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Evaluation the Effectiveness of Combinative Treatment of Cold Plasma Jet, Indonesian Honey, and Micro-Well Dressing to Accelerate Wound Healing
Abstract
A combinative treatment of cold plasma jet, honey solution, and micro-well dressing to accelerate acute wound healing of mouse skin was evaluated. A honey solution 1% in phosphate-buffered saline (PBS) 20 µL was dropped into micro-well dressing that is attached on an acute wound before a 2-minute cold plasma treatment. An inclined treatment style plasma jet with a 45° gradient was used. An infrared thermal camera was used to monitor the fate of the solution. To evaluate its effect, macroscopic evaluation and general staining were conducted. It was revealed that a combination of that honey and plasma treatment may not be efficacious. However, the related procedure functionalising micro-well dressing may provide a new insight in how to combine plasma jets and other solutions in animal or human models for skin-oriented treatment.
... Upaya memadukan plasma medis dan cairan untuk mengoptimasi kinerja plasma medis untuk penyembuhan luka sebelumnya telah dilakukan [12,13]. Telah dilaporkan bahwa kombinasi perlakuan plasma jet dan air dalam volume mikroliter mampu mempercepat penyembuhan luka akut non diabetik dengan cara mempromosikan inflammasi dan kontraksi luka secara signifikan dibandingkan hanya perlakuan plasma saja. ...
... Telah dilaporkan bahwa kombinasi perlakuan plasma jet dan air dalam volume mikroliter mampu mempercepat penyembuhan luka akut non diabetik dengan cara mempromosikan inflammasi dan kontraksi luka secara signifikan dibandingkan hanya perlakuan plasma saja. Nasruddin et al [13] juga telah mengkaji tentang efek perlakuan kombinatif plasma medis dan larutan madu berkonsentrasi rendah yang ditopang oleh pembalut berlubang (microwell dressing) bagi penyembuhan luka. Sementara Wahyuningtyas et al [14] telah melakukan studi perbandingan tentang potensi madu Manuka dan madu Indonesia guna mengoptimasi efektivitas plasma medis dalam mempercepat penyembuhan luka. ...
... Sementara Wahyuningtyas et al [14] telah melakukan studi perbandingan tentang potensi madu Manuka dan madu Indonesia guna mengoptimasi efektivitas plasma medis dalam mempercepat penyembuhan luka. Namun, obyek penelitian Nasruddin et al [13,14] dan Wahyuningtyas et al [14] adalah luka akut non diabetik. Hingga kini, penelitian dengan metode tersebut belum ada yang ditujukan pada luka diabetik. ...
The continued increase in the number of people with Diabetes Mellitus (DM) in Indonesia is a serious problem. One of the big problems for people with Diabetes Mellitus (DM) is the emergence of complications of diabetic wounds. To date the strategy for treatment of diabetic wounds has been limited to the use of wound dressing, cell therapy and oxygen therapy. The problem is that the strategy is not fully successful. Thus, it is very important to look for new strategies to improve the quality of diabetic wound healing, such as by applying a combination of plasma medicine and local natural product, like the extraction of Daun sirih (Piper betle) leaves. Plasma medicine is a relatively new and multidisciplinary study involving plasma science, biomedical, pharmaceutical and other health sciences aimed at applying plasma to therapeutic health. Plasma is the fourth phase of matter, after the solid, liquid and gas phase. The medical aspects of plasma are related to the ability of plasma to produce biological molecules Reactive Oxygen and Nitrogen Species (RONS). If RONS is controlled in the right dosage it can be efficacious for health therapy. This study intends to examine the effects of combinative treatment of plasma medicine and Piper betel leaf extract for proliferation phase of wound healing in diabetic small animal model. This study used male Balb c mice with acute wounds which were divided into 5 groups, namely groups of untreated normal mice (ND-TP), groups of untreated diabetic mice (D-TP), groups of diabetic mice wounds with Piper betel leaf extract (DS ), the wound group of diabetic mice with plasma medicine (DP) and the wound group of diabetic mice with plasma medicine and Piper betel leaf (DPS). The plasma medicine was treated on wound with condition non-contact style (the plasma jet did not touch the wound) with a distance of plasma jet reactor nozzle to the surface of wound about 20 mm, for 2 minutes, every day. Macroscopic observation of wounds is carried out every day from day 0 to 7. On day 7 it was seen that the size of the wound area for D-P-S was smaller than the other groups. The results of this study indicated that Piper betel leaf extract can potentially be used to optimize the performance of plasma medicine in accelerating diabetic wound healing during the proliferation phase. Further investigation, however, is important to be conducted to study the effect for all phases of wound healing and its mechanism histo-pathologically.
... Upaya memadukan plasma medis dan cairan untuk mengoptimasi kinerja plasma medis untuk penyembuhan luka sebelumnya telah dilakukan [12,13]. Telah dilaporkan bahwa kombinasi perlakuan plasma jet dan air dalam volume mikroliter mampu mempercepat penyembuhan luka akut non diabetik dengan cara mempromosikan inflammasi dan kontraksi luka secara signifikan dibandingkan hanya perlakuan plasma saja. ...
... Telah dilaporkan bahwa kombinasi perlakuan plasma jet dan air dalam volume mikroliter mampu mempercepat penyembuhan luka akut non diabetik dengan cara mempromosikan inflammasi dan kontraksi luka secara signifikan dibandingkan hanya perlakuan plasma saja. Nasruddin et al [13] juga telah mengkaji tentang efek perlakuan kombinatif plasma medis dan larutan madu berkonsentrasi rendah yang ditopang oleh pembalut berlubang (microwell dressing) bagi penyembuhan luka. Sementara Wahyuningtyas et al [14] telah melakukan studi perbandingan tentang potensi madu Manuka dan madu Indonesia guna mengoptimasi efektivitas plasma medis dalam mempercepat penyembuhan luka. ...
