Micromachined Bioreactor for in Vitro Cell Self-Assembly and 3D Tissue Formation

Abstract

A miniature bioreactor that enables cell self-assembly and 3D tissue formation was designed and microfabricated. The bioreactor recapitulates some of the key features of a capillary bed, allows in situ optical interrogation of the perfused 3D tissue, and provides for a high degree of control over fluid flow conditions. The bioreactor fluidic system employs two pumps and two filters to maintain stable perfusion rates through the tissue over time periods of several weeks. Tissue distribution of oxygen in a channel was modeled as a function of the perfusion cross-flow rate. In order to validate modeled mass transfer predictions within a tissue-containing channel, expression of hypoxiaregulated genes Heme Oxygenase -1 and Hif-3α were studied. The tissue phenotype in the bioreactor was assessed by in situ detection of cytochrome P450 1A activity in the cultured rat hepatocytes.