新型可降解防返流食管胃吻合支架的实验研究及吻合口愈合机制的探讨

Gastric Interposition for Esophageal Substitution has been the most used treatment for gastric tract reconstruction following esophagectomy, and currently the Hand-Suture Anastomosis and Stapling Anastomosis are majorly adopted in the esophago-gastric anastomoses. However, both two methods unavoidably link to comparatively complicate time-consuming surgical operation and high risk of anastomotic leakage or stenosis. Stented Anastomosis using biodegradable material is a recently emerging clinical application reflecting superiority in different aspects and has been demonstrated to carry remarkable practical effect in Gastrointestinal Anastomosis and Enteroenterostomy, nevertheless challenges remain in its applicability to Esophago-gastric anastomoses considering the complexity of the specified anastomosing site. The first-generation biodegradable anti-reflux anastomotic stent has been developed by our research group based on the previous patented product, and exhibit satisfying in vitro characteristics and applicability in stented anastomosis in practice through experiments in vivo and in vitro, despite that improvements are expected as to strengthen its degradation performance and amplify its diameter of inner cavity.This research aims to make improvement based on the previous product and to develop a new biodegradable anti-reflux Anastomotic Stent, and also to evaluate its clinical applicability, characteristics in vivo and in vitro comprehensively through systematic experiments in vivo and in vitro. In the meantime this research would explore the anastomosis healing mechanism after stent placement per the regarding experimental results concerning lower incidence of anastomotic leakage or stenosis, less  inflammatory  reaction, high proportion of Foxp3+ in inflammatory cells, and minor hyperplasia of fibrous tissue, and therefore to identify the correlation of Treg Cell, Inflammation Regulation, and Anastomosis Healing.

食管疾病手术切除术后消化道重建首选胃代食管术，术中食管胃吻合目前主要采用手工或圆形吻合器吻合法，但都存在操作复杂，耗时，术后吻合口瘘及狭窄发生率高等问题。可降解材料支架吻合术是一种新型消化道吻合技术，具多方面优势，在胃肠吻合中效果显著。但因食管胃吻合部位的特殊性，其在食管胃吻合适用性仍需改善。本课题根据既往专利设计，初步研制出第一代用于食管胃吻合的可降解防返流吻合支架，经体内外实验证实有较好体外特性及体内支架吻合可行性，但降解性及内腔直径等仍存不足。本课题拟根据前期研究基础优化支架，研制新型可降解防返流食管胃吻合支架，并通过系统的体内外实验，全面评价支架体内外特性及支架吻合可行性及疗效。同时结合前期实验结果：支架吻合组吻合口瘘及吻合口狭窄发生率低，炎症反应轻，炎症细胞中Foxp3+细胞比例高，纤维组织增生较轻等现象，探讨支架吻合术后吻合口愈合机制，明确Treg细胞-炎症-吻合口愈合相关性。

食管疾病手术切除术后消化道重建首选胃代食管术，术中食管胃吻合目前主要采用手工或圆形吻合器吻合法，但都存在操作复杂，耗时，术后吻合口瘘及狭窄发生率高等问题。可降解材料支架吻合术是一种新型消化道吻合技术，具多方面优势，在胃肠吻合中效果显著。但因食管胃吻合部位的特殊性，其在食管胃吻合适用性仍需改善。本课题设计了一种新型的可用于食管切除术后消化道重建的可降解防反流吻合支架，制作出了不同规格的实验样品。通过抗反流性能测试、可降解性能及径向支撑力测试等体外实验，表明该新型可降解防反流吻合支架具有良好的抗返流性能，可以逐步降解，并在体外降解过程中保持稳定的径向支撑力。课题组使用新型可降解抗反流食管胃吻合支架系统开展了一系列大动物实验，将吻合支架植入动物体内，经过随访观察、术后胃镜检查、病理检查、爆破压检测，证明了新型可降解抗反流吻合支架用于食管胃吻合的可行性、疗效和安全性，可有效降低吻合瘘及吻合口狭窄发生率。 发展了一套新型可降解抗反流吻合支架用于食管胃吻合的手术技术和手术方法，并初步探讨该吻合支架植入后吻合口愈合的机制。同时以此基础，结合材料学，将吻合支架与纳米药物颗粒及光固化水凝胶等材料相结合，制作出具有调控吻合口炎症反应的生物活性食管胃吻合支架。本课题获得实用新型专利授权4项，已申请发明专利2项，培养硕士研究生1名。目前以撰写相关论文一篇，待发表。同济大学本科生依托本课题参加第十六届 “挑战杯”上海市大学生课外学术科技作品比赛,并获得一等奖。