Sodium hyaluronate based multifunctional hydrogels delivering SiRNA for sustained silencing of SMAD3: A novel strategy to treat intrauterine adhesions

Intrauterine adhesion (IUA) plays a significant role in female infertility, primarily due to endometrial fibrosis resulting from abnormal activation of the endometrial TGF-β/SMAD3 signaling pathway. However, effectively preventing the high recurrence rate after IUA surgery remains a major challenge that needs to be addressed. To address this challenge, Herein, a novel in situ injectable QOHP@siRNA hydrogel is introduced for the prevention of IUA by silencing SMAD3 . This hydrogel addresses the challenges of poor uptake, short half-life, and rapid degradation of siRNA in the treatment of IUA. Additionally, it has demonstrated strong antibacterial activity against gram-negative bacilli and gram-positive cocci, as well as favorable endometrial adhesion and Internal hemostatic properties. The in vitro and in vivo experimental results demonstrate that QOHP@siRNA sustained SMAD3 silencing, anti-fibrotic effects, and microenvironment protection properties. Furthermore, it promotes endometrial angiogenesis and cellular proliferation, and ultimately restores fertility. This therapeutic strategy demonstrates significant potential for the treatment of IUA, while also providing novel insights into gene delivery vector-based therapies for other diseases.