Rinsing Chronic Wounds with a Nitric Oxide Containing Solution – A Safe Treatment Approach to Support Wound Healing

2020 ◽  
Vol 16 (4) ◽  
pp. 394-406
Author(s):  
Thorsten U. Meyer
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Safety Data ◽  
Wound Irrigation ◽  
Beneficial Effects ◽  
Physiological Processes ◽  
Therapeutic Benefits ◽  
Irrigation Solution ◽  
Mediator Agent

Background: Nitric oxide (NO) is known for decades to play a crucial role in many physiological processes: this includes acting as an anti-microbial mediator/agent, vasodilator, inhibitor of platelet aggregation, immune modulator, and tissue regeneration via regulation of epidermal cell migration, collagen deposition and cytokine/chemokine microenvironment, making it a key player in wound healing. Methods: In order to demonstrate the therapeutic benefits as well as the safety of a NO wound irrigation solution, a broad literature review summarizing efficacy and safety data was conducted. Results: Beneficial effects on wound healing have been demonstrated in several non-clinical and clinical studies. The combination of NO and wound rinsing seems to be a promising approach in terms of improved wound healing of chronic wounds. Conclusion: Based on the results, no safety concerns are expected for a daily 15 minutes use of a NOgenerating rinsing solution system for wound irrigation of diabetic foot ulcers in adults.

Role of Nitric Oxide in Wound Healing

2002 ◽  
Vol 4 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Beverly B. Childress ◽  
Joyce K. Stechmiller
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Growth Factors ◽  
Animal Studies ◽  
Chronic Wounds ◽  
Current Knowledge ◽  
Wound Care ◽  
Impaired Wound Healing ◽  
Normal Wound Healing ◽  
Age Related

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and suffer from a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatory forces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.

scholarly journals Resveratrol-Induced Signal Transduction in Wound Healing

2021 ◽  
Vol 22 (23) ◽  
pp. 12614
Author(s):  
Anna-Lisa Pignet ◽  
Marlies Schellnegger ◽  
Andrzej Hecker ◽  
Michael Kohlhauser ◽  
Petra Kotzbeck ◽  
...  
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Therapeutic Potential ◽  
Protective Effects ◽  
Oxidative Potential ◽  
Accelerate Wound Healing ◽  
Beneficial Effects ◽  
Relevant Variables ◽  
Systemic Side Effects

Resveratrol is a well-known polyphenol that harbors various health benefits. Besides its well-known anti-oxidative potential, resveratrol exerts anti-inflammatory, pro-angiogenic, and cell-protective effects. It seems to be a promising adjuvant for various medical indications, such as cancer, vascular, and neurodegenerative diseases. Additionally, resveratrol was shown to display beneficial effects on the human skin. The polyphenol is discussed to be a feasible treatment approach to accelerate wound healing and prevent the development of chronic wounds without the drawback of systemic side effects. Despite resveratrol’s increasing popularity, its molecular mechanisms of action are still poorly understood. To take full advantage of resveratrol’s therapeutic potential, a profound knowledge of its interactions with its targets is needed. Therefore, this review highlights the resveratrol-induced molecular pathways with particular focus on the most relevant variables in wound healing, namely inflammation, oxidative stress, autophagy, collagen proliferation and angiogenesis.

Challenges and opportunities of pH in chronic wounds

2019 ◽  
Vol 10 (11) ◽  
pp. 719-735 ◽  
Author(s):  
Laura A Wallace ◽  
Lauren Gwynne ◽  
Tobias Jenkins
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Clinical Parameter ◽  
Public Health Issue ◽  
Acidic Ph ◽  
Global Public Health ◽  
Oxygen Release ◽  
Physiological Processes ◽  
Challenges And Opportunities ◽  
Bacterial Toxicity

Regarded as a silent epidemic, chronic wounds are a global public health issue. Wound healing is a complex, synchronized cascade of physiological processes restoring the anatomic and functional integrity of the skin; however, chronic wounds fail to proceed through the wound healing cascade. Wound pH oscillates during wound healing, usually traversing from a neutral pH to an acidic pH, while chronic wounds perpetuate in an elevated alkaline milieu. Although a neglected clinical parameter, pH has implications for relatively all pathologies of wound healing affecting oxygen release, angiogenesis, protease activity, bacterial toxicity and antimicrobial activity. Despite the array of wound healing products currently marketed, understanding the implications of pH on arresting wound healing can stimulate innovation within this vast market.

