The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

Journal article


Levato, R., Webb, R., Otto, I., Mensinga, A., Zhang, Y., van Rijen, M., van Weeren, P., Khan, I. and Malda, J. 2017. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells. Acta Biomaterialia. 61, pp. 41-53. https://doi.org/10.1016/j.actbio.2017.08.005
AuthorsLevato, R., Webb, R., Otto, I., Mensinga, A., Zhang, Y., van Rijen, M., van Weeren, P., Khan, I. and Malda, J.
Abstract

Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials.

This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition.

Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models.

KeywordsBiofabrication; cartilage regeneration; chondroprogenitor cells; co-culture; hydrogel; stem cells
Year2017
JournalActa Biomaterialia
Journal citation61, pp. 41-53
PublisherElsevier
ISSN1742-7061
Digital Object Identifier (DOI)https://doi.org/10.1016/j.actbio.2017.08.005
Publication dates
Print01 Oct 2017
Publication process dates
Deposited26 Mar 2019
Accepted03 Aug 2017
Accepted author manuscript
Output statusPublished
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https://repository.canterbury.ac.uk/item/88z33/the-bio-in-the-ink-cartilage-regeneration-with-bioprintable-hydrogels-and-articular-cartilage-derived-progenitor-cells

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