Bioactive Vascular ECM Hydrogels Improve Endothelial Cell Function

Dissection or free rupture of the ascending aorta can result from a biomechanical weakening of the aortic wall due to formation of thoracic aortic aneurysm (TAA). We previously observed vasa vasorum remodeling in both... [ view full abstract ]

Dissection or free rupture of the ascending aorta can result from a biomechanical weakening of the aortic wall due to formation of thoracic aortic aneurysm (TAA). We previously observed vasa vasorum remodeling in both degenerative and bicuspid aortic valve-associated TAA specimens. These observations, combined with noted medial oxidative stress in bicuspid aortic valve-associated aortopathy and local chronic hypoxia in degenerative aneurysms may compromise endothelial function of the vasa vasorum in the setting of TAA. We hypothesized that extracellular matrix (ECM)-mediated signaling affects function of vasa vasorum-derived endothelial cells. To test this hypothesis, we developed hydrogels from decellularized porcine aortic adventitia and evaluated their influence on endothelial cell behaviors. The decellularization process was deemed adequate since DNA content was found to be ~35 ng DNA/mg tissue. Decellularized porcine ECMs stimulated primary human endothelial cell proliferation. The formation of tube-like structures by endothelial cells was increased, more mature, and stabilized on Matrigel™ substrates blended with pepsin-digested decellularized ECMs when compared with Matrigel™ alone. We conclude that the adventitial ECM provides important signaling cues that direct endothelial cell proliferation and enhance their ability to form networks of tube-like structures in vitro. Ongoing work involves the use of aortic ECM-based hydrogels to study matrix-derived mechanisms of microvascular dysfunction in the setting of TAA. The eventual clinical translation of this work is the development of vascular-ECM based biologic materials to treat the over 2.5 million people affected worldwide by dissection and/or rupture of TAA