Understanding the Potential Role and Delivery Approaches of Nitric Oxide in the Chronic Wound Healing Management

2020 ◽  
Vol 26 ◽  
Author(s):  
Mimansa Kandhwal ◽  
Tapan Behl ◽  
Arun Kumar ◽  
Sandeep Arora
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Chronic Wound ◽  
Lower Limbs ◽  
Diabetic Patients ◽  
Pharmacological Mechanism ◽  
Novel Treatments ◽  
Beneficial Effects ◽  
Chronic Ulcers

: Nitric oxide (NO) is a promising pharmaceutical component that has vasodilator, antibacterial and wound healing activity. Chronic ulcers are non-healing disorders that are generally associated with distortion of lower limbs. Among the severe consequence’s derivative of these diseases, are the problems of chronic wound progression. NO which is categorized as smallest gaseous neurotransmitter has beneficial effects in different phases of chronic inflammation. Defensive mechanism of NO is found useful in several severe conditions such as gestational healing, gastrointestinal healing and diabetic healing. The current review presents up to date collection of literature about role of NO in chronic ulcers due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. This review also collects the information about deficiency of NO synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes diabetic neuropathy; and this could be treated with vasodilators such as nitric oxide. Apart from pharmacological mechanism of NO, the article also reviewed and analyzed to elucidate the potential of a transdermal delivery of NO for the treatment of chronic ulcers.

Recent Advances in the Development of Nitric Oxide-Releasing Biomaterials and Their Application Potentials in Chronic Wound Healing

2021 ◽  
Author(s):  
Min Wu ◽  
Zhihui Lu ◽  
Keke Wu ◽  
Changwoo Nam ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Persistent Infection ◽  
Diabetic Foot ◽  
Chronic Wounds ◽  
Pressure Ulcers ◽  
Chronic Wound ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Nitric Oxide Releasing

Chronic wounds, such as pressure ulcers, vascular ulcers and diabetic foot ulcers (DFUs), often stays in a state of pathological inflammation and suffers from persistent infection, excess inflammation, and hypoxia,...

Arginine Metabolites in Wound Fluids From Pressure Ulcers: A Pilot Study

2008 ◽  
Vol 10 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Beverly Childress ◽  
Joyce K. Stechmiller ◽  
Gregory S. Schultz
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Pilot Study ◽  
Negative Pressure Wound Therapy ◽  
Chronic Wounds ◽  
Pressure Ulcers ◽  
Stage Iii ◽  
Wound Therapy ◽  
Before And After ◽  
Oxide Synthase

Compelling evidence suggests that nitric oxide (NO•), a metabolite of arginine, plays an important role in wound healing. Arginine is a semi-essential amino acid that is metabolized by nitric oxide synthase and arginase. One model for wound-healing regulation suggests the importance of strict reciprocal control of these enzymes in wounds. The purpose of this pilot study was to investigate arginine metabolism in wound fluids from patients with Stage III or IV pressure ulcers receiving negative pressure wound therapy (NPWT). Wound fluids were collected from 8 patients, aged 31—79 years, before and after initiation of NPWT on Days 1, 3, and 7. Wound fluids were analyzed for nitrates/nitrites (NOx), arginine, citrulline, proline, and ornithine. There were no significant differences between NOx, arginine, citrulline, proline, and ornithine concentrations before and after initiation of NPWT among the various timepoints. However, we observed a downward trend of NO•levels from baseline to Day 7 of NPWT treatment. Furthermore, we detected a decrease in arginine levels over the study period, suggesting that the iNOS/citrulline pathway predominated during the first 72 hr of treatment, and the arginase/ ornithine pathway dominated thereafter. Arginine and its metabolites are detectable in wound fluids from patients with Stage III or IV pressure ulcers on NPWT. Further studies on chronic wounds are warranted to correlate wound-healing outcomes with arginine metabolites at the cellular and molecular level over a longer period of time.

scholarly journals Antimicrobial efficacy and wound-healing property of a topical ointment containing nitric-oxide-loaded zeolites

2014 ◽  
Vol 63 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Michael Neidrauer ◽  
Utku K. Ercan ◽  
Aparna Bhattacharyya ◽  
Joshua Samuels ◽  
Jason Sedlak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Detection System ◽  
Cutaneous Wounds ◽  
Log Reduction ◽  
Gram Positive Bacteria ◽  
Obese Rats ◽  
Healing Property ◽  
Wound Healing Property

Topical delivery of nitric oxide (NO) through a wound dressing has the potential to reduce wound infections and improve healing of acute and chronic wounds. This study characterized the antibacterial efficacy of an ointment containing NO-loaded, zinc-exchanged zeolite A that releases NO upon contact with water. The release rate of NO from the ointment was measured using a chemiluminescence detection system. Minimum bactericidal concentration assays were performed using five common wound pathogens, including Gram-negative bacteria (Escherichia coli and Acinetobacter baumannii), Gram-positive bacteria (Staphylococcus epidermidis and meticillin-resistant Staphylococcus aureus) and a fungus (Candida albicans). The time dependence of antimicrobial activity was characterized by performing log-reduction assays at four time points after 1–8 h ointment exposure. The cytotoxicity of the ointment after 24 h was assessed using cultured 3T3 fibroblast cells. Minimum microbicidal concentrations (MMCs) for bacterial organisms (5×107 c.f.u.) ranged from 50 to 100 mg ointment (ml media)−1; the MMC for C. albicans (5×104 c.f.u.) was 50 mg ointment (ml media)−1. Five to eight log reductions in bacterial viability and three log reductions in fungal viability were observed after 8 h exposure to NO–zeolite ointment compared with untreated organisms. Fibroblasts remained viable after 24 h exposure to the same concentration of NO–zeolite ointment as was used in antimicrobial tests. In parallel studies, full-thickness cutaneous wounds on Zucker obese rats healed faster than wounds treated with a control ointment. These data indicate that ointment containing NO-loaded zeolites could potentially be used as a broad-spectrum antimicrobial wound-healing dressing.

