Prevascularized bladder acellular matrix hydrogel/silk fibroin composite scaffolds promote the regeneration of urethra in a rabbit model

OBJECTIVE: To evaluate the effects of urethral regeneration with prevascularized bladder acellular matrix hydrogel (BAMH)/silk fibroin (SF) composite scaffolds in a rabbit model. MATERIALS AND METHODS: BAMH/SF and collagen Type I hydrogel/SF (CH/SF) scaffolds were prepared and the structure of the scaffolds was assessed using scanning electron microscopy. BAMH/SF, CH/SF and SF scaffolds were incubated in the omentum of male rabbits for two weeks and then harvested for repairing autologous urethral defects. Histological analysis of the incubated scaffolds was performed to evaluate the neovascularization capacity, and the outcomes of urethroplasty were evaluated at one and three months post-operatively. RESULTS: The composited scaffolds were composed of a highly porous BAMH or CH buttressed by compact SF outer layer. The histological analysis of the incubated BAMH/SF revealed a signifcant increase of the neovascularization among three groups after a two-week incubation. At three months, the urethra maintained wide caliber in the BAMH/SF group. Strictures were found in the CH/SF and SF groups. Histologically, at one month, intact and multilayer epithelium occurred in the BAMH/SF group, and one layer epithelium was found in the CH/SF and SF groups. However, there was similar epithelial regeneration in BAMH/SF and CH/SF groups at three months (p > 0.05). Comparisons of smooth muscle content and vessel density among the SF, CH/SF and BAMH/SF revealed a significant increase at each time point (p < 0.05). CONCLUSION: Our results demonstrate that incubated BAMH/SF promote neovascularization, and prevascularized BAMH/SF promote the regeneration of the urethral epithelium and smooth muscle, which indicates its potential for urethral reconstruction.