Healing Effects of Iranian Dwarf Elder on Full-thickness Epidermal Thermal Injury in Wistar Rats

Background: Wound healing is a physiologic process that cells and tissues react when the skin is exposed to thermal injury. The inflammatory process has ‎essential effects on wound healing that includes coordination between immunological and biological responses. Chemical and herbal medicines are locally or systemically administrated to help wound healing. Herbal medicines have become more prevalent in recent years due to fewer side effects. Dwarf elder is used to treating inflammation and has been reported to possess antibacterial and antioxidant activities. This plant is also effective against burns, wounds, eczema, and infection. Objectives: In this study, we evaluated the topical application of dwarf elder on full-thickness epidermal thermal wounds in Wistar rats. Methods: Thirty adult male Wistar rats of about 300 g were used. The rats were randomly divided into three groups: Control group, vehicle group treated with an ointment base, and treatment group treated with elder ointment 10%. The animals were anesthetized and were created burn wounds with an area of 1 cm2 using the Meyer method. After 21 days, the wounds were photographed with a Canon camera. The wound area and healing degree were calculated. Slides were stained with H&E and examined by light microscopy and GraphPad Prism software. Data were analyzed by SPSS software using ANOVA and Tukey’s test. The significance level was considered at P < 0.05. Results: The wound area on the 21st day was significantly lower in the treatment group than in the control and vehicle groups. The epithelium thickness (μm) was significantly higher in the treatment group than in the control and vehicle groups. The blood vessels were significantly higher in the treatment group than in the other groups. Conclusions: The study showed that elder extract could be an effective remedy to repair and heal thermal injury and burn wounds.

THE USE OF IONTOPHORESIS WITH HYALURONIC ACID ASSOCIATED WITH GOLD NANOPARTICLES ACCELERATES WOUND HEALING IN RATS

This study aimed to investigate the effects of iontophoresis with HA associated to GNPs solution in an epithelial lesion model. Fifty Wistar rats (n=10/group) were randomly assigned to the following groups: epithelial lesion (EL); (EL+MIC); (EL+MIC+HA); (EL+MIC+GNPs); (EL+MIC+HA-GNPs). The animals induced to an epithelial lesion and treatment started 24 hours after injury with microcurrents (300µA) containing gel with HA (0.9%) and/or GNPs (30mg/Kg) in the electrodes (1mL) for seven days. The animals were sacrificed 12 hours after the last treatment application. Results demonstrated a reduction in the levels of pro-inflammatory cytokines (IFNϒ, IL-1β, TNFα, IL6) in the group in which the therapies were combined; an increase in the levels of anti-inflammatory cytokines (IL-4, IL-10) and growth factors (FGF, TGFβ) in EL+MIC+HA and EL+MIC+HA-GNPs groups. As for dichlorofluorescein (DCF) and nitrite levels, decreased in the combined therapy group when compared to the control group, as well as the oxidative damage (carbonyl and sulfhydryl). In antioxidant defense, there was an increase in glutathione (GSH) and a decrease in superoxide dismutase (SOD) in the combination therapy group. Histological analysis showed a reduction in the inflammatory infiltrate in groups treated with MIC and in the combination therapy group. An increase in contraction of the wound area was obtained in all treated groups when compared to the control group, proving that the proposed therapies are effective in the process of epithelial healing. The results of this study demonstrated that the associated therapies favor the tissue repair process more significantly compared to the isolated therapies.

Pulse Voltage Electrical Stimulation for Bacterial Inactivation and Wound Healing in Mice with Diabetes