... Sementara Wahyuningtyas et al [14] telah melakukan studi perbandingan tentang potensi madu Manuka dan madu Indonesia guna mengoptimasi efektivitas plasma medis dalam mempercepat penyembuhan luka. Namun, obyek penelitian Nasruddin et al [13,14] dan Wahyuningtyas et al [14] adalah luka akut non diabetik. Hingga kini, penelitian dengan metode tersebut belum ada yang ditujukan pada luka diabetik. ...
The continued increase in the number of people with Diabetes Mellitus (DM) in Indonesia is a serious problem. One of the big problems for people with Diabetes Mellitus (DM) is the emergence of complications of diabetic wounds. To date the strategy for treatment of diabetic wounds has been limited to the use of wound dressing, cell therapy and oxygen therapy. The problem is that the strategy is not fully successful. Thus, it is very important to look for new strategies to improve the quality of diabetic wound healing, such as by applying a combination of plasma medicine and local natural product, like the extraction of Daun sirih (Piper betle) leaves. Plasma medicine is a relatively new and multidisciplinary study involving plasma science, biomedical, pharmaceutical and other health sciences aimed at applying plasma to therapeutic health. Plasma is the fourth phase of matter, after the solid, liquid and gas phase. The medical aspects of plasma are related to the ability of plasma to produce biological molecules Reactive Oxygen and Nitrogen Species (RONS). If RONS is controlled in the right dosage it can be efficacious for health therapy. This study intends to examine the effects of combinative treatment of plasma medicine and Piper betel leaf extract for proliferation phase of wound healing in diabetic small animal model. This study used male Balb c mice with acute wounds which were divided into 5 groups, namely groups of untreated normal mice (ND-TP), groups of untreated diabetic mice (D-TP), groups of diabetic mice wounds with Piper betel leaf extract (DS ), the wound group of diabetic mice with plasma medicine (DP) and the wound group of diabetic mice with plasma medicine and Piper betel leaf (DPS). The plasma medicine was treated on wound with condition non-contact style (the plasma jet did not touch the wound) with a distance of plasma jet reactor nozzle to the surface of wound about 20 mm, for 2 minutes, every day. Macroscopic observation of wounds is carried out every day from day 0 to 7. On day 7 it was seen that the size of the wound area for D-P-S was smaller than the other groups. The results of this study indicated that Piper betel leaf extract can potentially be used to optimize the performance of plasma medicine in accelerating diabetic wound healing during the proliferation phase. Further investigation, however, is important to be conducted to study the effect for all phases of wound healing and its mechanism histo-pathologically.
... Nasruddin et al. [33] reported that a combination of plasma jet and water in a micro-litre volume was able to significantly accelerate the healing of acute wounds by promoting wound contraction, compared to plasma treatment alone. Nasruddin et al [34] also studied the effects of medical plasma treatment combined with low-concentration honey solutions supported by microwell dressings for wound healing, but the result was not significant. Wahyuningtyas et al [35] reported that a combination of plasma jet and Manuka honey is more effective than a combination of plasma jet and Indonesian honey for the improvement of acute wound healing. ...
... An atmospheric pressure plasma jet system that was developed based on Teschke et al. [42] and described previously [34] was applied in this experiment. A modification of the dimensions of the capillary quartz tube was conducted. ...
... The experimental animals, namely, Balb cmice, were anaesthetized via the peritoneal cavity by injection of 50 mg/kg ketamine (K) and 5 mg/kgxylazine (X) [45]. The protocol to make an acute wound on a small animal as described previously [34] was adopted. This protocol was applied to create 2 disc-shaped (4 mm in diameter), full-thickness skin wounds, including the panniculus, on both sides of the mouse dorsum using a disposable 4 mm biopsy punch. ...
Purpose: An investigation was carried out to determine the effect of an ethanolic extract of the natural product of Daun sirih or Piper betle leaves on the effectiveness of plasma jet treatment for cutaneous acute wound healing in a small animal model mimicking a clinical setting. Method: An atmospheric plasma jet using medical grade argon gas as a carrier gas was developed. The ethanolic extract of Piper betle leaf (EPB) was formulated. Optical emission spectroscopy and chemical methods were applied to evaluate the presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gas phase and in aqueous and ethanolic media. Small animals were classified into 5 groups, namely, Control (C), Plasma jet (P), Ethanolic extract of Piper betle leaf (EPB), Plasma jet followed by EPB (P-EPB) and EPB followed by plasma jet (EPB-P). The contact and meander styles of plasma jet treatment for wounds were applied daily on acute wounds for 1 min, either alone or before or after EPB treatments. Visual evaluation of wounds was conducted for 14 days. Microscopic evaluation was conducted on days 7, 11 and 14. General staining, namely, haematoxylin-eosin and Azan staining, was conducted to evaluate neoepithelialisation and new collagen formation. Results: This research showed that wound healing in the P group was faster than that in the other groups, while that in groups containing EPB was the same as that in C. In the P group, the number of days to reach peak inflammation was the fewest. On day 7, neoepithelialisation and new collagen formation in P were significantly higher than those in other groups. Conclusion: Plasma jet treatment alone is able to promote inflammation, neoepithelialisation and new collagen formation to accelerate acute wound healing; however, its admixture with EPB may impede such effectiveness. Based on the characterization of the ROS and RNS results, the ethanol solvent may play a primary role in impeding its effectiveness.
