Abstract
Arteriolar resistance vessels control flow to vascular beds. The structure, mechanics, and function of these blood vessels are critically important to our understanding of the mechanisms of cardiovascular disease pathogenesis. Additionally, in vitro arteriolar mimetic approaches are needed to improve the study of cardiovascular disease, because models based upon rodents vascular function and cells in standard culture containers do not accurately recapitulate the native multicellular architecture of a human vessel wall. Here, we describe novel, highly parallel, mass biofabrication of biomimetic tubular vessel constructs composed of biocompatible scaffold materials, pulmonary microvascular endothelial cells (HPMEC), extracellular matrix components including fibronectin and laminin 3, and human pulmonary artery smooth muscle cells (HPASMC). These constructs had a diameter of ~250 microns, and a length of 1–3 mm. Cells were incorporated into these constructs in patterns that mimic the layering and relative alignment observed in human pulmonary arterioles. Finite Element Analysis showed that the ultra‐thin cylindrical scaffold materials used here could be displaced by the cells in these biomimetic vascular walls to an extent that was similar to displacements of thicker tube composed of softer materials. HPMEC in these biomimetic vessel constructs produced more nitric oxide, and demonstrated higher phosophorylation levels of key nitric oxide signaling proteins (eNOS and Akt) than equal numbers of cells grown on equal surface areas that were flat. Additionally, HPASMC were aligned at tunable angles that mimicked in‐vivo organization using biomolecular micropatterning. Thus, biomimetic arterioles produced in this study exhibited improved endothelial functionality together with multi‐cellular layering and anatomically accurate cellular alignment, and provide a platform for investigation of microvascular function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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