Advances and Challenges in 3D Bioprinting of Cartilage Organoids: From Material Innovation to Functional Regeneration.

Articular cartilage injury and degenerative disorders are major contributors to joint dysfunction. Because cartilage is avascular and aneural, its intrinsic healing capacity is extremely limited, which continues to present a major clinical challenge. Cartilage organoids, defined as three-dimensional constructs that recapitulate key structural, cellular, and functional features of native cartilage tissue, including cell-cell and cell-matrix interactions, zonal organization, and responsiveness to biochemical and mechanical cues, have emerged as promising platforms for cartilage regeneration and disease research. In this context, three-dimensional (3D) bioprinting offers a powerful top-down strategy for fabricating such organoids with high spatial precision, complementing conventional bottom-up self-assembly approaches. This capability has opened new opportunities for the generation of cartilage constructs with complex architectures and biomimetic functions, highlighting their potential in personalized therapy, disease modeling, and regenerative medicine. This review provides a comprehensive overview of recent progress in 3D bioprinting for cartilage organoid engineering. First, it summarizes advances in bioink design, ranging from natural and synthetic hydrogels to composite and reinforced systems, such as the emerging attapulgite-polyvinyl alcohol platform, as well as stimulus-responsive smart materials. These materials are being developed to better replicate the biochemical and mechanical properties of the native extracellular matrix while maintaining suitable printability. Second, the review discusses the principles, optimization strategies, and application characteristics of major bioprinting techniques, including extrusion-based, photocuring-based, inkjet, and microfluidic bioprinting, with particular emphasis on balancing printing fidelity, structural complexity, and cell viability. In addition, it examines key strategies for promoting functional maturation and in vivo integration of cartilage organoids, including coculture systems, direct vascularization approaches, spatiotemporally controlled delivery of growth factors, dynamic mechanical stimulation, and emerging osteoimmunomodulatory interventions such as macrophage polarization and neutrophil extracellular trap clearance. Despite substantial advances, several critical challenges remain, including limited biomimetic accuracy in hierarchical architecture, instability of long-term cell phenotype, difficulties in vascularizing large-scale constructs, and the absence of standardized criteria for clinical translation. By identifying these bottlenecks and outlining future directions, including the development of 4D bioprinting materials and the integration of organ-on-a-chip systems with artificial intelligence-based optimization, this review aims to support the evolution of cartilage organoids from structural mimics toward truly functional regenerative constructs, ultimately facilitating their translation into clinically applicable therapies.