Skin Wound Healing In Rats Research Articles

Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats.

IntroductionImpaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals.ObjectivesWe investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats.MethodsDorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process.ResultsLA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2).ConclusionsOral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

The Effect of Combined Pulsed Wave Low-Level Laser Therapy and Human Bone Marrow Mesenchymal Stem Cell-Conditioned Medium on Open Skin Wound Healing in Diabetic Rats.

The nobility of this scientific study was to investigate the combined effects of pulsed wave low-level laser therapy (PWLLLT) and human bone marrow mesenchymal stem cell-conditioned medium (hBM-MSC-CM) on the biomechanical parameters of wounds in an experimental model for diabetes mellitus (DM). PWLLLT exhibited biostimulatory effects on wounds in diabetic animals. Secretomes can be administered into wounds by the use of BM-MSC-CM. Type I DM was induced in rats by streptozotocin (STZ). Two wounds were made on proximal and distal parts in the dorsal region of each rat. Rats were divided into four groups. The first group was considered as the control group. The second group received hBM-MSC-CM. The third group received PWLLLT. The fourth group received hBM-MSC-CM+LASER. hBM-MSC-CM was administrated twice intraperitoneally. The proximal wounds in the third and fourth groups were treated with a pulsed laser by 890 nm wavelength, 80 Hz frequency, and 0.2 J/cm(2) energy densities. On the 15th day, a standard sample from each healing wound was submitted for biomechanical examination. The data were analyzed by analysis of variance test. PWLLLT and hBM-MSC-CM, alone or in combination, significantly increased biomechanical parameters within the healing wounds. However, PWLLLT was statistically more effective compared with the hBM-MSC-CM. In the third and fourth groups, the numbers of wound closures were significantly enhanced in proximal part, contrary to the control ones. It was magnificently attained that PWLLLT significantly accelerated the wound healing process in the experimental model for STZ-induced type I DM rats.

Role of integrin-linked kinase signaling pathway in skin lesions and wound healing in diabetic rats

Objective To investigate the role of integrin-linked kinase (ILK) signaling pathway in the skin lesions and wound healing in diabetic rats. Methods Thirty-six SD rats were divided into diabetic wound group (D) and non-diabetic wound group (N) according to the random number table, with 18 rats in each group. 10 g/L streptozocin (60 mg/kg) was intraperitoneally injected in rats in group D, while the rats in group N were given same quantity of sodium citrate buffer. Two weeks after successful reproduction of diabetic model of rats in group D, two full-thickness skin of an area of 2 cm×2 cm was resected on both sides of back of rats in the two groups. Wounds of three rats of each group were photographed and examined on post injury day (PID) 1, 3, 7, 10, 14, and 21, and the wound healing rates were calculated. The non-injured skin and wound tissue (central part) on back of three rats of the rest 15 rats in the two groups were harvested on PID 3, 7, 10, 14, and 21, respectively. Morphology of the non-injured skin tissue was observed with HE staining, and the thickness of full-thickness skin and epidermis were measured. The mRNA expression levels of ILK, protein kinase B (Akt), and glycogen synthase kinase-3β (GSK-3β) in non-injured skin tissue were determined with real-time fluorescent quantitative RT-PCR. The protein expression levels of ILK, Akt, phosphorylated Akt, GSK-3β, and phosphorylated GSK-3β in non-injured skin tissue, and ILK, phosphorylated Akt in wound tissue were assessed with Western blotting. Data were processed with two independent-sample t test, one-way analysis of variance, SNK test and analysis of variance of factorial design. Results (1) After injury, the wound scabs of rats in group N were dry, and red granulation tissue with no excretion were seen when the scabs fell off, and the wound healed fast. After injury, excretion under the wound scabs of rats in group D was seen, and the scabs easily fell off with exposure of pink granulation tissue with much excretion, and the wounds healed slowly. Except for PID 3, the wound healing rate of rats in group D was significantly lower than that in group N on other PIDs (with t values from 3.858 to 13.738, P 0.05). (4) From PID 3 to 21, the protein expression levels of ILK, Akt and phosphorylated Akt in non-injured skin tissue of rats in group D were significantly lower than those in group N (with t values from 2.630 to 6.209, P 0.05); the protein expression level of phosphorylated GSK-3β in non-injured skin tissue of rats in group D was significantly higher than that in group N (t=4.131, P 0.05), and the protein expression level of phosphorylated Akt in wound tissue was significantly higher than that in non-injured skin tissue (F=117.329, P 0.05), and the protein expression level of phosphorylated Akt in wound tissue was significantly higher than that in non-injured skin tissue (F=184.120, P<0.001). Conclusions The skin lesion of diabetic rats may be related to the declined expression levels of ILK, Akt and phosphorylated Akt in the ILK signaling pathway. The refractory healing of wound in diabetic rats may be related to the declined expression level of phosphorylated Akt. Key words: Diabetes mellitus; Skin; Wound healing; Integrin-linked kinase; Protein kinase B; Glycogen synthase kinase-3β

Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway.

The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing.

Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System

To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. Rat skin was irradiated to 30 or 45Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence. The efficacy of bortezomib in wound healing of rat skin was assessed by the skin injury scale. We found that irradiation induced epidermal and dermal hyperplasia in rat and human skin. One hundred ninety-six preferentially expressed and 80 unique proteins in the irradiated fibrotic skin were identified. Through bioinformatic analysis, the ubiquitin-proteasome pathway showed a significant fold change and was investigated in greater detail. Invitro experiments demonstrated that irradiation resulted in a decline in the activity of the proteasome in human skin cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-β downstream signaling but not TGF-β secretion stimulated by irradiation in HaCaT and WS-1cells. Moreover, bortezomib ameliorated radiation-induced skin injury and attenuated epidermal hyperplasia. Our findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.

The influence of growth factors on skin wound healing in rats

IntroductionHealing is a process that restores the physical integrity of body structures. It is a dynamic, complex, multicellular process that involves the extracellular matrix, cytokines, blood cells, and growth factors. Growth factors are proteins that activate and stimulate cell proliferation through the activation of angiogenesis, mitogenesis, and gene transcription, accelerating the healing process. ObjectiveTo assess the influence of growth factors on the healing process of wounds made on the backs of female rats compared to the control wound, through macro and microscopy. MethodsThis study used 45 female Wistar rats, in which three wounds were made on the back. The first was the control wound, the second received epithelial growth factor injection, and the third received a combination of factors. Macroscopic and microscopic assessments were performed on the third, seventh, and 15th days of the experiment. For microscopic analysis, hematoxylin–eosin staining was utilized to assess the inflammatory process; vimentin, for assessment of blood vessels and fibroblasts, and Sirius Red for collagen assessment. ResultsIn the macroscopic assessment, the use of growth factors resulted in faster healing and decrease of granulation tissue on days seven and 15; (80.31% reduction in the control wound vs. 83.24% in the epithelial wound vs. 100% in the mixed wound). Utilizing microscopy, at the three stages of the experiment, there were no significant differences between the three wounds; however, when comparing the day of euthanization for each type of wound, there was a favorable outcome for epithelial and mixed wounds (between the third vs. 15th day, p<0.001, and in the comparison of the seventh vs. 15th day; p=0.002 and p=0.001 for epithelial and mixed wounds, respectively) with a higher number of fibroblasts, angiogenesis, and collagen type I. ConclusionThe use of growth factors accelerates healing, stimulates greater angiogenic activity, and accelerates fibroplasia and collagen maturation.

The Development of Technology for Topical Application of Xenon as Part of an External Agent and Its Effect on Rat Skin Wound Healing

We have developed an agent for external use to deliver xenon into the skin. Using the model of skin wound we have studied the effect of xenon on the process of wound healing in rats. It has been shown that the application of xenon-containing cream on wound surface significantly accelerates the healing process as compared to control animals where cream without xenon has been applied.

