Wound Area Ratio Research Articles

A hydrogel dressing loaded with tea tree oil nanoemulsion accelerates methicillin-resistant Staphylococcus aureus-infected wound healing

Drug-resistant bacterial infections can easily lead to delayed wound healing and pose a serious threat to patients' health. Therefore, it was imperative to develop wound dressings to solve this problem. Herein, we developed a hydrogel based on laponite and polyacrylamide (PAAG/LAP) and loaded with tea tree oil nano-emulsion (nanoTTO) by a simple one-step mixing method via the principle of photopolymerization and its potential use and safety for MRSA-infected skin wounds. The evaluation showed that the PAAG/LAP/nanoTTO30 % hydrogel exhibited excellent compressive resistance (∼85 kPa), good biocompatibility, and great antibacterial properties against MRSA in vitro and in vivo (over 90 %). Cell migration results showed that the relative wound area ratio of the PAAG/LAP/nanoTTO30 % hydrogel treatment group (∼55.18 %) was significantly lower than that of the control group (∼68.89 %). The results of the in vivo infection rat model showed that compared with other control groups, the PAAG/LAP/nanoTTO30 % hydrogel treatment group had the lowest relative wound area ratio (8.78 %) within 12 days. Moreover, the results showed the PAAG/LAP/nanoTTO30 % hydrogel could promote MRSA-infected wound healing by directly killing bacteria and promoting angiogenesis. In conclusion, our study provided an antibacterial hydrogel dressing that does not require loading antibiotics for wounds infected by drug-resistant bacteria, expecting to achieve infected wound healing.

The Effectiveness of Combination of Piper betle L. ethanol Extract and Manuka Honey Spray Gel to Accelerating Acute Wound Healing

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.

Comparison of the Effectiveness of Taro Leaf Stalk Extract (Colocasia Esculenta) with Gentamicin Sulfate Cream in the Wound Healing Process in White Rats

The purpose of this study was to determine the comparison of the effectiveness of taro leaf stalk extract (Colocasia esculenta) with gemtamicin sulfate cream in the wound healing process in white rats. This research is a quantitative research with a pure experimental approach. The results of this study consisted of the results of a comparison of the area of early and late wounds in the research rat group, the results of a comparison of the initial wound area and the average wound for 14 days, the results of a pre-post comparison with the research rat group. The results of research on the wound healing process using taro leaf stalk extract stated that the ratio of wound area at the beginning and end between taro petiole extract and control (NaCl) was insignificant, this is because 0.9% Nacl fluid is an effective physiological fluid for wound care by maintaining moisture, keeping granulation dry so that the wound remains in a balanced state that is not dry nor wet.

Hydrogel-Encapsulated Engineered Microbial Consortium as a Photoautotrophic "Living Material" for Promoting Skin Wound Healing.

Genetically modified engineered microorganisms have been encapsulated in hydrogels and used as "living materials" for the treatment of skin diseases. However, their applications are often limited by the epidermal dry, nutrient-poor environment and cannot maintain functions stably for an expected sufficient time. To solve this problem, a photoautotrophic "living material" containing an engineered microbial consortium was designed and fabricated. The engineered microbial consortium comprised Synechococcus elongatus PCC7942 for producing sucrose by photosynthesis and another heterotrophic engineered bacterium (Escherichia coli or Lactococcus lactis) that can utilize sucrose for the growth and secretion of functional biomolecules. These engineered microorganisms in the "living material" were proved to function stably for a longer time than only individual microbes. Subsequently, CXCL12-secreting engineered L. lactis was used to construct the "living material", and its effect on promoting wound healing was verified in a full-thickness rat-skin defect model. The wounds treated by our hydrogel-encapsulated engineered microbial consortium (HeEMC) healed faster, with a wound area ratio of only 13.2% at day 14, compared to the remaining 62.6, 51.4, and 40.8% of the control, PEGDA, and PEGDA/CS groups, respectively. In conclusion, we established an efficient living material HeEMC to offer promising applications in the treatment of skin diseases.

Wound healing in db/db mice with type 2 diabetes using non-contact exposure with an argon non-thermal atmospheric pressure plasma jet device.

