Neurogenic erectile dysfunction (nED) is one of the most common and intractable postoperative complications of rectal and prostate cancer surgery and sometimes accompanies patients lifelong. The transplantation of stem cells has been proved a promising way for treatment. However, the therapeutic efficacy is severely impaired by excessive cell loss and death and poor accumulation in the injury site along with the traditional implantation strategy. Herein, an EPO-loaded multifunctional hydrogel was designed. The hydrogels' adhesive property and mechanical strength were enhanced by adding catechol-catechol adducts, thus significantly improving adipose-derived stem cells (ADSC) retention and rescuing cell loss in the injury site. Meanwhile, the sustained release of EPO effectively ameliorated the viability and paracrine activity of ADSC, leading to enhanced migration of Schwann cells and differentiation of PC12 cells in vivo. On a bilateral cavernous nerve injury rat model, the present stem cell-EPO-hydrogel implanted strategy could significantly alleviate erectile dysfunction. The higher expression of Tuj1 and lower expression of GFAP in the major pelvic ganglia (MPG) indicated the acceleration of neural differentiation while the suppressing development of astrocytes. Also, the combined therapy restored the expression levels of eNOs, nNOs, and α-SMA in penile tissues, suggesting the rehabilitation of the penis. Further analysis of Masson trichrome staining and apoptosis evaluation of the corpus cavernosum showed the preservation of vascular endothelium content and the prevention of penile fibrosis after denervation. Overall, we believe that this combined strategy presents a promising way not only for restoring neurogenic erectile function but also for the clinical translation of stem cell therapy.

中文翻译：

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一种负载 EPO 的多功能水凝胶与脂肪干细胞协同作用，通过增强神经再生和阴茎康复来恢复神经源性勃起功能

神经源性勃起功能障碍 (nED) 是直肠癌和前列腺癌手术最常见和最棘手的术后并发症之一，有时会伴随患者终生。干细胞移植已被证明是一种很有前景的治疗方法。然而，随着传统的植入策略，过度的细胞损失和死亡以及损伤部位的不良积累严重损害了治疗效果。在此，设计了一种负载 EPO 的多功能水凝胶。通过添加儿茶酚-儿茶酚加合物，水凝胶的粘附性能和机械强度得到了增强，从而显着改善了脂肪干细胞 (ADSC) 的保留并挽救了损伤部位的细胞损失。同时，EPO的缓释有效地改善了ADSC的活力和旁分泌活性，导致雪旺细胞的迁移增强和体内PC12细胞的分化。在双侧海绵状神经损伤大鼠模型上，目前的干细胞-EPO-水凝胶植入策略可以显着缓解勃起功能障碍。盆腔主要神经节（MPG）中Tuj1的高表达和GFAP的低表达表明神经分化加速，同时抑制星形胶质细胞的发育。此外，联合治疗恢复了阴茎组织中 eNOs、nNOs 和 α-SMA 的表达水平，表明阴茎的康复。进一步分析Masson三色染色和海绵体细胞凋亡评估表明，去神经支配后血管内皮含量的保存和阴茎纤维化的预防。全面的，