Effect of topical mixture of honey, royal jelly and olive oil-propolis extract on skin wound healing in diabetic rats

Abstract Background Diabetic wound is a common complication of diabetes. The aim of this study was to evaluate the effects of topical application of mixture of honey, royal jelly and olive oil-propolis extract (Nika cream) on cutaneous wound healing in streptozotocin (STZ)-induced diabetic rats. Materials and methods In this interventional study, we prepared a new composition ointment entitled Nika cream. 42 Wistar male rats were divided randomly in normal and diabetic groups. Next, diabetes was induced by intraperitoneal injection of STZ (60 mg kg−1 body weight). The diabetic rats with marked hyperglycemia (serum glucose more than 200 mg/dl) were selected for the study. After anesthesia, full thickness skin of upper dorsal part of the rats was removed in 2 cm × 2 cm area. 24 h after the operation, wound in each animal was treated daily with Nika cream and phenytoin 1% in normal and diabetic groups. Control group received no treatment. Wound surface area was measured until 24th postoperative day. The time required for the completion of healing was also recorded. Results We demonstrated that Nika cream had distinct and non-exchangeable functions during the wound healing process. The progress of wound healing in diabetic animals was slower than in normal animals, and also healing effect of Nika cream compared with control and normal phenytoin 1% and diabetic test groups was significant (P Conclusion The results showed that Nika cream accelerate the wound healing in normal and diabetic subjects.

Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have properties that make them promising for the treatment of chronic nonhealing wounds. The major challenge is ensuring an efficient, safe, and painless delivery of BM-MSCs. Tissue-engineered skin substitutes have considerable benefits in skin damage resulting from chronic nonhealing wounds. Here, we have constructed a three-dimensional biomimetic scaffold known as collagen-chitosan sponge scaffolds (CCSS) using the cross-linking and freeze-drying method. Scanning electron microscopy images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve biostability using swelling and degradation assays. Furthermore, BM-MSCs were seeded in CCSS using the two-step seeding method to construct tissue-engineered skin substitutes. In addition, in this three-dimensional biomimetic CCSS, BM-MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM-MSCs exhibited a significant upregulated expression of proangiogenesis factors, including HIF-1α, VEGF, and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing.

Time-Dependent Resolution of Collagen Deposition During Skin Repair in Rats: A Correlative Morphological and Biochemical Study.

Skin samples were used to compare microscopy methods used to quantify collagen with potential applicability to resolve time-dependent collagen deposition during skin wound healing in rats. Skin wounds by secondary intention were made in rats and tissue fragments were collected every 7 days for 21 days. Collagen content determined by biochemical analysis was compared with collagen measured by point counting (PC) on histological skin sections stained by Gomori's trichrome method (Trichrome/PC), Sirius red under polarized light (PL) microscopy (Sirius red/PL-PC), and computational color segmentation (CS) applied to sections stained with Sirius red (Sirius red/PL-CS). All microscopy methods investigated resolved the time-dependent dynamics of collagen deposition in scar tissue during skin wound healing in rats. Collagen content measured by Sirius red/PL-PC and Sirius red/PL-CS was significantly lower when compared with Trichrome/PC. The Trichrome/PC method provided overestimated values of collagen compared with biochemical analysis. In the early stages of wound healing, which shows high production of noncollagenous molecules, Sirius red/PL-CS and Sirius red/PL-PC methods were more suitable for quantification of collagen fibers. Trichrome staining did not allow clear separation between collagenous and noncollagenous elements in skin samples, introducing a marked bias in collagen quantification.

The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study.

BackgroundWound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques.Material and MethodsForty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group): control group (Group I); full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies.ResultsChitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.ConclusionMSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment.

Repair of surgical wounds in rats using a 10% unripe Musa sapientum peel gel.

To investigate the efficacy of a 10% gel of unripe banana (Musa sapientum) peel in treating surgical wounds in rats. A longitudinal, prospective, randomized triple-blind study was conducted with 60 Wistar rats (Rattus norvegicus albinus) weighing approximately 400g. The animals were randomly divided into: control group (treated with gel containing no active ingredient) and study group (treated with 10% gel of unripe banana peel). The gel was applied every three days to a 4x4-cm surgical wound created on the back of each animal (day 0) in both groups. Tissue samples were collected for histological analysis on days 14, 21 and 28. On day 14, more extensive vascular proliferation (p=0.023), presence of mononuclear cells (p=0.000), fibroblast proliferation (p=0.012), re-epithelialization (p=0.000), and decreased presence of polymorphonuclear cells (p=0.010) were observed in the study group than in controls. No significant between-group difference in the presence of polymorphonuclear cells was found on day 21. Fibroblast proliferation was significantly greater (p=0.006) in the study group than in the control group on day 28. The 10% gel of unripe banana peel showed anti-inflammatory activity and stimulated wound healing in rat skin when compared with a gel containing no active ingredient.

