Epigallocatechin-3-gallate promotes wound healing response in diabetic mice by activating keratinocytes and promoting re-epithelialization.

Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol that exhibits anti-inflammatory and anti-oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re-epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re-epithelialization and wound healing in T2D-induced wounds. Murine models of wound healing in T2D were established via feeding high-fat high-fructose diet (HFFD) and the creation of full-thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re-epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch-like ECH-associated protein 1 (KEAP1), thereby inhibiting KEAP1-mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re-epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.

Copaifera langsdorffii Oleoresin-Loaded Nanostructured Lipid Carrier Emulgel Improves Cutaneous Healing by Anti-Inflammatory and Re-Epithelialization Mechanisms.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

Couroupita guianensis bark decoction: From Amazonian medicine to the UHPLC-HRMS chemical profile and its role in inflammation processes and re-epithelialization.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Amazon rainforest, the shamans of the Mayantuyacu site use the healing virtues of decoctions and teas from different parts of the Couroupita guianensis Aubl. (Lecythidaceae) trees as remedies in Ashaninka medicine. However, composition of the remedy and the underlying mechanism remain unclear. AIM OF THE STUDY: This study was designed to compare the metabolite profile of Couroupita guianensis bark decoction produced by Amazonian shamans with that obtained under standardised laboratory conditions and to investigate biological properties of both decoction and isolated constituents in skin wound healing process and inflammation. MATERIALS AND METHODS: The chemical analyses were carried out by Ultra-High-Performance Liquid Chromatography coupled with UV and High-Resolution Mass Spectrometry detectors (UHPLC-UV-HRMS). 1D and 2D-NMR experiments were performed to identify the main decoction constituents. The decoction and pure compound effect on keratinocyte migration was determined by the in vitro wound healing model; the mechanism of action was elucidated by western blot analysis. RESULTS: UHPLC-UV-HRMS analysis revealed the occurrence of polyphenolic compounds as catechins, ellagitannins and, notably, of unusual sulphated derivatives of ellagic acid isolated for the first time from Couroupita guianensis bark. A new natural sulphated molecule [4-(2″-O-sulphate- ß-D-glucuronopyranosyl) ellagic acid] was identified as the potential active compound responsible for the efficacy of bark decoction stimulating wound healing in human HaCaT keratinocytes. The molecular mechanism involved the induction of pro-migratory pathways mediated by ERK and AKT phosphorylation and the increase of MMP2 expression in HaCaT cells. At the same time, the treatment inhibited inflammation interfering with NFkB activation. CONCLUSION: Beyond identifying a new bioactive compound, the overall results scientifically validate the traditional use of Couroupita guianensis bark decoction as an anti-inflammatory remedy. Moreover, the beneficial effects on keratinocytes suggest promising therapeutic applications in skin diseases.

Lycium barbarum polysaccharide promotes corneal Re-epithelialization after alkaline injury.

Chemical injury of the cornea results in epithelial defect and subsequent stromal scarring and infection. Our study aims to evaluate the effectiveness of pre-treatment of Lycium barbarum polysaccharide (LBP) in promoting corneal re-epithelialization after alkaline burn. The corneas of C57BL/6J mice were pre-treated with topical phosphate-buffered saline or LBP (0.2/2/20 mg/mL) for 7 days, following by 0.1M sodium hydroxide injury for 30 s and washing with distilled water for another 30 s. Area of epithelial defect and thickness of cornea were evaluated. Inflammatory cytokines and water channel expression levels were assessed using immunohistochemistry and Western blot. Compared to the injury group, mice with 2 mg/mL LBP pre-treatment revealed a significant decrease in fluorescein stained area after injury (p = 0.025), with increased epithelial layer thickness (p = 0.004). The corneal opacity was significantly reduced in the group with 2 mg/mL LBP pre-treatment followed by injury (p = 0.02). The expression of matrix metalloproteinase 12 (p = 0.033), platelet derived growth factor-BB (p = 0.031), and aquaporin 5 (p = 0.022) resulted in a decrease in expression level in group with 2 mg/mL LBP pre-treatment. Our results showed that 2 mg/mL LBP, with no apoptotic effect on corneal cells, promoted corneal epithelial growth and minimized disruption of the collagen architecture after injury in vivo. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option for patients highly susceptible to ocular injury.

