Novel Microfluidic Colon with an Extracellular Matrix Membrane

Collagen is a key element of basal lamina in physiological systems that participates in cell and tissue culture. Its function is for cell maintenance and growth, angiogenesis, disease progression, and immunology. The goal of our present study was to integrate a micrometer resolution membrane that is synthesized out of rat-tail type I collagen in a microfluidic device with apical and basolateral chambers. The collagen membrane was generated by lyophilization. In order to evaluate the compatibility of the resulting membrane with organs-on-chips technology, it was sandwiched between layers of polydimethylsiloxane (PDMS) that had been prepared by replica molding, and the device was used to culture human colon caco 2 cells on the top of the membrane. Membrane microstructure, transport, and cell viability in the organs-on-chips were observed to confirm the suitability of our resulting membrane. Through transport studies, we compared diffusion of two different membranes: Transwell and our resulting collagen membrane. We found that mass transport of 40 kDa dextran was an order of magnitude higher through the collagen membrane than that through the Transwell membrane. Human colon caco 2 cells were cultured in devices with no, Transwell, or ECM membrane to evaluate the compatibility of cells on the ECM membrane compared to the other two membranes. We found that caco 2 cells cultured on the collagen membrane had excellent viability and function for extended periods of time compared to the other two devices. Our results indicate a substantial improvement in establishing a physiological microenvironment for in vitro organs-on-chips.