Tissue engineering. Ways of imitating nature

Two approaches to tissue engineering will be considered. The first consists of building a cell-matrix tissue equivalent that serves as a living substratum for endothelial, mesothelial or epithelial cells. These cells can constitute simple or stratified tissues and depend for their differentiation on diffusible support molecules from cells in the matrix and from the media provided. The matrix itself is primarily collagen, but is enriched by products from resident cells and exhibits attachment sites for cells of the surface tissues. Examples to be discussed will be a skin equivalent and a blood vessel equivalent. Necessary requirements for fabricating tissue and organ equivalents for grafting include a source of cultivatable cells and methods for selecting against cells that are known to provoke an immune response. In vitro responses that may be predictive of graft acceptance or rejection have been studied and depend on tests of the ability of cells to stimulate a response in mixed lymphocyte or cell mediated lympholysis reactions after cylokine induction of antigens typical of immune cells rather than tissue parenchymal cells. A second approach utilizes acellular materials that can be remodelled by like tissues adjacent to an implant in the body. The objective is that of providing both matrix substance and inducing and signaling molecules that encourage cell migration, cell propagation and cell differentiation. In vitro methods have been devised for studying these aspects of tissue reconstruction. They are based on the use of both approaches to tissue engineering. Beginning with a fully differentiated skin equivalent in vitro, a full thickness punch biopsy can be removed from it, leaving a 'wound bed' that can be refilled with a matrix that lends itself to remodelling by the tissues surrounding it. In this system the design of the matrix can be manipulated by modifying structural protein content as well as the content of signaling and regulating molecules.