... The efficacy of a combinative treatment of plasma jets and distilled water for acute wound healing using small experimental animals has recently been reported [30]. The possibility of a combinative treatment involving plasma medicine and liquid containing natural products derived from honey was also reported, but its efficacy to support wound healing was low [31]. ...
... Two types of honey with different origins, namely Indonesian and Manuka honeys, were used. As plasma jet treatment has been found to be more effective during the proliferative wound-healing phase [30][31][32], plasma treatments were only conducted during the aforementioned phase, on days 3 till 7. ...
... This research used an atmospheric pressure plasma jet system in which plasma is applied perpendicular to the wound. This system was developed based on Teschke et al. [33] and has been described previously [31]. It had a quartz tube with inner and outer diameters were 1.5 and 2.7 mm, respectively. ...
A comparative investigation was conducted to determine the effectiveness of Manuka and Indonesian honeys to support the application of plasma jet treatment during the proliferative phase of cutaneous wound healing in 8-week-old, BALB/c male mice. The effect of honey containing different concentrations to reactive oxygen and nitrogen species (RONS) produced by plasma jet in liquid medium using H2O2 as the indicator was conducted using chemical-enzymatic method. Plasma jet treatment was applied perpendicularly to wounds through holes punched in multiple micro-well dressings (MMD) using direct contact. Mice were divided into 4 groups: Hydrocolloid dressing alone (Control group or C), plasma application followed by hydrocolloid dressing (PH), plasma application followed by treatment with Indonesian honey (PI), and plasma application followed by treatment with Manuka honey (PM). Two full-thickness acute wounds were created on both sides of the mouse dorsum using a disposable biopsy punch. The wounds of the control group were covered with a hydrocolloid dressing (HD), whereas wounds in the other groups were covered with a HD from days 0 to 3, treated with plasma followed by 0.1 mL of the relevant honey or HD from days 4 to 7 post-wounding, and then were covered with a HD from days 8 to 14. Results showed that on day 7the wound area in the PI and PM groups was smaller than in the control group. On days 12, 13, and 14, however, the wound area in PI-treated mice was significantly larger than in PM mice. It is hypothesized that Manuka honey may better support plasma jet treatment than Indonesian honey on account of its chemical characteristics.
... Although glucose is a monomer, it is worth mentioning for the sake of completeness that glucose solutions were also treated by plasma either with the purpose of generating H2 [131] (the reader may compare this research with the earlier cited works of the same authors on cellulose [112,113] and lignin [126]) or to use glucose (fructose and sucrose as well) as inducers for the synthesis of porous MnO2 from KMnO4 solutions [132]. Furthermore, honeys (natural mixtures of glucose, fructose and other minor components) activated by atmospheric pressure plasma jet were suggested to be used for acute wound healing [133,134]. Although no decisive evidence was obtained about the favorable effect of such treatment on the acceleration of wound healing, the research highlights the scientific interest emerging in the medicine-oriented community to find non-conventional solutions of therapeutic issues. ...
... Т. 62. Вып. 7 1 2 3 honey solution in phosphate buffer saline above-liquid Ar AC plasma jet positive supportive effect on acute wound healing [133,134] Sodium alginate sodium alginate in H2O in-liquid bi-polar pulsed discharge with W electrodes depolymerization of sodium alginate [136] sodium alginate in HAuCl4 in-liquid bi-polar pulsed discharge with W electrodes ...
Non-equilibrium low-temperature atmospheric pressure plasma is a highly reactive medium that allows for the ecofriendly modification of nature-derived materials. This work reviews the field of liquid phase plasma modification of polymer-based materials derived from natural sources. Types of solution plasma systems are considered with respect to the efficiency of the generation of active species, their transport to and interaction with macromolecules. Tunable modification of plants (birch, willow, bamboo and vine shoots; barley, rice and rapeseed straw; perennial grasses), algae, plant-derived by-products and wastes (sawdust, bast fibers, nutshells, seeds, peels, press-cake and pomace), plant-derived polymers (cellulose, hemicellulose, lignin, starch, sodium alginate) and animal-derived polymer-based materials (chitosan, collagen, gelatin) by solution plasma treatment is compared to conventional wet chemistry methods. Synthesis of nano-biocomposites with advanced functionalities is also considered. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . </span
... Ozone also has a unique biological ability that is so much studied for use in the medical world [4]. It promotes the treatment of diabetes mellitus by reducing blood sugar levels and increasing oxygen supply into tissues [5,6]. Christopher Friedrich Schoonbein first used ozone to treat wounds and infections caused by anaerobic bacteria [5]. ...
... It promotes the treatment of diabetes mellitus by reducing blood sugar levels and increasing oxygen supply into tissues [5,6]. Christopher Friedrich Schoonbein first used ozone to treat wounds and infections caused by anaerobic bacteria [5]. Ozone can be delivered by EBOO (Extracorporeal Blood Oxygenation and Ozonation) method for wound healing therapy [7]. ...
Abstract.
