Biomechanical properties of an implanted engineered tubular gut-sphincter complex

Abstract

Neuromuscular diseases of the gut alter the normal motility patterns. Although surgical intervention remains the standard treatment, preservation of the sphincter attached to the rest of the gut is challenging. The present study aimed to evaluate a bioengineered gut-sphincter complex following its subcutaneous implantation for 4 weeks in rats. Engineered innervated human smooth muscle sheets and innervated human sphincters with a predefined alignment were placed around tubular scaffolds to create a gut-sphincter complex. The engineered complex was subcutaneously implanted in the abdomen of the rats for 4 weeks. The implanted tissues were vascularized. In vivo manometry revealed luminal pressure at the gut and the sphincter zone. Tensile strength, elongation at break and Young's modulus of the engineered complexes were similar to those of native rat intestine. Histological and immunofluorescence assays showed maintenance of smooth muscle circular alignment in the engineered tissue, maintenance of smooth muscle contractile phenotype and innervation of the smooth muscle. Electrical field stimulation induced relaxation of the smooth muscle of both the sphincter and the gut parts. Relaxation was partly inhibited by nitric oxide inhibitor indicating nitrergic contribution to relaxation. The present study has demonstrated for the first time a successfully developed and subcutaneously implanted a tubular human-derived gut-sphincter complex. The sphincteric part of Tubular Gut-Sphincter Complex (TGSC) maintained the basal tone characteristic of a native sphincter. The gut part also maintained its specific neuromuscular characteristics. The results of this study provide a promising therapeutic approach to restore gut continuity and motility. Copyright © 2016 John Wiley & Sons, Ltd.

Tissue engineering of the gastroesophageal junction

“…This was significantly higher than the ~110μN force generated by similarly constructed rings made from colonic wall SMCs, indicating a preservation of the higher tone phenotype. The same group used a cell sheet technique on a patterned substrate to make a tissue‐engineered duodenum using primary SMCs and NPCs (Zakhem, El Bahrawy, Orlando, & Bitar, 2016). These sheets were wrapped around a chitosan tube, and an engineered pyloric sphincter using the gel compaction method was placed at one end.…”

Bioengineering and regeneration of gastrointestinal tissue: where are we now and what comes next?

“…Tubular chitosan scaffolds were engineered and tested for their biocompatibility to support smooth muscle and neuronal survival, differentiation and funciton [40][41][42]. The tissues were further evaluated in vivo in rat models for survival, vascularization and function [43,44]. When anastomosed to the native intestine of the rats, the engineered chitosan-based intestine maintained a functional innervated musculature and acquired an epithelium layer [45].…”