TY - JOUR
T1 - Development of Intestinal Scaffolds that Mimic Native Mammalian Intestinal Tissue
AU - Ladd, Mitchell R.
AU - Costello, Cait M.
AU - Gosztyla, Carolyn
AU - Werts, Adam D.
AU - Johnson, Blake
AU - Fulton, William B.
AU - Martin, Laura Y.
AU - Redfield, Elizabeth J.
AU - Crawford, Bryan
AU - Panaparambil, Rohan
AU - Sodhi, Chhinder P.
AU - March, John C.
AU - Hackam, David J.
N1 - Publisher Copyright:
© 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - artificial intestine
KW - biodegradable polymers
KW - functional tissue engineering with intestinal scaffolds
KW - intestinal tissue engineering
KW - poly(glycerol sebacate) scaffold biomechanics
KW - short bowel syndrome
UR - http://www.scopus.com/inward/record.url?scp=85072509175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072509175&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2018.0239
DO - 10.1089/ten.tea.2018.0239
M3 - Article
C2 - 30652526
AN - SCOPUS:85072509175
SN - 1937-3341
VL - 25
SP - 1225
EP - 1241
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 17-18
ER -