Intestinal epithelial cell behavior on collagen substrates with biomimetic micro-topography

Modification of biomaterial scaffolds used in tissue engineering has traditionally focused more on chemical and mechanical properties than on topography. Microfabrication was used to produce topographic analogs of intestinal basal lamina crypts. A test pattern of micro-wells with dimensions (50-400 mum in diameter, 100 mum in depth) similar to those of native crypt structures was produced in a type I collagen membrane. Caco-2 cells attached and spread faster and to a greater extent on flat surfaces than on those with micro-well structures. It was found that Caco-2 cells were able to span across well structure with small diameters (i.e. 50 and 100 mum). Cells cultured on microwell surfaces had higher mitochondrial activity initially (3 days in culture), and then decreased to a level lower than that of cells seeded on flat surfaces after 7 days. Micro-well topography also affected differentiation; cells on patterned substrates had lower alkaline phosphatase and alanine aminopetidase activities than cells on flat surfaces. In general, the presence of crypt-like topography delayed cell spreading, migration, and differentiation. This study will aid in understanding the unique role intestinal topography plays in cell development and provide design parameters for a scaffold for tissue engineered intestine to treat intestinal disease.