The development of the reactor for a lower concentration of ozone need to be done. The tipe of reactor can be used for the application of medical ozone therapy. Medical ozone therapy can be produced by using double DBD plasma reactor with oxygen as source and variation of voltage. The influence of flowrate to ozone capacity was investigated using double DBD plasma reactor with cylinder-cylinder configuration. The high AC voltage was applied in the range of 0-2000 Volts and the frequency of 50 Hz. The pure oxygen inserted into the reactor with several variations in flow rate, i.e. 2 to 10 L/min. The results showed that the ozone concentration decreased with increasing gas flow rate. I-V characteristic shows that reactor has two regime current as function of voltage. This characteristic is difference with single dielectric DBD Plasma reactor. The suitable dose of ozone therapy for medical other than useful in numerous pathological conditions could be a powerful therapeutic resource to prevent the damages of aging and to improve many functions in human bodies without deleterious effects.
... Plasma medicine in this study is not blood but the fourth phase of matter, after solids, liquids, and gases. The plasma is an ionized gas (ionized gas) because there is a stable part (gas) and a reactive part (ions, energetic particles, and radicals) [9]. ...
... Beberapa penelitian yang terkait dengan plasma medicine yang dilakukan oleh para peneliti di berbagai negara, memperlihatkan potensi yang sangat besar dalam penerapan disiplin ilmu ini dalam dunia dunia kesehatan. Beberapa penelitian dalam bidang plasma medicine, antara lain adalah pemanfaatan plasma dapat membasmi mikroorganisme pada luka kronis sekaligus penyembuhan pada kanker [3,4], dan perawatan luka pada binatang tikus yang memadukan penggunaan plasma dengan madu [5]. Sampai saat ini tahapan pengembangan plasma medicine masih dalam tataran penelitian yang berfokus pada penyempurnaan disain alat agar sempurna dan lebih aman digunakan untuk kulit manusia [6]. ...
Plasma medicine adalah kajian baru yang bersifat multidisiplin yang berupaya menerapkan teknologi plasma untuk terapi kesehatan, seperti perawatan luka dan penyembuhan kanker. Pada saat ini plasma medicine penggunaanya masih berbasis manual yang pengoperasiannya mempunyai resiko tinggi pada manusia sebagai operator mesin. Penelitian ini bertujuan untuk merancang sebuah alat yang mampu menggerakan plasma medicine secara otomoatis dengan pengendali jarak jauh untuk mengurangi resiko kecelakaan kelistrikan pada operator manusia. Alat ini menggunakan konsep pada mesin cnc, drawing machine, dan axidraw yang di gerakan dengan 2 motor stepper nema 17 dan dikendalikan oleh komputer melalui arduino uno, lalu plasma medicine ditempatkan pada ujung alat ini. Diharapkan plasma medicine dapat digerakan secara leluasa dan menghasilkan hasil yang lebih optimal.
... Nasruddin and colleagues not only identified improved healing responses in Balb/c mice using an Ar plasma jet [85] but also determined in a follow-up study that moisturized wounds markedly increase the extent of gas plasma-promoted wound healing and myofibroblast formation [86]. However, combining with other methods, for example, medical honey, was less successful [87,88]. Such wound pre-conditioning has otherwise received only little attention in plasma medicine wound studies so far. ...
Defective wound healing poses a significant burden on patients and healthcare systems. In recent years, a novel reactive oxygen and nitrogen species (ROS/RNS) based therapy has received considerable attention among dermatologists for targeting chronic wounds. The multifaceted ROS/RNS are generated using gas plasma technology, a partially ionized gas operated at body temperature. This review integrates preclinical and clinical evidence into a set of working hypotheses mainly based on redox processes aiding in elucidating the mechanisms of action and optimizing gas plasmas for therapeutic purposes. These hypotheses include increased wound tissue oxygenation and vascularization, amplified apoptosis of senescent cells, redox signaling, and augmented microbial inactivation. Instead of a dominant role of a single effector, it is proposed that all mechanisms act in concert in gas plasma-stimulated healing, rationalizing the use of this technology in therapy-resistant wounds. Finally, addressable current challenges and future concepts are outlined, which may further promote the clinical utilization, efficacy, and safety of gas plasma technology in wound care in the future.
Acute wounds are injuries that occur suddenly to tissues that are prone to the risk of being infected. Therefore, acute wound care must be considered carefully. Piper betle leaf contains flavonoids that have a function in the wound healing process, Manuka honey also contains vitamins that can support the healing phase. The combination of Piper betle L. and manuka honey is made into a spray gel preparation because it has advantages over other topical preparations. The purpose of this study is to see how well a combination wound healing spray gel of Piper betle L. and Manuka honey works on an acute wound in mice. This study uses experimental research with a randomized, matched post-test-only control group design. The formulation taken was maceration extraction from Piper betle L. Simplicia powder with 70% ethanol then evaporated to acquire a concentrated concentrate. Spray gel preparations of a combination of Piper betle L extract and manuka honey were made with a concentration of 1% Piper betle L and Manuka honey, 3% Piper betle L and Manuka honey, and 5% Piper betle L and Manuka honey. Balb/c mice that had full-thickness acute wounds were divided into 7 treatment groups, namely SM1, SM2, SM3, M, KP, B, and D. Mice were treated for 14 days and the wound area ratio was calculated and analyzed by ANOVA. The test results showed a significant difference between groups SM3-M, SM5-M, M-SM3, M-SM5, KP-M, B-SM3, and BM with a significance value below 0.05 (p≤0.05) which proves that the spray gel combination of Piper betle L extract and Manuka honey, oxoferin, and base both have activity in accelerating acute wound healing.
