Detrusor bioengineering using a cell-enriched compressed collagen hydrogel

J Biomed Mater Res B Appl Biomater. 2020 Oct;108(7):3045-3055. doi: 10.1002/jbm.b.34633. Epub 2020 May 18.


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 × 106 cells 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.

Keywords: collagen; detrusor muscle; stem cells; tissue engineering; urinary bladder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen*
  • Female
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Myocytes, Smooth Muscle / metabolism*
  • Rats
  • Rats, Inbred Lew
  • Regeneration*
  • Tissue Engineering*
  • Urinary Bladder / injuries
  • Urinary Bladder / physiology*


  • Hydrogels
  • Collagen