The performance of silk scaffolds in a rat model of augmentation cystoplasty

Abhishek Seth, Yeun Goo Chung, Eun Seok Gil, Duong Tu, Debra Franck, Dolores Di Vizio, Rosalyn M. Adam, David L. Kaplan, Carlos R. Estrada, Joshua R. Mauney

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

The diverse processing plasticity of silk-based biomaterials offers a versatile platform for understanding the impact of structural and mechanical matrix properties on bladder regenerative processes. Three distinct groups of 3-D matrices were fabricated from aqueous solutions of Bombyx mori silk fibroin either by a gel spinning technique (GS1 and GS2 groups) or a solvent-casting/salt-leaching method in combination with silk film casting (FF group). SEM analyses revealed that GS1 matrices consisted of smooth, compact multi-laminates of parallel-oriented silk fibers while GS2 scaffolds were composed of porous (pore size range, 5-50μm) lamellar-like sheets buttressed by a dense outer layer. Bi-layer FF scaffolds were comprised of porous foams (pore size, ~400μm) fused on their external face with a homogenous, nonporous silk film. Silk groups and small intestinal submucosa (SIS) matrices were evaluated in a rat model of augmentation cystoplasty for 10 weeks of implantation and compared to cystotomy controls. Gross tissue evaluations revealed the presence of intra-luminal stones in all experimental groups. The incidence and size of urinary calculi was the highest in animals implanted with gel spun silk matrices and SIS with frequencies ≥57% and stone diameters of 3-4mm. In contrast, rats augmented with FF scaffolds displayed substantially lower rates (20%) and stone size (2mm), similar to the levels observed in controls (13%, 2mm). 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 defect sites supported by all matrix groups similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent uroplakin and p63 protein expression in all experimental groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by Fox3-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. In comparison to other biomaterial groups, cystometric analyses at 10 weeks post-op revealed that animals implanted with the FF matrix configuration displayed superior urodynamic characteristics including compliance, functional capacity, as well as spontaneous non voiding contractions consistent with control levels. Our data demonstrate that variations in scaffold processing techniques can influence the invivo functional performance of silk matrices in bladder reconstructive procedures.

Original languageEnglish (US)
Pages (from-to)4758-4765
Number of pages8
JournalBiomaterials
Volume34
Issue number20
DOIs
StatePublished - Jul 2013
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to thank Dr. Lin Huang for her help with statistical analyses. Suzanne White and staff at the Histology Core Facility at Beth Israel Deaconess Medical Center are acknowledged for technical assistance with tissue processing for histological analyses. This research was supported by the Tissue Engineering Resource Center , NIH/NIBIB P41 EB002520 (KAPLAN); NIH/NIDDK P50 DK065298-06 (ADAM); NIH/NIDDK T32-DK60442 (FREEMAN); NIH/NIDDK R00 DK083616-01A2 (MAUNEY).

Keywords

  • Bladder
  • Bladder tissue engineering
  • Silk
  • Wound healing

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