Yan Bingyang, Zhang Zhipei, Wang Xiaoping, Ni Yunfeng, Liu Yongshi, Liu Tao, Wang Wuping, Xing Hao, Sun Ying, Wang Jian, Li Xiao-Fei
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Artif Organs. 2017 May;41(5):461-469. doi: 10.1111/aor.12805. Epub 2016 Dec 7.
The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy. We designed a new cell sheet scaffold using the poly(lactic-co-glycolic acid) (PLGA) and poly(trimethylene carbonate) (PTMC) to make a porous membrane for seeding cells, and used the PLGA-PTMC cell-scaffold to pack the decellularized allogeneic trachea to construct a new type of TET. The TET was then implanted in the subcutaneous tissue for vascularization for 2 weeks. Orthotopic transplantation was then performed after implantation. The efficiency of the TET we designed was analyzed by histological examination and biomechanical analyses 4 weeks after surgery. Four weeks after surgery, both the number of chondrocytes and the amount of cartilage matrix were significantly higher than those contained in the traditional stem-cell-based TET. Besides, the coefficient of stiffness of TET was significantly larger than the traditional TET. This study provided a promising approach for the long-term functional reconstruction of long-segment tracheal defect, and the TET we designed had potential application prospects in the field of TET reconstruction.
长节段气管缺损的治疗需要有效的气管替代物移植,组织工程气管(TET)已被提议作为一种理想的气管替代物。TET用于节段性气管缺损重建失败的主要原因是TET软骨软化导致气道塌陷。维持TET结构的关键是软骨中软骨细胞的再生,软骨细胞可分泌大量软骨基质。为解决TET软骨软化问题,本研究提出了一种改进策略。我们设计了一种新型细胞片支架,使用聚乳酸-乙醇酸共聚物(PLGA)和聚碳酸三亚甲基酯(PTMC)制作用于接种细胞的多孔膜,并使用PLGA-PTMC细胞支架包裹去细胞化的同种异体气管以构建新型TET。然后将TET植入皮下组织进行血管化2周。之后进行原位移植。术后4周通过组织学检查和生物力学分析来分析我们设计的TET的效能。术后4周,软骨细胞数量和软骨基质量均显著高于传统基于干细胞的TET。此外,TET的刚度系数显著大于传统TET。本研究为长节段气管缺损的长期功能重建提供了一种有前景的方法,我们设计的TET在TET重建领域具有潜在的应用前景。