A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration

Giorgia Totonelli,Panagiotis Maghsoudlou,Massimo Garriboli,Johannes Riegler,Giuseppe Orlando,Alan J Burns,Neil J Sebire,Virpi V Smith,Jonathan M Fishman,Marco Ghionzoli,Mark Turmaine,Martin A Birchall,Anthony Atala,Shay Soker,Mark F Lythgoe,Alexander Seifalian,Agostino Pierro,Simon Eaton,Paolo De Coppi

doi:10.1016/j.biomaterials.2012.01.012

Giorgia Totonelli, Panagiotis Maghsoudlou + Show 17 more

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https://doi.org/10.1016/j.biomaterials.2012.01.012

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Abstract

Management of intestinal failure remains a clinical challenge and total parenteral nutrition, intestinal elongation and/or transplantation are partial solutions. In this study, using a detergent-enzymatic treatment (DET), we optimize in rats a new protocol that creates a natural intestinal scaffold, as a base for developing functional intestinal tissue. After 1 cycle of DET, histological examination and SEM and TEM analyses showed removal of cellular elements with preservation of the native architecture and connective tissue components. Maintenance of biomechanical, adhesion and angiogenic properties were also demonstrated strengthen the idea that matrices obtained using DET may represent a valid support for intestinal regeneration.

Highlights

Intestinal failure (IF), arising from anatomical or functional loss of intestine, is a condition characterized by the inability of the intestine to carry out its secretory and absorptive functions, necessitating macronutrient, water and electrolyte supplementation, in the form of artificial feeding and parenteral nutrition (PN)
We have previously shown that muscle tissue can be successfully decellularized [18] and used for repair of a surgically created defect of the abdominal wall [19,20] and the diaphragm [21]
Following perfusion with the detergent-enzymatic solution both through the superior mesenteric artery (SMA) and the intestinal lumen, the rat intestinal wall became macroscopically transparent with good preservation of the mesentery within 31 h (1 cycle of detergent-enzymatic treatment (DET); Fig. 1B)

Summary

Introduction

Intestinal failure (IF), arising from anatomical or functional loss of intestine, is a condition characterized by the inability of the intestine to carry out its secretory and absorptive functions, necessitating macronutrient, water and electrolyte supplementation, in the form of artificial feeding and parenteral nutrition (PN). IF reduces quality of life and has major PN-related co-morbidities such as liver disease, intravenous line sepsis and malnutrition. This leads to a survival rate of 86% in 1 year, which is reduced to 77% and 73% in 3 and 5 years respectively [1]. In 1999, the term “regenerative medicine” was first used to describe the use of natural human substances, such as genes, proteins, cells, and biomaterials to regenerate diseased or damaged human tissue [5,6] to restore normal function [7]. Tissue engineering is concerned with the manufacturing of tissue by combining appropriate cells with a scaffold [8] that can be either synthetic such as poly-glycolic acid (PGA) [9,10], naturally-derived such as collagen or decellularized

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