CHIMERIC NEOMORPHOGENESIS OF ORGANS BY CONTROLLED CELLULAR IMPLANTATION USING ARTIFICIAL MATRICES

摘要

Fibers of a biocompatible, biodegradable or non-biodegradable, synthetic polymer are provided, and are formed into a three-dimensional scaffold. The fibers of the scaffold may have a branched configuration extending outwardly from a central stem. The fibers provide sufficient surface area to permit attachment to the scaffold in vitro of an amount of cells effective to produce functional vascularized organ tissue in vivo. Fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns. The diffusion provides free exchange of nutrients, gases and waste to and from cells proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization. Cells derived from vascularized organ tissue are attached in vitro to the surface of the fibers uniformly throughout the scaffold and the cells are grown on the scaffold in a nutrient solution in vitro to form a cell-scaffold composition. Growth factors, compounds stimulating angiogenesis and immunomodulators may be provided in the cell-scaffold composition and the fibers may have a coating to enhance cell attachment. The cell-scaffold composition is implanted in a host at a location having adequate vascularization to allow growth of blood vessels into the cell-scaffold composition. Combinations of cell-scaffold compositions containing different cell populations may be implanted.