Abstract 18247: In Vitro Perfused Human Capillaries
Understanding the function and structure of the microcirculation is key to improving our understanding of pathophysiological process in many areas of cardiovascular disease including myocardial infraction and hypertension. Many of the techniques used to investigate the microcirculation include costly clinical human observations, in vivo animal studies, which require extrapolation of results to human, or in vitro models that lack the dynamic feature of perfusion. We have developed an in vitro model system of microtissues with perfused, living, dynamic human capillaries. In this work we demonstrate the ability to develop capillaries under two different pressure distributions and we assess features of the in vitro formed capillaries including permeability and shear rate. Our device consist of a PDMS casing consisting of two microfluidic channels on either side of 12 diamond shaped chambers containing stromal cells co-seeded with endothelial cells in a fibrin matrix. In both designs, formation of perfused vessels was encouraged by both mechnical and chemical stimuli. Finite element simulations demonstrate the ability to control the pressure distribution (Fig 1a & 1b) and subsequent interstitial flows within the two designs. Varying or equal transverse pressure drops across each tissue chamber were created by either decreasing or increasing the pressure at the pores (Figure 1c & 1d). Within 2-3 weeks of culture, a network of vessels (diameter=15-50µm) was observed (Fig 1e) in both designs. Perfusion of the vessels was confirmed at day 21 by perfusing FITC-dextran through the vessels by convection. The vessels were impermeable to 70 and 150 kDa FITC-dextran (Fig 1f). Microspheres tracked as they moved through the vessels revealed fluid velocities ranging from 0-4,000 µm/s at various locations along the vessel.
- © 2012 by American Heart Association, Inc.