3D Bioprinted Artificial Trachea with Epithelial Cells and Chondrogenic-Differentiated Bone Marrow-Derived Mesenchymal Stem Cells

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.

Biomedical grafts for tracheal tissue repairing and regeneration “Tracheal tissue engineering: an overview”

“…Scaffold seeded with chondrocytes enhanced biomechanical strength of cell‐scaffold construct, but chondrocytes, after implantation, became nonviable. On the other hand, the scaffold, seeded with epithelial cells, showed cell viability and better tracheal tissue regeneration in vivo (Bae et al, ; Go et al, ).…”

3D Bioprinting Strategies for the Regeneration of Functional Tubular Tissues and Organs

“…The rotating rod is provided as temporary support to the printed biomaterial for keeping a 3D shape and is removed when the printed structure is considered to be self-supporting. Sang-Woo Bae et al printed the artificial tracheal structure with a synthetic polymer (i.e., PCL) and cell-laden bioink (epithelial cells and bone-marrow stem cells) by sequential extruding on the rotating rod [119]. Qing Gao et al fabricated a hydrogel-based vascular structure with multilevel fluidic channels using a combination with co-axial bioprinting [31].…”

3D-bioprinted tracheal reconstruction: an overview

“…Recently, Bae et al used a similar approach co-culturing chondrogenic-differentiated bMSC and respiratory epithelial cells in one scaffold. Neocartilage formation, neo-epithelization and neovascularization could be observed (Bae et al, 2018). Chang et al 3D-printed a 10x10mm half-pipe-shaped PCL scaffold coated with rabbit MSC seeded in human-derived fibrin and then implanted for 8 weeks.…”