Recent advances in shape-programmable 4D hydrogel scaffolds for cartilage tissue regeneration

Shape-programmable 4D hydrogels are redefining the design principles, functional capabilities, and biological performance of engineered living tissues. By enabling spatiotemporal transformation of cell-laden constructs, these systems create dynamic architectures that more faithfully recapitulate developmental morphogenesis, postnatal tissue regeneration, architectural complexity, and the evolving mechanical anisotropy that guides cellular organization and function. This review systematically examines the underlying design strategies, fabrication technologies, and stimulus-responsive mechanisms that enable shape morphing in hydrogel systems. Recent advances in bioprinting modalities that permit the encoding of anisotropic architectures, graded crosslinking, and multiscale heterogeneity to support complex tissue geometries are highlighted. Particular emphasis is placed on emerging applications of shape-programmable hydrogels in cartilage tissue engineering, where dynamic morphing facilitates the formation of intricate cartilage structures, enhances extracellular matrix deposition, and promotes improved functional maturation. Finally, key challenges and future opportunities for translating 4D biofabrication toward clinically relevant therapies are discussed.