Developing biocompatible materials with improved angiogenic potential for surgical treatment of stress urinary incontinence and pelvic organ prolapse

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are two related conditions that significantly impair the quality of life. One in ten women will require primary surgery for SUI and POP. Surgical treatment of both conditions often necessitates the use of a surgical mesh material which is now known to be associated with serious complications in up to 40% of women in long term follow- up. Recently, the use of vaginal mesh products in urogyneacological procedures have been suspended in NHS hospitals in England. There appears to be an unmet and urgent need for better biomaterials to support the pelvic floor which are able to better integrate into tissues at the sites of implantation. The aim of this thesis was to develop a synthetic, degradable material for use in the female pelvic floor that can promote angiogenesis and that can integrate well into tissues. As a first step, an in vivo assay has been developed and optimized to allow effective screening of constructed biomaterials. Biomaterials were processed with electrospinning of polylactic acid (PLA) which is a commonly used, degradable polymer for soft tissue applications. Electrospun PLA scaffolds were functionalized by incorporation of Vitamin C and Estradiol and were tested for their effects on stimulating new blood vessel formation and extracellular matrix production. As a final step, mesenchymal stem cells (MSCs) were also tested for their ability to promote angiogenesis. The final biomaterials were always tested for suitability of their biomechanical properties for applications in the pelvic floor. Both Vitamin C and Estradiol could effectively be incorporated into the electrospun PLA scaffolds with desirable ultrastructural and mechanical properties. Vitamin C was released from the scaffolds over several weeks whereas Estradiol was released over months. Both drugs increased the angiogenic potential of scaffolds and extracellular matrix production. Estradiol releasing electrospun PLA scaffolds resulted in the most dramatic increase in new blood vessel formation. Also MSCs had a mild stimulatory effect on angiogenesis. Future work is underway to test the Estradiol releasing scaffolds in relevant animal models.