Detrusor bioengineering using a cell‐enriched compressed collagen hydrogel

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Abstract
Objective: The gold standard for bladder regeneration in end‐stage bladder disease is the use of intestinal tissue, which is however associated with significant long‐term complications. Our study aims to bioengineer functional detrusor muscle combining bladder smooth muscle cells (SMC) and SMC‐like adipose‐derived stem cells (pADSC) in compressed collagen (CC) hydrogels and to investigate biocompatibility and tissue regeneration of such detrusor‐equivalents in a rat detrusorectomy model.Methods: Compressed collagen hydrogels seeded with 1 × 106 or 4 × 106 SMC alone or in combination with pADSC in a 1:1 ratio were investigated. Morphology, phenotype, and viability as well as proteomic secretome analysis were assessed in the 1:1 co‐cultures and the respective monocultures. The hydrogels were implanted into rat bladders after partial detrusorectomy. Bladders were harvested 8 weeks after transplantation, and assessed for tissue morphology, detrusor regeneration, neo‐vascularization and ‐innervation.Results: Co‐cultured cells exhibited native SMC morphology, high viability and proliferated to form microtissues in vitro. The pro‐angiogenic factors angiogenin, vascular endothelial growth factor (VEGF)‐A and ‐D were increased in the secretome of the pADSC samples. After 8 weeks of in vivo, the regenerated bladder wall showed a multilayered structure containing all bladder wall components. The overall performance of the bladder wall regeneration of CC seeded with 4 × 106cells was significantly better than with 1 × 106 cells and the combination SMC:pADCS performed slightly better than SMC alone.Conclusion: Compressed collagen possesses an adequate regenerative potential to promote regeneration of bladder wall tissue in vivo. Seeded with a combination of pADSC and SMC this may well be the first step towards a functional bladder reconstruction especially in patients suffering of end‐stage bladder diseases.
Funding Information
  • Fromm Fellowship, Children's Research Center, Childrens University Hospital Zurich
  • Helmut Horten Foundation, University Zurich, Switzerland

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