分层管状组织工程化PLLA/gelatine纳米纤维在兔体内的结构性重塑效果及机制研究

如何快速有效地实现组织工程化尿道移植物植入体内后的管腔血管化和上皮化是长尿道重建和功能恢复的关键。我们前期研究表明：具有弱亲水性的导管支架在创伤部位能促进移植物内血管化。近期预实验我们发现：富含尿路上皮和平滑肌细胞的弱亲水性分层管状聚乳酸-明胶（PLLA/gelatine）纳米纤维可适时募集巨噬细胞而诱发促血管生成因子的适时高表达，以可控方式诱导支架内毛细管床形成，进而促进支架移植物的管腔上皮化和平滑肌细胞的定向再生，提示管腔血管化和上皮化在尿道重建中的重要地位。进一步生物学实验结果显示：其分层管状纳米纤维结构和弱亲水性还可①调节上皮和平滑肌细胞的表型表达和基质分泌；②维持缺损部位的管腔通畅。本项目拟解析该组织工程化尿道支架的结构和性能在调节管腔血管化和上皮化过程中的关键作用及机制；研究长尿道缺损后的结构性重塑是否依赖于移植物的管腔血管化和上皮化；为幼龄生命体长尿道缺损的治疗提供新的思路。

How to quickly and effectively realize the lumen vascularization and epithelization after the implantation of tissue-engineered urethral mucosal graft is the key to the reconstruction and functional recovery of the long urethra. Our previous studies showed that the weak hydrophilic catheter scaffold can promote the formation of capillary in the wound site. In recent pre experiments, we found that PLLA/ gelatine nanofibrous rich in urothelium and smooth muscle cells could timely recruit macrophages and induce the timely and high expression of angiogenic factors, induce the formation and remodeling of capillary bed in the scaffold in a controlled way, and then promote the lumen epithelization and orientational regeneration of smooth muscle cells along the nanofibrous graft. It is suggested that vascularization and epithelialization of lumen play an important role in urethra reconstruction. Further biological experiments showed that its stratified tubular nanofibrous architecture and weak hydrophilicity could also ① up-regulate the phenotype expression of epithelial and smooth muscle cells as well as the synthesis of matrix. ② maintain the lumen unobstructed at the defect site. This project intends to analyze the key role and mechanism of the structure and performance of the tissue-engineered urethral scaffold in the regulation of lumen vascularization and epithelialization. To study whether the structural remodeling of the long urethra defect depends on the vascularization and epithelialization of the graft, and to provide a new idea for the treatment of the long segment urethra defect of the young living body.