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Published Online: 17 September 2019

Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue

Publication: Tissue Engineering Part A
Volume 25, Issue Number 17-18

Abstract

The goal of this study was to develop a scaffold for the generation of an artificial intestine that specifically mimics the architecture and biomechanical properties of the native small intestine, and to evaluate the scaffold in vitro and in vivo. Scaffolds mimicking the microarchitecture of native intestine were fabricated from poly(glycerol sebacate) (PGS) with a thickness of 647 μm (±241 μm) and villus height of 340 μm (±29.5 μm). The scaffolds showed excellent biological properties, as 71.4% (±7.2%) and 58.7% (±12.7%) mass remained after 5 weeks of in vitro exposure to control and digestive media, respectively. Tensile properties of the scaffolds approached those of native porcine intestine and scaffolds maintained their mechanical properties over 6 weeks based on rheometer measurements. Scaffolds accommodated intestinal epithelial stem cells and demonstrated maintenance of size and microarchitecture after 12 weeks of omental implantation in mice. There was an expected amount of inflammation, but less tissue infiltration and tissue formation than anticipated. In conclusion, we developed novel scaffolds using PGS that mimic the microarchitecture and mechanical properties of native intestine with promise for use in artificial intestine for individuals with short bowel syndrome.
Graphical abstract

Impact Statement

This study is significant because it demonstrates an attempt to design a scaffold specifically for small intestine using a novel fabrication method, resulting in an architecture that resembles intestinal villi. In addition, we use the versatile polymer poly(glycerol sebacate) (PGS) for artificial intestine, which has tunable mechanical and degradation properties that can be harnessed for further fine-tuning of scaffold design. Moreover, the utilization of PGS allows for future development of growth factor and drug delivery from the scaffolds to promote artificial intestine formation.

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Information & Authors

Information

Published In

cover image Tissue Engineering Part A
Tissue Engineering Part A
Volume 25Issue Number 17-18September 2019
Pages: 1225 - 1241
PubMed: 30652526

History

Published online: 17 September 2019
Published ahead of print: 3 September 2019
Published in print: September 2019
Published ahead of production: 17 January 2019
Accepted: 5 December 2018
Received: 22 August 2018

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    Data Availability

    Raw and/or processed data will be made available upon request.

    Authors

    Affiliations

    Mitchell R. Ladd
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    Cait M. Costello
    Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York.
    Carolyn Gosztyla
    Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland.
    Adam D. Werts
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    Blake Johnson
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    William B. Fulton
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    Laura Y. Martin
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    Elizabeth J. Redfield
    Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York.
    Bryan Crawford
    Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland.
    Rohan Panaparambil
    Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
    Chhinder P. Sodhi
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
    John C. March
    Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York.
    David J. Hackam [email protected]
    Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.

    Notes

    Address correspondence to: David J. Hackam, MD, PhD, Division of Pediatric Surgery, The Johns Hopkins Children's Center, Johns Hopkins University, Room 7323, 1800 Orleans Street, Baltimore, MD 21287 [email protected]

    Disclosure Statement

    No competing financial interests exist.

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