Topical Oxygen Research Articles

A topical aqueous oxygen emulsion stimulates granulation tissue formation in a porcine second-degree burn wound

BackgroundOxygen is an essential substance for wound healing. Limited studies have shown that topical oxygen can influence healing. This study evaluated the effects of a Topical Oxygen Emulsion (TOE) on burn wound healing. MethodsA porcine second-degree burn wound model was used in the study. Burn wounds were randomly assigned to TOE, vehicle control, and no-treatment (air) groups. Effects of TOE on the granulation tissue formation and angiogenesis were studied using hematoxylin and eosin histological analysis. Protein production and gene expression of types I and III collagen and vascular endothelial growth factor (VEGF) were determined using immunofluorescent staining and Reverse Transcription and Polymerase Chain Reaction (RT-PCR), respectively. ResultsThe TOE treated wounds exhibited better angiogenesis and granulation tissue formation by histology examination. The immunofluorescence staining and RT-PCR analysis demonstrated that protein production and mRNA expression of VEGF and collagen III were significantly higher in TOE treatment group than vehicle alone and air control groups, while there was no significant difference in the level of collagen I. ConclusionsOur data demonstrate that TOE enhances burn wound healing via stimulating the expression of VEGF and type III collagen and strongly indicates the potential use of TOE in wounds.

A topical haemoglobin spray for oxygenating chronic venous leg ulcers: a pilot study.

Acute wounds will generally heal independently of any interventions, whereas chronic wounds are chronic for a reason and are unlikely to successfully heal without intervention. In the treatment of venous leg ulcers, the gold standard will always be compression therapy. However, many wounds still do not heal despite best practice. Therefore, the use of adjunct therapies alongside standard care become the priority for healing. This article describes a small evaluation, involving 17 patients with chronic venous leg ulcers, that set out to determine the effect of a topical oxygen therapy on wound size. The therapy comprises a canister that sprays pure haemoglobin in a water solution into the wound. The haemoglobin spray needs to be used at least once every 3 days, and no training is required on its use. Results showed the device helped promote wound healing in 14 out of 17 wounds treated for more than 2 weeks. These patients had previously been shown to be non-healing during a 4-week run-in period where they received standard care, including compression therapy.

Influence of oxygen on wound healing dynamics in healing-impaired diabetic mice

A previous experiment using an in vivo mouse model has proved that hypoxia increased angiogenesis during wound healing. It was hypothesised that one of the mechanisms for wound healing impairment in diabetes includes insufficient angiogenic ability in response to hypoxia. The current study aims to investigate the influence of hypoxia on wound healing in diabetic mice. Oxygen-impermeable (hypoxic group) and -permeable membranes (normoxic group) were used to control topical oxygen tension. Membranes were applied to symmetrical excisional wounds on diabetic mice. Wound area, granulated tissue thickness, and vascular density were analyzed. As results, a decrease in wound size on day 7 was observed in the normoxic group (20.7 ± 3.64%) compared with the hypoxic group (34.1 ± 4.98%). The normoxic group also showed significantly thicker granulated tissue than the hypoxic group (225.7 ± 54.7 vs 128.7 ± 42.4 µm). There was no significant difference in mean vascular density between normoxic and hypoxic groups (0.046 ± 0.022 vs 0.038 ± 0.017 mm2/mm2, p = 0.80). Contrary to healthy mice, diabetic mice have shown no enhancement of angiogenesis in hypoxic condition. The findings illustrate that neovascularisation in response to hypoxia is diminished in diabetic wounds.

