Natural Electrospun Scaffolds as an Alternative to Synthetic Mesh for Stress Urinary Incontinence

ABSTRACT Over 25% of adult women experience pelvic floor disorders including stress urinary incontinence (SUI). Stress urinary incontinence is characterized by involuntary urination when pressure is exerted on the bladder, such as coughing, sneezing, laughing, jogging and other forms of physical exercises. Incontinence can have a significant impact on a woman’s quality of life and while there are non-surgical interventions such as pelvic floor exercises and pessaries, the failure rate is up to 50%. Many women for which non-surgical interventions have been inadequate, resort to surgical solutions such as midurethral sling placement. Of the 300,000 patients who receive midurethral sling surgeries in the US every year, 2-3% experience mesh erosion and up to 20% remain incontinent which may require revision surgeries where more synthetic mesh is placed, compounding the problem. The primary objective of this Phase I STTR is to establish feasibility of a natural, coaxial electrospun scaffold to be used as an alternative to synthetic surgical mesh. Our team is developing a naturally derived scaffold that will dissolve over time and replace the support of the urethra with healthy formation of scar tissue. The Phase I project will focus on the fabrication of coaxial scaffolds using silk fibroin and polyhydroxybutyrate and the attachment and deposition of extracellular matrix (ECM) of fibroblasts to those scaffolds compared to state-of-the-art polypropylene. The deposition of ECM of fibroblasts onto the scaffold demonstrates feasibility of the scaffold to promote fibrous growth as the scaffold degrades over time. If our device is successful, we will decrease the complications and need for revision surgeries for thousands of women undergoing midurethral sling placements. We hypothesize that a coaxial scaffold with the combination of silk fibroin surrounding a PHB core will provide increased mechanical properties and cell attachment points. In Specific Aim 1, we will develop a tunable protocol to fabricate coaxial scaffolds of different weight percentages. In Specific Aim 2, we will validate that our coaxial scaffolds are mechanically strong enough to support the urethra by comparing to the properties defined by Lei et al. Finally, in Specific Aim 3, we will compare ECM deposition and proliferation of fibroblasts on the coaxially spun scaffolds to the synthetic polypropylene mesh. If all criterion are met and feasibility is developed, our device has the potential to move women’s health to a more biocompatible and effective alternative for stress urinary incontinence.