AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.5178
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RESEARCH ARTICLE

Primitive regenerated-tissue evolution in situ after implantation of a 3D-printed tracheal graft

Sen-Ei Shai1,2,3* ,  Yi-Ling Lai1 ,  Yi-Wen Hung4,5 ,  Chi-Wei Hsieh6 ,  Kuo-Chih Su7 ,  Chun-Hsiang Wang7 ,  Te-Hsin Chao8 ,  Yung-Tsung Chiu9 ,  Chia-Ching Wu6,10 ,  Shih-Chieh Hung11,12
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1 Department of Surgery, Division of Thoracic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
2 Department of Applied Chemistry, Faculty of Science and Technology, National Chi Nan University, Nantou, Taiwan
3 Department of Medicine, Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
4 Animal Radiation Therapy Research Center, Central Taiwan University of Science and Technology, Taichung, Taiwan
5 Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan
6 Department of Medicine, School of Medicine, National Cheng Kung University, Tainan, Taiwan
7 Department of Medical Research, Three-Dimensional Printing Research and Development Group, Taichung Veterans General Hospital, Taichung, Taiwan
8 Division of Colon and Rectal Surgery, Department of Surgery, Chiayi and Wangiao Branch, Taichung Veterans General Hospital, Chiayi, Taiwan
9 Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan
10 Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
11 Integrative Stem Cell Center, China Medical University Hospital, Taichung, Taiwan
12 Institute of New Drug Development, China Medical University, Taichung, Taiwan
IJB, 5178 https://doi.org/10.36922/ijb.5178
Submitted: 17 October 2024 | Accepted: 12 November 2024 | Published: 13 November 2024
(This article belongs to the Special Issue 3D Printing for Tissue Engineering and Regenerative Medicine-Series 2)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Tissue-engineered trachea offers a potential solution for patients needing long-segment tracheal resections. In our research, robust neotissue growth, including cartilage, muscle, adipose, and glands, was observed on the external surface of three-dimensional (3D)-printed tracheal grafts transplanted into a 3-month-old large-scale porcine, noticeable after 7 days. This study is the first to categorize the regeneration stages in detail, aiming for a clearer understanding of the cell development process, as previous studies have not fully elucidated the mechanisms of chondrogenesis and glandogenesis. We have identified four stages of chondrogenesis based on chondrocyte numbers, protein expression, and perichondrium presence. Muscle cells evolved from a fibroblast-like state, confirmed by alpha-smooth muscle actin and smooth muscle-myosin heavy chain markers, while initial adipose tissue resembling brown fat diminished over time. Gland development, marked by a change in MUC5B expression, paralleled the findings in native trachea epithelium and submucosal glands. Transforming growth factor-β1 and type XII collagen were key indicators in the emerging neotissue post-transplant.

Graphical abstract
Keywords
Primitive regenerated-tissue evolution
Vivid neotissue growth
Glandogenesis
Tracheal graft transplantation
Funding
This research was funded by the Ministry of Science and Technology, Taiwan (Grant No. MOST 110-2314-B-075A-013-1); Yen Tjing Ling Medical Foundation, Taiwan (Grant No. CI-112-9); Taichung Veterans General Hospital and National Yang-Ming University, Taiwan (Grant No. TCVGH-YM1100104); Taichung Veterans General Hospital and National Yang-Ming University, Taiwan (Grant No. TCVGH-YM1110105); and Taichung Veterans General Hospital, Taiwan, (Grant No. TCVGH-1104701C).
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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