3D打印可降解PCL/序贯缓释双诱导因子水凝胶仿生气管支架诱导原位再生及体内移植研究

长段气管缺损修复重建是胸外科领域的难题。同种异体主动脉移植替代气管已进入临床探索性研究阶段，但存在强度较差，软骨再生缓慢等问题。本课题在前期3D打印聚己内酯（PCL）气管外支架治疗气管软化症及长期气管重建研究基础上，提出了以3D打印为基础的可降解PCL/序贯缓释双诱导因子水凝胶气管支架能够加速诱导气管软骨有序再生的假说。本研究拟通过3D打印方法构建力学、形态仿生可降解PCL气管外支架；利用物理固载和化学固载结合方法构建可序贯缓释诱导内源性骨髓间充质干细胞迁移和分化因子（SDF-1和TGF-β）的水凝胶并打印成软骨形态；体外实验评估其物理特性、生物特性，并通过优化双因子释放曲线探寻最佳诱导方案；通过体内原位移植实验，采用GFP体内示踪方法研究其体内诱导内源性骨髓间充质干细胞迁移和分化的机制，并评价其临床应用效果。本项目的研究为长段气管缺损修复重建提供了一种新方法。

Reconstruction of long tracheal defects is a big challenge in thoracic surgery. Allogeneic aorta transplantation to replace trachea has been explored in a pilot clinical study, but there are some problems such as poor strength and slow cartilage regeneration. Based on the previous research of tracheomalacia treatment with 3D printed polycaprolactone (PCL) extractracheal scaffold and the long-term researches on tracheal reconstruction, we proposed that the biodegradable PCL/ sequential slow-release double-inducible factor hydrogel tracheal scaffold based on 3D printing can accelerate the orderly regeneration of tracheal cartilage. In this study, the mechanical and morphological biomimetic biodegradable PCL tracheal scaffold will be constructed by 3D printing. A sequential slow-release hydrogel loading inducing factors (SDF-1 and TGF-β) will be constructed to induce endogenous bone marrow mesenchymal stem cell migration and differentiated into tracheal cartilage. The physical and biological characteristics will be evaluated in vitro, and the optimal induction scheme will be explored by optimizing the two-factor release curve. The mechanism of inducing migration and differentiation of endogenous BMSC in vivo will be studied by in vivo orthotopic transplantation model using GFP tracer method, and its clinical effects will be evaluated. The Implementation of this project would provide a new method for the repair and reconstruction of long-segment tracheal defects.