Matrix bound nanovesicles from decellularized pericardium facilitate angiogenesis

Therapeutic angiogenesis is a regenerative medicine approach which aims to induce revascularization for tissue repair. Among the existing strategies used to promote angiogenesis, biomaterials derived from decellularized tissues and composed of extracellular matrix (dECM) possess intrinsic angiogenic and regenerative potential. Recently, a bioactive component of such ECM materials has been identified; specifically, matrix bound nanovesicles (MBV). MBV have been shown to possess highly bioactive and tissue-specific cargo, and the ability to induce a potent immunomodulatory and regenerative response. However, their angiogenic potential has not been studied yet. Herein, the angiogenic properties of MBV derived from bovine pericardia dECM is evaluated. MBV show cytocompatibility toward endothelial cells, enhancing their functional phenotype and inducing the expression of angiogenic markers. In the presence of MBV, endothelial cells form three-dimensional monolayered endothelial vessel-like structures in tube formation assay. MBV also enhance endothelial sprouting in aortic ring assay. Finally, in hind limb ischemia in vivo model, MBV prevent tissue necrosis and restore vascularization and tissue function. These results demonstrate the angiogenic potential of MBV from pericardia ECM and represent a promising approach for therapeutic angiogenesis in regenerative medicine applications.