A non-thermal atmospheric pressure plasma jet (APPJ) may stimulate cells and tissues or result in cell death depending on the intensity of plasma at the target; therefore, we herein investigated the effects of non-thermal plasma under non-contact conditions on the healing of full-thickness wounds in diabetic mice (DM+ group) and normal mice (DM- group). A hydrogen peroxide colorimetric method and high performance liquid chromatography showed that APPJ produced low amounts of reactive oxygen and nitrogen species. Ten-week-old male C57BL/6j mice with normal blood glucose levels (DM- group) and 10-week-old male C57BLKS/J Iar-+Leprdb/+Leprdb mice (DM+ group) received two full-thickness cutaneous wounds (4 mm in diameter) on both sides of the dorsum. Wounds were treated with or without the plasma jet or argon gas for 1 minute and were then covered with a hydrocolloid dressing (Hydrocolloid), according to which mice were divided into the following groups: DM+Plasma, DM+Argon, DM+Hydrocolloid, DM-Plasma, DM-Argon, and DM-Hydrocolloid. Exudate weights, wound areas, and wound area ratios were recorded every day. Hematoxylin and eosin staining was performed to assess re-epithelialization and α-SMA immunohistological staining to evaluate the formation of new blood vessels. Non-thermal plasma under non-contact conditions reduced the production of exudate. Exudate weights were smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups. The wound area ratio was smaller for plasma-treated wounds, and was also smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups on days 1–21 (p<0.01). Wound areas were smaller in the DM-Plasma group than in the DM-Argon group until day 14 and differences were significant on days 1–5 (p<0.01). The percentage of re-epithelialization was significantly higher in the DM+Plasma group than in the DM+Argon and DM+Hydrocolloid groups (p<0.01). The number of new blood vessels that had formed by day 7 was significantly higher in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups (p<0.05). These results indicate that treatment with the current non-thermal plasma APPJ device under non-contact conditions accelerated wound healing in diabetic mice.

THE EFFECT OF BETEL LEAF EXTRACT SPRAY ON HISTOPATHOLOGY OF WOUND HEALING

Wounds are referred to as 'Silent Epidemic' because they have a substantial impact if not treated properly. Betel leaf is known to contain compounds that may be used as wound healers. The purpose of this study was to test the spray activity of betel leaf extract (Piper betle L) in healing acute wounds in male Balb/C mice. Spray formula made with various concentrations of betel leaf extract by 3% (S1), 5% (S2) and 7% (S3). The acute wound healing activity test was 15 mice divided into 5 groups S1, S2, S3, P (positive control), and C (negative control). Interventions and observations were carried out for 14 days. The results of observational analysis by calculating the ratio of wound area then One Way Anova test and Post Hoc Tukey Cramer test. The results showed that spray of betel leaf extract with a concentration of 7% was not significantly different from P (p&gt;0.05). The conclusion in this study is that sprays of betel leaf extract 3%, 5%, and 7% may be used as an acute wound healer, the best healing activity is shown at a concentration of 7%.

Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes.

Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.

Topical co-administration of Teucrium polium hydroethanolic extract and Aloe vera gel triggered wound healing by accelerating cell proliferation in diabetic mouse model

Diabetic wounds are major issues in patients with diabetes. Medicinal plants of Teucrium polium and Aloe vera have antioxidant and anti-inflammatory properties that may be profitable for diabetic patients. This study was conducted to evaluate the effect of co-administration of ointments prepared from Teucrium polium hydroethanolic extract (TPEO) and Aloe vera gel (AVGO) on excisional wound healing in a diabetic mouse model. Following the induction of diabetes and circular excisional wound (7 mm), the mice were divided into six groups, namely (Ⅰ) control mice treated with mupirocin (as a standard drug), (Ⅱ and Ⅲ) the mice treated with 5 and 10 % TPEO, (Ⅳ and Ⅴ) the mice treated with 5 and 10 % AVGO, and (Ⅵ) the mice treated with a combination of 5% TPEO and 5% AVGO (TPEO+AVGO). To investigate the wound area, we further evaluated the wound area ratio, histological analysis and the serum levels of tissue antioxidant capacity (TAC) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), immunohistochemistry staining for vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), glucose transporter-1(GLUT-1) and collagen type 1 and mRNA expression levels for VEGF, IGF-1, GLUT-1 and fibroblast growth factor-2 (FGF-2). The results showed that administration of the ointments, especially in combination form, shortened the inflammatory phase and reduced the levels of tissue MDA, TNF-α and IL-1β compared to mupirocin group (P < 0.05). Moreover, fibroblasts proliferation, collagen deposition, VEGF, IGF-1, GLUT-1-positive cells and level of TAC, and expressions of VEGF, IGF-1, GLUT-1 and FGF-2 were significantly (P < 0.05) increased in TPEO and AVGO, and especially in the mice treated with the mixed form. Therefore, topical co-administration of TPEO + AVGO accelerated open diabetic wound healing through shortening the inflammatory phase and increasing cell proliferation and collagen deposition.

