Tissue-engineered gut-sphincter complexes and methods of making the same

Abstract

Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post. This innervated sphincter construct can also be transferred to the tubular scaffold such that the intestinal tissue construct and sphincter construct contact each other, and the resulting combined sphincter and intestinal tissue constructs can be further cultured about the scaffold until a unified tubular gut-sphincter complex is obtained.