Microfabrication tools

Microfabrication techniques have been widely utilized to exert spatial control over cell adhesion at the 1-100 m m scale to study diverse phenomena such as effects of cell spreading on cell fate and of surface topology on cell migration. Microfabrication tools are used to define the biochemical and cellular composition of a substrate on the micron scale. For hepatic tissue engineering, the phenotype of primary hepatocytes (liver cells) has been stabilized by co-cultivation with both liver and non-liver derived stromal cell types (i.e. fibroblasts). We have developed a photolithographic cell patterning technique to study the relative role of homotypic (hepatocyte-hepatocyte) and heterotypic (hepatocyte-stroma) interactions in stabilization of liver-specific functions in vitro. Cocultures were created in which the heterotypic interface varied over three orders of magnitude, while keeping the ratio of cell populations, as well as total cell number constant. Using this technique, we found that identical cell populations when rearranged spatially can produce different levels of function in the resultant tissue. Our current work focuses on understanding mechanistically the dynamics of functional upregulation and the role of reciprocal heterotypic interactions in hepatic cocultures Bhatia et al, 1999.

Microfabrication technique for controlling cell-cell interaction in co-culture (left). Effect of tissue architecture on tissue function (right).