title: Full-thickness oesophageal regeneration in pig using a polyurethane mucosal cell seeded graft.
abstract: Malignant oesophageal pathology typically requires resection of a portion of oesophagus. The aim of this study was to investigate attachment and growth of swine oesophageal mucosal cells on electrospun synthetic nanofibre matrices of varying chemistries and to determine whether a mucosal-seeded graft, in a swine animal model, could induce regeneration. Swine mucosal oesophageal cells were isolated and seeded them onto five different matrix materials. Matrix samples were cultured for up to 14 days, after which matrices were analysed for cell attachment. Attachment varied for each of the matrix materials tested, with the most rigid showing the lowest levels of attachment. Importantly, sections of these matrices illustrated that multiple layers of mucosal cells formed, mimicking endogenous oesophageal structure. A tdTomato reporter line (mucosaltdtcells) was created to enable cell tracking. As polyurethane matrix was found optimal through in vitro testing, a graft was prepared using mucosaltdtcells, along with an unseeded control, and implanted into swine for determination of oesophageal regeneration. Mucosal seeded polyurethane grafts initiated full thickness regeneration of the oesophagus, including epithelial, submucosal, and skeletal muscle layers which were highly vascularized. Interestingly, an unseeded graft showed similar regeneration, indicating that the role of cells in the process of oesophageal regeneration is still unclear. The electrospun polyurethane matrix does appear suitable for multilayered cellular attachment and growth of oesophageal mucosal cells, and implantation of polyurethane grafts initiated full thickness regeneration of the oesophagus, indicating potential for oesophageal reconstruction in humans. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Barron
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Blanco
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.|Mayo Clinic Physiology and Biomedical Engineering, Rochester, MN, USA.
authors.forename: Johnathon M
authors.initials: JM
authors.lastname: Aho
authors.affiliation: Nanofiber Solutions, Inc., Columbus, OH, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Chakroff
authors.affiliation: Nanofiber Solutions, Inc., Columbus, OH, USA.
authors.forename: Jed
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.|Mayo Clinic Division of Neonatal Medicine, Rochester, MN, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cassivi
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.|Mayo Clinic Division of Neonatal Medicine, Rochester, MN, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Carey
authors.affiliation: Mayo Clinic Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Wigle
mesh_terms: D000818:Animals; D004947:Esophagus / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D005109:Extracellular Matrix / Q000378:metabolism; D017930:Genes, Reporter; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D011140:Polyurethanes / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects*; D013552:Swine
chemical_list: D011140:Polyurethanes
keywords: oesophageal mucosal cells; oesophagus; pig; synthetic matrix; tissue engineering; tissue regeneration