Repair of injured urethras with silk fibroin scaffolds in a rabbit model of onlay urethroplasty

Background: Preclinical validation of scaffold-based technologies in animal models of urethral disease is desired to assess wound healing efficacy in scenarios that mimic the target patient population. This study investigates the feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously damaged urethras in a rabbit model of onlay urethroplasty. Materials and methods: A focal, partial thickness urethral injury was created in adult male rabbits (n = 12) via electrocoagulation and then onlay urethroplasty with 50 mm 2 BLSF grafts was carried out 2 wk after injury. Animals were randomly divided into three experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1 (n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were performed preoperatively and at 2 wk after injury in all groups as well as at 1 or 3 mo after scaffold grafting and included urethroscopy, retrograde urethrography (RUG), and histological and immunohistochemical analyses. Results: At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses of repaired urethral segments demonstrated a 39% reduction in urethral stenosis detected following electrocoagulation injury. Histological and immunohistochemical analyses revealed the formation of innervated, vascularized neotissues with alpha-smooth muscle actin+ and SM22 alpha+ smooth muscle bundles and pan-cytokeratin + epithelium at graft sites. Conclusions: These results demonstrate the feasibility of BLSF matrices to support the repair of previously damaged urethral tissues. (C) 2018 Elsevier Inc. All rights reserved.