Physicochemical, Pharmacologic, and in Vitro Cellular Effects of Loading Collagen Membranes with Zoledronic Acid

Purpose: There is a need for improved methods of reducing peri-implant bone loss. This study evaluated the structural, drug loading, drug release, and in vitro characteristics of collagen membranes impregnated with zoledronic acid (ZA). Materials and Methods: Two commercially available collagen barrier membranes (Bio-Gide and BME-10X) were loaded with ZA. The physicochemical and pharmacologic properties of the membranes were characterized with scanning electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. The ZA-loaded membrane's inhibition of osteoclasts and promotion of osteoblast growth was evaluated in vitro at ZA concentrations of 0, 10-4, 10-3, and 10-2 mol/L. Results: The disappearance of micropores between Bio-Gide collagen fibers and the formation of crystalloids on the surface of BME-10X membranes following ZA loading was evident under the microscope. Phosphorus was detected on the membranes, and amide shifts were observed. Greater amounts of ZA loading and slower ZA release were evident for Bio-Gide membranes. Osteoclast numbers were reduced with ZA, and a corresponding decrease in bone resorption was evident at higher ZA concentrations (P .05). After 7 days, at a ZA concentration of 10-3 mol/L, Bio-Gide membranes had an increased osteoblast proliferation index, while both types of membranes displayed increased alkaline phosphatase expression. Conclusion: Collagen membranes loaded with ZA provided delayed drug release. This study may offer a novel therapeutic strategy for minimizing peri-implant bone resorption. Keywords: collagen membranes, drug delivery systems, osteoblasts, osteoclasts, zoledronic acid