Proposal of intestinal tissue engineering combined with Bianchi’s procedure

Nakao, Motonao; Ueno, Takayoshi; Oga, Atsunori; Kuramitsu, Yasuhiro; Nakatsu, Hiroki; Oka, Masaaki

doi:10.1016/j.jpedsurg.2014.11.035

Cited by 13 publications

(12 citation statements)

References 33 publications

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“…The third limitation is the lower force generated by our engineered tissues compared to native rat intestines. A recent study reported force values generated by an implanted engineered intestine to be one-fourth of native intestine [36]. The forces generated by our engineered tissues were 50%-70% those of the native intestine.…”

Section: Discussionmentioning

confidence: 84%

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Zakhem

Elbahrawy

Orlando

et al. 2015

Surgery

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Background There is an urgent need for gut lengthening secondary to massive resections of the gastrointestinal (GI) tract. In this study, we propose to evaluate the remodeling, vascularization and functionality of a chitosan-based tubular neuro-muscular tissue upon subcutaneous implantation in the back of athymic rats. Methods Aligned innervated smooth muscle sheets were bioengineered using human smooth muscle and neural progenitor cells. The innervated sheets were wrapped around tubular chitosan scaffolds. The engineered tubular neuro-muscular 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 histological 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. Functionality of the implant was further characterized using real time force generation. Cholinergic response was demonstrated by robust contraction in response to Ach. VIP and EFS caused relaxation. In the presence of neurotoxin TTX, the magnitude of Ach-induced contraction and VIP-induced relaxation was attenuated while EFS-induced relaxation was completely abolished, indicating neuronal contribution to the response. Conclusion Our results indicated the successful subcutaneous implantation of engineered tubular neuro-muscular tissues. The tissues became vascularized and maintained their myogenic and neurogenic phenotype and function. This provides potential therapeutic prospects for providing implantable replacement GI segments for treating GI motility disorders.

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Section: Discussionmentioning

confidence: 84%

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Zakhem

Elbahrawy

Orlando

et al. 2015

Surgery

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“…Even though the forces generated by the engineered complexes were lower than the forces generated by the native intestine, it is important to note that the force patterns displayed by the engineered complexes are similar to those of native tissues (Zakhem, Elbahrawy, Orlando, et al, , b). Engineered gut tissues generating lower force than native gut tissues has also been a challenge in other studies (Nakao et al, ). In future studies involving anastomosis of the engineered complexes to native intestines, it will be interesting to evaluate whether host cells infiltrate the engineered tissues and increase the magnitude of force generated by the engineered tissues.…”

Section: Discussionmentioning

confidence: 99%

Biomechanical properties of an implanted engineered tubular gut-sphincter complex

Zakhem

Bahrawy

Orlando

et al. 2016

J Tissue Eng Regen Med

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Neuromuscular diseases of the gut alter the normal motility patterns. Although surgical intervention remains the standard treatment, preservation of the sphincter attached to the rest of the gut is challenging. The present study aimed to evaluate a bioengineered gut-sphincter complex following its subcutaneous implantation for 4 weeks in rats. Engineered innervated human smooth muscle sheets and innervated human sphincters with a predefined alignment were placed around tubular scaffolds to create a gut-sphincter complex. The engineered complex was subcutaneously implanted in the abdomen of the rats for 4 weeks. The implanted tissues were vascularized. In vivo manometry revealed luminal pressure at the gut and the sphincter zone. Tensile strength, elongation at break and Young's modulus of the engineered complexes were similar to those of native rat intestine. Histological and immunofluorescence assays showed maintenance of smooth muscle circular alignment in the engineered tissue, maintenance of smooth muscle contractile phenotype and innervation of the smooth muscle. Electrical field stimulation induced relaxation of the smooth muscle of both the sphincter and the gut parts. Relaxation was partly inhibited by nitric oxide inhibitor indicating nitrergic contribution to relaxation. The present study has demonstrated for the first time a successfully developed and subcutaneously implanted a tubular human-derived gut-sphincter complex. The sphincteric part of Tubular Gut-Sphincter Complex (TGSC) maintained the basal tone characteristic of a native sphincter. The gut part also maintained its specific neuromuscular characteristics. The results of this study provide a promising therapeutic approach to restore gut continuity and motility. Copyright © 2016 John Wiley & Sons, Ltd.

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“…SIS was previously used as a patch to repair an intestinal defect. [14] Follow-up studies using SIS as a tubular structure to repair the defect are needed. Urinary bladder matrix promoted epithelial regeneration by attracting bone-marrowderived cells to the site of injury.…”

Section: What Type Of Matrix Can Be Used As Support For the Cells?mentioning

confidence: 99%

Is bioengineering a possibility in gastrointestinal disorders?

Bitar

Zakhem

2015

Expert Review of Gastroenterology & Hepatology

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Proposal of intestinal tissue engineering combined with Bianchi’s procedure

Abstract: SIS has the potential for use as a scaffold that promotes the formation of a physical and physiological neointestine. Our present proposal approaches a novel surgical treatment in patients with short bowel syndrome.

Cited by 13 publications

References 33 publications

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold

Biomechanical properties of an implanted engineered tubular gut-sphincter complex

Is bioengineering a possibility in gastrointestinal disorders?

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