Injectable hyaluronic acid/nanohydroxyapatite composite hydrogels for localized drug delivery and bone repair

• Injectable HA/nHAp hydrogels developed via EDC/NHS crosslinking. • SrRan-loaded nHAp nanoparticles incorporated into HA hydrogel matrix. • Hydrogels show tunable mechanics, degradability, and injectability. • Sustained SrRan release achieved over 56 days from composite hydrogels. • HA/nHAp hydrogels are cytocompatible with NIH3T3 and MC3T3 cells. Bone repair, especially in osteoporotic bone fractures, remains a clinical challenge due to poor bone tissue quality and limited self-regeneration capability. Injectable hydrogels with drug delivery functionality offer an advanced strategy by enabling localized, sustained therapy with improved bioavailability and reduced systemic side effects. In this study, for the first time, injectable, biodegradable composite hydrogels composed of covalently crosslinked hyaluronic acid (HA) and nanohydroxyapatite (nHAp), either unmodified or loaded with strontium ranelate (SrRan), were developed for bone repair applications. These hydrogels could provide dual functionality by enabling localized, sustained drug delivery and supporting bone repair. The effect of nHAp content (0-70 wt%) on swelling, gel fraction, morphology, enzymatic degradation, mechanical and rheological properties, and injectability of the developed hydrogels was comprehensively evaluated. SrRan release kinetics were evaluated in three composite hydrogel formulations (30%, 50%, 70% SrRan-nHAp) to assess the influence of nanoparticle content on release rate and sustained delivery performance. All hydrogels exhibited shear-thinning behaviour, low injection forces (< 2.5 N) for manual delivery, and rapid post-injection viscosity recovery. Enzymatic degradation (with hyaluronidase) confirmed gradual hydrogel degradation with release of HA oligomers. SrRan-loaded composite hydrogels provided sustained SrRan release over 56 days. In vitro assays with NIH3T3 fibroblasts and MC3T3 preosteoblasts demonstrated excellent cytocompatibility of SrRan free HA/nHAp composite hydrogels across 0–70 wt% nHAp. Overall, the fabricated composite hydrogels demonstrated a versatile platform for bone repair, offering drug delivery functionality.