Promoting cell proliferation and collagen production with ascorbic acid 2-phosphate-releasing poly(l-lactide-co-ε-caprolactone) membranes for treating pelvic organ prolapse.

Abstract

Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and its production is controlled by ascorbic acid. Therefore, we investigated novel ascorbic acid 2-phosphate (A2P)-releasing poly(l-lactide-co-ε-caprolactone) (PLCLA2P) membranes in vitro to promote cell proliferation and extracellular matrix protein production to strengthen the natural support of the pelvic fascia for POP applications. We analysed the mechanical properties and the impact of PLCLA2P on cellular responses through cell culture analysis using human vaginal fibroblasts (hVFs) and human adipose-derived stem/stromal cells (hASCs) compared to PLCL. In addition, the A2P release from PLCLA2P membranes was assessed in vitro. The PLCLA2P demonstrated slightly lower tensile strength (2.2 ± 0.4 MPa) compared to PLCL (3.7 ± 0.6 MPa) for the first 4 weeks in vitro. The A2P was most rapidly released during the first 48 h of in vitro incubation. Our findings demonstrated significantly increased proliferation and collagen production of both hVFs and hASCs on A2P-releasing PLCLA2P compared to PLCL. In addition, extracellular collagen Type I fibres were detected in hVFs, suggesting enhanced collagen maturation on PLCLA2P. Moreover, increased extracellular matrix protein expression was detected on PLCLA2P in both hVFs and hASCs compared to plain PLCL. In conclusion, these findings highlight the potential of PLCLA2P as a promising candidate for promoting tissue regeneration in applications aimed for POP tissue engineering applications.