A microengineered system for the oriented capture and ex vivo culturing of an important and under-studied tissue, the intestinal crypt, will be designed and tested. The sustained culture of crypts on the array platform will be optimized by providing a lamina-propria-simulated microenvironment on the basal face of the oriented crypts, as well as by supplementing with a mixture of appropriate exogenously supplied signals. The sustained proliferation and differentiation of cells into the cell lineages found in colonic epithelium in vivo will be evaluated. The end goal will be to subject the polarized tissue to user-controlled fluidic microenvironments in a manner that recapitulates the in vivo state, and perform biological assays of living colonic crypts on the chip. The present grant will demonstrate the feasibility and potential for rationally microengineered technologies to address the specific needs of the gastrointestinal biology and disease research.