A Panax notoginseng saponins-loaded carboxymethyl chitosan/oxidized sodium alginate/poloxamer hydrogel for intrauterine adhesions therapy

A novel multifunctional double-network hydrogel composed of carboxymethyl chitosan-oxidized sodium alginate-poloxamer (PF127) loaded with Panax notoginseng saponins (OSA/CM/PF127@PNS) was developed for intrauterine adhesion therapy. FT-IR spectroscopy confirmed acetalation crosslinking between OSA and CMC, as evidenced by characteristic imine peak (1636 cm⁻ 1 ). SEM observations revealed the hydrogel possessed a porous microstructure, with robust self-healing capability validated (by rheological cyclic strain tests), a maximum swelling ratio of 1155%, and sustained PNS release reaching 52.2% at 24 h. In vitro degradation studies indicated the stability under physiological pH (7.4) was enhanced due to the dual-crosslinked network. Moreover, the hydrogel exhibited potent antibacterial activity (> 90% inhibition against E. coli and S. aureus ), antioxidant capacity, and excellent hemocompatibility (< 5% hemolysis). The hydrogel showed exceptional biocompatibility in cellular assays. Notably, PNS loading significantly suppressed pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6) at the mRNA level and inhibited NF- κ B signaling at the protein level. Furthermore, it promoted angiogenesis in vitro, evidenced by upregulated angiogenesis-related proteins. Therapeutically, the hydrogel significantly accelerated wound healing in a murine model (> 90% closure by day 9) and effectively promoted endometrial regeneration in a rat IUA model. This work provides a novel and promising strategy based on natural polymer-based hydrogels, demonstrating its potential for the treatment of intrauterine adhesions and regenerative medicine.