Wound healing is promoted by Musa paradisiaca (banana) extract in diabetic rats.

Impairments in wound healing commonly occur among patients with diabetes. Herbal medicines have a long history of usage in wound care management. Super green (SG) is a newly discovered natural product obtained from Musa paradisiaca. This study aimed to investigate the efficacy of the topical application of SG in healing surgical wounds in diabetic rats. Wistar rats received a one-time intraperitoneal injection of streptozotocin to induce type 1 diabetes. Full-thickness excisional skin wounds were created on the backs of the rats. The relevant groups were topically treated with the indicated concentrations of SG or vehicle dressing throughout the study duration. Histological analysis was performed and the mRNA levels of proinflammatory cytokines were measured to evaluate the improvement of wound closure. The wound area ratio of the SG (1/6000 dilution)-treated group was greatly reduced compared to that of the vehicle-treated group. The histological analysis showed fewer inflammatory cells, accelerated re-epithelialization, and increased collagen deposition in SG 1/6000-treated wounds. The gene expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were decreased and the levels of type I and type III collagen were increased after SG treatment. These results show that the most therapeutically efficacious concentration of SG (1/6000 dilution) can enhance wound repair in diabetic rats. SG has the potential to be a new treatment strategy for diabetic wounds.

γ-PGA hydrogel loaded with cell-free fat extract promotes the healing of diabetic wounds.

Diabetic wounds are one complication of persistent hyperglycemia and lead to neuropathy and vascular lesions in patients. The promotion of angiogenesis plays an important role in wound healing. Cell-free fat extract (Ceffe) is a cell-free fraction isolated from adipose that is enriched with a range of growth factors, the combination of which can synergistically induce angiogenesis. In this study, we prepared a wound dressing by loading Ceffe with the γ-PGA hydrogel (Ceffe-γ-PGA) to promote the healing of wounds in diabetic mice. The viscosity of Ceffe-γ-PGA was 9.2 pa s, and the water retention rate after 6 hours reached 50%. The slow-release effect of the Ceffe-γ-PGA hydrogel was investigated in vitro in PBS, and the cumulative release rate was 97% after 6 days. Water retention and viscosity analyses revealed that Ceffe-γ-PGA provided a moist environment for the wound surface. The therapeutic effect of the Ceffe-γ-PGA hydrogel on wound healing was studied in vivo in type-II diabetic male db/db mice. After 17 days of wound treatment, the wound area ratio of the Ceffe-γ-PGA group was reduced to 2% of the original, and the capillary density of the Ceffe-γ-PGA group reached 33 mm-2 and was 19 mm-2 higher than that of the untreated group. The cell proliferation rate in the Ceffe-γ-PGA group was 37% higher than that in the untreated group. These results support the use of this system as a promising therapeutic strategy for wound healing in patients with diabetes.

Topical estrogen application to wounds promotes delayed cutaneous wound healing in 80-week-old female mice.

Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However, whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82–85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3–14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1–14, re-epithelialization ratio was significantly higher on days 3–14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization.

Wound Healing in Streptozotocin-Induced Diabetic Rats Using Atmospheric-Pressure Argon Plasma Jet

In this study, we used an argon-based round atmospheric-pressure plasma jet (APPJ) for enhancing wound healing in streptozotocin (STZ) induced diabetic rats. The APPJ was characterized by optical emission spectroscopy. We induced Type 1 and Type 2 diabetes in rats with different amounts of STZ combined with normal and high-fat diets, respectively. The wound area ratio of all the plasma-treated normal and diabetic groups was greatly reduced (up to 30%) compared with that of the untreated groups during healing. Histological analysis revealed faster re-epithelialization, collagen deposition, less inflammation, and a complete skin structure in the plasma-treated groups was found as compared with the untreated control groups. In addition, the new blood vessels of plasma-treated tissues decreased more than untreated tissues in the middle (Day 14) and late (Day 21) stages of wound healing. The plasma-treated wounds demonstrated more transforming growth factor beta (TGF-β) expression in the early stage (Day 7), whereas they decreased in the middle and late stages of wound healing. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) increased after plasma treatment. In addition, plasma-treated water had a higher concentration of hydrogen peroxide, nitrite and nitrate when the plasma treatment time was longer. In summary, the proposed argon APPJ based on the current study could be a potential tool for treating diabetic wounds.

Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing

BackgroundDiabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. Materials and methodsExcisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0.5 μg/kg/d, i.p.) for 2 wk. The final-to-initial wound area ratio was measured for 14 d. Levels of superoxide anions and proinflammatory cytokines in the wound were determined. Angiogenesis was assessed using the Matrigel assay. Expression levels of proangiogenic factors and extracellular matrix proteins were measured. ResultsEx4 restored wound closure in diabetic rats and significantly suppressed the generation of superoxide anions and interleukin-6 in wounds. The number of circulating endothelial progenitor (CD34+/KDR+) cells increased significantly in Ex4-treated diabetic rats, which also showed increased capillary tube formation. Protein levels of vascular endothelial growth factor receptor-2, phosphorylated endothelial nitric oxide synthase, matrix metalloproteinase-2, and transforming growth factor-β were increased in diabetic rats receiving Ex4 therapy. Ex4-enhanced vascularity, dermal regeneration, and epidermal regeneration, while it decreased hemorrhaging and increased the number of proliferative cells in the dermis. ConclusionsEx4 accelerated excisional wound healing in subjects with diabetes. Glp-1R activation attenuates inflammatory response and enhances angiogenesis during the early proliferation phase of wound healing in diabetic subjects, while it enhances transforming growth factor-β/matrix metalloproteinase-mediated regeneration during the maturation phase. These results suggest that Ex4 could be used as a standard hypoglycemic agent in diabetic patients with wound injury.

The Relationship between Cutaneous Wounds Made on Obese Mice or Those with Decreased Body Weight and Serum Leptin Level

Purpose: Not all obese people have hyperglycemia. We wondered about the healing progress in obese people without hyperglycemia. The purpose of this study is to observe the cutaneous wound healing process. Methods: Three-week-old male mice were fed high-fat diets (containing 60% fat) in the diet group, and commercial diets in the control group, ad libitum for 15 weeks. Circle-full-thickness cutaneous wounds were made on the dorsal skin of mice. From day 0 to day 15 after wounding, we analyzed wound healing process. We measured the blood concentration of leptin, and observed the distribution of leptin-positive cells in each wound. Results: Mean body weight, the areas of subcutaneous fat and visceral fat, and the weight of epididymal fat in the diet group were significantly greater than those in the control group at 15 weeks after feeding. The diet group did not feed on the diet after wounding; their body weight decreased remarkably to the level of the control group. The ratio of wound area, re-epithelialization, and collagen fibers did not differ between the diet and control groups on each day. The blood concentration of leptin in the diet group was significantly greater than that in the control group before wounding and until day 6 after wounding (day 0, 10 hour and day 1: p < 0.01, day 6: p < 0.05). Conclusion: The results show that the wound healing process is similar between obese and non-obese mice, and that the decrease in the leptin level in the obese mouse to that in the non-obese mouse may depend on the decrease of body weight of obese mouse.

Randomized, controlled study of innovative spray formulation containing ozonated oil and α-bisabolol in the topical treatment of chronic venous leg ulcers.

Ozone therapy has a large clinical application in many therapeutic areas because of its well-known antimicrobial, immunological, and oxygenating properties. Recently, interest has grown regarding the application of ozonated oil for vascular leg ulcer treatment. The efficacy of an innovative spray formulation of ozonated oil and α-bisabolol combination in the topical treatment of chronic venous leg ulcers was evaluated compared with standard epithelialization cream. A randomized controlled trial was conducted. A total of 29 patients older than 18 years with chronic venous leg ulcers for less than 2 years' duration were assessed. Patients were randomized to receive daily application of both ozonated oil and α-bisabolol or the control cream (vitamin A, vitamin E, talc, and zinc oxide) for 30 days. Patients were evaluated on 4 different visits: at days 0, 7, 14, and 30. At each visit, the wound surfaces were measured. Wound area ratio and the speed of ulcer healing were calculated. At the end of treatment, the proportion of patients with complete ulcer healing was higher with ozonated oil and α-bisabolol formulation (25% vs 0%). Furthermore, the changes in ulcer surface area were significant for ozonated oil and α-bisabolol formulation only (P < .05), in particular, observing a significant and progressive reduction of the wound surface by 34%, 59%, and 73%, after 7, 14, and 30 days of treatment, respectively. The innovative spray formulation of ozonated oil and α-bisabolol combination shows promise as an important new therapeutic option in the adjuvant treatment of venous ulcers.

