A multilayer scaffold design with spatial arrangement of cells to modulate esophageal tissue growth.

Esophageal diseases may require resectioning of the damaged portion. The current standard of care requires the replacement of the esophagus with the stomach or the intestine. Such procedures have high rates of mortality and morbidity; therefore, the use of alternative conduits is needed. A tissue engineering approach that allows for the regeneration of esophageal tissues would have significant clinical application. A cell-seeded synthetic scaffold could replace the resected part of the esophagus and elicit tissue regrowth. In order to ideally recreate a functioning esophagus, its two crucial tissue layers should be induced: an epithelium on the luminal surface and a muscle layer on the exterior surface. To create a bioengineered esophagus with both tissue layers, a multilayer (ML) tubular scaffold design was considered. Luminal and exterior layers were electrospun with broad pore size to promote penetration and proliferation of mesenchymal stem cells on the lumen and smooth muscle cells on the external. These two layers would be separated by a thin layer with substantially narrower pore size intended to act as a barrier for the two cell types. This ML scaffold design was achieved via electrospinning by tuning the solution and the process parameters. Analysis of the scaffold demonstrated that this tuning enabled the production of three integrated layers with distinguishable microstructures and good mechanical integrity. In vitro validation was conducted on the separated unilayer components of the ML scaffold. The resultant proof-of-concept ML scaffold design could possibly support the spatial arrangement of cells needed to promote esophageal tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 324-331, 2019.

Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells.

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.