Bladder regeneration in a canine model using hyaluronic acid-poly(lactic-co-glycolic-acid) nanoparticle modified porcine small intestinal submucosa.

OBJECTIVE: • To determine if hyaluronic acid (HA) can be incorporated into porcine small intestinal submucosa (SIS) through poly (lactide-co-glycolide-acid) (PLGA) nanoparticles to improve the consistency of the naturally derived biomaterial and promote bladder tissue regeneration. METHODS: • Beagle dogs were subjected to 40% partial cystectomy followed by bladder augmentation with commercial SIS or HA-PLGA-modified SIS. • Urodynamic testing was performed before and after augmentation to assess bladder volume. • A scoring system was created to evaluate gross and histological presentations of regenerative bladders. RESULTS: • All dogs showed full-thickness bladder regeneration. • Histological assessment showed improved smooth muscle regeneration in the HA-PLGA-modified SIS group. • For both groups of dogs, urodynamics and graft measurements showed an approximate 40% reduction in bladder capacity and graft size from pre-augmentation to post-regeneration measurements. • Application of the scoring system and statistical analysis failed to show a significant difference between the groups. CONCLUSIONS: • SIS can be modified through the addition of HA-PLGA nanoparticles. The modified grafts showed evidence of improved smooth muscle regeneration on histological assessment, although this difference was not evident on a novel grading scale. • The volume loss and graft shrinkage experienced are consistent with previous models of SIS bladder regeneration at the 10-week time point. • Additional research into the delivery of HA and the long-term benefits of HA on bladder regeneration is needed to determine the full benefit of HA-PLGA-modified SIS. In addition, a more objective biochemical characterization will be needed to evaluate the quality of regeneration.

Temporal differentiation and maturation of regenerated rat urothelium.

OBJECTIVE: To determine if porcine small intestinal submucosa (SIS)-regenerated urothelium expresses markers of urothelial differentiation, uroplakin and zona occludens-1 (ZO-1), and whether their expression correlates with the histological appearance of the urothelium. MATERIALS AND METHODS: In all, 15 rats underwent partial cystectomy and bladder replacement with SIS. Regenerated bladders were harvested at either 2, 7, 14, 28, or 56 days after SIS grafting. Histological examination with haematoxylin and eosin staining was conducted to assess tissue regeneration. Immunohistochemistry was performed with uroplakin and ZO-1 antibodies. RESULTS: By 14 days after SIS grafting, the urothelial layer was completely confluent over the SIS. Expression of uroplakin and ZO-1, evident at 2 days after SIS grafting, progressed from a cytoplasmic pattern of expression to a mature pattern of cytoplasmic and membrane expression by 56 days after SIS grafting. CONCLUSION: In vivo tissue regeneration produces histologically and phenotypically mature urothelium within 2 weeks of SIS implantation. Regeneration of functional urothelium is probably essential for the subsequent development of the remaining bladder.