Engineered Microvessels with Strong Alignment and High Lumen Density Via Cell-Induced Fibrin Gel Compaction and Interstitial Flow

Abstract

The development of engineered microvessels with clinically relevant characteristics is a critical step toward the creation of engineered myocardium. Alignment is one such characteristic that must be achieved, as it both mimics native capillary beds and provides natural inlet and outlet sides for perfusion. A second characteristic that is currently deficient is cross-sectional lumen density, typically under 100 lumens/mm²; the equivalent value for human myocardium is 2000 lumens/mm². Therefore, this study examined the effects of gel compaction and interstitial flow on microvessel alignment and lumen density. Strong microvessel alignment was achieved via mechanically constrained cell-induced fibrin gel compaction following vasculogenesis, and high lumen density (650 lumens/mm²) was achieved by the subsequent application of low levels of interstitial flow. Low interstitial flow also conferred microvessel barrier function.