Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo

PLoS One. 2017 Dec 13;12(12):e0189428. doi: 10.1371/journal.pone.0189428. eCollection 2017.

Abstract

Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.

MeSH terms

  • Animals
  • Bioprinting / methods*
  • Cartilage / cytology*
  • Cell Proliferation
  • Chondrocytes / cytology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Printing, Three-Dimensional*
  • Tissue Scaffolds

Grants and funding

Funding by Sahlgrenska Academy at the University of Gothenburg and the Sahlgrenska University Hospital.