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Sample records for cutaneous wound repair

  1. uPARAP function in cutaneous wound repair.

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    Maryam G Rohani

    Full Text Available Optimal skin wound healing relies on tight balance between collagen synthesis and degradation in new tissue formation and remodeling phases. The endocytic receptor uPARAP regulates collagen uptake and intracellular degradation. In this study we examined cutaneous wound repair response of uPARAP null (uPARAP-/- mice. Full thickness wounds were created on dorsal surface of uPARAP-/- or their wildtype littermates. Wound healing evaluation was done by macroscopic observation, histology, gene transcription and biochemical analysis at specific intervals. We found that absence of uPARAP delayed re-epithelialization during wound closure, and altered stiffness of the scar tissue. Despite the absence of the uPARAP-mediated intracellular pathway for collagen degradation, there was no difference in total collagen content of the wounds in uPARAP-/- compared to wildtype mice. This suggests in the absence of uPARAP, a compensatory feedback mechanism functions to keep net collagen in balance.

  2. Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

    NARCIS (Netherlands)

    Cremers, Niels A. J.; Wever, Kimberley E.; Wong, Ronald J.; van Rheden, Rene E. M.; Vermeij, Eline A.; van Dam, Gooitzen M.; Carels, Carine E. L.; Lundvig, Ditte M. S.; Wagener, Frank A D T G

    2017-01-01

    Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was

  3. Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

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    Niels A. J. Cremers

    2017-02-01

    Full Text Available Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1 and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection.

  4. Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

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    Cremers, Niels A. J.; Wever, Kimberley E.; Wong, Ronald J.; van Rheden, René E. M.; Vermeij, Eline A.; van Dam, Gooitzen M.; Carels, Carine E.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

    2017-01-01

    Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection. PMID:28218659

  5. Effect of ginseng root polysaccharides on cutaneous wound repair in ...

    African Journals Online (AJOL)

    The 30 mg WGP group showed 85.0 % wound healing, while control group showed ... cells, resulting in increased fibroblast division, collagen synthesis, and production of blood cells during wound ... The skin plays a crucial role in maintaining.

  6. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair.

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    Huang, Sha; Lu, Gang; Wu, Yan; Jirigala, Enhe; Xu, Yongan; Ma, Kui; Fu, Xiaobing

    2012-04-01

    Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute to wound healing after skin injury. However, the role of BM-MSCs on repairing skin appendages in renewal tissues is incompletely explored. Moreover, most preclinical studies suggest that the therapeutic effects afforded by BM-MSCs transplantation are short-lived and relatively unstable. To assess whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery system can participate in cutaneous wound healing and sweat-gland repair in mice. For safe and effective delivery of BM-MSCs to wounds, epidermal growth factor (EGF) microspheres were firstly developed to both support cells and maintain appropriate stimuli, then cell-seeded microspheres were incorporated with biomimetic scaffolds and thus fabricated an engineered skin construct with epithelial differentiation and proliferative potential. The applied efficacy was examined by implanting them into excisional wounds on both back and paws of hind legs in mice. After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated wounds exhibited accelerated healing with increased re-epithelialization rates and less skin contraction. Furthermore, histological and immunofluorescence staining analysis revealed sweat glands-like structures became more apparent in BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM-MSCs were decreased gradually in later phases of healing progression. Our study suggests that BM-MSCs delivered by this EGF microspheres-based engineered skin model may be a promising strategy to repair sweat glands and improve cutaneous wound healing after injury and success in this study might provide a potential benefit for BM-MSCs administration clinically. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Biodegradable polymer nanofiber membrane for the repair of cutaneous wounds in dogs - two case reports

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    Lívia Gomes Amaral

    2016-12-01

    Full Text Available The study of wound healing and its treatment is extremely important in veterinary medicine due to the high frequency of wounds and the difficulty in treating wounds by second intention. Thus, the objective of this study was to evaluate the use of a nanofiber membrane made of biodegradable polymers as a method of wound treatment in dogs. This study comprised two dogs with bite wounds. Debridement and cleaning was performed followed by the application of the membrane. In one dog, the wound was in the left proximal calcaneal region with clinical signs of infection, necrotic tissue, and muscle and the gastrocnemius tendon were exposed. The wound displayed rapid formation of granulation tissue which became excessive, so it was necessary to debride several times. However, with the suspension of the use of the membrane, formation of this tissue was not observed, and the wound evolved to epithelialization and fast contraction. In the second dog, there was a deep wound on the medial aspect of the proximal right hind limb, with clinical signs of infection, with muscle exposure. Once the membrane was placed, granulation tissue formed, and the membrane was used until the level of this tissue reached the skin. The wound underwent rapid epithelialization and contraction, without developing exuberant granulation tissue. Efficient wound repair was observed and the dogs exhibited greater comfort during application and use of the membrane. More studies should be conducted in dogs focusing on the application of this membrane until the appearance of healthy granulation tissue, as continued use seems to stimulate the formation of exuberant granulation tissue.

  8. RIP4 is a target of multiple signal transduction pathways in keratinocytes: Implications for epidermal differentiation and cutaneous wound repair

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Stephanie [Charite, University Medicine Berlin, Institute of Physiology, Arnimallee 22, D-14195 Berlin (Germany); Munz, Barbara, E-mail: barbara.munz@charite.de [Charite, University Medicine Berlin, Institute of Physiology, Arnimallee 22, D-14195 Berlin (Germany)

    2010-01-01

    Receptor interacting protein 4 (RIP4) is an important regulator of epidermal morphogenesis during embryonic development. We could previously show that expression of the rip4 gene is strongly downregulated in cutaneous wound repair, which might be initiated by a broad variety of growth factors and cytokines. Here, we demonstrate that in keratinocytes, rip4 expression is controlled by a multitude of different signal transduction pathways, such as the p38 mitogen-activated protein kinase (MAPK) and the nuclear factor kappa B (NF-{kappa}B) cascade, in a unique and specific manner. Furthermore, we show that the steroid dexamethasone abolishes the physiological rip4 downregulation after injury and might thus contribute to the phenotype of reduced and delayed wound reepithelialization seen in glucocorticoid-treated patients. As a whole, our data indicate that rip4 expression is regulated in a complex manner, which might have therapeutic implications.

  9. Acceleration of cutaneous wound healing by brassinosteroids.

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    Esposito, Debora; Rathinasabapathy, Thirumurugan; Schmidt, Barbara; Shakarjian, Michael P; Komarnytsky, Slavko; Raskin, Ilya

    2013-01-01

    Brassinosteroids are plant growth hormones involved in cell growth, division, and differentiation. Their effects in animals are largely unknown, although recent studies showed that the anabolic properties of brassinosteroids are possibly mediated through the phosphoinositide 3-kinase/protein kinase B signaling pathway. Here, we examined biological activity of homobrassinolide (HB) and its synthetic analogues in in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full-thickness dermal wound, and the rate of wound closure was assessed daily for 10 days, with adenosine receptor agonist CGS-21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of transforming growth factor beta and intercellular adhesion molecule 1 were significantly lower, while tumor necrosis factor alpha was nearly suppressed in the wounds from treated mice. Our data suggest that topical application of brassinosteroids accelerates wound healing by positively modulating inflammatory and reepithelialization phases of the wound repair process, in part by enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in the wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing.

  10. Mechanics of cutaneous wound rupture.

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    Swain, Digendranath; Gupta, Anurag

    2016-11-07

    A cutaneous wound may rupture during healing as a result of stretching in the skin and incompatibility at the wound-skin interface, among other factors. By treating both wound and skin as hyperelastic membranes, and using a biomechanical framework of interfacial growth, we study rupturing as a problem of cavitation in nonlinear elastic materials. We obtain analytical solutions for deformation and residual stress field in the skin-wound configuration while emphasizing the coupling between wound rupture and wrinkling in the skin. The solutions are analyzed in detail for variations in stretching environment, healing condition, and membrane stiffness.

  11. Wnt signaling induces epithelial differentiation during cutaneous wound healing

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    Hocking Anne

    2006-01-01

    Full Text Available Abstract Background Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair. Results We determined that the expression of Wnt ligands that typically signal via the beta-catenin-independent pathway is up-regulated in the wound while the beta-catenin-dependent Wnt signaling is activated in the hair follicles adjacent to the wound edge. Ectopic activation of beta-catenin-dependent Wnt signaling with lithium chloride in the wound resulted in epithelial cysts and occasional rudimentary hair follicle structures within the epidermis. In contrast, forced expression of Wnt-5a in the deeper wound induced changes in the interfollicular epithelium mimicking regeneration, including formation of epithelia-lined cysts in the wound dermis, rudimentary hair follicles and sebaceous glands, without formation of tumors. Conclusion These findings suggest that adult interfollicular epithelium is capable of responding to Wnt morphogenic signals necessary for restoring epithelial tissue patterning in the skin during wound repair.

  12. Wound repair in Pocillopora

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    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo

    2016-01-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  13. Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing

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    Zhong Zheng, PhD

    2014-12-01

    Conclusions: Altogether, we demonstrated that in addition to reducing scar formation, FMOD also promotes angiogenesis. As blood vessels organize and regulate wound healing, its potent angiogenic properties will further expand the clinical application of FMOD for cutaneous healing of poorly vascularized wounds.

  14. Gene expression profiling of cutaneous wound healing

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    Wang Ena

    2007-02-01

    Full Text Available Abstract Background Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. Study Design This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days. 17.5K cDNA microarrays were utilized to profile the biopsy material. Results Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies and repair and angiogenesis genes in the later (4 to 8 days biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. Conclusion The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2

  15. Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses

    OpenAIRE

    Nadine Jetten; Nadia Roumans; Marion J. Gijbels; Andrea Romano; Post, Mark J.; de Winther, Menno P.J.; Van der Hulst, Rene R. W. J.; Sofia Xanthoulea

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macr...

  16. Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius.

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    Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

    2015-11-01

    Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing.

  17. Effect of astaxanthin on cutaneous wound healing

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    Meephansan J

    2017-07-01

    Full Text Available Jitlada Meephansan,1 Atiya Rungjang,1 Werayut Yingmema,2 Raksawan Deenonpoe,3 Saranyoo Ponnikorn3 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; 2Laboratory Animal Centers, Thammasat University, Pathum Thani, Thailand; 3Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand Abstract: Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing. Keywords: astaxanthin, wound healing, reactive oxygen species, antioxidant 

  18. Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing

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    Lange-Asschenfeldt, Susanne; Bob, Adrienne; Terhorst, Dorothea; Ulrich, Martina; Fluhr, Joachim; Mendez, Gil; Roewert-Huber, Hans-Joachim; Stockfleth, Eggert; Lange-Asschenfeldt, Bernhard

    2012-07-01

    There is a high demand for noninvasive imaging techniques for wound assessment. In vivo reflectance confocal laser scanning microscopy (CLSM) represents an innovative optical technique for noninvasive evaluation of normal and diseased skin in vivo at near cellular resolution. This study was designed to test the feasibility of CLSM for noninvasive analysis of cutaneous wound healing in 15 patients (7 male/8 female), including acute and chronic, superficial and deep dermal skin wounds. A commercially available CLSM system was used for the assessment of wound bed and wound margins in order to obtain descriptive cellular and morphological parameters of cutaneous wound repair noninvasively and over time. CLSM was able to visualize features of cutaneous wound repair in epidermal and superficial dermal wounds, including aspects of inflammation, neovascularisation, and tissue remodelling in vivo. Limitations include the lack of mechanic fixation of the optical system on moist surfaces restricting the analysis of chronic skin wounds to the wound margins, as well as a limited optical resolution in areas of significant slough formation. By describing CLSM features of cutaneous inflammation, vascularisation, and epithelialisation, the findings of this study support the role of CLSM in modern wound research and management.

  19. Effect of astaxanthin on cutaneous wound healing.

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    Meephansan, Jitlada; Rungjang, Atiya; Yingmema, Werayut; Deenonpoe, Raksawan; Ponnikorn, Saranyoo

    2017-01-01

    Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing.

  20. The Role of Neuromediators and Innervation in Cutaneous Wound Healing.

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    Ashrafi, Mohammed; Baguneid, Mohamed; Bayat, Ardeshir

    2016-06-15

    The skin is densely innervated with an intricate network of cutaneous nerves, neuromediators and specific receptors which influence a variety of physiological and disease processes. There is emerging evidence that cutaneous innervation may play an important role in mediating wound healing. This review aims to comprehensively examine the evidence that signifies the role of innervation during the overlapping stages of cutaneous wound healing. Numerous neuropeptides that are secreted by the sensory and autonomic nerve fibres play an essential part during the distinct phases of wound healing. Delayed wound healing in diabetes and fetal cutaneous regeneration following wounding further highlights the pivotal role skin innervation and its associated neuromediators play in wound healing. Understanding the mechanisms via which cutaneous innervation modulates wound healing in both the adult and fetus will provide opportunities to develop therapeutic devices which could manipulate skin innervation to aid wound healing.

  1. Repair of cutaneous wounds with the use of low cost surgical glue Reparo de feridas cutâneas usando cola cirúrgica de baixo custo

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    Sandro Cilindro de Souza

    2012-04-01

    Full Text Available BACKGROUND: The advantages of the cyanoacrylates in cutaneous synthesis have been often demonstrated in the literature. However, these products have been underutilized in Brazil due to the high costs of the 2-octil-cyanoacrylate. Besides, few studies have been done with the more economically accessible form, the 2-etil-cyanoacrylate, as a cutaneous tissue adhesive. OBJECTIVE: To evaluate the effectiveness of the closing of cutaneous lesions using ECA. METHOD: This was a prospective study in which 46 wounds were occluded using the low cost ECA as an alternative to intradermal suture. RESULTS: Excisions (97,8% and traumatic wounds (2,2% were treated with 2-etil-cyanoacrylate and deep relaxed sutures as synthesis method. Unaesthetic scars (22%, infection (2,1%, dehiscence (2,1% and contact allergic dermatitis (2,1% were the problems we found. There were no cases of necrosis or keloids. The results were considered satisfactory in most cases (97,3%. CONCLUSION: The use of 2-etil-cyanoacrylate was shown to be safe and with satisfactory cosmetic results in this group of patients.FUNDAMENTOS: As vantagens dos cianoacrilatos em síntese cutânea têm sido sobejamente mostradas na literatura. Entretanto, estes produtos têm sido subutilizados no Brazil devido aos elevados custos do 2-octilcianoacrilato. Ademais, a forma mais economicamente acessível, o 2-etilcianoacrilato, tem sido pouco estudada como adesivo cutâneo. OBJETIVO: Avaliação da eficácia do fechamento de lesões cutâneas usando o 2-etilcianoacrilato. MÉTODO: Estudo prospectivo no qual 46 feridas foram ocluídas usando o 2-etilcianoacrilato de baixo custo como alternativa a sutura intradérmica. RESULTADOS: Feridas excisionais (97,8% e traumática (2,2% foram tratadas com 2-etilcianoacrilato e suturas profundas relaxadoras como método de síntese. Cicatrizes inestéticas (22%, infecção (2,1%, deiscência (2,1% e dermatite alérgica de contato (2,1% foram os problemas encontrados. N

  2. Platelet gel for healing cutaneous chronic wounds.

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    Crovetti, Giovanni; Martinelli, Giovanna; Issi, Marwan; Barone, Marilde; Guizzardi, Marco; Campanati, Barbara; Moroni, Marco; Carabelli, Angelo

    2004-04-01

    Wound healing is a specific host immune response for restoration of tissue integrity. Experimental studies demonstrated an alteration of growth factors activity due to their reduced synthesis, increased degradation and inactivation. In wound healing platelets play an essential role since they are rich of alpha-granules growth factors (platelet derived growth factor--PDGF; transforming growth factor-beta--TGF-beta; vascular endothelial growth factor--VEGF). Topical use of platelet gel (PG), hemocomponent obtained from mix of activated platelets and cryoprecipitate, gives the exogenous and in situ adding of growth factors (GF). The hemocomponents are of autologous or homologous origin. We performed a technique based on: multicomponent apheretic procedure to obtain plasma rich platelet and cryoprecipitate; manual processing in an open system, in sterile environment, for gel activation. Every step of the gel synthesis was checked by a quality control programme. The therapeutic protocol consists of the once-weekly application of PG. Progressive reduction of the wound size, granulation tissue forming, wound bed detersion, regression and absence of infective processes were considered for evaluating clinical response to hemotherapy. 24 patients were enrolled. They had single or multiple cutaneous ulcers with different ethiopathogenesis. Only 3 patients could perform autologous withdrawal; in the others homologous hemocomponent were used, always considering suitability and traceability criteria for transfusional use of blood. Complete response was observed in 9 patients, 2 were subjected to cutaneous graft, 4 stopped treatment, 9 had partial response and are still receiving the treatment. In each case granulation tissue forming increased following to the first PG applications, while complete re-epithelization was obtained later. Pain was reduced in every treated patient. Topical haemotherapy with PG may be considered as an adjuvant treatment of a multidisciplinary process

  3. IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing.

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    Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C; Kim, Brian S; Wang, Kelvin; Bayat, Ardeshir; Artis, David; Volk, Susan W

    2016-02-01

    Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after exposure to allergens, pathogens, or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. In addition, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity after injury.

  4. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

    OpenAIRE

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S.; JUNG, Dong-In; Park, Hee-Myung

    2013-01-01

    Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 ...

  5. Cutaneous wound healing: Current concepts and advances in wound care

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    Klein, Kenneth C; Guha, Somes Chandra

    2014-01-01

    A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care.[1] It is a snapshot of a patient's total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors.[2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as used at our institution (CAMC), and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society) may vary widely from country to country and payment system.[3] In the USA, CMS (Centers for Medicare and Medicaid Services) approved indications for HBOT vary from that of the UHMS for logistical reasons.[1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise. PMID:25593414

  6. Cutaneous wound healing: Current concepts and advances in wound care

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    Kenneth C Klein

    2014-01-01

    Full Text Available A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care. [1] It is a snapshot of a patient′s total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors. [2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT, as used at our institution (CAMC, and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society may vary widely from country to country and payment system. [3] In the USA, CMS (Centers for Medicare and Medicaid Services approved indications for HBOT vary from that of the UHMS for logistical reasons. [1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise.

  7. Differences in cutaneous wound healing between dogs and cats.

    Science.gov (United States)

    Bohling, Mark W; Henderson, Ralph A

    2006-07-01

    Regardless of the species involved, wound healing follows a predictable course of overlapping phases. In spite of these commonalities, significant species differences in cutaneous wound healing have been uncovered in the Equidae and, more recently, between the dog and cat. It has also recently been shown that the subcutaneous tissues play an important supporting role in cutaneous wound healing, which may help to ex-plain healing differences between cats and dogs. These discoveries may improve veterinarians' understanding of problem wound healing in the cat and, hopefully, lead to better strategies for wound management in this sometimes troublesome species.

  8. Therapeutic potential of bone marrow-derived mesenchymal stem cells in cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Jerry S Chen

    2012-07-01

    Full Text Available Despite advances in wound care, many wounds never heal and become chronic problems that result in significant morbidity and mortality to the patient. Cellular therapy for cutaneous wounds has recently come under investigation as a potential treatment modality for impaired wound healing. Bone marrow-derived mesenchymal stem cells (MSCs are a promising source of adult progenitor cells for cytotherapy as they are easy to isolate and expand and have been shown to differentiate into various cell lineages. Early studies have demonstrated that MSCs may enhance epithelialization, granulation tissue formation, and neovascularization resulting in accelerated wound closure. It is currently unclear if these effects are mediated through cellular differentiation or by secretion of cytokines and growth factors. This review discusses the proposed biological contributions of MSCs to cutaneous repair and their clinical potential in cell-based therapies.

  9. Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.

    Science.gov (United States)

    Jetten, Nadine; Roumans, Nadia; Gijbels, Marion J; Romano, Andrea; Post, Mark J; de Winther, Menno P J; van der Hulst, Rene R W J; Xanthoulea, Sofia

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.

  10. Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing.

    Science.gov (United States)

    Guo, Yuanyuan; Yang, Zhiyin; Wu, Shan; Xu, Peng; Peng, Yinbo; Yao, Min

    2017-02-01

    The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage-related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.

  11. IL-33 accelerates cutaneous wound healing involved in upregulation of alternatively activated macrophages.

    Science.gov (United States)

    Yin, Hui; Li, Xiangyong; Hu, Shilian; Liu, Tao; Yuan, Baohong; Gu, Hongbiao; Ni, Qian; Zhang, Xiaofan; Zheng, Fang

    2013-12-01

    IL-33 is a recently recognized member of the IL-1 family and has been best identified as a potent inducer of Th2-type immune responses. Increasing evidence, however, indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration and repair. In this study, we further explore the potential effect of IL-33 in cutaneous wound healing. A full-thickness skin wound was generated on the back of mice and treated with IL-33 or vehicle intraperitoneally. Our results revealed that the levels of IL-33 mRNA and protein were significantly enhanced in incisional wound skin. Meantime, administration of IL-33 obviously accelerated wound healing with wounds gaping narrower and exhibiting enhanced reepithelialization. IL-33 upregulation also promoted the collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a direct effect of IL-33 on matrix synthesis. Furthermore, IL-33 facilitated the development of alternatively activated macrophages (AAM) in incisional wound tissue, which closely related to resolution of inflammation and promotion of wound repair. Taken together, these findings suggest that IL-33 may play a pivotal role in maintenance of cutaneous homeostasis and acceleration of normal wound healing.

  12. Image-guided plasma therapy of cutaneous wound

    Science.gov (United States)

    Zhang, Zhiwu; Ren, Wenqi; Yu, Zelin; Zhang, Shiwu; Yue, Ting; Xu, Ronald

    2014-02-01

    The wound healing process involves the reparative phases of inflammation, proliferation, and remodeling. Interrupting any of these phases may result in chronically unhealed wounds, amputation, or even patient death. Despite the clinical significance in chronic wound management, no effective methods have been developed for quantitative image-guided treatment. We integrated a multimodal imaging system with a cold atmospheric plasma probe for image-guided treatment of chronic wound. Multimodal imaging system offers a non-invasive, painless, simultaneous and quantitative assessment of cutaneous wound healing. Cold atmospheric plasma accelerates the wound healing process through many mechanisms including decontamination, coagulation and stimulation of the wound healing. The therapeutic effect of cold atmospheric plasma is studied in vivo under the guidance of a multimodal imaging system. Cutaneous wounds are created on the dorsal skin of the nude mice. During the healing process, the sample wound is treated by cold atmospheric plasma at different controlled dosage, while the control wound is healed naturally. The multimodal imaging system integrating a multispectral imaging module and a laser speckle imaging module is used to collect the information of cutaneous tissue oxygenation (i.e. oxygen saturation, StO2) and blood perfusion simultaneously to assess and guide the plasma therapy. Our preliminary tests show that cold atmospheric plasma in combination with multimodal imaging guidance has the potential to facilitate the healing of chronic wounds.

  13. Effect of Propolis on Experimental Cutaneous Wound Healing in Dogs

    Science.gov (United States)

    2015-01-01

    This study evaluates clinically the effect of propolis paste on healing of cutaneous wound in dogs. Under general anesthesia and complete aseptic conditions, two full thickness skin wounds (3 cm diameter) were created in each side of the chest in five dogs, one dorsal and one ventral, with 10 cm between them. These wounds were randomly allocated into two groups, control group (10 wounds) and propolis group (10 wounds). Both groups were represented in each dog. The wounds were cleaned with normal saline solution and dressed with macrogol ointment in control group and propolis paste in propolis group, twice daily till complete wound healing. Measurement of the wound area (cm2) was monitored planimetrically at 0, 7, 14, 21, 28, and 35 days after injury. The data were analyzed statistically. The results revealed a significant reduction in the wound surface area in the propolis group after 14 and 21 days compared to control group. The wound reepithelization, contraction, and total wound healing were faster in propolis group than in control group during five weeks of study. In conclusion, propolis paste has a positive impact on cutaneous wound healing and it may be suggested for treating various types of wounds in animals. PMID:26783495

  14. Abnormal pigmentation within cutaneous scars: A complication of wound healing

    Directory of Open Access Journals (Sweden)

    Sarah Chadwick

    2012-01-01

    Full Text Available Abnormally pigmented scars are an undesirable consequence of cutaneous wound healing and are a complication every single individual worldwide is at risk of. They present a challenge for clinicians, as there are currently no definitive treatment options available, and render scars much more noticeable making them highly distressing for patients. Despite extensive research into both wound healing and the pigment cell, there remains a scarcity of knowledge surrounding the repigmentation of cutaneous scars. Pigment production is complex and under the control of many extrinsic and intrinsic factors and patterns of scar repigmentation are unpredictable. This article gives an overview of human skin pigmentation, repigmentation following wounding and current treatment options.

  15. Evaluation of Therapeutic Intervention with a Natural Product in Cutaneous Wound Healing: The Use of Capybara Oil

    Directory of Open Access Journals (Sweden)

    Polyana Cury Marinho

    2013-01-01

    Full Text Available Capybara oil is commonly used for cutaneous wound healing in traditional South American medicine, although its beneficial effect has never been experimentally proven. The aim of this study was to investigate the effects of the topical application of capybara oil on skin wounds in Swiss mice. The following characteristics of the wounds were observed and evaluated: wound contraction and reepithelialization, the number of polymorphonuclear leukocytes and mast cells, the thickness of the neoepidermis, and the distribution of collagen and elastic fibers. Our study showed that oil extracted from subcutaneous capybara fat was beneficial for wound healing, indicating that capybara oil plays an important role in promoting tissue repair.

  16. Evaluation of therapeutic intervention with a natural product in cutaneous wound healing: the use of capybara oil.

    Science.gov (United States)

    Marinho, Polyana Cury; Neto-Ferreira, Rodrigo; José de Carvalho, Jorge

    2013-01-01

    Capybara oil is commonly used for cutaneous wound healing in traditional South American medicine, although its beneficial effect has never been experimentally proven. The aim of this study was to investigate the effects of the topical application of capybara oil on skin wounds in Swiss mice. The following characteristics of the wounds were observed and evaluated: wound contraction and reepithelialization, the number of polymorphonuclear leukocytes and mast cells, the thickness of the neoepidermis, and the distribution of collagen and elastic fibers. Our study showed that oil extracted from subcutaneous capybara fat was beneficial for wound healing, indicating that capybara oil plays an important role in promoting tissue repair.

  17. Complement deficiency promotes cutaneous wound healing in mice.

    Science.gov (United States)

    Rafail, Stavros; Kourtzelis, Ioannis; Foukas, Periklis G; Markiewski, Maciej M; DeAngelis, Robert A; Guariento, Mara; Ricklin, Daniel; Grice, Elizabeth A; Lambris, John D

    2015-02-01

    Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3(-/-) mice exhibit accelerated early stages of wound healing. Reconstitution of C3(-/-) mice with serum from C3(+/+) mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3(-/-) mice revealed a reduction in inflammatory infiltrate compared with C3(+/+) mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1(-/-) mice, but not C3aR(-/-) or C5aR2(-/-) mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing.

  18. Targeted Inhibition of PAI-1 Activity Impairs Epithelial Migration and Wound Closure Following Cutaneous Injury.

    Science.gov (United States)

    Simone, Tessa M; Longmate, Whitney M; Law, Brian K; Higgins, Paul J

    2015-06-01

    Objective: Aberrant plasminogen activator inhibitor-1 (PAI-1) expression and activity have been implicated in bleeding disorders, multiorgan fibrosis, and wound healing anomalies. This study details the physiological consequences of targeted PAI-1 functional inhibition on cutaneous injury repair. Approach: Dorsal skin wounds from FVB/NJ mice, created with a 4 mm biopsy punch, were treated topically with the small-molecule PAI-1 antagonist tiplaxtinin (or vehicle control) for 5 days and then analyzed for markers of wound repair. Results: Compared to controls, tiplaxtinin-treated wounds displayed dramatic decreases in wound closure and re-epithelialization. PAI-1 immunoreactivity was evident at the migratory front in all injury sites indicating these effects were due to PAI-1 functional blockade and not PAI-1 expression changes. Stimulated HaCaT keratinocyte migration in response to recombinant PAI-1 in vitro was similarly attenuated by tiplaxtinin. While tiplaxtinin had no effect on keratinocyte proliferation, cell cycle progression, or apoptosis, it effectively reduced collagen deposition, the number of Ki-67(+) fibroblasts, and incidence of differentiated myofibroblasts (i.e., smooth muscle α-actin immunoreactive cells), but not fibroblast apoptosis. Innovation: The role for PAI-1 in hemostasis and fibrinolysis is established; involvement of PAI-1 in cutaneous wound healing, however, remains unclear. This study tests the effect of a small-molecule PAI-1 inhibitor in a murine model of skin wound repair. Conclusion: Loss of PAI-1 activity significantly impaired wound closure. Re-epithelialization and fibroblast recruitment/differentiation were both reduced in tiplaxtinin-treated mice. Therapies directed at manipulation of PAI-1 expression and/or activity may have applicability as a treatment option for chronic wounds and scarring disorders.

  19. The Role of Iron in the Skin & Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Josephine Anne Wright

    2014-07-01

    Full Text Available In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS generated in the skin by ultraviolet (UVA 320-400 nm portion of the ultraviolet spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anaemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anaemia on wound healing using a variety of experimental methodology to establish anaemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialisation. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localised iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary haemochromatosis. Iron plays a key role in chronic ulceration and conditions such as Rheumatoid Arthritis (RA and Lupus Erythematosus are associated with both anaemia of chronic disease and dysregulation of local cutaneous iron haemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation.

  20. MicroRNAs as regulators of cutaneous wound healing

    Indian Academy of Sciences (India)

    Wing-Fu Lai; Parco M Siu

    2014-06-01

    MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, and have displayed important roles in areas spanning from embryonic development to skin physiology. Despite this, till now little is known about the significance of miRNAs in cutaneous wound healing. In this mini-review, we discuss the existing evidence on the roles of miRNAs in physiological processes relevant to cutaneous wound healing, followed by a highlight of the prospects and challenges of future development of miRNA-based wound therapies. With existing technologies of nucleic acid transfer and miRNA modulation, it is anticipated that once the roles of miRNAs in wound healing have been clarified, there will be a vast new vista of opportunities brought up for development of miRNA-targeted therapies for wound care.

  1. A coordinated approach to cutaneous wound healing: vibrational microscopy and molecular biology.

    Science.gov (United States)

    Andrew Chan, K L; Zhang, Guojin; Tomic-Canic, Marjana; Stojadinovic, Olivera; Lee, Brian; Flach, Carol R; Mendelsohn, Richard

    2008-10-01

    The repair of cutaneous wounds in the adult body involves a complex series of spatially and temporally organized processes to prevent infection and restore homeostasis. Three characteristic phases of wound repair (inflammation, proliferation including re-epithelialization and remodelling) overlap in time and space. We have utilized a human skin wound-healing model to correlate changes in genotype and pheno-type with infrared (IR) and confocal Raman spectroscopic images during the re-epithelialization of excisional wounds. The experimental protocols validated as IR images clearly delineate the keratin-rich migrating epithelial tongue from the collagen-rich wound bed. Multivariate statistical analysis of IR datasets acquired 6 days post-wounding reveal subtle spectral differences that map to distinct spatial distributions, which are correlated with immunofluorescent staining patterns of different keratin types. Images computed within collagen-rich regions expose complementary spatial patterns and identify elastin in the wound bed. The temporal sequence of events is explored through a comparison of gene array analysis with confocal Raman microscopy. Our approach demonstrates the feasibility of acquiring detailed molecular structure information from the various proteins and their subclasses involved in the wound-healing process.

  2. Cutaneous wound healing in aging small mammals: a systematic review.

    Science.gov (United States)

    Kim, Dong Joo; Mustoe, Thomas; Clark, Richard A F

    2015-01-01

    As the elderly population grows, so do the clinical and socioeconomic burdens of nonhealing cutaneous wounds, the majority of which are seen among persons over 60 years of age. Human studies on how aging effects wound healing will always be the gold standard, but studies have ethical and practical hurdles. Choosing an animal model is dictated by costs and animal lifespan that preclude large animal use. Here, we review the current literature on how aging effects cutaneous wound healing in small animal models and, when possible, compare healing across studies. Using a literature search of MEDLINE/PubMed databases, studies were limited to those that utilized full-thickness wounds and compared the wound-healing parameters of wound closure, reepithelialization, granulation tissue fill, and tensile strength between young and aged cohorts. Overall, wound closure, reepithelialization, and granulation tissue fill were delayed or decreased with aging across different strains of mice and rats. Aging in mice was associated with lower tensile strength early in the wound healing process, but greater tensile strength later in the wound healing process. Similarly, aging in rats was associated with lower tensile strength early in the wound healing process, but no significant tensile strength difference between young and old rats later in healing wounds. From studies in New Zealand White rabbits, we found that reepithelialization and granulation tissue fill were delayed or decreased overall with aging. While similarities and differences in key wound healing parameters were noted between different strains and species, the comparability across the studies was highly questionable, highlighted by wide variability in experimental design and reporting. In future studies, standardized experimental design and reporting would help to establish comparable study groups, and advance the overall knowledge base, facilitating the translatability of animal data to the human clinical condition.

  3. Effects of genistein on early-stage cutaneous wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyo [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Seung Min [Research Institute of Health Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Jung, In-Kyung [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lim, Yunsook [Department of Foods and Nutrition, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Jung-Hyun, E-mail: jjhkim@cau.ac.kr [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of)

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  4. Receptor-Interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing.

    Directory of Open Access Journals (Sweden)

    Andrew Godwin

    Full Text Available Wound healing consists of a complex, dynamic and overlapping process involving inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular level is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3 controls programmed necrosis in response to TNF-α during inflammation and has been shown to be highly induced during cutaneous wound repair. However, its role in wound healing remains to be demonstrated. To study this, we created dorsal cutaneous wounds on male wild-type (WT and RIPK3-deficient (Ripk3-/- mice. Wound area was measured daily until day 14 post-wound and skin tissues were collected from wound sites at various days for analysis. The wound healing rate in Ripk3-/- mice was slower than the WT mice over the 14-day course; especially, at day 7, the wound size in Ripk3-/- mice was 53% larger than that of WT mice. H&E and Masson-Trichrome staining analysis showed impaired quality of wound closure in Ripk3-/- wounds with delayed re-epithelialization and angiogenesis and defected granulation tissue formation and collagen deposition compared to WT. The neutrophil infiltration pattern was altered in Ripk3-/- wounds with less neutrophils at day 1 and more neutrophils at day 3. This altered pattern was also reflected in the differential expression of IL-6, KC, IL-1β and TNF-α between WT and Ripk3-/- wounds. MMP-9 protein expression was decreased with increased Timp-1 mRNA in the Ripk3-/- wounds compared to WT. The microvascular density along with the intensity and timing of induction of proangiogenic growth factors VEGF and TGF-β1 were also decreased or delayed in the Ripk3-/- wounds. Furthermore, mouse embryonic fibroblasts (MEFs from Ripk3-/- mice migrated less towards chemoattractants TGF-β1 and PDGF than MEFs from WT mice. These results clearly demonstrate that RIPK3 is an essential molecule to maintain the temporal manner of the

  5. Receptor-Interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing.

    Science.gov (United States)

    Godwin, Andrew; Sharma, Archna; Yang, Weng-Lang; Wang, Zhimin; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    Wound healing consists of a complex, dynamic and overlapping process involving inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular level is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3) controls programmed necrosis in response to TNF-α during inflammation and has been shown to be highly induced during cutaneous wound repair. However, its role in wound healing remains to be demonstrated. To study this, we created dorsal cutaneous wounds on male wild-type (WT) and RIPK3-deficient (Ripk3-/-) mice. Wound area was measured daily until day 14 post-wound and skin tissues were collected from wound sites at various days for analysis. The wound healing rate in Ripk3-/- mice was slower than the WT mice over the 14-day course; especially, at day 7, the wound size in Ripk3-/- mice was 53% larger than that of WT mice. H&E and Masson-Trichrome staining analysis showed impaired quality of wound closure in Ripk3-/- wounds with delayed re-epithelialization and angiogenesis and defected granulation tissue formation and collagen deposition compared to WT. The neutrophil infiltration pattern was altered in Ripk3-/- wounds with less neutrophils at day 1 and more neutrophils at day 3. This altered pattern was also reflected in the differential expression of IL-6, KC, IL-1β and TNF-α between WT and Ripk3-/- wounds. MMP-9 protein expression was decreased with increased Timp-1 mRNA in the Ripk3-/- wounds compared to WT. The microvascular density along with the intensity and timing of induction of proangiogenic growth factors VEGF and TGF-β1 were also decreased or delayed in the Ripk3-/- wounds. Furthermore, mouse embryonic fibroblasts (MEFs) from Ripk3-/- mice migrated less towards chemoattractants TGF-β1 and PDGF than MEFs from WT mice. These results clearly demonstrate that RIPK3 is an essential molecule to maintain the temporal manner of the normal progression

  6. Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice.

    Science.gov (United States)

    Valacchi, Giuseppe; Lim, Yunsook; Belmonte, Giuseppe; Miracco, Clelia; Zanardi, Iacopo; Bocci, Velio; Travagli, Valter

    2011-01-01

    Ozone is well recognized as a bactericidal agent and its beneficial effect on wound healing could be a consequence of this property. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects should be the results of oxidative reaction. For this reason, ozonated oils could be a way to deliver ozone messengers to the skin. This paper evaluated the therapeutic effects of three different grades of ozonated sesame oil in acute cutaneous wounds made in the skin of SKH1 mice. Specifically, wound closure rate, histological parameters, and the level of key proteins such as vascular endothelial growth factors and cyclin D1 have been analyzed in relation to the peroxide level present in the ozonated oil. Treatment with moderately ozonated sesame oil--expressed as peroxide value about 1,500)--has a faster wound closure rate in the first 7 days than treatment with oil containing either lower or higher peroxide value, and even with controls. Moreover, under the same treatment, an earlier and higher response of cells involved in wound repair, a higher angiogenesis, as well as an enhanced vascular endothelial growth factors and cyclin D1 expression were observed. The present study shows the validity of ozonated sesame oil in cutaneous wound healing and emphasizes the importance of the ozonation grade.

  7. Therapeutic effects of topical application of ozone on acute cutaneous wound healing.

    Science.gov (United States)

    Kim, Hee Su; Noh, Sun Up; Han, Ye Won; Kim, Kyoung Moon; Kang, Hoon; Kim, Hyung Ok; Park, Young Min

    2009-06-01

    This study was undertaken to evaluate the therapeutic effects of topical ozonated olive oil on acute cutaneous wound healing in a guinea pig model and also to elucidate its therapeutic mechanism. After creating full-thickness skin wounds on the backs of guinea pigs by using a 6 mm punch biopsy, we examined the wound healing effect of topically applied ozonated olive oil (ozone group), as compared to the pure olive oil (oil group) and non-treatment (control group). The ozone group of guinea pig had a significantly smaller wound size and a residual wound area than the oil group, on days 5 (Pozone group than that in the oil group on day 7. Immunohistochemical staining demonstrated upregulation of platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7, as compared with the oil group. In conclusion, these results demonstrate that topical application of ozonated olive oil can accelerate acute cutaneous wound repair in a guinea pig in association with the increased expression of PDGF, TGF-beta, and VEGF.

  8. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds.

    Science.gov (United States)

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

    2013-04-01

    Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Adult healthy beagle dogs (n = 10; 3-6 years old; 7.2-13.1 kg) were studied. Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

  9. Mesenchymal stem cells promote incision wound repair in a mouse ...

    African Journals Online (AJOL)

    Full-thickness cutaneous wounds (4 × 2 cm) were made by incision on the dorsal side of the mice. The wound was then ..... on age as well as the type and size of injury. In .... stem cells favour healing of the cutaneous radiation syndrome in a ...

  10. Matrix metalloproteinases in wound repair (review).

    Science.gov (United States)

    Ravanti, L; Kähäri, V M

    2000-10-01

    Wound repair is initiated with the aggregation of platelets, formation of a fibrin clot, and release of growth factors from the activated coagulation pathways, injured cells, platelets, and extracellular matrix (ECM), followed by migration of inflammatory cells to the wound site. Thereafter, keratinocytes migrate over the wound, angiogenesis is initiated, and fibroblasts deposit and remodel the granulation tissue. Cell migration, angiogenesis, degradation of provisional matrix, and remodeling of newly formed granulation tissue, all require controlled degradation of the ECM. Disturbance in the balance between ECM production and degradation leads to formation of chronic ulcers with excessive ECM degradation, or to fibrosis, for example hypertrophic scars or keloids characterized by excessive accumulation of ECM components. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all ECM components. So far, 20 members of the human MMP family have been identified. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, stromelysin-like MMPs, gelatinases, membrane-type MMPs (MT-MMPs), and other MMPs. In this review, the role of MMPs in normal wound repair as well as in chronic ulcers is discussed. In addition, the role of signaling pathways, in particular, mitogen-activated protein kinases (MAPKs) in regulating MMP expression is discussed as possible therapeutical targets for wound healing disorders.

  11. 635nm diode laser biostimulation on cutaneous wounds

    Science.gov (United States)

    Solmaz, Hakan; Gülsoy, Murat; Ülgen, Yekta

    2014-05-01

    Biostimulation is still a controversial subject in wound healing studies. The effect of laser depends of not only laser parameters applied but also the physiological state of the target tissue. The aim of this project is to investigate the biostimulation effects of 635nm laser irradiation on the healing processes of cutaneous wounds by means of morphological and histological examinations. 3-4 months old male Wistar Albino rats weighing 330 to 350 gr were used throughout this study. Low-level laser therapy was applied through local irradiation of red light on open skin excision wounds of 5mm in diameter prepared via punch biopsy. Each animal had three identical wounds on their right dorsal part, at which two of them were irradiated with continuous diode laser of 635nm in wavelength, 30mW of power output and two different energy densities of 1 J/cm2 and 3 J/cm2. The third wound was kept as control group and had no irradiation. In order to find out the biostimulation consequences during each step of wound healing, which are inflammation, proliferation and remodeling, wound tissues removed at days 3, 7, 10 and 14 following the laser irradiation are morphologically examined and than prepared for histological examination. Fragments of skin including the margin and neighboring healthy tissue were embedded in paraffin and 6 to 9 um thick sections cut are stained with hematoxylin and eosin. Histological examinations show that 635nm laser irradiation accelerated the healing process of cutaneous wounds while considering the changes of tissue morphology, inflammatory reaction, proliferation of newly formed fibroblasts and formation and deposition of collagen fibers. The data obtained gives rise to examine the effects of two distinct power densities of low-level laser irradiation and compare both with the non-treatment groups at different stages of healing process.

  12. In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing.

    Science.gov (United States)

    Li, Xiaoling; Fan, Rangrang; Tong, Aiping; Yang, Meijia; Deng, Jiaojiao; Zhou, Liangxue; Zhang, Xiaoning; Guo, Gang

    2015-11-10

    In situ gel-forming system as local drug delivery system in dermal traumas has generated a great interest. Accumulating evidence shows that antimicrobial peptides play pivotal roles in the process of wound healing. Here in this study, to explore the potential application of antimicrobial peptide in wound healing, biodegradable poly(L-lactic acid)-Pluronic L35-poly(L-lactic acid) (PLLA-L35-PLLA) was developed at first. Then based on this polymer, an injectable in situ gel-forming system composed of human antimicrobial peptides 57 (AP-57) loaded nanoparticles and thermosensitive hydrogel was prepared and applied for cutaneous wound healing. AP-57 peptides were enclosed with biocompatible nanoparticles (AP-57-NPs) with high drug loading and encapsulation efficiency. AP-57-NPs were further encapsulated in a thermosensitive hydrogel (AP-57-NPs-H) to facilitate its application in cutaneous wound repair. As a result, AP-57-NPs-H released AP-57 in an extended period and exhibited quite low cytotoxicity and high anti-oxidant activity in vitro. Moreover, AP-57-NPs-H was free-flowing liquid at room temperature, and can form non-flowing gel without any crosslink agent upon applied on the wounds. In vivo wound healing assay using full-thickness dermal defect model of SD rats indicated that AP-57-NPs-H could significantly promote wound healing. At day 14 after operation, AP-57-NPs-H treated group showed nearly complete wound closure of 96.78 ± 3.12%, whereas NS, NPs-H and AP-57-NPs group recovered by about 68.78 ± 4.93%, 81.96 ± 3.26% and 87.80 ± 4.62%, respectively. Histopathological examination suggested that AP-57-NPs-H could promote cutaneous wound healing through enhancing granulation tissue formation, increasing collagen deposition and promoting angiogenesis in the wound tissue. Therefore, AP-57-NPs-H might have potential application in wound healing.