Chronic wounds develop as a result of infection, commonly carried on by bacteria and form biofilms. MRSA is a kind of bacteria that can form biofilms. Recently, medical plasma technology has been applied to accelerate wound healing. The objective of the research was to investigate the response of cutaneous wounds in MRSA-infected animals to contact and non-contact therapy using medical plasma argon jet-type with histopathological and molecular approaches. Argon gas, with a purity of 99.995%, is utilized as a carrier gas for generating plasma medical at a flow rate of 1 standard liter per minute (slm). This experiment was divided into 4 treatment groups, K (infected wound without plasma treatment), CP (5 mm plasma treatment), NCP (20 mm plasma treatment), and CP-NCP (infected wound with 5 mm and 20 mm plasma combination treatment). The result of the observation obtained that contact plasma from day 3 to day 10 can remove bacterial biofilm and that non-contact plasma treatment from day 11 to day 16 is effective to accelerate wound healing. At day 17, the macroscopic biofilm area in the CP-NCP group began to decrease with an increasing percentage of re-epithelialization, and no necrotic cells were observed. TNF-α levels were observed significantly lower in the CP-NCP group at day 17 compared with other groups. In conclusion, contact-non-contact (CP-NCP) treatment is suggested for the management of chronic infections since it is beneficial for removing the bacterial biofilm layer and can promote wound healing.
Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model.
Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF, and CD34 levels were measured from the immunostained slices of wound margins.
Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF, and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations.
Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.
The loss of skin integrity is inevitable in life. Wound healing is a necessary sequence of events to reconstitute the body’s integrity against potentially harmful environmental agents and restore homeostasis. Attempts to improve cutaneous wound healing are therefore as old as humanity itself. Furthermore, nowadays, targeting defective wound healing is of utmost importance in an aging society with underlying diseases such as diabetes and vascular insufficiencies being on the rise. Because chronic wounds’ etiology and specific traits differ, there is widespread polypragmasia in targeting non-healing conditions. Reactive oxygen and nitrogen species (ROS/RNS) are an overarching theme accompanying wound healing and its biological stages. ROS are signaling agents generated by phagocytes to inactivate pathogens. Although ROS/RNS’s central role in the biology of wound healing has long been appreciated, it was only until the recent decade that these agents were explicitly used to target defective wound healing using gas plasma technology. Gas plasma is a physical state of matter and is a partially ionized gas operated at body temperature which generates a plethora of ROS/RNS simultaneously in a spatiotemporally controlled manner. Animal models of wound healing have been vital in driving the development of these wound healing-promoting technologies, and this review summarizes the current knowledge and identifies open ends derived from in vivo wound models under gas plasma therapy. While gas plasma-assisted wound healing in humans has become well established in Europe, veterinary medicine is an emerging field with great potential to improve the lives of suffering animals.
Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model.
Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF and CD34 levels were measured from the immunostained slices of wound margins.
Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations.
Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.
Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model.
Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF and CD34 levels were measured from the immunostained slices of wound margins.
Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations.
Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.
Purpose
This investigation aimed to compare the effectiveness of two styles of plasma jet treatment (i.e., contact and non-contact styles) for two biological materials, namely, wound related bacteria and acute wounds.
Method
An atmospheric plasma jet operated at a frequency of 18.32 kHz and high AC voltage with a peak-to-peak voltage of 9.58 kV and a current of 55.2 mA was applied. Argon gas was used as the carries gas of plasma jet generation and was fixed at a flow rate of 1 standard liters per minute (slm).Two biological materials (i.e., wound related bacteria and acute wound) were applied as experimental objects. The sample groups were based on the two styles of plasma jet treatment: contact and non-contact styles. Microbial inhibition zone calculation and macroscopic and histological observations were also performed.
Results
This investigation emphasized that the contact and non-contact styles of plasma jet treatment had significantly different effects for wounds and wound-related chronic bacteria. On the one hand, the contact style was visually attractive and more effective for inactivate bacteria. On the other hand, it caused negative effects, such as damaging normal tissue, significantly impeding wound healing and impeding the growing of new epithelial tissue. The non-contact style, however, was less effective at inactivating bacteria; however, it could accelerate wound healing.
Conclusion
In the context of wound healing, the non-contact style of plasma jet treatment may be better than the contact style of plasma jet treatment.
Plasma-treated water (PTW), i.e. distilled water (DW) exposed to low-temperature atmospheric pressure helium plasma, exhibited strong bactericidal activity against Escherichia coli in suspension even within a few minutes of preparation. This effect was enhanced under acidic conditions. The bactericidal activity of PTW was attenuated according to first-order kinetics and the half-life was highly temperature dependent. The electron spin resonance (ESR) signal of an adduct of the superoxide anion radical () was detected in an aqueous solution using a spin-trapping reagent mixed with PTW, and adding superoxide dismutase to the PTW resulted in a loss of the bactericidal activity and weakening of the ESR adduct signal of in the spin-trapping. These results suggest that plays an important role in imparting bactericidal activity to PTW. Moreover, molecular nitrogen was required both in the ambient gas and in the DW used to prepare the PTW. We, therefore, suggest that the reactive molecule in PTW with bactericidal effects is not a free reactive oxygen species but nitrogen atom(s)-containing molecules that release , such as peroxynitrous acid (ONOOH) or peroxynitric acid (O2NOOH). Considering the activation energy for degradation of these species, we conclude that peroxynitric acid stored in PTW induces the bactericidal effect.
Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.
Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen species and other components of plasma. The outcome of first clinical trials regarding wound healing is pointed out.
Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo-treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.
