Nickel-Based Metal-Organic Frameworks Promote Diabetic Wound Healing via Scavenging Reactive Oxygen Species and Enhancing Angiogenesis

Chronic diabetic wounds remain a worldwide challenge for both the clinic and research. Given the vicious circle of oxidative stress and inflammatory response as well as the impaired angiogenesis of the diabetic wound tissues, the wound healing process is disturbed and poorly responds to the current treatments. In this work, a nickel-based metal-organic framework (MOF, Ni-HHTP) with excellent antioxidant activity and proangiogenic function is developed to accelerate the healing process of chronic diabetic wounds. The Ni-HHTP can mimic the enzymatic catalytic activities of antioxidant enzymes to eliminate multi-types of reactive species through electron transfer reactions, which protects cells from oxidative stress-related damage. Moreover, this Ni-based MOF can promote cell migration and angiogenesis by activating transforming growth factor-beta 1 (TGF-beta 1) in vitro and reprogram macrophages to the anti-inflammatory phenotype. Importantly, Ni-HHTP effectively promotes the healing process of diabetic wounds by suppressing the inflammatory response and enhancing angiogenesis in vivo. This study reports a versatile and promising MOF-based nanozyme for diabetic wound healing, which may be extended in combination with other wound dressings to enhance the management of diabetic or non-healing wounds. A nickel-based metal-organic framework-based nanozyme (Ni-HHTP) with electron transport function as well as nickel superoxide dismutase is designed to simultaneously eliminate reactive oxygen and nitrogen species (RONS) and enhance angiogenesis for the treatment of chronic diabetic wounds. Ni-HHTP significantly accelerates the healing process of diabetic wounds in vivo by suppressing inflammatory responses and promoting angiogenesis.image