IADR Abstract Archives
Local Delivery of VEGF-Hydrogel in developing MRONJ lesion modulates socket healing and systemic cytokine response.
Objectives: Aetiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ) was classically considered to involve direct suppression of osteoclast-induced bone remodelling and cytotoxic effects of Zoledronic acid (ZA). However, recent literature points towards local and systemic suppression of angiogenesis contributing to this process. Hence, this study was designed to examine the effect of locally delivered VEGF-hydrogel on in situ angiogenesis and systemic cytokine response.
Methods: VEGF-165 loaded hydrogel was used in ZA-induced rat MRONJ, following extraction of maxillary molars and creation of a defect. After four weeks rats were sacrificed and gross examination and histological assessment were conducted to evaluate effect of VEGF. Histological assessment involved quantification of osteonecrotic areas, inflammatory infiltrate, total vascularity (von Willebrand Factor, vWF immunostaining) and microvessel density (CD105). Furthermore, to assess the systemic response induced by VEGF gel, peripheral (plasma) cytokine assay was performed using multiplex ELISA analysis.
Results: Gross evaluation of the lesion showed significantly reduced osteonecrosis in the presence of VEGF. Histomorphometric assessment of osteonecrosis showed significantly higher areas of necrotic bone (empty lacunae) in untreated animals compared to the VEGF treated group (71648±6785µm2 vs 11919±2920µm2, p<0.0001). Significantly higher areas of inflammatory infiltrate were noted in the untreated group, in comparison to the VEGF treated group (54873±6035 vs 8802±2559 µm2, p=0.0002). Total vascularity (vWF) was significantly higher in the VEGF treated group (577.0±60.2µm2) compared to the untreated group (139.8±23.2µm2, p<0.0001) suggesting a positive role of VEGF gel on total vascularity. Furthermore, neovascularization (CD105) was significantly improved (393.4±36.5µm2), in comparison to control group (68.6±17.0µm2; p<0.0001). Notably, the peripheral cytokine levels were found to be significantly skewed towards enhanced healing, in the presence of locally-delivered VEGF supporting the positive effect of VEGF.
Conclusions: Sustained-local delivery of VEGF can be employed as a valuable preventive modality in susceptible patients following dental manipulation, while on anti-resorptive medications.
Methods: VEGF-165 loaded hydrogel was used in ZA-induced rat MRONJ, following extraction of maxillary molars and creation of a defect. After four weeks rats were sacrificed and gross examination and histological assessment were conducted to evaluate effect of VEGF. Histological assessment involved quantification of osteonecrotic areas, inflammatory infiltrate, total vascularity (von Willebrand Factor, vWF immunostaining) and microvessel density (CD105). Furthermore, to assess the systemic response induced by VEGF gel, peripheral (plasma) cytokine assay was performed using multiplex ELISA analysis.
Results: Gross evaluation of the lesion showed significantly reduced osteonecrosis in the presence of VEGF. Histomorphometric assessment of osteonecrosis showed significantly higher areas of necrotic bone (empty lacunae) in untreated animals compared to the VEGF treated group (71648±6785µm2 vs 11919±2920µm2, p<0.0001). Significantly higher areas of inflammatory infiltrate were noted in the untreated group, in comparison to the VEGF treated group (54873±6035 vs 8802±2559 µm2, p=0.0002). Total vascularity (vWF) was significantly higher in the VEGF treated group (577.0±60.2µm2) compared to the untreated group (139.8±23.2µm2, p<0.0001) suggesting a positive role of VEGF gel on total vascularity. Furthermore, neovascularization (CD105) was significantly improved (393.4±36.5µm2), in comparison to control group (68.6±17.0µm2; p<0.0001). Notably, the peripheral cytokine levels were found to be significantly skewed towards enhanced healing, in the presence of locally-delivered VEGF supporting the positive effect of VEGF.
Conclusions: Sustained-local delivery of VEGF can be employed as a valuable preventive modality in susceptible patients following dental manipulation, while on anti-resorptive medications.