The purpose of this study was to investigate the effectiveness of Indonesian honey in wound healing compared to Tegaderm hydrocolloid dressing and Manuka honey. Three groups of male mice were treated to produce 2 circular, full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Manuka honey, or hydrocolloid (control). Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic findings on days 3, 7, 11, and 14 after wounding were obtained. The ratios of wound areas for honey groups on day 3 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the control group wound area peaked on day 5 and rapidly decreased until day 14. On day 3, myofibroblasts and new blood capillaries in wound tissue of honey groups were observed, but were not seen in the control group. After day 7, microscopic findings were almost the same among the 3 groups. These results indicate that Indonesian honey is almost as effective for wound healing as Manuka honey and hydrocolloid dressing. .
An emerging field of plasma medicine is discussed, where non‐equilibrium plasmas are shown to be able to initiate, promote, control, and catalyze various complex behaviors and responses in biological systems. More importantly, it will be shown that plasma can be tuned to achieve the desired medical effect, especially in medical sterilization and treatment of different kind of skin diseases. Wound healing and tissue regeneration can be achieved following various types of plasma treatment in a multitude of wound pathologies. Non‐equilibrium plasmas will be shown to be non‐destructive to tissue, safe, and effective in inactivation of various parasites and foreign organisms.
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Plasma is an ionised gas that is typically generated in high-temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature.
Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells.
We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated.
The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.
Previously we have reported in vitro evidence suggesting that that H2O2 may support wound healing by inducing VEGF expression in human keratinocytes (C. K. Sen et al., 2002, J. Biol. Chem.277, 33284-33290). Here, we test the significance of H2O2 in regulating wound healing in vivo. Using the Hunt-Schilling cylinder approach we present the first evidence that the wound site contains micromolar concentrations of H2O2. At the wound site, low concentrations of H2O2 supported the healing process, especially in p47(phox)- and MCP-1-deficient mice in which endogenous H2O2 generation is impaired. Higher doses of H2O2 adversely influenced healing. At low concentrations, H2O2 facilitated wound angiogenesis in vivo. H2O2 induced FAK phosphorylation both in wound-edge tissue in vivo and in human dermal microvascular endothelial cells. H2O2 induced site-specific (Tyr-925 and Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H2O2. Adenoviral gene delivery of catalase impaired wound angiogenesis and closure. Catalase overexpression slowed tissue remodeling as evidenced by a more incomplete narrowing of the hyperproliferative epithelium region and incomplete eschar formation. Taken together, this work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes.
Honey-impregnated wound dressings are now available on drug tariff in the UK, though the modes of action of honeys with antibacterial and wound healing properties are not entirely clear. The action of some but not all of these honeys is linked to the production of hydrogen peroxide on dilution of the honey with wound exudate. The present study investigates both free radical production and the antioxidant potential of some honeys, properties which may have a role to play in wound healing.
Free radical production and quenching of three honey types (manuka, antibacterial but non-peroxide-producing; pasture, antibacterial peroxide-producing; commercial heat processed, non-antibacterial) was investigated by electron paramagnetic resonance (EPR) spectroscopy; quenching was also examined using a superoxide quenching assay.
All honeys tested had antioxidant potential, with manuka able to completely quench added radicals within 5 min of spiking. Only the peroxide-producing honey (pasture PS9) was found to form radicals on dilution.
The ability to modulate production and quenching of free radicals may contribute to the demonstrated ability of some honeys to help in resolving the state of inflammation typifying chronic wounds.
Background:
Secondary nasal deformities and retardation of development due to treatment of nasal hemangioma during infancy are a challenge when it comes to nasal reconstruction. In order to evaluate nasal repair and reconstruction in these patients, the authors compared the ease and outcomes of using expanded forehead, nasolabial sulcus, and medial upper arm tube flaps.
Methods:
According to the deformities and patients' wishes, flaps were selected; using autogeneic rib cartilage, auricle cartilage, or silica gel as a scaffold or without framework; the inner lining were made by the residual scar tissue or the distal end of transferred flap. The esthetical and functional scores were recorded by the Nasal Appearance and Function Evaluation Questionnaire score to evaluate the effectiveness of the methods.
Results:
From January 2010 to December 2015, 34 patients were included. Postoperative follow-up went for 12 to 36 months. The expanded forehead flap was used in 28 patients, the nasolabial sulcus flap in 5 patients, and the medial upper arm tube flap in 1 patient. Regarding framework, 20 patients used rib cartilage, 8 patients used auricle cartilage, 1 patient used silicone, and 5 patients did not use any framework. All patients reported the increasing nasal appearance and function evaluation.
Conclusion:
Repair of secondary nasal defects following treatment of hemangiomas in infants and young children using an expanded frontal flap and autogenous cartilage framework is a reliable method with great long-term esthetic results. The nasolabial sulcus flap is a relatively simple method, especially for patients with a unilateral nasal alar defect. Supporting structure is needed and appropriate overcorrection is necessary.
Thermal imaging detects infrared radiation from an object, producing a thermogram that can be interpreted as a surrogate marker for cutaneous blood flow. To date, high-resolution cameras typically cost tens of thousands of dollars. The FLIR ONE is a smartphone-compatible miniature thermal imaging camera that currently retails at under $200. In a proof-of-concept study, patients and healthy volunteers were assessed with thermal imaging for (1) detecting and mapping perforators, (2) defining perforasomes, and (3) monitoring free flaps. Preoperative, intraoperative, and postoperative thermograms can assist in the planning, execution, and monitoring of free flaps, and the FLIR ONE provides a low-cost adjunct that could be applied to other areas of burns and plastic surgery.
