PPARgamma delivered by Ch-GNPs onto titanium surfaces inhibits implant-induced inflammation and induces bone mineralization of MC-3T3E1 osteoblast-like cells.

OBJECTIVES: To deliver the efficacy and safety of Ch-GNPs (Chitosan gold nanoparticles) conjugated anti-inflammatory molecules peroxisome proliferator activated receptor gamma (PPARgamma) on implant surface titanium (Ti) to reduce implant-induced inflammation. MATERIALS AND METHODS: The Ch-GNPs were conjugated with the PPARgamma cDNA through a coacervation process. Conjugation was cast over Ti surfaces by dipping, and cells were seeded on different sizes (6 x 6 x 0.1 cm and 1 x 1 x 0.1 cm; n = 3) of Ti surfaces. The size of Ch-GNPs and surface characterization of Ti was performed using UV-vis spectroscopy, TEM (Transmission electron microscopy) and EDX (energy-dispersive X-ray). The DNA conjugation and transfection capacity of Ch-GNPs were simultaneously confirmed by agarose gel electrophoresis, beta-galactosidase staining, and immunoblotting. RESULTS: The Ch-GNPs were well dispersed and spherical in shape, with average size around 10-20 nm. Ti surfaces coated with Ch-GNPs/LacZ, as transfection efficacy molecule, showed strong beta-galactosidase staining in MC-3T3 E1 cells. Cells cultured on Ch-GNPs/PPARgamma-coated Ti surfaces were able to inhibit implant-induced inflammation by simultaneously suppressing the expression of tumor necrosis factor- alpha (TNF-alpha), interleukin-1 beta (IL-1beta), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-2 (MMP-2). The inhibition mechanism of Ch-GNPs/PPARgamma was due to inhibition of both reactive oxygen species (ROS) and nitric oxide (NO) secretion (n = 3; P < 0.05). In addition, Ch-GNPs/PPARgamma was able to increase expression of bone morphogenetic protein (BMP-7) and runt-related transcription factor-2 (RUNX-2). Furthermore, alkaline phosphatase activity (ALP) was also increased than that in control (n = 3; P < 0.01). Whereas, expression of receptor activator of NF-kappaB ligand (RANKL) was decreased. CONCLUSIONS: The novel gene delivery materials, like Ch-GNPs, can carry the PPARgamma cDNA into the required areas of the implant surfaces, thus aiding to inhibit inflammation and promote osteoblast function. Thus, the PPARgamma on implant surfaces may promote its clinical application on peri-implantitis or periodontitis like diseases.