Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Currently gastrointestinal segments are considered the gold standard for bladder reconstructive procedures However significant complications including chronic urinary tract infection metabolic abnormalities urinary stone formation bowel dysfunction and secondary malignancies are associated with this approach Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties biodegradable features and processing plasticity In the present study we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model Over the course of 70 d implantation period H&E and Masson s trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site Prominent uroplakin and contractile protein expression (alpha-actin calponin and SM22 alpha) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration in contrast to parallel assessments of small intestinal submucosa (SIS) and polyglycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic Inflammatory responses Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation In addition cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity and voided volume while maintaining similar degrees of compliance relative to the control group These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications (C) 2010 Elsevier Ltd All rights reserved