4.6 Article

Tissue Engineered Tubular Construct for Urinary Diversion in a Preclinical Porcine Model

Journal

JOURNAL OF UROLOGY
Volume 188, Issue 2, Pages 653-660

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.juro.2012.03.119

Keywords

urinary diversion; tissue engineering; regenerative medicine; tissue scaffolds; swine

Funding

  1. EU [LSHB-CT-2006-037409]
  2. NWO Casimir from the Netherlands Organisation of Scientific Research and Development [018.003.023]
  3. AGIKO stipendium from ZonMw
  4. Radboud University Nijmegen Medical Center [920-03-456]

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Purpose: The ileal conduit has been considered the gold standard urinary diversion for patients with bladder cancer and pediatric patients. Complications are mainly related to the use of gastrointestinal tissue. Tissue engineering may be the technical platform on which to develop alternatives to gastrointestinal tissue. We developed a collagen-polymer conduit and evaluated its applicability for urinary diversion in pigs. Materials and Methods: Tubular constructs 12 cm long and 15 mm in diameter were prepared from bovine type I collagen and Vypro (R) II synthetic polymer mesh. Characterized tubes were sterilized, seeded with and without primary porcine bladder urothelial cells, and implanted as an incontinent urostomy using the right ureter in 10 female Landrace pigs. At 1 month the newly formed tissue structure was functionally and microscopically evaluated by loopogram and immunohistochemistry, respectively. Results: The survival rate was 80% with 1 related and 1 unrelated death. By 1 month the collagen was resorbed and a retroperitoneal tunnel had formed that withstood 40 cm H2O water pressure. In 5 cases the tunnel functioned as a urostomy. Histological analysis revealed a moderate immune response, neovascularization and urothelial cells in the construct lumen. The polymer mesh provoked fibroblast deposition and tissue contraction. No major differences were observed between cellular and acellular constructs. Conclusions: After implanting the tubular constructs a retroperitoneal tunnel was formed that functioned as a urinary conduit in most cases. Improved large tubular scaffolds may generate alternatives to gastrointestinal tissue for urinary diversion.

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