The effect of CoolClot hemostatic agent on skin wound healing in rats

BackgroundHemostatic agents can play a key role in controlling severe hemorrhage after trauma. Previously, some criteria have been defined for improving the quality of these products; one of them is that the hemostat causes no further tissue injury. CoolClot is a recently introduced hemostatic agent that its effects on wound healing have not yet been examined, which this study aims to address. Materials and methodsThirty-four adult male Sprague–Dawley rats were assigned randomly to two groups (n = 17): a study group where CoolClot hemostatic agent was applied on their wounds, and a control group whose wounds were washed only with sterile saline. The rats underwent dorsal full-thickness skin excisional wounds (20 mm diameter). On day 12 after wounding, seven rats were chosen in a random manner from each of the groups of study and control, and their skin biopsies from the wound sites were sent for histologic examination. Skin samples of the remaining rats in each group were taken on the 21st d after wound creation. Wound healing was also monitored photographically. In addition, wound surface temperature after wounding, and the application of CoolClot was recorded. ResultsThere was no significant difference between the groups of study and control regarding the examined histopathologic parameters. The maximum increase in wound surface temperature was 1.56°C. ConclusionsOne-time topical usage of CoolClot has no significant negative effect on the wound healing process. In addition, no significant increase in wound surface temperature will occur after the application of this agent.

Does dexamethasone act in neuropeptides SP and CGRP in neurogenic inflammation of the skin? An experimental study.

To investigate the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) after subcutaneous injection of dexamethasone prior to skin incision in rats. Twenty seven Wistar-EPM-1 rats were randomly divided into three groups. The sham group (SG) of rats was injected with 0.9 % saline. The second group (Dexa) was injected with 1.0 mg/kg dexamethasone, and the third group (Dexa+) was injected with 10.0 mg/kg dexamethasone. In all groups, the three subcutaneous injections were performed 30 minutes prior to the surgical skin incision and tissue collection. SP and CGRP (15 kDa pro-CGRP and 5 kDa CGRP) were quantified by Western Blotting. No statistically significant differences (p>0.05) were found in pro-CGRP, CGRP and SP values in all three groups. The anti-inflammatory effect of dexamethasone did not occur when the substance P and calcitonin gene-related peptide levels were altered during the neurogenic inflammation process of skin wound healing in rats.

Comparison of the Effect of Low-Level Laser and Phenytoin Therapy on Skin Wound Healing in Rats.

Different modalities have been used to achieve better results in wound healing among which are laser and pharmacological agents. To our knowledge, there is no investigation to compare phenytoin and laser together. In this study, we aimed to evaluate laser and phenytoin efficacy and compare their effect on wound healing. We used 60 rats. The animals were divided into 4 groups, 15 rats in each and each group was subdivided into 3 subgroups for which postoperative evaluation was performed on days 3, 7, and 14. After general anesthesia and back hair shaving of each rat, an excisional wound was made. The wounds in group 2 were treated with 1% phenytoin cream. In group 3, the wounds were irradiated with diode laser. The wounds of group 4 were treated with both phenytoin cream and laser administration. The animals of group 1 served as control. For histopathological evaluation, hematoxylin and eosin staining was used. Polymorphonuclear leucocytes (PMNs), re-epithelization, fibroblasts, new vessels and collagen were evaluated. Faster reduction in polymorphonuclear cells after 7 and 14 days and more collagen fibers on the third day in laser treated group was statistically significant (P < .05) .The result for the phenytoin treated group were not better than control group. When both laser and phenytoin were used samples showed more collagen fibers on the third day, which was statistically significant (P < .05). It seems that low level laser is effective in skin wound healing and have better results than phenytoin application.

