Abstract
Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a rabbit model of urethra repair. A bi-layer silk fibroin matrix was fabricated by a solvent-casting/salt leaching process in combination with silk fibroin film casting to generate porous foams buttressed by homogeneous silk fibroin films. Ventral onlay urethroplasty was performed with silk fibroin grafts (Group 1, N = 4) (Width×Length, 1×2 cm2) in adult male rabbits for 3 m of implantation. Parallel control groups consisted of animals receiving small intestinal submucosa (SIS) implants (Group 2, N = 4) or urethrotomy alone (Group 3, N = 3). Animals in all groups exhibited 100% survival prior to scheduled euthanasia and achieved voluntary voiding following 7 d of initial catheterization. Retrograde urethrography of each implant group at 3 m post-op revealed wide urethral calibers and preservation of organ continuity similar to pre-operative and urethrotomy controls with no evidence of contrast extravasation, strictures, fistulas, or stone formation. Histological (hematoxylin and eosin and Masson's trichrome), immunohistochemical, and histomorphometric analyses demonstrated that both silk fibroin and SIS scaffolds promoted similar extents of smooth muscle and epithelial tissue regeneration throughout the original defect sites with prominent contractile protein (α-smooth muscle actin and SM22α) and cytokeratin expression, respectively. De novo innervation and vascularization were also evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Following 3 m post-op, minimal acute inflammatory reactions were elicited by silk fibroin scaffolds characterized by the presence of eosinophil granulocytes while SIS matrices promoted chronic inflammatory responses indicated by mobilization of mononuclear cell infiltrates. The results of this study demonstrate that bi-layer silk fibroin scaffolds represent promising biomaterials for onlay urethroplasty, capable of promoting similar degrees of tissue regeneration in comparison to conventional SIS scaffolds, but with reduced immunogenicity.
Highlights
The urethra serves as a crucial outlet conduit through which urine is expelled from the urinary tract
We evaluated the efficacy of an acellular, bi-layer silk fibroin matrix to mediate tissue regeneration in a rabbit model of onlay urethroplasty
Ventral onlay urethroplasty was a feasible approach for surgical integration of both small intestinal submucosa (SIS) and silk fibroin scaffolds into urethral defects (Figure 2A–C)
Summary
The urethra serves as a crucial outlet conduit through which urine is expelled from the urinary tract. It has a major role in the urinary continence mechanism [1], and in the adult male, an intact urethra is essential for the adequate anterograde transport of seminal fluid and fertility [2]. A wide variety of congenital and acquired pathologies including hypospadias, epispadias, strictures, fistulas, malignancy, and straddle injuries can compromise the normal functionality of the urethra necessitating organ reconstruction [3,4,5,6,7]. End-to-end anastomosis is frequently used to repair short, non complex urethral defects wherein organ continuity is surgically restored by aligning and joining normal tissue segments [8]. Given the limitations associated with conventional surgical approaches, there exists a substantial need for the development of alternative strategies for urethral tissue replacement
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