The clinical observation of topical oxygen therapy combined with Bactroban ointment in the treatment of indwelling needle tape allergies

Objective To explore the clinical efficacy of topical oxygen therapy combined with Bactroban ointment in the treatment of indwelling needle tape allergies.Methods 40 patients with indwelling needle tape allergies were randomly divided into control group and treatment group,20 cases in each group.Control group received conventional Bactroban ointment,treatment group received topical oxygen therapy on the basis of conventional treatment,10-15 min each time,2 times a day.The wound healing time and efficacy of two groups were compared and statistically analyzed.Result The treatment effective rate and wound healing time in treatment group were significantly better than those in control group [95％ vs.55％,(2.75 ± 0.62)d vs.(5.34 ± 1.08) d,P ＜ 0.05].Conclusion Topical oxygen therapy combined with Bactroban ointment is better than simply using Bactroban ointment,with quick and good curative effect,worthy of clinical application. Key words: Topical oxygen therapy; Bactroban ointment; Tape allergies

Novel post-treatment care after ablative and fractional CO2 laser resurfacing

Objective: This study evaluates a topical oxygen emulsion (TOE) to reduce adverse effects after skin rejuvenation with a fully ablative CO2 laser alone and in combination with a fractional ablative CO2 laser. Materials and methods: Patients (n = 100) seeking skin rejuvenation underwent CO2 laser resurfacing. Group A patients (n = 34) received a single deep fractional laser treatment followed by application of Aquaphor™ immediately after treatment for 24 h and TOE every 6 h for the next 6 days. Group B patients (n = 66) underwent both deep fractional and fully ablative laser resurfacing followed by application of TOE every 6 h for 7 consecutive days. Results: Patients in both groups showed clinical improvement and a 7.1% overall incidence of adverse effects which included milia (5.1% overall) and hyperpigmentation (3.1% overall). For milia, Group A and Group B individual adverse effect rates were 11.8% and 1.5%, respectively; for hyperpigmentation, individual rates were 0.0% and 3.1%, respectively. Conclusion: The elimination of petrolatum products in the post-skin care regimen has significantly reduced the incidence of post-procedure complications when compared with the use of TOE, resulting in the lowest incidence of complications in fully ablative or fractional resurfacing published thus far.

Oxygen and wound care: A review of current therapeutic modalities and future direction

While the importance of oxygen to the wound healing process is well accepted, research and technological advances continue in this field and efforts are ongoing to further utilize oxygen as a therapeutic modality. In this paper, the authors briefly review the role of oxygen in wound healing and discuss the distinct mechanism of action as well as the advantages and disadvantages of the three major oxygen-based therapies currently in clinical use (Hyperbaric Oxygen and Topical Oxygen and Continuous Diffusion of Oxygen), as well as review the existing literature regarding these distinct therapeutic modalities.

XXXV Congreso Nacional de la Sociedad Española de Diálisis y Trasplante. Bilbao, 9-11 de mayo de 2013

The role of oxygen in wound healing is universally accepted and does not require any further evidence; however the controversy as to whether oxygen delivery systems have the potential to improve wound healing remains to be concluded. Topical oxygen treatment (TOT) involves the delivery of 100% oxygen for a mean of 90 min, once a day at an atmospheric pressure slightly above 1 atm abs. The use of TOT gained increasing interest recently. The current manuscript will summarize the pros and cons of TOT in the view of the available literature.

Microfluidic wound bandage: Localized oxygen modulation of collagen maturation

AbstractRestoring tissue oxygenation has the potential to improve poorly healing wounds with impaired microvasculature. Compared with more established wound therapy using hyperbaric oxygen chambers, topical oxygen therapy has lower cost and better patient comfort, although topical devices have provided inconsistent results. To provide controlled topical oxygen while minimizing moisture loss, a major issue for topical oxygen, we have devised a novel wound bandage based on microfluidic diffusion delivery of oxygen. In addition to modulating oxygen from 0 to 100% in 60 seconds rise time, the microfluidic oxygen bandage provides a conformal seal around the wound. When 100% oxygen is delivered, it penetrates wound tissues as measured in agar phantom and in vivo wounds. Using this microfluidic bandage, we applied the oxygen modulation to 8 mm excisional wounds prepared on diabetic mice. Treatment with the microfluidic bandage demonstrated improved collagen maturity in the wound bed, although only marginal differences were observed in total collagen, microvasculature, and external closure rates. Our results show that proper topical oxygen can improve wound parameters underneath the surface. Because of the ease of fabrication, the oxygen bandage represents an economical yet practical method for oxygen wound research.

