Restoring articular cartilage: insights from structure, composition and development

Alba Pueyo Moliner, Keita Ito, Frank Zaucke, Daniel J Kelly, Mylène de Ruijter, Jos Malda*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Articular cartilage can withstand substantial compressive and shear forces within the joint and also reduces friction during motion. The exceptional mechanical properties of articular cartilage stem from its highly organized extracellular matrix (ECM). The ECM is composed mainly of collagen type II and is pivotal in conferring mechanical durability to the tissue within its proteoglycan-rich matrix. Articular cartilage is prone to injury and degeneration, and current treatments often fail to restore the mechanical function of this tissue. A key challenge is replicating the intricate collagen-proteoglycan network, which is essential for the long-lasting restoration and mechanical durability of the tissue. Understanding articular cartilage development, which arises between late embryonic and early juvenile development, is vital for the creation of durable therapeutic strategies. The development of the articular ECM involves the biosynthesis, fibrillogenesis and self-assembly of the collagen type II network, which, along with proteoglycans and minor ECM components, shapes the architecture of adult articular cartilage. A deeper understanding of these processes could inform biomaterial-based therapies aimed at improving therapeutic outcomes. Emerging biofabrication technologies offer new opportunities to integrate developmental principles into the creation of durable articular cartilage implants. Bridging fundamental biology with innovative engineering offers novel approaches to generating more-durable 3D implants for articular cartilage restoration.

Original languageEnglish
Pages (from-to)291-308
Number of pages18
JournalNature reviews. Rheumatology
Volume21
Issue number5
Early online date28 Mar 2025
DOIs
Publication statusPublished - May 2025

Bibliographical note

Publisher Copyright:
© Springer Nature Limited 2025.

Funding

A.P.M., M.d.R., K.I. and J.M. would like to acknowledge the support of the Dutch Research Council (NWO), project LS-NeoCarE (NWA.1389.20.192) and the Gravitation Program \u201CMaterials Driven Regeneration\u201D (024.003.013). J.M. would like to acknowledge support from the European Research Council (ERC) under the European Union\u2019s Horizon Europe research and innovation programme (Re-COLL: 101142063). F.Z. would like to acknowledge funding from the Deutsche Forschungsgemeinschaft (ZA 561/3-2, project number 407168728) within the research unit FOR2722. D.J.K. would like to acknowledge support from Science Foundation Ireland (22/FFP-A/11042) and the European Research Council (ERC) under the European Union\u2019s Horizon Europe research and innovation programme (4D BOUNDARIES: 101019344). J.M. and D.J.K. would like to acknowledge the European Commission (m2M: 101191729).

FundersFunder number
Dutch Research Council (NWO)LS-NeoCarE (NWA.1389.20.192), 024.003.013
European Research Council (ERC) under the European Union's Horizon Europe research and innovation programme4D BOUNDARIES: 101019344
Deutsche ForschungsgemeinschaftZA 561/3-2, 407168728, FOR2722
Science Foundation Ireland22/FFP-A/11042
European Commissionm2M: 101191729

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