Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Barron, Matthew; Blanco, Ellen W.; Aho, Johnathon M.; Chakroff, Jason; Johnson, Jed; Cassivi, Stephen D.; Carey, William A.; Wigle, Dennis A.

doi:10.1002/term.2386

Cited by 15 publications

(17 citation statements)

References 20 publications

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“…In the last few years, tissue engineering (TE) has emerged as a promising solution for the replacement of physiological esophageal functions [7][8][9]. This field of science has deeply benefited from meaningful progresses in biomaterial science, nanotechnologies, bioreactor technology, molecular biology, and stem cells discovery [10,11].…”

Section: Introductionmentioning

confidence: 99%

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering

Pisani

Croce

Chiesa

et al. 2020

IJMS

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Aim of work was to locate a simple, reproducible protocol for uniform seeding and optimal cellularization of biodegradable patch minimizing the risk of structural damages of patch and its contamination in long-term culture. Two seeding procedures are exploited, namely static seeding procedures on biodegradable and biocompatible patches incubated as free floating (floating conditions) or supported by CellCrownTM insert (fixed conditions) and engineered by porcine bone marrow MSCs (p-MSCs). Scaffold prototypes having specific structural features with regard to pore size, pore orientation, porosity, and pore distribution were produced using two different techniques, such as temperature-induced precipitation method and electrospinning technology. The investigation on different prototypes allowed achieving several implementations in terms of cell distribution uniformity, seeding efficiency, and cellularization timing. The cell seeding protocol in stating conditions demonstrated to be the most suitable method, as these conditions successfully improved the cellularization of polymeric patches. Furthermore, the investigation provided interesting information on patches’ stability in physiological simulating experimental conditions. Considering the in vitro results, it can be stated that the in vitro protocol proposed for patches cellularization is suitable to achieve homogeneous and complete cellularizations of patch. Moreover, the protocol turned out to be simple, repeatable, and reproducible.

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Section: Introductionmentioning

confidence: 99%

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering

Pisani

Croce

Chiesa

et al. 2020

IJMS

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“…Esophageal epithelial cells (EECs) are another cell source that can be easily obtained by endoscopy and used to seed the intraluminal surface of a scaffold. Many studies have utilized mucosal cells as a cell source in conjunction with various types of matrices [28][29][30][31][32]. These studies demonstrate epithelial regeneration when seeded scaffolds are used, while epithelia regeneration was absent in the absence of cells.…”

mentioning

confidence: 99%

“…These studies describe regeneration of the esophagus in up to 4 weeks with the presence of an epithelial layer and a disorganized or absent muscle layer. However, more recent studies using silk scaffolding [39][40][41], Poly lactic-co-glycolic acid (PLGA) [42,43], and polyurethane (PU) [28] describe smooth muscle and fibroblast regeneration followed by a squamous epithelial lining. The second objective of this study was to evaluate the feasibility of bridging a long intrathoracic esophageal gap with either an autologous EEC seeded or AF-MSC seeded polyurethane (Biostage™) graft in a porcine model of esophageal loss.…”

mentioning

confidence: 99%

Polyurethane scaffolds seeded with autologous cells can regenerate long esophageal gaps: An esophageal atresia treatment model

Jensen

Wanczyk

Sharma

et al. 2019

Journal of Pediatric Surgery

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Background: Pediatric patients suffering from long gap esophageal defects or injuries are in desperate need of innovative treatment options. Our study demonstrates that two different cell sources can adhere to and proliferate on a retrievable synthetic scaffold. In feasibility testing of translational applicability, these cell seeded scaffolds were implanted into piglets and demonstrated esophageal regeneration. Methods: Either porcine esophageal epithelial cells or porcine amniotic fluid was obtained and cultured in 3 dimensions on a polyurethane scaffold (Biostage). The amniotic fluid was obtained prior to birth of the piglet and was a source of mesenchymal stem cells (AF-MSC). Scaffolds that had been seeded were implanted into their respective Yucatan mini-swine. The cell seeded scaffolds in the bioreactor were evaluated for cell viability, proliferation, genotypic expression, and metabolism. Feasibility studies with implantation evaluated tissue regeneration and functional recovery of the esophagus. Results: Both cell types seeded onto scaffolds in the bioreactor demonstrated viability, adherence and metabolism over time. The seeded scaffolds demonstrated increased expression of VEGF after 6 days in culture. Once implanted, endoscopy 3 weeks after surgery revealed an extruded scaffold with newly regenerated tissue. Both cell seeded scaffolds demonstrated epithelial and muscle regeneration and the piglets were able to eat and grow over time. Conclusions: Autologous esophageal epithelial cells or maternal AF-MSC can be cultured on a 3D scaffold in a bioreactor. These cells maintain viability, proliferation, and adherence over time. Implantation into piglets demonstrated esophageal regeneration with extrusion of the scaffold. This sets the stage for translational application in a neonatal model of esophageal atresia.

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“…Those difficulties mainly arise from the immunogenicity and low biocompatibility of the materials [17]. In recent years, each technology has gradually developed, and good research results have come to emerged [18–21]. Among them, in the report of decellularized esophagus, Guillaume et al reported that they had transplanted and obtained long-term survival after recellularization of decellularized porcine esophagus, and it is said to be an excellent method in terms of strength and tissue compatibility [21].…”

Section: Discussionmentioning

confidence: 99%

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing

Takeoka¹,

Matsumoto²,

Taniguchi³

et al. 2019

PLoS ONE

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Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.

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Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft

Cited by 15 publications

References 20 publications

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering

Polyurethane scaffolds seeded with autologous cells can regenerate long esophageal gaps: An esophageal atresia treatment model

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing

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