Angiogenic Response to Bioactive Glass Promotes Bone Healing in an Irradiated Calvarial Defect

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Abstract
Localized radiation is an effective treatment modality for carcinomas, yet the associated reduction of the host vasculature significantly inhibits the tissue's regenerative capacity. Low concentrations of bioactive glass (BG) possess angiogenic potential, and we hypothesized that localized BG presentation would increase neovascularization and promote healing in an irradiated bone defect. An isolated calvarial region of Sprague-Dawley rats was irradiated 2 weeks before surgery. Bilateral critical-sized defects were created and immediately filled with a BG-loaded collagen sponge or an empty sponge as an internal control. Histological analysis of calvaria collected after 2 weeks demonstrated greater neovascularization within the defect in the presence of BG than with collagen alone. Noninvasive ultrasound imaging at 4 weeks detected less contrast agent in the brain below BG-treated defects than in the nearby untreated defects and images of treated defects acquired at 2 weeks. The reduced ability to detect contrast agent in BG-treated defects suggested greater attenuation of ultrasound signal due to early bone formation. Micro-computed tomography imaging at 12 weeks demonstrated significantly greater bone volume fraction within BG-treated defects than in controls. These results suggest that neovascularization induced by localized BG delivery promotes bone regeneration in this highly compromised model of bone healing and may offer an alternative approach to costly growth factors and their potential side-effects.