Ascending and Descending Aortic ECM Hydrogels for Modeling Aortic Wall Biology

Abstract

Although in vitro modeling systems are becoming increasingly advanced, the complex pathophysiology of aortic diseases remains a challenge to mimic and adequately replicate. Biomechanical weakening of the vessel wall, medial degeneration and remodeling are all hallmarks of aneurysmal diseases via incompletely understood mechanisms. Understanding what factors disrupt the multi-layer biology of large blood vessels during the progression of aneurysmal disease can aid in the unmet clinical need to slow or halt disease progression. In particular, the microvascular network of the vasa vasorum provides the primary blood supply to the outer aortic wall and is a key component of inter-layer vascular health. Different origins of the vasa vasorum correspond to the anatomically specific functions of the aortic regions, which can further pertain to the differing origins of vascular wall cells and putative differences in the composition of extracellular matrix (ECM). Biologic scaffolds produced from ECM are useful biomaterials to understand biological processes and address wound healing, stem cell differentiation, and angiogenesis for both in vitro and in vivo disease models. In the present study, we investigated putative differences in composition and structure between ascending and descending aorta-derived ECM to better understand intra- and inter-layer cell-matrix interactions relevant to vasa vasorum function in the aorta. Ascending and descending aortic ECM (AECM) hydrogels were shown to retain bioactivity and influence contractility of human vasa vasorum-associated pericytes. A comprehensive understanding of the effect of layer-specific ECM on cells in different aortic regions could help uncover novel disease mechanisms.