Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin Grafts

Saif Affas, Frank Mattias Schäfer, Khalid Algarrahi, Vivian Cristofaro, Maryrose P. Sullivan, Xuehui Yang, Kyle Costa, Bryan Sack, Mehrnaz Gharaee-Kermani, Jill A. Macoska, Gokhan Gundogdu, Catherine Seager, Carlos R. Estrada, Joshua R. Mauney*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The ability of bi-layer silk fibroin (BLSF) matrices to mediate functional tissue formation in porcine bladders subjected to acute partial bladder outlet obstruction (pBOO) was investigated. Sixteen female swine were fitted with a transient urinary catheter containing controlled release valves capable of producing either mild (m-pBOO, 35 ± 10 cmH2O, N = 5) or severe (s-pBOO, 70 ± 15 cmH2O, N = 11) urinary outlet resistance for 2 or 4 weeks, respectively. After obstructive insults, augmentation cystoplasty was performed with BLSF grafts and animals were harvested up to 3 months postrepair. Urodynamic evaluations of swine after m-pBOO and s-pBOO injury displayed significant reductions in bladder capacity reflecting 63% ± 19% and 39% ± 13% of noninjured levels, while the s-pBOO cohort demonstrated a 61% decline in bladder compliance from baseline. By 3 months postreconstruction, bladder capacity and compliance in the augmented s-pBOO group were significantly increased over post-pBOO values reflecting 79% ± 19% and 171% ± 75% of baseline quantities, respectively. Neotissues with contractile properties were present at graft sites in both injury groups and displayed SM22α+ smooth muscle, pan-cytokeratin+ epithelia, vessels lined with CD31+ endothelial cells, and neurofilament 200+ nerve trunks. We demonstrate that BLSF scaffolds can support improvements in bladder capacity and compliance and promote the formation of neotissues in diseased bladders. The search for an ideal "off-the-shelf" biomaterial for augmentation cystoplasty remains elusive and current scaffold configurations are hampered by mechanical and biocompatibility restrictions. In addition, preclinical evaluations of potential scaffold designs for bladder repair are limited by the lack of tractable large animal models of obstructive bladder disease that can mimic clinical pathology. The results of this study describe a novel, minimally invasive, porcine model of partial bladder outlet obstruction that simulates clinically relevant phenotypes. Utilizing this model, we demonstrate that acellular, bi-layer silk fibroin grafts can support the formation of vascularized, innervated bladder tissues with functional properties.

Original languageEnglish (US)
Pages (from-to)855-866
Number of pages12
JournalTissue Engineering - Part A
Volume25
Issue number11-12
DOIs
StatePublished - Jun 2019

Keywords

  • bladder
  • regeneration
  • silk fibroin

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin Grafts'. Together they form a unique fingerprint.

  • Cite this

    Affas, S., Schäfer, F. M., Algarrahi, K., Cristofaro, V., Sullivan, M. P., Yang, X., Costa, K., Sack, B., Gharaee-Kermani, M., Macoska, J. A., Gundogdu, G., Seager, C., Estrada, C. R., & Mauney, J. R. (2019). Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin Grafts. Tissue Engineering - Part A, 25(11-12), 855-866. https://doi.org/10.1089/ten.tea.2018.0113