Oxygen: Implications for Wound Healing

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. 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. 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. 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. 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.

Continuous Topical Oxygen for the Treatment of Chronic Wounds

Oxygen is essential for all stages of wound healing. Previous research has shown topical administration of oxygen to have positive effects on wound healing. In this study, the application of transdermal continuous topical oxygen therapy (TCOT) was evaluated for its effect on chronic wound healing in 9 patients. After 4 weeks of treatment, mean wound surface area and wound infection checklist scores were significantly reduced. Signs of bacterial damage were also reduced. Findings from this study suggest TCOT may be beneficial in promoting chronic wound healing.

Influence of Oxygen on Wound Healing Dynamics: Assessment in a Novel Wound Mouse Model under a Variable Oxygen Environment

IntroductionAlthough oxygen is essential for the wound healing process, tissue hypoxia is known to stimulate angiogenesis. To explore these inconsistent findings, we estimated the influence of the oxygen environment on wound healing with our original model.MethodsExperiment 1 (Establishment of the model): To modify the topical oxygen tension, oxygen impermeable (polyvinylidene chloride) and permeable (polymethylpentene) membranes were applied to symmetrical excisional wounds in ddy mice (n = 6). Oxygen tension under the membrane was quantified with a device using photo-quenching technique. Experiment 2 (Influence of oxygen environment on wound healing): The wound area, granulation thickness and vascular density were analyzed under different oxygen environments (n = 24).ResultsExperiment 1: The permeable group maintained equivalent oxygen level to atmosphere (114.1±29.8 mmHg on day 7), while the impermeable group showed extremely low oxygen tension (5.72±2.99 mmHg on day 7). Accordingly, each group was defined as the normoxia group and the hypoxia group. Experiment 2: Percent decrease in wound size was significantly enhanced in the normoxia group (11.1±1.66% on day 7) in comparison with the hypoxia group (27.6±3.47% on day 7). The normoxia group showed significantly thicker granulation tissue than the hypoxia group (491.8±243.2 vs. 295.3±180.9 µm). Contrarily, the vascular density of the hypoxia group significantly increased on day 7 (0.046±0.025 vs. 0.011±0.008 mm2/mm2).ConclusionsOur original model successfully controlled local oxygen concentration around the wound, and the hypoxic wounds showed increased angiogenesis but with a smaller amount of granulation tissue and delayed wound closure. Enhanced neovascularization in the hypoxic group likely implies compensative response to an insufficient ambient oxygen supply.

Topical Oxygen Therapy is not Hyperbaric Therapy and the Two Treatments Should Not be Confused

Topical Oxygen Therapy is not Hyperbaric Therapy and the Two Treatments Should Not be Confused

The role of oxygen‐associated therapies for the healing of chronic wounds, particularly in patients with diabetes

This paper discusses the role of molecular oxygen as an aid to wound healing, and the potential value of the three major therapies which allow the delivery of oxygen to the wound site: Hyperbaric Oxygen Therapy (HBOT), Topical Oxygen Therapy (TOT) and a new sterile wound dressing, Oxyzyme™. We summarize studies which have been undertaken using these interventions, and discuss their reported effect on chronic, non-healing wounds, in particular, on ulcers associated with Diabetes. The main conclusions drawn from the studies reviewed indicate that therapeutic oxygen can be used as an aid to the healing of chronic wounds; and benefits are clearly evident with the use of both HBOT and TOT. There is also potential for the use of a new, portable, topical oxygen delivery system, oxyzyme. However its use is still embryonic and studies on its effectiveness are limited. More robust measures of its efficacy are urgently needed.

