Background
There is an urgent need for gut lengthening secondary to massive resections of the
gastrointestinal tract. In this study, we propose to evaluate the remodeling, vascularization,
and functionality of a chitosan-based, tubular neuromuscular tissue on subcutaneous
implantation in the back of athymic rats.
Methods
Aligned innervated smooth muscle sheets were bioengineered with the use of human smooth
muscle and neural progenitor cells. The innervated sheets were wrapped around tubular
chitosan scaffolds. The engineered tubular neuromuscular tissue was implanted subcutaneously
in the back of athymic rats. The implant was harvested after 14 days and assessed
for morphology, vascularization, and functionality.
Results
Gross examination of the implants showed healthy color with no signs of inflammation.
The implanted tissue became vascularized as demonstrated by gross and histologic analysis.
Chitosan supported the luminal patency of the tissue. The innervated muscle remodeled
around the tubular chitosan scaffold. Smooth muscle maintained its circumferential
alignment and contractile phenotype. The functionality of the implant was characterized
further by the use of real-time force generation. A cholinergic response was demonstrated
by robust contraction in response to acetylcholine. Vasoactive intestinal peptide-,
and electrical field stimulation–caused relaxation. In the presence of neurotoxin
tetrodotoxin, the magnitude of acetylcholine-induced contraction and vasoactive intestinal
peptide-induced relaxation was attenuated whereas electrical field stimulation–induced
relaxation was completely abolished, indicating neuronal contribution to the response.
Conclusion
Our results indicated the successful subcutaneous implantation of engineered tubular
neuromuscular tissues. The tissues became vascularized and maintained their myogenic
and neurogenic phenotype and function, which provides potential therapeutic prospects
for providing implantable replacement GI segments for treating GI motility disorders.
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Article info
Publication history
Published online: June 19, 2015
Accepted:
May 9,
2015
Footnotes
Supported by NIH/NIDDK R01DK071614 and Wake Forest School of Medicine Institutional Funds.
Dr. Mostafa Elbahrawy is a visitor - Department of Pediatric Surgery, Al-Azhar University, School of Medicine, Cairo, Egypt.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
