From microtissues to macro solutions - The future of scalable and automated cartilage tissue engineering

The burden of articular cartilage damage on society continues to rise. Suitable treatment is necessary to reduce pain, improve quality of life, and avoid progression into osteoarthritis. Current regenerative cartilage repair strategies remain limited in clinical practice due to high costs, complex logistics, patient burden, and poor reimbursement. To ensure that treatment innovations effectively reach the patient, the focus during development should be on automated and scalable solutions. A promising concept is using cartilage microtissues as building blocks in a modular approach to create larger cartilage constructs. By enabling controlled microtissue assembly and reproducible, scalable manufacturing, this could lead to the efficient production of tissue-engineered cartilage implants. Several automated, scalable steps have been described in literature, ranging from cell isolation and expansion to microtissue formation and harvesting, and finally to macrotissue assembly and maturation. However, integrating all these steps into a single, cost-effective, and automated process remains a conceptual idea. This review focuses on potential routes and key choices that should be considered in the early design process of future ready-to-implant tissue-engineered cartilage implants. Furthermore, the added value of investigating and implementing automatic quality measures and cleaning protocols, as well as the recommended regulatory checks and cost-effectiveness implications, are discussed. The translational potential of this article: Leveraging microtissues for cartilage tissue engineering in a scalable, automated, and GMP-compliant manner could address the growing burden of articular cartilage damage. This review shows the translational potential of this approach by focusing on the early implementation of these concepts in the design process of cartilage tissue-engineered solutions, ensuring compatibility and viability within current healthcare systems.