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4-Axis printing microfibrous tubular scaffold and tracheal cartilage application

4轴打印微纤维管状支架及其气管软骨应用

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Abstract

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.

摘要

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China

    Dong Lei  (雷东), Zenghe Liu  (刘增贺), Chuanglong He  (何创龙), Feng-Ling Qing  (卿凤翎) & Zhengwei You  (游正伟)

  2. Shanghai Belt and Road Joint Laboratory of Advanced Fiber and Low-dimension Materials (Donghua University), College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China

    Dong Lei  (雷东), Bin Luo  (罗彬), Yifan Guo  (郭一凡), Shaofei Wang  (王少飞), Huixia Xuan  (轩慧霞), Ao Shen  (沈傲), Yi Zhang  (张轶), Zenghe Liu  (刘增贺) & Zhengwei You  (游正伟)

  3. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    Yong Xu  (徐勇)

  4. Department of Mechanical Engineering and Automation, Shanghai University, Shanghai, 200072, China

    Di Wang  (汪地) & Hao Yang  (杨浩)

  5. Shanghai Key Lab of Tissue Engineering, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China

    Guangdong Zhou  (周广东)

  6. Research Institute of Plastic Surgery, Weifang Medical University, Weifang, 261053, China

    Guangdong Zhou  (周广东)

Authors
  1. Dong Lei  (雷东)
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  2. Bin Luo  (罗彬)
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  3. Yifan Guo  (郭一凡)
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  4. Di Wang  (汪地)
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  6. Shaofei Wang  (王少飞)
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  7. Huixia Xuan  (轩慧霞)
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  9. Yi Zhang  (张轶)
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  10. Zenghe Liu  (刘增贺)
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  11. Chuanglong He  (何创龙)
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  12. Feng-Ling Qing  (卿凤翎)
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  13. Yong Xu  (徐勇)
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Contributions

Author contributions 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.

Corresponding authors

Correspondence to Yong Xu  (徐勇), Guangdong Zhou  (周广东) or Zhengwei You  (游正伟).

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Conflict of interest The authors declare no conflict of interest.

Additional information

Dong Lei is a PhD student at the State Key Laboratory for Modification of Chemical Fibers and Polymer Materials at Donghua University. From 2013 to now, he has been conducting his master and doctoral research at Donghua University. His current research involves biomaterials, 3D printing and tissue regeneration.

Yong Xu received his MCs degree from the Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine in 2018. Now he is continuing to study for a PhD degree in the Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine. His research interests focus on cartilage regenerative biomaterials and functional tracheal reconstruction.

Guangdong Zhou is a professor of Medical College of Shanghai Jiao Tong University, Executive Vice-Director of National Center for Tissue Engineering Research, Former Secretary-General and Executive Director of Tissue Engineering and Regenerative Medicine Branch of Chinese Society of Biomedical Engineering. His research interests focus on the functional cartilage regeneration and clinical application transformation, construction of cartilage in vitro and precise regulation of its three-dimensional morphology (auricle, trachea, etc.), and repair of various cartilage defects in large animals.

Zhengwei You is a professor and the chair of Department of Composite Materials at Donghua University. He received his BSc degree from Shanghai Jiao Tong University and PhD degree from Shanghai Institute of Organic Chemistry. He conducted his postdoctoral research at Georgia Institute of Technology and University of Pittsburgh. Prior to joining Donghua University, he was an innovation manager in Bayer Material Science. His current research involves smart polymers, biomaterials, 3D printing, and stretchable electronics.

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Lei, D., Luo, B., Guo, Y. et al. 4-Axis printing microfibrous tubular scaffold and tracheal cartilage application. Sci. China Mater. 62, 1910–1920 (2019). https://doi.org/10.1007/s40843-019-9498-5

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  • DOI: https://doi.org/10.1007/s40843-019-9498-5

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