Strategies for inducing Resilience in the Tissue-Engineered Intestine

Brigham And Women'S Hospital, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Short bowel syndrome is a devastating disorder for which no satisfactory therapies currently exist. The fundamental pathophysiological derangement in this disorder is a deficiency of intestinal absorptive surface area. In a novel approach to this problem, tissue-engineering techniques have been applied to create a prototype neointestine. Preliminary studies have suggested that the engineered neointestine can be induced to develop an epithelium that reproduces critical functions of native small intestine such as absorption, barrier and immunity, however more investigation is needed in order to make the neointestine a viable option for intestinal replacement. This proposal is designed to characterize the biology of the tissue-engineered neointestine with regards to epithelial resilience, a critical attribute of native intestinal tissue. We hypothesize that fundamental differences in epithelial resilience exist between engineered and native intestine and that an understanding of these differences will lead to optimization epithelial resilience in the engineered intestine. The aims of the study are: 1) To compare the epithelial response to injury in tissue-engineered and native intestine. 2) To optimize epithelial resilience in the engineered neointestine. [unreadable] [unreadable]