High-viscosity hydrogels in cartilage injury and osteochondral defect repair: mechanisms, design strategies, and clinical translation.
TL;DR
Although challenges remain regarding long-term mechanical durability, degradation-regeneration matching, and clinical standardization, HVHs represent a promising paradigm that integrates dynamic network engineering, mechanobiological regulation, osteochondral reconstruction, and translational adaptability.
Abstract
Cartilage injury and osteochondral defects remain major clinical challenges owing to the limited intrinsic regenerative capacity of cartilage and the inability of current treatments to restore durable hyaline tissue. Conventional hydrogels often fail under joint loading because of insufficient mechanical stability, poor interfacial integration, and limited biological responsiveness. In this review, high-viscosity hydrogels (HVHs) are considered within a performance-based framework that integrates post-deployment cohesion and structural retention, viscoelastic energy dissipation, and reversible network reconfiguration to provide both mechanical support and biological regulation. Through multilevel design strategies, including double-network structures, reversible crosslinking, nanocomposite reinforcement, and stimuli-responsive modules, HVHs establish highly cohesive yet reconfigurable matrices capable of stress dissipation, self-adaptation, and sustained bioactive factor delivery. Beyond structural functions, HVHs actively regulate mechanobiological signaling by modulating matrix stiffness, stress relaxation, immune responses, and stem-cell fate, thereby promoting chondrogenic differentiation, suppressing hypertrophy, and facilitating extracellular matrix deposition. Recent advances in gradient and biphasic HVH systems further enable coordinated regeneration of cartilage and subchondral bone, supporting functional osteochondral integration through spatially controlled mechanical and biochemical cues. Emerging technologies such as 3D/4D printing, artificial intelligence-assisted material optimization, and organoid-based validation are accelerating the development of personalized and adaptive regenerative platforms. Although challenges remain regarding long-term mechanical durability, degradation-regeneration matching, and clinical standardization, HVHs represent a promising paradigm that integrates dynamic network engineering, mechanobiological regulation, osteochondral reconstruction, and translational adaptability. This review summarizes recent advances in HVH design and application, highlighting their potential to reshape future strategies for cartilage and osteochondral regeneration through intelligent, biomimetic, and clinically translatable material systems.