聚苯胺/聚己内酯高导电纳米支架构建组织工程血管的研究

Clinically there are yet no small caliber vascular substitutes with good biocompatibility and long-term patency. The research on vascular tissue engineering would provide a new way to solve this problem. As the existing vascular tissue engineering scaffolds' physical and chemical properties as well as their biocompatibility cannot meet the needs of blood vessel construction and the clinical application, the hypothesis is innovatively bringing out conductive polymer tissue engineering vascular stents. An interdisciplinary program combining materials science, the bioelectronics, tissue engineering, etc. would be carried. Using technology such as electrospinning, hydrogel and inkjet, this study explores a highly conductive nano polyaniline / polycaprolactone (PCL) stent manufacturing methods, expecting a unique conductivity of double carriers for electron and ion. An interdisciplinary program combining materials science, the bioelectronics, tissue engineering, etc. would be carried. Using technology such as electrospinning, hydrogel and inkjet, this study explores a highly conductive nano polyaniline / polycaprolactone (PCL) stent manufacturing methods, expecting a unique conductivity of double carriers for electron and ion. Also, with a new vascular bioreactor combined electrical stimulating and fluid stimulating, the tendency of adhesion, growth and proliferation of seed cells would be promoted by compound stimulus, and its functional protein would by enhanced, with a view to enhancing the endothelialthation levels and function rate of the tissue engineering vascular that was build. The research is expected to optimize the structuring of tissue engineering blood vessels, as well as to promote future clinical applications.

临床上尚无具有良好生物相容性和长期通畅率的小口径血管代用品，组织工程血管的研究可为解决这一难题提供新途径。本研究针对现有组织工程血管支架理化性能和生物相容性不能满足血管构建及临床应用的瓶颈，提出导电高分子组织工程血管支架研究新构想，通过材料学、生物电子学和组织工程学交叉学科研究方法，应用静电纺丝、水凝胶及喷墨等技术手段，建立新的具有高导电性的纳米聚苯胺/聚己内酯（PCL）血管支架的制备方法，以期该支架拥有独特的电子和离子双重载流子导电性，提供优良细胞界面；同时，组建新型电场-流体刺激血管生物反应器，研究在复合刺激下促进种子细胞趋向性粘附、生长与增殖，并增强其功能蛋白表达，以期提高所构建组织工程血管的内皮化程度及功能化率，从而提高小口径血管代用品研究水平，并为血管疾病治疗提供技术支撑。

目前临床上缺乏具有良好生物相容性和长期通畅率的小口径血管代用品，组织工程血管的研究可为解决解决这一难题提供途径。本研采用聚苯胺（具有金属的导电性和塑料的可加工性。）与聚己内酯（PCL）结合，制备具有高导电性的聚苯胺/聚己内酯（PCL）血管支架，该支架拥有独特的电子和离子双重载流子导电性，提供优良的细胞界面，同时组建新型的生物反应器，在复合刺激下促进细胞粘附于血管。我们首先使用静电纺丝等技术制备具有仿生学结构的PCL纳米血管支架，然后采用喷涂、水凝胶等方法将聚苯胺材料完整覆盖于血管支架表面，制备聚苯胺/PCL组织工程血管，通过与脂肪干细胞来源的内皮祖细胞共培养，经过组织学、免疫学等相关检测，证明该新型血管支架具有良好的生物相容性，细胞生长良好。在体外将细胞置入生物反应器内，在生物脉冲电刺激和流体压力刺激下，构建了新型小口径组织工程血管。我们还进行了动物实验，首先将聚苯胺/PCL细胞补片植入动物体内，证明其具有良好的生物相容性，无生物毒性，然后将新型高电导性的组织工程血管在动物体内行血管移植，实验表明与普通PCL血管相比，其具有较好的中期通畅率。综合上述结果，本研究为研究新型组织工程血管奠定了坚实的工作基础，该新型导电高分子组织工程血管可促进种子细胞的趋向性粘附、生长和增殖，并增强其蛋白表达，可提高所构建组织工程血管的内皮化率及功能化率，有望对血管疾病的治疗提供技术支撑。项目资助发表SCI论文9篇，中文论文1篇。培养博士研究生4名，硕士生2名，其中3名已经取得博士学位，1名取得硕士学位，2名在读。项目投入经费66.5000万元，支出41.1805万元，各项支出基本与预算相符。剩余经费25.3195万元，剩余经费计划用于本项目研究后续支出。