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Serial Analysis of Tracheal Restenosis After 3D-Printed Scaffold Implantation: Recruited Inflammatory Cells and Associated Tissue Changes

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Tracheal restenosis is a major obstacle to successful tracheal replacement, and remains the greatest challenge in tracheal regeneration. However, there have been no detailed investigations of restenosis. The present study was performed to analyze the serial changes in recruited inflammatory cells and associated histological changes after tracheal scaffold implantation. Asymmetrically porous scaffolds, which successfully prevented tracheal stenosis in a partial trachea defect model, designed with a tubular shape by electrospinning and reinforced by 3D-printing to reconstruct 2-cm circumferential tracheal defect. Serial rigid bronchoscopy, micro-computed tomography, and histology [H&E, Masson’s Trichrome, IHC against α-smooth muscle actin (α-SMA)] were performed 1, 4, and 8 weeks after transplantation. Progressive stenosis developed especially at the site of anastomosis. Neutrophils were the main inflammatory cells recruited in the early stage, while macrophage infiltration increased with time. Recruitment of fibroblasts peaked at 4 weeks and deposition of α-SMA increased from 4 weeks and was maintained through 8 weeks. During the first 8 weeks post-transplantation, neutrophils and macrophages played significant roles in restenosis of the trachea. Antagonists to these would be ideal targets to reduce restenosis and thus play a pivotal role in successful tracheal regeneration.

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Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI14C0184 to S. K. K), by a Grant from the Seoul National University Hospital Research Fund (Grant Number: 0320140360 to S. K. K) and by the Education and Research Encouragement Fund of the Seoul National University Hospital (2016, to H. W. S).

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Author notes

  1. Hee-Jin Ahn and Roza Khalmuratova have contributed equally to this work.

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

    Hee-Jin Ahn, Eun-Jae Chung, Hyun-Woo Shin & Seong Keun Kwon

  2. Obstructive Upper Airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, 103 Daehak-ro, Seoul, 03080, Korea

    Roza Khalmuratova & Hyun-Woo Shin

  3. Department of Nature-Inspired Nanoconvergence Systems, Korea Institute of Machinery and Materials, Gajeongbuk-ro 156, Daejeon, 34103, Korea

    Su A. Park

  4. Department of Biomedical Sciences, Seoul National University Graduate School, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

    Hyun-Woo Shin

  5. Cancer Research Institute and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

    Hyun-Woo Shin

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  1. Hee-Jin Ahn
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Correspondence to Hyun-Woo Shin or Seong Keun Kwon.

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Ethical standard

All protocols were performed in accordance with the guidelines of the Animal Care Ethics Committee of Seoul National University Hospital (IACUC No. 15-0268-C1A1).

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Ahn, HJ., Khalmuratova, R., Park, S.A. et al. Serial Analysis of Tracheal Restenosis After 3D-Printed Scaffold Implantation: Recruited Inflammatory Cells and Associated Tissue Changes. Tissue Eng Regen Med 14, 631–639 (2017). https://doi.org/10.1007/s13770-017-0057-y

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  • DOI: https://doi.org/10.1007/s13770-017-0057-y

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