Quercetin-loaded composite materials for bone regeneration: a review of carriers, controlled release, and mechanistic advances

Quercetin is a natural flavonoid with strong antioxidant, anti-inflammatory, and osteogenic effects, showing great promise for bone regeneration. However, its poor solubility, low bioavailability, and rapid degradation limit clinical use. Innovative quercetin-loaded composite biomaterials address these challenges by providing precise, controlled release and enhancing therapeutic efficacy. In recent years, quercetin-loaded composite materials have shown significant research progress in the field of bone tissue engineering. Studies indicate that in vitro experiments demonstrate the excellent biocompatibility of these materials, which promote osteogenic differentiation, induce macrophage polarization toward the M2 phenotype, scavenge reactive oxygen species, exert antibacterial effects, and enhance angiogenesis. In vivo studies confirm that quercetin-loaded composite materials increase bone volume, density, and vascularization, with various signaling pathways. This review integrates novel mechanistic insights, addresses challenges like optimal dosing and smart responsiveness, and outlines pathways for quercetin composites in repairing complex bone defects, paving the way for advanced regenerative therapies with strong clinical potential.