The combined effect of laser and oral administration of Iranian propolis extract on skin wound healing in male rats

Background: To date, a lot of research has been carried out on the effect of medications and surgical methods on the treatment of wounds, but no ideal achievement has been obtained yet. This study was conducted to investigate the single and combined effect of laser and propolis on skin wound healing in male rats. Methods: 40 Wistar male rats (200-250 g) were divided into 4 groups (n= 10). All animals were anesthetized and sterile skin wound was created by surgical scissors. Control group had no treatment, the second group was treated with laser (10 mW), the third group was treated with oral propolis (100 mg /kg; 3 times /day) and the forth group was treated with both laser and propolis. The wound healing level was measured based on the wound area and urinary hydroxyproline content. Results: Urinary hydroxyproline content was increased in groups treated with laser, propolis and combined laser and propolis compared to the control group (P<0.01, 0.05 and 0.01, respectively). Also at the end of the treatment period, the wound extent was significantly lower in the laser, propolis, and combined laser and propolis groups than the control (P<0.05, 0.05 and 0.01, respectively). There was no significant difference between treatment groups. Conclusion: Our results showed that oral administration of propolis or low power laser radiation can increase the wound healing rate.

Immunomodulator 'mushroom beta glucan' induces Wnt/β catenin signalling and improves wound recovery in tilapia and rat skin: a histopathological study.

The present study aims to investigate the effects of mushroom beta glucan (MBG) on wound recovery in partial hepatectomy (PH) in Nile tilapia (Oreochromis niloticus) and in rat skin wound healing examination. Following PH, we focussed on the effects on liver repair ability using in vitro and in vivo tests. In vitro, we examined whether the MBG has an impact on liver cell proliferation, mainly through 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays and bromodeoxyuridine (BrdU) cell proliferation assay detection method. Results showed that MBG treatment was remarkable in enhancing cell proliferation of hepatocytes and in maintaining the cellular viability. Immunohistochemical staining to analyse Wnt/β-catenin signalling also showed that MBG has the effect of promoting cell proliferation of liver tissues after PH surgery.

Effect of chitosan film containing carvacrol , a phenolic monoterpene, on wound healing in rats

Carvacrol, a phenolic monoterpene present in the oregano essential oil. The aim of this study was to investigate the wound healing activity of carvacrol incorporated to chitosan bioactive films on excision wound model in rats. Wistar rats, weighing 250-300 g, were anesthetized and an excisional wound was performed. Rats were treated with chitosan bioactive film; chitosan bioactive film containg carvacrol 0.5% or 1%, for 3, 7, 14 or 21 days. The residual wounds were analyzed and removed. Serial histological sections were obtained and stained by histochemical techniques (Hematoxilin/Eosin and Sirius red). Experimental protocols were approved by the Animal Care and Use Committee at the UFS/Brazil. Carvacrol incorporated to chitosan films reduced wound areas (p < 0.01) and tissue edema (p < 0.001), induced earlier granulation tissue formation, increased cell proliferation, increased ephitelization rates (p < 0.01) and improved collagenization when compared to the control group. It is suggested that carvacrol incorporated to chitosan films has a potential use on skin wound healing of rats. Financial support: FAPITEC/SE/Brazil; CNPq/Brazil and CAPES/Brazil.

Albusite: A Novel Synthetic Gel for Promotion of Skin Wound Healing in Rats

The current study was performed to evaluate the effect of Albusite gel on the healing process of excisional wounds in diabetic and control rats. Fifty-two Sprague Dawley male rats were used to evaluate the effects of Albusite Gel (synthetic gel) on the healing of full-thickness skin wounds. The control group (n = 2 6) and study group (n = 26) were divided into two groups (n = 13). Wounds were assessed by wound measurements and collection of samples at 9 (A, C) and 21 days (B, D) post-wounding to evaluate the healing process. Variables of interest were gross and microscopic histopathological characteristics were reflective of wound healing. Topical Albusite gel was applied for wound A and B, once a day. Each rat was anesthetized and a round full thickness excisional wound with 150 cm2 area was performed on the right dorsolateral side of each rat. There was little difference between the case and control groups. Wound healing processes and wound closure in the intervention group began sooner and completed more quickly respectively, but both of them did not show a statistically significant difference (p>0.05). The healing of Albusite treated wound was better than the control wounds grossly. The study wounds were biopsied at days 9 and 21, so this might not show different effects of the Albusite gel group in appropriate time. Therefore, further studies are recommended with more sample size and less biopsy interval.

Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats.

Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.