  13. Non-invasive objective devices for monitoring the inflammatory, proliferative and remodelling phases of cutaneous wound healing and skin scarring.

    Science.gov (United States)

    Ud-Din, Sara; Bayat, Ardeshir

    2016-08-01

    Objective evaluation of cutaneous wounds through the use of non-invasive devices is important for diagnosis, monitoring treatment response and can lead to the development of improved theranostic strategies. The need for objective monitoring of wound healing and scar formation is evident as this enables accurate diagnosis, evaluation and prognosis for clinicians and allows for the standardisation and validation of methodology for researchers. Therefore, this review provides an overview of the current application of non-invasive objective technologies for the assessment of wound healing through the different phases of repair. We propose that cutaneous healing parameters can be split into three core domains: anatomical, mechanical and physiological. These categories can be further subdivided with respect to specific phases of healing. There is no single instrument, which can measure all the parameters of healing simultaneously; thus, it is important to choose the correct device for the particular healing characteristics being monitored. However, multiprobe systems, which include a number of devices connected to one main unit, are useful as they enable multiple measurements of different parameters. Many of the devices have not been validated against histological examination. Additionally, some of the instruments have not been evaluated in all wound or scar types and may not be useful throughout all phases of cutaneous wound healing. In conclusion, non-invasive objective devices are useful in the assessment of cutaneous wound healing, as these tools can link the treatment and diagnosis by evaluating response to treatment and thus could aid as a marker for healing and scar maturation.

  14. Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors

    Science.gov (United States)

    Escuin-Ordinas, Helena; Li, Shuoran; Xie, Michael W.; Sun, Lu; Hugo, Willy; Huang, Rong Rong; Jiao, Jing; de-Faria, Felipe Meira; Realegeno, Susan; Krystofinski, Paige; Azhdam, Ariel; Komenan, Sara Marie D.; Atefi, Mohammad; Comin-Anduix, Begoña; Pellegrini, Matteo; Cochran, Alistair J.; Modlin, Robert L.; Herschman, Harvey R.; Lo, Roger S.; McBride, William H.; Segura, Tatiana; Ribas, Antoni

    2016-01-01

    BRAF inhibitors are highly effective therapies for the treatment of BRAFV600-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. PMID:27476449

  15. Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil

    OpenAIRE

    Castellucci, Léa; Jamieson, Sarra E; Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Lessa, Marcus; Fakiola, Michaela; Jesus, Amélia Ribeiro de; Miller, E. Nancy; Carvalho, Edgar M.; Blackwell, Jenefer M.

    2012-01-01

    Leishmania braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. In the mouse, Fli1 was identified as a gene influencing enhanced wound healing and resistance to CL caused by L. major. Polymorphism at FLI1 is associated with CL caused by L. braziliensis in humans, with an inverse association observed for ML disease. Here we extend the analysis to look at other wound healing genes, including CTGF, TGFB1, TGFBR1/2, SMADS 2/3/4/7 and FLII, all functionally linked along with FLI1 in ...

  16. The Review on Properties of Aloe Vera in Healing of Cutaneous Wounds.

    Science.gov (United States)

    Hashemi, Seyyed Abbas; Madani, Seyyed Abdollah; Abediankenari, Saied

    2015-01-01

    Treatment of wounds is very important and was subject of different investigations. In this regard, natural substance plays crucial role as complementary medicine. Various studies reported that aloe vera has useful effects on wounds especially cutaneous wounds healing. Therefore in the current review, we examined the effect of aloe vera on cutaneous wound healing and concluded that although aloe vera improves the wound healing as well as other procedures both clinically and experimentally, more studies are still needed to approve the outcomes.

  17. Paracrine action of mesenchymal stromal cells delivered by microspheres contributes to cutaneous wound healing and prevents scar formation in mice.

    Science.gov (United States)

    Huang, Sha; Wu, Yan; Gao, Dongyun; Fu, Xiaobing

    2015-07-01

    Accumulating evidence suggests that mesenchymal stromal cells (MSCs) participate in wound healing to favor tissue regeneration and inhibit fibrotic tissue formation. However, the evidence of MSCs to suppress cutaneous scar is extremely rare, and the mechanism remains unidentified. This study aimed to demonstrate whether MSCs-as the result of their paracrine actions on damaged tissues-would accelerate wound healing and prevent cutaneous fibrosis. For efficient delivery of MSCs to skin wounds, microspheres were used to maintain MSC potency. Whether MSCs can accelerate wound healing and alleviate cutaneous fibrosis through paracrine action was investigated with the use of a Transwell co-culture system in vitro and a murine model in vivo. MSCs cultured on gelatin microspheres fully retained their cell surface marker expression profile, proliferation, differentiation and paracrine potential. Co-cultures of MSCs and fibroblasts indicated that the benefits of MSCs on suppressing fibroblast proliferation and its fibrotic behavior induced by inflammatory cytokines probably were caused by paracrine actions. Importantly, microspheres successfully delivered MSCs into wound margins and significantly accelerated wound healing and concomitantly reduced the fibrotic activities of cells within the wounds and excessive accumulation of extracellular matrix as well as the transforming growth factor-β1/transforming growth factor-β3 ratio. This study provides insight into what we believe to be a previously undescribed, multifaceted role of MSC-released protein in reducing cutaneous fibrotic formation. Paracrine action of MSCs delivered by microspheres may thus qualify as a promising strategy to enhance tissue repair and to prevent excessive fibrosis during cutaneous wound healing. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  18. Sodium carboxymethylation-functionalized chitosan fibers for cutaneous wound healing application

    Science.gov (United States)

    Yan, Dong; Zhou, Zhong-Zheng; Jiang, Chang-Qing; Cheng, Xiao-Jie; Kong, Ming; Liu, Ya; Feng, Chao; Chen, Xi-Guang

    2016-12-01

    A water absorption biomaterial, sodium carboxymethylation-functionalized chitosan fibers (Na-NOCC fibers) were prepared, applied for cutaneous wound repair, and characterized by FTIR and NMR. The water absorption of Na-NOCC fibers increased significantly with substitution degree rising, from 3.2 to 6.8 g/g, and higher than that of chitosan fibers (2.2 g/g) confirmed by swelling behavior. In the antibacterial action, the high degree of substitution of Na-NOCC fibers exhibited stronger antibacterial activities against E. coli (from 66.54% up to 88.86%). The inhibition of Na-NOCC fibers against S. aureus were above 90%, and more effective than E. coli. The cytotoxicity assay demonstrated that Na-NOCC2 fibers were no obvious cytotoxicity to mouse fibroblasts. Wound healing test and histological examination showed that significantly advanced granulation tissue and capillary formation in the healing-impaired wounds treated with Na-NOCC fibers, as compared to those treated with gauze, which demonstrated that Na- NOCC fibers could promote skin repair and might have great application for wound healing.

  19. Sodium carboxymethylation-functionalized chitosan fibers for cutaneous wound healing application

    Science.gov (United States)

    Yan, Dong; Zhou, Zhong-Zheng; Jiang, Chang-Qing; Cheng, Xiao-Jie; Kong, Ming; Liu, Ya; Feng, Chao; Chen, Xi-Guang

    2016-09-01

    A water absorption biomaterial, sodium carboxymethylation-functionalized chitosan fibers (Na-NOCC fibers) were prepared, applied for cutaneous wound repair, and characterized by FTIR and NMR. The water absorption of Na-NOCC fibers increased significantly with substitution degree rising, from 3.2 to 6.8 g/g, and higher than that of chitosan fibers (2.2 g/g) confirmed by swelling behavior. In the antibacterial action, the high degree of substitution of Na-NOCC fibers exhibited stronger antibacterial activities against E. coli (from 66.54% up to 88.86%). The inhibition of Na-NOCC fibers against S. aureus were above 90%, and more effective than E. coli. The cytotoxicity assay demonstrated that Na-NOCC2 fibers were no obvious cytotoxicity to mouse fibroblasts. Wound healing test and histological examination showed that significantly advanced granulation tissue and capillary formation in the healing-impaired wounds treated with Na-NOCC fibers, as compared to those treated with gauze, which demonstrated that Na- NOCC fibers could promote skin repair and might have great application for wound healing.

  20. AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

    OpenAIRE

    Yuanyuan Guo; Cai Lin; Peng Xu; Shan Wu; Xiujun Fu; Weidong Xia; Min Yao

    2016-01-01

    Autophagy is essential in physiological and pathological processes, however, the role of autophagy in cutaneous wound healing and the underlying molecular mechanism remain elusive. We hypothesized that autophagy plays an important role in regulating wound healing. Here, we show that enhanced autophagy negatively impacts on normal cutaneous healing process and is related to chronic wounds as demonstrated by the increased LC3 in diabetic mice skin or patients’ chronic wounds. In addition, inhib...

  1. Influence of sensory neuropeptides on human cutaneous wound healing process.

    Science.gov (United States)

    Chéret, J; Lebonvallet, N; Buhé, V; Carre, J L; Misery, L; Le Gall-Ianotto, C

    2014-06-01

    Close interactions exist between primary sensory neurons of the peripheral nervous system (PNS) and skin cells. The PNS may be implicated in the modulation of different skin functions as wound healing. Study the influence of sensory neurons in human cutaneous wound healing. We incubated injured human skin explants either with rat primary sensory neurons from dorsal root ganglia (DRG) or different neuropeptides (vasoactive intestinal peptide or VIP, calcitonin gene-related peptide or CGRP, substance P or SP) at various concentrations. Then we evaluated their effects on the proliferative and extracellular matrix (ECM) remodeling phases, dermal fibroblasts adhesion and differentiation into myofibroblasts. Thus, DRG and all studied neuromediators increased fibroblasts and keratinocytes proliferation and act on the expression ratio between collagen type I and type III in favor of collagen I, particularly between the 3rd and 7th day of culture. Furthermore, the enzymatic activities of matrix metalloprotesases (MMP-2 and MMP-9) were increased in the first days of wound healing process. Finally, the adhesion of human dermal fibroblasts and their differentiation into myofibroblasts were promoted after incubation with neuromediators. Interestingly, the most potent concentrations for each tested molecules, were the lowest concentrations, corresponding to physiological concentrations. Sensory neurons and their derived-neuropeptides are able to promote skin wound healing. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Evaluation of dense collagen matrices as medicated wound dressing for the treatment of cutaneous chronic wounds.

    Science.gov (United States)

    Helary, Christophe; Abed, Aicha; Mosser, Gervaise; Louedec, Liliane; Letourneur, Didier; Coradin, Thibaud; Giraud-Guille, Marie Madeleine; Meddahi-Pellé, Anne

    2015-02-01

    Cutaneous chronic wounds are characterized by an impaired wound healing which may lead to infection and amputation. When current treatments are not effective enough, the application of wound dressings is required. To date, no ideal biomaterial is available. In this study, highly dense collagen matrices have been evaluated as novel medicated wound dressings for the treatment of chronic wounds. For this purpose, the structure, mechanical properties, swelling ability and in vivo stability of matrices concentrated from 5 to 40 mg mL(-1) were tested. The matrix stiffness increased with the collagen concentration and was associated with the fibril density and thickness. Increased collagen concentration also enhanced the material resistance against accelerated digestion by collagenase. After subcutaneous implantation in rats, dense collagen matrices exhibited high stability without any degradation after 15 days. The absence of macrophages and neutrophils evidenced their biocompatibility. Subsequently, dense matrices at 40 mg mL(-1) were evaluated as drug delivery system for ampicillin release. More concentrated matrices exhibited the best swelling abilities and could absorb 20 times their dry weight in water, allowing for an efficient antibiotic loading from their dried form. They released efficient doses of antibiotics that inhibited the bacterial growth of Staphylococcus Aureus over 3 days. In parallel, they show no cytotoxicity towards human fibroblasts. These results show that dense collagen matrices are promising materials to develop medicated wound dressings for the treatment of chronic wounds.

  3. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    Science.gov (United States)

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-09-12

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair.

  4. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

    Science.gov (United States)

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  5. Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study.

    Science.gov (United States)

    Brufani, Mario; Ceccacci, Francesca; Filocamo, Luigi; Garofalo, Barbara; Joudioux, Roberta; La Bella, Angela; Leonelli, Francesca; Migneco, Luisa M; Bettolo, Rinaldo Marini; Farina, Paolo M; Ashcroft, Gillian S; Routley, Claire; Hardman, Matthew; Meda, Clara; Rando, Gianpaolo; Maggi, Adriana

    2009-01-01

    New 17beta-estradiol (E2) derivatives 1-11 were synthesized from an estrone derivative by addition of organometallic reagents prepared from protected alpha,omega-alkynols and further elaboration of the addition products. The estrogenic activity of these novel compounds was determined using in vitro binding competition assay and transactivation analysis. Among the E2 derivatives synthesized, compound 2 showed the highest transactivation potency and was therefore tested for its ability to modulate cutaneous wound healing in vivo. Compound 2's ability to accelerate wound healing in ovariectomized mice and decrease the production of inflammatory molecules was comparable to that of E2. However, the activity of compound 2 was not superimposable to E2 with regard to the cells involved in the wound repairing process. When locally administered, compound 2 did not show any systemic activity on ER. This class of compounds with clear beneficial effects on wound healing and suitable for topical administration may lead to the generation of innovative drugs for an area of unmet clinical need.

  6. Transforming growth factor Beta 3 is required for excisional wound repair in vivo.

    Directory of Open Access Journals (Sweden)

    Mark Le

    Full Text Available Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-ß isoforms-TGF- ß 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-ß 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF- ß 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-ß 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-ß 3 or neutralizing antibody against TGF-ß 3 (NAB in the wounds. Our results demonstrate that TGF-ß 3 does not promote epithelialization. However, TGF-ß 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-ß 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.

  7. The Review on Properties of Aloe Vera in Healing of Cutaneous Wounds

    Science.gov (United States)

    Hashemi, Seyyed Abbas; Madani, Seyyed Abdollah; Abediankenari, Saied

    2015-01-01

    Treatment of wounds is very important and was subject of different investigations. In this regard, natural substance plays crucial role as complementary medicine. Various studies reported that aloe vera has useful effects on wounds especially cutaneous wounds healing. Therefore in the current review, we examined the effect of aloe vera on cutaneous wound healing and concluded that although aloe vera improves the wound healing as well as other procedures both clinically and experimentally, more studies are still needed to approve the outcomes. PMID:26090436

  8. Cutaneous wound closure materials: an overview and update.

    Science.gov (United States)

    Al-Mubarak, Luluah; Al-Haddab, Mohammed

    2013-10-01

    On a daily basis, dermasurgeons are faced with different kinds of wounds that have to be closed. With a plethora of skin closure materials currently available, choosing a solution that combines excellent and rapid cosmetic results with practicality and cost-effectiveness can be difficult, if not tricky. We aimed to review the available skin closure materials over the past 20 years and the scientific claims behind their effectiveness in repairing various kinds of wounds. The two authors independently searched and scrutinised the literature. The search was performed electronically using Pub Med, the Cochrane Database, Google Scholar and Ovid as search engines to find articles concerning skin closure materials written since 1990. Many factors are involved in the choice of skin closure material, including the type and place of the wound, available materials, physician expertise and preferences, and patient age and health. Evidence-based main uses of different skin closure materials are provided to help surgeons choose the appropriate material for different wounds.

  9. Cutaneous wound closure materials: An overview and update

    Directory of Open Access Journals (Sweden)

    Luluah Al-Mubarak

    2013-01-01

    Full Text Available Introduction: On a daily basis, dermasurgeons are faced with different kinds of wounds that have to be closed. With a plethora of skin closure materials currently available, choosing a solution that combines excellent and rapid cosmetic results with practicality and cost-effectiveness can be difficult, if not tricky. Objectives: We aimed to review the available skin closure materials over the past 20 years and the scientific claims behind their effectiveness in repairing various kinds of wounds. Materials and Methods: The two authors independently searched and scrutinised the literature. The search was performed electronically using Pub Med, the Cochrane Database, Google Scholar and Ovid as search engines to find articles concerning skin closure materials written since 1990. Conclusion: Many factors are involved in the choice of skin closure material, including the type and place of the wound, available materials, physician expertise and preferences, and patient age and health. Evidence-based main uses of different skin closure materials are provided to help surgeons choose the appropriate material for different wounds.

  10. 游离旋股外侧动脉降支皮瓣在小腿难治性创面软组织缺损的修复应用%The repair application of the lateral femoral cutaneous artery flap for soft tissue defects of refractory ;wounds on leg

    Institute of Scientific and Technical Information of China (English)

    刘伟; 刘圣曜; 刘强; 陈铭青; 严志强; 区广鹏; 黄瑞良; 余斌

    2016-01-01

    目的:游离旋股外侧动脉降支皮瓣在小腿难治性创面修复软组织缺损中的临床疗效。方法:2007年10月至2016年1月,先用VSD促进肉芽组织的生长,待肉芽组织生长满意后再应用游离旋股外侧动脉降支解剖特点设计皮瓣,修复创面缺损患者12例,旋髂浅腹股沟皮瓣8例,切取皮瓣后与受区血管吻合修复缺损创面。结果:20例患者随访,随访时间6~24个月,平均12个月,皮瓣全部成活,仅1例皮瓣边缘小面积坏死,经换药创面愈合,皮瓣色泽、质地良好。股四头肌肌力正常,膝关节伸、屈0°~150°。结论:旋股外侧动脉降支皮瓣修复难治性创面软组织缺损,皮瓣供区直接缝合,缩短治疗周期,安全有效,因此是修复创面组织缺损的理想皮瓣之一。%Objective The clinical effect of the lateral femoral cutaneous artery flap for soft tissue defects of leg wounds. Methods From October 2007 to January 2016, VSD was firstly used to promote the growth of granulation tissue. When the growth of granulation tissue became satisfactory, flaps were designed based on the anatomical characteristics of the lateral femoral cutaneous artery. We repaired 20 cases of wound defects by cutting flaps that coincide with the recipient vessels. Result 20 cases were followed up for 6 to 24 months, 12 months on average. All flaps were survived and only one case had small area of necrosis flap which was healed by replacing medicines. In all cases, wounds were healed and flaps showed good color and good texture. The strength of quadriceps muscle was good and the extension of knee flexion was 0° to 150°. Conclusion To The lateral femoral cutaneous artery flap is used for soft tissue defects of refractory wounds on leg , flap donor sites are sutured directly, the treatment period is shorten and the method is safe and effective. The lateral femoral cutaneous artery flap is one of ideal choices for wound tissue

  11. Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

    Science.gov (United States)

    Cremers, Niels A. J.; Suttorp, Maarten; Gerritsen, Marlous M.; Wong, Ronald J.; van Run-van Breda, Coby; van Dam, Gooitzen M.; Brouwer, Katrien M.; Kuijpers-Jagtman, Anne Marie; Carels, Carine E. L.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

    2015-01-01

    Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full-thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than three times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epi)dermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower numbers of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, αSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1β, TNF-α, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly formed collagen (type III) was lower in 7-day wounds after splinting, whereas, VEGF and MMP-9 were increased. In summary, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting may facilitate higher myofibroblast numbers and increase the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in patients with

  12. Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing.

    Science.gov (United States)

    Krishnaswamy, Venkat Raghavan; Manikandan, Mayakannan; Munirajan, Arasambattu Kannan; Vijayaraghavan, Doraiswamy; Korrapati, Purna Sai

    2014-12-01

    Chronic cutaneous wound (CCW) is a major health care burden wherein the healing process is slow or rather static resulting in anatomical and functional restriction of the damaged tissue. Dysregulated expression and degradation of matrix proteins, growth factors and cytokines contribute to the disrupted and uncoordinated healing process of CCW. Therefore, therapeutic approaches for effective management of CCW should be focused towards identifying and manipulating the molecular defects, such as reduced bioavailability of the pro-healing molecules and elevated activity of proteases. This study essentially deals with assessing the expression and integrity of an extracellular matrix protein, Dermatopontin (DPT), in CCW using real-time quantitative reverse transcriptase PCR and immunological techniques. The results indicate that, despite DPT's high mRNA expression, the protein levels are markedly reduced in both CCW tissue and its exudate. To elucidate the cause for this contradiction in mRNA and protein levels, the stability of DPT is analyzed in the presence of wound exudates and various proteases that are naturally elevated in CCW. DPT was observed to be degraded at higher rates when incubated with certain recombinant proteases or chronic wound exudate. In conclusion, the susceptibility of DPT protein to specific proteases present at high levels in the wound milieu resulted in the degradation of DPT, thus leading to impaired healing response in CCW.

  13. The Role of Poly N Acetyl Glucosamine Nanofibers in Cutaneous Wound Healing

    Science.gov (United States)

    Buff-Lindner, Amanda Haley

    Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increases in wound closure, antibacterial activities and innate immune responses. Treatment with nanofibers results in increased defensin, small antimicrobial peptides, expression both in vitro and in vivo. Induction of defensin expression results in bacterial clearance in a cutaneous wound model. Our data show that Akt1 plays a central role in the regulation of these activities. Interestingly, pGlcNAc treatment of cutaneous wounds in mice results in decreased scar sizes. Additionally, treatment of cutaneous wounds with pGlcNAc results in increased elasticity and a rescue of tensile strength. Masson Trichrome staining suggests that pGlcNAc treated wounds exhibit decreased collagen content as well as increased collagen alignment with collagen fibers oriented similarly to unwounded tissue. Utilizing a fibrin gel assay to analyze the effect of pGlcNAc nanofiber treatment on fibroblast alignment in vitro, pGlcNAc stimulation of embedded fibroblasts results in fibroblasts alignment as compared to untreated controls, by a process that is Akt1 dependent. Our data show that in Akt1 null animals pGlcNAc treatment does not increase tensile strength or elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in wound closure, the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

  14. Skin appendage-derived stem cells: cell biology and potential for wound repair.

    Science.gov (United States)

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

    2016-01-01

    Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

  15. Wound repair and regeneration: Mechanisms, signaling, and translation

    Science.gov (United States)

    Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

    2015-01-01

    The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

  16. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Scharstuhl, A.; Cremers, N.A.J.; Pennings, S.W.C.; Paske, J. Te; Rheden, R. van; Breda, C. van Run-van; Regan, R.F.; Russel, F.G.M.; Carels, C.E.L.; Maltha, J.C.; Wagener, F.A.D.T.G.

    2014-01-01

    Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal

  17. Gonadal hormones differently modulate cutaneous wound healing of chronically stressed mice.

    Science.gov (United States)

    Romana-Souza, Bruna; Assis de Brito, Thatiana L; Pereira, Gabriela R; Monte-Alto-Costa, Andréa

    2014-02-01

    Gonadal hormones influence physiological responses to stress and cutaneous wound healing. The aim of this study was to investigate the role of gonadal hormones on cutaneous wound healing in chronically stressed mice. Male and female mice were gonadectomized, and after 25 days, they were spun daily at 115 rpm for 15 min every hour until euthanasia. Twenty-eight days after the gonadectomy, an excisional lesion was created. The animals were killed 7 or 14 days after wounding, and the lesions were collected. Myofibroblast density, macrophage number, catecholamine level, collagen deposition, and blood vessel number were evaluated. In the intact and gonadectomized groups, stress increased the plasma catecholamine levels in both genders. In intact groups, stress impaired wound contraction and re-epithelialization and increased the macrophage number in males but not in females. In addition, stress compromised myofibroblastic differentiation and blood vessel formation and decreased collagen deposition in males but not in females. In contrast to intact mice, wound healing in ovariectomized female mice was affected by stress, while wound healing in castrated male mice was not. In conclusion, gender differences contribute to the cutaneous wound healing of chronically stressed mice. In addition, androgens contribute to the stress-induced impairment of the healing of cutaneous wounds but estrogens inhibit it.

  18. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Scharstuhl, A.; Cremers, N.A.J.; Pennings, S.W.C.; Paske, J. Te; Rheden, R. van; Breda, C. van Run-van; Regan, R.F.; Russel, F.G.M.; Carels, C.E.L.; Maltha, J.C.; Wagener, F.A.D.T.G.

    2014-01-01

    Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal

  19. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Na-Young Park

    2010-01-01

    Full Text Available Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA, a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage. We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

  20. Combination of adrenomedullin with its binding protein accelerates cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Juan-Pablo Idrovo

    Full Text Available Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM and its binding protein-1 (AMBP-1 is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle or AM/AMBP-1 (96/320 μg kg BW was topically applied to the wound daily and wound size measured. At days 3, 7, and 14, skin samples were collected from the wound sites. AM/AMBP-1 treated group had significantly smaller wound surface area than the vehicle group over the 14-day time course. At day 3, AM/AMBP-1 promoted neutrophil infiltration (MPO, increased cytokine levels (IL-6 and TNF-α, angiogenesis (CD31, VEGF and TGFβ-1 and cell proliferation (Ki67. By day 7 and 14, AM/AMBP-1 treatment decreased MPO, followed by a rapid resolution of inflammation characterized by a decrease in cytokines. At the matured stage, AM/AMBP-1 treatment increased the alpha smooth muscle actin expression (mature blood vessels and Masson-Trichrome staining (collagen deposition along the granulation area, and increased MMP-9 and decreased MMP-2 mRNA expressions. TGFβ-1 mRNA levels in AM/AMBP-1 group were 5.3 times lower than those in the vehicle group. AM/AMBP-1 accelerated wound healing by promoting angiogenesis, collagen deposition and remodeling. Treatment also shortened the days to reach plateau for wound closure. Thus, AM/AMBP-1 may be further developed as a therapeutic for cutaneous wound healing.

  1. Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice.

    Science.gov (United States)

    Chen, Bin; Kao, Huang-Kai; Dong, Ziqing; Jiang, Zhaohua; Guo, Lifei

    2017-01-01

    Negative-pressure wound therapy and pulsed radiofrequency energy are two clinical modalities used to treat soft-tissue wounds. They are purported to affect healing differently. The aim of this experimental study was to contrast the two modalities at a mechanistic level and to investigate whether their combined therapy could achieve additive and complementary effects on wound healing. Full-thickness dorsal cutaneous wounds of diabetic, db/db, mice were treated with either negative-pressure wound therapy, pulsed radiofrequency energy, or combined therapies. Macroscopic healing kinetics were examined. Epidermal regeneration (proliferation rate and length of reepithelialization) and neovascularization (blood vessel density) were investigated. Messenger RNA levels indicative of angiogenic (basic fibroblast growth factor), profibrotic (transforming growth factor-β), epidermal proliferative (keratinocyte growth factor), and extracellular matrix remodeling (collagen 1) processes were measured in wound tissues. All three treatment groups displayed faster wound healing. The negative-pressure wound therapy/pulsed radiofrequency energy combined therapy led to significantly faster healing than either the negative-pressure wound therapy or pulsed radiofrequency energy therapy alone. Epidermal regeneration and neovascularization were enhanced in all three groups. The two negative-pressure wound therapy groups (alone and combined with pulsed radiofrequency energy) demonstrated more significant increases in expression of all assayed growth factors than the pulsed radiofrequency energy group. Furthermore, the combined therapy exhibited a more profound elevation in collagen 1 expression than either of the two therapies alone. Combining the negative-pressure wound therapy and pulsed radiofrequency energy modalities can achieve additive benefits in cutaneous healing, and the two therapies can be easily used together to complement each other in clinical wound treatments.

  2. Biostimulative effects of 809 nm diode laser on cutaneous skin wounds

    Science.gov (United States)

    Solmaz, Hakan; Gülsoy, Murat; Ülgen, Yekta

    2015-03-01

    The use of low-level laser therapy (LLLT) for therapeutic purposes in medicine has become widespread recently. There are many studies in literature supporting the idea of therapeutic effects of laser irradiation on biological tissues. The aim of this study is to investigate the biostimulative effect of 809nm infrared laser irradiation on the healing process of cutaneous incisional skin wounds. 3-4 months old male Wistar Albino rats weighing 300 to 350 gr were used throughout this study. Lowlevel laser therapy was applied through local irradiation of 809nm infrared laser on open skin incisional wounds of 1 cm length. Each animal had six identical incisions on their right and left dorsal region symmetrical to each other. The wounds were separated into three groups of control, 1 J/cm2 and 3 J/cm2 of laser irradiation. Two of these six wounds were kept as control group and did not receive any laser application. Rest of the incisions was irradiated with continuous diode laser of 809nm in wavelength and 20mW power output. Two of them were subjected to laser irradiation of 1 J/cm2 and the other two were subjected to laser light with energy density of 3 J/cm2. Biostimulation effects of irradiation were studied by means of tensile strength tests and histological examinations. Wounded skin samples were morphologically examined and removed for mechanical and histological examinations at days 3, 5 and 7 following the laser applications. Three of the six fragments of skin incisions including a portion of peripheral healthy tissue from each animal were subjected to mechanical tests by means of a universal tensile test machine, whereas the other three samples were embedded in paraffin and stained with hematoxylin and eosin for histological examinations. The findings of the study show that tissue repair following laser irradiation of 809nm has been accelerated in terms of tissue morphology, strength and cellular content. These results seem to be consistent with the results of many

  3. Healing of chronic cutaneous wounds by topical treatment with basic fibroblast growth factor.

    Science.gov (United States)

    Fu, Xiaobing; Shen, Zuyao; Guo, Zhenrong; Zhang, Mingliang; Sheng, Zhiyong

    2002-03-01

    To evaluate the safety and efficacy of topical application of recombinant bovine basic fibroblast growth factor (rbFGF) on the healing of chronic cutaneous wounds. Twenty-eight patients with thirty-three chronic cutaneous wounds resulting from trauma, diabetes mellitus, pressure sore and radiation injuries were enrolled in this prospective, open-label crossover trial. Prior to treatment with rbFGF, all wounds failed to heal with conventional therapies within 4 weeks. All wounds were locally treated with rbFGF at a dose of 150 AU/cm(2). Healing time and the quality of wounds were used to evaluate the efficacy of the treatment. Healing of all chronic wounds was expedited. During the study, eighteen wounds completely healed within 2 weeks, four healed within 3 weeks, and another eight completely healed within 4 weeks. Only three wounds failed to heal within 4 weeks, but healed at 30, 40 and 42 days after treatment with rbFGF. Thus, compared with conventional therapies, the effective rate of rbFGF treatment within 4 weeks was 90.9%. Histological assessment showed more abundant capillary sprouts or tubes and that fibroblasts were differentiated in wounds treated with rbFGF. No adverse side effects related to basic fibroblast growth factor were observed. Our results indicate that rbFGF could be used to accelerate healing in chronic wounds. It is our belief that this may be a more effective method of chronic wound management.

  4. Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical Evidence

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    Sara Ud-Din

    2014-10-01

    Full Text Available Electrical stimulation (ES has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC, alternating current (AC, high-voltage pulsed current (HVPC, low-intensity direct current (LIDC and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used.

  5. Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing.

    Science.gov (United States)

    Xanthoulea, Sofia; Deliaert, An; Romano, Andrea; Rensen, Sander S; Buurman, Wim A; van der Hulst, Rene' R W J

    2013-12-01

    The aim of the current study was to investigate the effect of nicotine in an experimental mouse model of cutaneous injury and healing responses, during the inflammatory phase of repair. Nicotine injection in full-thickness excisional skin wounds minimally affected inflammatory mediators like TNF, IL-6 and IL-12 while it induced a down-regulation in the expression of growth factors like VEGF, PDGF, TGF-β1 and TGF-β2, and the anti-inflammatory cytokine IL-10. Analysis of wound closure rate indicated no significant differences between nicotine and saline injected controls. In-vitro studies using bone marrow derived macrophages, resident peritoneal macrophages and RAW 264.7 macrophages, indicated that nicotine down-regulates TNF production. Moreover, nicotine was shown to down-regulate VEGF, PDGF and TGF-β1 in both bone marrow derived macrophages and RAW 264.7 cells. Using an NF-κB luciferase reporter RAW 264.7 cell line, we show that nicotine effects are minimally dependent on NF-κB inhibition. Moreover, nicotinic acetylcholine receptor (nAChR) subunit expression analyses indicated that while β2 nAChR subunit is expressed in mouse macrophages, α7 nAChR is not. In conclusion, while skin inflammatory parameters were not significantly affected by nicotine, a down-regulation of growth factor expression in both mouse skin and macrophages was observed. Reduced growth factor expression by nicotine might contribute, at least in part, to the overall detrimental effects of tobacco use in wound healing and skin diseases.

  6. Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility.

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    Soung-Hoon Lee

    Full Text Available BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK signaling pathways. Valproic acid (VPA is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA, collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

  7. The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing.

    Science.gov (United States)

    Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang; Choi, Kang-Yell

    2015-06-29

    Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5(-/-) mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)-Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. © 2015 Lee et al.

  8. The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing

    Science.gov (United States)

    Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang

    2015-01-01

    Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. PMID:26056233

  9. Laminins: Roles and Utility in Wound Repair.

    Science.gov (United States)

    Iorio, Valentina; Troughton, Lee D; Hamill, Kevin J

    2015-04-01

    Significance: Laminins are complex extracellular macromolecules that are major players in the control of a variety of core cell processes, including regulating rates of cell proliferation, differentiation, adhesion, and migration. Laminins, and related extracellular matrix components, have essential roles in tissue homeostasis; however, during wound healing, the same proteins are critical players in re-epithelialization and angiogenesis. Understanding how these proteins influence cell behavior in these different conditions holds great potential in identifying new strategies to enhance normal wound closure or to treat chronic/nonhealing wounds. Recent Advances: Laminin-derived bioactive peptides and, more recently, laminin-peptide conjugated scaffolds, have been designed to improve tissue regeneration after injuries. These peptides have been shown to be effective in decreasing inflammation and granulation tissue, and in promoting re-epithelialization, angiogenesis, and cell migration. Critical Issues: Although there is now a wealth of knowledge concerning laminin form and function, there are still areas of some controversy. These include the relative contribution of two laminin-based adhesive devices (focal contacts and hemidesmosomes) to the re-epithelialization process, the impact and implications of laminin proteolytic processing, and the importance of laminin polymer formation on cell behavior. In addition, the roles in wound healing of the laminin-related proteins, netrins, and LaNts are still to be fully defined. Future Directions: The future of laminin-based therapeutics potentially lies in the bioengineering of specific substrates to support laminin deposition for ex vivo expansion of autologous cells for graft formation and transplantation. Significant recent advances suggest that this goal is within sight.

  10. Laminins: Roles and Utility in Wound Repair

    OpenAIRE

    Iorio, Valentina; Troughton, Lee D.; Hamill, Kevin J.

    2015-01-01

    Significance: Laminins are complex extracellular macromolecules that are major players in the control of a variety of core cell processes, including regulating rates of cell proliferation, differentiation, adhesion, and migration. Laminins, and related extracellular matrix components, have essential roles in tissue homeostasis; however, during wound healing, the same proteins are critical players in re-epithelialization and angiogenesis. Understanding how these proteins influence cell behavio...

  11. A bioengineered drug-Eluting scaffold accelerated cutaneous wound healing In diabetic mice.

    Science.gov (United States)

    Yin, Hao; Ding, Guoshan; Shi, Xiaoming; Guo, Wenyuan; Ni, Zhijia; Fu, Hong; Fu, Zhiren

    2016-09-01

    Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients.

  12. Topical application of dressing with amino acids improves cutaneous wound healing in aged rats.

    Science.gov (United States)

    Corsetti, Giovanni; D'Antona, Giuseppe; Dioguardi, Francesco Saverio; Rezzani, Rita

    2010-09-01

    The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflammation accelerates wound closure with subsequent increased fibroblast function and collagen synthesis. On the contrary, prolonged chronic inflammation results in very limited wound healing. Using histological and immunohistochemical techniques, we investigated the effects of a new wound dressing called Vulnamin that contains four essential amino acids for collagen and elastin synthesis plus sodium ialuronate (Na-Ial), compared with Na-Ial alone, in closure of experimental cutaneous wounds of aged rats. Our results showed that the application of Vulnamin dressings modulated the inflammatory response with a reduction in the number of inflammatory cells and inducible nitric oxide synthase (iNOS) immunolocalisation, while increasing endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta1 (TGF-beta1) immunolocalisation. Furthermore, the dressing increased the distribution density of fibroblasts and aided the synthesis of thin collagen fibers resulting in a reduction in healing time. The nutritive approach using this new wound dressing can provide an efficacious and safe strategy to accelerate wound healing in elderly subjects, simplifying therapeutic procedures and leading to an improved quality of life. 2009 Elsevier GmbH. All rights reserved.

  13. Plasminogen is a critical regulator of cutaneous wound healing.

    Science.gov (United States)

    Sulniute, Rima; Shen, Yue; Guo, Yong-Zhi; Fallah, Mahsa; Ahlskog, Nina; Ny, Lina; Rakhimova, Olena; Broden, Jessica; Boija, Hege; Moghaddam, Aliyeh; Li, Jinan; Wilczynska, Malgorzata; Ny, Tor

    2016-05-02

    Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen-deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

  14. Modulation of cutaneous wound healing by ozone: differences between young and aged mice.

    Science.gov (United States)

    Lim, Yunsook; Phung, Anh D; Corbacho, Ana M; Aung, Hnin Hnin; Maioli, Emanuela; Reznick, Abraham Z; Cross, Carroll E; Davis, Paul A; Valacchi, Giuseppe

    2006-01-05

    Cutaneous tissues are frequently exposed to prooxidative environments, including UV radiation and air pollutants. Among the latter, ozone (O(3)) is of particular concern because of its high and dominating presence in photochemical smog. It is well known that O(3) depletes small molecular weight antioxidants, oxidizes proteins, induces lipid peroxidation and activates cellular responses in various tissues. Using an in vivo model (SKH-1 hairless mice), the interaction between O(3) exposure (0.5ppmx6h/day) and age was examined in relation to cutaneous wound healing. Compared to younger (8 weeks) mice, older (18 months) mice exposed to O(3) (day 0 to day 9 after wounding) exhibited delayed wound closure, increased lipid peroxidation (measured as 4-HNE protein adducts) and protein oxidation (measured as carbonyls concentration) and decreased levels of P-IkappaBalpha and TGFbeta protein. These findings support the hypothesis that oxidant pollutant exposure and age interact so as to disrupt normal wound healing processes.

  15. Design of a portable imager for near-infrared visualization of cutaneous wounds

    Science.gov (United States)

    Peng, Zhaoqiang; Zhou, Jun; Dacy, Ashley; Zhao, Deyin; Kearney, Vasant; Zhou, Weidong; Tang, Liping; Hu, Wenjing

    2017-01-01

    A portable imager developed for real-time imaging of cutaneous wounds in research settings is described. The imager consists of a high-resolution near-infrared CCD camera capable of detecting both bioluminescence and fluorescence illuminated by an LED ring with a rotatable filter wheel. All external components are integrated into a compact camera attachment. The device is demonstrated to have competitive performance with a commercial animal imaging enclosure box setup in beam uniformity and sensitivity. Specifically, the device was used to visualize the bioluminescence associated with increased reactive oxygen species activity during the wound healing process in a cutaneous wound inflammation model. In addition, this device was employed to observe the fluorescence associated with the activity of matrix metalloproteinases in a mouse lipopolysaccharide-induced infection model. Our results support the use of the portable imager design as a noninvasive and real-time imaging tool to assess the extent of wound inflammation and infection.

  16. Effects of Rat's Licking Behavior on Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Abolghasem Esmaeili

    2010-01-01

    Full Text Available Objective(sWound licking has been shown to advance wound healing among humans and many other animals. The present study evaluates the licking effects on healing of skin wound in rats. Materials and MethodsTwenty four rats were assigned to 4 different groups randomly and two 3 cm longitudinal full thickness incisions were made on each dorsal and ventral side of rats. The ventral incisions were considered as treated wounds because of contact to saliva as rats lick them easily and dorsal incisions as control wounds. Clinical changes and histopathological effects of rat saliva on wound healing were evaluated every day and on 3, 7, 14 and 21 days post-operation respectively. ResultsHistologic and clinical evaluation of treated wounds showed better healing than control wounds. ConclusionThis study showed that licking behavior can promote wound healing. Thus salivary compounds could be isolated, be mass produced and may have potential to become as common as antibiotic cream.

  17. Repair of open compound lower extremity wounds%下肢开放复杂伤口与创面的修复

    Institute of Scientific and Technical Information of China (English)

    朱敬民; 陈传功; 种亚林; 郝天智; 鲁刚; 周智; 随志甫; 刘静杰; 屠晓军; 罗金超; 范宝玉

    2008-01-01

    Objective To explore the repair of the open compound wounds in lower extremities caused by multiple factors. Methotis Transplantation of cutaneous.musculo-cutaneous or greater omentum flaps were applied to 155 patients of open compound lower extremity wounds. Results The wound healing rate following first operation was 50% and that following two operations was 14.8%.While the wounds were healed in 7.7% of patients after three operations. Conclusion Transplantations of cutaneous,musculo-cutaneous or greater omentum flaps ale effective to repair and reconstruct the open compound lower extremity wounds.%目的 探讨多种原因造成的下肢开放复杂伤口与创面的修复.方法 应用皮瓣、肌皮瓣、大网膜移植等方法,对155例下肢复杂伤口与创面进行修复.结果 一次手术愈合率为50%;两次手术愈合率为14.8%;三次手术愈合率为7.7%.结论 皮瓣、肌皮瓣以及大网膜移植,可以有效修复多种原因造成的下肢复杂伤口与创面.

  18. Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway.

    Science.gov (United States)

    Wu, Xue; Yang, Longlong; Zheng, Zhao; Li, Zhenzhen; Shi, Jihong; Li, Yan; Han, Shichao; Gao, Jianxin; Tang, Chaowu; Su, Linlin; Hu, Dahai

    2016-03-01

    Wound healing is a highly orchestrated, multistep process, and delayed wound healing is a significant symptomatic clinical problem. Keratinocyte migration and re-epithelialization play the most important roles in wound healing, as they determine the rate of wound healing. In our previous study, we found that Src, one of the oldest proto‑oncogenes encoding a membrane-associated, non-receptor protein tyrosine kinase, promotes keratinocyte migration. We therefore hypothesized that Src promotes wound healing through enhanced keratinocyte migration. In order to test this hypothesis, vectors for overexpressing Src and small interfering RNAs (siRNAs) for silencing of Src were used in the present study. We found that the overexpression of Src accelerated keratinocyte migration in vitro and promoted wound healing in vivo without exerting a marked effect on cell proliferation. The extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways play important roles in Src-accelerated keratinocyte migration. Further experiments demonstrated that Src induced the protein expression of matrix metalloproteinase-2 (MMP-2) and decreased the protein expression of E-cadherin. We suggest that ERK signaling is involved in the Src-mediated regulation of MMP-2 expression. The present study provided evidence that Src promotes keratinocyte migration and cutaneous wound healing, in which the regulation of MMP-2 through the ERK pathway plays an important role, and thus we also demonstrated a potential therapeutic role for Src in cutaneous wound healing.

  19. The Effect of Propofol Anesthesia on Cutaneous Wound Healing in Rats

    Directory of Open Access Journals (Sweden)

    Alireza Raayat Jahromi

    2016-12-01

    Full Text Available Background & Objective: The present study surveys the effects of propofol on cutaneous wound healing in rats. Materials & Methods: 36 adult female Strague-Dawely rats were divided into three groups randomly; in group one propofol (60 mg/kg and ketamine (40 mg/kg combination; in group two ketamine (50 mg/kg, and in group three propofol (100 mg/kg was injected intraperitoneally. Following routine surgical preparation, 1.5×1.5 cm wounds were created on the back of the rats. Wound size was evaluated daily and then the wound area was calculated by Digimizer software. Following euthanasia on day 21 after wounding, 1×1 cm skin samples were collected for histopathological evaluations and hydroxyproline content. Results: Wound size and hydroxyproline content showed no significant difference in propofol group compared to ketamine and propofol-ketamine groups. Fibroblast content and vascularity revealed no significant difference between groups. Inflammatory cell infiltration in ketamine group, collagen deposition in ketamine-propofol groups, and epithelial regeneration in propofol group were significantly higher in comparison with others. Conclusion: In conclusion, single use of propofol has no adverse effect on cutaneous wound healing in rats compared to ketamine, but evaluation of its positive effects on wound healing necessitates more detailed studies.

  20. Effect of autologous platelet-rich plasma application on cutaneous wound healing in dogs.

    Science.gov (United States)

    Jee, Cho-Hee; Eom, Na-Young; Jang, Hyo-Mi; Jung, Hae-Won; Choi, Eul-Soo; Won, Jin-Hee; Hong, Il-Hwa; Kang, Byeong-Teck; Jeong, Dong Wook; Jung, Dong-In

    2016-03-01

    This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs.