Honey is known as a popular healing agent against tropical infections and wounds. However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing under hypoxic condition is still not explored. In this study, we examined whether honey dilution have wound healing potential under hypoxic stress. The anti-oxidant potential and healing efficacy of honey dilution on in vitro wound of human epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2 ) and normoxia is explored by NBT assay. The cell survival % quantified by MTT assay to select 4 honey dilutions like 10, 1, 0.1 and 0.01 v/v % and the changes in cellular function was observed microscopically. Further, the cell proliferation, migration, cell-cell adhesion and relevant gene expression were studied by flow-cytometry, migration/scratch assay, immuno- cytochemistry and RT-PCR respectively. The expression pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F-actin, p63 and hypoxia marker Hif 1 α were examined. Honey dilution in 0.1% v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%). Its wound healing potential was quantified by immuno-cytochemistry and real-time PCR for the associated molecular features that were responsible for cell proliferation and migration. Our data showed that honey dilution can be effective in hypoxic wound healing. Additionally, it reduced superoxide generation and supplied favorable bio-ambience for cell proliferation, migration and differentiation during hypoxic wound healing. These findings may reveal the importance of honey as an alternative and cost effective therapeutic natural product for wound healing in hypoxic condition. This article is protected by copyright. All rights reserved.
© 2015 by the Wound Healing Society.
A simple technique is tested to improve the contractile effect of a cold plasma jet on acute wounds of mice. Distilled water on the order of microliters is dropped onto wounds before treatment. To assess the fate of the water, an infrared thermal imager is applied. To evaluate the healing effect, macroscopic and immunohistological studies are conducted. Regarding the wound contractile effect, we show that combination treatment of plasma with dropped water seemed to have a greater effect than plasma treatment alone. Plasma may modify the wound surface through such water, chemically and physically. The histological stiffness of the wound surface during maturation and remodeling, however, may also influence the fate of the water during treatment.
It has been about two and a half years since the publication of the first IEEE Special Issue dedicated to the “Atmospheric Pressure Plasma Jets and Their Applications” in November 2012. Fig. 1 shows the publications on the atmospheric pressure plasma jet (APPJ) in the last decade from Web of Science. It clearly shows that this topic has been significantly grown in the past one decade and is still growing.
Driven by extensive basic research on plasma effects on living cells and microorganisms, plasma medicine has been developed as innovative medical research field during the last years. Besides partially established applications of plasma to treat materials or devices to allow effective medical applications with respect to biocompatibility or microbiological safety, respectively, the primary focus of plasma‐medical research is the direct application of plasma as part of therapeutic concepts. Even if a huge number of atmospheric pressure plasma sources for biomedical applications are described in the literature and characterized by in vitro microbiology and cell biology, there is only a limited number of in vivo experience with animals or human beings up to now. Research in plasma medicine has been mainly focused on applications in dermatology and aesthetic surgery with the aim to support tissue regeneration to improve healing of infected and/or chronic wounds as well as to treat infective and inflamed skin diseases. In general, there are four cold atmospheric plasma sources which were tested comprehensively in animals as well as human beings with respect both to its therapeutic potential and the safety of its application.
Three clinical trials with cold atmospheric pressure plasma sources have been carried out yet. All three studies realized in Germany are focused on ulcer treatment. Two cold atmospheric pressure plasma sources got a CE marking as medical device in 2013. This marks a very important step to bring plasma medicine into the clinical daily routine!
In future, it will become a general practical requirement to adapt special plasma sources to specific medical applications. Consequently, it is one of the main requirements for the physical and technical field of research and development in plasma medicine to find solutions for modular and flexible plasma devices which are adaptive to some extent e.g. to variable target areas. Based on this as well as together with comprehensive basic research to get much more insight into detailed mechanisms of plasma‐induced effects on living structures and the particular role of single plasma components, further fields of plasma application in vivo will be opened or extended, respectively, with both new targets like cancer treatment or new application sites like teeth, lung, eyes, nasal cavity or gastrointestinal tract. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.
Atmospheric-pressure plasmas (APPs) have attracted great interest and have been widely applied in biomedical applications, as due to their non-thermal and reactive properties, they interact with living tissues, cells and bacteria. Various types of plasma sources generated at atmospheric pressure have been developed to achieve better performance in specific applications. This article presents an overview of the general characteristics of APPs and a brief summary of their biomedical applications, and reviews a wide range of these sources developed for biomedical applications. The plasma sources are classified according to their power sources and cover a wide frequency spectrum from dc to microwaves. The configurations and characteristics of plasma sources are outlined and their biomedical applications are presented.
Recently, a plasma flow has been applied to medical treatment using effects of various kinds of stimuli such as chemical species, charged particles, heat, light, shock wave and electric fields. Among them, the chemical species are known to cause an inactivation of cell viability. However, the mechanisms and key factors of this event are not yet clear. In this study, we focused on the effect of H2O2 in plasma-treated culture medium because it is generated in the culture medium and it is also chemically stable compared with free radicals generated by the plasma flow. To elucidate the significance of H2O2, we assessed the differences in the effects of plasma-treated medium and H2O2-added medium against inactivation of HeLa cell viability. These two media showed comparable effects on HeLa cells in terms of the survival ratios, morphological features of damage processes, permeations of H2O2 into the cells, response to H2O2 decomposition by catalase and comprehensive gene expression. The results supported that among chemical species generated in a plasma-treated culture medium, H2O2 is one of the main factors responsible for inactivation of HeLa cell viability.
