Australian Dental Research Foundation Special Research Supplement 2017

Abstract

BRONJ was considered to be due to direct suppression of bone remodelling and cytotoxic effects of zoledronic acid (ZA) on bone and oral mucosal cells. However, recent literature suggests that suppressed angiogenesis contributes significantly to the pathogenesis of this condition. This in vitro and in vivo study examined the effect of locally delivered VEGF-hydrogel and local gene expression in rat BRONJ model. In vitro release study with 200 ng of rat VEGF-165 (Biovision) loaded into 500 lL hydrogel (Hystem-HP) prior to cross-linking and incubated in release media that was sampled and quantified using ELISA, over 28-days. In vivo, a BRONJ model using Sprague-Dawley rats was established by weekly intraperitoneal injection of ZA (three weeks), followed by extraction of maxillary first two molars and creation of a 5 mm defect which received either VEGF-containing hydrogel, HA gel alone or no gel. ZA was continued for four weeks post-surgery, prior to sacrifice. Gross examination, micro-CT evaluation and histological assessment was conducted to evaluate the effect of VEGF local delivery. Histological assessment involved quantification of osteonecrotic areas, total vascularity (von Willebrand Factor, vWF immunostaining) and specifically, the microvessel density (CD105 immunostaining). Furthermore, to assess molecular level changes during bone and soft tissue healing, gene expression analysis was conducted on the bone and gingival tissue samples from defect area.