  1. Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

    Science.gov (United States)

    Roth, Sigal; Amzel, Tal; Harel-Adar, Tamar; Tamir, Eran; Grynspan, Frida; Shoseyov, Oded

    2013-01-01

    Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds. PMID:23259631

  2. In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates*

    Science.gov (United States)

    Sabino, Fabio; Hermes, Olivia; Egli, Fabian E.; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N.; Smola, Hans; auf dem Keller, Ulrich

    2015-01-01

    Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease

  3. In vivo assessment of protease dynamics in cutaneous wound healing by degradomics analysis of porcine wound exudates.

    Science.gov (United States)

    Sabino, Fabio; Hermes, Olivia; Egli, Fabian E; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N; Smola, Hans; auf dem Keller, Ulrich

    2015-02-01

    Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease

  4. Chronic stress impairs the local immune response during cutaneous repair in gilthead sea bream (Sparus aurata, L.).

    Science.gov (United States)

    Mateus, Ana Patrícia; Anjos, Liliana; Cardoso, João R; Power, Deborah M

    2017-07-01

    Scale removal in fish triggers a damage-repair program to re-establish the lost epidermis and scale and an associated local immune response. In mammals, chronic stress is known to delay wound healing and to modulate the cutaneous stress axis, but this is unstudied in teleost fish the most successful extant vertebrates. The present study was designed to test the hypothesis that chronic stress impairs cutaneous repair in teleost fish as a consequence of suppression of the immune response. The hypothesis was tested by removing the scales and damaging the skin on one side of the body of fish previously exposed for 4 weeks to a chronic crowding stress and then evaluating cutaneous repair for 1 week. Scale removal caused the loss of the epidermis although at 3days it was re-established. At this stage the basement membrane was significantly thicker (p=0.038) and the hypodermis was significantly thinner (p=0.016) in the regenerating skin of stressed fish relative to the control fish. At 3days, stressed fish also had a significantly lower plasma osmolality (p=0.015) than control fish indicative of reduced barrier function. Chronic stress caused a significant down-regulation of the glucocorticoid receptor (gr) in skin before damage (time 0, p=0.005) and of star at 3 and 7days (p<0.05) after regeneration relative to control fish. In regenerating skin key transcripts of cutaneous repair, pcna, colivα1 and mmp9, and the inflammatory response, tgfβ1, csf-1r, mpo and crtac2, were down-regulated (p<0.05) by chronic stress. Irrespective of chronic stress and in contrast to intact skin many hyper pigmented masses, putative melanomacrophages, infiltrated the epidermis of regenerating skin. This study reveals that chronic stress suppresses the local immune response to scale removal and impairs the expression of key transcripts of wound healing. Elements of the stress axis were identified and modulated by chronic stress during cutaneous repair in gilthead seabream skin. Copyright

  5. Effects of genistein on early-stage cutaneous wound healing.

    Science.gov (United States)

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.

  6. Human skin transcriptome during superficial cutaneous wound healing.

    Science.gov (United States)

    Nuutila, Kristo; Siltanen, Antti; Peura, Matti; Bizik, Jozef; Kaartinen, Ilkka; Kuokkanen, Hannu; Nieminen, Tapio; Harjula, Ari; Aarnio, Pertti; Vuola, Jyrki; Kankuri, Esko

    2012-01-01

    Healing of the epidermis is a crucial process for maintaining the skin's defense integrity and its resistance to environmental threats. Compromised wound healing renders the individual readily vulnerable to infections and loss of body homeostasis. To clarify the human response of reepithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. In all, 25 biopsies from eight patients qualified for the study. All samples were analyzed by genome-wide microarrays. Here, we identified the genes associated with normal skin reepithelialization over time and organized them by similarities according to their induction or suppression patterns during wound healing. Our results provide the first elaborate insight into the transcriptome during normal human epidermal wound healing. The data not only reveal novel genes associated with epidermal wound healing but also provide a fundamental basis for the translational interpretation of data acquired from experimental models.

  7. Analysis of a Mathematical Model of Ischemic Cutaneous wounds

    CERN Document Server

    Friedman, Avner; Xue, Chuan

    2009-01-01

    Chronic wounds represent a major public health problem affecting 6.5 million people in the United States. Ischemia represents a serious complicating factor in wound healing. In this paper we analyze a recently developed mathematical model of ischemic dermal wounds. The model consists of a coupled system of partial differential equations in the partially healed region, with the wound boundary as a free boundary. The extracellular matrix (ECM) is assumed to be viscoelastic, and the free boundary moves with the velocity of the ECM at the boundary of the open wound. The model equations involve the concentrations of oxygen, cytokines, and the densities of several types of cells. The ischemic level is represented by a parameter which appears in the boundary conditions, 0 <= gamma < 1; gamma near 1 corresponds to extreme ischemia and gamma = 0 corresponds to normal non-ischemic conditions. We establish global existence and uniqueness of the free boundary problem and study the dependence of the free boundary on...

  8. Wound Healing Effect of Slightly Acidic Electrolyzed Water on Cutaneous Wounds in Hairless Mice via Immune-Redox Modulation.

    Science.gov (United States)

    You, Hae Sun; Fadriquela, Ailyn; Sajo, Ma Easter Joy; Bajgai, Johny; Ara, Jesmin; Kim, Cheol Su; Kim, Soo-Ki; Oh, Jin Rok; Shim, Kwang Yong; Lim, Hyun Kyo; Lee, Kyu-Jae

    2017-01-01

    Acidic electrolyzed water is an innovative sanitizer having a wide-spectrum of applications in food industry, and healthcare industry but little is known on its effect and mechanism in wound healing. The study was conducted to identify the effect and mechanism of slightly acidic electrolyzed water (SAEW) on cutaneous wounds in hairless mice. SAEW (pH: 5-6.5, oxidation reduction potential: 800 mV, chlorine concentration: 25 ppm) was prepared through electrolysis of water and was applied to the wounds of hairless mice three times a day for seven days. Wound size, immune response and oxidative stress were explored and compared to conventional agents such as Betadine and alcohol. We found that SAEW-treated group showed the highest wound reduction percentage (phealing. In line, SAEW treatment decreased pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, keratinocyte chemoattractant, and tumor necrosis factor-α] in serum. Other hallmarks of wound healing, matrixmetalloproteinases (MMP)1 and MMP9 were also upregulated. Collectively, our study indicates that SAEW is effective in wound healing of hairless mice via immune-redox modulation, and heals better/faster than conventional agents.

  9. Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats

    Science.gov (United States)

    2011-01-01

    Background Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. Methods The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. Results After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ. Conclusion The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts. PMID:21982053

  10. Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats

    Directory of Open Access Journals (Sweden)

    Yu Bo

    2011-10-01

    Full Text Available Abstract Background Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. Methods The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81% and erythromycin ointment, respectively (5 mg of ointment were applied on each wound. To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. Results After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ. Conclusion The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.

  11. Fibrin/platelet plug counteracts cutaneous wound contraction: the hypothesis of "skipping stone".

    Science.gov (United States)

    Farahani, Ramin Mostofi Zadeh

    2007-01-01

    Cutaneous wound contraction and epithelialization act collaboratively to minimize the exposed wound surface. However excessive wound contraction is undesirable due to the resultant disfigurement and scarring. Fibrin clot has greater stiffness than surrounding tissue and mechanical strain further enhances its stiffness. On the contrary, skin exhibits diminished stiffness when affected by high strain rates. Therefore during early stages of wound healing, the contractile wound border is confronted by fibrin clot forming a high strain region in the interface of contractile tissue and fibrin clot--which is evidenced by computer simulation. Due to the stress relaxation property of skin, the contractile strain is partly neutralized. Meanwhile, gradually the stiffness of fibrin clot decreases which is followed by another cycle of wound contraction. This cyclic pattern of contraction resembles the movement of a stone over water or "skipping stone". The stone bounces repeatedly when thrown across the surface of water with reduction of jumping altitude with each bounce till the stone stops completely. This hypothesis is further supported by the observed initial delay in wound contraction and the chronological correlation of enhanced wound contraction with loss of superficial eschar and substitution of fibrin clot with granulation tissue. Also there is evidence that fibrin inhibits fibroblast-mediated contraction of collagen. Furthermore, modest increase in wound contraction rate in fibrinogen deficient mice and fibrin-mediated diminished wound contraction are agreement with the proposed hypothesis.

  12. Evaluation of Topical Tocopherol Cream on Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Teoh Seong Lin

    2012-01-01

    Full Text Available Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I diabetic rats receiving control cream , (II diabetic rats receiving 0.06% tocopherol cream , and (III diabetic rats receiving 0.29% tocopherol cream . Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing.

  13. Evaluation of Topical Tocopherol Cream on Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Lin, Teoh Seong; Abd Latiff, Azian; Abd Hamid, Noor Aini; Wan Ngah, Wan Zurinah bt; Mazlan, Musalmah

    2012-01-01

    Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream (n = 6), (II) diabetic rats receiving 0.06% tocopherol cream (n = 6), and (III) diabetic rats receiving 0.29% tocopherol cream (n = 6). Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly (P < 0.05) compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing. PMID:23097676

  14. Oxidative stress in normal and impaired wound repair.

    Science.gov (United States)

    Schäfer, Matthias; Werner, Sabine

    2008-08-01

    A large percentage of the population suffers from wound healing abnormalities, in particular aged individuals, patients with diabetes, and those treated with immunosuppressive drugs, chemo- or radiotherapy. The mechanisms underlying the impaired healing response are still poorly understood. Recent studies provided strong evidence for a role of oxidative stress in the pathogenesis of non-healing ulcers. Therefore, it is of major importance to identify and functionally characterize the factors involved in the generation and detoxification of reactive oxygen species (ROS). This will provide the basis for the development of new strategies for therapeutic intervention. In this review we summarize the current information about the roles of low molecular weight antioxidants and ROS-detoxifying enzymes in normal and impaired wound repair, and we report on the consequences of their modulation at the wound site.

  15. Keratinocyte-derived follistatin regulates epidermal homeostasis and wound repair

    Science.gov (United States)

    Antsiferova, Maria; Klatte, Jennifer E; Bodó, Enikö; Paus, Ralf; Jorcano, José L; Matzuk, Martin M; Werner, Sabine; Kögel, Heidi

    2014-01-01

    Activin is a growth and differentiation factor that controls development and repair of several tissues and organs. Transgenic mice overexpressing activin in the skin were characterized by strongly enhanced wound healing, but also by excessive scarring. In this study, we explored the consequences of targeted activation of activin in the epidermis and hair follicles by generation of mice lacking the activin antagonist follistatin in keratinocytes. We observed enhanced keratinocyte proliferation in the tail epidermis of these animals. After skin injury, an earlier onset of keratinocyte hyperproliferation at the wound edge was observed in the mutant mice, resulting in an enlarged hyperproliferative epithelium. However, granulation tissue formation and scarring were not affected. These results demonstrate that selective activation of activin in the epidermis enhances reepithelialization without affecting the quality of the healed wound. PMID:19079322

  16. Gene therapy and cutaneous wound healing%基因治疗与皮肤创面愈合

    Institute of Scientific and Technical Information of China (English)

    朱平; 严励

    2009-01-01

    Cutaneous wound healing is a complicated multiatep process with numerous mediators that act in a network of activation and inhibition processes. Nonhealing chronic wounds decrease the quality of Life. Recombinant growth factors, currently used in clinic, fail to provide a sustained repair function at the wound due to their inadequate biological availability and transient half-time. Recent attention has focused on gene therapy, which might become a significant treatment modality for those wound healing pathologies refractory to other wound management approaches. This review discusses the potentials and limitations of current genetherapy for the treatment of wounds, current ongoing clinical trials, and possible future directions in this exciting field.%皮肤创面愈合过程是一个多因素参与的复杂过程,慢性、难愈创面严重影响了人们的生活质量.重组生长因子已经在临床用于改善创面愈合,但由于半衰期短、生物利用度低等原因,使得其临床疗效欠佳.近年来,随着基因工程技术的不断发展,基因治疗已经成为改善创面愈合的一种新的治疗方法.本文就目前基因治疗方法的优缺点、治疗性基因选择和正在进行的临床试验等方面进行了综述.

  17. Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats

    Directory of Open Access Journals (Sweden)

    Chen Wei-Cheng

    2012-11-01

    Full Text Available Abstract Background Lonicera japonica Thunb. (Caprifoliaceae, a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE was investigated for its healing efficiency in a rat excision wound model. Methods Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w LJEE ointment, or the reference standard drug, 0.2% (w/w nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. Results LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. Conclusions The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair.

  18. Biodegradable Gelatin Microcarriers Facilitate Re-Epithelialization of Human Cutaneous Wounds - An In Vitro Study in Human Skin.

    Science.gov (United States)

    Lönnqvist, Susanna; Rakar, Jonathan; Briheim, Kristina; Kratz, Gunnar

    2015-01-01

    The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds.

  19. Pathological axes of wound repair: Gastrulation revisited

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    Aller Maria-Angeles

    2010-09-01

    Full Text Available Abstract Post-traumatic inflammation is formed by molecular and cellular complex mechanisms whose final goal seems to be injured tissue regeneration. In the skin -an exterior organ of the body- mechanical or thermal injury induces the expression of different inflammatory phenotypes that resemble similar phenotypes expressed during embryo development. Particularly, molecular and cellular mechanisms involved in gastrulation return. This is a developmental phase that delineates the three embryonic germ layers: ectoderm, endoderm and mesoderm. Consequently, in the post-natal wounded skin, primitive functions related with the embryonic mesoderm, i.e. amniotic and yolk sac-derived, are expressed. Neurogenesis and hematogenesis stand out among the primitive function mechanisms involved. Interestingly, in these phases of the inflammatory response, whose molecular and cellular mechanisms are considered as traces of the early phases of the embryonic development, the mast cell, a cell that is supposedly inflammatory, plays a key role. The correlation that can be established between the embryonic and the inflammatory events suggests that the results obtained from the research regarding both great fields of knowledge must be interchangeable to obtain the maximum advantage.

  20. Pathological axes of wound repair: gastrulation revisited.

    Science.gov (United States)

    Aller, Maria-Angeles; Arias, Jose-Ignacio; Arias, Jaime

    2010-09-14

    Post-traumatic inflammation is formed by molecular and cellular complex mechanisms whose final goal seems to be injured tissue regeneration.In the skin -an exterior organ of the body- mechanical or thermal injury induces the expression of different inflammatory phenotypes that resemble similar phenotypes expressed during embryo development. Particularly, molecular and cellular mechanisms involved in gastrulation return. This is a developmental phase that delineates the three embryonic germ layers: ectoderm, endoderm and mesoderm. Consequently, in the post-natal wounded skin, primitive functions related with the embryonic mesoderm, i.e. amniotic and yolk sac-derived, are expressed. Neurogenesis and hematogenesis stand out among the primitive function mechanisms involved.Interestingly, in these phases of the inflammatory response, whose molecular and cellular mechanisms are considered as traces of the early phases of the embryonic development, the mast cell, a cell that is supposedly inflammatory, plays a key role.The correlation that can be established between the embryonic and the inflammatory events suggests that the results obtained from the research regarding both great fields of knowledge must be interchangeable to obtain the maximum advantage.

  1. Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing.

    Science.gov (United States)

    Dreymueller, Daniela; Denecke, Bernd; Ludwig, Andreas; Jahnen-Dechent, Willi

    2013-01-01

    In adults, repair of deeply injured skin wounds results in the formation of scar tissue, whereas in embryos wounds heal almost scar-free. Macrophages are important mediators of wound healing and secrete cytokines and tissue remodeling enzymes. In contrast to host defense mediated by inflammatory M1 macrophages, wound healing and tissue repair involve regulatory M2/M2-like macrophages. Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound healing. In the present study, we asked whether atopical application of ex vivo generated, embryonic stem cell-derived macrophages (ESDM) improve wound healing in mice. ESDM were tested side by side with bone marrow-derived macrophages (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like macrophage subtype as indicated by their reduced responsiveness to lipopolysaccharide, reduced expression of Toll-like receptors, and reduced bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture, ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds had more scar formation compared to wounds receiving BMDM or cell-free treatment. Our data indicate that atopical application of ex vivo generated macrophages is not a suitable cell therapy of dermal wounds.

  2. Effects of Autologous Platelets Rich Plasma on Full-thickness Cutaneous Wounds Healing in Goats

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    A.H. AL-Bayati

    2013-12-01

    Full Text Available This investigation was designed to evaluate the role of Platelet-Rich Plasma (PRP on healing of experimentally wounded skin in ten adult bucks, aged 2-3 years and weighing 25-30 kg. The animals divided randomly and equally into (control and treatment groups. Four of 3×3 cm of full-thickness square cutaneous wounds was induced on both sides of the lateral thoracic region of each animal under the effect of local anesthetic proceeding by xylazine hydrochloride as a sedative. A pair of left wounds was treated by injection with 5 mL of autonomous PRP (treatment group, 2 mm lateral to the wound edges and in the wound center. While, the right wound were injected by 5 mL of sterile saline by the same procedure (control group. Each group was divided into five subgroups (four wounds of each, for morph metrical and histopathological evaluations of wound healing process represented by percent of wound contraction, epithelialization and total healing at 3, 7, 14, 21 and 28 days post-wounding. The morphometrical appearance of the wounds which treated with PRP, showed that the contraction, re-epithelialization and healing percent were statically significant (p<0.05 in comparison with control wounds during four weeks study. Based on histopathological results, there was re-epithelialization of epidermis, with highly cellular granulation tissue, well differentiated keratinocytes of epidermis with scar formation in the dermis of the sectioned skin. We conclude that local injection of PRP leads to accelerate and improvement of wound healing in comparison to control wounds.

  3. Noninvasive imaging technologies for cutaneous wound assessment: A review.

    Science.gov (United States)

    Paul, Dereck W; Ghassemi, Pejhman; Ramella-Roman, Jessica C; Prindeze, Nicholas J; Moffatt, Lauren T; Alkhalil, Abdulnaser; Shupp, Jeffrey W

    2015-01-01

    The ability to phenotype wounds for the purposes of assessing severity, healing potential and treatment is an important function of evidence-based medicine. A variety of optical technologies are currently in development for noninvasive wound assessment. To varying extents, these optical technologies have the potential to supplement traditional clinical wound evaluation and research, by providing detailed information regarding skin components imperceptible to visual inspection. These assessments are achieved through quantitative optical analysis of tissue characteristics including blood flow, collagen remodeling, hemoglobin content, inflammation, temperature, vascular structure, and water content. Technologies that have, to this date, been applied to wound assessment include: near infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarization spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, and spectral/hyperspectral imaging. We present a review of the technologies in use or development for these purposes with three aims: (1) providing basic explanations of imaging technology concepts, (2) reviewing the wound imaging literature, and (3) providing insight into areas for further application and exploration. Noninvasive imaging is a promising advancement in wound assessment and all technologies require further validation.

  4. Factor VII deficiency impairs cutaneous wound healing in mice.

    Science.gov (United States)

    Xu, Zhi; Xu, Haifeng; Ploplis, Victoria A; Castellino, Francis J

    2010-01-01

    Skin keratinocytes express tissue factor (TF) and are highly associated with skin wound healing. Although it has been demonstrated that perivascular TF expression in granulation tissue formed after dermal injury is downregulated during healing, studies of the mechanism of factor (F) VII, a TF ligand, in skin wound healing are lacking. We reported the use of a dermal punch model to demonstrate that low-expressing FVII mice (approximately 1% of wild type [WT]) exhibited impaired skin wound healing compared with WT controls. These low-FVII mice showed defective reepithelialization and reduced inflammatory cell infiltration at wound sites. This attenuated reepithelialization was associated with diminished expression of the transcription factor early growth response 1 (Egr-1). In vitro, Egr-1 was shown to be essential for the FVIIa-induced regulation of keratinocyte migration and inflammation. Both Egr-1 upregulation and downstream inflammatory cytokine appearance in keratinocytes depended on FVIIa/TF/protease-activated receptor 2 (PAR-2)-induced signaling and did not require subsequent generation of FXa and thrombin. The participation of Egr-1 in FVIIa-mediated regulation of keratinocyte function was confirmed by use of Egr-1-deficient mice, wherein a significant delay in skin wound healing after injury was observed, relative to WT mice. The results from these studies demonstrate an in vivo mechanistic relationship between FVIIa, Egr-1 and the inflammatory response in keratinocyte function during the wound healing process.

  5. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2016-10-14

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  6. Management of minor acute cutaneous wounds: importance of wound healing in a moist environment.

    Science.gov (United States)

    Korting, H C; Schöllmann, C; White, R J

    2011-02-01

    Moist wound care has been established as standard therapy for chronic wounds with impaired healing. Healing in acute wounds, in particular in minor superficial acute wounds - which indeed are much more numerous than chronic wounds - is often taken for granted because it is assumed that in those wounds normal phases of wound healing should run per se without any problems. But minor wounds such as small cuts, scraps or abrasions also need proper care to prevent complications, in particular infections. Local wound care with minor wounds consists of thorough cleansing with potable tap water or normal saline followed by the application of an appropriate dressing corresponding to the principles of moist wound treatment. In the treatment of smaller superficial wounds, it appears advisable to limit the choice of dressing to just a few products that fulfil the principles of moist wound management and are easy to use. Hydroactive colloid gels combining the attributes of hydrocolloids and hydrogels thus being appropriate for dry and exuding wounds appear especially suitable for this purpose - although there is still a lack of data from systematic studies on the effectiveness of these preparations. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  7. Electrospun 3D Fibrous Scaffolds for Chronic Wound Repair

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    Huizhi Chen

    2016-04-01

    Full Text Available Chronic wounds are difficult to heal spontaneously largely due to the corrupted extracellular matrix (ECM where cell ingrowth is obstructed. Thus, the objective of this study was to develop a three-dimensional (3D biodegradable scaffold mimicking native ECM to replace the missing or dysfunctional ECM, which may be an essential strategy for wound healing. The 3D fibrous scaffolds of poly(lactic acid-co-glycolic acid (PLGA were successfully fabricated by liquid-collecting electrospinning, with 5~20 µm interconnected pores. Surface modification with the native ECM component aims at providing biological recognition for cell growth. Human dermal fibroblasts (HDFs successfully infiltrated into scaffolds at a depth of ~1400 µm after seven days of culturing, and showed significant progressive proliferation on scaffolds immobilized with collagen type I. In vivo models showed that chronic wounds treated with scaffolds had a faster healing rate. These results indicate that the 3D fibrous scaffolds may be a potential wound dressing for chronic wound repair.

  8. Effect of aqueous extract of Elaeagnus angustifolia fruit on experimental cutaneous wound healing in rats.

    Science.gov (United States)

    Mehrabani Natanzi, Mahboobeh; Pasalar, Parvin; Kamalinejad, Mohammad; Dehpour, Ahmad Reza; Tavangar, Seyed Mohammad; Sharifi, Roya; Ghanadian, Naghmeh; Rahimi-Balaei, Maryam; Gerayesh-Nejad, Siavash

    2012-01-01

    The present study was conducted to investigate the histological changes and wound healing effect of aqueous extract of Elaeagnus angustifolia. After creating full-thickness skin wounds on the back of 45 male Sprague-Dawley rats they were randomly divided into three groups. Treated group received the extract, positive control group were treated with mupirocin ointment 2% and control group did not receive any treatment. Wound healing rates were calculated on days 3, 5, 8, 10, 12 and 15 post-wounding and the wound tissues were harvested at 5, 10, and 15 days for histological analysis and hydroxyproline content measurement. The results indicated a significant increase in the percentage of wound contraction and hydroxyproline content in the treated group comparing to the control and positive control groups. A significant increase in the assigned histological scores was observed at 10 and 15 days in the treated and positive control groups compared to the control group. The results demonstrate that aqueous extract of Elaeagnus angustifolia accelerates cutaneous wound healing, and its effect may be due to the increased re-epithelialization and collagen deposition in wound and so it can be considered as a therapeutic agent for wound healing.

  9. Effect of Aqueous Extract of Elaeagnus angustifolia Fruit on Experimental Cutaneous Wound Healing in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Rahimi-Balaei

    2012-09-01

    Full Text Available The present study was conducted to investigate the histological changes and wound healing effect of aqueous extract of Elaeagnus angustifolia. After creating full-thickness skin wounds on the back of 45 male Sprague-Dawley rats they were randomly divided into three groups. Treated group received the extract, positive control group were treated with mupirocin ointment 2% and control group did not receive any treatment. Wound healing rates were calculated on days 3, 5, 8, 10, 12 and 15 post-wounding and the wound tissues were harvested at 5, 10, and 15 days for histological analysis and hydroxyproline content measurement. The results indicated a significant increase in the percentage of wound contraction and hydroxyproline content in the treated group comparing to the control and positive control groups. A significant increase in the assigned histological scores was observed at 10 and 15 days in the treated and positive control groups compared to the control group. The results demonstrate that aqueous extract of Elaeagnus angustifolia accelerates cutaneous wound healing, and its effect may be due to the increased re-epithelialization and collagen deposition in wound and so it can be considered as a therapeutic agent for wound healing.

  10. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity

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    Zhang Jianing

    2010-03-01

    Full Text Available Abstract Background fatty acids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigat the effect of fatty acid extracts from dried Lucilia sericata larvae on murine cutaneuous wound healing as well as angiogenesis. Results On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fatty acid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fatty acid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fatty acid extracts group were higher than that of vaseline group. Component analysis of the fatty acid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fatty acids in total and the ratio of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid (PUFA was: 20.57%:60.32%:19.11%. Conclusions Fatty acid extracts from dried Lucilia sericata larvae, four fifths of which are unsaturated fatty acids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts.

  11. [Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel].

    Science.gov (United States)

    Chengde, Xia; Haiping, Di; Jidong, Xue; Yaohua, Zhao; Xiaoliang, Li; Qiang, Li; Xihua, Niu; Yonglin, Li; Hongkai, Lian

    2015-05-01

    To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect. From February 2006 to June 2013, 10 patients with soft tissue defect on lower shank and foot were included. The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap, or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap. The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot. The wound area ranged from 40 cm x 21 cm to 22 cm x 15 cm, with flap size from 48 cm x 26 cm to 25 cm x 18 cm. Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus. The kirschner wires were removed at 4 weeks and pedicles were cut off 5-8 weeks postoperatively. Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting. All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness. During the follow-up period of 3 months to 2 years follow up, the ambulatory function of injured legs recovered gradually with satisfactory appearance. The reanastomosed posterior tibial vessel on the healthy side was recovered. Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot. It is a safe and effective method for limb salvage.

  12. Effects of supplementation with different edible oils on cutaneous wound healing.

    Science.gov (United States)

    Otranto, Marcela; Do Nascimento, Adriana Paulino; Monte-Alto-Costa, Andréa

    2010-01-01

    Fatty acids are bioactive molecules, but their effects on cutaneous wound healing are not well understood. Our aim was to investigate the effects of supplementation with edible oils on cutaneous healing. Thirty days before wounding, rats were started on daily supplements of sunflower oil, linseed oil, fish oil, or water. Supplementation lasted until euthanasia. On day 0, an excisional wound was made on the back of each animal. Fourteen days later, the animals were euthanized, and the wound and adjacent skin were collected. Wound closure was higher in the control group compared with the other groups at days 7 and 14. Inflammatory cells were abundant in the control, linseed, and fish groups, but scarce in the sunflower group. Large numbers of myofibroblasts were observed in the control and sunflower groups. The linseed and fish groups presented a high density of dilated blood vessels. The control and sunflower groups showed a moderate density of collagen fibers; a high density of fibers was observed in the linseed and fish groups. Hydroxyproline levels were lowest in the control and sunflower groups. Supplementation with different types of edible oils delayed wound closure and affected the inflammatory infiltrate and collagen deposition.

  13. Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing

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    Huang, Xin [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Burns, Beijing Jishuitan Hospital, Beijing 100035 (China); Zhang, Yaqing; Zhang, Xiangmei [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Xu, Ling, E-mail: lingxu@pku.edu.cn [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Shenzhen Key Laboratory for Polymer Science, Peking University Shenzhen Institute, Shenzhen 518057 (China); Chen, Xin, E-mail: xchin@vip.sina.com [Department of Burns, Beijing Jishuitan Hospital, Beijing 100035 (China); Wei, Shicheng [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing 100081 (China)

    2013-12-01

    A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague–Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing. - Highlights: • The hydrogels were prepared by a facile and green method, radiation crosslinking. • The biodegradability and mechanical strength can be regulated by composition. • The hydrogels promote fibroblasts proliferation and neovascularization. • The hydrogels lead to earlier tissue granulation and re-epithelialization. • The hydrogels are ideal wound healing materials with excellent biocompatibility.

  14. Dose-effect relationships in total body irradiation on the healing of cutaneous wounds

    Institute of Scientific and Technical Information of China (English)

    冉新泽; 程天民; 林远; 屈纪富; 刘都户; 艾国平; 阎国和; 王文昌; 许汝福

    2003-01-01

    ObjectiveTo study the effects of dosages of total body irradiation on the healing process of cutaneous wounds and to observe the changes of wound area at different periods after injury.star rats. The single dosage varied from 1 to 8 Gy. Within 1 h after irradiation, two whole thickness circular cutaneduced on the back of the animals (combined injury groups). Same wounds were produced on rats with no irradiation (single wound group). Wound healing was observed at different points after injury. ResultsAfter total body irradiation with the dose of 1,2,3,4,5,6, 7 or 8 Gy, the wound healing was obviously retarded as the dosages increased. The wound area remained was larger in the large dosage groups than in the small dosage groups. Seven days after injury, there was 33.5% wound surface left unhealed in the single wound group, whereas in the combined injury groups, 35.4%, 38.1%, 41.6%, 48.8%, 53.9%, 63.7%, 69.2% and 73.9% of the wound surfaces remained unhealed, respectively. Statistical analysis showed marked correlations between the varioustimes after total body irradiation and various dosages to the percentage of unhealed wound surface. Nine dose-effect relation formulae were deduced according to the statistical results.ConclusionsIn soft tissue trauma combined with radiation injury, the delay of wound healingis related to the dose of radiation inflicted. It is also related to the time between injury and time of observation.

  15. Effect of pomegranate peel polyphenol gel on cutaneous wound healing in alloxan-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    YAN Huan; PENG Ke-jun; WANG Qiu-lin; GU Zheng-yi; LU Yao-qin; ZHAO Jun; XU Fang

    2013-01-01

    Background Pomegranate (punica granatum) belongs to the family Punicaceae,and its peel has been used as a traditional Chinese medicine because of its efficacy in restraining intestine,promoting hemostasis,and killing parasites.Pomegranate peel has been reported to possess wound-healing properties which are mainly attributed to its polyphenol extracts.The purpose of this study was to investigate the effect of pomegranate peel polyphenols (PPP) gel on cutaneous wound healing in diabetic rats.Methods Alloxan-induced diabetic rats were given incisional wounds on each side of the mid-back and then treated daily with PPP gel (polyphenol mass fraction =30%) post-wounding.Rats were sacrificed on days 4,7,14,and 21post-wounding to assess the rates of wound closure,histological characteristics; and to detect the contents of hydroxyproline,production of nitric oxide (NO),and activities of NO synthase (NOS),as well as the expressions of transforming growth factor-β1 (TGF-β1),vascular endothelial growth factor (VEGF),and epidermal growth factor (EGF)in wound tissue.Results Wound closure was significantly shortened when PPP gel was applied to the wounds of diabetic rats.Histological examination showed the ability of PPP gel to increase fibroblast infiltration,collagen regeneration,vascularization,and epithelialization in the wound area of diabetic rats.In addition,PPP gel-treated diabetic rats showed increased contents of hydroxyproline,production of NO,and activities of NOS and increased expressions of TGF-β1,VEGF,and EGF in wound tissues.Conclusion PPP gel may be a beneficial method for treating wound disorders associated with diabetes.

  16. Evaluation of Therapeutic Intervention with a Natural Product in Cutaneous Wound Healing: The Use of Capybara Oil

    OpenAIRE

    2013-01-01

    Capybara oil is commonly used for cutaneous wound healing in traditional South American medicine, although its beneficial effect has never been experimentally proven. The aim of this study was to investigate the effects of the topical application of capybara oil on skin wounds in Swiss mice. The following characteristics of the wounds were observed and evaluated: wound contraction and reepithelialization, the number of polymorphonuclear leukocytes and mast cells, the thickness of the neoepide...

  17. Induction of Specific MicroRNAs Inhibits Cutaneous Wound Healing*

    Science.gov (United States)

    Pastar, Irena; Khan, Aly Azeem; Stojadinovic, Olivera; Lebrun, Elizabeth A.; Medina, Mayrin Correa; Brem, Harold; Kirsner, Robert S.; Jimenez, Joaquin J.; Leslie, Christina; Tomic-Canic, Marjana

    2012-01-01

    Chronic nonhealing wounds, such as venous ulcers (VUs), are a widespread and serious medical problem with high morbidity and mortality. The molecular pathology of VUs remains poorly understood, impeding the development of effective treatment strategies. Using mRNA expression profiling of VUs biopsies and computational analysis, we identified a candidate set of microRNAs with lowered target gene expression. Among these candidates, miR-16, -20a, -21, -106a -130a, and -203 were confirmed to be aberrantly overexpressed in a cohort study of 10 VU patients by quantitative PCR and in situ hybridizations. These microRNAs were predicted to target multiple genes important for wound healing, including early growth response factor 3, vinculin, and leptin receptor (LepR). Overexpression of the top up-regulated miRNAs, miR-21 and miR-130a, in primary human keratinocytes down-regulated expression of the endogenous LepR and early growth response factor 3. The luciferase reporter assay verified LepR as a direct target for miR-21 and miR-130a. Both miR-21 and miR-130a delayed epithelialization in an acute human skin wound model. Furthermore, in vivo overexpression of miR-21 inhibited epithelialization and granulation tissue formation in a rat wound model. Our results identify a novel mechanism in which overexpression of specific set of microRNAs inhibits wound healing, resulting in new potential molecular markers and targets for therapeutic intervention. PMID:22773832

  18. A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

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    Liang Dong

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

  19. A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

    Science.gov (United States)

    Dong, Liang; Hao, Haojie; Liu, Jiejie; Ti, Dongdong; Tong, Chuan; Hou, Qian; Li, Meirong; Zheng, Jingxi; Liu, Gang

    2017-01-01

    Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

  20. Nitric oxide-releasing polymer incorporated ointment for cutaneous wound healing.

    Science.gov (United States)

    Kang, Youngnam; Kim, Jihoon; Lee, Yeong Mi; Im, Sooseok; Park, Hansoo; Kim, Won Jong

    2015-12-28

    This work demonstrates the development of nitric oxide-releasing ointment and its potential on efficient wound healing. Nitric oxide-releasing polymer was successfully synthesized, which is composed of biocompatible Pluronic F127, branched polyethylenimine and 1-substituted diazen-1-ium-1,2-diolates. The synthesized nitric oxide-releasing polymer was incorporated into the PEG-based ointment which not only facilitated nitric oxide release in a slow manner, but also served as a moisturizer to enhance the wound healing. As compared to control groups, the nitric oxide-releasing ointment showed the accelerated wound closure with enhanced re-epithelialization, collagen deposition, and blood vessel formation in vivo. Therefore, this nitric oxide-based ointment presents the promising potential for the efficient strategy to heal the cutaneous wound.

  1. Myosin II does not contribute to wound repair in Dictyostelium cells

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    Shigehiko Yumura

    2014-09-01

    Full Text Available Cells are always subjected to mechanical stresses, resulting in wounds of the cell membrane, but cells are able to repair and reseal their wounded membrane. Previous reports have shown that actin and myosin II accumulate around the wound and that the constriction of this purse-string closes the membrane pore. Here, we developed a microsurgical wound assay to assess wound repair in Dictyostelium cells. Fluorescent dye that had been incorporated into the cells leaked out for only 2–3 sec after wounding, and a GFP-derived, fluorescent Ca2+ sensor showed that intracellular Ca2+ transiently increased immediately after wounding. In the absence of external Ca2+, the cell failed to repair itself. During the repair process, actin accumulated at the wounded sites but myosin II did not. The wounds were repaired even in myosin II null cells to a comparable degree as the wild-type cells, suggesting that myosin II does not contribute to wound repair. Thus, the actomyosin purse-string constriction model is not a common mechanism for wound repair in eukaryotic cells, and this discrepancy may arise from the difference in cell size.

  2. Evaluation of healing of infected cutaneous wounds treated with different energy densities

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    Santos, Nicole R. S.; Cangussú, Maria C. T.; N. dos Santos, Jean; Pinheiro, Antonio L. B.

    2011-03-01

    We aimed assess the effects of different energy densities of the association of red/IR laser light on the healing of cutaneous wounds infected Staphylococcus aureus. Background: Wound infection is the most common complication on healing wounds and cause both vascular and cellular responses on the tissue. Several therapeutics is used for improving wound healing including the use of different light sources, such as the Laser. Some energy densities present positive photobiological effects on the healing process. Material and Methods: 24 young adult male Wistar rats, under general anesthesia, had their dorsum shaven, cleaned and a 1 x 1cm cutaneous wound created with a scalpel and left without no suturing or dressings. The wounds were infected with Staphylococcus aureus and were randomly divided in 8 subgroups of 3 animals in each: Control, Group 10J/cm2, Group 20J/cm2, and Group 30J/cm2, 7 and 14 days each group. Laser phototherapy was carried out with a diode (λ680nm/790nm, P= 30mW/40mW, CW, Laser, Ø = 3mm, PD=424mW/cm2 and 566mW/cm2, t=11.8/ 8.8 sec, E=0.35J) and started immediately after surgery and repeated at every other day during 7 days. Laser light was applied on 4 points around wounded area. The animals were killed at either 8th or 15th day after contamination. Specimens were taken, routinely cut and processed to wax, stained and underwent histological analysis. The results were statistically analyzed. Results: Both 20 and 30J/cm2 caused intense collagen deposition at the end of the experimental time. But, when 20 J/cm2 was used the fibers were also well organized. Conclusion: Our results indicate that irradiated subjects showed improved wound healing being the 20 J/cm2 the energy the caused better histological response.

  3. Oxidant and antioxidant events during epidermal growth factor therapy to cutaneous wound healing in rats.

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    Kalay, Zeynep; Cevher, Sule Coskun

    2012-08-01

    Cutaneous wound healing is a highly complex process, which includes inflammation, cell proliferation, matrix deposition and remodelling phases. Various growth factors, like epidermal growth factor (EGF), play an important role during wound healing. However, little is known about relationship between EGF and oxidant-antioxidant events in cutaneous wound healing models. Thus we planned to evaluate the connection between EGF therapy and oxidative stress in dermal tissue followed by wounding. Fifty-four adult male Wistar-albino rats were randomly divided into three groups: control, untreated and topical EGF administrated group. A linear full-thickness excision of 40 mm in length on both sides of spinal cord was made on the back of each rat and sutured under anaesthesia and sterile conditions. Excision was closed with 4/0 atraumatic silk suture. EGF solution was freshly prepared at 10 ng/ml dose in thilotears gel under aseptic conditions. Following the surgery, 1 ml of EGF solution was administered to wound strips one time in everyday. The animals were euthanised and wound tissues were collected on days 1, 5, 7 and 14. Thiobarbituric acid reactive substans (TBARS), glutathione (GSH), reactive nitrogen oxide species (NOx), ascorbic acid levels and superoxide dismutase activity were measured spectrophotometrically. TBARS levels decreased and NOx levels increased on day 5 after operation, and GSH levels were increased on day 14 in EGF administered group compared with untreated group. Our data showed that EGF may act like an antioxidant by scavenging toxic oxidation products in wound tissue. In addition, it may contribute healing of the wound tissue in earlier stages and suggest a potential effective role for antioxidant therapies, especially until day 5.

  4. The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.

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    Nishikori, Yoriko; Shiota, Naotaka; Okunishi, Hideki

    2014-11-01

    Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.

  5. Organic light emitting diode improves diabetic cutaneous wound healing in rats.

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    Wu, Xingjia; Alberico, Stephanie; Saidu, Edward; Rahman Khan, Sazzadur; Zheng, Shijun; Romero, Rebecca; Sik Chae, Hyun; Li, Sheng; Mochizuki, Amane; Anders, Juanita

    2015-01-01

    A major complication for diabetic patients is chronic wounds due to impaired wound healing. It is well documented that visible red wavelengths can accelerate wound healing in diabetic animal models and patients. In vitro and in vivo diabetic models were used to investigate the effects of organic light emitting diode (OLED) irradiation on cellular function and cutaneous wound healing. Human dermal fibroblasts were cultured in hyperglycemic medium (glucose concentration 180 mM) and irradiated with an OLED (623 nm wavelength peak, range from 560 to 770 nm, power density 7 or 10 mW/cm2 at 0.2, 1, or 5 J/cm2). The OLED significantly increased total adenosine triphosphate concentration, metabolic activity, and cell proliferation compared with untreated controls in most parameters tested. For the in vivo experiment, OLED and laser (635 ± 5 nm wavelength) treatments (10 mW/cm2 , 5 J/cm2 daily for a total of seven consecutive days) for cutaneous wound healing were compared using a genetic, diabetic rat model. Both treatments had significantly higher percentage of wound closure on day 6 postinjury and higher total histological scores on day 13 postinjury compared with control. No statistical difference was found between the two treatments. OLED irradiation significantly increased fibroblast growth factor-2 expression at 36-hour postinjury and enhanced macrophage activation during initial stages of wound healing. In conclusion, the OLED and laser had comparative effects on enhancing diabetic wound healing.

  6. Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing.

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    Huang, Xin; Zhang, Yaqing; Zhang, Xiangmei; Xu, Ling; Chen, Xin; Wei, Shicheng

    2013-12-01

    A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague-Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing.

  7. Stellera chamaejasme and its constituents induce cutaneous wound healing and anti-inflammatory activities

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    Kim, Myungsuk; Lee, Hee Ju; Randy, Ahmad; Yun, Ji Ho; Oh, Sang-Rok; Nho, Chu Won

    2017-01-01

    Stellera chamaejasme L. (Thymelaeaceae) is a perennial herb that is widely used in traditional Chinese medicine to treat tumours, tuberculosis and psoriasis. S. chamaejasme extract (SCE) possesses anti-inflammatory, analgesic and wound healing activities; however, the effect of S. chamaejasme and its active compounds on cutaneous wound healing has not been investigated. We assessed full-thickness wounds of Sprague-Dawley (SD) rats and topically applied SCE for 2 weeks. In vitro studies were performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW 264.7 macrophages to determine cell viability (MTT assay), cell migration, collagen expression, nitric oxide (NO) production, prostaglandin E2 (PGE2) production, inflammatory cytokine expression and β-catenin activation. In vivo, wound size was reduced and epithelisation was improved in SCE-treated SD rats. In vitro, SCE and its active compounds induced keratinocyte migration by regulating the β-catenin, extracellular signal-regulated kinase and Akt signalling pathways. Furthermore, SCE and its active compounds increased mRNA expression of type I and III collagen in Hs68 fibroblasts. SCE and chamechromone inhibited NO and PGE2 release and mRNA expression of inflammatory mediators in RAW 264.7 macrophages. SCE enhances the motility of HaCaT keratinocytes and improves cutaneous wound healing in SD rats. PMID:28220834

  8. Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

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    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients.

  9. Local arginase 1 activity is required for cutaneous wound healing.

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    Campbell, Laura; Saville, Charis R; Murray, Peter J; Cruickshank, Sheena M; Hardman, Matthew J

    2013-10-01

    Chronic nonhealing wounds in the elderly population are associated with a prolonged and excessive inflammatory response, which is widely hypothesized to impede healing. Previous studies have linked alterations in local L-arginine metabolism, principally mediated by the enzymes arginase (Arg) and inducible nitric oxide synthase (iNOS), to pathological wound healing. Over subsequent years, interest in Arg/iNOS has focused on the classical versus alternatively activated (M1/M2) macrophage paradigm. Although the role of iNOS during healing has been studied, Arg contribution to healing remains unclear. Here, we report that Arg is dynamically regulated during acute wound healing. Pharmacological inhibition of local Arg activity directly perturbed healing, as did Tie2-cre-mediated deletion of Arg1, revealing the importance of Arg1 during healing. Inhibition or depletion of Arg did not alter alternatively activated macrophage numbers but instead was associated with increased inflammation, including increased influx of iNOS(+) cells and defects in matrix deposition. Finally, we reveal that in preclinical murine models reduced Arg expression directly correlates with delayed healing, and as such may represent an important future therapeutic target.

