Since most of the bodyâ??s extracellular matrix (ECM) is composed of collagen and elastin,\nwe believe the choice of these materials is key for the future and promise of tissue engineering. Once it\nis known how elastin content of ECM guides cellular behavior (in 2D or 3D), one will be able to harness\nthe power of collagen-elastin microenvironments to design and engineer stimuli-responsive tissues.\nMoreover, the implementation of such matrices to promote endothelial-mesenchymal transition\nof primary endothelial cells constitutes a powerful tool to engineer 3D tissues. Here, we design\na 3D collagen-elastin scaffold to mimic the native ECM of heart valves, by providing the strength\nof collagen layers, as well as elasticity. Valve interstitial cells (VICs) were encapsulated in the\ncollagen-elastin hydrogels and valve endothelial cells (VECs) cultured onto the surface to create\nan in vitro 3D VEC-VIC co-culture. Over a seven-day period, VICs had stable expression levels of integrin-- and F-actin and continuously proliferated, while cell morphology changed to more\nelongated. VECs maintained endothelial phenotype up to day five, as indicated by low expression\nof F-actin and integrin--, while transformed VECs accounted for less than 7% of the total VECs in\nculture. On day seven, over 20% VECs were transformed to mesenchymal phenotype, indicated by\nincreased actin filaments and higher expression of integrin These findings demonstrate that our\n3D collagen-elastin scaffolds provided a novel tool to study cell-cell or cell-matrix interactions in vitro,\npromoting advances in the current knowledge of valvular endothelial cell mesenchymal transition.
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