PhD Thesis Defense: Rebecca Thomson
"Naturally-Derived Electrospun Scaffolds as an Alternative to Surgical Mesh for Pelvic Floor Reconstructive Surgeries"
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Abstract: Stress urinary incontinence (SUI) affects over 25% of adult women, yet current treatment options remain limited to synthetic polypropylene mesh. This treatment option is associated with complications such as mesh exposure and tissue erosion, while the alternative, autologous fascia, presents challenges due to inconsistent properties and additional surgical site morbidity. This dissertation details the development and characterization of composite electrospun scaffolds combining polyhydroxybutyrate (PHB) and silk fibroin (SF) as potential alternatives that balance mechanical support with biological integration.
Initial studies on homogeneous PHB/SF blends (100/0, 75/25, 50/50, 25/75, 0/100) revealed a fundamental tradeoff: PHB-dominant scaffolds exhibited superior mechanical strength but limited cell attachment, while SF-dominant scaffolds enhanced biological activity but reduced mechanical integrity. To overcome this limitation and integrate the benefits of both materials, coaxial electrospun scaffolds were developed with a PHB core and SF sheath. Overall, scaffolds with lower PHB core concentrations and a consistent SF sheath demonstrated higher tensile strength and storage modulus than those with higher PHB concentrations, attributed to the formation of denser fiber networks with enhanced fiber-fiber interactions.
Once establishing a deep understanding of material structure-property relationships, in vitro degradation and initial inflammatory responses were measured. Enzymatic degradation studies demonstrated that coaxial scaffolds maintained structural integrity for a longer duration than homogeneous blends, with controlled degradation profiles enabling compositional tuning to better match native tissue regeneration rates. To further assess in vivo integration potential, immunological assessment with THP-1-derived macrophages showed that coaxial scaffolds promoted a balanced inflammatory response characterized by moderate initial IL-1β expression that decreased by 72 hours, strategic upregulation of IL-1RA, and controlled MMP/TIMP ratios favorable for tissue remodeling. These findings establish that 4% and 5% wt/v PHB 5% wt/v SF coaxial scaffolds are promising candidates for pelvic floor reconstruction, offering tunable mechanical properties, controlled degradation, and favorable immunomodulatory characteristics to decrease complications associated with current treatment options.
Thesis Committee: Douglas Van Citters (Chair), Katherine Hixon, Ryan Halter, Isaac Rodriguez (SweetBio)