Background: Treatment of wounds in diabetes often gets less than perfect healing. One of the reasons for the difficulty in treating wounds in diabetes is the growth of aerobic and anaerobic bacteria. This study aims to determine the pulse voltage and treatment time that can optimally inactivate bacteria, and their effect on wound healing in mice suffering from diabetes. Methods: The study used electrical stimulation with a direct voltage of 10 volts given a pulse voltage of 50-80 volts, a width of 50 µs, and the number of pulses of 65 per second. The research samples were Staphylococcus aureus (S. aureus) and Pseudo-monas aeruginosa (P. aeruginosa) bacteria that grew on beef and mice (Mus musculus) with diabetes. The treatment for S. aureus and P. aeruginosa bacteria was carried out using a pulse voltage of 50-80 volts for 5-15 min/day and repeated for 3 days. Meanwhile, treatment of mice wounds was carried out with a pulse voltage of 80 volts for 15 min/day and repeated for 7 days. Results: The results showed that treatment with a pulse voltage of 50-80 volts and a treatment time of 5-15 min significantly reduced the number of S. aureus and P. aeruginosa bacteria in beef (p£0.05). Treatment with a pulse voltage of 80 volts for 15 min made beef free from bacteria. Meanwhile, treatment with a pulse voltage of 80 volts for 15 min per day for seven days resulted in the wound state of three mice in the maturation phase and two mice in the proliferation phase on day 8 with an average wound area of 0.108 cm 2. Conclusion: The treatment with a pulse voltage of 80 volts for 15 min made the beef sterile, the mice wounds healed quickly, and the mice not stressed. The higher the blood glucose level, the slower the wound healing process.

Accelerative Effect of Cinnamon Nanoparticles as well as HAMLET on Healing of Wounds Infected with MRSA in Diabetic Rats

Objective. The aim of the present study was to investigate the effect of cinnamon nanoparticles (CNPs) on healing of wounds infected with methicillin-resistant Staphylococcus aurous with human alpha-lactalbumin made lethal to tumor cells sensitization in diabetic rats. Methods. We included fifty diabetic male rats and divided them into 5 groups. There were 10 rats in each group as follows: CONTROL group: we did not infect the CONTROL group. The wound was only covered with sterile saline 0.9% solution (0.1 mL). INFCTD group: in this group, the wounds were infected with MRSA and covered with sterile saline 0.9% solution (0.1 mL). INFCTD-HMLT group: in this group, the wounds were infected with MRSA and HAMLET (100 μg). INFCTD-CNM group: in this group, the wounds were infected with MRSA and 0.1 mL CNPs (1 mg/mL) were applied topically to wounds. INFCTD-HMLT-CNM group: in this group, the wounds were infected with MRSA, HAMLET (100 μg), and 0.1 mL CNPs (1 mg/mL). Results. Bacteriology, wound area reduction measurements, biochemistry, histomorphometrical studies, hydroxyproline levels, and reverse transcription polymerase chain reaction for caspase-3, Bcl-2, and p53 showed significant difference between rats in the INFCTD-HMT-CNM group in comparison with other groups ( P < 0.05 ). Conclusions. Accelerated healing of diabetic wounds infected with MRSA showed that local application of cinnamon nanoparticles along with HAMLET sensitization on S. aureus-infected wound could be taken into consideration.

Effect of the clathrate complex of selenopyran and β-cyclodextrin on the rate of healing of a conditionally aseptic full-thickness planar wound in rats

Introduction. Selenopyran is an organic selenium compound with sharply hydrophobic properties. An increase in solubility in water (and as a consequence – and bioavailability) is possible due to the formation of inclusion complexes with cyclodextrins.Aim. The aim of this work was to study the effect of a gel containing a clathrate complex of selenopyran with β-cyclodextrin on the rate of wound healing on a model of a conditionally aseptic full-thickness planar wound in rats.Materials and methods. The object of the study was a gel containing a clathrate complex of selenopyran with β-cyclodextrin (the content of selenopyran in the gel was 0.1 %). A model of a full-thickness planar wound in sexually mature male rats was used. 20 individuals were divided into 2 groups – intact (without treatment) and experimental (received gel treatment). Efficacy was assessed by the change in wound area at 3, 5, 7, 9, 11 and 14 days after application of wound.Results and discussion. The results of the study showed that the relative area of the wounds in the treated animals by the 3rd day of the experiment was less than in the intact ones. On the fifth day of the experiment, the differences were statistically significant (57.49 ± 12.51 % in treated animals versus 85.27 ± 26.61 % in intact animals). By the 14th day of the experiment, there were practically no differences in the groups of animals.Conclusion. The results obtained indicate that when using a gel containing selenopyran in combination with β-cyclodextrin, it accelerates the transition from the inflammation phase to the proliferation phase. This is most likely due to the antioxidant properties of selenopyran. Considering the lower concentration of selenopyran in comparison with the therapeutic concentrations of other antioxidants (taurine, allantoin), it can be considered as a promising wound healing agent for further study.

