title: Bi-layer silk fibroin grafts support functional tissue regeneration in a porcine model of onlay esophagoplasty.
abstract: Partial circumferential, full thickness defects of the esophagus can occur as a result of organ perforation or tumour resection, or during surgical reconstruction of strictured segments. Complications associated with autologous tissue flaps conventionally utilized for defect repair necessitate the development of new graft options. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated for their potential to support functional restoration of partial circumferential defects in a porcine model of esophageal repair. Onlay thoracic esophagoplasty with BLSF matrices (~3 x 1.5 cm) was performed in adult swine (N = 6) for 3 months of implantation. All animals receiving BLSF grafts survived with no complications and were capable of solid food consumption. Radiographic esophagrams revealed preservation of organ continuity with no evidence of contrast extravasation or strictures. Fluoroscopic analysis demonstrated peristaltic contractions. Ex vivo tissue bath studies displayed contractile responses to carbachol, electric field stimulation, and KCl while isoproterenol produced tissue relaxation. Histological and immunohistochemical evaluations of neotissues showed a stratified, squamous epithelium, a muscularis mucosa composed of smooth muscle bundles, and a muscularis externa organized into circular and longitudinal layers, with a mix of striated skeletal muscle fascicles interspersed with smooth muscle. De novo innervation and vascularization were observed throughout the graft sites and consisted of synaptophysin-positive neuronal boutons and vessels lined with CD31-positive endothelial cells. The results of this study demonstrate that BLSF scaffolds can facilitate constructive remodeling of partial circumferential, full thickness esophageal defects in a large animal model. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Algarrahi
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Franck
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Division of Urology, Veterans Affairs Boston Healthcare System, West Roxbury, MA, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cristofaro
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Savarino
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Saif
authors.initials: S
authors.lastname: Affas
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Frank-Mattias
authors.initials: FM
authors.lastname: Schäfer
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghezzi
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Jennings
authors.affiliation: Animal Resource at Children's Hospital, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Nedder
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
authors.forename: David L
authors.identifier: 0000-0003-3287-3175
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA.|Division of Urology, Veterans Affairs Boston Healthcare System, West Roxbury, MA, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Maryrose P
authors.initials: MP
authors.lastname: Sullivan
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Estrada
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.|Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Joshua R
authors.identifier: 0000-0002-3186-3664
authors.initials: JR
authors.lastname: Mauney
mesh_terms: D000818:Animals; D004944:Esophagoplasty; D005349:Fibroins / Q000494:pharmacology*; D008954:Models, Biological; D012038:Regeneration / Q000187:drug effects*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005349:Fibroins