Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue

Mitchell R. Ladd, Cait M. Costello, Carolyn Gosztyla, Adam D. Werts, Blake Johnson, William B. Fulton, Laura Y. Martin, Elizabeth J. Redfield, Bryan Crawford, Rohan Panaparambil, Chhinder Sodhi, John C. March, David Hackam

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)1225-1241
Number of pages17
JournalTissue Engineering - Part A
Volume25
Issue number17-18
DOIs
StatePublished - Sep 1 2019

Fingerprint

Scaffolds
Intestines
Tissue
Small Intestine
Short Bowel Syndrome
Glycerol
tebufenozide
Intercellular Signaling Peptides and Proteins
Polymers
Mechanical properties
Swine
Stem Cells
Epithelial Cells
Maintenance
Rheometers
Inflammation
Stem cells
Drug delivery
Tensile properties
Infiltration

Keywords

  • artificial intestine
  • biodegradable polymers
  • functional tissue engineering with intestinal scaffolds
  • intestinal tissue engineering
  • poly(glycerol sebacate) scaffold biomechanics
  • short bowel syndrome

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Ladd, M. R., Costello, C. M., Gosztyla, C., Werts, A. D., Johnson, B., Fulton, W. B., ... Hackam, D. (2019). Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue. Tissue Engineering - Part A, 25(17-18), 1225-1241. https://doi.org/10.1089/ten.tea.2018.0239

Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue. / Ladd, Mitchell R.; Costello, Cait M.; Gosztyla, Carolyn; Werts, Adam D.; Johnson, Blake; Fulton, William B.; Martin, Laura Y.; Redfield, Elizabeth J.; Crawford, Bryan; Panaparambil, Rohan; Sodhi, Chhinder; March, John C.; Hackam, David.

In: Tissue Engineering - Part A, Vol. 25, No. 17-18, 01.09.2019, p. 1225-1241.

Research output: Contribution to journalArticle

Ladd, MR, Costello, CM, Gosztyla, C, Werts, AD, Johnson, B, Fulton, WB, Martin, LY, Redfield, EJ, Crawford, B, Panaparambil, R, Sodhi, C, March, JC & Hackam, D 2019, 'Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue', Tissue Engineering - Part A, vol. 25, no. 17-18, pp. 1225-1241. https://doi.org/10.1089/ten.tea.2018.0239
Ladd MR, Costello CM, Gosztyla C, Werts AD, Johnson B, Fulton WB et al. Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue. Tissue Engineering - Part A. 2019 Sep 1;25(17-18):1225-1241. https://doi.org/10.1089/ten.tea.2018.0239
Ladd, Mitchell R. ; Costello, Cait M. ; Gosztyla, Carolyn ; Werts, Adam D. ; Johnson, Blake ; Fulton, William B. ; Martin, Laura Y. ; Redfield, Elizabeth J. ; Crawford, Bryan ; Panaparambil, Rohan ; Sodhi, Chhinder ; March, John C. ; Hackam, David. / Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue. In: Tissue Engineering - Part A. 2019 ; Vol. 25, No. 17-18. pp. 1225-1241.
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