Quercetin in bone regeneration: optimization of drug delivery system and study of its synergistic mechanism with bone tissue engineering.

Skeletal diseases impose a heavy global burden, creating an urgent demand for safe and effective therapeutic strategies for bone regeneration. Quercetin, a natural flavonoid compound, has attracted considerable attention owing to its potential to promote bone formation and inhibit bone resorption. Nevertheless, its poor solubility and low bioavailability limit its clinical application. The integration of drug delivery systems with bone tissue engineering offers a promising approach to address these challenges. This review examines the latest advances in quercetin-based drug delivery systems and their synergistic mechanisms with bone tissue engineering. It systematically discusses various strategies, including hydrogels, hydroxyapatite, biofunctional scaffolds, phospholipid carriers, metal complexes, nanomaterials, and medicinal chemical modifications, and presents the core advantages of these approaches in achieving targeted delivery, controlled release, and enhanced bioactivity of quercetin. Furthermore, this review highlights the central role of these delivery systems in potentiating the pro-regenerative effects of quercetin. These advances not only provide practical solutions to overcome the inherent limitations of quercetin but also significantly broaden its application prospects in bone tissue engineering.