Modeling and design of oriented collagen-based tissue analogs

The engineering of wholly bioartificiaJ tissues from tissue-equivalents is a promising research area, the prototype tissue-equivalent being reconstituted type I collagen gel with entrapped tissue cells. The fundamental design requirement is that the bioartificial tissue perform the mechanical and biological functions of the natural tissue over an extended period of in vivo use. Presumably, this will require mimicking the characteristic orientation of fibers and cells of the natural tissue. In the particular case of a media-equivalent developed for a bioartificiaJ artery from smooth muscle cell (SMC) populated tubular collagen gel (Weinberg and Bell, 1986). the important design variables are Una) size (thickness and lumen diameter), mechanical strength in response to stresses typical of the artery, and the circumferential orientation of the collagen fibrils and SMC, which leads to strengthening of the tube against cirumferential stress. We have previously presented an anisotropic biphasic theory of the dynamics and mechanics of tissue-equivalents (Barocas and Tranquille, 1994). Our theory accounts for strain-induced réorientation of the collagen fibrils comprising the gel, as well as biased cell traction and migration in response to the oriented fibrils (contact guidance), where the strain arises due to fraction exerted by the cells on the fibrils. By solving the model equations, we are able to predict cell traction-induced compaction and evolution of orientation in a tissue-equivalent for a given initial state (cell and collagen concentrations and orientations, geometry and dimensions of the tissue-equivalent). We will discuss here the use of our theory to address the important design issues in a media-equivalent, particularly the issue of SMC and fibril orientation. A number of methods have been proposed to generate the desired circumferential orientation in media-equivalents, including magnetically aligning the fibrils during gelation (Tranquille et al., 1995) and/or restricting the subsequent compaction (L'Heureux et al., 1993). Our model allows comparison of various methods and provides a basis for optimization of a media-equivalent given the design variables stated above.