title: Bilayer silk fibroin grafts support functional oesophageal repair in a rodent model of caustic injury.
abstract: Surgical repair of caustic oesophageal injuries with autologous gastrointestinal segments is often associated with dysmotility, dysphagia and donor site morbidity, and therefore alternative graft options are needed. Bilayer silk fibroin (BLSF) scaffolds were assessed for their ability to support functional restoration of damaged oesophageal tissues in a rat model of onlay oesophagoplasty. Transient exposure of isolated oesophageal segments with 40% NaOH led to corrosive oesophagitis and a 91% reduction in the luminal cross-sectional area of damaged sites. Oesophageal repair with BLSF matrices was performed in injured rats (n = 27) as well as a nondiseased cohort (n = 12) for up to 2 months after implantation. Both implant groups exhibited >80% survival rates, displayed similar degrees of weight gain, and were capable of solid food consumption following a 3-day liquid diet. End-point μ-computed tomography of repaired sites demonstrated a 4.5-fold increase in luminal cross-sectional area over baseline injury levels. Reconstructed oesophageal conduits from damaged and nondiseased animals produced comparable contractile responses to KCl and electric field stimulation while isoproterenol generated similar tissue relaxation responses. Histological and immunohistochemical evaluations of neotissues from both implant groups showed formation of a stratified, squamous epithelium with robust cytokeratin expression as well as skeletal and smooth muscle layers positive for contractile protein expression. In addition, synaptophysin positive neuronal junctions and vessels lined with CD31 positive endothelial cells were also observed at graft sites in each setting. These results provide preclinical validation for the use of BLSF scaffolds in reconstructive strategies for oesophageal repair following caustic injury.
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Algarrahi
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Franck
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Savarino
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.|Division of Urology, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cristofaro
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Saif
authors.initials: S
authors.lastname: Affas
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Frank-Mattias
authors.initials: FM
authors.lastname: Schäfer
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.|Division of Urology, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts, USA.|Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Maryrose P
authors.initials: MP
authors.lastname: Sullivan
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Estrada
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joshua R
authors.identifier: 0000-0002-3186-3664
authors.initials: JR
authors.lastname: Mauney
mesh_terms: D000818:Animals; D002424:Caustics; D004195:Disease Models, Animal; D004947:Esophagus / Q000187:drug effects / Q000293:injuries* / Q000473:pathology*; D005260:Female; D005349:Fibroins / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002424:Caustics; D005349:Fibroins