  10. Laser scanning microscopy as a means to assess the augmentation of tissue repair by exposition of wounds to tissue tolerable plasma

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    Vandersee, Staffan; Richter, Heike; Lademann, Jürgen; Beyer, Marc; Kramer, Axel; Knorr, Fanny; Lange-Asschenfeldt, Bernhard

    2014-11-01

    Confocal laser scan microscopy (CLSM) has emerged as a tool for in vivo assessment of cutaneous conditions. In particular, its use in wound healing assessment has increasingly moved into focus. In this context, the application of tissue tolerable plasma (TTP) for wound treatment has recently become one of the most innovative therapeutic modalities. We analyzed wound healing parameters such as area decline and histomorphological characteristics of tissue repair in six subjects with vacuum-generated wounds on the forearm with a four-armed design: (A) no treatment, (B) treatment with TTP, (C) treatment with octenidine, and (D) sequential treatment with TTP and octenidine. Assessment of the wounds was conducted during six visits over the course of two weeks. The wounds were analyzed by photography and CLSM. TTP treatment led to a more rapid area decline that was statistically significant in comparison to other treatment groups. Besides mild pain, it was well tolerated. Morphologically, wound healing was found to initiate from the edges with the formation of dendritic structures consisting of keratinocytes. CLSM is a valuable tool for assessing the dynamics of wound healing. TTP, for reasons that still need to be investigated, can accelerate wound repair.

  11. Polysaccharides of Aloe vera induce MMP-3 and TIMP-2 gene expression during the skin wound repair of rat.

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    Tabandeh, Mohammad Reza; Oryan, Ahmad; Mohammadalipour, Adel

    2014-04-01

    Polysaccharides are the main macromolecules of Aloe vera gel but no data about their effect on extracellular matrix (ECM) elements are available. Here, mannose rich Aloe vera polysaccharides (AVP) with molecular weight between 50 and 250 kDa were isolated and characterized. Open cutaneous wounds on the back of 45 rats (control and treated) were daily treated with 25mg (n=15) and 50 mg (n=15) AVP for 30 days. The levels of MMP-3 and TIMP-2 gene expression were analyzed using real time PCR. The levels of n-acetyl glucosamine (NAGA), n-acetyl galactosamine (NAGLA) and collagen contents were also measured using standard biochemical methods. Faster wound closure was observed at day 15 post wounding in AVP treated animals in comparison with untreated group. At day 10 post wounding, AVP inhibited MMP-3 gene expression, while afterwards MMP-3 gene expression was upregulated. AVP enhanced TIMP-2 gene expression, collagen, NAGLA and NAGA synthesis in relation to untreated wounds. Our results suggest that AVP has positive effects on the regulation of ECM factor synthesis, which open up new perspectives for the wound repair activity of Aloe vera polysaccharide at molecular level.

  12. Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies

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    Pence, Brandt D.; Woods, Jeffrey A.

    2014-01-01

    Significance: Impaired cutaneous wound healing is a major health concern. Obesity has been shown in a number of studies to impair wound healing, and chronic nonhealing wounds in obesity and diabetes are a major cause of limb amputations in the United States. Recent Advances: Recent evidence indicates that aberrant wound site inflammation may be an underlying cause for delayed healing. Obesity, diabetes, and other conditions such as stress and aging can result in a chronic low-level inflammatory state, thereby potentially affecting wound healing negatively. Critical Issues: Interventions which can speed the healing rate in individuals with slowly healing or nonhealing wounds are of critical importance. Recently, physical exercise training has been shown to speed healing in both aged and obese mice and in older adults. Exercise is a relatively low-cost intervention strategy which may be able to be used clinically to prevent or treat impairments in the wound-healing process. Future Directions: Little is known about the mechanisms by which exercise speeds healing. Future translational studies should address potential mechanisms for these exercise effects. Additionally, clinical studies in obese humans are necessary to determine if findings in obese rodent models translate to the human population. PMID:24761347

  13. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy.

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    Lee, Dylan E; Ayoub, Nagi; Agrawal, Devendra K

    2016-03-09

    Mesenchymal stem cells (MSCs) (also known as multipotent mesenchymal stromal cells) possess the capacity for self-renewal and multi-lineage differentiation, and their ability to enhance cutaneous wound healing has been well characterized. Acting via paracrine interactions, MSCs accelerate wound closure, increase angiogenesis, promote resolution of wound inflammation, favorably regulate extracellular matrix remodeling, and encourage regeneration of skin with normal architecture and function. A number of studies have employed novel methods to amplify the delivery and efficacy of MSCs. Non-traditional sources of MSCs, including Wharton's jelly and medical waste material, have shown efficacy comparable to that of traditional sources, such as bone marrow and adipose tissue. The potential of alternative methods to both introduce MSCs into wounds and increase migration of MSCs into wound areas has also been demonstrated. Taking advantage of the associations between MSCs with M2 macrophages and microRNA, methods to enhance the immunomodulatory capacity of MSCs have shown success. New measures to enhance angiogenic capabilities have also exhibited effectiveness, often demonstrated by increased levels of proangiogenic vascular endothelial growth factor. Finally, hypoxia has been shown to have strong wound-healing potential in terms of increasing MSC efficacy. We have critically reviewed the results of the novel studies that show promise for the continued development of MSC-based wound-healing therapies and provide direction for continued research in this field.

  14. Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing.

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    Kuck, Monika; Strese, Helene; Alawi, Seyed Arash; Meinke, Martina C; Fluhr, Joachim W; Burbach, Guido J; Krah, Martin; Sterry, Wolfram; Lademann, Jürgen

    2014-02-01

    The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. A synthetic uric acid analog accelerates cutaneous wound healing in mice.

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    Srinivasulu Chigurupati

    Full Text Available Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions.

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

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    Mukai, Kanae; Komatsu, Emi; Nakajima, Yukari; Urai, Tamae; Nasruddin; Sugama, Junko; Nakatani, Toshio

    2014-01-01

    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.

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

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    Kanae Mukai

    Full Text Available 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.

  18. Young coconut juice can accelerate the healing process of cutaneous wounds

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    Radenahmad Nisaudah

    2012-12-01

    Full Text Available Abstract Background Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ, presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. Methods Four groups of female rats (6 in each group were included in this study. These included sham-operated, ovariectomized (ovx, ovx receiving estradiol benzoate (EB injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2 level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β antibodies. Results Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group. Conclusions This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

  19. Therapeutic Potential of Noble Nanoparticles for Wound Repair

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    Timur Saliyev

    2014-12-01

    Full Text Available Introduction. Nanoparticles made of noble metals, such as gold and silver, have a great potential to be effectively employed for wound management. The nano-size of such particles provides an opportunity to enlarge the contacting area, which results in more effective anti-bacterial action and faster wound repair. It must be noted that the shape of noble nanoparticles might play a crucial role in the manifestation of their anti-microbial properties. The modern state of technology allows fabrication of the nanoparticles with the desired shape and physical properties. In order to provide efficacy and close contact with the wound, the noble nanoparticles can be incorporated into a special matrix made of a cryogel (based on polymethyl methacrylate. This combination might serve as a foundation for developing completely new types of wound dressing.Materials and methods. We have developed a few methods for synthesizing gold and silver nanoparticles of different shapes and sizes. After fabrication of metallic nanoparticles, they were characterized by using Tunneling Electron Microscopy (TEM and Malvern Zetasizer system in order to determine the average population size and consistency. The silver nanoparticles was synthesized using sodium borohydride reduction of silver nitrate. The synthesis of gold nanoparticles was conducted by using the Turkevich method.Results. We have developed a synthetic cryogel based on polyacrylamide (by cryogelation reaction at several temperatures. At the second step, we developed a method for conjugating fabricated gold and silver nanoparticles to the surface (or pores of cryogel through covalent bonds so they can provide antibacterial action within the wound. By following the developed protocol, we were able to obtain an approximate cryogel layer (1 cm thickness with embedded gold and silver nanoparticles. This conjugate was analyzed and confirmed using Scanning Electron Microscopy (SEM and TEM.Discussion. The obtained

  20. Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis.

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    Xiaobo Liang

    Full Text Available BACKGROUND: COUP-TF interacting protein 2 [(Ctip2, also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/- mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/- mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. METHODOLOGY/PRINCIPAL FINDINGS: Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2 and Ctip2(ep-/- animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep-/- mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. CONCLUSIONS/SIGNIFICANCE: Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.

  1. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

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    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  2. Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography.

    Science.gov (United States)

    Yousefi, Siavash; Qin, Jia; Dziennis, Suzan; Wang, Ruikang K

    2014-01-01

    Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

  3. Avocado/soybean unsaponifiables: a novel regulator of cutaneous wound healing, modelling and remodelling.

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    Oryan, Ahmad; Mohammadalipour, Adel; Moshiri, Ali; Tabandeh, Mohammad R

    2015-12-01

    We investigated the effects of avocado/soybean unsaponifiables (ASU) on the healing response of cutaneous wound defect in rats. Sixty male rats were randomly divided into three groups including control, vehicle and treatment (n = 20 in each group). A 2 × 2 cm(2) wound defect was made on the dorsum. The control, vehicle and treatment groups were treated daily with topical application of saline, cream and cream/ASU for 10 days, respectively. The wounds were monitored daily. The animals were euthanised at 10, 20 and 30 days post injury (D). The dry matter, hydroxyproline, collagen, n-acetyl glucosamine (NAGLA) and n-acetyl galactosamine (NAGAA) contents of the skin samples were measured and the histopathological and biomechanical characteristics of the samples were investigated. Statistics of P < 0·05 was considered significant. Treatment significantly increased tissue glycosaminoglycans and collagen contents at various stages of wound healing compared to controls. Treatment modulated inflammation, improved fibroplasia and produced high amounts of scar tissue at short term. At long term, treatment reduced the scar tissue size and increased the quality and rate of wound contraction and reepithelisation compared to controls. The treated lesions were more cosmetically pleasing and had significantly higher biomechanical characteristics than controls. ASU was effective in rat wound healing.

  4. Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography

    Science.gov (United States)

    Yousefi, Siavash; Qin, Jia; Dziennis, Suzan; Wang, Ruikang K.

    2014-07-01

    Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

  5. Wound healing potential of topical bacteriophage therapy on diabetic cutaneous wounds.

    Science.gov (United States)

    Mendes, João J; Leandro, Clara; Corte-Real, Sofia; Barbosa, Raquel; Cavaco-Silva, Patrícia; Melo-Cristino, José; Górski, Andrzej; Garcia, Miguel

    2013-01-01

    Chronic wounds that fail to heal are a common complication of diabetes mellitus and the most common precipitating reason for nontraumatic lower limb amputation. Unfortunately, the bacterial species that cause these infections are becoming more resistant to antibiotics, making them increasingly difficult to treat. We assessed the feasibility of combating chronic bacterial infections with a topically delivered bacteriophage cocktail in two animal models of diabetes mellitus. Microbiological, planimetric, and histological parameters were compared in debrided infected wounds with or without topical bacteriophage treatment. We determined that bacteriophage treatment effectively decreased bacterial colony counts and improved wound healing, as indicated by smaller epithelial and dermal gaps, in Staphylococcus aureus and Pseudomonas aeruginosa infections but was not as effective against Acinetobacter baumannii. Although the improvements were more significant in the rodent model than in the porcine model, our results suggest that topically administered bacteriophage treatment may be effective in resolving chronic infections, especially when applied in conjunction with wound debridement. These findings have important implications for the feasibility of using topical antimicrobial therapies to safely treat chronic infections in diabetes mellitus patients. © 2013 by the Wound Healing Society.

  6. Sugar-coating wound repair: a review of FGF-10 and dermatan sulfate in wound healing and their potential application in burn wounds.

    Science.gov (United States)

    Plichta, Jennifer K; Radek, Katherine A

    2012-01-01

    Thousands of patients suffer from burn injuries each year, yet few therapies have been developed to accelerate the wound healing process. Most fibroblast growth factors (FGFs) have been extensively evaluated but only a few have been found to participate in the wound healing process. In particular, FGF-10 is robustly increased in the wound microenvironment after injury and has demonstrated some ability to promote wound healing in vitro and in vivo. Glycosaminoglycans are linear carbohydrates that participate in wound repair by influencing cytokine/growth factor localization and interaction with cognate receptors. Dermatan sulfate (DS) is the most abundant glycosaminoglycan in human wound fluid and has been postulated to be directly involved in the healing process. Recently, the combination of FGF-10 and DS demonstrated the potential to accelerate wound healing via increased keratinocyte proliferation and migration. Based on these preliminary studies, DS may serve as a cofactor for FGF-10, and together they are likely to expedite the healing process by stimulating keratinocyte activity. As a specific subtype of wounds, the overall healing process of burn injuries does not significantly differ from other types of wounds, where optimal repair results in matrix regeneration and complete reepithelialization. At present, standard burn treatment primarily involves topical application of antimicrobial agents, while no routine therapies target acceleration of reepithelialization, the key to wound closure. Thus, this novel therapeutic combination could be used in conjunction with some of the current therapies, but it would have the unique ability to initiate wound healing by stimulating keratinocyte epithelialization.

  7. Taurine improves the wound healing process in cutaneous leishmaniasis in mice model, based on stereological parameters

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    Soheil Ashkani-Esfahani

    2014-01-01

    Full Text Available Background: Cutaneous Leishmaniasis is a self-limiting disease caused by protozoan parasites of the genus Leishmania, which affects the skin with full-thickness wounds, which are prone to scar formation even after treatment. Taurine (Tu is one of the most abundant amino acids that has antioxidant and anti-inflammatory effects, which play an important role in the process of wound healing. Herein, we have investigated the effects of Tu on cutaneous Leishmaniasis wounds and L. major promastigotes. Materials and Methods: Eighteen mice were induced with Leishmaniasis wounds (with L. Major on the base of their tails and divided into three groups, T1: Treated with Tu injection, T2: Treated with Tu gel, and C: No treatment. Treatments were carried out every 24 hours for 21 days. The volume densities of the collagen bundles and vessels, vessel′s length density and diameter, and fibroblast populations were estimated by stereological methods. Flow cytometry was used in order to investigate the direct Tu effect on parasites. The Mann-Whitney U test was used and P ≤ 0.05 was considered to be statistically significant. Results: The numerical density of the fibroblasts, volume density of the collagen bundles, and length densities of the vessels in groups T1 and T2 were significantly higher than in group C (P < 0.05. The fibroblast numerical density of group T1 was higher than that of group T2 (P = 0.02. Incidentally, Tu had no direct effect on L. major parasites according to the flow cytometry analysis. Conclusion: Tu showed the ability to improve the wound healing process and tissue regeneration although it had no direct anti-leishmaniasis effect.

  8. Blockade of glucocorticoid receptors improves cutaneous wound healing in stressed mice.

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    de Almeida, Taís Fontoura; de Castro Pires, Taiza; Monte-Alto-Costa, Andréa

    2016-02-01

    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic-pituitary-adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway. © 2016 by the Society for Experimental Biology and Medicine.

  9. Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse

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    Takashi Kitano

    2017-01-01

    Full Text Available Background. We investigated the effects of loss of inducible nitric oxide synthase (iNOS on the healing process of cutaneous excisional injury by using iNOS-null (KO mice. Population of granulation tissue-related cell types, that is, myofibroblasts and macrophages, growth factor expression, and reepithelialization were evaluated. Methods. KO and wild type (WT mice of C57BL/6 background were used. Under general anesthesia two round full-thickness excision wounds of 5.0 mm in diameter were produced in dorsal skin. After specific intervals of healing, macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR were employed to evaluate the healing process. Results. The loss of iNOS retards granulation tissue formation and reepithelialization in excision wound model in mice. Detailed analyses showed that myofibroblast appearance, macrophage infiltration, and mRNA expression of transforming growth factor b and of collagen 1α2 were all suppressed by lacking iNOS. Conclusions. iNOS is required in the process of cutaneous wound healing. Lacking iNOS retards macrophage invasion and its expression of fibrogenic components that might further impair fibrogenic behaviors of fibroblasts.

  10. Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-alpha expression.

    Science.gov (United States)

    Lai, Jiann-Jyh; Lai, Kuo-Pao; Chuang, Kuang-Hsiang; Chang, Philip; Yu, I-Chen; Lin, Wen-Jye; Chang, Chawnshang

    2009-12-01

    Cutaneous wounds heal more slowly in elderly males than in elderly females, suggesting a role for sex hormones in the healing process. Indeed, androgen/androgen receptor (AR) signaling has been shown to inhibit cutaneous wound healing. AR is expressed in several cell types in healing skin, including keratinocytes, dermal fibroblasts, and infiltrating macrophages, but the exact role of androgen/AR signaling in these different cell types remains unclear. To address this question, we generated and studied cutaneous wound healing in cell-specific AR knockout (ARKO) mice. General and myeloid-specific ARKO mice exhibited accelerated wound healing compared with WT mice, whereas keratinocyte- and fibroblast-specific ARKO mice did not. Importantly, the rate of wound healing in the general ARKO mice was dependent on AR and not serum androgen levels. Interestingly, although dispensable for wound closure, keratinocyte AR promoted re-epithelialization, while fibroblast AR suppressed it. Further analysis indicated that AR suppressed wound healing by enhancing the inflammatory response through a localized increase in TNF-alpha expression. Furthermore, AR enhanced local TNF-alpha expression via multiple mechanisms, including increasing the inflammatory monocyte population, enhancing monocyte chemotaxis by upregulating CCR2 expression, and enhancing TNF-alpha expression in macrophages. Finally, targeting AR by topical application of a compound (ASC-J9) that degrades AR protein resulted in accelerated healing, suggesting a potential new therapeutic approach that may lead to better treatment of wound healing.

  11. Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats.

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    Kant, Vinay; Kumar, Dinesh; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2017-05-15

    Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocin-induced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats. Open cutaneous excision wound was created on the back of each of the 60 diabetic rats. Wound-inflicted rats were equally divided into three groups namely, control, gel treated, and SP + curcumin treated. Normal saline, pluronic gel, and SP (0.5 × 10(-6)M) + curcumin (0.15%) were topically applied once daily for 19 d to these control, gel-treated, and SP + curcumin groups, respectively. SP + curcumin combination significantly accelerated wound closure and decreased messenger RNA expressions of tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell-derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase, and activities of superoxide dismutase, catalase, and glutathione peroxidase in granulation-healing tissue, compared with control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth-associated protein 43-positive nerve fibers, and thick regenerated epithelial layer. The combination of SP and curcumin accelerated wound healing in diabetic rats and both the drugs were compatible at the doses used in this study. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: Role of COL1A1

    OpenAIRE

    Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Carvalho, Edgar M.; Blackwell, Jenefer M.; Castellucci, Léa

    2015-01-01

    Previous studies have demonstrated a role for wound healing genes in resolution of cutaneous lesions caused by Leishmania spp. in both mice and humans, including the gene FLI1 encoding Friend leukaemia virus integration 1. Reduction of Fli1 expression in mice has been shown to result in up-regulation of collagen type I alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression is involved in a...

  13. Use of metyrapone to treat pituitary-dependent hyperadrenocorticism in a cat with large cutaneous wounds.

    Science.gov (United States)

    Daley, C A; Zerbe, C A; Schick, R O; Powers, R D

    1993-03-15

    Metyrapone, a drug that inhibits cortisol production, was used to lower plasma cortisol concentration and alleviate skin lesions caused by pituitary-dependent hyper-adrenocorticism in a cat. Plasma cortisol concentration was documented by ACTH stimulation test results. During metyrapone treatment, alopecia, thin skin, and large cutaneous wounds resolved. Metyrapone was administered orally at a dosage of 65 mg/kg of body weight, every 12 hours. Metyrapone may be used in conjunction with surgery in the management of pituitary-dependent hyperadrenocorticism in cats.

  14. Primary cutaneous mucormycosis in a patient with burn wounds due to Lichtheimia ramosa.

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    Kaur, Ravinder; Bala, Kiran; Ahuja, Rajeev B; Srivastav, Prabhat; Bansal, Umesh

    2014-10-01

    Mucormycosis is usually an invasive mycotic disease caused by fungi in the class mucormycetes. Here we report a case of cutaneous mucormycosis due to Lichtheimia ramosa in a 20-year-old female patient with burn injuries. She was admitted to the hospital with accidental flame burns covering 60 % total burn surface area. After 15 days of admission to hospital, the burn wound showed features of fungal infection. Culture showed white cottony growth belonging to the Mucorales order. Morphological identification confirmed it as L. ramosa. She was managed surgically and medically with the help of amphotericin B. Patient survived due to prompt diagnosis and appropriate medical and surgical treatment. Early diagnosis is critical in prevention of morbidity and mortality associated with the disease. Fungal infection in burn wounds can be difficult to diagnose and manage.

  15. An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head.

    Science.gov (United States)

    Mace, Kimberly A; Pearson, Joseph C; McGinnis, William

    2005-04-15

    We used wounded Drosophila embryos to define an evolutionarily conserved pathway for repairing the epidermal surface barrier. This pathway includes a wound response enhancer from the Ddc gene that requires grainy head (grh) function and binding sites for the Grh transcription factor. At the signaling level, tyrosine kinase and extracellular signal-regulated kinase (ERK) activities are induced in epidermal cells near wounds, and activated ERK is required for a robust wound response. The conservation of this Grh-dependent pathway suggests that the repair of insect cuticle and mammal skin is controlled by an ancient, shared control system for constructing and healing the animal body surface barrier.

  16. MiRNA与皮肤伤口愈合%MicroRNA in Cutaneous Wound Healing

    Institute of Scientific and Technical Information of China (English)

    杨涛; 孙慧勤; 邹仲敏; 粟永萍

    2012-01-01

    MiRNA是真核生物体内约由22个核苷酸组成的内源性非编码单链RNA,可调节基因转录.它通过其5’非翻译区(UTR)与目标mRNA的3′端非翻译区相结合,从而抑制后者的转录后翻译和降解,进而调节一系列生物学过程,包括生物体生长、发育和疾病等.研究表明,miRNA在干细胞分化、肿瘤形成、血管发生、内耳形成等过程中均发挥重要作用,已成为调节生物学过程的核心因子.伤口愈合是一个与多种类型细胞、细胞因子及细胞外基质相关的过程,它受机体多种因素紧密调控.伤口愈合过程一般被分为三个阶段:炎症反应期,肉芽生长期和组织重建期.已有大量证据证实miRNA在皮肤创伤愈合过程中发挥重要作用,并且miRNA在不同的愈合阶段发挥不同的作用.本文就miRNA在皮肤形态、胎儿无痕愈合及成人伤口愈合各环节中的作用做一综述.%MiRNAs are ~22-nucleotide-long endogenously expressed non-coding single-strain KNAs that regulate the gene transcription. They could modulate the growth, development and diseases of organism by inhibition of post-transcriptional translation and degradation of mRNA, through binding its 5' UTR to 3'UTR of mRNA. It has been proposed that miRNAs play a significant role in differentiation of stem cells, formation of cancer, angiogenesis, development of inner ear, and so on, which has been a core factor of regulation of biological processes. Cutaneous wound healing is a complex biologic process involved in several type of cells, cytokines and extracellular matrix, which is strictly regulated by lots of factors. It has been divided into 3 phases: inflammation, granulation proliferation and tissue reconstruction. A large number of evidence suggested that miRNAs play a significant role in this process, and specific miRNAs are expressed in specific phases. This article reviews the role of miRNA in skin morphogenesis, fetal scarless healing and different

  17. Cutaneous squamous cell carcinoma presenting as a wound with discharging sinus tracts in a wild African lion (Panthera leo).

    Science.gov (United States)

    Mwase, M; Mumba, C; Square, D; Kawarai, S; Madarame, H

    2013-11-01

    A female wild African lion (Panthera leo) was presented with an 8-month history of a wound with multiple discharging sinus tracts on the left paw. Microscopical examination revealed squamous cell carcinoma (SCC). To the best of our knowledge, this is the first report of cutaneous SCC in an African lion. Cutaneous SCC presenting as discharging sinus tracts lined by neoplastic squamous cells has not been reported previously in animals.

  18. Ultrastructural changes in blood vessels in epidermal growth factor treated experimental cutaneous wound model.

    Science.gov (United States)

    Kılıçaslan, Seda M Sarı; Cevher, Sule Coşkun; Peker, Emine G Güleç

    2013-11-01

    This study investigates the impact of epidermal growth factor (EGF) on blood vessels, specifically on the development of intussusceptive angiogenesis in cutaneous wound healing. Excisional wounds were formed on both sides of the medulla spinalis in dorsal location of the rats. The control and EGF-treated groups were divided into two groups with respect to sacrifice day: 5 d and 7 d. EGF was topically applied to the EGF-treated group once a day. The wound tissue was removed from rats, embedded in araldite and paraffin, and then examined under transmission electron and light microscopes. The ultrastructural signs of intussusceptive angiogenesis, such as intraluminal protrusion of endothelial cells and formation of the contact zone of opposite endothelial cells, were observed in the wound. Our statistical analyses, based on light microscopy observations, also confirm that EGF treatment induces intussusceptive angiogenesis. Moreover, we found that induction of EGF impact on intussusceptive angiogenesis is higher on the 7th day of treatment than on the 5th day. This implies that the duration of EGF treatment is important. This research clarifies the effects of EGF on the vessels and proves that EGF induces intussusceptive angiogenesis, being a newer model with respect to sprouting type.

  19. A 3D assessment tool for accurate volume measurement for monitoring the evolution of cutaneous leishmaniasis wounds.

    Science.gov (United States)

    Zvietcovich, Fernando; Castañeda, Benjamin; Valencia, Braulio; Llanos-Cuentas, Alejandro

    2012-01-01

    Clinical assessment and outcome metrics are serious weaknesses identified on the systematic reviews of cutaneous Leishmaniasis wounds. Methods with high accuracy and low-variability are required to standarize study outcomes in clinical trials. This work presents a precise, complete and noncontact 3D assessment tool for monitoring the evolution of cutaneous Leishmaniasis (CL) wounds based on a 3D laser scanner and computer vision algorithms. A 3D mesh of the wound is obtained by a commercial 3D laser scanner. Then, a semi-automatic segmentation using active contours is performed to separate the ulcer from the healthy skin. Finally, metrics of volume, area, perimeter and depth are obtained from the mesh. Traditional manual 3D and 3D measurements are obtained as a gold standard. Experiments applied to phantoms and real CL wounds suggest that the proposed 3D assessment tool provides higher accuracy (error 3D assessment tool provides high accuracy metrics which deserve more formal prospective study.

  20. Automated multidimensional image analysis reveals a role for Abl in embryonic wound repair.

    Science.gov (United States)

    Zulueta-Coarasa, Teresa; Tamada, Masako; Lee, Eun J; Fernandez-Gonzalez, Rodrigo

    2014-07-01

    The embryonic epidermis displays a remarkable ability to repair wounds rapidly. Embryonic wound repair is driven by the evolutionary conserved redistribution of cytoskeletal and junctional proteins around the wound. Drosophila has emerged as a model to screen for factors implicated in wound closure. However, genetic screens have been limited by the use of manual analysis methods. We introduce MEDUSA, a novel image-analysis tool for the automated quantification of multicellular and molecular dynamics from time-lapse confocal microscopy data. We validate MEDUSA by quantifying wound closure in Drosophila embryos, and we show that the results of our automated analysis are comparable to analysis by manual delineation and tracking of the wounds, while significantly reducing the processing time. We demonstrate that MEDUSA can also be applied to the investigation of cellular behaviors in three and four dimensions. Using MEDUSA, we find that the conserved nonreceptor tyrosine kinase Abelson (Abl) contributes to rapid embryonic wound closure. We demonstrate that Abl plays a role in the organization of filamentous actin and the redistribution of the junctional protein β-catenin at the wound margin during embryonic wound repair. Finally, we discuss different models for the role of Abl in the regulation of actin architecture and adhesion dynamics at the wound margin.

  1. Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    2014-01-01

    Full Text Available Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM remodeling (Ballard et al., 2006 increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to “cancerization” of the tumor microenvironment.

  2. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

    Science.gov (United States)

    Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

    2017-10-01

    Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Enhanced Cutaneous Wound Healing In Vivo by Standardized Crude Extract of Poincianella pluviosa.

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    Fernanda Giacomini Bueno

    Full Text Available Wound healing is a complex process that involves several biological events, and a delay in this process may cause economic and social problems for the patient. The search continues for new alternative treatments to aid healing, including the use of herbal medicines. Members of the genus Caesalpinia are used in traditional medicine to treat wounds. The related species Poincianella pluviosa (DC. L.P. Queiroz increases the cell viability of keratinocytes and fibroblasts and stimulates the proliferation of keratinocytes in vitro. The crude extract (CE from bark of P. pluviosa was evaluated in the wound-healing process in vivo, to validate the traditional use and the in vitro activity. Standardized CE was incorporated into a gel and applied on cutaneous wounds (TCEG and compared with the formulation without CE (Control for 4, 7, 10, or 14 days of treatment. The effects of the CE on wound re-epithelialization; cell proliferation; permeation, using photoacoustic spectroscopy (PAS; and proteins, including vascular endothelial growth factor (VEGF, superoxide dismutase 2 (SOD-2 and cyclooxygenase 2 (COX-2 were evaluated. The TCEG stimulated the migration of keratinocytes at day 4 and proliferation on the following days, with a high concentration of cells in metaphase at 7 days. Type I collagen formed more rapidly in the TCEG. PAS showed that the CE had permeated through the skin. TCEG stimulated VEGF at day 4 and SOD-2 and COX-2 at day 7. The results suggest that the CE promoted the regulation of proteins and helped to accelerate the processes involved in healing, promoting early angiogenesis. This led to an increase in the re-epithelialized surface, with significant mitotic activity. Maturation of collagen fibers was also enhanced, which may affect the resistance of the extracellular matrix. PAS indicated a correlation between the rate of diffusion and biological events during the healing process. The CE from P. pluviosa appears promising as an aid in

  4. Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.

    Directory of Open Access Journals (Sweden)

    Nicholas S Greaves

    Full Text Available BACKGROUND: The influence of skin substitutes upon angiogenesis during wound healing is unclear. OBJECTIVES: To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention. METHODS: On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4. In all cases, site 1 healed by secondary intention (control, site 2 was treated with collagen-GAG scaffold (CG, cadaveric decellularised dermis (DCD was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft. Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis. RESULTS: Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035, oxyhaemoglobin concentration (p = 0.0005, and vessel number derived from CD31-based immunohistochemistry (p = 0.046 were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP (p = 0.021 and prokineticin 2 (PROK2 (p = 0.004. CONCLUSION: Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses.

  5. Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells.

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    Ou, Lingling; Shi, Ying; Dong, Wenqi; Liu, Chunming; Schmidt, Thomas J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Fan, Daping; Ai, Walden

    2015-05-01

    Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.

  6. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation.

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    Luana Graziella Bandeira

    Full Text Available Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice.

  7. The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

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    Christoforidis JB

    2013-01-01

    Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

  8. Expression of Kruppel-like factor KLF4 in mouse hair follicle stem cells contributes to cutaneous wound healing.

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    Juan Li

    Full Text Available BACKGROUND: Kruppel-like factor KLF4 is a transcription factor critical for the establishment of the barrier function of the skin. Its function in stem cell biology has been recently recognized. Previous studies have revealed that hair follicle stem cells contribute to cutaneous wound healing. However, expression of KLF4 in hair follicle stem cells and the importance of such expression in cutaneous wound healing have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative real time polymerase chain reaction (RT-PCR analysis showed higher KLF4 expression in hair follicle stem cell-enriched mouse skin keratinocytes than that in control keratinocytes. We generated KLF4 promoter-driven enhanced green fluorescence protein (KLF4/EGFP transgenic mice and tamoxifen-inducible KLF4 knockout mice by crossing KLF4 promoter-driven Cre recombinase fused with tamoxifen-inducible estrogen receptor (KLF4/CreER™ transgenic mice with KLF4(flox mice. KLF4/EGFP cells purified from dorsal skin keratinocytes of KLF4/EGFP transgenic mice were co-localized with 5-bromo-2'-deoxyuridine (BrdU-label retaining cells by flow cytometric analysis and immunohistochemistry. Lineage tracing was performed in the context of cutaneous wound healing, using KLF4/CreER™ and Rosa26RLacZ double transgenic mice, to examine the involvement of KLF4 in wound healing. We found that KLF4 expressing cells were likely derived from bulge stem cells. In addition, KLF4 expressing multipotent cells migrated to the wound and contributed to the wound healing. After knocking out KLF4 by tamoxifen induction of KLF4/CreER™ and KLF4(flox double transgenic mice, we found that the population of bulge stem cell-enriched population was decreased, which was accompanied by significantly delayed cutaneous wound healing. Consistently, KLF4 knockdown by KLF4-specific small hairpin RNA in human A431 epidermoid carcinoma cells decreased the stem cell population and was accompanied by compromised

  9. Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice

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    Napoleão M. Argolo Neto

    Full Text Available Abstract: Chronic cutaneous lesions affect 15% of diabetic human patients and represent a risk 15 to 46 times larger of limb amputations compared to people with normal glycemia. It is assumed that half of these amputations could be prevented by early treatment of wounds, for example, with proper cell therapy. Objectives: In this study, the action of the autologous transplant of mesenchymal stem-cells (MSC was evaluated compared to the treatment with autologous platelet rich plasma (PRP in the cicatrization of cutaneous lesions induced in diabetic mice. These animals were previously treated with streptozootocin to induce diabetes mellitus and round wounds of 1.5cm in diameter were created in the posterior region. Diameters of the wounds and healing time were evaluated during 30 days and the results were submitted to variance analysis and Tukey's test average. It was noticed that the animals treated with MSC presented a more accelerated cicatrization of the cutaneous lesion than the animals treated with PRP. However, the treatment with PRP presented better results than just the daily asepsis of the lesions with saline or covering them with semi-permeable bandage. Besides, the use of semi-permeable bandage kept the cutaneous lesions of diabetic mice did not interfere negatively with cicatrization, proved to be harmless to use, but kept the cutaneous lesions more hydrated than the ones exposed to the environment.

  10. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

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    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

  11. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

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    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing.

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    Jun, Joon-Il; Kim, Ki-Hyun; Lau, Lester F

    2015-06-16

    Neutrophil infiltration constitutes the first step in wound healing, although their timely clearance by macrophage engulfment, or efferocytosis, is critical for efficient tissue repair. However, the specific mechanism for neutrophil clearance in wound healing remains undefined. Here we uncover a key role for CCN1 in neutrophil efferocytosis by acting as a bridging molecule that binds phosphatidylserine, the 'eat-me' signal on apoptotic cells and integrins αvβ3/αvβ5 in macrophages to trigger efferocytosis. Both knockin mice expressing a mutant CCN1 that is unable to bind αvβ3/αvβ5 and mice with Ccn1 knockdown are defective in neutrophil efferocytosis, resulting in exuberant neutrophil accumulation and delayed healing. Treatment of wounds with CCN1 accelerates neutrophil clearance in both Ccn1 knockin mice and diabetic Lepr(db/db) mice, which suffer from neutrophil persistence and impaired healing. These findings establish CCN1 as a critical opsonin in skin injury and suggest a therapeutic potential for CCN1 in certain types of non-healing wounds.

  13. Insulin catalyzes the curcumin-induced wound healing: an in vitro model for gingival repair.

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    Singh, Neetu; Ranjan, Vishal; Zaidi, Deeba; Shyam, Hari; Singh, Aparna; Lodha, Divya; Sharma, Ramesh; Verma, Umesh; Dixit, Jaya; Balapure, Anil K

    2012-01-01

    Human gingival fibroblasts (hGFs) play a major role in the maintenance and repair of gingival connective tissue. The mitogen insulin with IGFs etc. synergizes in facilitating wound repair. Although curcumin (CUR) and insulin regulate apoptosis, their impact as a combination on hGF in wound repair remains unknown. Our study consists of: 1) analysis of insulin-mediated mitogenesis on CUR-treated hGF cells, and 2) development of an in vitro model of wound healing. Apoptotic rate in CUR-treated hGF cells with and without insulin was observed by AnnexinV/PI staining, nuclear morphological analysis, FACS and DNA fragmentation studies. Using hGF confluent cultures, wounds were mechanically created in vitro and incubated with the ligands for 48 h in 0.2% fetal bovine serum DMEM. CUR alone showed dose-dependent (1-50 μM) effects on hGF. Insulin (1 μg/ml) supplementation substantially enhanced cell survival through up-regulation of mitogenesis/anti-apoptotic elements. The in vitro model for gingival wound healing establishes that insulin significantly enhanced wound filling faster than CUR-treated hGF cells over 48 h. This reinforces the pivotal role of insulin in supporting CUR-mediated wound repair. The findings have significant bearing in metabolic dysfunctions, e.g. diabetes, atherosclerosis, etc., especially under Indian situations.

  14. Brazilian red propolis improves cutaneous wound healing suppressing inflammation-associated transcription factor NFκB.

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    Corrêa, Flavia Regina Sobreira; Schanuel, Fernanda Seabra; Moura-Nunes, Nathalia; Monte-Alto-Costa, Andréa; Daleprane, Julio Beltrame

    2017-02-01

    The use of natural products in wound healing has been extensively studied in the context of complementary and alternative medicine. Propolis, a natural product, is a polyphenol-rich resin used for this purpose. This study aimed to investigate the effect of Brazilian Red Propolis Extract (BRPE) on inflammation and wound healing in mice, using a tissue repair model. The BRPE polyphenol content was analyzed by liquid chromatography coupled to mass spectrometry (LC/MS). A full-thickness excision lesion was created, and mice were treated orally with daily doses of vehicle solution (water-alcohol solution containing 2% of ethanol, control group) or 100mg/kg of BRPE (P100 group) during nine consecutive days. BRPE chemical composition analysis showed that this complex matrix contains several phenolic compounds such as phenolic acids, phenolic terpenes and flavonoids (especially catechins, flavonols, chalcones, isoflavones, isoflavans, pterocarpans and bioflavonoids). After BRPE administration, it was observed that, when compared to the control group, P100 group presented faster wound closure (p<0.001); less neutrophils per mm(2) (p<0.05) and macrophages (p<0.01) in tissue analyses, down regulation of the inflammatory transcription factor pNF-κB protein expression, and reduced production of inflammatory cytokine, such as TGF-β, TNF-α (p<0.0001), and IL-6 (p<0.001). These findings suggest a positive role of BRPE oral administration in the wound healing process via suppressing the inflammatory response during tissue repair. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Treatment with corticosterone delays cutaneous wound healing in male and female salamanders.

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    Thomas, Jessica R; Woodley, Sarah K

    2015-05-15

    In vertebrates, exposure to stressors and stress hormones has a number of physiological effects including modulation of immune function. These effects on immune function have been well studied in mammals, but less is known in other groups, in particular amphibians. To analyze the effects of exposure to stressors and the stress hormone corticosterone, we monitored cutaneous wound healing as a measure of integrated immunity in male and female semi-terrestrial salamanders (Desmognathus ochrophaeus) that were chased to induce endogenous release of corticosterone or were treated with physiologically relevant doses of corticosterone. As predicted, subjects treated daily with corticosterone healed more slowly than did controls. In contrast, subjects that had been chased daily healed at the same rate as controls. Surprisingly, repeated chasing did not elevate plasma corticosterone despite causing drops in body mass and survival. Additionally, females healed more slowly than males, possibly due to energetic constraints.

  16. Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound angiogenesis and repair.

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    Stefater, James A; Rao, Sujata; Bezold, Katie; Aplin, Alfred C; Nicosia, Roberto F; Pollard, Jeffrey W; Ferrara, Napoleone; Lang, Richard A

    2013-03-28

    The treatment of festering wounds is one of the most important aspects of medical care. Macrophages are important components of wound repair, both in fending off infection and in coordinating tissue repair. Here we show that macrophages use a Wnt-Calcineurin-Flt1 signaling pathway to suppress wound vasculature and delay repair. Conditional mutants deficient in both Wntless/GPR177, the secretory transporter of Wnt ligands, and CNB1, the essential component of the nuclear factor of activated T cells dephosporylation complex, displayed enhanced angiogenesis and accelerated repair. Furthermore, in myeloid-like cells, we show that noncanonical Wnt activates Flt1, a naturally occurring inhibitor of vascular endothelial growth factor-A-mediated angiogenesis, but only when calcineurin function is intact. Then, as expected, conditional deletion of Flt1 in macrophages resulted in enhanced wound angiogenesis and repair. These results are consistent with the published link between enhanced angiogenesis and enhanced repair, and establish novel therapeutic approaches for treatment of wounds.

  17. Age-associated changes in regenerative capabilities of mesenchymal stem cell: impact on chronic wounds repair.

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    Yao, Bin; Huang, Sha; Gao, Dongyun; Xie, Jiangfan; Liu, Nanbo; Fu, Xiaobing

    2016-12-01

    Mesenchymal stem cells (MSCs) represent an ideal source of autologous cell-based therapy for chronic wounds. Functional characteristics of MSCs may benefit wound healing by exerting their multi-regenerative potential. However, cell ageing resulting from chronic degenerative diseases or donor age could cause inevitable effects on the regenerative abilities of MSCs. A variety of studies have shown the relationship between MSC ageing and age-related dysfunction, but few associate these age-related impacts on MSCs with their ability of repairing chronic wounds, which are common in the elderly population. Here, we discuss the age-associated changes of MSCs and describe the potential impacts on MSC-based therapy for chronic wounds. Furthermore, critical evaluation of the current literatures is necessary for understanding the underlying mechanisms of MSC ageing and raising the corresponding concerns on considering their possible use for chronic wound repair. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  18. Laser phototherapy improves early stage of cutaneous wound healing of rats under hyperlipidic diet.

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    Uzêda-E-Silva, Virgínia Dias; Rodriguez, Tania Tavares; Rocha, Isadora Almeida Rios; Xavier, Flávia Calo Aquino; Dos Santos, Jean Nunes; Cury, Patrícia Ramos; Ramalho, Luciana Maria Pedreira

    2016-09-01

    The aim of this study was to evaluate the influence of laser photobiomodulation in cutaneous healing of rats under a hyperlipidic diet. Forty-eight Wistar Albinus rats, weaned, received standard diet (SD) or hyperlipidic diet (HD) for 20 weeks. The groups were divided into SD rats and HD rats, SD-irradiated rats (LSD), and HD-irradiated rats (LHD). Standard cutaneous wound (1 cm(2)) was created on the dorsum of each rat. The irradiation started immediately after surgery and every 48 h for 7 or 14 days (λ660 nm, 40 mW, 6 J/cm(2), ϕ 0,04 cm(2), CW), when they were killed under deep anesthesia. The specimens were removed, routinely processed, stained with hematoxylin/eosin (H/E), and evaluated by light microscopy. Rats fed with hyperlipidic diet had greater intensity in the inflammatory process and prolonged hyperemia. At day 7, the intensity of inflammation was reduced in LSD and LHD groups when compared to their control groups, SD (p = 0.002) and HD (p = 0.02). There was an increase in fibroblast proliferation and collagen deposition, especially in the LHD group. At day 14, the HD group presented more intensive hyperemia than the SD group. It can be concluded that the hyperlipidic diet modified the inflammation pattern in wound healing and that laser light has a positive biomodulative effect on the healing process only in early stages.

  19. Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

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    Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

    2016-08-01

    In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.

  20. 创面修复长路漫漫%It's a long way to go to apprehend wound repair

    Institute of Scientific and Technical Information of China (English)

    王一兵

    2014-01-01

    Wound healing is a complicated process,involving the activity of multiple cells and various cytokines.Chronic wound or intractable wound has already become a big challenge for clinicians.There are imbalances in the healing process of chronic wound,such as inflammatory response,cell proliferation,and remodeling of extracellular matrix.Combination of tissue transplantation and vacuum sealing drainage may be the optimum selection for wound repair.Besides the chronic wound,more attention should be paid to experimental and clinical studies on early-stage of healing of fresh wound and granulation wound in middle and late stages.

  1. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

    Science.gov (United States)

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

    2013-01-01

    Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 years old; 7.2–13.1 kg) were studied. Methods Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. Résumé Contexte Les cellules souches adultes ont été largement étudiées dans les approches de bio-ingénierie pour la thérapie de réparation tissulaire. Nous évaluons l

  2. Gap junction remodeling in skin repair following wounding and disease.

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    Churko, Jared M; Laird, Dale W

    2013-05-01

    In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change cellular phenotypes and lead to diseases of the skin. We also consider the therapeutic value of targeting connexins in wound healing.

  3. Modulation of Wound Healing and Scar Formation by MG53 Protein-mediated Cell Membrane Repair*

    Science.gov (United States)

    Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M.; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

    2015-01-01

    Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53−/− mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. PMID:26306047

  4. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

  5. Tissue repair genes: the TiRe database and its implication for skin wound healing.

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    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

    2016-04-19

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org.

