Organic-Inorganic Hyaluronic Acid/Sumecton Nanocomposite Hydrogels for Osteogenic Applications

While their biocompatibility and extracellular matrix-mimetic properties make hyaluronic acid (HA)-based hydrogels attractive biomaterials for bone regenerative applications, their limited mechanical stability and insufficient osteogenic activity restrict broader utility. Here, we present an organic-inorganic nanocomposite hydrogel integrating catechol-functionalized HA with Sumecton clay (SU) nanosheets as multifunctional inorganic junction domains. Oxidative crosslinking of dopamine-functionalized HA established the primary hydrogel network, while the resulting hybrid network exhibited injectability and structural recovery following deformation. Incorporation of 2% SU increased the compressive modulus from approximately 4.6 to 6.0 kPa and delayed hydrogel degradation, while only modestly affecting equilibrium water content. The hybrid hydrogels also exhibited antimicrobial and catechol-mediated antioxidant activities, establishing a multifunctional microenvironment suited to tissue regeneration. SU-containing hydrogels promoted the osteogenic differentiation of encapsulated stem cells, as evidenced by increased alkaline phosphatase activity and matrix mineralization. SAG was incorporated into SU with a loading efficiency of approximately 95%, and SU@SAG-containing hydrogels further enhanced osteogenic differentiation and mineralization. Gene expression analysis showed increased expression of Hedgehog-associated markers together with modulation of Wnt/β-catenin-related genes, suggesting signaling responses associated with enhanced osteogenesis. Collectively, this study demonstrates an organic-inorganic network engineering strategy to develop structurally robust and biologically functional HA-based nanocomposite hydrogels for bone regenerative applications.