Osteoblast Response to Titanium Surfaces Coated with Strontium Ranelate-Loaded Chitosan Film

Purpose: Improving the peri-implant bone quality has notable clinical value in cases of osteoporosis following implant insertion. Materials and Methods: In this study, strontium ranelate-loaded chitosan film was produced on a titanium surface in different concentrations of strontium ranelate (SR) (0, 2, 20, 40, and 80 mmol/L of the strontium ion [Sr2+]) with the expectation of utilizing the bone healing-enhancement effect of Sr2+. The physicochemical properties of SR-loaded chitosan films were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The release/dissolution mechanism was tested by inductively coupled plasma optical emission spectrometry (ICP-OES), and in vitro cell responses were evaluated using primary osteoblasts (POBs) in terms of cell proliferation, alkaline phosphatase (ALP) activity, and quantitative analysis of key osteoblastic gene expression. Results: XRD and FTIR observation showed that only a few SRs reacted chemically with chitosan through hydrogen bonds or conjugate action. The initial burst release (70% to 85%) of Sr2+ occurred in the first 3 days and was followed by a slower release stage. At a low concentration (2 mmol/L or 20 mmol/L), SR-loaded chitosan film promoted cell responses of POBs with enhanced proliferation, ALP activity, and expression levels of bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, and osteocalcin, but at a high concentration (40 mmol/L or 80 mmol/L), it inhibited POB growth. Conclusion: These results indicated that SR-loaded chitosan film on a titanium surface promotes osteoblast proliferation and differentiation in a dose-dependent manner, which may represent a new approach in the treatment of a titanium implant. Keywords: chitosan, drug-releasing membrane, osteoblast, strontium ranelate, titanium surface coating