Generation of an artificial intestine for the management of short bowel syndrome

Abstract

Purpose of review To discuss the current state of the art in artificial intestine generation in the treatment of short bowel syndrome. Recent findings Short bowel syndrome defines the condition in which patients lack sufficient intestinal length to allow for adequate absorption of nutrition and fluids, and thus need parenteral support. Advances towards the development of an artificial intestine have improved dramatically since the first attempts in the 1980s, and the last decade has seen significant advances in understanding the intestinal stem cell niche, the growth of complex primary intestinal stem cells in culture, and fabrication of the biomaterials that can support the growth and differentiation of these stem cells. There has also been recent progress in understanding the role of the microbiota and the immune cells on the growth of intestinal cultures on scaffolds in animal models. Despite recent progress, there is much work to be done before the development of a functional artificial intestine for short bowel syndrome is successfully achieved. Summary Continued concerted efforts by cell biologists, bioengineers and clinician-scientists will be required for the development of an artificial intestine as a clinical treatment modality for short bowel syndrome.

Biomanufacturing Seamless Tubular and Hollow Collagen Scaffolds with Unique Design Features and Biomechanical Properties

“…Their structural design incorporates a multifolded lumen and a multilayer muscle cell arrangement that allows for muscle contraction and relaxation, required for large volume changes needed for urine to flow without rupturing the lumen surface at a higher fluid shear stress ( Figure A,B). It gets even more complicated in the case of small intestine as its lumen is filled with microprotrusion known as villi, which are essential for nutrients absorption . For TE hollow or tubular neo‐organs to be successful in preclinical and clinical settings, it is absolutely necessary to provide scaffolds with the desired shape and design with adequate mechanical strength required in reconstructed neo‐tissues or neo‐organs, which have not been possible to achieve using standard biomanufacturing techniques.…”

The Development of Newborn Porcine Models for Evaluation of Tissue-Engineered Small Intestine

“…2,6,7 The development of a tissue-engineered small intestine (also known as an artificial intestine) has emerged as a potential investigative option for the treatment of children with SBS. [8][9][10][11][12][13][14][15] The requirements for the successful development of a functional intestinal graft in the laboratory include the following: (1) a source of progenitor cells with the capacity to grow and differentiate into a well-differentiated absorptive intestinal mucosal surface, (2) a scaffold capable of supporting cellular growth, (3) adequate vascularization of the newly engineered tissue, and (4) an intact neural network to promote peristalsis. [9][10][11][12][13][14][15][16][17] Most investigators have utilized rodent models to evaluate the potential efficacy of each of these components, and while such studies have yielded some very useful proofof-concept data, they have been limited by the physical and structural differences between rodents and humans.…”