Dermaplaning, Topical Oxygen, and Photodynamic Therapy: A Systematic Review of the Literature

Noninvasive procedures for facial rejuvenation are becoming an increasingly popular component of a comprehensive skin care regimen. Concurrently, many new treatment methods are now available to both the plastic surgeon and the aesthetician. Because these techniques have become an integral part of many cosmetic practices, this study aimed to assess the existing evidence-based literature as to their clinical efficacy; to provide an objective overview of some of the most popular noninvasive rejuvenation strategies such as dermaplaning, oxygen therapy, and light therapy; to discuss recent pertinent scientific evidence-based literature; and to provide treatment recommendations based on these findings. A systematic review was performed in August 2009 using PubMed and the following keywords: "dermaplaning," "oxygen therapy," and "light therapy." All peer-reviewed articles then were screened independently by three plastic surgeons. The search identified 42 English-written, peer-reviewed manuscripts. The overall amount of scientific data supporting these methods was found to be scarce, anecdotal, and not well documented. Nevertheless, all three noninvasive therapies have become increasingly popular in the cosmetic market because many patients and physicians or surgeons report being pleased with their results. Although the evidence supporting these nonsurgical methods is suboptimal, their uses continue to expand. As with any plastic surgery procedure, providing patients with realistic expectations is essential to achieving optimal outcomes and patient satisfaction. Therefore, critical investigation is warranted. In addition, these methods are most effective when included within a comprehensive skin care regimen consisting of sunscreen, vitamin therapy, and lifestyle modification.

Oxygen in acute and chronic wound healing

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.

Topical Dissolved Oxygen Penetrates Skin: Model and Method

It has been commonly perceived that skin receives its oxygen supply from the internal circulation. However, recent investigations have shown that a significant amount of oxygen may enter skin from the external overlying surface. A method has been developed for measuring the transcutaneous penetration of human skin by oxygen as described herein. This method was used to determine both the depth and magnitude of penetration of skin by topically applied oxygen. An apparatus consisting of human skin samples interposed between a topical oxygen source and a fluid filled chamber that registered changes in dissolved oxygen. Viable human skin samples of variable thicknesses with and without epidermis were used to evaluate the depth and magnitude of oxygen penetration from either topical dissolved oxygen (TDO) or topical gaseous oxygen (TGO) devices. This model effectively demonstrates transcutaneous penetration of topically applied oxygen. Topically applied dissolved oxygen penetrates through >700 microm of human skin. Topically applied oxygen penetrates better though dermis than epidermis, and TDO devices deliver oxygen more effectively than TGO devices.

Evidence-Based Recommendations for the Use of Topical Oxygen Therapy in the Treatment of Lower Extremity Wounds

Topical oxygen therapy provides another tool in the armamentarium of clinicians treating refractory lower extremity wounds. Devices suitable for providing topical oxygen therapy in a clinical setting have recently become available. This article reviews the evidence to justify the use of this treatment modality, including in vitro, preclinical data, and clinical data. It also provides a protocol for how to administer topical oxygen therapy as well as guidance on patient selection and management to optimize outcomes. Randomized controlled trials are not yet reported and clearly necessary. The current body of evidence suggests that topical oxygen therapy may be considered as a second line of therapy for refractory wounds.

TOPICAL OXYGEN THERAPY INDUCES VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION AND IMPROVES CLOSURE OF CLINICALLY PRESENTED CHRONIC WOUNDS

