DEVELOPING A TISSUE ENGINEERED AUTOLOGOUS FASCIAL GRAFT FOR PELVIC FLOOR RECONSTRUCTIVE SURGERY

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are common problems that affect many women. Approximately 1 in 10 women will require surgery to treat one or both conditions during their lifetime. Recently, surgical repair has utilized non-degradable synthetic mesh which has led to an incidence of serious complications such as exposure in up to 15% of patients. The main aim of this thesis was to produce a pelvic floor repair material (PFRM), composed of an electrospun synthetic polymeric scaffold seeded with autologous fibroblasts, that is robust enough for surgical handling and has adequate mechanical properties to enforce/or reinforce repair techniques used for SUI and POP at the point of implantation and beyond. We produced and evaluated 5 polymeric scaffolds and identified that 2, random fibre electrospun scaffolds composed of PLA and PU, most closely resembled native vaginal tissue in mechanical properties whilst having the best handling characteristics. The response of fibroblasts on scaffolds to mechanical conditioning was then evaluated using three simple models. Dynamic uniaxial tension (stretch) using near physiological strains led to organization of the extracellular matrix and was the most promising conditioning technique. Future work will further assess responses of scaffolds and cell/scaffold combinations to repetitive stretch. The response of fibroblasts on scaffolds to a variety of bioactive factors added to the culture media was also assessed. Dexamethasone and Ascorbic acid supplementation led to significant increases in the production of ECM proteins and mechanical properties of cell-seeded polymeric scaffolds. In future, it may be useful to integrate these factors into polymeric scaffolds so that they are released into the wound bed with the aim of providing an ongoing stimulus for ECM production and the maintenance of the mechanical integrity of healing tissues.