Melatonin-Loaded Hydrogel Modulates Circadian Rhythms and Alleviates Oxidative Stress and Inflammation to Promote Wound Healing.

Circadian rhythm disruption, commonly caused by factors such as jet lag and shift work, is increasingly recognized as a critical factor impairing wound healing. Although melatonin is known to regulate circadian rhythms and has potential in wound repair, its clinical application is limited by low bioavailability. To address these challenges, we developed an alginate-based dual-network hydrogel as a delivery system for melatonin, ensuring its stable and sustained release at the wound site. This approach enhances the efficacy of melatonin in modulating the wound healing process. We investigated the effects of circadian rhythm disruption on the wound microenvironment under the influence of the melatonin-loaded hydrogel with a focus on its biocompatibility, hemostatic properties, and antioxidant response functions. Additionally, we elucidated the mechanisms by which the melatonin-loaded hydrogel system promotes wound healing. Our findings provide insights into the relationship between circadian rhythm disruption and wound healing, offering a promising strategy for the management of chronic wounds associated with circadian rhythm disorders.