4-Axis printing microfibrous tubular scaffold and tracheal cartilage application
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Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction. The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine. Here, we present a reliable method to rapidly fabricate tissue-engineered tubular scaffold with hierarchical structure via 4-axis printing system. The fabrication process can be adapted to various biomaterials including hydrogels, thermoplastic materials and thermosetting materials. Using polycaprolactone (PCL) as an example, we successfully fabricated the scaffolds with tunable tubular architecture, controllable mesh structure, radial elasticity, good flexibility, and luminal patency. As a preliminary demonstration of the applications of this technology, we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate) (PGS) bio-spring and electrospun gelatin nanofibers. The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse, which showed great potential for tracheal cartilage reconstruction.
Keywords3D printing tissue engineering tubular scaffold tracheal cartilage
管状组织大段缺损的重建是临床治疗上的一个难题. 如何设 计并制备具有理想结构的功能管状支架用于管状组织修复仍然是 再生医学中的一个主要挑战. 本研究采用4轴打印系统快速地制备 了具有多级结构的管状组织工程支架, 该方法适用于多种生物材 料, 如水凝胶、热塑性生物材料以及热固性生物材料. 以聚己内酯 (PCL)为例, 我们成功制备了管状结构可调、类编织网格结构可控, 径向弹性、轴向柔性及管腔开放性良好的支架. 作为管状组织再 生的初步应用, 我们利用4轴打印技术制备了聚癸二酸甘油酯 (PGS)的热固性生物弹簧, 并与静电纺技术相结合制备了杂化的 PGS/明胶纳米纤维管状支架. 该支架接种软骨细胞后在体外培养 和裸鼠皮下植入均可形成成熟的管状软骨组织, 有望应用于气管 软骨重建.
This work was supported by the National Key Research and Development Program of China (2018YFB1105602 and 2017YFC1103900), the National Natural Science Foundation of China (21574019, 81320108010, 81571823 and 81871502), the Natural Science Foundation of Shanghai (18ZR1401900), the Fundamental Research Funds for the Central Universities, DHU Distinguished Young Professor Program (LZA2019001), the Science and Technology Commission of Shanghai (17DZ2260100 and 15DZ1941600), the Program for Shanghai Outstanding Medical Academic Leader, and the Program of Shanghai Technology Research Leader.
Lei D designed and performed all experiments, analyzed the data and prepared the manuscript. Xu Y performed the chondrocytes culture and trachea reconstruction. Luo B and Shen A contributed to 3D printing. Guo Y performed SEM characterization and statistic analysis. Liu Z and Wang S performed PGS polymer synthesis. Wang D and Yang H performed the manufacture of receivers. Xuan H contributed to electrospinning. Zhang Y contributed to mechanical testing. He C and Qing FL contributed to the discussion and analysis of the experimental result. Zhou G discussed the concept and contributed to the writing of the manuscript. You Z supervised the whole work and wrote the manuscript.