The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma

Background: The development and pathogenetic substantiation of the new agents used for local therapy of thermal trauma (TT) is an urgent problem in medicine. Melatonin (MT) is an endogenous factor of homeostasis regulation with pleiotropic potential. The aim of our study was to assess the morphology, expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), indicators of repair, oxidative destruction of lipids in the skin lesion focus in the dynamics of experimental TT under the conditions of using the original dermal film (DF) with MT. Methods and Results: The experiment was performed on 104 male Wistar rats weighing 200-240 g. For modeling TT II degree according to ICD-10 a relative area of 3.5% of the body surface, an interscapular region isolated from the surrounding tissues, was immersed in distilled water at 98-99 °C for 12 sec. DF based on sodium carboxymethylcellulose with an area of 12 cm2 with MT at a concentration of 5 mg/g was applied daily for five days. The wound area and epithelialization rate were calculated. The content of MMP-9 and VEGF in the burn wound was assessed by an immunohistochemical method. In the homogenate of the burn wound, the content of LPO products was assessed. Morphological and biochemical studies were performed on Days 5, 10 and 20 after TT induction. With experimental TT from Day 5 to Day 20, the absolute area of the burn wound decreases by 35%, the rate of epithelialization increases, the number of neutrophils in the focus of thermal damage decreases, while the representation of lymphocytes, histiocytes, and fibroblasts increases; the expression of MMP-9 and VEGF increases; predominantly secondary and final LPO products in the heptane phase accumulate, the final products of LPO in the isopropanol phase of the lipid extract. The use of MT in the composition of DF daily for 5 days with experimental TT leads to a decrease in the area of the wound defect (by 46% of the original area on Day 20), an increase in the rate of its epithelialization, an increase in the content of lymphocytes and fibroblasts in the burn wound on Days 5, 10 and 20 of TT, a decrease in the representation of neutrophils and macrophages on Days 5 and 10, as well as an increase in VEGF expression on Days 5 and 10, MMP-9 - on Day 5 and a decrease in MMP-9 expression on Days 10 and 20 of TT. In addition, the use of MT in the composition of DF leads to a decrease in the content of predominantly secondary and end products of LPO in the heptane and isopropanol phases of the burn wound on Days 10 and 20 of TT. Correlation analysis revealed that a decrease in the burn surface area under a local application of MT occurs with an increase in the content of VEGF in the wound area and a decrease in the content of MMP-9 and secondary and final LPO products in the heptane phase and the isopropanol phase. On Day 20, there were direct moderate correlations between the absolute burn surface area, on one hand, and secondary and final LPO products, on the other, in the heptane phase (R=0.51, R=0,68; P<0.05) and the isopropanol phase (R=0.44, R=0.46; P<0.05), respectively. Conclusion: The results obtained expand the existing understanding of the role of changes in the expression of MMP-9 and VEGF in the pathogenesis of TT. We believe that the repair-stimulating effect of MT in the DF, which we established during TT at the preclinical stage, is associated with the LPO-limiting effect of MT and a change in the expression of MMP-9 and VEGF in the burn wound and is a prerequisite for further study of the mechanism of action and the effectiveness of MT application in clinical conditions in TT.

Evaluation of the safety and healing potential of a fibroin-aloe gel film for the treatment of diabetic foot ulcers

Objective: This study aimed to develop a wound dressing prepared from the blending of silkworm fibroin and aloe gel extract for use in the treatment of diabetic foot ulcers (DFUs). Methods: Fibroin extracted from silkworm cocoons and aloe gel extract were dissolved in deionised water. pH levels were then adjusted with lactic acid solution. A simple casting technique was used to obtain the fibroin–aloe gel film. The surface morphology, hardness, flexibility and infrared spectrum of the sterilised film were tested. Swelling ratio was measured from changes in weight. The cytocompatibility of the film to human dermal fibroblast was determined using XTT assay. Hard-to-heal DFUs (grade I Wagner score) were treated with the film for four weeks. The application site was assessed for allergic reactions and/or sensitisation. Wound size was measured using standardised digital photography. Results: A total of five hard-to-heal DFUs were treated. The obtained film sterilised with ozonation showed a non-porous structure. The elongation at break and tensile strength of the wet film were 9.00±0.95% and 6.89±1.21N, respectively. Fourier-transform infrared spectroscopy data indicated the presence of amides I, II and III, of peptide linkage, which are the chemical characteristics of the fibroin. Functional groups relating to healing activity of the aloe gel extract were also found. The swelling ratio of the film immersed in water for 24 hours was 0.8±0.01. In three DFUs (40–50mm2 in size), a wound area reduction of 0.4–0.8mm2/day was observed and were healed in 2–3 weeks. The remaining two SFUs (500mm2 in size) showed a wound area reduction of 4mm2/day and were almost closed at four weeks. No allergic reaction or infection was observed in any of the wounds. Conclusion: The obtained film showed a non-porous structure, and its strength and flexibility were adequate for storage and handling. The film tended to increase the proliferation of fibroblasts. The wound dressing showed potential for accelerating the healing rate of DFUs.