  6. Assessment of laser photobiomodulation and polarized light on the healing of cutaneous wounds on euthyroid and hypothyroid induced rats

    Science.gov (United States)

    Ramalho, Luciana Maria Pedreira; Weyll, Barbara Mayoral Pedroso; da Costa Lino, Maíra Dória M.; Ramalho, Maria Jose Pedreira; Barbosa Pinheiro, Antonio Luis

    2010-02-01

    The aim of this study was to assess the influence of low-level laser therapy (LLLT) or polarized light (PL) in cutaneous wound healing of hypothyroid rats at dosages of 20 or 40J/cm2. Bioestimulatory effects of Laser radiation and Polarized light are recognized alternative therapies to improve healing on systemic disease patients, but their usefulness in the improvement of hypothyroidism healing impairment is uncertain till date. Forty Wistar rats were used in this study. Hypothyroidism was propylthiouracil- induced. Standard excisional cutaneous wounds were created without suturing and LLLT (λ660nm, 30mW, φ 3mm) or PL (λ 400-2000nm, 40mW, φ 10mm) was applied every 48 hours up to seven days on experimental groups. The rats were killed on the eighth day when wound contraction was assessed. The healing features were evaluated by light microscopy (H/E and Sirius Red). The cutaneous wounds of hypothyroid rats showed delayed healing process characterized by reduced thickness of epithelial layers, incipient formation of disorganized collagen fibers and wound contraction to a lesser extent (FISHER, p=0.0276), when compared to the euthyroid group. The use of both the Laser and Polarized Light on hypothyroid rats increased the amount of fibroblasts and the thickness of collagen fibers, especially on the L 20J/cm2 group. Euthyroid rats have still demonstrated more regular collagen fibers pattern than hypothyroid rats. It was therefore concluded that hypothyroidism delays wound healing and both Laser photobiomodulation and Polarized Light at 20j/cm2 dosages had improved the healing process in hypothyroid rats.

  7. Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Junghae Ko

    2011-06-01

    Full Text Available BackgroundTo accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF and vascular endothelial growth factor (VEGF into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds.MethodsStreptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group.ResultsIn both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant.ConclusionBoth non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.

  8. Development of an acquisition protocol and a segmentation algortihm for wounds of cutaneous Leishmaniasis in digital images

    Science.gov (United States)

    Diaz, Kristians; Castañeda, Benjamín; Miranda, César; Lavarello, Roberto; Llanos, Alejandro

    2010-03-01

    We developed a protocol for the acquisition of digital images and an algorithm for a color-based automatic segmentation of cutaneous lesions of Leishmaniasis. The protocol for image acquisition provides control over the working environment to manipulate brightness, lighting and undesirable shadows on the injury using indirect lighting. Also, this protocol was used to accurately calculate the area of the lesion expressed in mm2 even in curved surfaces by combining the information from two consecutive images. Different color spaces were analyzed and compared using ROC curves in order to determine the color layer with the highest contrast between the background and the wound. The proposed algorithm is composed of three stages: (1) Location of the wound determined by threshold and mathematical morphology techniques to the H layer of the HSV color space, (2) Determination of the boundaries of the wound by analyzing the color characteristics in the YIQ space based on masks (for the wound and the background) estimated from the first stage, and (3) Refinement of the calculations obtained on the previous stages by using the discrete dynamic contours algorithm. The segmented regions obtained with the algorithm were compared with manual segmentations made by a medical specialist. Broadly speaking, our results support that color provides useful information during segmentation and measurement of wounds of cutaneous Leishmaniasis. Results from ten images showed 99% specificity, 89% sensitivity, and 98% accuracy.

  9. Gap Junction Remodeling in Skin Repair Following Wounding and Disease

    National Research Council Canada - National Science Library

    Jared M. Churko; Dale W. Laird

    2013-01-01

    In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change...

  10. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

    Science.gov (United States)

    Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

    2015-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.

  11. A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds.

    Science.gov (United States)

    Regulski, Matthew; Jacobstein, Douglas A; Petranto, Russell D; Migliori, Vincent J; Nair, Girish; Pfeiffer, Darelle

    2013-12-01

    Despite the introduction of advanced wound care modalities over the last 15 years, chronic wounds are an increasing problem. Few single options are available for clinicians to treat recalcitrant wounds such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). A retrospective, single-center study was conducted at an outpatient wound care center to evaluate the clinical effect of a human cellular repair matrix (h-CRM) on chronic wounds that had failed to heal. Data from all patients who had received this treatment modality during a period of 2 years were abstracted. Standard care included weekly visits, regular debridement, offloading DFUs, compression for VLUs, and h-CRM for wounds >4 weeks duration. A total of 66 patients (30 male, 36 female, mean age 71.1 [± 8.8] years) received h-CRM treatment for 67 wounds (34 VLUs, 27 DFUs, and six other chronic wounds). The average wound size at baseline was 6.65 (± 9.68) cm2, and the average wound duration before h-CRM treatment was 38 (±70.8) weeks. Fifty (50) patients (74.6%) had failed to heal using other advanced therapies. After 12 weeks of care, 51 of the 67 wounds (76.1%) were healed: 23 of 34 (67.6%) VLUs and 23 of 27 (85.2%) DFUs. Average time to closure in these wounds was 5.8 (±2.5) weeks. No significant differences were found between proportions of VLUs and DFUs healed. No adverse events or recurrences occurred during an average follow-up time of 20.4 months (range 11 to 32 months). Overall, patients received an average of 3.8 applications of h-CRM, and 3.2 applications were used among patients that healed. The study results suggest h-CRM may benefit patients with chronic wounds. Prospective, randomized clinical studies are warranted.

  12. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

    OpenAIRE

    Li Hu; Juan Wang; Xin Zhou; Zehuan Xiong; Jiajia Zhao; Ran Yu; Fang Huang; Handong Zhang; Lili Chen

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell mi...

  13. Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

    Directory of Open Access Journals (Sweden)

    Park Na-Young

    2011-11-01

    Full Text Available Abstract Background Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. Methods Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet, DM (diabetic mice fed AIN 93 G purified rodent diet, VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet, and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet. After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. Results Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. Conclusions These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response.

  14. Wound-related complications and clinical outcomes following open globe injury repair.

    Science.gov (United States)

    Kong, George Y X; Henderson, Robert H; Sandhu, Sukhpal S; Essex, Rohan W; Allen, Penelope J; Campbell, William G

    2015-08-01

    Careful surgical management of traumatic wounds is important in open globe injury repair. This study examines the clinical outcomes following repair of open globe injuries with particular focus on wound-related issues. Retrospective, cohort study of consecutive open globe injuries presenting to a tertiary referral eye hospital from 1 January 2009 to 31 December 2011. A total of 267 eyes of 263 patients, mainly male (82.5%) with a mean age of 44.8 (range: 4-97) years. Average follow up was 6.9 months. All cases classified according to Ocular Trauma Classification Group. Visual outcomes, risk factors for and rates of postoperative complications and endophthalmitis. There were 83 globe ruptures, 182 penetrating and 2 perforating eye injuries, of which 43 cases had intraocular foreign body. Factors contributing to final visual acuity (VA) globe rupture (OR = 4.64, [1.99-10.8]), retinal detachment (OR = 3.40, [1.19-9.74]) and age ≥50 (OR = 2.45, [1.05-5.74]). Wound leak occurred in 44 eyes (16%). Of these, 18 (41%) proceeded to re-suturing. Factors contributing to wound leak were stellate-shaped wound (OR = 3.28, [1.39-7.73]) and delayed presentation (OR = 2.80, [1.02-7.71]). Ten eyes (3.7%) developed endophthalmitis. Factors associated with endophthalmitis were delayed presentation (OR = 8.91, [1.71-46.6]), microbial keratitis (OR = 12.5, [1.85-85.0]) and lens capsule breach (OR = 12.4, [1.85-83.1]). Wound leak is an important postoperative complication of open globe injury repair. Delayed presentation is an important risk factor for postoperative wound leak and endophthalmitis. Prompt and meticulous wound management of open globe injury may reduce these complications. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

  15. Mathematical Model of an Innate Immune Response to Cutaneous Wound in the Presence of Local Hypoxia.

    Science.gov (United States)

    Saiko, Guennadi; Cross, Karen; Douplik, Alexandre

    We developed a 2D multi-agent stochastic model of interaction between cellular debris, bacteria and neutrophils in the surface cutaneous wound with local hypoxia. Bacteria, which grow logistically with a maximum carrying capacity, and debris are phagocytosed by neutrophils with probability determined by the partial pressure of oxygen in the tissue, pO 2  = 4-400 mmHg, according to the Michaelis-Menten equation with K m  = 40 mmHg. The influx of new neutrophils depends linearly (k = 0.05-0.2) on the amount of (a) platelets and (b) neutrophils, which are in contact with bacteria or debris. Each activated neutrophil can accomplish a certain amount of phagocytosis, n max  = 5-20, during its lifespan, T = 1-5 days. The universe of outcomes consists of (a) bacteria clearance (high k and n max ), (b) infection is not cleared by neutrophils (low k and nmax), and (c) intermittent (quasiperiodic) bursts of inflammation. In the absence of infection, phagocytosis stops within 48 h. We found that pO 2 alone did not change the type of outcome, but affects the number of recruited neutrophils and inflammation duration (in the absence of infection by up to 10 and 5 %, respectively).

  16. [Comparative description and retrospective analisis of modern methods of surgical wounds closure for intraoperative prophylaxis of development of pathologic cutaneous cicatrices].

    Science.gov (United States)

    Stavyts'kyĭ, S O; Avetikov, D S; Lokes, K P; Rozkolupa, O O; Boĭko, I V

    2014-05-01

    The experience of application of various methods of closure was presented for the head and neck cutaneous wound surfaces after elective operative interventions. The variant of the postoperative results estimation and optimization of the wounds healing by primary closure was proposed.

  17. From repair to regeneration: biomaterials to reprogram the meniscus wound microenvironment.

    Science.gov (United States)

    Mauck, Robert L; Burdick, Jason A

    2015-03-01

    When the field of tissue engineering first arose, scaffolds were conceived of as inert three-dimensional structures whose primary function was to support cellularity and tissue growth. Since then, advances in scaffold and biomaterial design have evolved to not only guide tissue formation, but also to interact dynamically with and manipulate the wound environment. At present, these efforts are being directed towards strategies that directly address limitations in endogenous wound repair, with the goal of reprogramming the local wound environment (and the cells within that locality) from a state that culminates in an inferior tissue repair into a state in which functional regeneration is achieved. This review will address this approach with a focus on recent advances in scaffold design towards the resolution of tears of the knee meniscus as a case example. The inherent limitations to endogenous repair will be discussed, as will specific examples of how biomaterials are being designed to overcome these limitations. Examples will include design of fibrous scaffolds that promote colonization by modulating local extracellular matrix density and delivering recruitment factors. Furthermore, we will discuss scaffolds that are themselves modulated by the wound environment to alter porosity and modulate therapeutic release through precise coordination of scaffold degradation. Finally, we will close with emerging concepts in local control of cell mechanics to improve interstitial cell migration and so advance repair. Overall, these examples will illustrate how emergent features within a biomaterial can be tuned to manipulate and harness the local tissue microenvironment in order to promote robust regeneration.

  18. Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

    Science.gov (United States)

    Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

    2015-11-01

    Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p wound closure and vascularity (p fibroblasts results in delayed wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

  19. Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

    Science.gov (United States)

    Li, Haichang; Duann, Pu; Lin, Pei-Hui; Zhao, Li; Fan, Zhaobo; Tan, Tao; Zhou, Xinyu; Sun, Mingzhai; Fu, Minghuan; Orange, Matthew; Sermersheim, Matthew; Ma, Hanley; He, Duofen; Steinberg, Steven M; Higgins, Robert; Zhu, Hua; John, Elizabeth; Zeng, Chunyu; Guan, Jianjun; Ma, Jianjie

    2015-10-02

    Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring. Although MG53 is absent from keratinocytes and fibroblasts, remarkable defects in skin architecture and collagen overproduction are observed in mg53(-/-) mice, and these animals display delayed wound healing and abnormal scarring. Recombinant human MG53 (rhMG53) protein, encapsulated in a hydrogel formulation, facilitates wound healing and prevents scarring in rodent models of dermal injuries. An in vitro study shows that rhMG53 protects against acute injury to keratinocytes and facilitates the migration of fibroblasts in response to scratch wounding. During fibrotic remodeling, rhMG53 interferes with TGF-β-dependent activation of myofibroblast differentiation. The resulting down-regulation of α smooth muscle actin and extracellular matrix proteins contributes to reduced scarring. Overall, these studies establish a trifunctional role for MG53 as a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing. Targeting the functional interaction between MG53 and TGF-β signaling may present a potentially effective means for promoting scarless wound healing. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds.

    Science.gov (United States)

    Nguyen, Khang T; Seth, Akhil K; Hong, Seok J; Geringer, Matthew R; Xie, Ping; Leung, Kai P; Mustoe, Thomas A; Galiano, Robert D

    2013-01-01

    Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm-impaired wounds using the TallyHo mouse, a clinically relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll-like receptor (TLR) expression were noted in unwounded skin or noninoculated wounds of diabetic and wild-type mice. However, diabetic biofilm-containing wounds had significantly less TLR 2, TLR 4, interleukin-1β, and tumor necrosis factor-α expression than wild-type wounds with biofilm (all p oxidative burst activity. This translated into a log-fold greater bacterial burden and significant delay of wound epithelization for biofilm-impaired diabetic wounds at 10 days postwounding. These results suggest that impaired recognition of bacterial infection via the TLR pathway leading to inadequate cytokine stimulation of antimicrobial host responses may represent a potential mechanism underlying diabetic susceptibility to wound infection and ulceration.

  1. Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice.

    Science.gov (United States)

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice.

  2. Wound repair in the marine worm Sipunculus nudus (Sipunculidae

    Directory of Open Access Journals (Sweden)

    G D’Ancona Lunetta

    2005-09-01

    Full Text Available The cells and molecules involved in the wound healing of Sipunculus nudus were studied. An incision,5 mm in length, was cut longitudinally at a site opposite the anus and 10 mm from the introvert. Thehistological study performed at different times showed an involvement of both Type I and Type IIgranulocytes in the process of healing. The former were capable of extracellular digestion and theywere immunoreactive to anti-IL-4, -IL-10 and -epidermal growth factor (EGF antibodies (Abs; thelatter were involved in the synthesis of connective tissue from 24 h after the incision, thereby causingthe initial closing of the wound. After 70 h, a continuous layer of Type II granulocytes was found on thesides of the wound where the future muscle tissue would be formed; many of these granulocytes hadbeen partially degranulated. It was not possible to establish any existing relationship between thefunctions of Type I granulocytes and their reactivity to anti-IL-4, -IL-10 and -EGF Abs.

  3. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  4. High Mobility Group Box Protein-1 in Wound Repair

    Directory of Open Access Journals (Sweden)

    Mauro Patrone

    2012-09-01

    Full Text Available High-mobility group box 1 protein (HMGB1, a member of highly conserved non-histone DNA binding protein family, has been studied as transcription factor and growth factor. Secreted extracellularly by activated monocytes and macrophages or passively released by necrotic or damaged cells, extracellular HMGB1 is a potent mediator of inflammation. Extracellular HMGB1 has apparently contrasting biological actions: it sustains inflammation (with the possible establishment of autoimmunity or of self-maintaining tissue damage, but it also activates and recruits stem cells, boosting tissue repair. Here, we focus on the role of HMGB1 in physiological and pathological responses, the mechanisms by which it contributes to tissue repair and therapeutic strategies base on targeting HMGB1.

  5. Topical Delivery of Mesenchymal Stem Cells “Secretomes” in Wound Repair

    Directory of Open Access Journals (Sweden)

    Indah Julianto

    2016-11-01

    Full Text Available Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC, which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes. Recent studies revealed that human placental membranes are a rich source of MSCs for tissue regeneration and repair. This review provides a concise summary of current knowledge of biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role MSCs have in each phase of the wound-healing process, and clinical reports transplatation MSCs – secretomes in chronical ulcer.

  6. Cytokines and growth factors in wound drainage fluid from patients undergoing incisional hernia repair.

    Science.gov (United States)

    Di Vita, Gaetano; Patti, Rosalia; D'Agostino, Pietro; Caruso, Giuseppe; Arcara, Matteo; Buscemi, Salvatore; Bonventre, Sebastiano; Ferlazzo, Viviana; Arcoleo, Francesco; Cillari, Enrico

    2006-01-01

    Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction drain was inserted in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on postoperative days 1-4 and the amount was recorded each time. Growth factors and cytokines production was evaluated as the whole amount produced over a 24-hour period. In all patients, the amount of drain fluid from surgical wounds was more copious the first day after surgery, it decreased significantly afterward. The presence of all cytokines was highest on postoperative day 1, decreasing over the following days. More specifically, the production of IL-1 ra, IL-6, IL-1alpha, and IL-10 on postoperative day 1 fell sharply on postoperative days 3 and 4, whereas, after an initial reduction, interferon-gamma showed an increase from day 2 onward. Vascular endothelial-derived growth factor production increased progressively after the operation reaching statistical significance only on day 4. As for basic fibroblast growth factor, it showed an opposite pattern: it was higher on postoperative day 1 decreasing thereafter. This analysis of cytokine and growth factor production in the drain fluid will lead us to a better evaluation of the events that follow a surgical wound and to a better understanding of the healing process.

  7. Surgical tip: Repair of acute Achilles rupture with Krackow suture through a 1.5 cm medial wound.

    Science.gov (United States)

    Lui, T H

    2010-03-01

    Acute Achilles tendon ruptures is one of the commonest tendon injury of the foot and ankle. The management of this problem is still controversial. Treatment can be classified into non-surgical and surgical types. Surgical management can be subdivided into open repair, percutaneous with or without adjunct of arthroscopy. In compare with non-surgical management, surgical management will decrease the tendon re-rupture rate. However, the possible surgical complications including wound breakdown and sural nerve injury are still quite significant. Percutaneous repair technique has the advantage of less chance of wound breakdown, but the rate of tendon re-rupture is higher than that after open tendon repair, because the repair is usually weaker than that achieved in open repair. Lui have described an endoscopic assisted repair with the Krackow locking suture. However, the technique is complicated and six portal wounds are needed. A simpler way of applying the Krackow suture through the portal wound has been described for reattachment of Achilles tendon insertion after endoscopic calcaneoplasty. We describe a mini-open approach of Achilles tendon repair with the Krackow locking suture. By means of release of the medial edge of the investing fascia, the Achilles tendon can be mobilized easily and the Krackow locking suture can be applied through a 1.5cm medial wound. Hopefully, this can improve the strength of repair and maintaining the advantage of minimally invasive tendon repair.

  8. Repairing effects of Iran flora on wound healing

    Directory of Open Access Journals (Sweden)

    Mohammad Afshar

    2015-04-01

    Full Text Available The skin is the largest and the heaviest organ in the human body which, in addition to its important roles in the protection, waste removal, and contribution to vitamin D synthesis. As an important sensory organ, it can play a major role in the maintenance of homeostasis in the body. Total loss of of the skin integrity can cause harms and diseases that lead to physical disability and even death. Therefore, one of the main problem faced by medical science so far, is the question of .wound healing in the shortest possible time and with minimal side effects. Increasing the wound healing rate leads to positive financial and health results. Thus, several studies on new therapeutic techniques such as use of chemical drugs, herbal medication and homeopathy have been done. Moreover, physical methods such as laser therapy and other treatmentshave been constantly improving. In recent decades, the use of herbal medicine, as an effective method, has been progressing in most countries including Iran. In the traditional medicine of Iran various methods of using plants for the treatment of diseases are common. This is actually justifiable due to the geographic diversity of the flora in Iran. In the present paper the effectivity of the cut healing properties of some medicinal herbs in Iran is discussed.

  9. Photobiomodulation therapy action in wound repair skin induced in aged rats old: time course of biomarkers inflammatory and repair.

    Science.gov (United States)

    Fiorio, Franciane Barbieri; Dos Santos, Solange Almeida; de Melo Rambo, Caroline Sobral; Dalbosco, Camila Guerra; Serra, Andrey Jorge; de Melo, Brunno Lemes; Leal-Junior, Ernesto Cesar Pinto; de Carvalho, Paulo de Tarso Camillo

    2017-07-05

    Previous studies have discussed an inverse correlation between age and wound healing, because it relates to the association of aging with a gradual decrease in healing capacity. Treatment with photobiomodulation therapy (PBMT) improves wound healing by inducing increases in mitotic activity, numbers of fibroblasts, collagen synthesis, and neovascularization. Therefore, this study aimed to evaluate the effects of PBMT in cutaneous wound healing in aged rats. A punch biopsy of 8 mm in diameter was performed to produce a skin wound. The study included 45 male rats, of which 15 were young (30 days) and 30 were elderly (500 days). The 45 animals were distributed into 3 experimental groups, which were subjected to skin wounds and 1 aged group received PBMT, with a 30-mW laser beam (power density of 1.07 W/cm(2)), beam area of 0.028 cm(2), and λ660 nm produced through active phosphide Gallium-Aluminum-Indio (InGaAIP). The PBMT application took the form of a single-point transcutaneous method, with a total energy of 2 joules per wound site, energy density of 72 J/cm(2), and time of 1 min and 7 s. Analysis was performed to verify the effect of PBMT on the quantity of collagen I and III, metalloproteinase 3 and 9 (MMP-3 and MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2) and of vascular endothelial growth factor (VEGF) at the wound site by immunohistochemistry, cytokine-induced neutrophil chemoattractant (CINC)-1, by enzyme-linked immunosorbent assay (ELISA) and interleukin (IL)-6 real-time polymerase chain reaction (RT-PCR). That we conclude LLLT is effective in the modulation of inflammatory mediators IL-6, CINC-1, VEGF, MMP-3, MMP-9 and TIMP-2 as well as increased collagen production in aged animals during different phases of the tissue regeneration process. However, the effects of PBMT obtained in the aged animals (aged LLLT group) suggest that new dosimetries should be tested to achieve better results.

  10. Effectiveness of Changing the Application of Japanese Honey to a Hydrocolloid Dressing in Between the Inflammatory and Proliferative Phases on Cutaneous Wound Healing in Male Mice.

    Science.gov (United States)

    Mukai, Kanae; Komatsu, Emi; Yamanishi, Misa; Hutakuchi, Misako; Kanzaka, Kayo; Uno, Yuka; Yamazaki, Shizuka; Kato, Shizuka; Yamamoto, Tomomi; Hattori, Mayumi; Nakajima, Yukari; Urai, Tamae; Asano, Kimi; Murakado, Naoko; Okuwa, Mayumi; Nakatani, Toshio

    2017-01-01

    The aim of this study was to investigate the effects of changing the application of Japanese honey to a hydrocolloid dressing (HCD) in between the inflammatory and proliferative phases on cutaneous wound healing in 8-week-old, BALB/cCrSlc male mice. Mice were divided into 4 groups: acacia honey followed by a HCD, buckwheat flour honey followed by a HCD, Chinese milk vetch honey followed by a HCD, and a HCD alone (control group). All mice received 2 full-thickness wounds on both sides of the dorsum using a Disposable Biopsy Punch. The wounds of the control group were covered with a HCD, whereas wounds in the other groups were treated with 0.1 mL of the relevant type of honey until day 3 post-wound and then were covered with a HCD from days 4 to 14. In the experimental groups, the wound area ratio was significantly smaller in the inflammatory phase but significantly larger in the proliferative phase. Reepithelialization, collagen deposition, and wound contraction were significantly delayed compared with those in the control group. The re-expansion of the wounds in the proliferative phase could not be prevented, and reepithelialization, collagen deposition, and wound contraction were delayed compared with those upon the use of a HCD. The study's authors concluded that these methods do not promote cutaneous wound healing better than the use of a HCD alone.

  11. A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure

    NARCIS (Netherlands)

    Vermolen, F.J.; Javierre, E.

    2011-01-01

    A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes,

  12. A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure

    NARCIS (Netherlands)

    Vermolen, F.J.; Javierre, E.

    2011-01-01

    A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes, w

  13. Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration

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    Aleksandra Gavrilovska-Brzanov

    2016-02-01

    CONCLUSIONS: Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common.

  14. Reversible cortical blindness following successful surgical repair of two stab wounds in the heart.

    Science.gov (United States)

    El Gatit, A; Abdul Razeq, M; El Snaini, F; Saad, K; Zaiton, A

    2008-03-01

    This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient presented in a state of pre cardiac arrest (shock and low cardiac output status), following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle, and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly, but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy, Electroencephalograms (EEGs) and Computed Tomography Scans revealed no abnormalities, apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later, the patient regained his vision gradually and was discharged on the 7(th) postoperative day without any remarks.

  15. The Role of Connexins in Wound Healing and Repair: Novel Therapeutic Approaches

    Science.gov (United States)

    Wong, Pui; Tan, Teresa; Chan, Catherine; Laxton, Victoria; Chan, Yin Wah Fiona; Liu, Tong; Wong, Wing Tak; Tse, Gary

    2016-01-01

    Gap junctions are intercellular proteins responsible for mediating both electrical and biochemical coupling through the exchange of ions, second messengers and small metabolites. They consist of two connexons, with (one) connexon supplied by each cell. A connexon is a hexamer of connexins and currently more than 20 connexin isoforms have been described in the literature thus far. Connexins have a short half-life, and therefore gap junction remodeling constantly occurs with a high turnover rate. Post-translational modification, such as phosphorylation, can modify their channel activities. In this article, the roles of connexins in wound healing and repair are reviewed. Novel strategies for modulating the function or expression of connexins, such as the use of antisense technology, synthetic mimetic peptides and bioactive materials for the treatment of skin wounds, diabetic and pressure ulcers as well as cornea wounds, are considered. PMID:27999549

  16. REVERSIBLE CORTICAL BLINDNESS FOLLOWING SUCCESSFUL SURGICAL REPAIR OF TWO STAB WOUNDS IN THE HEART

    Directory of Open Access Journals (Sweden)

    Zaiton A

    2008-01-01

    Full Text Available This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient presented in a state of pre cardiac arrest (shock and low cardiac output status, following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle, and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly, but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy, Electroencephalograms (EEGs and Computed Tomography Scans revealed no abnormalities, apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later, the patient regained his vision gradually and was discharged on the 7th postoperative day without any remarks.

  17. High-Throughput Microplate-Based Assay to Monitor Plasma Membrane Wounding and Repair

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    Sarika Pathak-Sharma

    2017-07-01

    Full Text Available The plasma membrane of mammalian cells is susceptible to disruption by mechanical and biochemical damages that frequently occur within tissues. Therefore, efficient and rapid repair of the plasma membrane is essential for maintaining cellular homeostasis and survival. Excessive damage of the plasma membrane and defects in its repair are associated with pathological conditions such as infections, muscular dystrophy, heart failure, diabetes, and lung and neurodegenerative diseases. The molecular events that remodel the plasma membrane during its repair remain poorly understood. In the present work, we report the development of a quantitative high-throughput assay that monitors the efficiency of the plasma membrane repair in real time using a sensitive microplate reader. In this assay, the plasma membrane of living cells is perforated by the bacterial pore-forming toxin listeriolysin O and the integrity and recovery of the membrane are monitored at 37°C by measuring the fluorescence intensity of the membrane impermeant dye propidium iodide. We demonstrate that listeriolysin O causes dose-dependent plasma membrane wounding and activation of the cell repair machinery. This assay was successfully applied to cell types from different origins including epithelial and muscle cells. In conclusion, this high-throughput assay provides a novel opportunity for the discovery of membrane repair effectors and the development of new therapeutic compounds that could target membrane repair in various pathological processes, from degenerative to infectious diseases.

  18. Antimicrobial activity of copaíba (Copaifera langsdorffii oleoresin on bacteria of clinical significance in cutaneous wounds

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    D.S. Masson

    2013-01-01

    Full Text Available The present study was designed to evaluate the in vitro antimicrobial activity of Copaifera langsdorffii oleoresin, which has been used in folk medicine as an anti-inflammatory, antibacterial, healing among others. The oleoresin was tested against Gram-positive (Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis and Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria related to infections in cutaneous wounds. Antimicrobial activity was determined by the minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC assays. Copaiba oleoresin showed antimicrobial activity only against the Gram-positive bacteria with MIC of 200 μg/mL, 400 μg/mL and 1100 μg/mL for S. aureus, S. pyogenes and E. faecalis, respectively. MBC values were the same as MIC for S. aureus and S. pyogenes and for E. faecalis it was 1200 μg/mL. Considering that infection significantly impairs the wound healing process, we believe that the use of copaiba oleoresin as a component of a topical formulation could be a valuable adjunct in the treatment of infected wounds, mainly in the case of wounds infected by Gram-positive microorganisms.

  19. Assessment of the effects of laser or LED photobiomodulation on hypothyroid rats of cutaneous wound healing: A morphometric study.

    Science.gov (United States)

    De Castro, Isabele Cardoso Vieira; Paraguassú, Gardênia Matos; dod Reis Júnior, João Alves; Xavier, Flávia Caló Aquino; Rodriguez, Tânia Tavares; Ramalho, Maria José Pedreira; Pinheiro, Antônio L. B.; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Hypothyroid has been associated to a disruption of the body's metabolism, including the healing process. Laser and LED have been shown to be effective on improving healing in many situations, but their benefit in the improvement of healing on hypothyroidism remains unknown. The aim of this study was to assess, morphometrically, the influence of Laser (λ660nm, 24 J/cm2, 40mW, CW, spot output= 4mm2;) and LED (λ630nm ± 20, 24 J/cm2, 150mW, CW, spot output= 0.5 cm2) on the wound healing of rats with Hypothyroid. Under general anesthesia, a standard surgical wound (1cm2) was created on the dorsum of 72 male Wistar rats divided into 6 groups of 12 animals each: G1: Euthyroid; G2: Euthyroid + Laser; G3: Euthyroid + LED; G4: Hypothyroid; G5: Hypothyroid + Laser and G6: Hypothyroid + LED. Hypothyroidism was induced in rats with propylthiouracil (0.05g/100mL) administered orally for 4 weeks and maintained until the end of the experiment. Rats were irradiated after surgery each 48h then killed after 7 and 14 days. Statistical analysis was performed using ANOVA and Tukey's test. Hypothyroid rats with phototherapy laser or LED showed significant less wound contraction than euthyroid's rats at the 7th day (pphotobiomodulation using 24 J/cm2 per session improved cutaneous wound healing in hypothyroid rats.

  20. Histological study of wound repair with topical aloe vera gel in rat

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    Nasrin Takzaree

    2015-12-01

    Full Text Available Background: One of the most important issues in medical sciences is wound healing and repair. Application of natural ingredients and herbs for treating ulcers has been in the history of human life. Nowadays, due to the lack of side effects of medicinal plants and a variety of effective compounds in plants, as well as numerous disadvantages of synthetic drugs there has been tendency to use medicinal plants in clinic. Aloe vera is an herbal drug used for treatment of dermal diseases. In this study we evaluated, effects of aloe vera on the wound healing through the microscopic techniques and cell counting. Methods: In this experimental study, sixty Wistar rats weighing 200-250 g were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5´1.5 mm dimension was made on the back of the neck. Rats were randomly divided to control and experimental group’s. Each group was divided to three subgroups with 4, 7, and 14 study days. In 1st experimental group aloe vera was used twice on the wound surface and in 2nd experimental group was used once daily and the positive control group were applied phenytoin cream 1% from the zero days of surgery. The control group did not get any treatment on the wound surface. For histological studies, during the fourth, seventh and fourteenth day’s rats were sacrificed and samples were taken from the wound area and adjacent skin. After histological staining with hematoxylin and eosin (H&E and Masson's trichrome stains, the cells were counted, wound surface and wound healing were investigated. Results: The macroscopic and microscopic evaluation showed that wound healing increased because the fibroblast numbers in two experimental groups improved compared with control group. The percentage of wound healing on different days in the experimental and control groups were significant. Data were analyzed by using one-way ANOVA test and P< 0.05 was significant. Conclusion: Present study showed

  1. Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats

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    Ebaid Hossam

    2011-12-01

    Full Text Available Abstract Background Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS production. Whey protein (WP is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN, a wounded diabetic group (WD and a wounded diabetic group orally supplemented with whey protein (WDWP at a dose of 100 mg/kg body weight. Results Whey protein was found to significantly decrease the levels of malondialdehyde (MDA, nitric oxide (NO and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1β, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. Conclusion In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines.

  2. Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing.

    Science.gov (United States)

    Volksdorf, Thomas; Heilmann, Janina; Eming, Sabine A; Schawjinski, Kathrin; Zorn-Kruppa, Michaela; Ueck, Christopher; Vidal-Y-Sy, Sabine; Windhorst, Sabine; Jücker, Manfred; Moll, Ingrid; Brandner, Johanna M

    2017-06-01

    Tight junction (TJ) proteins are known to be involved in proliferation and differentiation. These processes are essential for normal skin wound healing. Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin wound healing models and tissue samples of acute and chronic human wounds and observed major differences in localization/expression of these proteins, with chronic wounds often showing a loss of the proteins at the wound margins and/or in the regenerating epidermis. Knockdown experiments in primary human keratinocytes showed that decreased claudin-1 expression resulted in significantly impaired scratch wound healing, with delayed migration and reduced proliferation. Activation of AKT pathway was significantly attenuated after claudin-1 knockdown, and protein levels of extracellular signal-related kinase 1/2 were reduced. For occludin, down-regulation had no impact on wound healing in normal scratch assays, but after subjecting the cells to mechanical stress, which is normally present in wounds, wound healing was impaired. For both proteins we show that most of these actions are independent from the formation of barrier-forming TJ structures, thus demonstrating nonbarrier-related functions of TJ proteins in the skin. However, for claudin-1 effects on scratch wound healing were more pronounced when TJs could form. Together, our findings provide evidence for a role of claudin-1 and occludin in epidermal regeneration with potential clinical importance. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Acute Ultraviolet Radiation Perturbs Epithelialization but not the Biomechanical Strength of Full-thickness Cutaneous Wounds

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Lerche, Catharina M; Wulf, Hans Christian;

    2016-01-01

    We hypothesized that priming of the skin with ultraviolet radiation (UVR) before being injured would enhance wound healing. Four groups, each comprising 20 immunocompetent hairless mice, were exposed to simulated solar irradiation in escalating UVR doses; 0 standard erythema dose (SED) = control, 1...... (P exposure of dorsal skin. In the excisional wounds, epithelial coverage decreased (P = 0.024) by increasing the UVR dose, whereas there was no significant difference (P = 0.765) in wound MPO levels. Neither wound width (P = 0.850) nor breaking strength (P...

  4. Wound repair and anti-oxidative capacity is regulated by ITGB4 in airway epithelial cells.

    Science.gov (United States)

    Liu, Chi; Liu, Hui-jun; Xiang, Yang; Tan, Yu-rong; Zhu, Xiao-lin; Qin, Xiao-qun

    2010-08-01

    Integrin beta 4 (ITGB4) is a structural adhesion molecule which engages in maintaining the integrity of airway epithelial cells. Its specific cytomembrane structural feature strongly indicates that ITGB4 may engage in many signaling pathways and physiologic processes. However, in addition to adhesion, the specific biologic significance of ITGB4 in airway epithelial cells is almost unknown. In this article, we investigated the expression and functional properties of ITGB4 in airway epithelial cells in vivo and in vitro. Human bronchial epithelial cell line (16HBE14O-cells) and primary rat tracheal epithelial cells (RTE cells) were used to determine ITGB4 expression under ozone tress or mechanical damage, respectively. An ovalbumin (OVA)-challenged asthma model was used to investigate ITGB4 expression after antigen exposure in vivo. In addition, an ITGB4 overexpression vector and ITGB4 silence virus vector were constructed and transfected into RTE cells. Then, wound repair ability and anti-oxidation capacity was evaluated. Our results demonstrated that, on the edge of mechanically wounded cell areas, ITGB4 expression was increased after mechanical injury. After ozone stress, upregulation expression of ITGB4 was also detected. In the OVA-challenged asthma model, ITGB4 expression was decreased on airway epithelial cells accompanying with structural disruption and damage of anti-oxidation capacity. Besides, our study revealed that upregulation of ITGB4 promotes wound repair ability and anti-oxidative ability, while such abilities were blocked when ITGB4 was silenced. Taken together, these results showed that ITGB4 was a new interesting molecule involved in the regulation of wound repair and anti-oxidation processes for airway epithelial cells.

  5. Biomodulative effects of polarized light on the healing of cutaneous wounds on nourished and undernourished Wistar rats.

    Science.gov (United States)

    Pinheiro, Antonio Luiz Barbosa; Meireles, Gyselle Cynthia Silva; Carvalho, Carolina Montagn; de Barros Vieira, Alessandro Leonardo; dos Santos, Jean Nunes; Ramalho, Luciana Maria Pedreira

    2006-10-01

    This study aimed to evaluate, by light microcopy, the differences in healing process of cutaneous wounds on nourished or undernourished rats following illumination by polarized light (lambda400-2000 nm) with 20 or 40 J/cm(2). There are some reports in the literature on different effects of polarized light on wound healing. Amongst the factors that interfere with wound healing one is the nutritional status of the subject. Thirty nourished or undernourished Wistar rats had one standardized surgical wound created on the dorsum and were divided into six groups: group 1, control (standard diet); group 2, control (Northeastern Brazilian Basic Diet [DBR]); group 3, standard diet + polarized light (20 J/cm(2)); group 4, standard diet + polarized light (40 J/cm(2)); group 5, DBR + polarized light (20 J/cm(2)); group 6, DBR + polarized light (40 J/cm(2)). The first application of treatment was carried out immediately after wounding and repeated every 24 h during 7 days. The animals were sacrificed, and specimens were taken and routinely processed to wax, cut, and stain with hematoxylin and eosin (H&E) and Sirius Red. These were then analyzed under light microscopy. The analysis included re-epitheliialization, inflammatory infiltrate, and fibroblastic proliferation. Sirius Red-stained slides were used to perform descriptive analysis of collagen. The analysis of the results showed better results in these groups illuminated with 20 J/cm(2). It is concluded that nutritional status influenced the progression of the healing process as well as the quality of the healed tissue, and that the use of polarized light resulted in a positive biomodulatory effect.

  6. Efficacy of Acorus calamus on collagen maturation on full thickness cutaneous wounds in rats

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    Thangavel Ponrasu

    2014-01-01

    Full Text Available Background: The rhizomes of Acorus calamus and their essential oil are widely used in the flavoring industry and production of alcoholic beverages in Europe. Recent reports have confirmed the presence of several pharmacological components in the rhizomes of A. calamus. Objective: The objective of this study was to find out the efficacy of topical administration of ethanolic extract of A. calamus on dermal wound healing in rats. Wound healing is a natural process occurring in living organisms, which results in a complete or partial remodeling of injured tissue and ultimately progresses to the formation of a fibrous scar. Several natural products have been reported to augment the wound healing process. Materials and Methods: An ethanolic extract of A. calamus was prepared and its wound-healing efficacy was studied. An excision wound was made on the back of the rat and 200 μL (40 mg/kg body weight of the A. calamus extract was applied topically once daily for the treated wounds. The control wounds were treated with 200 μL of phosphate buffered saline. Results: The granulation tissues formed were removed at 4, 8 and 12 days and biochemical parameters such as deoxyribonucleic acid, total protein, total collagen, hexosamine and uronic acids were measured. The amount of type I/III collagen formed in control and treated wound tissues was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The epithelialization time, tensile strength and histological examination of the wounds were also studied. Biochemical analyses of the granulation tissues revealed a significant increase in collagen, hexosamine and uronic acid when compared with the control. The tensile strength of extract treated wounds was found to increase by 112%. A significant reduction in lipid peroxide levels suggested that A. calamus possesses antioxidant components. Conclusions: The results strongly confirm the beneficial effects of A. calamus in augmenting the wound

  7. The influence of a PHI-5-loaded silicone membrane, on cutaneous wound healing in vivo.

    NARCIS (Netherlands)

    Rossum, M.M. van; Vooijs, D.P.P.; Walboomers, X.F.; Hoekstra, M.J.; Spauwen, P.H.M.; Jansen, J.A.

    2007-01-01

    This study investigated whether a novel ionogenic substance, containing amongst others zinc and rubidium (PHI-5; Dermagenics Inc, Memphis, TN, USA), could improve the healing of full-thickness skin wounds. Uniform wounds were created on the right flank of guinea pigs. Micro-grooved silicone rubber m

  8. Evaluation of Cinnamomum osmophloeum Kanehira Extracts on Tyrosinase Suppressor, Wound Repair Promoter, and Antioxidant

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    Man-Gang Lee

    2015-01-01

    Full Text Available Cinnamomum osmophloeum Kanehira belongs to the Lauraceae family of Taiwan’s endemic plants. In this study, C. osmophloeum Kanehira extract has shown inhibition of tyrosinase activity on B16-F10 cellular system first. Whether extracts inhibited mushroom tyrosinase activity was tested, and a considerable inhibition of mushroom tyrosinase activity by in vitro assays was presented. Animal experiments of C. osmophloeum Kanehira were carried out by observing animal wound repair, and the extracts had greater wound healing power than the vehicle control group (petroleum jelly with 8% DMSO, w/v. In addition, the antioxidant capacity of C. osmophloeum Kanehira extracts in vitro was evaluated. We measured C. osmophloeum Kanehira extract’s free radical scavenging capability, metal chelating, and reduction power, such as biochemical activity analysis. The results showed that a high concentration of C. osmophloeum Kanehira extract had a significant scavenging capability of free radical, a minor effect of chelating ability, and moderate reducing power. Further exploration of the possible physiological mechanisms and the ingredient components of skincare product for skin-whitening, wound repair, or antioxidative agents are to be done.

  9. The potential of nanoporous anodic aluminium oxide membranes to influence skin wound repair.

    Science.gov (United States)

    Parkinson, Leigh G; Giles, Natalie L; Adcroft, Katharine F; Fear, Mark W; Wood, Fiona M; Poinern, Gerard E

    2009-12-01

    Cells respond to changes in the environment by altering their phenotype. The ability to influence cell behavior by modifying their environment provides an opportunity for therapeutic application, for example, to promote faster wound healing in response to skin injury. Here, we have modified the preparation of an aluminium oxide template to generate large uniform membranes with differing nano-pore sizes. Epidermal cells (keratinocytes) and dermal cells (fibroblasts) readily adhere to these nanoporous membranes. The pore size appears to influence the rate of cell proliferation and migration, important aspects of cell behavior during wound healing. The suitability of the membrane to act as a dressing after a burn injury was assessed in vivo; application of the membrane demonstrated adherence and conformability to the skin surface of a pig, with no observed degradation or detrimental effect on the repair. Our results suggest that keratinocytes are sensitive to changes in topography at the nanoscale level and that this property may be exploited to improve wound repair after tissue injury.

  10. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

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    Lingying Liu

    Full Text Available BACKGROUND: Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs could on wound healing in a rat model of severe burn and its potential mechanism. METHODS: Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI, and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. RESULTS: We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. CONCLUSION: The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

  11. pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1.

    Science.gov (United States)

    Lindner, Haley Buff; Felmly, Lloyd McPherson; Demcheva, Marina; Seth, Arun; Norris, Russell; Bradshaw, Amy D; Vournakis, John; Muise-Helmericks, Robin C

    2015-01-01

    Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity. pGlcNAc treated wounds exhibit decreased collagen content, increased collagen organization and decreased myofibroblast content. A fibrin gel assay was used to assess the regulation of fibroblast alignment in vitro. In this assay, fibrin lattice is formed with two pins that provide focal points upon which the gel can exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded fibroblasts results in cellular alignment as compared to untreated controls, by a process that is Akt1 dependent. We show that Akt1 is required in vivo for the pGlcNAc-induced increased tensile strength and elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

  12. pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1.

