Abstract

Tracheal resection has limited applicability. Although various tracheal replacement strategies were performed using artificial prosthesis, synthetic stents and tissue transplantation, the best method in tracheal reconstruction remains to be identified. Recent advances in tissue engineering enabled 3D bioprinting using various biocompatible materials including living cells, thereby making the product clinically applicable. Moreover, clinical interest in mesenchymal stem cell has dramatically increased. Here, rabbit bone marrow-derived mesenchymal stem cells (bMSC) and rabbit respiratory epithelial cells were cultured. The chondrogenic differentiation level of bMSC cultured in regular media (MSC) and that in chondrogenic media (d-MSC) were compared. Dual cell-containing artificial trachea were manufactured using a 3D bioprinting method with epithelial cells and undifferentiated bMSC (MSC group, n = 6) or with epithelial cells and chondrogenic-differentiated bMSC (d-MSC group, n = 6). d-MSC showed a relatively higher level of glycosaminoglycan (GAG) accumulation and chondrogenic marker gene expression than MSC in vitro. Neo-epithelialization and neo-vascularization were observed in all groups in vivo but neo-cartilage formation was only noted in d-MSC. The epithelial cells in the 3D bioprinted artificial trachea were effective in respiratory epithelium regeneration. Chondrogenic-differentiated bMSC had more neo-cartilage formation potential in a short period. Nevertheless, the cartilage formation was observed only in a localized area.

Highlights

  • The trachea is a hollow cylindrical organ composed of 15–20 C-shaped cartilages with fibroelastic ligaments [1]

  • Using a 3D bioprinter, we developed a novel biocompatible artificial trachea with epithelial cells + bone marrow-derived mesenchymal stem cells (bMSC) (MSC group) and with epithelial cells + chondrogenic-differentiated bMSC (d-mesenchymal stem cells (MSC) group)

  • We evaluated the results obtained from the animal study according to the chondrogenic differentiation level of bMSC

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Summary

Introduction

The trachea is a hollow cylindrical organ composed of 15–20 C-shaped cartilages with fibroelastic ligaments [1]. Stenosis and tumor in the trachea require surgical intervention with tracheal resection [2] and in such cases, circumferential resection and end-to-end anastomosis are generally considered the optimal surgical methods. These procedures are applicable only in particular conditions. With the developments in tissue engineering, tracheal replacement strategies were diversified from the use of prostheses and synthetic stents to tissue transplantation [3]. Wurtz et al reported on tracheal replacement with an aortic homograft combined with an intraluminal stent to support the structural integrity [5]. No satisfying methods in the aspect of multilayered structure and its function in tracheal reconstruction have been identified [7,8,9]

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