Ascorbic acid 2-phosphate-releasing poly-l-lactide-co-epsilon-caprolactone membranes enhance tissue regeneration: first in vivo insights for pelvic organ prolapse

Pelvic organ prolapse (POP) significantly impacts women's health and quality of life. There is a critical need for alternative biomaterials for surgical POP repair, driven by complications associated with conventional non-absorbable vaginal meshes. As ascorbic acid 2-phosphate (A2P) has been demonstrated to enhance collagen production and cell proliferation in vitro, this study investigated absorbable A2P-releasing poly-l-lactide-co-epsilon-caprolactone (PLCL) membranes in the first in vivo study to evaluate their potential to promote tissue regeneration for POP treatment. Biomaterials (PLCL, PLCL4%A2P, PLCL8%A2P and commercial polypropylene (PP) mesh) were implanted subcutaneously on the abdominal fascia of female Sprague-Dawley rats, and tissue samples were collected for tensile testing and histological analysis at 1-week, 1-month and 6-month time points. Histological samples were analysed using X-ray micro-computed tomography, histological stains, and primary antibodies targeting type I and type III collagen to assess connective tissue regeneration and material degradation. The PLCLA2P groups demonstrated enhanced tissue strength without increased stiffness, compensating for material degradation through tissue regeneration. Moreover, collagen amount was increased in the PLCL4%A2P and PLCL8%A2P groups, without signs of adverse fibrosis. Our results suggest that A2P-releasing PLCL4%A2P and PLCL8%A2P membranes enhance tissue strength and collagen deposition in vivo, being a potential alternative for POP repair.