    Directory of Open Access Journals (Sweden)

    Haley Buff Lindner

    Full Text Available Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc, a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity. pGlcNAc treated wounds exhibit decreased collagen content, increased collagen organization and decreased myofibroblast content. A fibrin gel assay was used to assess the regulation of fibroblast alignment in vitro. In this assay, fibrin lattice is formed with two pins that provide focal points upon which the gel can exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded fibroblasts results in cellular alignment as compared to untreated controls, by a process that is Akt1 dependent. We show that Akt1 is required in vivo for the pGlcNAc-induced increased tensile strength and elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

  13. Biological evaluation of human hair keratin scaffolds for skin wound repair and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Songmei; Sang, Lin [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); Zhang, Yaping [Engineering Research Center of Biomass Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Wang, Xiaoliang [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China); Li, Xudong, E-mail: xli20004@yahoo.com [National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 (China)

    2013-03-01

    The cytocompatibility, in vivo biodegradation and wound healing of keratin biomaterials were investigated. For the purposes, three groups of keratin scaffolds were fabricated by freeze-drying reduced solutions at 2 wt.%, 4 wt.% and 8 wt.% keratins extracted from human hairs. These scaffolds exhibited evenly distributed high porous structures with pore size of 120-220 {mu}m and the porosity > 90%. NIH3T3 cells proliferated well on these scaffolds in culture lasting up to 22 days. Confocal micrographs stained with AO visually revealed cell attachment and infiltration as well as scaffold architectural stability. In vivo animal experiments were conducted with 4 wt.% keratin scaffolds. Early degradation of subcutaneously implanted scaffolds occurred at 3 weeks in the outermost surface, in concomitant with inflammatory response. At 5 weeks, the overall porous structure of scaffolds severely deteriorated while the early inflammatory response in the outermost surface obviously subsided. A faster keratin biodegradation was observed in repairing full-thickness skin defects. Compared with the blank control, keratin scaffolds gave rise to more blood vessels at 2 weeks and better complete wound repair at 3 weeks with a thicker epidermis, less contraction and newly formed hair follicles. These preliminary results suggest that human hair keratin scaffolds are promising dermal substitutes for skin regeneration. - Highlights: Black-Right-Pointing-Pointer Preparation of highly-interconnected human hair keratin scaffolds. Black-Right-Pointing-Pointer Long-term cell culturing and in vivo animal experiments with keratin scaffolds. Black-Right-Pointing-Pointer Biodegradation is dependent on implantation site and function Black-Right-Pointing-Pointer Early vascularization and better repair in treating full-thickness skin wounds. Black-Right-Pointing-Pointer A thicker epidermis, less contraction and newly formed hair follicles are observed.

  14. Whole ovary immunohistochemistry for monitoring cell proliferation and ovulatory wound repair in the mouse

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    Singavarapu Rajasekhar

    2010-08-01

    Full Text Available Abstract Background Ovarian surface epithelial cells are thought to be a precursor cell type for ovarian carcinoma. It has been proposed that an increased rate of ovarian surface epithelial cell proliferation during ovulatory wound repair contributes to the accumulation of genetic changes and cell transformation. The proliferation of ovarian surface epithelial cells during ovulatory wound repair has been studied primarily using immunohistochemical staining of paraffin-embedded ovary sections. However, such analyses require complex reconstruction from serially-cut ovary sections for the visualization and quantification of the cells on the ovarian surface. In order to directly visualize the proliferation and organization of the ovarian surface epithelial cells, we developed a technique for immunohistochemical staining of whole mouse ovaries. Using this method, we analyzed cell proliferation and morphologic changes in mouse ovarian surface epithelial cells during follicle growth and ovulatory wound repair. Methods Three-week old FVB/N female mice were superovulated by sequential administration of pregnant mare's serum gonadotropin (PMSG and human chorionic gonadotropin (hCG. Ten hours after hCG administration, mice were given 5-bromo-2-deoxyuridine (BrdU and euthanized two hours after BrdU administration for ovary isolation. The levels of incorporated BrdU in the ovarian surface epithelial cells were measured by staining paraffin-embedded ovary sections and whole ovaries with the BrdU antibody. Re-epithelialization of the ovarian surface after ovulatory rupture was visualized by immunohistochemical staining with E-cadherin and Keratin 8 in paraffin-embedded ovary sections and whole ovaries. Results We determined that active proliferation of ovarian epithelial surface cells primarily occurs during antral follicle formation and, to a lesser extent, in response to an ovulatory wound. We also demonstrated that ovarian surface epithelial cells exhibit a

  15. Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing.

    Science.gov (United States)

    Hattori, Yoshiaki; Falgout, Leo; Lee, Woosik; Jung, Sung-Young; Poon, Emily; Lee, Jung Woo; Na, Ilyoun; Geisler, Amelia; Sadhwani, Divya; Zhang, Yihui; Su, Yewang; Wang, Xiaoqi; Liu, Zhuangjian; Xia, Jing; Cheng, Huanyu; Webb, R Chad; Bonifas, Andrew P; Won, Philip; Jeong, Jae-Woong; Jang, Kyung-In; Song, Young Min; Nardone, Beatrice; Nodzenski, Michael; Fan, Jonathan A; Huang, Yonggang; West, Dennis P; Paller, Amy S; Alam, Murad; Yeo, Woon-Hong; Rogers, John A

    2014-10-01

    Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.

  16. The battle of the bulge: re-evaluating hair follicle stem cells in wound repair.

    Science.gov (United States)

    Garcin, Clare L; Ansell, David M

    2017-02-01

    The hair follicle has an established role in wound re-epithelialisation, a phenomenon that has been appreciated since at least the first half of the last century. The bulge niche, one location of hair follicle epithelial stem cells has been of particular interest to researchers over recent years, with numerous studies showing its ability to directly contribute to epidermal repair. However, recent work has highlighted other progenitor regions of the hair follicle that appear to act as stem cells during epidermal repair. In addition, several studies within the last 12 months have questioned the importance of the bulge during re-epithelialisation, producing conflicting literature. Here we provide a new model to demonstrate how several important differences in experimental design between studies could account for these seemingly opposing findings, which may have implications for how future studies are conducted.

  17. Clinical and histological findings of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans) housed in unheated outdoor enclosures.

    Science.gov (United States)

    Negrini, Joao; Ginel, Pedro J; Novales, Manuel; Guerra, Rafael; Mozos, Elena

    2016-10-01

    Cutaneous wounds are common in chelonians. The clinical and histological features of wound healing in these species are not well described and this prevents evaluation of new therapies. To describe clinical and histopathological features of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans). Twenty four healthy adult females housed in outdoor facilities with free access to water and exposed to daily variations in temperature. Full thickness 6 mm skin biopsy punch wounds were created in the rear limbs. The turtles were assigned to Group 1 (n = 12 for clinical evaluation) and Group 2 (n = 12 for microscopic study). Group 1 was photographed on Day 1 and weekly, until 28 days post wounding. Wound retraction was expressed as the percentage of perimeter reduction. For Group 2, three skin wounds were sampled at 2, 7, 14, 21, 28, 42, 60 and 135 days post wounding for histological study. The avidin-biotin-peroxidase (ABC) staining method was used to evaluate five commercial antibodies. Wound contraction was limited; crust persisted at least 28 days. Re-epithelialization was complete by Day 14 in many animals; active inflammation persisted until 28 days; connective tissue re-constitution and remodelling was achieved from 42 to 135 days. Antibodies AE1/AE3, Factor VIII, MAC 387, CD3 and NCL-MSA showed cross reactivity with the cell counterpart in turtle tissues. Second intention wound healing progressed slowly and with an indolent behaviour. Microscopically there was marked overlapping of the inflammatory and proliferative phases over a long time period. © 2016 ESVD and ACVD.

  18. Synergistic Effect of Honey and Propolis on Cutaneous Wound Healing in Rats.

    Science.gov (United States)

    Takzaree, Nasrin; Hadjiakhondi, Abbas; Hassanzadeh, Gholamreza; Rouini, Mohammad Reza; Manayi, Azadeh

    2016-04-01

    Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day's rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (Pwound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (Pwound healing in rats has a synergistic effect.

  19. Image-guided cold atmosphere plasma (CAP) therapy for cutaneous wound

    Science.gov (United States)

    Yu, Zelin; Ren, Wenqi; Gan, Qi; Li, Jiahong; Li, XiangXiang; Zhang, Shiwu; Jin, Fan; Cheng, Cheng; Ting, Yue; Xu, Ronald X.

    2016-03-01

    Bacterial infection is one of the major factors contributing to the compromised healing in chronic wounds. Sometimes bacteria biofilms formed on the wound are more resistant than adherent bacteria. Cold atmosphere plasma (CAP) has already shown its potential in contact-free disinfection, blood coagulation, and wound healing. In this study, we integrated a multimodal imaging system with a portable CAP device for image-guided treatment of infected wound in vivo and evaluated the antimicrobial effect on Pseudomonas aeruginosa sample in vitro.15 ICR mice were divided into three groups for therapeutic experiments:(1) control group with no infection nor treatment (2) infection group without treatment (3) infection group with treatment. For each mouse, a three millimeters punch biopsy was created on the dorsal skin. Infection was induced by Staphylococcus aureus inoculation one day post-wounding. The treated group was subjected to CAP for 2 min daily till day 13. For each group, five fixed wounds' oxygenation and blood perfusion were evaluated daily till day 13 by a multimodal imaging system that integrates a multispectral imaging module and a laser speckle imaging module. In the research of relationship between therapeutic depth and sterilization effect on P.aeruginosa in agarose, we found that the CAP-generated reactive species reached the depth of 26.7μm at 30s and 41.6μm at 60s for anti-bacterial effects. Image-guided CAP therapy can be potentially used to control infection and facilitate the healing process of infected wounds.

  20. Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound healing and inhibits pro-inflammatory cytokines.

    Science.gov (United States)

    Gürgen, Seren Gülşen; Sayın, Oya; Cetin, Ferihan; Tuç Yücel, Ayşe

    2014-06-01

    The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar-Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.

  1. Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

    Science.gov (United States)

    Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

    2011-03-01

    This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

  2. Wound repair during arm regeneration in the red starfish Echinaster sepositus

    KAUST Repository

    Ben Khadra, Yousra

    2015-06-24

    Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post-traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; in order to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re-epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, re-differentiation and/or migration. This article is protected by copyright. All rights reserved.

  3. Keratinocyte-targeted overexpression of the glucocorticoid receptor delays cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Ana Sanchis

    Full Text Available Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC analogs, which act through the ligand-dependent transcription factor GC-receptor (GR. GR function is exerted through DNA-binding-dependent and -independent mechanisms, classically referred to as transactivation (TA and transrepression (TR. Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown. We evaluated skin wound healing in transgenic mice with keratinocyte-restricted expression of either wild type GR or a mutant GR that is TA-defective but efficient in TR (K5-GR and K5-GR-TR mice, respectively. Our data show that at days (d 4 and 8 following wounding, healing in K5-GR mice was delayed relative to WT, with reduced recruitment of granulocytes and macrophages and diminished TNF-α and IL-1β expression. TGF-β1 and Kgf expression was repressed in K5-GR skin whereas TGF-β3 was up-regulated. The re-epithelialization rate was reduced in K5-GR relative to WT, as was formation of granulation tissue. In contrast, K5-GR-TR mice showed delays in healing at d4 but re-established the skin breach at d8 concomitant with decreased repression of pro-inflammatory cytokines and growth factors relative to K5-GR mice. Keratinocytes from both transgenic mice closed in vitro wounds slower relative to WT, consistent with the in vivo defects in cell migration. Overall, the delay in the early stages of wound healing in both transgenic models is similar to that elicited by systemic treatment with dexamethasone. Wound responses in the transgenic keratinocytes correlated with reduced ERK activity both in vivo and in vitro. We conclude that the TR function of GR is sufficient for negatively regulating early stages of wound closure, while TA by GR is required for delaying later stages of healing.

  4. An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy

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    Rifkin Lucas H

    2012-05-01

    Full Text Available Abstract Purpose To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. Methods A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD. Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. Results No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664. Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753. With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895. Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint. Conclusions We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

  5. Comparative study of topical green and red propolis in the repair of wounds induced in rats.

    Science.gov (United States)

    Batista, Lara Lívia Valença; Campesatto, Eliane Aparecida; Assis, Maria Lysete Bastos de; Barbosa, Ana Paula Fernandes; Grillo, Luciano Aparecido Meireles; Dornelas, Camila Braga

    2012-12-01

    To evaluate the healing action of green and red propolis, correlating it with the content of flavonoids. We performed quantification of total flavonoids of green and red propolis ethanol extracts for subsequent incorporation in ointment base to 20%. We used 20 Wistar rats divided into four groups: 0.9% saline (S), ointment base (B), green propolis ointment (G) and red propolis ointment (R). All animals were submitted to excisional lesions in the midian back region. The rats were treated daily for 15 days. During this period we observed weight, body temperature and diameters of the wounds. For histological analysis, samples were collected from wounds. At the end of the experiment we performed blood collection and removal of the kidney and liver for biochemical and histological analyzes. The levels of total flavonoids of green (4.50%) and red (5.92%) propolis were high (> 2%), but, while the latter showed a content larger than the former, the evolution of green propolis was better in the repair of wounds, both macroscopically and histologically. There were no nephrotoxicity or hepatotoxicity, a result confirmed by biochemical tests (ALT and albumin). Propolis influenced the reduction of total cholesterol, triglycerides and glucose. There was no correlation between total flavonoid contents and the healing action of propolis. This reveals the need for elucidation of the flavonoids found in each class of propolis to unravel which one(s) would be important for the healing process.

  6. Electric field as a potential directional cue in homing of bone marrow-derived mesenchymal stem cells to cutaneous wounds.

    Science.gov (United States)

    Zimolag, Eliza; Borowczyk-Michalowska, Julia; Kedracka-Krok, Sylwia; Skupien-Rabian, Bozena; Karnas, Elzbieta; Lasota, Slawomir; Sroka, Jolanta; Drukala, Justyna; Madeja, Zbigniew

    2017-02-01

    Bone marrow-derived cells are thought to participate and enhance the healing process contributing to skin cells or releasing regulatory cytokines. Directional cell migration in a weak direct current electric field (DC-EF), known as electrotaxis, may be a way of cell recruitment to the wound site. Here we examined the influence of electric field on bone marrow adherent cells (BMACs) and its potential role as a factor attracting mesenchymal stem cells to cutaneous wounds. We observed that in an external EF, BMAC movement was accelerated and highly directed with distinction of two cell populations migrating toward opposite poles: mesenchymal stem cells migrated toward the cathode, whereas macrophages toward the anode. Analysis of intracellular pathways revealed that macrophage electrotaxis mostly depended on Rho family small GTPases and calcium ions, but interruption of PI3K and Arp2/3 had the most pronounced effect on electrotaxis of MSCs. However, in all cases we observed only a partial decrease in directionality of cell movement after inhibition of certain proteins. Additionally, although we noticed the accumulation of EGFR at the cathodal side of MSCs, it was not involved in electrotaxis. Moreover, the cell reaction to EF was very dynamic with first symptoms occurring within <1min. In conclusion, the physiological DC-EF may act as a factor positioning bone marrow cells within a wound bed and the opposite direction of MSC and macrophage movement did not result either from utilizing different signalling or redistribution of investigated cell surface receptors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Clinical and histopathologic findings in cutaneous sting ray wounds: a case report

    OpenAIRE

    Tartar, Danielle; Limova, Marketa; North, Jeffrey

    2013-01-01

    Human injuries related to stingray attacks include deep puncture wounds, envenomation, and foreign body reactions owing to retained tail fragments. Herein we report a patient who sustained a stingray injury that produced a subcutaneous granulomatous dermatitis and panniculitis with necrobiosis and review the topic of stingray injuries.

  8. Study of Diabetic cutaneous wound healing in rats treated with Lactobacillus Casei and its Exopolysaccharide

    Directory of Open Access Journals (Sweden)

    Saeed Ahmadi Majid

    2016-06-01

    Full Text Available Probiotics are live microorganisms (in most cases, bacteria that are similar to beneficial microorganisms found in the human gut. They are also called "friendly bacteria" or "good bacteria". Lactobacillus derived from products, including culture supernatants have been used for their wound healing and antiviral properties as they are believed to boost energy and to be effective remedies for allergies, common cold, lactose intolerance, and have also been shown to reduce cholesterol levels and the risk of colon cancer. Therefore, the purpose of this experiment is to study the effect of Lactobacillus casei on Diabetic wound healing. This study was designed to investigate the amount of exopolysaccharide (EPS production by L. Casei, L. Brevis, L. Bulgaricus and L. Plant arum from the genus Lactobacillus applying the phenol-sulfuric acid method and the antagonistic effects of these bacteria on some pathogenic bacteria. L. casei was selected for its high exopolysaccharide and fucoid colonise production. The animals were injected by streptozotocin at the dose of 55 mg/kg of the body weight intraperitoneal streptozotocin induced diabetes within 3 days by destroying the beta cells. Wistar male rats divided into 4 groups; 2 experimental groups, a control and a negative control (n =6; and a full-thickness wound (1× 1cm was made on the back of each rat. The current study showed a significant reduction in inflammation and a significant acceleration in wound healing on the rats treated by Lactobacillus casei as compared to control and negative control groups.

  9. Effects of flavonoids from Martynia annua and Tephrosia purpurea on cutaneous wound healing

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    Santram Lodhi

    2016-08-01

    Full Text Available Objective: Martynia annua L. (M. annua, (Martyniaccae has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea, (Fabaceae has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M. annua leaves and aerial parts of T. purpurea. Materials and Methods: Methanol fraction of M. annua (MAF-C and ethyl acetate fraction of T. purpurea (TPF-A were evaluated for healing potential in dead-space and burn wound models. An ointment (5% w/w of MAF-C and TPF-A, pongamol (0.2 and 0.5% w/w and luteolin (0.2 and 0.5% w/w was applied topically twice a day. The effects were compared with Povidone Iodine ointment with respect to protein, collagen content, enzymatic assay and histopathological finding of granuloma tissues. Results: Ethanol extracts of M. annua and T. purpureawere exhibited total flavonoid contents of 126.2 ± 4.69 and 171.6 ± 6.38 mg (quercetin equivalent, respectively. HPLC fingerprinting confirmed the presence of luteolin in M. annua and quercetin in T. purpurea. TPF-A and MAF-C ointments (5% w/w significantly increases the hydroxyproline and protein contents. Luteolin and pongamol ointments were also found to be effective in both wound models. Conclusion: Our findings suggested that 5% w/w ointment of TPF-A and MAF-C fractions were more effective than isolated flavonoids in wound healing which may be due to synergistic interactions between the flavonoids and other constituents.

  10. Nitrite to nitrate molar ratio is inversely proportional to oxidative cell damages and granulocytic apoptosis at the wound site following cutaneous injury in rats.

    Science.gov (United States)

    Zunić, Gordana; Colić, Miodrag; Vuceljić, Marina

    2009-06-01

    Nitric oxide (NO) metabolism in response to the inflammatory cell infiltration and their apoptosis at the wound site, using a model of subcutaneously implanted sponges in Albino Oxford rats, were examined. The injured animals were sacrificed at days 1, 2 and 3 after the injury. Nitrites, nitrates (final products of NO metabolism), malondialdehyde (an indicator of oxidative cell damages), urea (product of arginase activity) and other parameters were measured both in plasma and wound fluid samples. Nitrite to nitrate molar ratio and sum of nitrites and nitrates (NO(x)) were calculated. The total cell numbers were at similar level throughout the examined period, but a gradual decrease of viable granulocytes, mainly due to the increased apoptosis, and the increase of monocyte-macrophage number occurred after the second day. A gradual increase of wound fluid nitrates, NO(x) and malondialdehyde suggested the increases of both NO and free oxygen radicals production. Interestingly, wound fluid nitrites peaked at the first day decreasing to the corresponding plasma levels thereafter. Wound fluid nitrite to nitrate molar ratio gradually decreased and negatively correlated both with the number of apoptotic cells (r= -0.752, poxidative cell damages and cell apoptosis at the wound site early after the cutaneous wound. Moreover, the obtained findings suggest that measurement of both nitrites and nitrates contribute to better insight into overall wound NO metabolism.

  11. A Double-Edged Sword: The Role of VEGF in Wound Repair and Chemoattraction of Opportunist Pathogens

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    Eric Birkenhauer

    2015-03-01

    Full Text Available Wound healing is a complex process essential to repairing damaged tissues and preventing infection. Skin is the first line of defense, a chief physical barrier to microbe entry. Wound healing is a physical rebuilding process, but at the same time it is an inflammatory event. In turn, molecules for wound repair are secreted by fibroblasts and others present at the wound site. Vascular endothelial growth factor (VEGF is a critical cytokine that exhibits chemoattractant properties, recruiting other immune cells to the site. Although generally beneficial, VEGF may also act as a chemoattractant for invading microorganisms, such as Pseudomonas aeruginosa. P. aeruginosa is problematic during wound infection due to its propensity to form biofilms and exhibit heightened antimicrobial resistance. Here, we explored the influence of VEGF gradients (in a microfluidic device wound model on the motility and chemotactic properties of P. aeruginosa. At lower concentrations, VEGF had little effect on motility, but as the maximal concentration within the gradient increased, P. aeruginosa cells exhibited directed movement along the gradient. Our data provide evidence that while beneficial, VEGF, in excess, may aid colonization by P. aeruginosa. This highlights the necessity for the efficient resolution of inflammation. Understanding the dynamics of wound colonization may lead to new/enhanced therapeutics to hasten recovery.

  12. Designing a New Nano-Plant Composite of Cucurbita pepo for Wound Repair of Skin in Male Albino Mice: A New Nano Approach for Skin Repair

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    Nooshin Naghsh

    2013-06-01

    Full Text Available Background & Objective : The Cucurbita pepo is one of plants that are functional in traditional therapy. This plant has antioxidant and skin damage repair properties. This study investigated the effect of Cucurbita pepo nano silver as a new nano-plant composition in wound repair skin in male mice.   Materials & Methods: In this investigation, male albino mice were places in 8 groups, each containing 8 animals. Group I – VIII were treated with nano silver (500, 250, and 125 ppm concentrations and different concentrations of extracts [70%, 50%, and 25%] and the control group received a mixture of 25% Cucurbita pepo extract (125 ppm nano silver. The eighth group, as control, was treated with sterile deionizer water after the induction of wound skin. The average diameter of the wounds was measured 28 days after treatment in the control and treatment groups. These data were analyzed using the t-test and ANOVA statistical method.   Results: The results of this study showed that ethanol extraction (80% has its highest repair effect 28 days post treatment. The average diameter of the wounds in the control group was 1.16 ±. 0.46 cm, which was decreased to 0 cm and 0.12 ±. 0.23 cm in the ethanol extract (70% of the Cucurbita pepo and component groups, respectively (p value ≤ 0.01.   Conclusion: In this project, nano silver-Cucurbita pepo ethanol extraction for wound repair in albino male mice was more effective than single materials. These findings show that the repair synergic effects are between alcoholic extract and nano silver in this nano composite.

  13. Topical Administration of Acylated Homoserine Lactone Improves Epithelialization of Cutaneous Wounds in Hyperglycaemic Rats.

    Directory of Open Access Journals (Sweden)

    Lijuan Huang

    Full Text Available Clinicians often experience delayed epithelialization in diabetic patients, for which a high glucose condition is one of the causes. However, the mechanisms underlying delayed wound closure have not been fully elucidated, and effective treatments to enhance epithelialization in patients with hyperglycaemia have not been established. Here we propose a new reagent, acylated homoserine lactone (AHL, to improve the delayed epithelialization due to the disordered formation of a basement membrane of epidermis in hyperglycaemic rats. Acute hyperglycaemia was induced by streptozotocin injection in this experiment. Full thickness wounds were created on the flanks of hyperglycaemic or control rats. Histochemical and immunohistochemical analyses were performed to identify hyperglycaemia-specific abnormalities in epidermal regeneration by comparison between groups. We then examined the effects of AHL on delayed epithelialization in hyperglycaemic rats. Histological analysis showed the significantly shorter epithelializing tissue (P < 0.05, abnormal structure of basement membrane (fragmentation and immaturity, and hypo- and hyperproliferation of basal keratinocytes in hyperglycaemic rats. Treating the wound with AHL resulted in the decreased abnormalities of basement membrane, normal distribution of proliferating epidermal keratinocytes, and significantly promoted epithelialization (P < 0.05 in hyperglycemic rats, suggesting the improving effects of AHL on abnormal epithelialization due to hyperglycemia.

  14. Development of a novel sodium fusidate-loaded triple polymer hydrogel wound dressing: Mechanical properties and effects on wound repair.

    Science.gov (United States)

    Jin, Sung Giu; Kim, Kyeong Soo; Kim, Dong Wuk; Kim, Dong Shik; Seo, Youn Gee; Go, Toe Gyung; Youn, Yu Seok; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2016-01-30

    To develop a novel sodium fusidate-loaded triple polymer hydrogel dressing (TPHD), numerious polyvinyl alcohol-based (PVA) hydrogel dressings were prepared with various hydrophilic polymers using the freeze-thaw method, and their hydrogel dressing properties were assessed. Among the hydrophilic polymers tested, sodium alginate (SA) improved the swelling capacity the most, and polyvinyl pyrrolidone (PVP) provided the greatest improvement in bioadhesive stength and mechanical properties. Thus, PVA based-TPHDs were prepared using different ratios of PVP:SA. The effect of selected PVP:SA ratios on the swelling capacity, bioadhesive strength, mechanical properties, and drug release, permeation and deposition characteristics of sodium fusidate-loaded PVA-based TPHDs were assessed. As the ratio of PVP:SA increased in PVA-loaded TPHD, the swelling capacity, mechanical properties, drug release, permeation and deposition were improved. The TPHD containing PVA, PVP, SA and sodium fusidate at the weight ratio of 10/6/1/1 showed excellent hydrogel dressing properties, release, permeation and deposition of drug. Within 24h, 71.8 ± 1.3% of drug was released. It permeated 625.1 ± 81.2 μg/cm(2) through the skin and deposited of 313.8 ± 24.1 μg/cm(2) within 24h. The results of in vivo pharmacodynamic studies showed that sodium fusidate-loaded TPHD was more effective in improving the repair process than was a commercial product. Thus, this sodium fusidate-loaded TPHD could be a novel tool in wound care.

  15. Self-assembling peptide nanofiber scaffolds accelerate wound healing.

    Directory of Open Access Journals (Sweden)

    Aurore Schneider

    Full Text Available Cutaneous wound repair regenerates skin integrity, but a chronic failure to heal results in compromised tissue function and increased morbidity. To address this, we have used an integrated approach, using nanobiotechnology to augment the rate of wound reepithelialization by combining self-assembling peptide (SAP nanofiber scaffold and Epidermal Growth Factor (EGF. This SAP bioscaffold was tested in a bioengineered Human Skin Equivalent (HSE tissue model that enabled wound reepithelialization to be monitored in a tissue that recapitulates molecular and cellular mechanisms of repair known to occur in human skin. We found that SAP underwent molecular self-assembly to form unique 3D structures that stably covered the surface of the wound, suggesting that this scaffold may serve as a viable wound dressing. We measured the rates of release of EGF from the SAP scaffold and determined that EGF was only released when the scaffold was in direct contact with the HSE. By measuring the length of the epithelial tongue during wound reepithelialization, we found that SAP scaffolds containing EGF accelerated the rate of wound coverage by 5 fold when compared to controls without scaffolds and by 3.5 fold when compared to the scaffold without EGF. In conclusion, our experiments demonstrated that biomaterials composed of a biofunctionalized peptidic scaffold have many properties that are well-suited for the treatment of cutaneous wounds including wound coverage, functionalization with bioactive molecules, localized growth factor release and activation of wound repair.

  16. Prevalence of cutaneous pathological conditions and factors associated with the presence of skin wounds in working equids in tropical regions of Veracruz, Mexico.

    Science.gov (United States)

    Sánchez-Casanova, Rubí Elena; Masri-Daba, María; Alonso-Díaz, Miguel Ángel; Méndez-Bernal, Adriana; Hernández-Gil, Mariano; Fernando-Martínez, José Antonio

    2014-03-01

    A wide spectrum of welfare issues is encountered on working equids. The objectives of this study were: (i) to determine the prevalence of cutaneous lesions in working equids in tropical regions of the North-Central of Veracruz State, Mexico, (ii) to identify the most prevalent cutaneous pathological conditions in this population of working equids, and (iii) to identify risk factors associated to the presence of work-related skin wounds. A number of 467 working equids presented for treatment at Donkey Sanctuary Mobile Clinic Program - National Autonomous University of Mexico from seven different villages in the North-Central region of Veracruz State were evaluated. Animals with signs of cutaneous pathology underwent a physical examination and samples were obtained of exudates, hair, and tissue for cytology examination, fungal cultures, and dermo-histopathology examination. The overall prevalence of cutaneous pathological conditions in working equids was 20.6 %. The prevalence per species was 22.6 % for horses, 18.2 % for donkeys, and 14.3 % for mules. The most common cause of skin lesions was trauma (abrasions, lacerations, and abscesses) followed in frequency by parasitic dermatitis and sarcoids. No strong associations among species were observed (P > 0.20). Multivariate analysis showed that there was greater association between BCS and age with the presence of skin wounds (P Veracruz, Mexico.

  17. An international eDelphi study identifying the research and education priorities in wound management and tissue repair.

    LENUS (Irish Health Repository)

    2012-02-01

    Aim. To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. Background. A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. Design. The study used a survey method. Methods. A four-round eDelphi technique was used to collect responses from an international population of health professionals across 24 countries. Results. Responses were obtained from 360 professionals representing many health care settings. The top education priorities related to the standardisation of all foundation education programmes in wound care, the inclusion of wound care in all professional undergraduate and postgraduate education programmes, selecting dressings and the prevention of pressure ulcers. The top research priorities related to the dressing selection, pressure ulcer prevention and wound infection. Conclusion. Professionals from different backgrounds and countries who are engaged in wound management share a common set of priorities for research and education. Most notably, the priorities identified relate to long-established clinical challenges in wound care and underpin the principles of good patient care practices. The priorities are closely allied to an ageing population and identify many challenges ahead for practitioners engaged in wound management services. Relevance to clinical practice. The provision of wound care is a major investment of health service resources and remains a clinical challenge today. Research is essential to building evidence-based practice and fundamental to development of quality in standards of practice; education is central to achieving competence to deliver effective care. The

  18. Effects of aroeira (Schinus terebinthifoliu Raddi oil on cutaneous wound healing in rats

    Directory of Open Access Journals (Sweden)

    Lígia Reis Moura Estevão

    2013-03-01

    Full Text Available PURPOSE: To evaluate the effects of aroeira (Schinus terebinthifolius ointment on skin wound healing in rats. METHODS: Adult male rats (n=20 were divided into four groups of five animals each, as follows: G4, G7, G14 and G21, which corresponds to 4th, 7th, 14th and 21th days postoperatively. Each animal were made two incisions on the skin, including the subcutaneous tissue, in the right and left sides of thoracic region, separated by a distance of two inches. The right lesion was treated with base ointment (vaseline, lanolin; the left one was treated with base ointment containing 5% of aroeira oil. At the end of each experimental period the lesions were evaluated for the contraction degree. Then held the collection of fragments that were fixed in 10% formalin and processed for paraffin embedding. In the histological sections (5μm was evaluated the morphology and quantified the collagen and blood vessels. The data obtained were submitted to ANOVA test complemented by Tukey-Kramer test (p<0.05. RESULTS: The contraction of the lesions was higher in wounds treated with aroeira oil than in controls at 7th and 14th days (p<0.01, whereas in the 21st day all lesions were already completely healed. The morphology showed granulation tissue more developed, with fibroblasts more bulky and collagen fibers more arranged in the experimental group at 4th, 7th and 14th days. The morphometry showed a significant increase in the quantification of collagen fibers in the experimental group at 7th and 14th days (p<0.05. CONCLUSION: The aroeira oil accelerates the healing process of wounds as a macroscopic, morphological and morphometrical analysis.

  19. Inhibition of PAI-1 Via PAI-039 Improves Dermal Wound Closure in Diabetes.

    Science.gov (United States)

    Rebalka, Irena A; Raleigh, Matthew J; D'Souza, Donna M; Coleman, Samantha K; Rebalka, Alexandra N; Hawke, Thomas J

    2015-07-01

    Diabetes impairs the ability to heal cutaneous wounds, leading to hospitalization, amputations, and death. Patients with diabetes experience elevated levels of plasminogen activator inhibitor 1 (PAI-1), regardless of their glycemic control. It has been demonstrated that PAI-1-deficient mice exhibit improved cutaneous wound healing, and that PAI-1 inhibition improves skeletal muscle repair in mice with type 1 diabetes mellitus, leading us to hypothesize that pharmacologically mediated reductions in PAI-1 using PAI-039 would normalize cutaneous wound healing in streptozotocin (STZ)-induced diabetic (STZ-diabetic) mice. To simulate the human condition of variations in wound care, wounds were aggravated or minimally handled postinjury. Following cutaneous injury, PAI-039 was orally administered twice daily for 10 days. Compared with nondiabetic mice, wounds in STZ-diabetic mice healed more slowly. Wound site aggravation exacerbated this deficit. PAI-1 inhibition had no effect on dermal collagen levels or wound bed size. PAI-039 treatment failed to improve angiogenesis in the wounds of STZ-diabetic mice and blunted angiogenesis in the wounds of nondiabetic mice. Importantly, PAI-039 treatment significantly improved epidermal cellular migration and wound re-epithelialization compared with vehicle-treated STZ-diabetic mice. These findings support the use of PAI-039 as a novel therapeutic agent to improve diabetic wound closure and demonstrate the primary mechanism of its action to be related to epidermal closure.

  20. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.

    Science.gov (United States)

    Ito, Mayumi; Liu, Yaping; Yang, Zaixin; Nguyen, Jane; Liang, Fan; Morris, Rebecca J; Cotsarelis, George

    2005-12-01

    The discovery of long-lived epithelial stem cells in the bulge region of the hair follicle led to the hypothesis that epidermal renewal and epidermal repair after wounding both depend on these cells. To determine whether bulge cells are necessary for epidermal renewal, here we have ablated these cells by targeting them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK) using a Keratin 1-15 (Krt1-15) promoter. We show that ablation leads to complete loss of hair follicles but survival of the epidermis. Through fate-mapping experiments, we find that stem cells in the hair follicle bulge do not normally contribute cells to the epidermis which is organized into epidermal proliferative units, as previously predicted. After epidermal injury, however, cells from the bulge are recruited into the epidermis and migrate in a linear manner toward the center of the wound, ultimately forming a marked radial pattern. Notably, although the bulge-derived cells acquire an epidermal phenotype, most are eliminated from the epidermis over several weeks, indicating that bulge stem cells respond rapidly to epidermal wounding by generating short-lived 'transient amplifying' cells responsible for acute wound repair. Our findings have implications for both gene therapy and developing treatments for wounds because it will be necessary to consider epidermal and hair follicle stem cells as distinct populations.

  1. Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications

    Science.gov (United States)

    2017-01-01

    The chronic nature and associated complications of nonhealing wounds have led to the emergence of nanotechnology-based therapies that aim at facilitating the healing process and ultimately repairing the injured tissue. A number of engineered nanotechnologies have been proposed demonstrating unique properties and multiple functions that address specific problems associated with wound repair mechanisms. In this outlook, we highlight the most recently developed nanotechnology-based therapeutic agents and assess the viability and efficacy of each treatment, with emphasis on chronic cutaneous wounds. Herein we explore the unmet needs and future directions of current technologies, while discussing promising strategies that can advance the wound-healing field. PMID:28386594

  2. CEACAM1 deficiency delays important wound healing processes.

    Science.gov (United States)

    LeBlanc, Sarah; Arabzadeh, Azadeh; Benlolo, Samantha; Breton, Valérie; Turbide, Claire; Beauchemin, Nicole; Nouvion, Anne-Laure

    2011-11-01

    Cutaneous wound healing is a complex process that requires the coordination of many cell types to achieve proper tissue repair. Four major overlapping processes have been identified in wound healing: hemostasis, inflammation, reepithelialization and granulation tissue formation, and tissue remodeling. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a glycoprotein expressed in epithelial, endothelial, lymphoid, and myeloid cells. Given its known roles in angiogenesis, cell migration, and immune functions, we hypothesized that CEACAM1 might also be involved in cutaneous wound healing and that a number of relevant CEACAM1-positive cell types might contribute to wound healing. To evaluate the role of CEACAM1 in these processes, 6-mm-diameter skin wounds were inflicted on Ceacam1(-/-) and wild-type mice. Herein, we demonstrate that CEACAM1 deletion indeed affects wound healing in three key ways. Infiltration of F4/80(+) macrophages was decreased in Ceacam1(-/-) wounds, altering inflammatory processes. Reepithelialization in Ceacam1(-/-) wounds was delayed. Furthermore, the vascular density of the granulation tissue in Ceacam1(-/-) wounds was significantly diminished. These results confirm CEACAM1's role as an important regulator of key processes in cutaneous wound healing, although whether this works via a specific cell type or alterations in the functioning of multiple processes remains to be determined.

  3. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

    Science.gov (United States)

    Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

    2017-03-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

  4. Delivery of plasmid DNA expression vector for keratinocyte growth factor-1 using electroporation to improve cutaneous wound healing in a septic rat model.

    Science.gov (United States)

    Lin, Michael P; Marti, Guy P; Dieb, Rami; Wang, Jiaai; Ferguson, Mark; Qaiser, Rabia; Bonde, Pramod; Duncan, Mark D; Harmon, John W

    2006-01-01

    We have previously shown that wound healing was improved in a diabetic mouse model of impaired wound healing following transfection with keratinocyte growth factor-1 (KGF-1) cDNA. We now extend these findings to the characterization of the effects of DNA plasmid vectors delivered to rats using electroporation (EP) in vivo in a sepsis-based model of impaired wound healing. To assess plasmid transfection and wound healing, gWIZ luciferase and PCDNA3.1/KGF-1 expression vectors were used, respectively. Cutaneous wounds were produced using an 8 mm-punch biopsy in Sprague-Dawley rats in which healing was impaired by cecal ligation-induced sepsis. We used National Institutes of Health image analysis software and histologic assessment to analyze wound closure and found that EP increased expression of gWIZ luciferase vector up to 53-fold compared with transfection without EP (p < 0.001). EP-assisted plasmid transfection was found to be localized to skin. Septic rats had a 4.7 times larger average wound area on day 9 compared with control (p < 0.001). Rats that underwent PCDNA3.1/KGF-1 transfection with EP had 60% smaller wounds on day 12 compared with vector without EP (p < 0.009). Quality of healing with KGF-1 vector plus EP scored 3.0 +/- 0.3 and was significantly better than that of 1.8 +/- 0.3 for treatment with vector alone (p < 0.05). We conclude that both the rate and quality of healing were improved with DNA plasmid expression vector for growth factor delivered with EP to septic rats.

  5. Cosmetic Surgical Repair of Contaminated Wounds Versus Traditional Loose Approximation: Does It Increase the Rate of Wound Infections?

    Directory of Open Access Journals (Sweden)

    P. Yavari

    2007-02-01

    Full Text Available Background:The cosmetic result of the surgical scar has long been considered by surgeons as an important factor for patient satisfaction.On the other hand,there has been an old teaching that perfect closure of contaminated wounds increases the rate of infection. We decided to look into this matter and see if this is a fact or a myth. Methods: In this prospective randomized study conducted on 200 patients with suppurative or gangrenous appendicitis,we closed the wounds with a cosmetic subcuticular suture of 4/0 nylon in 100 patients and in the other 100 patients the wound was approximated loosely with a few stitches of 3/0 nylon in vertical mattress fashion during a 14-month period.Results:There was no significant difference in the rate of wound infection between these two groups.Conclusions:This study shows that perfect closure of the wound with subcuticular closure,which gives a very good cosmetic result in comparison with traditional loose closure, does not increase the rate of wound infection.

  6. Fibrin adhesive implant in wound healing repair of dental sockets with topical application of epsilon aminocaproic acid: histological analysis.

    Science.gov (United States)

    Padovan, Luis Eduardo M; Okamoto, Tetuo; Rezende, Maria Cristina Rossifini Alves; Curvêllo, Victor Prado; Nicolielo, Daniela; Matsumoto, Mariza Akemi

    2005-05-01

    The aim of the study was to evaluate wound healing repair of dental sockets after topical application of 5% epsilon-aminocaproic acid (EACA) and the use of fibrin adhesive implant in rats under anticoagulant therapy with warfarin. Sixty Albinus wistar rats were used, divided into three groups of 20. In Group I, the animals were given 0.1 mL/100 mg of 0.9% saline solution per day, beginning 6 days before dental extraction and continuing throughout the experimental period. In Group II, the animals received 0.03 mL of sodium warfarin daily, beginning 6 days before the surgery and continuing until the day of sacrifice; after tooth extractions, the sockets were filled with fibrin adhesive material. In Group III the animals were treated as in Group II, and after extractions, the sockets were irrigated with 5 mL of 5% EACA and filled with the same fibrin adhesive material. All groups presented biological phases of wound healing repair, the differences being evident only in the chronology. The results obtained in Group III were very similar to those of Group I in the last period of wound repair, whereas Group II presented a late chronology compared to the other groups.

  7. Effects of LED phototherapy on relative wound contraction and reepithelialization during tissue repair in hypothyroid rats: morphometric and histological study.

    Science.gov (United States)

    Paraguassú, Gardênia Matos; da Guarda, Milena Góes; Xavier, Flávia Calo Aquino; Cangussu, Maria Cristina Teixeira; Rodriguez, Tânia Tavares; Ramalho, Maria José Pedreira; Pinheiro, Antônio Luis Barbosa; Ramalho, Luciana Maria Pedreira

    2014-03-01

    The aim of this study was to assess morphometrically and histologically, the effects of light-emitting diode (LED) (λ630 ± 20 nm) phototherapy on reepithelialization and wound contraction during tissue repair in hypothyroid rats. Thyroid hormone deficiency has been associated with disorders of tissue repair. LED phototherapy has been studied using several healing models, but their usefulness in the improvement of hypothyroidism wound healing remains unknown. Under general anesthesia, a standard surgical wound (1 cm(2)) was produced on the dorsum of 48 male Wistar rats divided into four groups of 12 animals each: EC-control euthyroid, ED-euthyroid + LED, HC-control hypothyroid, and HD-Hypothyroid + LED. The irradiation started immediately after surgery and was repeated every other day for 7 and 14 days. Photographs of the wound were taken at the day of the surgical procedure and on days 8 and 15 after surgery, when animals' deaths occurred. The specimens were removed, routinely processed, and stained with hematoxylin/eosin. Seven days after the surgery, it was possible to observe statistically significant reductions in the wound area of the irradiated euthyroid group, in comparison to hypothyroid group, irradiated and non-irradiated (ANOVA, p < 0.05). The reepithelialization was significantly higher in the euthyroid and hypothyroid groups irradiated with LED than in the non-irradiated groups (Fisher's test, p < 0.05). No significant difference was found in the experimental period of 14 days among the groups. The hypothyroidism delayed wound healing and the LED phototherapy, at these specific parameters, improved the process of reepithelialization in the presence of hypothyroidism.

  8. 面部挫裂伤的急诊美容修复%The aesthetic repair of facial lacerating wound

    Institute of Scientific and Technical Information of China (English)

    王量; 杨东运; 陶灵; 刘剑毅; 陈亮; 李世荣

    2012-01-01

    Objective To analyzed the experience in the aesthetic repair of facial lacerating wound. Methods To observed the healing effects of 87 emergency facial lacerating wound cases with aesthetic repair from 2009 to 2012. Results All the cases were primary healed, there was no obvious hypertrophic scar and no disfunction,the secondary repair was not required. The results were satisfactory. Conclusion Early stage aesthetic repair with plastic surgical principles and techniques of facial trauma could prevent the secondary treatment and relieve the pain of the patients.lt should be emphasized that tissue preserving could lessen deformity postoperative in the repairment of facial lacerating wound.%目的:总结面部挫裂伤的急诊整形美容外科修复经验,为临床工作提供指导.方法:对2009年至2012年间我科急诊整形美容修复的87例面部挫裂伤患者术后效果进行观察.结果:87例患者随访均Ⅰ期愈合,均无明显瘢痕增生,无功能障碍,无需进行Ⅱ期修复,效果满意.结论:面部挫裂伤后遵循整形外科基本原则的急诊整形美容精细修复,可达到无需或减少后续治疗,为患者减少痛苦,减轻负担.特别要提出在挫裂伤修复中对组织的保留,可减轻术后畸形.

  9. The repair of impaired epidermal barrier function in rats by the cutaneous application of linoleic acid.

    Science.gov (United States)

    Prottey, C; Hartop, P J; Black, J G; McCormack, J I

    1976-01-01

    Epidermal barrier function in rats was experimentally impaired by two separate means, namely, by rendering the animals deficient in essential fatty acids and by evoking a primary cutaneous irritant response by treating with a solution of sodium laurate. Impaired barrier function was manifested by a greatly increased rate of transepidermal water loss. Application to the skin of sunflower seed oil, which is rich in linoleic acid, rapidly restored to normal the abnormally high rates of transepidermal water loss in both experimental cases, and it was shown with the essential fatty acid-deficient rats that there was a concomitant incorporation of linoleic acid of the sunflower seed oil into epidermal lipids. Cutaneous application of olive oil, which is low in linoleic acid but rich in the non-essential oleic acid, did not influence epidermal barrier function. A close relationship of barrier function and essential fatty acids is indicated.

