Recent advances in urologic tissue engineering

Roth, Christopher G.; Kropp, Bradley P.

doi:10.1007/s11934-009-0022-y

Cited by 26 publications

(12 citation statements)

References 30 publications

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“…In order for complete bladder repair to occur, biomaterial configurations must support reconstitution of both the smooth muscle compartment as well as the urothelium to restore organ contractile and permeability functions, respectively [8,9]. Previous studies have investigated the use of natural polymers such as small intestine submucosa (SIS) and bladder acellular matrix (BAM) as alternative biomaterials for bladder regeneration [10,11].…”

Section: Introductionmentioning

confidence: 99%

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

Mauney¹,

Cannon²,

Lovett³

et al. 2011

Biomaterials

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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.

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Section: Introductionmentioning

confidence: 99%

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

Mauney¹,

Cannon²,

Lovett³

et al. 2011

Biomaterials

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“…Biomaterials provide a template for initial defect stabilization and also serve as a conduit for host tissue ingrowth. In order for complete bladder repair to occur, scaffolds must support reconstitution of both the smooth muscle compartment as well as the urothelium to restore organ contractile and barrier functions, respectively [8]. Collagen-based matrices derived from decellularized tissues including small intestinal submucosa (SIS) or bladder acellular matrix (BAM) have been shown to enhance bladder defect healing through the release of endogenous growth factors and extracellular matrix (ECM) cues in various animal models [9–11], however limitations in their mechanical integrity and biocompatibility often result in deleterious fibrosis [12], graft contracture [13], and calcification [14].…”

Section: Introductionmentioning

confidence: 99%

The effect of manipulation of silk scaffold fabrication parameters on matrix performance in a murine model of bladder augmentation

et al. 2011

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Autologous gastrointestinal segments are utilized as the primary option for bladder reconstructive procedures despite their inherent morbidity and significant complication rate. Multi-laminate biomaterials derived from Bombyx mori silk fibroin and prepared from a gel spinning process may serve as a superior alternative for bladder tissue engineering due to their robust mechanical properties, biocompatibility, and processing plasticity. In the present study, we sought to determine the impact of variations in winding (axial slew rate: 2 and 40 mm/sec) and post-winding (methanol and lyophilization) fabrication parameters on the in vivo performance of gel spun silk scaffolds in a murine model of bladder augmentation. Three silk matrix groups with distinct structural and mechanical properties were investigated following 10 weeks of implantation including our original prototype previously shown to support bladder regeneration, Group 1 (2mm/sec, methanol) as well as Group 2 (40mm/sec, methanol) and Group 3 (40mm/sec, lyophilization) configurations. Non surgical animals were assessed in parallel as controls. Quantification of residual scaffold area demonstrated that while Group 1 and 2 scaffolds were largely intact, processing parameters utilized for Group 3 led to significantly higher degrees of scaffold degradation in comparison to Group 1. Histological (hematoxylin and eosin, masson’s trichrome) and immunohistochemical (IHC) analyses showed comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within the original defect site throughout all matrix groups similar to controls. Parallel evaluations demonstrated transitional urothelial formation with prominent uroplakin and p63 protein expression supported by Group 1 and 3 scaffolds, while Group 2 variants supported a thin, immature epithelium composed primarily of uroplakin-negative, p63-positive basal cells. Voided stain on paper analysis revealed similar voiding patterns between all matrix groups; however Group 2 animals displayed substantially lower voided volumes with increased frequency in comparison to controls. In addition, cystometric assessments revealed all matrix groups supported comparable degrees of bladder compliance similar to control levels. The results of this study demonstrate that selective alterations in winding and post-winding fabrication parameters can enhance the degradation rate of gel spun silk scaffolds in vivo while preserving their ability to support bladder tissue regeneration and function.

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“…1,2 Tissue engineering principles have been successfully applied to provide implantable cell-seeded matrices for use in the reconstruction, repair, augmentation, or replacement of laminarly organized luminal organs and tissue structures, such as a bladder or a bladder component, typically composed of urothelial and smooth muscle cell (SMC) layers. [3][4][5][6][7] SMCs may be derived from the patient's own tissue, including the bladder, urethra, ureter, and other urogenital tissue. However, there are challenges associated with the primary organ as the source of cells for a therapeutic product.…”

Section: Introductionmentioning

confidence: 99%

Regeneration of Native-Like Neo-Urinary Tissue from Nonbladder Cell Sources

Basu

Jayo

Ilagan

et al. 2012

Tissue Engineering Part A

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Urinary pathology requiring urinary diversion, partial or full bladder replacement, is a significant clinical problem affecting ~14,000 individuals annually in the United States alone. The use of gastrointestinal tissue for urinary diversion or bladder reconstruction/replacement surgeries is frequently associated with complications. To try and alleviate or reduce the frequency of these complications, tissue engineering and regenerative medicine strategies have been developed using bio-absorbable materials seeded with cells derived from the bladder. However, bladder-sourced cells may not always be suitable for such applications, especially in patients with bladder cancer. In this study, we describe the isolation and characterization of smooth muscle cells (SMCs) from porcine adipose and peripheral blood that are phenotypically and functionally indistinguishable from bladder-derived SMCs. In a preclinical Good Laboratory Practice study, we demonstrate that autologous adipose- and peripheral blood-derived SMCs may be used to seed synthetic, biodegradable tubular scaffold structures and that implantation of these seeded scaffolds into a porcine cystectomy model leads to successful de novo regeneration of a tubular neo-organ composed of urinary-like neo-tissue that is histologically identical to native bladder. The ability to create urologic structures de novo from scaffolds seeded by autologous adipose- or peripheral blood-derived SMCs will greatly facilitate the translation of urologic tissue engineering technologies into clinical practice.

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Recent advances in urologic tissue engineering

Cited by 26 publications

References 30 publications

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

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

The effect of manipulation of silk scaffold fabrication parameters on matrix performance in a murine model of bladder augmentation

Regeneration of Native-Like Neo-Urinary Tissue from Nonbladder Cell Sources

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