Exploring cartilage development and disease models: applications of cartilage organoids.

Abstract

Cartilage is an avascular and aneural connective tissue vital for joint function, yet its limited intrinsic regenerative capacity poses significant challenges for treating injuries and degenerative diseases such as osteoarthritis (OA). Conventional models-including animal studies, cell lines, and primary chondrocyte cultures-exhibit considerable limitations in accurately replicating the native cartilage microenvironment, species-specific relevance, and differentiation potential. Recently, cartilage organoids have emerged as transformative tools that closely emulate the architecture, cellular heterogeneity, and extracellular matrix (ECM) properties of native cartilage, thereby offering a physiologically relevant platform for investigation. This review systematically examines the mechanisms governing chondrogenesis, including chondrocyte differentiation and matrix synthesis, as well as the construction of cartilage disease models. We focus on recent advances in cartilage organoid research, covering cultivation techniques, structural and functional characteristics, and diverse characterization methodologies. Furthermore, we highlight their applications in simulating pathological features of cartilage diseases, drug screening, toxicity testing, and gene therapy exploration. Current technological limitations-such as challenges in vascularization and mechanical strength-are discussed, together with future directions for developing multifunctional organoids and associated ethical and clinical considerations. This review aims to provide insights into the translational potential of cartilage organoids in regenerative medicine and disease modeling.