Curcumin-based smart responsive hydrogels: A controlled release system for bone defect regeneration

The repair of bone tissue injuries and defects remains a major clinical challenge. This is particularly pronounced in aging populations, which face a growing incidence of osteoporosis-related fractures, traumatic bone defects, and regenerative deficiencies following bone tumor resection. Current strategies, such as autografts and allografts, are limited in efficacy. While bioactive molecules like growth factors and stem cells show promise, their clinical use is hindered by poor in vivo stability and inadequate retention at the target site, often necessitating high doses that introduce toxicity risks and compromise therapeutic outcomes. Curcumin, a natural polyphenol from turmeric, shows promise for bone repair via anti-inflammatory, antioxidant, and osteogenic effects. Yet, its clinical translation is hindered by poor solubility, rapid metabolism, and low bioavailability. To overcome these issues, smart responsive hydrogels, as advanced delivery platforms, can respond to physiological cues or applied stimuli, enabling precise spatiotemporal curcumin release with high biocompatibility and tunable kinetics. This review summarizes recent advances in smart curcumin-loaded hydrogels for bone repair, focusing on design strategies, response mechanisms, therapeutic efficacy, and ongoing challenges, thereby guiding future research directions.