The effect of 17β-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model.

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.

17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration.

Comparison of the Cutaneous Wound Healing of Ovariectomized Mouse at 12 Weeks with That of SHAM and Estrogen-Administered Mice

The aim of this experiment was to investigate the effect of 17β-estradiol on cutaneous wound healing in 12-week ovariectomized (OVX) female mice. Eight-week-old female mice were divided into three groups: administration of 17β-estradiol after OVX (OVX + 17β-estradiol), OVX, and sham (SHAM). Four weeks after surgery, the mice received two full-thickness cutaneous wounds. 17β-Estradiol at 0.01 g/day was administered on the backs of mice in the OVX + 17β-estradiol group every day. Plasma 17β-estradiol level in the OVX + 17β-estradiol group was thus significantly higher than in the SHAM and OVX groups, but there was no significant difference between SHAM and OVX groups. The ratio of wound area was not significantly different among the three groups. However, the period required to reach a ratio of wound area of 0.15 in the OVX + 17β-estradiol group was significantly shorter than in the SHAM and OVX groups. These results indicate that cutaneous wound healing in young OVX mice was promoted by the administration of 17β-estradiol compared with that in SHAM and OVX mice without such administration, but there was no difference between the latter two groups that did not differ in 17β-estradiol level.

The Effect of 17β-Estradiol Administration on Cutaneous Wound Healing in 24-Week Ovariectomized Female Mice

Estrogen replacement promotes cutaneous wound healing in 8–10-week young ovariectomized female mice. However, research using aged ovariectomized female mice has not been reported, to the best of our knowledge. Therefore, we investigated the effect of 17β-estradiol on cutaneous wound healing using 24-week middle-aged ovariectomized female mice. Twenty-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX), and sham (SHAM). After 4 weeks, the mice received two full-thickness wounds. Then, the OVX + 17β-estradiol group was administered 17β-estradiol at 0.01 g/day until healing. The ratio of wound area in the OVX + 17β-estradiol group was significantly decreased compared with that in the OVX group. The numbers of neutrophils and macrophages in the OVX + 17β-estradiol group were significantly smaller than those in the OVX group. In addition, the ratio of myofibroblasts in the OVX + 17β-estradiol group was significantly higher than that in the OVX group. These data suggested that exogenous continuous 17β-estradiol administration promotes cutaneous wound healing in 24-week OVX female mice by reducing wound area, shortening inflammatory response, and promoting wound contraction. However, it is unclear whether the effect of exogenous estrogen on wound healing outweighs the delay of wound healing due to advanced age.

Effects of Three Types of Japanese Honey on Full-Thickness Wound in Mice

Although many previous studies reported that honey promotes wound healing, no study has examined the effects of Japanese honey. The aim of this study was to investigate the effects of three types of Japanese honey, Acacia, Buckwheat flour, and Chinese milk vetch honey, on wound healing in comparison with hydrocolloid dressing. Circular full-thickness skin wounds were produced on male mice. Japanese honey or hydrocolloid dressing was applied daily to the mice for 14 days. The ratio of wound area for the hydrocolloid dressing group increased initially in the inflammatory and early proliferative phases and then decreased rapidly to heal with scarring. However, the ratios of wound area for the Japanese honey groups decreased in the inflammatory phase, increased in the proliferative phase, and decreased in the proliferative phase, and some wounds were not completely covered with new epithelium. These findings indicate that using Japanese honey alone has limited benefit, but since it reduces wound size in the inflammatory phase, it is possible to apply a combined treatment in which Japanese honey is applied only in the inflammatory phase, followed by hydrocolloid dressing from the proliferative phase, which would effectively contract the wound.