Women with pelvic
organ prolapse (POP) have bothersome
complaints
that significantly affect their quality of life. While native tissue
repair is associated with high recurrence rates, polypropylene knitted
implants have caused specific implant-related adverse events that
have detrimental, often irreversible, effects. We hypothesize that
surgical outcome can be improved with a tissue-engineered solution
using an absorbable implant that mimics the natural extracellular
matrix (ECM) structure, releases estrogen, and activates collagen
metabolism by fibroblasts as the main regulators of wound healing.
To this aim, we produced electrospun poly-4-hydroxybutyrate (P4HB)
scaffolds and biofunctionalized them with estradiol (E2). The cell–implant
interactions relevant for POP repair were assessed by seeding primary
POP vaginal fibroblasts isolated from patients on electrospun P4HB
scaffolds with 1%, 2%, or 5% E2 and without E2. To test our hypothesis
on whether ECM mimicking structures should improve regeneration, electrospun
P4HB was compared to knitted P4HB implants. We evaluated vaginal fibroblast
proliferation, ECM deposition, and metabolism by quantification of
collagen, elastin, and matrix metalloproteinases and by gene expression
analysis for 28 days. We established effective E2 drug loading with
a steady release over time. Significantly higher cell proliferation,
collagen-, and elastin deposition were observed on electrospun P4HB
scaffolds as compared to knitted P4HB. For this study, physical properties
of the scaffolds were more determinant on the cell response than the
release of E2. These results indicate that making these electrospun
P4HB scaffolds E2-releasing appears to be technically feasible. In
addition, electrospun P4HB scaffolds promote the cellular response
of vaginal fibroblasts and further studies are merited to assess if
their use results in improved surgical outcomes in case of POP repair.