Two is Better than One: Evaluation of Single Versus Staged Approaches for Tubular Substitution Urethroplasty with Acellular Silk Fibroin Biomaterials in Rabbits.

Background: Acellular bi-layer silk fibroin (BLSF) scaffolds represent potential alternatives to autologous tissue grafts for substitution urethroplasty (SU) given their ability to repair focal urethral defects in animal models. However, in patients with a severe fibrotic urethral plate, single or staged SU are often required to restore organ continuity. Currently, the feasibility of tubular BLSF grafts for urethral replacement is unknown. Therefore, the objective of this study was to evaluate the efficacy of BLSF biomaterials for SU using single and staged approaches.

Methods: Single (N = 4) and staged (N = 5) SU with BLSF grafts were carried out in adult male rabbits, and animals were maintained for 3 months. Nonsurgical control animals (NSC, N = 3) were evaluated in parallel.

Results: All rabbits survived until harvest and displayed voluntary voiding after initial catheterization with no evidence of severe complications. At 3 months, retrograde urethrograms revealed relative urethral calibers treated with both single and staged approaches were restored to 80 ± 26% and 129 ± 27% of NSC levels. In addition, staged SU led to significantly higher degrees of scaffold degradation as well as urethral patency in respect to the single stage repairs. Histological and immunohistochemical evaluations demonstrated that both surgical techniques supported the formation of innervated, vascularized neotissues resembling NSC. However, neotissues from single stage repairs presented with elevated levels of fibrosis and reduced smooth muscle relative to NSC and the staged cohort.

Conclusions: Single and staged SU with BLSF grafts are feasible for tubular urethral replacement, but staged reconstruction results in improved functional tissue regeneration.