Hyaluronic acid-based self-healing hydrogels with controlled mechanical stiffness and hydrolytic stability
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Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to biocompatibility and enzymatic degradability. However, controlling their mechanical properties and degradation rates remains challenging. We hypothesized that carbodihydrazide-modified HA (HA-CDH) and oxidized diol-modified HA (odHA) could form effective hydrogels with tunable mechanical stiffness. These hydrogels exhibited enhanced hydrolytic stability due to resonance structures while maintaining enzymatic degradability. The incorporation of free adipic acid dihydrazide (ADH) enhanced self-healing properties of HA-CDH/odHA hydrogels for 3D printing applications. The increased stability and enhanced mechanical stiffness significantly influenced osteogenic and chondrogenic cell differentiation in vitro. These results suggest that natural polysaccharide-based hydrogels with improved physical properties have significant potential for tissue engineering, particularly in cartilage and bone regeneration.