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Detrusor bioengineering using a cell-enriched compressed collagen hydrogel


Smolar, Jakub; De Nardo, Daniele; Reichmann, Ernst; Gobet, Rita; Eberli, Daniel; Horst, Maya (2020). Detrusor bioengineering using a cell-enriched compressed collagen hydrogel. Journal of Biomedical Materials Research. Part B, 108(7):3045-3055.

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 × 10$^{6}$ or 4 × 10$^{6}$ 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 × 10$^{6}$ cells was significantly better than with 1 × 10$^{6}$ 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.

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 × 10$^{6}$ or 4 × 10$^{6}$ 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 × 10$^{6}$ cells was significantly better than with 1 × 10$^{6}$ 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
04 Faculty of Medicine > University Children's Hospital Zurich > Clinic for Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > Biomaterials
Physical Sciences > Biomedical Engineering
Language:English
Date:1 October 2020
Deposited On:19 Jan 2021 16:33
Last Modified:02 Feb 2021 22:06
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1552-4973
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/jbm.b.34633
PubMed ID:32420687

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