<p>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&#xa0;cm⁻<sup>1</sup>). 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&#xa0;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 (&gt; 90% inhibition against <i>E. coli</i> and <i>S. aureus</i>), antioxidant capacity, and excellent hemocompatibility (&lt; 5% hemolysis). The hydrogel showed exceptional biocompatibility in cellular assays. Notably, PNS loading significantly suppressed pro-inflammatory cytokines (TNF-<i>α</i>, IL-1<i>β</i>, IL-6) at the mRNA level and inhibited NF-<i>κ</i>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 (&gt; 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.</p>

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

  • Niu Haoting,
  • Tang Shuo,
  • Li Moyong,
  • Guo Lilu,
  • Qin Lulu,
  • Jiang Liuyun,
  • Chen Anji,
  • Hu Xiang

摘要

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-1β, IL-6) at the mRNA level and inhibited NF-κB 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.