Effects of the Hydnophytum formicarum plant extract on collagen density, angiogenesis, wound length, and re-epithelialization in wound healing: Experimental study on rats.

BACKGROUND: The formation of scar tissue in the wound healing process is associated with fibroblasts that are produced during the proliferation phase (3-14 days after surgery/injury). One of the strategies to suppress the formation of excessive scar tissue is to use wound care material. The use of herbal extracts is currently being investigated by researchers, as it allows avoiding the side effects of synthetic drugs. The Hydnophytum formicarum extract has antioxidant and anti-inflammatory potential. OBJECTIVES: The aim of the study was to analyze the effects of the Hydnophytum formicarum plant extract on collagen density, angiogenesis, wound length, and re-epithelialization in wound healing. MATERIAL AND METHODS: Twenty-four Sprague-Dawley rats were divided into 2 groups: the control group; and the treatment group. Skin wounds were made on the dorsum of the rats, using the biopsy punch technique. Four rats from each group were sacrificed on days 4, 7 and 14 after injury. Collagen density, angiogenesis, wound length, and re-epithelialization were analyzed using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. RESULTS: There were significant differences in the results of the angiogenesis analysis, wound length and re-epithelialization between the treatment and control groups. When considering angiogenesis, there were fewer vessels in the treatment group, but they were more mature as compared to the control group. There was also a meaningful interaction between the application of the Hydnophytum formicarum extract and the necropsy day with regard to collagen density and the re-epithelialization rate. No secondary infection was found in either group. CONCLUSIONS: The topical use of the Hydnophytum formicarum extract affected the formation of scar tissue, as indicated by the positive area of collagen, the extent of angiogenesis, wound length, and the re-epithelialization rate in the early, middle and final granulation phases. The inhibition of angiogenesis through the application of Hydnophytum formicarum was probably related to the formation of scar tissue in the wound.

Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model.

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. ß-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, ß-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the ß-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with ß-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the ß-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1ß and IL-6. After ß-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. ß-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of ß-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.

The effects of photobiomodulation using LED on the repair process of skin graft donor sites.

The benefits of photobiomodulation (PBM) applied to wounds are well-described in the literature; however, its effects in skin graft donor sites have been poorly studied. The aim of this study is to evaluate the effects of LED PBM on re-epithelialization and wound quality of the skin donor site and on pain during repair process. This is a case series study that part of the patients received standard treatment and the others received standard treatment combined with PBM. Data collection was performed at the Burn Unit at a Public Hospital, Brazil. The study had 21 participants and 25 donor sites, 13 in the control group (conventional treatment with Membracel® bandage) and 12 in the experimental group (Membracel® + LED). Irradiation parameters were 1.53 J/cm2, 2.55 mW/cm2, 660 nm, 600 s in the immediate postoperative period as well as on the 1st, 3rd, 5th, and 7th days postoperatively. Pain was measured using the visual analog scale. The Bates-Jensen scale was used to monitor the re-epithelialization process and measurements were performed of donor skin sites in the postoperative period. Quantitative variables were expressed as mean ± standard deviation or median and interquartile range [p25; p75]. The comparison of the distribution of these variables between groups was performed using the Mann-Whitney test. No differences between groups were found for re-epithelialization time, area or quality of the wound. Regarding pain, a significant reduction was found on the 5th postoperative day in the experimental group compared to the control group. PBM did not induce changes in the re-epithelialization period, wound area or wound quality scores of the Bates-Jensen Scale but did induce a reduction in pain compared to the group treated with Membracel® alone.

Combination of Full-Field and Fractional Erbium: YAG Laser for Nonhealing Wounds.

