biocompatibility of the coatings was evaluated using live/dead stain confocal imaging and MTS cell proliferation assay. Osseointegration was determined by measuring BMP-2 protein expression using ELISA. PLGA coatings exhibited a smooth surface morphology, whereas the chitosan coatings exhibited a rough structure. Raman spectroscopy, XRD, and DSC data indicated no evidence of physicochemical incompatibility issues of metronidazole with PLGA and high and low molecular weight chitosan. Metronidazole delivered via high (n = 3, p < 0.01) and low molecular weight chitosan (n = 3, p < 0.01) coatings had significantly enhanced antimicrobial activity against Prevotella intermedia (P. intermedia) compared to when delivered via PLGA coatings (n = 3). Treponema denticola was also tested and was found to be significantly susceptible to metronidazole loaded in low molecular weight chitosan (n = 3, p < 0.05) compared to when delivered via PLGA coatings (n = 3). In addition, chitosan coatings were shown to be more biocompatible and with good osseointegration potential compared to PLGA coatings as demonstrated by higher cell viability and bone morphogenic protein-2 (BMP-2) levels, respectively. A titanium implant surface coated with metronidazole that is delivered via chitosan was successfully developed and can be considered as an appealing strategy for prevention and treatment of peri-implant infection.