scholarly journals Nitric Oxide Release from Antimicrobial Peptide Hydrogels for Wound Healing

Biomolecules ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Joana Durão ◽  
Nuno Vale ◽  
Salomé Gomes ◽  
Paula Gomes ◽  
Cristina C. Barrias ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Initial Increase ◽  
No Donor ◽  
Collagen Production ◽  
Nitric Oxide Release ◽  
Lysine Residues

Nitric oxide (NO) is an endogenously produced molecule that has been implicated in several wound healing mechanisms. Its topical delivery may improve healing in acute or chronic wounds. In this study an antimicrobial peptide was synthesized which self-assembled upon a pH shift, forming a hydrogel. The peptide was chemically functionalized to incorporate a NO-donor moiety on lysine residues. The extent of the reaction was measured by ninhydrin assay and the NO release rate was quantified via the Griess reaction method. The resulting compound was evaluated for its antimicrobial activity against Escherichia coli, and its effect on collagen production by fibroblasts was assessed. Time-kill curves point to an initial increase in bactericidal activity of the functionalized peptide, and collagen production by human dermal fibroblasts when incubated with the NO-functionalized peptide showed a dose-dependent increase in the presence of the NO donor within a range of 0–20 μM.

scholarly journals Honey for Wound Healing, Ulcers, and Burns; Data Supporting Its Use in Clinical Practice

2011 ◽  
Vol 11 ◽  
pp. 766-787 ◽  
Author(s):  
Noori Al-Waili ◽  
Khelod Salom ◽  
Ahmad A. Al-Ghamdi
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Clinical Practice ◽  
Antibacterial Agent ◽  
Chronic Wounds ◽  
Healing Process ◽  
Tissue Growth ◽  
Gastric Ulcers ◽  
Therapeutic Effects ◽  
Stimulation Of

The widespread existence of unhealed wounds, ulcers, and burns has a great impact on public health and economy. Many interventions, including new medications and technologies, are being used to help achieve significant wound healing and to eliminate infections. Therefore, to find an intervention that has both therapeutic effect on the healing process and the ability to kill microbes is of great value. Honey is a natural product that has been recently introduced in modern medical practice. Honey's antibacterial properties and its effects on wound healing have been thoroughly investigated. Laboratory studies and clinical trials have shown that honey is an effective broad-spectrum antibacterial agent. This paper reviews data that support the effectiveness of natural honey in wound healing and its ability to sterilize infected wounds. Studies on the therapeutic effects of honey collected in different geographical areas on skin wounds, skin and gastric ulcers, and burns are reviewed and mechanisms of action are discussed. (Ulcers and burns are included as an example of challenging wounds.) The data show that the wound healing properties of honey include stimulation of tissue growth, enhanced epithelialization, and minimized scar formation. These effects are ascribed to honey's acidity, hydrogen peroxide content, osmotic effect, nutritional and antioxidant contents, stimulation of immunity, and to unidentified compounds. Prostaglandins and nitric oxide play a major role in inflammation, microbial killing, and the healing process. Honey was found to lower prostaglandin levels and elevate nitric oxide end products. These properties might help to explain some biological and therapeutic properties of honey, particularly as an antibacterial agent or wound healer. The data presented here demonstrate that honeys from different geographical areas have considerable therapeutic effects on chronic wounds, ulcers, and burns. The results encourage the use of honey in clinical practice as a natural and safe wound healer.

scholarly journals Cellular Signalling and Photobiomodulation in Chronic Wound Repair

2021 ◽  
Vol 22 (20) ◽  
pp. 11223
Author(s):  
Thobekile S. Leyane ◽  
Sandy W. Jere ◽  
Nicolette N. Houreld
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Cellular Proliferation ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Atp Production ◽  
Therapeutic Benefits

Photobiomodulation (PBM) imparts therapeutically significant benefits in the healing of chronic wounds. Chronic wounds develop when the stages of wound healing fail to progress in a timely and orderly frame, and without an established functional and structural outcome. Therapeutic benefits associated with PBM include augmenting tissue regeneration and repair, mitigating inflammation, relieving pain, and reducing oxidative stress. PBM stimulates the mitochondria, resulting in an increase in adenosine triphosphate (ATP) production and the downstream release of growth factors. The binding of growth factors to cell surface receptors induces signalling pathways that transmit signals to the nucleus for the transcription of genes for increased cellular proliferation, viability, and migration in numerous cell types, including stem cells and fibroblasts. Over the past few years, significant advances have been made in understanding how PBM regulates numerous signalling pathways implicated in chronic wound repair. This review highlights the significant role of PBM in the activation of several cell signalling pathways involved in wound healing.

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