MICROFLUIDICS BIOREACTOR: A PLATFORM FOR STUDYING CAPILLARY MORPHOGENESIS IN RESPONSE TO BIOCHEMICAL AND BIOPHYSICAL CUES

摘要

The in vivo microvasculature is a dynamic structure which is influenced by both biochemical (e.g. cytokines, growth factors) and biophysical factors (e.g. shear stress, interstitial flow). Important regulators of this structure are the endothelial cells which are normally quiescent but under certain conditions are able to form new vascular sprouts. Investigations into the mechanism of capillary morphogenesis of human endothelial cells warrant an in vitro model that closely mimics the physiological in vivo microenvironment. To this end, we have developed a novel microfabricated system which permits 2D and 3D culture of endothelial cells in biologically derived (e.g. type I collagen) or synthetic (self assembling peptides) scaffolds and delivers control flow rates and pressures. This system offers tremendous flexibility with regard to scaffold physical and chemical properties, physiologically relevant mechanical stress induced by surface shear and interstitial flow as well as chemotactic gradients. In addition we are able to directly monitor the progression of vascular networks in response to these critical factors. The bioreactor (Fig. 1) consists of two media channels for delivering cell culture media and a central cell culture gel "cage" for housing scaffold. With the scaffold in place, the two media channels are isolated from each other; this geometry permits the establishment of gradients in both pressure and chemotactic factors across the gel "cage" region. In addition our unique flow circuit design permits the control of both surface shear and interstitial flow in the system.