Plasma medicine is a new medical field with first very promising practical
studies. However, basic research needs to be done to minimize risk and
provide a scientific fundament for medical therapies. Therapeutic
application of plasmas at or in the human body is a challenge both for
medicine and plasma physics. Today, concepts of tailor-made plasma sources
which meet the technical requirements of medical instrumentation are still
less developed. To achieve selected effects and to avoid potential risks, it
is necessary to know how to control composition and densities of reactive
plasma components by external operation parameters. Therefore, a profound
knowledge on plasma physics and chemistry must be contributed by physical
research. Therapeutic applications required cold, non-thermal plasmas
operating at atmospheric pressure. These plasmas are a huge challenge for
plasma diagnostics, because usually they are small scale, constricted or
filamentary, and transient. Regarding the manageability in everyday medical
life, atmospheric pressure plasma jets (APPJ) and dielectric barrier
discharges (DBD) are of special interest for medical applications. Working
in open air atmospheres, complex plasma chemistry must be expected.
Considering that, a great deal of effort combining experimental
investigation and modelling is necessary to provide the required knowledge
on plasma sources for therapeutic applications.
The mechanisms of generation and transportation of a chemically active species in a tube generated by dielectric barrier discharge have been analyzed by experimental and computational methods to elucidate the sterilization mechanism. The obtained results are: i) Nitrogen oxide is an important sterilization factor. ii) Two‐dimensional profiles of emission intensities that expand between the wire and ground in a cross section of the tube were generated by streamer propagation and relaxation processes. iii) A twin vortex was induced in the cross section of the tube by the discharge. Chemically active species, probably transported from the discharge region to the upper region of the tube by the twin vortex, were concentrated by the circular flow.
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Because light-emitting diodes (LEDs) are low-coherent, quasimonochromatic, and nonthermal, they are an alternative for low level laser therapy, and have photobiostimulative effects on tissue repair. However, the molecular mechanism(s) are unclear, and potential effects of blue and/or green LEDs on wound healing are still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm), and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the skin of ob/ob mice were significantly decreased on day 7 following exposure to green LEDs, and complete reepithelialization was accelerated by red and green LEDs compared with the control mice. To better understand the molecular mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts in vitro by measuring mRNA and protein levels of cytokines secreted by fibroblasts during the process of wound healing and on the migration of HaCat keratinocytes. The results suggest that some cytokines are significantly increased by exposure to LEDs, especially leptin, IL-8, and VEGF, but only by green LEDs. The migration of HaCat keratinocytes was significantly promoted by red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound healing by inducing migratory and proliferative mediators, which suggests that not only red LEDs but also green LEDs can be a new powerful therapeutic strategy for wound healing.
Research using low frequency atmospheric pressure plasma jets (LF jet) is becoming increasingly more common. We carried out experiments to evaluate the sterilizing effects of this technology on oral pathogenic microorganisms (S.mutans, C.albicans and E. faecalis) and to determine its potential for clinical application. We performed the direct exposure test on a solid surface, indirect exposure test on a liquid phase, and ROS (reactive oxygen species) inhibitory test. The results showed the LF jet had microbicidal effects on oral pathogens, and that the ROS influenced this sterilization effect. The experiments of this study revealed that LF jet had a sterilizing effect on oral pathogenic microorganisms present in both the solid and liquid phases. The sterilizing mechanism was considered to be related to the effect of superoxide anion radicals. These results indicate that LF jets may represent a novel technology that can be applied to the field of clinical dentistry.
Abundant evidence leaves no doubt that reactive oxygen species (ROS) are not only inevitable by-products of oxygen metabolism but also play a role in cellular signaling. ROS are produced by a family of NADPH oxidases for signaling purposes and mediate or augment the effects of insulin, growth factors, cytokines and G-protein-coupled receptors. Disturbances of ROS signaling leading to overproduction of these intermediates inflict oxidative damage of cell components in the course of various diseases. Restoration of proper ROS signaling, especially inhibition of cellular sources of ROS, may thus provide new ways of therapy.
Wound repair of the integument is reviewed in the context of new developments in cell biology and biochemistry. Injury of the skin and concomitant blood vessel disruption lead to extravasation of blood constituents, followed by platelet aggregation and blood clotting. These events initiate inflammation and set the stage for repair processes. The macrophage plays a pivotal role in the transition between wound inflammation and repair (granulation tissue formation), since this cell both scavenges tissue debris and releases a plethora of biologically active substances that include growth factors. Although concrete evidence is lacking, growth factors are probably at least partially responsible for the angiogenesis and fibroplasia (granulation tissue) that gradually fill the wound void. If the epidermal barrier is disrupted during injury, reepithelialization begins within 24 hours and proceeds first over the margin of residual dermis and subsequently over granulation tissue. The signals for angiogenesis, fibroplasia, neomatrix formation, and reepithelialization in wound repair are not known, but a number of possibilities are discussed. Matrix remodeling is the last stage of wound repair and gradually increases the scar tensile strength to 70% to 80% of normal skin.
WHERE there is a superficial wound in the skin, new epidermis covers the denuded area by migration from the hair follicles and sweat gland ducts within the wound and from the surface epidermis at the wound edges. It has been found that epithelization is retarded by the dry scab which normally covers a superficial wound, and if the formation of the scab is prevented, the rate of epithelization is markedly increased.
The propagation of an atmospheric pressure plasma jet (APPJ) is investigated by use of an intensified charge coupled device (ICCD) camera. It is shown that the APPJ is mainly an electrical phenomenon and not a flow related one. The jet does not consist of a voluminous plasma. Much more, the presented plasma source acts like a "plasma gun" blowing small "plasma bullets" out of its mouth. Furthermore, the interaction of the jet with a surface has been investigated.