Bilirubin-Albumin Nanoparticle-Encapsulated Hydrogels for the Treatment of Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is characterized by the displacement or even protrusion of the uterus and adnexal tissues into or through the vaginal orifice, severely compromising the physical and mental well-being of the patients. Current treatment methods, including surgery and mechanical restoration, are associated with significant side effects and high recurrence rates. Herein, we fabricated supramolecular hydrogels encapsulating bilirubin-albumin nanoparticles for POP therapy. The hydrogels feature a hollow porous structure, exhibiting a volumetric swelling ratio of over 60% in a simulated vaginal environment within 24 h and a bilirubin release efficiency of 80% within the same period. The hydrogels also possess excellent stability and self-healing capability, making them suitable for transvaginal injection. In vitro and in vivo experiments demonstrate that the hydrogels efficiently inhibit reactive oxygen species, thereby inducing the PPAR/TGF-β/MMP1 signaling pathway to promote extracellular matrix remodeling and exerting good therapeutic efficacy against POP. These results demonstrate that the bilirubin-albumin nanoparticle-encapsulated hydrogels hold therapeutic potential against POP, offering a promising strategy for POP treatment based on supramolecular biomaterials.