Chondrobags: a high throughput alginate-fibronectin micromass platform for in vitro human cartilage formation

Kimia Witte, María C de Andrés, Julia Wells, Matthew J Dalby, Manuel Salmeron-Sanchez, Richard O C Oreffo

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Abstract

The maintenance and expansion of the cells required for formation of tissue-engineered cartilage has, to date, proven difficult. This is, in part, due to the initial solid phase extracellular matrix demanded by the cells inhabiting this avascular tissue. Herein, we engineer an innovative alginate-fibronectin microfluidic-based carrier construct (termed a chondrobag) equipped with solid phase presentation of growth factors that support skeletal stem cell chondrogenic differentiation while preserving human articular chondrocyte phenotype. Results demonstrate biocompatibility, cell viability, proliferation and tissue-specific differentiation for chondrogenic markers SOX9, COL2A1 and ACAN. Modulation of chondrogenic cell hypertrophy, following culture within chondrobags loaded with TGF-β1, was confirmed by down-regulation of hypertrophic genes COL10A1 and MMP13. MicroRNAs involved in the chondrogenesis process, including miR-140, miR-146b and miR-138 were observed. Results demonstrate the generation of a novel high-throughput, microfluidic-based, scalable carrier that supports human chondrogenesis with significant implications therein for cartilage repair-based therapies.
Original languageEnglish
Article number045034
Number of pages14
JournalBiofabrication
Volume12
Issue number4
Early online date8 Sep 2020
DOIs
Publication statusE-pub ahead of print - 8 Sep 2020

Keywords

  • biofabrication
  • droplet-based microfluidics
  • stem cells
  • chondrogenesis
  • hydrogels
  • fibronectin

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    Witte, K., de Andrés, M. C., Wells, J., Dalby, M. J., Salmeron-Sanchez, M., & Oreffo, R. O. C. (2020). Chondrobags: a high throughput alginate-fibronectin micromass platform for in vitro human cartilage formation. Biofabrication, 12(4), [045034]. https://doi.org/10.1088/1758-5090/abb653