Application of Different Scaffolds for Bladder Wall Regeneration: The Bladder as a Natural Bioreactor

Abstract

We investigated the potential of different scaffolds for in vivo construction of bladder muscular and urothelial wall. Bladder wall was used as a bioreactor to create a model of the natural environment for cellular interactions, growth, and differentiation. Forty rabbits were divided into 10 groups. Different scaffolds were implanted between bladder mucosa and seromuscular layer. Scaffolds used in each group were one layer or a three-layered combination of tissue-engineered pericardium (TEP), biofilm, and polyglycolic acid (PGA). In all groups, a biopsy of full thickness of bladder was dissected. Muscular and urothelial layers were separated and minced into small fragments. Fragments were seeded above the urothelial layer and urothelial fragments were placed on the scaffold under the seromuscular layer. One group served as control and no scaffold was inserted between the separated bladder layers. After 2 and 6 weeks, biopsies were performed for histologic examinations (trichrome, smooth muscle α-actin, and pancytokeratin AE1/AE3, CD34, CD31). Histopathological examinations showed granulomatous reaction and severe inflammation in biofilm-containing groups. Samples with TEP alone and with PGA-coated TEP as scaffolds revealed more organized bladder wall in two different layers with mature urothelial and smooth muscle cells. The number of CD34+ cells and CD31+ microvessels increased continuously during 6 weeks. Our results demonstrated the effective role of PGA-coated TEP as a potential scaffold for muscular and urothelial fragment seeding in bladder wall acting as a natural bioreactor. Biodegradable scaffolds could be helpful in association with acellular matrices to optimize the cell attachment and in vivo bladder wall construction.