Tissue-Engineered Trachea from a 3D-Printed Scaffold Enhances Whole-Segment Tracheal Repair in a Goat Model

Abstract

Traditional treatment therapies for tracheal stenosis often cause severe postoperative complications. To solve the current difficulties, novel and more suitable long-term treatments are needed. A 3D-printed scaffold representing the whole segment of goat trachea was engineered with autologous auricular cartilage cells. TETs underwent mechanical analysis followed by in vivo implantations in order to evaluate the feasibility and clinical potential. 3D-printed TETs were successfully cellularized, as observed by scanning electron microscopy. Mechanical force compression studies revealed that both PCL scaffolds and TETs have a more robust compressive strength than does the native trachea. In vivo implantation of TETs resulted in significantly higher mean postoperative survival times in the experimental group 65.00±24.01 days (n=5), than the control group, 17.60±3.51 (n=5). Tracheal narrowing was confirmed by bronchoscopy and CT examination in the engineered goat trachea transplantation model. However, unlike that of the control group, we did not observe the presence of tissue necrosis in the experimental TET group. Furthermore, an encouraging epithelial-like tissue formation was observed implying functional maturation of the TETs in vivo. This is the first detailed study employing orthotopic transplantation of a whole 3D-printed TET in large animals. We believe these results signify a major milestone in the development of TETs. Funding Statement: This study was supported by National Natural Science Fund of China (grant numbers 31200735, 81671833, 81670372), Shanghai Science and Technology Development Fund (grant numbers 15411966800, 12ZR1446500，16CR3078B), Science and Technology Development Fund of Shanghai Pudong(grant number PKJ2012-Y48, PKJ2016-Y33), Shanghai Municipal Commission of Health and Family Planning(grant numbers 20144Y0166), the Biomedical Engineering fund of Shanghai Jiao Tong University (grant numbers YG2012MS36, YG2016MS28), Collaborative Innovation Center for Translational Medicine at Shanghai Jiao Tong University School of Medicine(grant number TM201504), Scientific research project of Ai You foundation(grant number 2017SCMC-AY002), the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University, China. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: The Laboratory Animal Management Committee of School of Medicine of Shanghai Jiaotong University approved all animal experiments.