Bi-layer Silk Fibroin Grafts Support Functional Esophageal Repair in a Rodent Model of Caustic Injury

摘要

Surgical repair of caustic esophageal injuries with autologous gastrointestinal segments is often associated with dysmotility, dysphagia, and donor site morbidity and therefore alternative graft options are needed. Bi-layer silk fibroin (BLSF) scaffolds were assessed for their ability to support functional restoration of damaged esophageal tissues in a rat model of onlay esophagoplasty. Transient exposure of isolated esophageal segments with 40% NaOH led to corrosive esophagitis and a 91% reduction in the luminal cross-sectional area of damaged sites. Esophageal repair with BLSF matrices was performed in injured rats (N=27) as well as a nondiseased cohort (N=12) for up to 2 m of implantation. Both implant groups exhibited >80% survival rates, displayed similar degrees of weight gain, and were capable of solid food consumption following a 3 d 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 esophageal 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 esophageal repair following caustic injury.