Stable‐Dynamic Hydrogels Mimicking the Pericellular Matrix for Articular Cartilage Repair

The fixed network of traditional covalent hydrogels restricts interactions with chondrocytes, limiting effective cartilage regeneration. In contrast, dynamic hybrid hydrogels interact with the chondrocyte cytoskeleton, alleviating intracellular stress and inhibiting abnormal actin polymerization. This modulation suppresses the activation of the Notch signaling pathway, ultimately promoting chondrogenic gene expression.

Abstract

Cartilage regeneration requires a specialized biomechanical environment. Macroscopically, cartilage repair requires a protracted, stable mechanical environment, whereas microscopically, it involves dynamic interactions between cells and the extracellular matrix. Therefore, this study aims to design a hydrogel that meets the complex biomechanical requirements for cartilage repair. Dynamic hybrid hydrogels with temporal stability at the macroscale and dynamic properties at the microscale are successfully synthesized. The dynamic hybrid hydrogel simulates the stress relaxation and viscoelasticity of the pericellular matrix, facilitating effective interactions between the extracellular matrix and cells. The in vitro and in vivo experiments demonstrated that the hybrid hydrogel significantly promoted cartilage repair. The dynamic hybrid hydrogel alleviates abnormal actin polymerization, reduces intracellular stress, and increases the volume of individual cells. By modulating the cytoskeleton, the hybrid hydrogel inhibits Notch signal transduction in both the receptor and ligand cells, resulting in an improved cartilage phenotype. This study introduces an effective hybrid hydrogel scaffold that modulates the chondrocyte cytoskeleton and Notch signaling pathways by establishing an appropriate biomechanical environment, thus offering a promising material for cartilage repair.