Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing

Abstract

Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.

Enhanced healing efficacy of an optimized gabapentin-melittin nanoconjugate gel-loaded formulation in excised wounds of diabetic rats

“…However, accumulating evidence indicates a role of oxidative stress in the pathogenesis of delayed healing of wounds (Schäfer & Werner, 2008 ). This is of particular significance in diabetes (Deng et al, 2021 ) to the extent of recommending the use of antioxidants to treat diabetic wounds (Zhang et al, 2021 ). Therefore, we have explored the potential of optimized GPN-MLT formula to prevent oxidative stress induced by wounding.…”

RJX Improves Wound Healing in Diabetic Rats

“…Hyperglycemia-triggered oxidative stress with amplified intracellular production of reactive oxygen species causing lipid peroxidation of cellular membranes and tissue level deficiency of anti-oxidant defense enzymes is one of the implicated contributors to nonhealing diabetic wounds ( 10 , 11 ). Antioxidant-loaded hydrogels and SOD-loaded hydrogels have been proposed as platforms that could improve diabetic wound healing by decreasing ROS generation and oxidative stress in chronic wounds ( 14 , 42 ). A recent study discovered significant micronutrient deficiencies in patients with DFUs ( 43 ).…”

Nanotechnologies for Reactive Oxygen Species“Turn-On” Detection

“…Thanks to these precise ROS detection methods, remarkable progress has been witnessed in unveiling the relevant biological mechanisms and uncovering the apparently paradoxical roles of distinct ROS in human health and disease. Small molecule fluorescent probes, especially reaction-based “turn-on” fluorescent probes, are generally useful owing to their high levels of sensitivity and capability to be applied in temporal and spatial sampling for in vivo and live cell imaging ( Wu et al, 2019 ; Wang et al, 2020 ; Zhang et al, 2021 ). Alternatively, great varieties of nanomaterials with peculiar ROS-regulating abilities have been fabricated to support ROS science in the aspects of ROS generation, depletion, transition, and detection ( Zhou Z. et al, 2016 ); these nanotechnologies finally benefit the ROS-based therapeutic outcomes ( Yang et al, 2019 ; Yu et al, 2020 ; Zhang et al, 2021 ; Zheng et al, 2021 ).…”

“…Small molecule fluorescent probes, especially reaction-based “turn-on” fluorescent probes, are generally useful owing to their high levels of sensitivity and capability to be applied in temporal and spatial sampling for in vivo and live cell imaging ( Wu et al, 2019 ; Wang et al, 2020 ; Zhang et al, 2021 ). Alternatively, great varieties of nanomaterials with peculiar ROS-regulating abilities have been fabricated to support ROS science in the aspects of ROS generation, depletion, transition, and detection ( Zhou Z. et al, 2016 ); these nanotechnologies finally benefit the ROS-based therapeutic outcomes ( Yang et al, 2019 ; Yu et al, 2020 ; Zhang et al, 2021 ; Zheng et al, 2021 ). Nanoparticles exhibit tunable properties in size, shape, and function that make them flexible in process and product control for a wide range of applications ( He et al, 2021 ; Yang et al, 2021 ; Yin et al, 2021 ).…”