Garriboli, Massimo;
(2025)
Development of new strategies for Bladder Tissue Engineering.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
For both children and adults with end-stage bladder disease, the need is to provide a low-pressure, compliant urine-storage reservoir. The most performed surgical procedure to augment or replace the bladder uses a vascularised, reconfigured segment of bowel (enterocystoplasty). Although this procedure can provide continence and enhance quality of life, it is commonly associated with serious complications including long-term risk of urine infections, stones, mucus production, metabolic derangement, and malignancy. Tissue engineering of the bladder is a solution that has been proposed as a means of avoiding these complications. Typically, this relies upon the incorporation of a natural or synthetic biomaterial into the bladder, which may or not be pre-cultured with autologous cells. Despite some high-profile reports, critical evaluation of the literature reveals little evidence that bladder tissue engineering can yet achieve a functional outcome equivalent to current surgical techniques and thus there remains an unmet clinical need. The aim of the project was to explore new strategies for developing bladder regeneration through tissue engineering approach. The project has been developed following 3 directions: 1) To develop a natural bladder-derived scaffold from porcine bladder through a decellularisation protocol and perform a full characterization to investigate the scaffold properties. Normal urothelial cells were cultured from human biopsies (children undergoing bladder surgery) and the interaction between scaffold and cells was investigated. A reseeded scaffold with alive cells and a reconstituted functionality was obtained. 2) Alternative sources of urothelium were explored by investigating a) methods to culture and expand cells from normal and diseased bladders using co-cultures with 3T3 feeder layers; b) methods for isolating urothelial cells from amniotic fluid. 3) An in-vivo xenogeneic bladder augmentation in immunosuppressed pigs was designed and performed using a sero-muscular intestine patch lined with human urothelial cells to explore feasibility of an alternative surgical technique called "composite cystoplasty".
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of new strategies for Bladder Tissue Engineering |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204854 |
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