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Development of an autologous fibroblast impregnated tissue for use in urological procedures for stress urinary incontinence and pelvic organ prolapse repair

Mangera, Altaf (2011) Development of an autologous fibroblast impregnated tissue for use in urological procedures for stress urinary incontinence and pelvic organ prolapse repair. MD thesis, University of Sheffield.

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Abstract

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) lead to significant interference in the quality of life of the millions of women affected by them. The treatment options for these women include surgical prostheses which are currently fraught with high failure and complication rates. Our aim was to explore tissue engineering as a solution to the problems of prosthetic failure. The objective was to identify suitable scaffolds that may be used to produce tissue engineered prostheses, with autologous fibroblasts, for use in women with SUI/ POP. Seven candidate scaffolds; Alloderm, cadaveric dermis, polypropylene, porcine dermis, sheep forestomach, porcine small intestinal submucosa and thermoannealed poly(l)lactic acid were investigated. We seeded 800 000 oral fibroblasts to 2cm2 of each scaffold. We assessed the metabolic activity and proliferation of attached cells using AlamarBlue and DAPI staining, contraction using serial photographs, biomechanical properties using a uniaxial tensiometer, collagen production using Sirius red and immunofluorescence staining, and extracellular matrix production using scanning electron microscopy. In addition, the effect of mechanical restraint, simple variable stress and ascorbate-2-phosphate on the above parameters of the tissue engineered prostheses were also investigated. Two scaffolds; porcine small intestinal submucosa and thermoannealed poly(l) lactic acid have been identified as suitable matrices for supporting fibroblast attachment and new extracellular matrix production. Both scaffolds showed cells proliferated and increased their metabolic activity over 14 days of culture. Immunostaining also revealed new collagen I, III and elastin. The mechanical properties of the two scaffolds when cellularised were also close to those of native tissue. We have also shown that mechanical and chemical modulation of the culture environment may be beneficial in producing tissue engineered prostheses with improved properties. Further work will now take these findings in to in vivo models.

Item Type: Thesis (MD)
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield)
Depositing User: Mr Altaf Mangera
Date Deposited: 08 Aug 2012 15:04
Last Modified: 08 Aug 2013 08:49
URI: http://etheses.whiterose.ac.uk/id/eprint/2567

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