Microfiber-Reinforced GelMA Hydrogels with Tunable Poisson's Ratio Enhance Chondrogenesis under Dynamic Loading

Hydrogels are widely used in cartilage tissue engineering but fail to replicate key mechanical features of native cartilage, particularly its near-zero Poisson's ratio, which governs lateral deformation under load. Here, we demonstrate that matching deformation behavior in addition to compressive stiffness may contribute to the enhanced chondrogenic response under physiological mechanical stimulation. Human articular chondrocytes were encapsulated in GelMA hydrogels reinforced with melt electrowritten scaffolds engineered to independently tune the effective compressive modulus and Poisson's ratio. Reinforcement increased the compressive modulus from 33 kPa (neat GelMA) to 245-345 kPa, while reducing the Poisson's ratio from 0.42 to 0.12 in hybrid designs, approaching native cartilage values. Under dynamic loading, constructs matching both properties showed significantly higher expression of the chondrogenic markers SOX9 and ACAN compared to both neat GelMA and lattice-reinforced constructs, which exhibited a physiologically relevant compressive modulus but a higher Poisson's ratio, along with increased COL2A1 expression compared to the latter specifically. Histological analysis confirmed enhanced and more homogeneous extracellular matrix deposition, with up to 76% GAG and 36% collagen type II coverage. These findings suggest that lateral deformation behavior, alongside compressive stiffness, contributes to directing chondrocyte matrix synthesis under mechanical stimulation, establishing Poisson's ratio as an important and previously underexplored design parameter in cartilage tissue engineering, and providing a framework for engineering mechanically instructive biomaterials for load-bearing tissues.