Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process (original) (raw)
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European cells & materials, 2012
Wound healing requires a fine balance between the positive and deleterious effects of reactive oxygen species (ROS); a group of extremely potent molecules, rate limiting in successful tissue regeneration. A balanced ROS response will debride and disinfect a tissue and stimulate healthy tissue turnover; suppressed ROS will result in infection and an elevation in ROS will destroy otherwise healthy stromal tissue. Understanding and anticipating the ROS niche within a tissue will greatly enhance the potential to exogenously augment and manipulate healing. Tissue engineering solutions to augment successful healing and remodelling of wounded or diseased tissue rely on a controlled balance between the constructive and destructive capacity of the leukocyte secretome, including ROS. This review comprehensively considers leukocyte derived ROS in tissue repair with particular interest in surgical intervention with inclusion of a biomaterial. The article considers ROS fundamental chemistry, for...
Revisiting the essential role of oxygen in wound healing
The American Journal of Surgery, 2003
Hypoxemia, caused by disrupted vasculature, is a key factor that limits wound healing. Correcting hypoxemia through the administration of supplemental oxygen (O(2)) can have significant beneficial impact on wound healing in the perioperative and outpatient settings. Beyond its role as a nutrient and antibiotic, O(2) may support vital processes such as angiogenesis, cell motility, and extracellular matrix formation. Recent discoveries highlight a novel aspect, addressing the role of O(2) in wound healing via the production of reactive oxygen species (ROS). Almost all wound-related cells possess specialized enzymes that generate ROS (including free radicals and H(2)O(2)) from O(2). Defect in these enzymes is associated with impaired healing. Low wound pO(2) is expected to compromise the function of these enzymes. At low concentrations, ROS serve as cellular messengers to support wound healing. The use of systemic hyperbaric O(2) therapy presents potential advantages, as well as risks. There is evidence to suspect that the use of pressure and systemic pure O(2) may not be essential in wound care. Elimination of these factors by using sub-pure systemic O(2) under normobaric conditions may significantly minimize the risk of O(2) toxicity. Furthermore, opportunities to treat dermal wounds using topical O(2) therapy warrant further investigation. Given that many growth factors require ROS for their function, it is reasonable to assume that approaches to correct wound pO(2) will serve as an effective adjunct in treating chronic wounds.
Emerging ROS-Modulating Technologies for Augmentation of the Wound Healing Process
ACS Omega
Reactive oxygen species (ROS) is considered a double-edged sword. The slightly elevated level of ROS helps in wound healing by inhibiting microbial infection. In contrast, excessive ROS levels in the wound site show deleterious effects on wound healing by extending the inflammation phase. Understanding the ROS-mediated molecular and biomolecular mechanisms and their effect on cellular homeostasis and inflammation thus substantially improves the possibility of exogenously augmenting and manipulating wound healing with the emerging antioxidant therapeutics. This review comprehensively delves into the relationship between ROS and critical phases of wound healing and the processes underpinning antioxidant therapies. The manuscript also discusses cutting-edge antioxidant therapeutics that act via ROS scavenging to enhance chronic wound healing.
Oxygen, oxidants, and antioxidants in wound healing: an emerging paradigm
Annals of the New York Academy of Sciences, 2002
Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for "natural remedies" has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.
Oxygen: Implications for Wound Healing
Advances in Wound Care, 2012
Background: Oxygen is vital for healing wounds. It is intricately involved in numerous biological processes including cell proliferation, angiogenesis, and protein synthesis, which are required for restoration of tissue function and integrity. Adequate wound tissue oxygenation can trigger healing responses and favorably influence the outcomes of other treatment modalities. The Problem: Chronic ischemic wounds fail to heal appropriately secondary to extreme hypoxia that leads to cellular demise. Wound tissue hypoxia is typically greater at the center of the wound. Accordingly, oxygen requirements of the regenerating tissue will vary. Basic/Clinical Science Advances: As oxygen levels decrease within the wound, cell response mechanisms (hypoxia inducible factor [HIF]) trigger the transcription of genes that promote cell survival and angiogenesis. HIF stabilizers are currently being tested to determine wound healing potential. Clinically, topical oxygen therapy (TOT) has been proved as an effective therapeutic modality for chronic wounds. TOT is reputed to have several advantages over hyperbaric oxygen therapy. Namely, TOT has a lower risk of oxygen toxicity, it is less expensive and is relatively easy to apply to target areas. Clinical Care Relevance: Wound tissue oxygen is necessary for appropriate wound healing; however, the relative complexity of the healing process requires a multifaceted approach for successful healing outcomes. A key component of this multifaceted approach should be specific oxygen dosing as a function of tissue hypoxia. Conclusion: New treatment approaches that exploit cell hypoxia sensing and response mechanisms and that enable the precise application of oxygen therapy to hypoxic areas of regenerating tissue are very promising. j 225
Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair
International Journal of Molecular Sciences
Our understanding of the role of oxygen in cell physiology has evolved from its longrecognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions.
Oxygen, Oxidants, and Antioxidants in Wound Healing
Annals of The New York Academy of Sciences, 2002
A BSTRACT : Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for "natural remedies" has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.
Oxygen in Wound Healing?More than a Nutrient
World Journal of Surgery, 2004
This article provides an overview of the role of oxygen in wound healing. The understanding of this role has undergone a major evolution from its long-recognized importance as an essential factor for oxidative metabolism, to its recognition as an important cell signal interacting with growth factors and other signals to regulate signal transduction pathways. Our laboratory has been engaged in thestudy of animal models of skin ischemia to explore in vivo the impact of hypoxia as well as the use of oxygen as a therapeutic agent either alone or in combination with other agents such as growth factors. We have demonstrated a synergistic effect of systemic hyperbaric oxygen and growth factors that has been substantiated by Hunt's group. Within the past 10 years research in the field of wound healing has given new insight into the mechanism of action of hypoxia and hyperoxia as modifiers of the normal time-course of wound healing. The article concludes with a discussion of why hypoxia and hyperoxia intercurrently play an important role in wound healing. Hypoxia-inducible factor 1 is crucial in that interplay.