1. Chronic wounds, especially in diabetics, represent a serious threat to human health. 2. Correcting a compromised state of tissue oxygenation by the administration of supplemental O(2) is known to benefit wound healing. Beyond its role as a nutrient and antibiotic, O(2) supports wound healing by driving redox signaling. 3. Hyperbaric oxygen (HBO) therapy is widely used and approved by Center for Medicare and Medicaid Services to treat specific ulcerations. The current literature supports the notion that approaches to topically oxygenate wounds may be productive. 4. Here, we present the results of two simultaneous studies testing the effects of HBO and portable topical oxygen (TO) therapies. These two therapeutic approaches have several contrasting features. 5. In total, 1854 patients were screened in outpatient wound clinics for non-randomized enrolments into the HBO (n = 32; 31% diabetic) and TO (n = 25; 52% diabetic) studies. 6. Under the conditions of the present study, HBO treatment seemed to benefit some wounds while not benefiting others. Overall, HBO did not result in statistically significant improvements in wound size in the given population over the time monitored in the present study. 7. However, TO significantly improved wound size. Among the three O(2)-sensitive genes (VEGF, TGFbeta1 and COL1A1) studied in wound edge tissue biopsies, TO treatment was associated with higher VEGF165 expression in healing wounds. Expression of the other genes mentioned was not affected by TO. There was no significant change in the expression levels of any of genes studied in patients in the HBO study. This establishes a link between VEGF gene expression and healing outcome for TO therapy. 8. Taken together, the present study provides evidence demonstrating that TO treatment benefits wound healing in patients suffering from chronic wounds. Treatment with TO is associated with an induction of VEGF expression in wound edge tissue and an improvement in wound size.

051 Topical Oxygen Alters Angiogenesis-Related Growth Factor Expression in Chronic Diabetic Foot Ulcers

Objective: Following tissue vascular and oxygen delivery disruption, normal wound healing is a complex process requiring restoration of supplies of oxygen and other nutrients through blood vessel regeneration, or angiogenesis. Angiogenesis is stimulated by synergistic interactions of growth factors and cytokines secreted by damaged cells in wound tissues exhibiting hypoxia, high lactate levels, and inflammation. Chronic wounds, often complications of diabetes, are characterized by chronic hypoxia, inflammation, and insufficient growth factor secretion. To test growth factor sensitivity to reversed hypoxia in chronic human wounds, we administered pure oxygen topically to chronic foot ulcers in diabetic humans and used molecular probes to measure growth factors previously found to regulate angiogenesis and improve delayed healing, i.e., VEGF et al. Methods: By multiplex ELISA assays of growth factor cytokines, we quantified pg/ug levels of total proteins detectable in fluids collected from human diabetic plantar wounds after exposure to topical oxygen delivered in 0–50 mm Hg pulses during 90-minute treatments 4 days per week over a 5 week protocol. Wounds that had failed to heal for at least 4 weeks were infused with a maximum of 1.06 ATM of oxygen at 1 minute intervals in a lower limb enclosing chamber. Findings: Our initial data show increased expression in angiogenesis-related growth factors (bFGF, HB-EGF, HGF, KGF, VEGF) in wound fluid from chronic diabetic foot ulcers using the Topical Hyperbaric Oxygen Chamber (Advanced Hyperbaric Technologies, Inc., Farmingdale, NJ). Secretion of the most crucial angiogenic factor, VEGF, was increased by 8-fold to well over 10-fold using the described protocol. Conclusions: These data show evidence of a molecular mechanism for the scientific basis of topical hyperbaric oxygen-modulated growth factor expression in chronic diabetic wounds, previously unresponsive to standard wound care. We conclude that topically applied hyperbaric oxygen alters angiogenesis-related growth factor expression in wound fluids from chronic diabetic foot ulcers in a manner consistent with renewed healing. Acknowledgments: Advanced Hyperbaric Technologies, Inc., Farmingdale, NJ.

The Role of Oxygen in Wound Healing: A Review of the Literature

The presence of oxygen is necessary for normal wound healing. Oxygen has been given as a therapeutic modality to assist and speed wound healing. The objective was to summarize the role of oxygen in wound healing. A literature review of clinical and basic science studies regarding oxygen and wound healing was conducted. Hypoxia appears to jump start wound healing via hypoxia-inducible factor 1alpha and reepithelialization. Nonetheless, oxygen is often required to start or sustain other wound healing processes. Both the absence and the presence of oxygen have effects on wound healing; however, its role is not completely understood. Although hyperbaric oxygen and topical oxygen therapy have been described in aiding wound healing, case-controlled prospective studies are lacking and evidence for their efficacy is inconsistent. The authors have indicated no significant interest with commercial supporters.