缓释尿源干细胞外泌体的复合成孔水凝胶促进全层海绵状尿道修复的实验研究

尿道下裂术后并发症的发生率居高不下，原因在于缺损的尿道海绵体难以修复。因此，促进尿道海绵体的修复、重建全层海绵状尿道是解决该问题的关键。研究证实，体外构建工程化海绵状尿道的修复效果不佳。而在异位尿道开口的近端和背侧往往存在相对健康的海绵体组织，那么促进周边海绵体组织的再生有望成为重建海绵状尿道的突破点。尿源干细胞来源的外泌体（USC-Exos）被报道具备较强的促血管新生能力，在多种组织损伤中具有一定的修复作用。我们前期研究发现缓释USC-Exos的复合成孔水凝胶可显著促进尿道海绵体的修复，改善组织血供与顺应性，但其是否可用于全层海绵体状尿道的修复，目前仍不明确。因此，本研究拟首先利用口腔黏膜瓣重建缺损的尿道管壁，再使用复合成孔水凝胶填充并修复口腔粘膜瓣外侧的尿道海绵体缺损，进一步明确其对全层海绵状尿道的修复作用。该研究将为解决尿道重建中尿道海绵体修复难、并发症多的临床难题提供新的思路。

The incidence of postoperative complications after hypospadias repair has always been high, because the corpus spongiosum defect was difficult to repair. Therefore, promoting the repair of corpus spongiosum defect and reconstruction of full-thickness spongy urethra is the key to solving this problem. Some studies had demonstrated that the effect of constructing engineered spongy urethra in vitro was not ideal and the spongy urethra cannot be repaired through this way. However, it had been confirmed that relatively healthy corpus spongiosum tissues existed at the proximal and dorsal side of the ectopic urethral orifice. Thus, promoting the regeneration of the surrounding corpus spongiosum tissue may be a breakthrough point in the reconstruction of the spongy urethra. Exosomes secreted by urine derived stem cells (USC-Exos) had been reported to have strong abilities in promoting angiogenesis and have certain roles in repairing many kinds of tissue injury. In our previous work, the void-forming hydrogel was used to encapsulate USC-Exos, preparing a composite void-forming hydrogel that can slow-release USC-sEVs. We found that the composite void-forming hydrogel encapsulated with USC-Exos can significantly promote the repair of the corpus spongiosum and improve the blood supply and compliance of the urethral tissue. But it is still unclear whether it can be used for the repair of the full-thickness spongy urethra. Therefore, in this study, we intend to use an oral mucosal flap to reconstruct the defective urethra firstly, then apply the composite void-forming hydrogel to fill and repair the corpus spongiosum defect. The role of the composite pore-forming hydrogel in repairing the full-thickness spongy urethra will be further clarified. This research will provide new ideas and strategies to solve the complicated problems in urethral reconstruction that corpus spongiosum is difficult to repair and incidence of postoperative complications is high.