A clinical-grade acellular matrix for esophageal replacement

J Tissue Eng Regen Med. 2019 Dec;13(12):2191-2203. doi: 10.1002/term.2983. Epub 2019 Nov 7.

Abstract

In pathologies of the esophagus such as esophageal atresia, cancers, and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality, and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix. Following the decontamination step, porcine esophagi were decellularized in a bioreactor with sodium dodecyl sulfate and ethylenediaminetetraacetic acid for 3 days and were rinsed with deionized water. DNA was eliminated by a 3-hr DNase treatment. To remove any residual detergent, the matrix was then incubated with an absorbing resin. The resulting porcine esophageal matrix was characterized by the assessment of the efficiency of the decellularization process (DNA quantification), evaluation of sterility and absence of cytotoxicity, and its composition and biomechanical properties, as well as the possibility to be reseeded with mesenchymal stem cells. Complete decellularization with the preservation of the general structure, composition, and biomechanical properties of the native esophageal matrix was obtained. Sterility was maintained throughout the process, and the matrix showed no cytotoxicity. The resulting matrix met clinical grade criteria and was successfully reseeded with mesenchymal stem cells..

Keywords: clinical grade; decellularization; decellularized scaffold; esophagus; mesenchymal stem cells; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Esophagus / chemistry*
  • Extracellular Matrix / chemistry*
  • Materials Testing*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Swine
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*