Bladder wall replacement by tissue engineering and autologous keratinocytes in minipigs

Abstract

To develop a tissue-engineered bladder wall replacement with autologous cells and a biodegradable scaffold, as whenever there is a lack of native urological tissue the bladder is reconstructed with different bowel segments, which has inevitable complications. Skin biopsies were taken from six minipigs, and primary fibroblast and keratinocyte cell cultures established. A partial resection of the urinary bladder was reconstructed by a cell-seeded scaffold covered with completely differentiated epithelium and supported by a mucosa-free pedicled ileum graft. Each pig was assessed urodynamically and by cystography before operation and every month until explantation; the pigs were killed at 1, 2 and 3 months after augmentation. Control groups (of six pigs each) with bladder augmentation with complete or denuded ileum were used. The bladders were assessed histologically and by distensibility measurements The differentiated keratinocyte epithelium was still present on the reconstructed bladder wall after 3 months. The overall shrinkage rate was 6.5%. The engineered bladder wall had lower distensibility than the native one. The inflammatory reaction present initially had disappeared after 3 months. The implanted, tissue-engineered substitution of the bladder wall is not only a bridging graft, but also a complete reconstruction. With this model, extended bladder wall substitution seems feasible and should be investigated in further studies.