  10. Fibronectin and wound healing.

    Science.gov (United States)

    Grinnell, F

    1984-01-01

    I have tried to briefly review the evidence (summarized in Table II) indicating that fibronectin is important in cutaneous wound healing. Fibronectin appears to be an important factor throughout this process. It promotes the spreading of platelets at the site of injury, the adhesion and migration of neutrophils, monocytes, fibroblasts, and endothelial cells into the wound region, and the migration of epidermal cells through the granulation tissue. At the level of matrix synthesis, fibronectin appears to be involved both in the organization of the granulation tissue and basement membrane. In terms of tissue remodeling, fibronectin functions as a nonimmune opsonin for phagocytosis of debris by fibroblasts, keratinocytes, and under some circumstances, macrophages. Fibronectin also enhances the phagocytosis of immune-opsonized particles by monocytes, but whether this includes phagocytosis of bacteria remains to be determined. In general, phagocytosis of bacteria has not appeared to involve fibronectin. On the contrary, the presence of fibronectin in the wound bed may promote bacterial attachment and infection. Because of the ease of experimental manipulations, wound healing experiments have been carried out on skin more frequently than other tissues. As a result, the possible role of fibronectin has not been investigated thoroughly in the repair of internal organs and tissues. Nevertheless, it seems reasonable to speculate that fibronectin plays a central role in all wound healing situations. Finally, the wound healing problems of patients with severe factor XIII deficiencies may occur because of their inability to incorporate fibronectin into blood clots.

  11. Wnt-4 expression is increased in fibroblasts after TGF-beta1 stimulation and during fetal and postnatal wound repair.

    Science.gov (United States)

    Colwell, Amy S; Krummel, Thomas M; Longaker, Michael T; Lorenz, H Peter

    2006-06-01

    Wnt-4 is a mitogen expressed during postnatal repair and scar formation; however, its expression profile during scarless repair is unknown. Transforming growth factor (TGF)-beta1 has high expression during healing with scar formation. Whether TGF-beta1 directly influences Wnt-4 expression in fetal or postnatal fibroblasts has not been examined. Primary fetal and postnatal mouse fibroblasts were stimulated with TGF-beta1 and Wnt-4 expression quantitated by real-time polymerase chain reaction. Fetal E17 and postnatal mouse excisional wounds were also analyzed for Wnt-4 expression by real-time polymerase chain reaction. In E17 fibroblasts after TGF-beta1 stimulation, Wnt-4 expression increased 4-fold at 1 hour (p stimulation, but peak expression was larger and relatively delayed, with a 17-fold increase at 12 hours (p fetal skin, Wnt-4 expression was 3.5-fold greater compared with 3-week-old mice (p fetal scarless and postnatal scarring mouse wound repair. The authors' data suggest that TGF-beta directly increases Wnt-4 expression in fetal and postnatal fibroblasts and that Wnt-4 is increased in both fetal and postnatal repair.

  12. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

    Science.gov (United States)

    Guo, Shang-Chun; Tao, Shi-Cong; Yin, Wen-Jing; Qi, Xin; Yuan, Ting; Zhang, Chang-Qing

    2017-01-01

    Chronic wounds have become an economic, social, and public health burden and need advanced treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds because it contains an abundance of growth factors secreted by platelets. The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors from platelets. This study is the first to show that these exosomes may exert the function of PRP. PRP-Exos can effectively induce proliferation and migration of endothelial cells and fibroblasts to improve angiogenesis and re-epithelialization in chronic wounds. We regulated YAP to verify the PRP-Exos-dependent effect on fibroblast proliferation and migration through YAP activation. In vivo, we observed the cutaneous healing process in chronic wounds treated with PRP-Exos in a diabetic rat model. We provide evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. PMID:28042318

  13. Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing.

    Science.gov (United States)

    Boniakowski, Anna E; Kimball, Andrew S; Jacobs, Benjamin N; Kunkel, Steven L; Gallagher, Katherine A

    2017-07-01

    The healing of cutaneous wounds is dependent on the progression through distinct, yet overlapping phases of wound healing, including hemostasis, inflammation, proliferation, and resolution/remodeling. The failure of these phases to occur in a timely, progressive fashion promotes pathologic wound healing. The macrophage (MΦ) has been demonstrated to play a critical role in the inflammatory phase of tissue repair, where its dynamic plasticity allows this cell to mediate both tissue-destructive and -reparative functions. The ability to understand and control both the initiation and the resolution of inflammation is critical for treating pathologic wound healing. There are now a host of studies demonstrating that metabolic and epigenetic regulation of gene transcription can influence MΦ plasticity in wounds. In this review, we highlight the molecular and epigenetic factors that influence MΦ polarization in both physiologic and pathologic wound healing, with particular attention to diabetic wounds. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trostrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    . An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time...... of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although...

  15. Skin wound healing and phytomedicine: a review.

    Science.gov (United States)

    Pazyar, Nader; Yaghoobi, Reza; Rafiee, Esmail; Mehrabian, Abolfath; Feily, Amir

    2014-01-01

    Skin integrity is restored by a physiological process aimed at repairing the damaged tissues. The healing process proceeds in four phases: hemostasis, inflammation, proliferation and remodeling. Phytomedicine presents remedies, which possess significant pharmacological effects. It is popular amongst the general population in regions all over the world. Phytotherapeutic agents have been largely used for cutaneous wound healing. These include Aloe vera, mimosa, grape vine, Echinacea, chamomile, ginseng, green tea, jojoba, tea tree oil, rosemary, lemon, soybean, comfrey, papaya, oat, garlic, ginkgo, olive oil and ocimum. Phytotherapy may open new avenues for therapeutic intervention on cutaneous wounds. This article provides a review of the common beneficial medicinal plants in the management of skin wounds with an attempt to explain their mechanisms.

  16. Thrombin as important factor for cutaneous wound healing: comparison of fibrin biomatrices in vitro and in a rat excisional wound healing model.

    Science.gov (United States)

    Gugerell, Alfred; Pasteiner, Waltraud; Nürnberger, Sylvia; Kober, Johanna; Meinl, Alexandra; Pfeifer, Sabine; Hartinger, Joachim; Wolbank, Susanne; Goppelt, Andreas; Redl, Heinz; Mittermayr, Rainer

    2014-01-01

    Fibrin biomatrices have been used for many years for hemostasis and sealing and are a well-established surgical tool. The objective of the present study was to compare two commercially available fibrin biomatrices regarding the effect of their thrombin concentration on keratinocytes and wound healing in vitro and in vivo. Keratinocytes showed significant differences in adhesion, viability, and morphology in the presence of the fibrin matrices in vitro. A high thrombin concentration (800-1,200 IU/mL) caused deteriorated cell compatibility. By using a thrombin inhibitor, those differences could be reversed. In a rat excisional wound healing model, we observed more rapid wound closure and less wound severity in wounds treated with a fibrin matrix containing a lower concentration of thrombin (4 IU/mL). Furthermore, fewer new functional vessels and a lower level of vascular endothelial growth factor were measured in wounds after 7 days treated with the matrix with higher thrombin concentration. These in vivo results may be partially explained by the in vitro biocompatibility data. Additionally, results show that low thrombin biomatrices were degraded faster than the high thrombin material. Hence, we conclude that the composition of fibrin biomatrices influences keratinocytes and therefore has an impact on wound healing.

  17. Maggot therapy for repairing serious infective wound in a severely burned patient

    Directory of Open Access Journals (Sweden)

    WU Jun-cheng

    2012-04-01

    Full Text Available 【Abstract】The larvae of musca domestica were put in use to discard the dead tissue of a case of severe burn. A total of 50 000 aseptic maggots were put onto the infective wound surface, and aseptic dressings overlaid the surface. Three days later, another 20 000 maggots were put onto the wound for the second therapy. After twice maggot debridement, most necrotic muscle tissues of the wound were cleaned up, and eventually fresh granulation tissue grew and later the wound was covered and healed by 3 times of skin grafting. The result demonstrates that maggot therapy is safe and effective with no adverse complications except pain. Key words: Biological therapy; Wound infection; Burns; Wound healing; Debridement

  18. EPO reverses defective wound repair in hypercholesterolaemic mice by increasing functional angiogenesis.

    Science.gov (United States)

    Elsherbiny, Ahmed; Högger, Dominik C; Borozadi, Meisam Khorrami; Schmidt, Christian A; Plock, Jan; Largo, Rene D; Lindenblatt, Nicole; Giovanoli, Pietro; Contaldo, Claudio

    2012-11-01

    This study aims to elucidate the effect of erythropoietin (EPO) on the microcirculation during wound healing in mice genetically depleted of apolipoprotein E (ApoE(-/-)). The skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. Animals received Recormon(®) 1000 U kg(-1) body weight (BW) intra-peritoneally (i.p.) at day 1, 3, 5, 7, 9 and 11 post-wounding at a concentration of 100 Uml(-1) (n=42). Normal healing and vehicle-treated wild type animals (WT) served as controls. The microcirculation of the wound was analysed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Microtomography (micro-CT) analysis of casted wound microvessels was performed allowing three-dimensional (3D) histomorphometric analysis. Tissue samples were examined ex vivo for wound scoring and for expression analysis of EPO-Receptor (Epo-R) and endothelial nitric oxide synthase (eNOS). Upon EPO treatment, the total wound score in ApoE(-/-) mice was increased by 23% on day 3, by 26% on day 7 and by 18% on day 13 when compared to untreated ApoE(-/-) mice (all PEpo-R expression (4.6-fold on day 3 and 13.5-fold on day 7) and eNOS expression (2.4-fold on day 7) (all PEPO treatment reverses microvascular dysfunction during wound healing in hypercholesterolaemic mice by inducing new vessel formation and by providing the wound with more oxygen.

  19. Effect of a Semisolid Formulation of Linum usitatissimum L. (Linseed Oil on the Repair of Skin Wounds

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    Eryvelton de Souza Franco

    2012-01-01

    Full Text Available The purpose of this study was to investigate the effects of a semisolid formulation of linseed oil, SSFLO (1%, 5%, or 10% or in natura linseed oil on skin wounds of rats. We used wound models, incisional and excisional, to evaluate, respectively, the contraction/reepithelialization of the wound and resistance to mechanical traction. The groups (n=6 treated with SSFLO (1% or 5% began the process of reepithelialization, to a significant extent (P<.05, on the sixth day, when compared to the petroleum jelly control group. On 14th day for the groups treated with SSFLO (1% or 5%, 100% reepithelialization was found, while in the petroleum jelly control group, this was only 33.33%. Our study showed that topical administration of SSFLO (1% or 5% in excisional wounds allowed reepithelialization in 100% of treated animals. Therefore, a therapeutic potential of linseed oil, when used at low concentrations in the solid pharmaceutical formulations, is suggested for the process of dermal repair.

  20. Transforming growth factor-β (TGF-β) activation in cutaneous wounds after topical application of aloe vera gel.

    Science.gov (United States)

    Takzaree, Nasrin; Hadjiakhondi, Abbas; Hassanzadeh, Gholamreza; Rouini, Mohammad Reza; Manayi, Azadeh; Zolbin, Masoumeh Majidi

    2016-12-01

    Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-β gene expression in the wound bed. Sixty Wistar rats weighing 200-250 g were placed under anesthesia in sterile conditions. A square 1.5 cm × 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson's Trichrome. Wound surface and wound healing were evaluated separately. TGF-β gene expression was analyzed by RT-PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-β gene expression, ultimately accelerating the wound healing process.

  1. Histopathological and clinical evaluation of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rats: an experimental study.

    Science.gov (United States)

    Barati, Fardin; Javanbakht, Javad; Adib-Hashemi, Farajollah; Hosseini, Ehsan; Safaeie, Reyhaneh; Rajabian, Mojtaba; Razmjoo, Mostafa; Sedaghat, Reza; Aghamohammad Hassan, Mehdi

    2013-07-17

    Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. The aim of this study was to evaluate clinical and histopathological alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rat. In present study 24 Wister -albino rats weighing 150-200 g were selected and divided to two treatment groups as Nitrofurazone ointment (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM) route. Furthermore, upon preparation of dorsal region of the animal for surgery, a piece of full-thickness skin removed (2 × 2 cm). In order to comparing wounds healing clinically and histologically, once every four days from the commencement, the wounds were photographed and the healed surface was measured by Scion image software. The clinical findings indicated that the Kombucha fungus resulted in precipitating healing than Nitrofurazone; however, it was not significant (p > 0.05). In order to pathological comparing of wound healing process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days. Additionally, the histopathological results demonstrated that there was inflammation in Nitrofurazone group through twelveth day, somehow the epithelium was formed and abundant vessels were visible. Although on 16th day and the previous days the healing condition of Kombucha fungus was considered as minimal rate, revealing it is similar to Nitrofurazone group on 20th day. To wrap up. These observations suggest that the Kombucha fungus healing quality was rapid from 12th day to the end of the research, whereas no significant difference was observed. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196.

  2. The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.

    Directory of Open Access Journals (Sweden)

    Inna Maltseva

    Full Text Available Corneal epithelial wound repair involves the migration of epithelial cells to cover the defect followed by the proliferation of the cells to restore thickness. Heparan sulfate proteoglycans (HSPGs are ubiquitous extracellular molecules that bind to a plethora of growth factors, cytokines, and morphogens and thereby regulate their signaling functions. Ligand binding by HS chains depends on the pattern of four sulfation modifications, one of which is 6-O-sulfation of glucosamine (6OS. SULF1 and SULF2 are highly homologous, extracellular endosulfatases, which post-synthetically edit the sulfation status of HS by removing 6OS from intact chains. The SULFs thereby modulate multiple signaling pathways including the augmentation of Wnt/ß-catenin signaling. We found that wounding of mouse corneal epithelium stimulated SULF1 expression in superficial epithelial cells proximal to the wound edge. Sulf1⁻/⁻, but not Sulf2⁻/⁻, mice, exhibited a marked delay in healing. Furthermore, corneal epithelial cells derived from Sulf1⁻/⁻ mice exhibited a reduced rate of migration in repair of a scratched monolayer compared to wild-type cells. In contrast, human primary corneal epithelial cells expressed SULF2, as did a human corneal epithelial cell line (THCE. Knockdown of SULF2 in THCE cells also slowed migration, which was restored by overexpression of either mouse SULF2 or human SULF1. The interchangeability of the two SULFs establishes their capacity for functional redundancy. Knockdown of SULF2 decreased Wnt/ß-catenin signaling in THCE cells. Extracellular antagonists of Wnt signaling reduced migration of THCE cells. However in SULF2- knockdown cells, these antagonists exerted no further effects on migration, consistent with the SULF functioning as an upstream regulator of Wnt signaling. Further understanding of the mechanistic action of the SULFs in promoting corneal repair may lead to new therapeutic approaches for the treatment of corneal injuries.

  3. Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair

    Directory of Open Access Journals (Sweden)

    Theoret Christine L

    2008-01-01

    Full Text Available Abstract Background Wound healing in horses is fraught with complications. Specifically, wounds on horse limbs often develop exuberant granulation tissue which behaves clinically like a benign tumor and resembles the human keloid in that the evolving scar is trapped in the proliferative phase of repair, leading to fibrosis. Clues gained from the study of over-scarring in horses should eventually lead to new insights into how to prevent unwanted scar formation in humans. cDNA fragments corresponding to CTNNB1 (coding for β-catenin and PECAM1, genes potentially contributing to the proliferative phase of repair, were previously identified in a mRNA expression study as being up-regulated in 7 day wound biopsies from horses. The aim of the present study was to clone full-length equine CTNNB1 and PECAM1 cDNAs and to study the spatio-temporal expression of mRNAs and corresponding proteins during repair of body and limb wounds in a horse model. Results The temporal pattern of the two genes was similar; except for CTNNB1 in limb wounds, wounding caused up-regulation of mRNA which did not return to baseline by the end of the study. Relative over-expression of both CTNNB1 and PECAM1 mRNA was noted in body wounds compared to limb wounds. Immunostaining for both β-catenin and PECAM1 was principally observed in endothelial cells and fibroblasts and was especially pronounced in wounds having developed exuberant granulation tissue. Conclusion This study is the first to characterize equine cDNA for CTNNB1 and PECAM1 and to document that these genes are expressed during wound repair in horses. It appears that β-catenin may be regulated in a post-transcriptional manner while PECAM1 might help thoracic wounds mount an efficient inflammatory response in contrast to what is observed in limb wounds. Furthermore, data from this study suggest that β-catenin and PECAM1 might interact to modulate endothelial cell and fibroblast proliferation during wound repair in the

  4. Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

    NARCIS (Netherlands)

    Cremers, N.A.J.; Suttorp, M.; Gerritsen, M.M.; Wong, R.J.; Run-van Breda, C. van; Dam, G.M. van; Brouwer, K.M.; Kuijpers-Jagtman, A.M.; Carels, C.E.L.; Lundvig, D.M.; Wagener, F.A.D.T.G.

    2015-01-01

    Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orch

  5. Injectable Polyurethane Composite Scaffolds Delay Wound Contraction and Support Cellular Infiltration and Remodeling in Rat Excisional Wounds

    Science.gov (United States)

    Adolph, Elizabeth J.; Hafeman, Andrea E.; Davidson, Jeffrey M.; Nanney, Lillian B.; Guelcher, Scott A.

    2011-01-01

    Injectable scaffolds present compelling opportunities for wound repair and regeneration due to their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound width and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable polyurethane biocomposite scaffold that enhances cutaneous wound healing in a rat model. PMID:22105887

  6. The alarmin HMGB-1 influences healing outcomes in fetal skin wounds.

    Science.gov (United States)

    Dardenne, Adrienne D; Wulff, Brian C; Wilgus, Traci A

    2013-01-01

    In mice, cutaneous wounds generated early in development (embryonic day 15, E15) heal scarlessly, while wounds generated late in gestation (embryonic day 18, E18) heal with scar formation. Even though both types of wounds are generated in the same sterile uterine environment, scarless fetal wounds heal without inflammation, but a strong inflammatory response is observed in scar-forming fetal wounds. We hypothesized that altered release of alarmins, endogenous molecules that trigger inflammation in response to damage, may be responsible for the age-related changes in inflammation and healing outcomes in fetal skin. The purpose of this study was to determine whether the alarmin high-mobility group box-1 (HMGB-1) is involved in fetal wound repair. Immunohistochemical analysis showed that in unwounded skin, E18 keratinocytes expressed higher levels of HMGB-1 compared with E15 keratinocytes. After injury, HMGB-1 was released to a greater extent from keratinocytes at the margin of scar-forming E18 wounds, compared with scarless E15 wounds. Furthermore, instead of healing scarlessly, E15 wounds healed with scars when treated with HMGB-1. HMGB-1-injected wounds also had more fibroblasts, blood vessels, and macrophages compared with control wounds. Together, these data suggest that extracellular HMGB-1 levels influence the quality of healing in cutaneous wounds. © 2013 by the Wound Healing Society.

  7. The efficacy of moisture retentive ointment in the mangement of cutaneous wounds and ulcers: A multicenter clinical trial

    Directory of Open Access Journals (Sweden)

    Atiyeh B

    2003-01-01

    Full Text Available Local management of chronic wounds and ulcers remains one of the most costly unsolved problems in health care today. With proper clinical management, most chronic wound healing problems can be resolved and healing expected, though recurrence may be common. The recent logarithmic growth in our knowledge about wound healing and the appreciation of the importance of a moist environment in optimal wound healing has led to the introduction of new and exciting therapeutic modalities. In view of the many practical disadvantages as well as the serious complications of currently available moisture retentive dressings when applied to chronic contaminated wounds, a prospective multicenter clinical trial was conducted from December 1999 to November 2000 to evaluate the safety and efficacy of a newly introduced moisture retentive ointment (MEBO: Moist Exposed Burn Ointment (Julphar - Gulf Pharmaceutical Industries, UAE in the local wound care of problematic non-healing wounds. The active component of the ointment is β-sitosterol in a base of beeswax, sesame oil and other components. Though it was not a comparative study, the ointment was found to induce rapid reduction in ulcer size even after a prolonged stagnant state with other therapeutic modalities without complications such as skin maceration, unmanageable excessive exudation, and wound infection. As expected with such chronic wounds, the healing potential of local ointment application is limited by the mere size of the original defect and the underlying pathologies and associated diseases. however, the safety and practicality of simple ointment application was found to be a valid alternative treatment for local management of chronic wounds.

  8. Rapid Healing of Cutaneous Leishmaniasis by High-Frequency Electrocauterization and Hydrogel Wound Care with or without DAC N-055: A Randomized Controlled Phase IIa Trial in Kabul

    Science.gov (United States)

    Steiner, Reto; Wentker, Pia; Mahfuz, Farouq; Stahl, Hans-Christian; Amin, Faquir Mohammad; Bogdan, Christian; Stahl, Kurt-Wilhelm

    2014-01-01

    Background Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1st), after wound closure (2nd) and after 6 months (3rd). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p = 0.83). In patients with Leishmania-positive 2nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of

  9. Rapid healing of cutaneous leishmaniasis by high-frequency electrocauterization and hydrogel wound care with or without DAC N-055: a randomized controlled phase IIa trial in Kabul.

    Directory of Open Access Journals (Sweden)

    Ahmad Fawad Jebran

    2014-02-01

    Full Text Available Anthroponotic cutaneous leishmaniasis (CL due to Leishmania (L. tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL.From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC followed by daily moist-wound-treatment (MWT with polyacrylate hydrogel with (group I or without (group II pharmaceutical sodium chlorite (DAC N-055. Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immunohistopathological analyses were taken prior to EC (1(st, after wound closure (2(nd and after 6 months (3(rd. The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d and II (54 patients, 42 d; p = 0.83. In patients with Leishmania-positive 2(nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08. Superinfections occurred in both groups at the same rate (8.8%. Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158 were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes.Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of wound closure in a subgroup of patients with parasite persistence warrant

  10. Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation.

    Science.gov (United States)

    Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

    2016-01-01

    Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.

  11. Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation

    Directory of Open Access Journals (Sweden)

    Li Z

    2016-06-01

    Full Text Available Zehao Li,1 Meifeng Liu,1 Huijuan Wang,1 Song Du21School of Chemistry and Chemical Engineering, Guangdong Provincial Key Laboratory for Green Chemical Product Technology, South China University of Technology, Guangzhou, 2Guangdong Jiabao Pharmaceutical Co., Ltd., Qingyuan, People’s Republic of ChinaAbstract: Madecassoside (MA is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was <12% even at 37°C and <5% at 4°C within 1 month. In vitro skin permeation, skin distribution, and burn wound healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.Keywords: madecassoside liposomes, double-emulsion method, skin permeation, wound-healing effect, transdermal property

  12. Recombinant 1F9 spidroin microgels for murine full-thickness wound repairing.

    Science.gov (United States)

    Moisenovich, M M; Malyuchenko, N V; Arkhipova, A Yu; Goncharenko, A V; Kotlyarova, M S; Davydova, L I; Vasil'eva, T V; Bogush, V G; Agapov, I I; Debabov, V G; Kirpichnikov, M P

    2016-01-01

    The study of the stimulating effect of the microgels (MGs) based on recombinant 1F9 spidroin on the regeneration of the deep skin wound in mice was carried out. The use of spidroin MGs was shown to increase significantly the quality of healing compared to the control. The introduction of the MG in the wound edges led to recovery of all the structural elements of the skin: the epidermis, the dermis, including vascular and nervous network, in the periphery of the wound underlying muscles, and skin appendages (sebaceous and sweat glands and hair follicles) was revealed.

  13. Evaluation of the effect of LED radiation in the repair of skin wounds on the dorsum of rats with iron deficiency anemia

    Science.gov (United States)

    de Oliveira, Susana Carla Pires Sampaio; de Carvalho Monteiro, Juliana Santos; dos Santos Aciole, Gilberth Tadeu; DeCastro, Isabele Cardoso V.; Menezes, Diego Silva; de Fátima Lima Ferreira, Maria; dos Santos, Jean Nunes; Zanin, Fátima; Barbosa Pinheiro, Antônio Luiz

    2010-05-01

    Iron deficiency anemia causes reduction on the level of hemoglobin and of the number of RBC and affects around 35% of the human population. Laser and LED therapies have been successfully used on wound healing studies. The aim of the present study was to assess histologically the effect of LED Phototherapy on the healing of cutaneous wounds on anemic rats. Fifty one 21 days old male wistar rats weighting around 50 g were kept under iron free die (Sem ferro-AIN93-G) during 15 days in order to induce anemia. Non treated animals acted as controls. A standartized cutaneous wound was created on the dorsum of each animal whom were distributed into four groups: Group I—Anemia+LED, Group II—Non anemic+LED, Group III—Anemia+no treatment, Group IV—No anemic+no-treatment. Irradiation started immediately after surgery and repeated at 48 h intervals during 21 days. Animal death occurred after 7, 14 and 21 days after wounding. The results of the histologic analysis showed that LED Phototherapy stimulated fibroblastic proliferation. It is concluded that LED irradiation improves wound healing on iron deficient anemic animals.

  14. Maggot therapy for repairing serious infective wound in a severely burned patient

    Institute of Scientific and Technical Information of China (English)

    WU Jun-cheng; LU Ren-rong; HUO Ran; FU Hong-bin

    2012-01-01

    The larvae of musca domestica were put in use to discard the dead tissue of a case of severe burn.A total of 50 000 aseptic maggots were put onto the infective wound surface,and aseptic dressings overlaid the surface.Three days later,another 20 000 maggots were put onto the wound for the second therapy.After twice maggot debridement,most necrotic muscle tissues of the wound were cleaned up,and eventually fresh granulation tissue grew and later the wound was covered and healed by 3 times of skin grafting.The result demonstrates that maggot therapy is safe and effective with no adverse complications except pain.

  15. Platelet-rich fibrin versus albumin in surgical wound repair: a randomized trial with paired design

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Ågren, Sven Per Magnus; Jørgensen, Lars Nannestad

    2010-01-01

    To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial.......To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial....

  16. Platelet-rich fibrin versus albumin in surgical wound repair: a randomized trial with paired design

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Ågren, Sven Per Magnus; Jørgensen, Lars Nannestad

    2010-01-01

    To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial.......To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial....

  17. Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation

    OpenAIRE

    Li Z; Liu M; Wang H; Du S

    2016-01-01

    Zehao Li,1 Meifeng Liu,1 Huijuan Wang,1 Song Du21School of Chemistry and Chemical Engineering, Guangdong Provincial Key Laboratory for Green Chemical Product Technology, South China University of Technology, Guangzhou, 2Guangdong Jiabao Pharmaceutical Co., Ltd., Qingyuan, People’s Republic of ChinaAbstract: Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane per...

  18. Topical Moltkia coerulea hydroethanolic extract accelerates the repair of excision wound in a rat model

    Institute of Scientific and Technical Information of China (English)

    Mohammad Reza Farahpour; Aydin Dilmaghanian; Maisam Faridy; Esmaeil Karashi

    2016-01-01

    Purpose:To evaluate the effect of a hydroethanolic extract of Moltkia coerulea ointment (MCO) on the healing of excision wound in a rat model.Methods:Circular surgical full thickness excision wound,with 314 mm2 size,was induced in the anterior-dorsal side of each rat.Three different doses of MCO (1%,3% and 6%) were administrated.On Day 3,7,14 and 21,the tissue was sampled and immune cells,fibroblasts and fibrocytes distribution per one mm2 of wound area,collagen density and re-epithelialization were analyzed.Moreover,the total flavnoid,phenols and anti-oxidant potential of the MCO were evaluated.Ultimately,the percentage of wound contraction in different groups was compared with each other.Results:Hydroethanolic extract of MCO significantly (p < 0.05) increased wound contraction percentage.The animals in medium and high dose MCO-treated groups exhibited remarkably (p < 0.05) higher fibroblast and fibrocyte distribution and significantly (p < 0.05) lower immune cells infiltration.On Day 7 after injury,MCO up-regulated neovascularization in a dose-dependent way.Conclusion:Our data showed that MCO shortened the inflammation phase by provoking the fibroblast proliferation.Moreover,MCO promoted the healing process by up-regulating the angiogenesis and provoking the structural cells proliferation as well as increasing the collagen synthesis,cross-linking,and deposition.

  19. Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

    Science.gov (United States)

    Wu, Chia-Lung; Kimmerling, Kelly A.; Little, Dianne; Guilak, Farshid

    2017-01-01

    High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity. PMID:28317846

  20. Laser induced wounding of the plasma membrane and methods to study the repair process.

    Science.gov (United States)

    Jimenez, Ana J; Maiuri, Paolo; Lafaurie-Janvore, Julie; Perez, Franck; Piel, Matthieu

    2015-01-01

    Cells are constantly exposed to agents that can trigger the perforation of their plasma membrane. This damage occurs naturally, and the frequency and intensity depends on how much cells are exposed to damaging threats. The following protocol is a simple and powerful method to damage the plasma membrane using laser ablation. It allows the induction of a single and localized wound at the plasma membrane of cultured cells, which can be followed with fast time-lapse imaging. The first part of the protocol describes simple cell culture techniques and the material ideal to make the experiments. A second part of the protocol gives advice about the procedures to make effective wounds in cells while ensuring a good survival rate. We also propose different ways to follow the opening and closure of the plasma membrane. Finally, we describe the procedure to efficiently analyze the data acquired after single cell photodamage to characterize the wounding process.

  1. Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair

    Science.gov (United States)

    Sperandio, Felipe F.; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C.; Giudice, Fernanda S.; Hamblin, Michael R.; Sousa, Suzana C.O.M.

    2015-01-01

    Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm2, 660nm, 100mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. PMID:25411997

  2. Cellular and molecular mechanisms of repair in acute and chronic wound healing.

    Science.gov (United States)

    Martin, P; Nunan, R

    2015-08-01

    A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.

  3. In vitro construction of tissue engineered skin for wound repair after escharectomy of third degree scald: An experimental study

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    Zhong-feng MA

    2016-01-01

    Full Text Available Objective  To observe the practicability and effect of tissue engineered skin for repairing the wound after escharectomy of third degree scald (TDSE in rat model. Methods  Epithelial cells and fibroblasts from newborn SD rats were isolated by enzyme digestion method and cultured in vitro, and porcine acellular dermal matrix (PADM without cytotoxicity was prepared by hyperosmotic saline/sodium hydroxide method. The fibroblasts were mixed with bovine type Ⅰ collagen and inoculated on the surface of PADM. Third passage of cultured epidermal cells from newborn SD rats were inoculated on the collagen surface of the dermal matrix to obtain tissue engineered skin, and it was used to prepare epidermal cell sheet. Forty-eight SD rats with TDSE wound were randomly divided into two groups, then tissue engineered skin (experiment group, and epidermal cell sheet (control group graftings were performed to cover the wounds respectively. Finally, gross observation and histological changes were observed in grafted area. The wound healing rate and wound contraction rate were compared between the two groups. Microvessel count (MVC was performed with antiCD34 monoclonal antibody immunohistochemical staining technique, and vascular endothelial cells were labeled. Basal membrane of the skin was identified by immunohistochemical anti-Laminin staining technique. Results  There was no obvious sign of acute rejection of the graft in both groups. The graft survival rate was 75.05%±3.69%, 83.12%±3.13% and 92.03%±3.87% at the 2th, 4th and 6th week respectively in the experimental group. The graft survival rate was 77.63%±3.23%, 83.17%±3.92% and 91.09%±3.35% at the 2th, 4th and 6th week in the control group. There was no significant difference between the two groups (P>0.05, but the contraction rate of the grafts was 9.13%±2.27%, 18.52%±3.40%, 23.92%±3.01% at the 2th, 4th, 6th week, respectively, in the experimental group, and 14.21%±3.05%, 29.12%±3

  4. Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

    Institute of Scientific and Technical Information of China (English)

    Fei; Li; Shao-Zhen; Zhao

    2014-01-01

    Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

  5. An experimental study of the effects of Matricaria chamomilla extract on cutaneous burn wound healing in albino rats.

    Science.gov (United States)

    Jarrahi, Morteza

    2008-03-20

    Previous studies conducted on the anti-inflammatory, antimicrobial and antioxidant effects of Matricaria chamomilla (chamomile) extract led us to study the effect of topical chamomile extract on burn wound healing in albino rats. Thirty male albino rats (250-300 g) were randomly divided into three groups, as control, vehicle, and treatment. Second-degree burning was induced in 20% of whole surface area of animal body by placing the back of animal into boiling water for 8s. Animals of control group received no treatment. Animals of vehicle and treatment groups were treated topically by olive oil and extract dissolved in olive oil twice a day respectively from the first day of burn induction to complete wound healing. The percentage of wound healing was calculated weekly. The results showed that there was significant difference (p < 0.05) between vehicle and treatment groups. So we concluded that the chamomile extract in the form of rubbing oil had a good potential for acceleration of burn wound healing in rats.

  6. MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2.

    Science.gov (United States)

    Wu, Yan; Zhong, Julia Li; Hou, Ning; Sun, Yaolan; Ma, Benting; Nisar, Muhammad Farrukh; Teng, Yan; Tan, Zhaoli; Chen, Keping; Wang, Youliang; Yang, Xiao

    2017-02-01

    Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Effects of Pistacia atlantica (subsp. Mutica oil extracts on antioxidant activities during experimentally induced cutaneous wound healing in rats

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Hamidi

    2015-01-01

    Full Text Available The fruits of Pistacia atlantica (subsp. mutica have been used traditionally for the treatment of peptic ulcer, as a mouth freshener and have recently been introduced as a source of antioxidant vegetable oils. The aim of this study was to investigate the antioxidant activity of the gel forms, from P. atlantica (subsp. mutica oil extraction on enzymatic antioxidants in experimental wound created in rat. A square-shaped skin defect (2×2 cm was created aseptically by surgical excision at the first thoracic vertebrae. Then animals were randomly allocated in four groups (I, untreated controls; II, topically treated base gel; III, topically treated 5% gel; IV, topically treated 10% gel. Blood sampling was accomplished at 3, 7, 10, 14 and 21 days post-injury. Samples were collected for measuring antioxidant enzymes activities (superoxide dismutase, catalase and glutathione peroxidase activity in red cells and lipid peroxidation (plasma malondialdehyde. The data analysis generally evidenced that the activities of the main antioxidant enzymes began to decrease significantly at 7 days after the wound was created in control and base gel groups. This remarkable decline became more evident in the period between 10 to 21 days post injury but increased progressively in P. atlantica (subsp. mutica treatment groups, especially in gel 10% treatment group during wound healing. The results of this study suggest that excision of the wound leads to oxidative stress and topical administration of P. atlantica (subsp. mutica gels causes remarkable changes in antioxidant parameter during wound closure (especially gel 10% via pro-oxidative, and antioxidant activity can improve oxidative stress.

  8. 注重创面修复的美学效果%Lay emphasis on the aesthetic effect of wound repair

    Institute of Scientific and Technical Information of China (English)

    张国安

    2012-01-01

    "Survival first" has been the leading rule in burn surgery for a long time. However,the life quality of patients in future should also be emphasized on the strategic level during the early treatment of patients with massive burn. Aesthetics is also extremely important in wound repair,and it should form a clear conception in the mind of the attending surgeons.Therefore, the aesthetic effect of each surgical intervention should be elaborated with all enough attention. Moreover,we should constantly improve our techniques and skills to obtain presentable postoperative appearance. In addition,we should emphasize the application of new techniques and materials in wound repair,with which to improve aesthetic effect.In conclusion,we should pay more attention to promoting the aesthetic effect in the treatment of burns and traumatic wounds to maintain our superior status in burn treatment in the world.

  9. Wound healing: a new approach to the topical wound care.

    Science.gov (United States)

    Öztürk, Ferdi; Ermertcan, Aylin Türel

    2011-06-01

    Cutaneous wound healing is a complex and well-coordinated interaction between inflammatory cells and mediators, establishing significant overlap between the phases of wound healing. Wound healing is divided into three major phases: inflammatory phase, proliferative phase, and remodeling phase. Unlike the acute wound, the nonhealing wound is arrested in one of the phases of healing, typically the inflammatory phase. A systematic approach to the management of the chronic nonhealing wound emphasizes three important elements of wound bed preparation in chronic wounds: debridement, moisture, and countering bacterial colonization and infection. In this article, wound-healing process and new approaches to the topical wound care have been reviewed.

  10. Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity

    Institute of Scientific and Technical Information of China (English)

    Konstantinos A Ekmektzoglou; Georgios C Zografos; Stavros K Kourkoulis; Ismene A Dontas; Panagiotis K Giannopoulos; Katerina A Marinou; Maria V Poulakou; Despina N Perrea

    2006-01-01

    AIM: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing.METHODS: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastomotic dehiscence and leakage.RESULTS: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [△s = △s (t)] were recorded for each test,permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastomotic failure. Quantitative data were obtained concerning the anastomotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison.CONCLUSION: This experimental model provides an excellent method of measuring anastomotic strength.Despite the relative small number of specimens used,this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure.

  11. Dermal Influence on Epidermal Resurfacing during the Repair of Split Thickness Wounds.

    Science.gov (United States)

    1986-06-01

    Normal Skin Collagen Biosynthesis Assay: Effects of 68 Repeated Sampling. Fig 12. Time Course for the Incorporation of 14C-proline by Minced Porcine Skin...69 Fig 13. Time Course for Relative Collagen Biosynthesis (%RCB) 70 Measured in Porcine Skin. Fig 14. The Effect of Platelet Homogenate Fraction (PHF...wound healing is made by a variety of measurements Including collagen deposition in sponge implants (Viljanto, 1964), histology of serial cross

  12. Pivotal role of ATP in macrophages fast tracking wound repair and regeneration.

    Science.gov (United States)

    Kotwal, Girish J; Sarojini, Harshini; Chien, Sufan

    2015-09-01

    Chronic wounds occurring during aging or diabetes pose a significant burden to patients. The classical four-phase wound healing process has a 3-6 day lag before granulation starts to appear and it requires an intermediate step of activation of resident fibroblasts during the remodeling phase for production of collagen. This brief communication discusses published articles that demonstrate how the entire wound healing process can be fast tracked by intracellular ATP delivery, which triggers a novel pathway where alternatively activated macrophages play absolutely critical and central roles. This novel pathway involves an increase in proinflammatory cytokines (TNF, IL-1β, IL-6) and a chemokine (MCP-1) release. This is followed by activation of purinergic receptor (a family of plasma membrane receptors found in almost all mammalian cells), production of platelets and platelet microparticles, and activation of ATP-dependent chromatin remodeling enzymes. The end result is a massive influx and in situ proliferation of macrophages, increases in vascular endothelial growth factors that promote neovascularization, and most prominently, the direct production of collagen.

  13. MODULATION OF THE INFLAMMATORY CYTOKINES AND CYTOPROTECTIVE ENZYME BY BILIRUBIN TREATMENT TO ENHANCE CUTANEOUS WOUND HEALING IN RATS

    Directory of Open Access Journals (Sweden)

    Raju Prasad

    2017-06-01

    Full Text Available Inflammation is the main process of wound healing where expression of certain cytokines likes Interleukin-10 (IL-10 and Tumour necrosis factor ∝ (TNF ∝ plays an important role. In view of the antioxidant potential of bilirubin, the present study was aimed to evaluate time-dependent (day 3, 7, 14 wound healing effects of bilirubin ointment (0.3% in excisional wound model in rats. Thirty-six acclimatized healthy male Wistar rats (120-150g were divided into control and treated groups containing 18 rats each. Each group was further sub- divided into three sub-groups (day 3, 7 and 14 days, n= 6. The ointment base (soft paraffin 90%, lanolin 5% and hard paraffin 5% and bilirubin ointment (0.3% were applied topically once daily for 14 days in control and treated group respectively. The wound area was determined on days 3, 7, and 14. The mRNA expression of TNF ∝ gene and IL-10 gene were determined on days 3, 7 and 14 by Real Time PCR and their protein levels by ELISA method. The protein expression of cyto-protective enzyme HO-1 (Heme oxygenage-1 and growth factor VEGF (Vascular growth factor was determined by western blotting method. The mRNA expression and protein level of TNF ∝ was significantly reduced and IL-10 was significantly increased whereas the expression of HO-1 enzyme and VEGF was significantly increased in treated group on days 3, 7 and 14. It may be concluded that the bilirubin has pro-healing potential.

  14. “Sugar-coating wound repair: A review of FGF-10 and dermatan sulfate in wound healing and their potential application in burn wounds”

    OpenAIRE

    Plichta, Jennifer K.; Radek, Katherine A.

    2012-01-01

    Thousands of patients suffer from burn injuries each year, yet few therapies have been developed to accelerate the wound healing process. Most fibroblast growth factors (FGFs) have been extensively evaluated, but only a few have been found to participate in wound healing. In particular, FGF-10 is robustly increased in the wound microenvironment following injury and has demonstrated some ability to promote wound healing in vitro and in vivo. Glycosaminoglycans (GAGs) are linear carbohydrates t...

  15. In vivo and in vitro cellular response to PEG-based hydrogels for wound repair

    Science.gov (United States)

    Waldeck, Heather

    Biomaterials are continuously being explored as a means to support, improve, or influence wound healing processes. Understanding the determining factors controlling the host response to biomaterials is crucial in developing strategies to employ materials for biomedical uses. In order to evaluate the host response to poly(ethylene glycol) (PEG)-based hydrogels, both in vivo and in vitro studies were performed to determine its efficacy as a dermal wound treatment and to investigate the mechanisms controlling cell-material interaction, respectively. The results of an in vivo study using a full thickness wound in a rat model demonstrated that both soluble and immobilized bioactive factors could be incorporated into a PEG-based semi-interpenetrating network (sIPN) to enhance the rate and the quality of dermal wound healing. To gain a better understanding of the results observed in vivo, in vitro studies were then conducted to examine the dynamics and mechanisms of the cell-material interaction. Degradation of the sIPN was explored as an influential factor in both mediating cellular response and controlling solute transport from the material. As degradation through gelatin dissolution could be influenced by simple alterations to the material formulation, these results provide facile guidelines to control the delivery of high molecular weight compounds. Further investigation of the cellular response to PEG-based biomaterials focused on key factors influencing cell-material interaction. Specifically, the role of the beta1 integrin subunit and several serum proteins (TGF-aalpha, IL-1beta and PDGF-BB) in mediating cellular response was explored. As cell-material interactions are based on commonly occurring interfaces between cells and molecules of the native extracellular environment, these studies provided insight into the mechanisms controlling the observed cellular response. Finally, the inflammatory response of primary monocytes to biomaterials was examined. Monocytes

  16. [Problems posed during surgical repair of a gunshot wound in the mandible].

    Science.gov (United States)

    Roulaud, J P; Tournaire, J; Roux, R

    1975-09-01

    The authors present a case of a balistic lesion of the labio-mental region after attempted suicide. They expose the different procedures used for its repair and attempt to analyze the problems which arose from the therapeutic standpoint. They lay stress on the necessity to immobilize these mandibular fragments in good occlusion, as rapidly as possibly.

