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

Abstract

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 (α-actin, calponin, and SM22α) 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, voided volume, and flow rate 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.

Experimental bladder regeneration using a poly-L-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells

“…11 In the present study, we aimed to use a bilayer scaffold based on poly-l-lactide/silk fibroin (PL-SF) for bladder augmentation. The inner porous layer of the scaffold was designed to promote cell proliferation and the second outer layer to serve as a barrier to fluid penetration.…”

Inosculation of Blood Vessels Allows Early Perfusion and Vitality of Bladder Grafts—Implications for Bioengineered Bladder Wall

“…The bladder was brought external to the body cavity and exposed. The dome of the bladder was incised 12,13 and a donor graft from the dome of a syngeneic, wild-type male mouse bladder, *5 mm in diameter, was sewn on with a running 8-0 Vicryl suture (Ethicon). The urethra was catheterized with a 24-gauge angiocatheter (BD Biosciences), and the bladder was inflated to verify a watertight anastomosis.…”

“…5 However, a 50% rate of survival for mice postbladder transplant is consistent with other studies and is likely due to the technical challenge of creating a watertight anastomosis. 12 In addition, mice less than 5 months post-BMT exhibited only a 30% survival rate on bladder transplant. Thus, to achieve nearly 50% survival rate, we chose to use animals between 5 and 8 months post-BMT for these studies.…”

Evaluation of Biomaterials for Bladder Augmentation using Cystometric Analyses in Various Rodent Models

“…We have previously reported the use of a bladder augmentation model in mice to determine the potential of silk fibroin-based scaffolds to mediate tissue regeneration and functional voiding characteristics. 11,12 Cystometric analyses of this model have shown that variations in structural and mechanical implant properties can influence the resulting urodynamic features of the tissue engineered bladders 11,12 . Positive correlations between the degree of matrixmediated tissue regeneration determined histologically and functional compliance and capacity evaluated by cystometry were demonstrated in this model 11,12 .…”

“…11,12 Cystometric analyses of this model have shown that variations in structural and mechanical implant properties can influence the resulting urodynamic features of the tissue engineered bladders 11,12 . Positive correlations between the degree of matrixmediated tissue regeneration determined histologically and functional compliance and capacity evaluated by cystometry were demonstrated in this model 11,12 . These results therefore suggest that functional evaluations of biomaterial configurations in rodent bladder augmentation systems may be a useful format for assessing scaffold properties and establishing in vivo feasibility prior to large animal studies and clinical deployment.…”