Mechanical strain is an important signal that influences the behavior and properties of cells in a wide variety of tissues. Physiologically similar mechanical strain can revert cultured cells to a more normal phenotype. Here, we have demonstrated that 3% equibiaxial (EB) and uniaxial strains confer favorable protein expression in cultured rabbit corneal fibroblasts (RCFs), with approximately 35% and 65% reduction in expression of a-smooth muscle actin (a-SMA), respectively. We have designed a novel bioreactor that is capable of imparting up to 7% EB strain and up to 6% EB strain using a cornea-shaped post. Additional features of the bioreactor include the application of shear stress to cells in culture and the ability to image cells using optical coherence microscopy (OCM) without being removed from the system. Biotechnol. Bioeng. 2012; 109: 31893198. (C) 2012 Wiley Periodicals, Inc.