BACKGROUND: To evaluate the outcomes of a heterogeneous group of patients with chronic ulcer receiving a combination regimen of full-field and fractional erbium-doped yttrium aluminum garnet (erbium: YAG) laser applications. METHODS: Enrolled in this study were patients with chronic ulcer who had received at least 2 erbium: YAG laser sessions. Fractional applications followed the initial full-field application for debridement. The therapeutic outcomes were evaluated by serial photographs. The primary outcome measure was the proportion of patients achieving complete re-epithelialization at the first year. RESULTS: Forty-three treatment regions from 23 patients between 40 and 90 years (F: M = 11:12; age: 60.3 ± 15.5 years, mean ± SD) were eligible. The ulcers' median duration was 24 months (min-max: 2-240 months). The median number of laser sessions was 5 (min-max: 2-12). Of arterial (n = 13), immunologic (n = 9), venous (n = 8), diabetic (n = 8), and mechanical ulcers (n = 5), the primary outcome measure was achieved in 69%, 77.7%, 75%, 88.8%, and 100% of the groups, respectively. CONCLUSION: Full-field erbium: YAG laser applications preserve the vascular architecture and enable delicate debridement. Ongoing maintenance fractional laser sessions promote wound healing. Similar to the previous reports of erbium: YAG laser in venous and diabetic ulcers, arterial ulcers, and ulcers of immunologic origin demonstrated an objective treatment response along with different adjuvant approaches.

Evaluation of the alcoholic extract of Dipteryx alata Vogel almonds and bark in skin wound healing in C57BL6 mice / [Avaliação do extrato alcoólico da casca e da semente da Dipteryx alata Vogel na cicatrização da pele de camundongos C57BL/6]

The aim of this study was to evaluate the topical application of alcoholic extracts of Dipteryx alata Vogel almonds and bark in skin wound healing in mice. Fifty-four C57BL/6 mice were equally distributed into three groups: Control, Almond, and Bark. A 9 mm skin fragment was resected from the dorsal region of the animals' thorax. The wounds were submitted to topical application of base cream (vehicle), 10% hydroalcoholic almond extract, or bark extract twice a day. Macroscopic, histological, and immunohistochemical evaluations were conducted on the 7th, 14th, and 21st postoperative days. No significant difference was observed regarding skin wound area among groups, with the parameter presenting only a temporal effect on healing (p>0.05). The almond and control groups exhibited more intense collagenization than the bark group (p<0.05). Dipteryx alata Vogel showed to be inert in the wound healing process in mice.(AU)

O objetivo deste estudo foi avaliar a aplicação tópica do extrato alcoólico da semente e da casca da Dipteryx alata Vogel na cicatrização de feridas cutâneas, em camundongos. Um total de 54 camundongos C57BL/6 foram utilizados neste estudo, distribuídos em três grupos de 18 animais (controle, semente e casca). Em todos os animais, um fragmento de pele foi ressecado da região dorsal do tórax utilizando-se instrumento de punção de 9mm de diâmetro, após o qual foi realizada aplicação tópica de creme base (veículo), extrato hidroalcoólico 10% de semente ou casca, duas vezes ao dia. As avaliações macroscópica, histológica e imuno-histoquímica foram realizadas no sétimo, 14º e 21º dias de pós-operatório. Não foi observada diferença significativa quanto à área da ferida cutânea entre os grupos, apenas um efeito temporal na cicatrização (P>0,05), indicando estágio possivelmente mais avançado desse processo. Porém, na avaliação histológica, os grupos semente e controle apresentaram colagenização mais intensa que o grupo casca (P<0,05). Dipteryx alata Vogel mostrou-se inerte no processo de cicatrização de feridas em camundongos.(AU)

Tratamento de ferida cirúrgica cutânea em ratos com óleo-resina de copaíba (copaíba reticulata) / Treatment of surgical wounds in rats with copaiba oil-resin (copaiba reticulata)

Foi avaliada a atividade cicatrizante do óleo-resina de copaíba "in natura" em feridas cirúrgicas cutâneas induzidas em ratos. Setenta e dois ratos foram distribuídos em três grupos: Grupo Controle Negativo (GCN), Grupo Controle Positivo (GCP) e Grupo Óleo-resina de Copaíba (GOC). A avaliação da hiperemia por escore na macroscopia mostrou que a chance de um animal apresentar um grau de hiperemia baixo quando tratado com o óleo-resina de copaíba é 1,46 vezes maior que um animal tratado com ácidos graxos essenciais e 2,14 vezes maiores que a chance de um animal tratado com óleo mineral. Com relação ao infiltrado inflamatório na microscopia a probabilidade de ser menor ocorre no GOC em comparação com os GCN e GCP. Em relação ao tempo de reepitelização, a chance de um animal apresentar uma reepitelização mais lenta tratado com ácidos graxos essenciais é de 1,2 vezes a chance de um animal tratado com óleo-resina de copaíba. A análise histológica mostrou que o tecido cicatricial após o tratamento com óleo-resina de copaíba apresentou maior contração da ferida e consequentemente redução do tamanho da ferida visto pela aproximação de anexos da pele no corte histológico. Concluiu-se que o tratamento com óleo-resina de copaíba proporciona maior contração da ferida e aproximação dos anexos da pele.

