Cellular therapy and tissue engineering for cartilage repair

Alena Zelinka, Anke J Roelofs, Rita A Kandel, Cosimo De Bari

Research output: Contribution to journalReview articlepeer-review

21 Citations (Scopus)
8 Downloads (Pure)

Abstract

Articular cartilage (AC) has limited capacity for repair. The first attempt to repair cartilage using tissue engineering was reported in 1977. Since then, cell-based interventions have entered clinical practice in orthopaedics, and several tissue engineering approaches to repair cartilage are in the translational pipeline towards clinical application. Classically, these involve a scaffold, substrate or matrix to provide structure, and cells such as chondrocytes or mesenchymal stromal cells to generate the tissue. We will discuss the advantages and drawbacks of the use of various cell types, natural and synthetic scaffolds, multiphasic or gradient-based scaffolds, and self-organizing or self-assembling scaffold-free systems, for the engineering of cartilage constructs. Several challenges persist including achieving zonal tissue organization and integration with the surrounding tissue upon implantation. Approaches to improve cartilage thickness, organization and mechanical properties include mechanical stimulation, culture under hypoxic conditions, and stimulation with growth factors or other macromolecules. In addition, advanced technologies such as bioreactors, biosensors and 3D bioprinting are actively being explored. Understanding the underlying mechanisms of action of cell therapy and tissue engineering approaches will help improve and refine therapy development. Finally, we discuss recent studies of the intrinsic cellular and molecular mechanisms of cartilage repair that have identified novel signals and targets and are inspiring the development of molecular therapies to enhance the recruitment and cartilage reparative activity of joint-resident stem and progenitor cells. A one-fits-all solution is unrealistic, and identifying patients who will respond to a specific targeted treatment will be critical.

Original languageEnglish
Pages (from-to)1547-1560
Number of pages13
JournalOsteoarthritis and Cartilage
Volume30
Issue number12
Early online date20 Sept 2022
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Acknowledgements
We would like to thank Drs. M Mozafari, Sang Jin and Anthony Atala for providing the right-hand image in Fig. 2(C).

Funding
The authors are grateful to the Medical Research Council (grant numbers MR/L020211/1 and MR/L022893/1; CDB, AJR), Versus Arthritis (formerly Arthritis Research UK, grant numbers 20050, 20775, 20865, 21156, and 21800; CDB, AJR), Biosplice Therapeutics (CDB, AJR), and the Canadian Institute of Health Research (AZ, RAK) for supporting their research.

Keywords

  • Tissue engineering
  • Stem Cells
  • Regenerative Medicine
  • Osteoarthritis
  • Cartilage repair

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