神经损伤性勃起功能障碍（CNI-ED）临床缺乏有效治疗手段，迫切需要新的治疗方法。申请人发现人脂肪干细胞来源细胞外囊泡（hASCs-EVs）能促进CNI-ED勃起功能恢复，但促神经修复能力有限。文献报道褪黑素（MT）能促进CNI-ED神经保护和修复，防止海绵体纤维化。申请人采用MT体外预处理hASCs获得EVs，发现其促神经再生和抗纤维化能力得到增强。据此提出假说，MT预处理hASCs-EVs通过关键microRNA进行细胞间信号传递，通过上调海绵体神经和平滑肌中SIRT1的表达，激活PI3K-AKT、WNT-βcatenin通路，保护和促进神经修复；抑制TGFβ信号通路，抗海绵体纤维化。结合体外机制研究和体内MT预处理hASCs-EVs复合水凝胶缓释材料治疗CNI-ED大鼠动物模型，评价其治疗有效性和安全性，为MT预处理hASCs-EVs治疗CNI-ED的临床转化提供理论基础和技术支持。

Cavernous nerve injury erectile dysfunction (CNI-ED) has no effective treatments. New therapies are urgently needed. We have previously found that human adipose-derived stem cell-derived extracellular vesicles (hASCs-EVS) can promote the recovery of erectile function in CNI-ED rats，but has limited effects in promoting nerve regeneration. It is reported that melatonin (MT) can facilitate CNI-ED neuroprotection and repair, as well as preventing cavernous fibrosis. We have used MT to pretreat hASCs to obtain EVs and found that their ability to promote nerve regeneration was better than EVs without pretreatment. Thus we hypothesized that MT pretreated hASCs-EVs in vitro up-regulated SIRT1 expression in cavernosal and smooth muscle through key microRNA signaling. It protects and promotes nerve regeneration by activation of PI3K-AKT, WNT-βcatenin pathway. We intend to use a composite biomaterial which contains sustained-release hydrogel seeded with melatonin pretreated hASCs and comprehensively evaluate the efficacy and safety of this material in the treatment of CNI-ED rats, providing theoretical basis and technical support for the clinical transformation of this material in the treatment of CNI-ED.