Intrauterine adhesion (IUA) is characterized by endometrial stromal replaced with fibrous tissue during the trauma or operation induced injury. Current clinic IUA management mainly involves surgical removal of the connective tissues and physical separation and often results in reoccurrence. It is of clinic interest to directly address the issue via facilitating the endometrial repair and thereby inhibiting the formation of re-adhesion. To this end, we designed a nanocomposite aloe/poloxamer hydrogel for β-estradiol (E2) intrauterine delivery to exert multi-therapeutic effects and promote endometrial regeneration for IUA treatment. Nanoparticulate decellularized uterus (uECMNPs) was prepared to encapsulate E2 (E2@uECMNPs), which improved the solubility and prolonged cargo release. Then, E2@uECMNPs were further embedded into the thermosensitive aloe-poloxamer hydrogel (E2@uECMNPs/AP). Multiple components from E2@uECMNPs/AP system could collectively promote proliferation and inhibit apoptosis of endometrial stromal cells. E2@uECMNPs/AP significantly increased morphological recovery and decreased uterine fibrosis rate compared with IUA rats in other groups in vivo. Additionally, the levels of Ki67, cytokeratin, and estrogen receptor β were all up-regulated, along with the decreased expression of TGF-β1 and TNF-α in the uterus from rats receiving E2@uECMNPs/AP therapy. Taken together, in situ administration of E2@uECMNPs/AP hydrogel could effectively promote endometrial regeneration and prevent the re-adhesion.

子宫内粘连（IUA）的特征是在创伤或手术引起的损伤期间子宫内膜间质被纤维组织替代。当前的临床IUA管理主要涉及结缔组织的手术切除和物理分离，并经常导致复发。通过促进子宫内膜修复从而抑制再粘连的形成来直接解决该问题具有临床兴趣。为此，我们设计了一种用于子宫内β-雌二醇（E2）的纳米复合芦荟/泊洛沙姆水凝胶，以发挥多种治疗作用并促进子宫内膜再生以进行IUA治疗。制备了纳米颗粒的去细胞子宫（uECMNPs）来封装E2（E2 @ uECMNPs），从而改善了溶解度并延长了货物释放时间。然后，E2uECMNPs进一步嵌入到热敏芦荟泊洛沙姆水凝胶（E2uECMNPs / AP）中。E2 @ uECMNPs / AP系统的多种成分可以共同促进子宫内膜间质细胞的增殖并抑制其凋亡。与其他组的IUA大鼠相比，E2 @ uECMNPs / AP显着提高了形态学恢复并降低了子宫纤维化率。此外，接受E2uECMNPs / AP治疗的大鼠子宫中Ki67，细胞角蛋白和雌激素受体β的水平均上调，而TGF-β1和TNF-α的表达降低。综上所述，原位施用E2 @ uECMNPs / AP水凝胶可有效促进子宫内膜再生并防止再次粘连。E2 @ uECMNPs / AP系统的多种成分可以共同促进子宫内膜间质细胞的增殖并抑制其凋亡。与其他组的IUA大鼠相比，E2 @ uECMNPs / AP显着提高了形态学恢复并降低了子宫纤维化率。此外，接受E2uECMNPs / AP治疗的大鼠子宫中Ki67，细胞角蛋白和雌激素受体β的水平均上调，而TGF-β1和TNF-α的表达降低。综上所述，原位施用E2 @ uECMNPs / AP水凝胶可有效促进子宫内膜再生并防止再次粘连。E2 @ uECMNPs / AP系统的多种成分可以共同促进子宫内膜间质细胞的增殖并抑制其凋亡。与其他组的IUA大鼠相比，E2 @ uECMNPs / AP显着提高了形态学恢复并降低了子宫纤维化率。此外，接受E2uECMNPs / AP治疗的大鼠子宫中Ki67，细胞角蛋白和雌激素受体β的水平均上调，而TGF-β1和TNF-α的表达降低。综上所述，原位施用E2 @ uECMNPs / AP水凝胶可有效促进子宫内膜再生并防止再次粘连。接受E2uECMNPs / AP治疗的大鼠子宫中Ki67，细胞角蛋白和雌激素受体β的水平均上调，而TGF-β1和TNF-α的表达降低。综上所述，原位施用E2 @ uECMNPs / AP水凝胶可有效促进子宫内膜再生并防止再次粘连。接受E2uECMNPs / AP治疗的大鼠子宫中Ki67，细胞角蛋白和雌激素受体β的水平均上调，而TGF-β1和TNF-α的表达降低。综上所述，原位施用E2 @ uECMNPs / AP水凝胶可有效促进子宫内膜再生并防止再次粘连。