Ascorbic acid 2-phosphate-releasing poly-l-lactide-co-epsilon-caprolactone membranes enhance tissue regeneration: first <i>in vivo</i> 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 <i>in vitro</i>, this study investigated absorbable A2P-releasing poly-l-lactide-co-epsilon-caprolactone (PLCL) membranes in the first <i>in vivo</i> study to evaluate their potential to promote tissue regeneration for POP treatment. Biomaterials (PLCL, PLCL_4%A2P, PLCL_8%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 PLCL_A2P groups demonstrated enhanced tissue strength without increased stiffness, compensating for material degradation through tissue regeneration. Moreover, collagen amount was increased in the PLCL_4%A2P and PLCL_8%A2P groups, without signs of adverse fibrosis. Our results suggest that A2P-releasing PLCL_4%A2P and PLCL_8%A2P membranes enhance tissue strength and collagen deposition <i>in vivo</i>, being a potential alternative for POP repair.