Abstract
Wound healing is a well-tuned biological process, which is achieved via consecutive and overlapping phases including hemostasis, inflammatory-related events, cell proliferation and tissue remodeling. Several factors can impair wound healing such as oxygenation defects, aging, and stress as well as deleterious health conditions such as infection, diabetes, alcohol overuse, smoking and impaired nutritional status. Growing evidence suggests that reactive oxygen species (ROS) are crucial regulators of several phases of healing processes. ROS are centrally involved in all wound healing processes as low concentrations of ROS generation are required for the fight against invading microorganisms and cell survival signaling. Excessive production of ROS or impaired ROS detoxification causes oxidative damage, which is the main cause of non-healing chronic wounds. In this context, experimental and clinical studies have revealed that antioxidant and anti-inflammatory strategies have proven beneficial in the non-healing state. Among available antioxidant strategies, treatments using mitochondrial-targeted antioxidants are of particular interest. Specifically, mitochondrial-targeted peptides such as elamipretide have the potential to mitigate mitochondrial dysfunction and aberrant inflammatory response through activation of nucleotide-binding oligomerization domain (NOD)-like family receptors, such as the pyrin domain containing 3 (NLRP3) inflammasome, nuclear factor-kappa B (NF-κB) signaling pathway inhibition, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2).
Highlights
Wound healing is a well-tuned biological process, which is achieved via consecutive and overlapping phases including hemostasis, inflammatory-related events, cell proliferation and tissue remodeling [1,2]
The complex molecular andformation cellular processes wound healing occur in overlapping phases consisting of inflammation, of the ofgranulation tissue including myofibroblast consisting of inflammation, formation the granulation tissue including myofibroblast accumulation, accumulation, extracellular matrixof synthesis, angiogenesis, re-epithelialization, and tissue extracellular synthesis, remodeling matrix
Whereas production of reactive oxygen species (ROS) is essential to initiate wound repair, excessive amount of ROS generation is deleterious in wound healing
Summary
Wound healing is a well-tuned biological process, which is achieved via consecutive and overlapping phases including hemostasis, inflammatory-related events, cell proliferation and tissue remodeling [1,2]. Excessive and uncontrolled oxidative stress contribute to sustaining and deregulating inflammation processes, which play a central in themicroorganisms pathogenesis ofand chronic concentrations of ROS generation are required to fight againstrole invading cell non-healing wounds [6,7]. This review will and deregulating inflammation processes, which play a central role in state the pathogenesis of chronic examine the role of redox signaling and oxidative stress in the etiology of impaired wound healing, non-healing wounds [6,7]. Antioxidant and anti-inflammatory properties of several antioxidant with a particular focusbeneficial on the development of treatment strategies on mitochondrial-targeted strategies have proven to improve non-healing state [8,9,10]. Of redox signaling and oxidative stress in the etiology of impaired wound healing, with a particular focus on the development of treatment strategies based on mitochondrial-targeted antioxidants
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