The healing activity of "in natura" oil-resin of copaíba resin was evaluated in cutaneous surgical wounds induced in rats. Seventy-two rats were divided into three groups: Negative Control Group (GCN), Positive Control Group (GCP) and Copaíba Oil-Resin Group (GOC). Evaluation of hyperemia by macroscopic score showed that the chance of an animal presenting a low degree of hyperemia when treated with copaiba oil-resin is 1.46 times higher than an animal treated with essential fatty acids and 2.14 times greater than the chance of an animal treated with mineral oil. With regard to inflammatory infiltrate under microscopy the probability of being smaller occurs in GOC compared to GCN and GCP. Regarding the time of re-epithelialization, the chance of an animal having a slower reepithelization treated with essential fatty acids is 1.2 times the chance of an animal treated with copaiba oil-resin. Histological analysis showed that cicatricial tissue after treatment with copaiba oil-resin presented greater contraction of the wound due to the approximation of skin attachments. It was concluded that the treatment with copaiba oil-resin provides greater contraction of the wound and approximation of the skin attachments.

Medicinal Plants as Efficacious Agents for Diabetic Foot Ulcers: A Systematic Review of Clinical Studies.

A diabetic foot ulcer (DFU) is a chronic, nonhealing wound that occurs in approximately 15% to 25% of patients with diabetes, and amputation is necessary in approximately 5% to 24% of these patients. Medicinal plants have demonstrated promising wound healing activities in animal models of DFUs as well as in clinical studies. These plants, which are described as medicinal in different regions of the world, are not considered to be standard medicinal treatments in Western medicine at this time. Some medicinal products, such as bromelain-an herbal protease currently used for enzymatic debridement of wounds-have been obtained from plants, showing the important role of these natural products as sources of wound healing agents. This paper aims to review clinical studies on the effects of medicinal plants in patients with DFUs based on the improvement of local and systemic parameters related to wound healing. Electronic databases including PubMed, Scopus, and Cochrane Library were searched for studies from inception through May 2019 using the keywords "diabetic foot ulcer" and "plant," "phytochemical," "extract," or "herb." Inclusion criteria were controlled or before-after clinical studies with English-language full-text in which topical or systemic herbal preparations for DFUs were evaluated by considering outcomes such as reduction of wound healing time and wound area, markers of inflammation and oxidative stress, and number of cases requiring amputation. Studies on non-herbal materials and human studies other than clinical trials were excluded. Fourteen studies were included in the present review. Herbal medicines were administered as add-on therapy to standard wound care in the form of topical (cream, gel, oil) or systemic (capsule, decoction, injection) preparations. Parameters such as ulcer width and depth, phagocytic function, tumor necrosis factor α level, epithelialization, vascularization, and wound closure were evaluated in clinical trials, several of which were significantly improved in patients compared with their baseline values or control group. Per the studies included in this review, medicinal plants can be recommended as promising adjuvant therapies to conventional wound care to accelerate wound healing in patients with DFUs.

Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.

In-vivo wound healing activity of a novel composite sponge loaded with mucilage and lipoidal matter of Hibiscus species.

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats.

Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p < 0.05) higher than the control after 21-day treatment and wound closure was ~99% without any adverse systemic reactions. Histological analysis qualitatively revealed an enhanced re-epithelialization and collagen deposition. Moreover, results also showed an improved rate of collagen synthesis and angiogenesis in the group treated with the hydrogel film loaded with Simvastatin. Thus, the present study demonstrated that developed film holds great potential for the acceleration of diabetic wound healing by its pro-angiogenic effect, faster re-epithelialization and increased collagen deposition.

Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds.

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.

Microcurrent electrotherapy improves palatal wound healing: Randomized clinical trial.

BACKGROUND: This study was conducted to assess the clinical, immunological, and patient-centered outcomes of microcurrent electrotherapy on palatal wound healing. METHODS: This was a parallel, double-masked randomized clinical trial, in which 53 patients with ridge preservation indications were selected and randomly assigned to one of two groups. In the control (sham) group (n = 27), palatal wounds, after free gingival grafts (FGG) harvest, received sham application of electrotherapy. In the test (electrotherapy treatment [EE]) group (n = 26), palatal wounds, after FGG harvest, received application of microcurrent electrotherapy protocol. Clinical parameters, patient-centered outcomes, and inflammatory markers were evaluated, up to 90 days postoperatively. RESULTS: The EE group achieved earlier wound closure (P <0.001) and epithelialization (P <0.05; P = 0.03) at 7 and 14 days after harvest when compared with the sham group. Painful symptomatology was reported less frequently in the EE group than in the sham group at 3-day follow-up (P = 0.008). Likewise, an improvement in Oral Health Impact Profile was reported 2 days after the procedure by the EE group (P = 0.04). In addition, favorable modulation of inflammatory wound healing markers occurred when electrotherapy was applied. CONCLUSION: Within the limits of the present study, it can be concluded that the use of a low-intensity electrotherapy protocol may accelerate palatal wound healing and decrease patient discomfort after FGG harvest.

Thyroxine restores severely impaired cutaneous re-epithelialisation and angiogenesis in a novel preclinical assay for studying human skin wound healing under "pathological" conditions ex vivo.

Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.e. hypoxia [5% O2], oxidative damage [10 mM H2O2], absence of insulin, excess glucose). Under these "pathological" conditions, dermal-epidermal split formation and dyskeratosis were prominent in organ-cultured human skin, and epidermal reepithelialisation was significantly impaired (p < 0.001), associated with reduced keratinocyte proliferation (p < 0.001), cytokeratin 6 expression (p < 0.001) and increased apoptosis (p < 0.001). Moreover, markers of intracutaneous angiogenesis (CD31 immunoreactivity and the number of of CD31 positive cells and CD31 positive vessel lumina) were significantly reduced. Since we had previously shown that thyroxine promotes wound healing in healthy human skin ex vivo, we tested whether this in principle also occurs under "pathological" wound healing conditions. Indeed, thyroxine administration sufficed to rescue re-epithelialisation (p < 0.001) and promoted both epidermal keratinocyte proliferation (p < 0.01) and angiogenesis in terms of CD31 immunoreactivity and CD31 positive cells under "pathological" conditions (p < 0.001) ex vivo. This demonstrates the utility of this pragmatic short-term ex vivo model, which recapitulates some key parameters of impaired human skin wound healing, for the preclinical identification of promising wound healing promoters.

Topical administration of hydroethanolic extract of Trifolium pratense (red clover) accelerates wound healing by apoptosis and re-epithelialization.

We investigated the wound healing effects of an ointment prepared from a hydroethanolic extract of Trifolium pratense (red clover) in Wistar rats. An animal model was prepared by making 314 mm2 full thickness skin excisions in all animals. Rats were divided into four experimental groups. Group 1 was a non-intervention control. Groups 2, 3 and 4 were treated topically with ointments containing 1.5, 3.0 and 6% (w/v) T. pretense extract, respectively. We evaluated the effects of these ointments by histological analysis of collagen production, epidermis thickness, fibroblast distribution and wound contraction ratio, and also by estimating expression of Bax, Bcl-2 and p53. Collagen production, epidermis thickness, fibroblast distribution and wound contraction ratio were significantly increased in groups 2 - 4 compared to group 1. Groups 2 - 4 also exhibited significantly increased levels of Bcl-2 mRNA and reduced mRNA levels of Bax and p53 compared to group 1. Groups 2 - 4 exhibited accelerated healing by up-regulating Bcl-2 expression, reducing p53 and Bax levels, and by promoting the proliferative phase of healing. We suggest that a hydroethanolic extract of T. pratense in commercial ointments may be useful for promoting wound healing.