Prevention of medication-related osteonecrosis of the jaw in a rat animal model

<b>Aims</b>\ud \ud - This study aimed to evaluate the efficacy of a novel polyethylene glycol-heparin hydrogel (starPEG-heparin) incorporating arginylglycylaspartic acid (RGD) coupled with rhBMP-2 for the prevention of MRONJ development at the time of dentoalveolar surgery.\ud \ud <b>Methods</b>\ud \ud - Twenty-four (24) skeletally mature rats were divided into three equal groups (n=8) receiving two doses of intravenous zoledronic acid prior to surgery. In all animals, the right first molar of the mandible was extracted and closed using 6/0 prolene. Group 1 animals had the sockets left empty, group 2 had starPEG-heparin/RGD hydrogel without rhBMP-2 placed into the extraction socket whilst group 3 had the aforementioned hydrogel with rhBMP-2. Samples were analyzed using immunohistochemical (IHC), microcomputed tomography (µCT), scanning electron microscopy (SEM) and enzyme linked immunosorbent assays (ELISA).\ud \ud <b>Results</b>\ud \ud - ELISA results of serum CTX demonstrated a downward trend during the housing period. µCT analysis of samples showed greater bone formation in group 3 compared to other groups as expected. H&E staining from group 1 displayed results consistent with MRONJ. IHC and histological staining demonstrated an increase in osteoclastic action and angiogenesis in interventional groups compared to controls although, the angiogenesis results were not significant. SEM analysis of samples confirmed increased osteocyte density surrounding the extraction socket in groups 2 and 3 compared to group 1.\ud \ud <b>Conclusions</b>\ud \ud - Results indicate that a starPEG-heparin/RGD hydrogel combined with rhBMP-2 can increase osteoclastic action, localized angiogenesis and increased bone healing compared to both hydrogel-alone, or no intervention in a MRONJ rat animal model