Use of a flowable wound matrix to treat lower limb vascular ulcers

Objectives: This study is aimed at assessing the safety and effectiveness of an advanced flowable wound matrix (FWM) in the treatment of hard-to-heal vascular leg ulcers that often involve deep structures, are irregular and/or tunnelled or excavated. Methods: Records of patients seen at our Vascular Surgery Unit, at the University of Campania ‘Luigi Vanvitelli’, for hard-to-heal vascular leg ulcers between January 2018 and January 2020 were retrospectively reviewed. For each wound aetiology, area and complications were recorded and evaluated. Every patient received one or more applications of FWM and was followed up. Results: A total of 22 patients (18 female/four male), mean age 63±8.5 years, were treated. The initial wound area ranged from 4–58cm2. After wound bed preparation, FWM was applied. Treatment was well tolerated and effective—rate of complications was low, graft take was very satisfactory, and no graft loss, rejection or superimposed infections were observed. Healing time was short: 85% of ulcers healed after 12 weeks. Most importantly, there was a decrease in the rate and level of amputations as compared with standard wound care. Conclusions: The data presented indicate that FWM is an option for the treatment of hard-to-heal vascular leg ulcers, particularly for those with an irregular cavity. Declaration of interest: The authors have no conflicts of interest.

Evaluating Effectiveness of Medical Grade Honey-Containing Alginate Dressing in Patients with Chronic Lower Extremity Wounds

Background: Chronic wounds of the lower extremities are challenging to treat. Recently, honey-based dressings have been shown beneficial effects in diabetic foot ulcers and venous ulcers. Here, we compared Medihoney alginate with a standard alginate dressing in lower extremity chronic wounds.Methods: We performed retrospective chart reviews of 37 patients between January 2019 and January 2021 with chronic lower extremity wounds who were treated with an Algisite M dressing (group A) or a Medihoney alginate dressing (group B). Microorganisms isolated from wound cultures, weekly decrease in wound area over 4 weeks, the number of patients who achieved complete wound closure, and the amount of time required for wound closure were compared between the two groups. Results: Sixteen patients were assigned to group A and 21 to group B. The isolated microorganisms were confirmed as methicillin-susceptible Staphylococcus aureus most commonly, followed by methicillin-resistant S. aureus. Wound area decreased from 12.71 to 2.34 cm² in group A and from 14.07 to 1.71 cm² in group B (P<0.05). Seven patients achieved complete wound closure in group A (43.75%) and 15 patients in group B (71.43%). Mean duration of wound closure was 36.31 days in group A and 34.62 days in group B.Conclusion: Considering the more rapid decrease in wound area in group B, application of a honey-containing alginate dressing to lower extremity chronic wounds, especially those infected with antibiotic-resistant bacteria, was proved to be a good treatment option.

Effect of a topical gel based on Adelmidrol + Trans-traumatic acid in the treatment of diabetic foot ulcers: an open-label study

BACKGROUND:Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aims to evaluate the effect of a medical device gel based on Adelmidrol + Trans traumatic acid in the healing process of diabetic foot ulcers. METHODS: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel applied daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: a) wound area, measured drawing a map of the ulcer then calculated with Photoshop6 tools, b) clinical appearance of the ulcer, assessed recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, granulation tissue. RESULTS: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No adverse events treatment-related were observed. CONCLUSIONS: The results of this open-label study show the potential benefits of Adelmidrol + Trans traumatic acid topical administration to promote re-epithelialization of diabetic foot ulcers. Further studies need to confirm the observed results.