  17. Modulation of MCP-1, TGF-β1, and α-SMA Expressions in Granulation Tissue of Cutaneous Wounds Treated with Local Vitamin B Complex: An Experimental Study

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    Carla P. Martinelli-Kläy

    2014-11-01

    Full Text Available Vitamin B complex can modulate the inflammatory response and activate wound healing. However, the action mechanisms involved in this process are still unclear. The aim of this study was to evaluate the effects of vitamin B complex on the modulation of monocyte chemotactic protein (MCP-1, transforming growth factor (TGF-β1, and α-smooth muscle actin (α-SMA in granulation tissue growth. Cutaneous ulcers on Wistar rats were topically treated with vitamin B complex. MCP-1, TGF-β1, and α-SMA expressions were evaluated 24, 72, and 168 h after the treatment. Inflammatory cells were counted and collagen fibril staining was performed. After 24 h, more mononuclear cells (p ≤ 0.01 and a higher MCP-1 (p ≤ 0.05 and TGF-β1 (p ≤ 0.01 expression were observed. After 72 h, the number of fibroblasts and mononuclear cells (p ≤ 0.05 was elevated. After 168 h, an increased number of fibroblasts, myofibroblasts, and blood vessels (p ≤ 0.01 as well as a strong intensity of collagen fibril staining were seen. At that point, the cells presented a higher TGF-β1 expression (p ≤ 0.05, and the size of the ulcer area was decreased (p ≤ 0.01. We can conclude that vitamin B complex may stimulate a positive modulation of MCP-1, TGF-β1, and α-SMA expressions in granulation tissue of cutaneous ulcers. © 2014 S. Karger AG, Basel

  18. Repair of Staphylococcus aureus-infected wound with gene-modified C3H10T1/2 cells expressing BPI-BD3 fusion antibiotic peptide

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    Xin-ran ZHANG

    2015-10-01

    Full Text Available Objective To study the antibacterial and tissue reparative effect of BPI-BD3 gene-modified mesenchymal stem cells in a mouse model of wound infection. Methods C3H10T1/2 cells were transfected with recombinant adenovirus vector pAdxsi-BPI-BD3, the expression of BPI-BD3 fusion protein was verified by RT-PCR and Western blotting. Excision wound with a diameter of 1cm was inoculated with Staphylococcus aureuswas made on the back of 30 mice. The mice were randomly divided into 3 groups (10 each. Mice in group T were injected with BPI-BD3 gene-modified C3H10T1/2 cells through caudal vein, those in group C were injected with unmodified C3H10T1/2 cells, and in group N were injected with PBS as control. The wound repair result was evaluated by estimation of the percentage of remaining wound area and the amount of wound bacteria under the scar, followed by observation of pathological changes. Inflammatory reactions of the wounds were assessed accordingly. Results The amount of bacteria under the scar was less in group T than in the other two groups (P<0.05. It was also found that the wound healing process was faster in group T than in group C and group N. Pathological observation showed that the inflammatory reaction in group T was also significantly milder than in the other two groups. Conclusion BPI-BD3 gene-modified mesenchymal stem cells may enhance wound repair by controlling infection and promoting tissue regeneration, thus it may be promising in clinical application. DOI: 10.11855/j.issn.0577-7402.2015.09.07

  19. Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

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    Mona Zarifpour

    2017-05-01

    Full Text Available Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI. Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume, consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

  20. Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40

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    Kligman Lorraine H

    2001-08-01

    Full Text Available Abstract Background SPARC is a matricellular protein involved in cell-matrix interactions. From expression patterns at the wound site and in vitro studies, SPARC has been implicated in the control of wound healing. Here we examined the function of SPARC in cutaneous wound healing using SPARC-null mice and dermal fibroblasts derived from them. Results In large (25 mm wounds, SPARC-null mice showed a significant delay in healing as compared to wild-type mice (31 days versus 24 days. Granulation tissue formation and extracellular matrix protein production were delayed in small 6 mm SPARC-null wounds initially but were resolved by day 6. In in vitro wound-healing assays, while wild-type primary dermal fibroblasts showed essentially complete wound closure at 11 hours, wound closure of SPARC-null cells was incomplete even at 31 hours. Addition of purified SPARC restored the normal time course of wound closure. Treatment of SPARC-null cells with mitomycin C to analyze cell migration without cell proliferation showed that wound repair remained incomplete after 31 hours. Cell proliferation as measured by 3H-thymidine incorporation and collagen gel contraction by SPARC-null cells were not compromised. Conclusions A significant delay in healing large excisional wounds and setback in granulation tissue formation and extracellular matrix protein production in small wounds establish that SPARC is required for granulation tissue formation during normal repair of skin wounds in mice. A defect in wound closure in vitro indicates that SPARC regulates cell migration. We conclude that SPARC plays a role in wound repair by promoting fibroblast migration and thus granulation tissue formation.

  1. Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.

    Science.gov (United States)

    Agis, Hermann; Collins, Amy; Taut, Andrei D; Jin, Qiming; Kruger, Laura; Görlach, Christoph; Giannobile, William V

    2014-01-01

    Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds.

  2. A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair.

    Directory of Open Access Journals (Sweden)

    Michèle Telorack

    2016-01-01

    Full Text Available The tripeptide glutathione is the most abundant cellular antioxidant with high medical relevance, and it is also required as a co-factor for various enzymes involved in the detoxification of reactive oxygen species and toxic compounds. However, its cell-type specific functions and its interaction with other cytoprotective molecules are largely unknown. Using a combination of mouse genetics, functional cell biology and pharmacology, we unraveled the function of glutathione in keratinocytes and its cross-talk with other antioxidant defense systems. Mice with keratinocyte-specific deficiency in glutamate cysteine ligase, which catalyzes the rate-limiting step in glutathione biosynthesis, showed a strong reduction in keratinocyte viability in vitro and in the skin in vivo. The cells died predominantly by apoptosis, but also showed features of ferroptosis and necroptosis. The increased cell death was associated with increased levels of reactive oxygen and nitrogen species, which caused DNA and mitochondrial damage. However, epidermal architecture, and even healing of excisional skin wounds were only mildly affected in the mutant mice. The cytoprotective transcription factor Nrf2 was strongly activated in glutathione-deficient keratinocytes, but additional loss of Nrf2 did not aggravate the phenotype, demonstrating that the cytoprotective effect of Nrf2 is glutathione dependent. However, we show that deficiency in glutathione biosynthesis is efficiently compensated in keratinocytes by the cysteine/cystine and thioredoxin systems. Therefore, our study highlights a remarkable antioxidant capacity of the epidermis that ensures skin integrity and efficient wound healing.

  3. Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.

    Directory of Open Access Journals (Sweden)

    Hermann Agis

    Full Text Available Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds.

  4. The nuclear hormone receptor coactivator NRC is a pleiotropic modulator affecting growth, development, apoptosis, reproduction, and wound repair.

    Science.gov (United States)

    Mahajan, Muktar A; Das, Sharmistha; Zhu, Hong; Tomic-Canic, Marjana; Samuels, Herbert H

    2004-06-01

    Nuclear hormone receptor coregulator (NRC) is a 2,063-amino-acid coregulator of nuclear hormone receptors and other transcription factors (e.g., c-Fos, c-Jun, and NF-kappaB). We and others have generated C57BL/6-129S6 hybrid (C57/129) NRC(+/-) mice that appear outwardly normal and grow and reproduce. In contrast, homozygous deletion of the NRC gene is embryonic lethal. NRC(-/-) embryos are always smaller than NRC(+/+) embryos, and NRC(-/-) embryos die between 8.5 and 12.5 days postcoitus (dpc), suggesting that NRC has a pleotrophic effect on growth. To study this, we derived mouse embryonic fibroblasts (MEFs) from 12.5-dpc embryos, which revealed that NRC(-/-) MEFs exhibit a high rate of apoptosis. Furthermore, a small interfering RNA that targets mouse NRC leads to enhanced apoptosis of wild-type MEFs. The finding that C57/129 NRC(+/-) mice exhibit no apparent phenotype prompted us to develop 129S6 NRC(+/-) mice, since the phenotype(s) of certain gene deletions may be strain dependent. In contrast with C57/129 NRC(+/-) females, 20% of 129S6 NRC(+/-) females are infertile while 80% are hypofertile. The 129S6 NRC(+/-) males produce offspring when crossed with wild-type 129S6 females, although fertility is reduced. The 129S6 NRC(+/-) mice tend to be stunted in their growth compared with their wild-type littermates and exhibit increased postnatal mortality. Lastly, both C57/129 NRC(+/-) and 129S6 NRC(+/-) mice exhibit a spontaneous wound healing defect, indicating that NRC plays an important role in that process. Our findings reveal that NRC is a coregulator that controls many cellular and physiologic processes ranging from growth and development to reproduction and wound repair.

  5. Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

    Directory of Open Access Journals (Sweden)

    Carolina de Lourdes Julião Vieira Rocha

    2012-09-01

    Full Text Available CONTEXTO: A terapia a laser de baixa intensidade (LLLT tem sido relatada como importante moduladora da cicatrização de feridas cutâneas aumentando a proliferação fibroblástica associada ao aumento da expressão da citocina fator transformador de crescimento- β2 (TGF-βB2. OBJETIVO: No presente estudo foram avaliados os efeitos da LLLT sobre a expressão da enzima ciclooxigenase 2 (COX2 no sítio do reparo tecidual utilizando o modelo experimental com camundongos diabéticos não obesos (NOD para estudar a cicatrização de feridas cutâneas. MÉTODOS: Foram utilizados 30 camundongos NOD, destes 14 ficaram diabéticos e foram divididos em dois grupos: o grupo I (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e o grupo II (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e tratados com LLLT. O grupo II foi submetido à LLLT nos seguintes parâmetros: 15 mW de potência, dose de 3,8 J/cm² e tempo de aplicação de 20 segundos. Após sete dias do ato cirúrgico e após aplicação do laser, os animais foram eutanasiados com sobredose de anestesia e amostras das feridas foram colhidas para posterior análise histopatológica, histomorfométrica e imuno-histoquímica. RESULTADOS: A LLLT promoveu a inibição da expressão da COX2 em feridas cutâneas de camundongos diabéticos. CONCLUSÃO: Em conjunto, os resultados sugeriram que a LLLT é capaz de modular negativamente a expressão da enzima COX2 contribuindo para o controle da resposta inflamatória em feridas cutâneas de camundongos NOD.BACKGROUND: Low-level laser therapy (LLLT has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2. OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD to study

  6. Corneal Wound Repair After Rose Bengal and Green Light Crosslinking: Clinical and Histologic Study.

    Science.gov (United States)

    Gallego-Muñoz, Patricia; Ibares-Frías, Lucía; Lorenzo, Elvira; Marcos, Susana; Peréz-Merino, Pablo; Bekesi, Nandor; Kochevar, Irene E; Martínez-García, M Carmen

    2017-07-01

    To evaluate corneal wound healing after treatment with a new collagen crosslinking protocol using rose bengal dye and green light (RGX). One cornea of 20 New Zealand rabbits was de-epithelialized (DE) in an 8-mm diameter circle and, in another group (n = 25), the DE corneas were then stained with 0.1% rose bengal for 2 minutes and exposed to green light (532 nm) for 7 minutes (RGX). The contralateral eyes without treatment acted as controls. The animals were clinically followed including fluorescein staining and pachymetry. Healing events were analyzed after euthanasia at 2, 30, and 60 days. Cell death (TUNEL assay), cell proliferation (5-bromo-2'-deoxyuridine incorporation), and cell differentiation to myofibroblasts (α-SMA labeling) were carried out. In addition, loss of keratocytes and subsequent repopulation of the corneal stroma were quantified on hematoxylin-eosin-stained sections. Wound closure was slower after RGX (4.4 days) then after DE (3.3 days). Cell death was restricted to the anterior central stroma, and the cellular decrease did not differ significantly between RGX and DE corneas. Cell proliferation in the epithelium and stroma appeared at 2 days. In both DE and RGX corneas, recovery of the epithelium was complete at day 30, although cell repopulation of the stroma was not complete at 60 days. The healing response in corneas after RGX is very similar to that observed after DE alone, suggesting that, along with its short treatment time and limited effect on keratocytes, RGX displays good potential for clinical cornea stiffening.

  7. The First Cut Is the Deepest: The History and Development of Safe Treatments for Wound Healing and Tissue Repair.

    Science.gov (United States)

    Hobson, David W; Schuh, JoAnn C L; Zurawski, Daniel V; Wang, Jianyong; Arbabi, Sam; McVean, Maralee; Funk, Kathleen A

    2016-09-01

    As the skin is the primary barrier to infection, the importance of wound healing has been understood since ancient times. This article provides a synopsis on the symposium presentations focusing on how wounds were traditionally treated, what models and pathology endpoints exist to study wound healing, special considerations for wound healing studies, an overview of regulatory aspects of new pharmaceutical and medical device development, and the clinical relevance of such models. The clinical treatment of small and large wounds is also considered.

  8. Oriented cell division: new roles in guiding skin wound repair and regeneration.

    Science.gov (United States)

    Yang, Shaowei; Ma, Kui; Geng, Zhijun; Sun, Xiaoyan; Fu, Xiaobing

    2015-11-18

    Tissue morphogenesis depends on precise regulation and timely co-ordination of cell division and also on the control of the direction of cell division. Establishment of polarity division axis, correct alignment of the mitotic spindle, segregation of fate determinants equally or unequally between daughter cells, are essential for the realization of oriented cell division. Furthermore, oriented cell division is regulated by intrinsic cues, extrinsic cues and other cues, such as cell geometry and polarity. However, dysregulation of cell division orientation could lead to abnormal tissue development and function. In the present study, we review recent studies on the molecular mechanism of cell division orientation and explain their new roles in skin repair and regeneration. © 2015 Authors.

  9. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Directory of Open Access Journals (Sweden)

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  10. Repair of wounded monolayers of cultured bovine aortic endothelial cells is inhibited by calcium spirulan, a novel sulfated polysaccharide isolated from Spirulina platensis.

    Science.gov (United States)

    Kaji, Toshiyuki; Fujiwara, Yasuyuki; Inomata, Yuki; Hamada, Chieko; Yamamoto, Chika; Shimada, Satomi; Lee, Jung-Bum; Hayashi, Toshimitsu

    2002-03-08

    Calcium spirulan (Ca-SP) is a novel sulfated polysaccharide isolated from a blue-green alga Spirulina platensis. Ca-SP inhibits thrombin by activation of heparin cofactor II. Therefore, it could serve as an origin of anti-atherogenic medicines. Since maintenance of vascular endothelial cell monolayers is important for prevention of vascular lesions such as atherosclerosis, the effect of Ca-SP at 20 microg/ml or less on the repair of wounded bovine aortic endothelial cell monolayers in culture was investigated in the present study. When the monolayers were wounded and cultured in the presence of Ca-SP, the polysaccharide inhibited the appearance of the cells in the wounded area. The inhibition was also observed even when the repair was promoted by excess basic fibroblast growth factor, which is one of the autocrine growth factors that are involved in the endothelial cell monolayer maintenance. On the other hand, Ca-SP inhibited the cell growth and the incorporation of [3H]thymidine into the acid-insoluble fraction of proliferating endothelial cells, suggesting that Ca-SP inhibits endothelial cell proliferation. From these results, it is concluded that Ca-SP may retard the repair process of damaged vascular endothelium through inhibition of vascular endothelial cell proliferation by induction of a lower ability to respond to stimulation by endogenous basic fibroblast growth factor.

  11. Comment on “Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing”

    Directory of Open Access Journals (Sweden)

    Hongling Li

    2015-01-01

    Full Text Available A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used “Tegaderm” as a semiocclusive dressing film and stated that it exerted a “splinting effect” on the wound margins and controlled contraction. Indeed, the “Tegaderm” itself can serve as a dressing film to isolate the wound bed with outside environments while the “splinting effect” is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and “Tegaderm,” our experimental group propose an alternative method named “combined-suturing” technique that is not only suturing the silicone splints but also securing the “Tegaderm” around the wound. The specific reasons and operative procedures are explained in detail in this letter.

  12. Pectoralis Muscle Flap Repair Reduces Paradoxical Motion of the Chest Wall in Complex Sternal Wound Dehiscence

    Science.gov (United States)

    Zeitani, Jacob; Russo, Marco; Pompeo, Eugenio; Sergiacomi, Gian Luigi; Chiariello, Luigi

    2016-01-01

    Background The aim of the study was to test the hypothesis that in patients with chronic complex sternum dehiscence, the use of muscle flap repair minimizes the occurrence of paradoxical motion of the chest wall (CWPM) when compared to sternal rewiring, eventually leading to better respiratory function and clinical outcomes during follow-up. Methods In a propensity score matching analysis, out of 94 patients who underwent sternal reconstruction, 20 patients were selected: 10 patients underwent sternal reconstruction with bilateral pectoralis muscle flaps (group 1) and 10 underwent sternal rewiring (group 2). Eligibility criteria included the presence of hemisternum diastases associated with multiple (≥3) bone fractures and radiologic evidence of synchronous chest wall motion (CWSM). We compared radiologically assessed (volumetric computed tomography) ventilatory mechanic indices such as single lung and global vital capacity (VC), diaphragm excursion, synchronous and paradoxical chest wall motion. Results Follow-up was 100% complete (mean 85±24 months). CWPM was inversely correlated with single lung VC (Spearman R=−0.72, p=0.0003), global VC (R=−0.51, p=0.02) and diaphragm excursion (R=−0.80, p=0.0003), whereas it proved directly correlated with dyspnea grade (Spearman R=0.51, p=0.02) and pain (R=0.59, p=0.005). Mean CWPM and single lung VC were both better in group 1, whereas there was no difference in CWSM, diaphragm excursion and global VC. Conclusion Our study suggests that in patients with complex chronic sternal dehiscence, pectoralis muscle flap reconstruction guarantees lower CWPM and greater single-lung VC when compared with sternal rewiring and it is associated with better clinical outcomes with less pain and dyspnea. PMID:27733997

  13. Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway.

    Science.gov (United States)

    Xing, Wei; Guo, Wei; Zou, Cun-Hua; Fu, Ting-Ting; Li, Xiang-Yun; Zhu, Ming; Qi, Jun-Hua; Song, Jiao; Dong, Chen-Hui; Li, Zhuang; Xiao, Yong; Yuan, Pei-Song; Huang, Hong; Xu, Xiang

    2015-08-01

    Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear. The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism. Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing. We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin. Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound. Copyright © 2015. Published by Elsevier Ireland Ltd.

  14. Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis.

    Science.gov (United States)

    Terc, Joshua; Hansen, Ashleigh; Alston, Laurie; Hirota, Simon A

    2014-05-13

    The intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis. It is thought that the increased permeability in patients with IBD may be driven by alterations in the epithelial wound healing response. To this end considerable study has been undertaken to identify signaling pathways that may accelerate intestinal epithelial wound healing and normalize the barrier dysfunction observed in IBD. In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response. Mutations and reduced mucosal expression of the PXR are associated with IBD, and others have reported that PXR agonists can dampen intestinal inflammation. Furthermore, stimulation of the PXR has been associated with increased cell migration and proliferation, two of the key processes involved in wound healing. We hypothesized that PXR agonists would enhance intestinal epithelial repair. Stimulation of Caco-2 intestinal epithelial cells with rifaximin, rifampicin and SR12813, all potent agonists of the PXR, significantly increased wound closure. This effect was driven by p38 MAP kinase-dependent cell migration, and occurred in the absence of cell proliferation. Treating mice with a rodent specific PXR agonist, pregnenolone 16α-carbonitrile (PCN), attenuated the intestinal barrier dysfunction observed in the dextran sulphate sodium (DSS) model of experimental colitis, an effect that occurred independent of the known anti-inflammatory effects of PCN. Taken together our data indicate that the activation of the PXR can enhance intestinal epithelial repair and suggest that targeting the PXR may help to normalize intestinal barrier dysfunction observed in patients with IBD

  15. CICATRIZATION OF WOUNDS

    Science.gov (United States)

    Carrel, Alexis; Hartmann, Alice

    1916-01-01

    1. A method for measuring the area of a wound not geometric in form is described. 2. The rate of cicatrization of a wound is greater at the beginning than at the end of the period of repair. It depends on the area rather than on the age of the wound. There is a constant relation between the size of a wound and the rate of cicatrization. The larger the wound the greater is the rate of cicatrization. Two wounds of different size have a tendency to become equal. 3. The rate is proportional to the area, but diminishes less rapidly than the area. 4. The process of contraction is the more important factor in the repair of a wound. Epidermization completes the work of contraction. After the wound is healed, the cicatrix as a rule expands. 5. The curve representing the diminution of the size of an aseptic wound while it cicatrizes is regular and geometric. PMID:19868052

  16. Time-dependent Appearances of Myofibroblasts during the Re-pair of Contused Skeletal Muscle in Rat and Its Application for Wound Age Determination

    Institute of Scientific and Technical Information of China (English)

    YU Tian-shui; GUAN Da-wei; CHANG Lin; WANG Xu; ZHAO Rui; ZHANG Hai-dong; BAI Ru-feng

    2015-01-01

    Objective To research the relation between the time-dependent appearances of myofibroblasts during the repair of contused skeletal muscle in rat and wound age determination. Methods A total of 35 SD male rats were divided into the control and six injured groups according to wound age as fol-lows: 12 h, 1 d, 5 d, 7 d, 10 d and 14 d after injury. The appearances of myofibroblasts were detected by HE staining, immunohistochemistry and confocal laser scanning microscopy. Masson’s trichrome staining was utilized to examine collagen accumulation in the contused areas. Results Immunohistochemical stain-ing showed that α-SMA+ myofibroblasts were initially observed at 5 d post-injury. The average ratio of myofibroblasts was highest at 14 d post-injury, with all samples, ratios more than 50%. In the other five groups, the average of α-SMA positive ratios were less than 50%. The collagen stained areas in the contused zones, concomitant with myofibroblast appearance, were increasingly augmented along with ad-vances of posttraumatic interval. Conclusion The immunohistochemical detection of myofibroblasts can be applied to wound age determination. The myofibroblasts might be involved in collagen deposition during the repair of contused skeletal muscle in rat.

  17. Catecholamine stress alters neutrophil trafficking and impairs wound healing by β2-adrenergic receptor-mediated upregulation of IL-6.

    Science.gov (United States)

    Kim, Min-Ho; Gorouhi, Farzam; Ramirez, Sandra; Granick, Jennifer L; Byrne, Barbara A; Soulika, Athena M; Simon, Scott I; Isseroff, R Rivkah

    2014-03-01

    Stress-induced hormones can alter the inflammatory response to tissue injury; however, the precise mechanism by which epinephrine influences inflammatory response and wound healing is not well defined. Here we demonstrate that epinephrine alters the neutrophil (polymorphonuclear leukocyte (PMN))-dependent inflammatory response to a cutaneous wound. Using noninvasive real-time imaging of genetically tagged PMNs in a murine skin wound, chronic, epinephrine-mediated stress was modeled by sustained delivery of epinephrine. Prolonged systemic exposure of epinephrine resulted in persistent PMN trafficking to the wound site via an IL-6-mediated mechanism, and this in turn impaired wound repair. Further, we demonstrate that β2-adrenergic receptor-dependent activation of proinflammatory macrophages is critical for epinephrine-mediated IL-6 production. This study expands our current understanding of stress hormone-mediated impairment of wound healing and provides an important mechanistic link to explain how epinephrine stress exacerbates inflammation via increased number and lifetime of PMNs.

  18. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L A

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  19. 人工真皮修复慢性创面疗效观察%The efficacy of artificial dermis in the repair of chronic wounds

    Institute of Scientific and Technical Information of China (English)

    余继超; 邱加崇; 彭文要; 陈柏秋; 刘冰峰; 梁健勤; 刘旭盛

    2012-01-01

    or skin flap transplantation for wound healing and the wounds in 14 patients were healed by wound dressing with remarkable scar formation.In the study group,the average length of hospital stay was ( 31.4 ± 1.1 )days; the wounds in the patients were covered with artificial dermis with little scar formation,7 of whom with bigger wounds were treated by skin grafting after wound bed preparation ( granulation tissue growth ) by artificial dermis.Conclusions Artificial dermis could accelerate the healing speed of chronic wounds.Wound repair with artificial dermis could shorten length of hospital stay and decrease surgical duration and risks.It is worth popularizing.

  20. Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review

    Science.gov (United States)

    Ho, Jasmine; Walsh, Claire; Yue, Dominic; Dardik, Alan; Cheema, Umber

    2017-01-01

    Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach. PMID:28616360

  1. A Bilayer Engineered Skin Substitute for Wound Repair in an Irradiation-Impeded Healing Model on Rat

    OpenAIRE

    2015-01-01

    Objective: An engineered skin substitute is produced to accelerate wound healing by increasing the mechanical strength of the skin wound via high production of collagen bundles. During the remodeling stage of wound healing, collagen deposition is the most important event. The collagen deposition process may be altered by nutritional deficiency, diabetes mellitus, microbial infection, or radiation exposure, leading to impaired healing. This study describes the fabrication of an engineered bila...

  2. 碱性成纤维细胞生长因子加速慢性难愈合创面愈合%Healing of chronic cutaneous wounds by topical treatment with basic fibroblast growth factor

    Institute of Scientific and Technical Information of China (English)

    付小兵; 沈祖尧; 郭振荣; 张明良; 盛志勇

    2002-01-01

    Objective To evaluate the safety and efficacy of topical application of recombinant bovine basic fibroblast growth factor (rbFGF) on the healing of chronic cutaneous wounds. Methods Twenty-eight patients with thirty-three chronic cutaneous wounds resulting from trauma, diabetes mellitus, pressure sore and radiation injuries were enrolled in this prospective, open-label crossover trial. Prior to treatment with rbFGF, all wounds failed to heal with conventional therapies within 4 weeks. All wounds were locally treated with rbFGF at a dose of 150?AU/cm2. Healing time and the quality of wounds were used to evaluate the efficacy of the treatment.Results Healing of all chronic wounds was expedited. During the study, eighteen wounds completely healed within 2 weeks, four healed within 3 weeks, and another eight completely healed within 4 weeks. Only three wounds failed to heal within 4 weeks, but healed at 30, 40 and 42 days after treatment with rbFGF. Thus, compared with conventional therapies, the effective rate of rbFGF treatment within 4 weeks was 90.9%. Histological assessment showed more abundant capillary sprouts or tubes and that fibroblasts were differentiated in wounds treated with rbFGF. No adverse side effects related to basic fibroblast growth factor were observed.Conclusions Our results indicate that rbFGF could be used to accelerate healing in chronic wounds. It is our belief that this may be a more effective method of chronic wound management.%目的 观察重组中碱性成纤维细胞生长因子(rbFGF)对慢性难愈合创面(溃疡)的促修复作用并探讨其促修复机制。方法 本组28例共33个慢性难愈合创面,其中创伤性溃疡12例(13个创面)、压迫性溃疡9例(13个创面),糖尿病溃疡4例,放射性溃疡3例。所有创面经清创后用rbFGF治疗(150?AU/cm2创面,每天1次)。结果 所有经rbFGF治疗的创面都产生了明显的愈合,其中2周内愈合为18例,2-3周内愈合为4

  3. Superficial wounding model for epidermal barrier repair studies: comparison of Erbium:YAG laser and the suction blister method.

    Science.gov (United States)

    Ferraq, Younes; Black, David R; Theunis, Jennifer; Mordon, Serge

    2012-09-01

    Wound-healing studies use mainly mechanical methods for wound induction, which are laborious and difficult to standardize. Objective of this study was to evaluate the Erbium:Yttrium-Aluminium-Garnet (Er:YAG) laser method as a model of epidermis ablation on human skin in vivo and to compare the quality and healing rates of Er:YAG laser and suction blister (SB) wounds. Er:YAG laser and SB wounds were made on the forearms of 10 healthy volunteers. Post-wounding measurements including wound surface area (WSA) from photographs, wound depth from 3D volume analysis, trans-epidermal water loss (TEWL), laser doppler blood flow (LDBF), and optical coherence tomography (OCT) imaging were made daily over 7 days. Biopsies were taken on Days 4 and 7. 3D analysis showed laser wounds to be shallower and more uniform in depth than SB: 54 ± 14 µm versus 140 ± 102 µm, respectively, with histology demonstrating complete epidermal removal using SB. SB wounds were more variable in size with a WSA of 0.47 ± 0.24 cm(2) compared to 1.17 ± 0.14 cm(2) for laser wounds. Healing rates were similar in both groups, as measured by TEWL, LDBF, and WSA. OCT imaging on Days 3-4 revealed new epidermis below the fibrin clot, similar to histology, and a visible stratum corneum on Day 7, but no apparent epidermal hyperplasia in contrast to histology. Compared to the SB model, Er:YAG laser achieved rapid standardized epidermal ablation, which despite morphological differences, was similar in terms of epidermal regeneration/barrier formation. Copyright © 2012 Wiley Periodicals, Inc.

  4. Sirtuin-6 deficiency exacerbates diabetes-induced impairment of wound healing.

    Science.gov (United States)

    Thandavarayan, Rajarajan A; Garikipati, Venkata Naga Srikanth; Joladarashi, Darukeshwara; Suresh Babu, Sahana; Jeyabal, Prince; Verma, Suresh K; Mackie, Alexander R; Khan, Mohsin; Arumugam, Somasundaram; Watanabe, Kenichi; Kishore, Raj; Krishnamurthy, Prasanna

    2015-10-01

    Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However, the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyse the role of SIRT6 in cutaneous wound healing, paired 6-mm stented wound was created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and nonsense siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6-siRNA-treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31-staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor-κB (NF-κB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α and interleukin-1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF-κB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that the activation of SIRT6 signalling might be a potential therapeutic approach for promoting wound healing in diabetics.

  5. Effect of UV irradiation on cutaneous cicatrices

    DEFF Research Database (Denmark)

    Due, Eva; Rossen, Kristian; Sorensen, Lars Tue

    2007-01-01

    The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV...

  6. Histological evaluation of the healing properties of Dead Sea black mud on full-thickness excision cutaneous wounds in BALB/c mice.

    Science.gov (United States)

    Abu-al-Basal, Mariam A

    2012-04-01

    Dead Sea (DS) mud and salts are known for their therapeutic and cosmetic properties. Previous studies confirmed their efficacy in treating the more frequent skin diseases such as psoriasis and atopic dermatitis. Therefore, this study aimed to evaluate the wound healing potential of natural and compounded skin-care product (facial mask) of DS black mud in BALB/c mice. Two full-thickness excision round wounds were created on the dorsum region of mouse. Each wound of mice test group were treated topically with 50 microL of 0.1% natural or compounded DS black mud or 50 microL of 0.2% nitrofurazone once a day for 2 consecutive days and the mice control group were left untreated. Healing was assessed by measuring the granulation tissue weight and percentage of wound contraction at day 3, 7, 14 and 21 after wounding. In addition to period of epithelialization and histological evaluation of the regenerated wound area at day 7 and 14 after wounding. Results revealed that DS black mud accelerate wound healing process by enhancing granulation, wound contraction, epithelialization, angiogenesis and collagen deposition. This may be due to high content of minerals and trace elements that possibly act as anti-microbial, anti-inflammatory and antioxidant with enhancement effect on cell proliferation, migration and fibroblast cellular activity. However, the healing property of DS black mud compounded in skin-care product was greater than that of natural black mud, when compared to reference drug, nitrofurazone.

  7. [New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

    Science.gov (United States)

    Fu, X B

    2016-01-01

    Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

  8. Application of Skin Flap to the Complex Wound Repair%皮瓣在修复重建复杂创面中的应用

    Institute of Scientific and Technical Information of China (English)

    陈文斌; 朱晓; 刘志安

    2013-01-01

    目的:探讨皮瓣在修复重建复杂创面中的应用。方法:自1997年7月至2012年8月,应用游离皮瓣、带血管蒂岛状皮瓣修复20例因肿瘤或外伤形成的复杂性创面,创面有重要组织外露或功能部位,缺损最大约13cm×35cm最小10cm×20cm,切取相应的大小的皮瓣覆盖创面,继发性创面直接缝合或以植断层皮片覆盖。结果:20例患者皮瓣全部成活,修复后的形态自然、功能恢复程度良好,随访1个月到2年余形态自然。结论:对于复杂的创面修复,术前精心设计、针对每个患者的创面的特点,具体问题,具体分析,选择适合的皮瓣可以最大程度地修复创面,形态和功能都能得到很好的满足。%Objective To study the application of skin flap to the complex wound repair. Method Free or island skin flap were used to repair 20 cases with complex wound which resulted from trauma or tumor,and were characterized by the exposure of important tissue or locating in function area. The maxim of the defect area was 13cm×35cm,and the minimum of the area was 10cm×20cm. The skin flap of the same size was cut off to cover the atea,while the secondary defect was cured by direct suture or skin graft. Result All the skin flap of 20 cases survived completely,with natural structure and good function. After 1 month to 2 years of follow-up, it still showed a natural appearance. Conclusion The complex wound can be repaired well both in appearance and function after careful operation-designing and appropriate flap-selecting according to the characteristics of each wound.

  9. 弱激光促进糖尿病大鼠模型皮肤创伤愈合的实验研究%Study of Low-Level Laser Therapy Facilitates Cutaneous Wound Healing in Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    马慧; 李迎新; 崔欲晓; 陈洪丽; 康美玲; 董晓曦

    2011-01-01

    To investigate the effect of low-level laser therapy on healing of cutaneous excisional wounds in diabetic rats. The dorsal cutaneous excisional wounds of 32 diabetic rats were divided randomly into 4 groups. Three groups were irradiated with a 630 nm semiconductor laser each with respective three power densities of 5,10 and 15 mW/cm2, whereas the fourth group served as a control. Low-level laser irradiation can obviously accelerate wound contraction,reduce inflammatory reaction significantly, speed fibroblasts proliferation and collagen synthesis, promote epithelial cells and capillaries regeneration, promote wound healing.Effect of low-level laser therapy with 15 mW/cm2 is most obvious. Before and after the experiment blood glucose levels of all groups were no significant difference. It can be concluded that low-level laser therapy have bene?cial effects on wound healing in diabetic rats,and the outcomes have a relationship with optical parameters.%探讨弱激光对糖尿病大鼠皮肤创伤愈合过程的影响.32只糖尿病大鼠背部皮肤全层创口随机分为4组,分别为:功率密度5、10和15 mW/cm2的630nm半导体激光照射组及空白对照组.弱激光照射能明显加速创面收缩,减轻炎症反应,加快成纤维细胞的增殖和胶原蛋白的合成,促进上皮细胞和毛细血管再生,促进创伤愈合.其中功率密度15 mW/cm2的弱激光治疗组疗效最为明显.实验前后各组大鼠血糖水平均无显著差异.弱激光对糖尿病大鼠皮肤创伤愈合确实存在促进作用,且疗效存在光学参数依赖性.

  10. Porous polymer scaffold for on-site delivery of stem cells--Protects from oxidative stress and potentiates wound tissue repair.

    Science.gov (United States)

    Geesala, Ramasatyaveni; Bar, Nimai; Dhoke, Neha R; Basak, Pratyay; Das, Amitava

    2016-01-01

    Wound healing by cell transplantation techniques often suffer setbacks due to oxidative stress encountered at injury sites. A porous polyethyleneglycol-polyurethane (PEG-PU) scaffold that facilitates cell delivery and boosts tissue repair was developed through semi-interpenetrating polymer network approach. The key physico-chemical properties assessed confirms these polymeric matrices are highly thermostable, barostable, degrade at an acidic pH (5.8), biodegradable, cytocompatible and possess excellent porosity. Mechanism of cellular penetration into porous polymer networks was evident by a ≥6 - fold increase in gene expression of MMP-13 and MMP-2 via activation of Akt and Erk. H2O2-induced apoptosis of mouse bone marrow stem cells (BMSCs) was abrogated in presence of polymer networks indicating a protective effect from oxidative stress. Transplantation of BMSC + PEG-PU at murine excisional splint wound site depicted significant increase in fibroblast proliferation, collagen deposition, anti-oxidant enzyme activities of catalase, SOD and GPx. Furthermore it significantly decreased expression of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8, etc) with a concomitant increase in anti-inflammatory cytokines (IL-10, IL-13) at an early healing period of day 7. Finally, immunostaining revealed an enhanced engraftment and vascularity indicating an accelerated wound tissue closure. This pre-clinical study demonstrates the proof-of-concept and further necessitates their clinical evaluation as potential cell delivery vehicle scaffolds.

  11. Evaluation of the effect of laser radiation on fibroblast proliferation in repair of skin wounds of rats with iron deficiency anemia

    Science.gov (United States)

    DeCastro, Isabele C. V.; Oliveira-Sampaio, Susana C. P.; Monteiro, Juliana S. de C.; Ferreira, Maria de Fátima L.; Cangussu, Maria T.; N. dos Santos, Jean; Pinheiro, Antonio Luiz B.

    2011-03-01

    The aim of this study was to assess the effect of low- level laser therapy (LLLT) on fibroblast proliferation on wound repair of rats with Iron deficiency anemia since there is no reports on literature about this subject. Iron deficiency anemia was induced on 36 newborn rats then an excisional wound was created on the dorsum of the animals which were divided into four groups: (I) - non-anemic, (II) - Anemic, (III) - non-anemic + LLLT, (IV) Anemic+ LLLT. The animals in each group were sacrificed at 7, 14 and 21 days. Laser irradiation was performed on each group (λ660nm,40Mw,CW) by contact mode with a dose of 2,5J/ cm2 in four points on the area of the wound and total of 10J/cm2 per session. Data were evaluated by analysis of variance (ANOVA) followed by Paired t-test. The results showed LLLT was able to stimulate fibroblastic proliferation in rats with iron deficiency anemia at the 21st day while at control group (III) no statistically significant differences was found.

  12. Heparin-Based Coacervate of FGF2 Improves Dermal Regeneration by Asserting a Synergistic Role with Cell Proliferation and Endogenous Facilitated VEGF for Cutaneous Wound Healing.

    Science.gov (United States)

    Wu, Jiang; Ye, Jingjing; Zhu, Jingjing; Xiao, Zecong; He, Chaochao; Shi, Hongxue; Wang, Yadong; Lin, Cai; Zhang, Hongyu; Zhao, Yingzheng; Fu, Xiaobing; Chen, Hong; Li, Xiaokun; Li, Lin; Zheng, Jie; Xiao, Jian

    2016-06-13

    Effective wound healing requires complicated, coordinated interactions and responses at protein, cellular, and tissue levels involving growth factor expression, cell proliferation, wound closure, granulation tissue formation, and vascularization. In this study, we develop a heparin-based coacervate consisting of poly(ethylene argininylaspartate digylceride) (PEAD) as a storage matrix, heparin as a bridge, and fibroblast growth factor-2 (FGF2) as a cargo (namely heparin-FGF2@PEAD) for wound healing. First, in vitro characterization demonstrates the loading efficiency and control release of FGF2 from the heparin-FGF2@PEAD coacervate. The following in vivo studies examine the wound healing efficiency of the heparin-FGF2@PEAD coacervate upon delivering FGF2 to full-thickness excisional skin wounds in vivo, in comparison with the other three control groups with saline, heparin@PEAD as vehicle, and free FGF2. Collective in vivo data show that controlled release of FGF2 to the wounds by the coacervate significantly accelerates the wound healing by promoting cell proliferation, stimulating the secretion of vascular endothelial growth factor (VEGF) for re-epithelization, collagen deposition, and granulation tissue formation, and enhancing the expression of platelet endothelial cell adhesion molecule (CD31) and alpha-smooth muscle actin (α-SMA) for blood vessel maturation. In parallel, no obvious wound healing effect is found for the control, vehicle, and free FGF2 groups, indicating the important role of the coavervate in the wound healing process. This work designs a suitable delivery system that can protect and release FGF2 in a sustained and controlled manner, which provides a promising therapeutic potential for topical treatment of wounds.

  13. Topical application of Acalypha indica accelerates rat cutaneous wound healing by up-regulating the expression of Type I and III collagen.

    Science.gov (United States)

    Ganeshkumar, Moorthy; Ponrasu, Thangavel; Krithika, Rajesh; Iyappan, Kuttalam; Gayathri, Vinaya Subramani; Suguna, Lonchin

    2012-06-26

    Acalypha indica Linn. (Acalypha indica) vernacularly called Kuppaimeni in Tamil, has been used as a folklore medicine since ages for the treatment of wounds by tribal people of Tamil Nadu, Southern India. The present study investigates the biochemical and molecular rationale behind the healing potential of Acalypha indica on dermal wounds in rats. Acalypha indica extract (40 mg/kg body weight) was applied topically once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of various biochemical and biophysical analyses and to observe histopathological changes with and with-out extract treatment. The serum levels of pro-inflammatory cytokine tumor necrosis factor (TNF-α) was measured at 12 h, 24 h, 48 h and 72 h post-wounding using ELISA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to study the expression pattern of transforming growth factor [TGF-β1], collagen 1 α (I) [Col 1 α (I)] and collagen 3 α (I) [Col 3 α (I)]. Likewise, linear incision wounds were created and treated with the extract and used for tensile strength measurements. Wound healing in control rats was characterized by less inflammatory cell infiltration, lack of granulation tissue formation, deficit of collagen and significant decrease in biomechanical strength of wounds. Acalypha indica treatment mitigated the oxidative stress and decreased lipid peroxidation with concomitant increase in ascorbic acid levels. It also improved cellular proliferation, increased TNF-α levels during early stages of wound healing, up-regulated TGF-β1 and elevated collagen synthesis by markedly increasing the expression of Col 1 α (I) and Col 3 α (I). Increased rates of wound contraction, epithelialization, enhanced shrinkage temperature and high tensile strength were observed in the extract treated rats. Acalypha indica extract was shown to augment the process of dermal wound healing by its ability to increase collagen

  14. Wound healing, angiotensin-converting enzyme inhibition, and collagen-containing products: a case study.

    Science.gov (United States)

    Buscemi, Charles P; Romeo, CarolAnn

    2014-01-01

    The effects of multiple medications may impair or enhance wound healing. A review of the literature for drug side effects identified cell culture and case studies of angiotensin-converting enzyme inhibitors (ACEIs) impairing collagen deposition in cutaneous wounds; these medications have also been used to prevent or minimize keloid formation. A 71-year-old male patient presented with a venous leg ulcer (VLU), having incurred a crushing injury and fracture requiring surgical repair 16 years earlier. The patient's history was significant for obesity, smoking 1 cigar daily, hypertension, and lower extremity venous insufficiency; medications included amlodipine and lisinopril. The wound initially responded well to advanced wound products and compression, but wound healing subsequently stalled. A collagen-containing alginate dressing was added to the treatment regimen and the wound closed within 2 weeks. We postulate that lisinopril may have contributed to the observed delayed healing and targeted this potential impediment to wound healing with a readily available topical collagen-containing product resulting in a rapid wound closure after a significant delay in progress toward wound healing.

  15. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  16. Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages.

    Science.gov (United States)

    Luo, Xiaochun; Huang, Ping; Yuan, Baohong; Liu, Tao; Lan, Fang; Lu, Xiaoyan; Dai, Liangcheng; Liu, Yunjun; Yin, Hui

    2016-06-01

    Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix, has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization. AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing.

  17. Incisional wound healing in transforming growth factor-beta1 null mice.

    Science.gov (United States)

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B

    2000-01-01

    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  18. A potential wound healing-promoting peptide from frog skin.

    Science.gov (United States)

    Liu, Han; Mu, Lixian; Tang, Jing; Shen, Chuanbin; Gao, Chen; Rong, Mingqiang; Zhang, Zhiye; Liu, Jie; Wu, Xiaoyang; Yu, Haining; Lai, Ren

    2014-04-01

    Cutaneous wound healing is a dynamic, complex, and well-organized process that requires the orchestration of many different cell types and cellular processes. Transforming growth factor β1 is an important factor that plays a key role during wound healing. Amphibian skin has been proven to possess excellent wound healing ability, whilst no bioactive substrate related to it has ever been identified. Here, a potential wound healing-promoting peptide (AH90, ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami. It showed potential wound healing-promoting activity in a murine model with full thickness dermal wound. AH90 promoted release of transforming growth factor β1 through activation of nuclear factor-κB and c-Jun NH2-terminal kinase mitogen-activated protein kinases signaling pathways, while inhibitors of nuclear factor-κB and c-Jun NH2-terminal kinase inhibited the process. In addition, the effects of AH90 on Smads family proteins, key regulators in transforming growth factor β1 signaling pathways, could also be inhibited by transforming growth factor β1 antibody. Altogether, this indicated that AH90 promoted wound healing by inducing the release of transforming growth factor β1. This current study may facilitate the understanding of effective factors involved in the wound repair of amphibians and the underlying mechanisms as well. Considering its favorable traits as a small peptide that greatly promoting generation of endogenous wound healing agents (transforming growth factor β1) without mitogenic effects, AH90 might be an excellent template for the future development of novel wound-healing agents.

  19. Absorbable Polydioxanone (PDS) suture provides fewer wound complications than polyester (ethibond) suture in acute Tendo-Achilles rupture repair

    LENUS (Irish Health Repository)

    Baig, M N

    2017-05-01

    We prospectively studied acute Achilles tendon rupture in patients over a two 2-year period and reviewed the causes, outcome and complications. There were 53 patients included with acute Achilles rupture with minimum follow up period of 6 months. We compared the outcomes including infection rate and Boyden score between the two groups repaired by Polydioxanone and Polyester respectively. All infected cases had a suture repair using the polyester suture. The difference in the infection rate was highly significant between the 2 groups (p=0.001). All 34 patients (100%) in the PDS group had good \\/ excellent results based on the Boyden clinical assessment. Conversely, only 16 patients 9(68.4%) had good or excellent results IN Polyester repair group. Patients treated with a non- absorbable suture (ethibond) material for repair had a higher incidence infection and worse Boyden scores than the absorbable PDS group.

  20. The local effect of Persian Gulf brittle star (Ophiocoma erinaceus alcoholic extract on cutaneous wound healing in Balb/C mouse

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2014-11-01

    Results: Significant changes in proliferation of inflammatory cells (on the 12th day, epithelium thickness (on the 6th day, more angiogenesis (on the 6th- 9th day, in the experimental wounds were compared with those in the control group. However, experimental group with positive control were not significantly different in these days. Conclusion: Findings of this research indicated that the topical application of brittle star extract posse positive impact on wound healing process.

  1. A scaffold-enhanced light-activated surgical adhesive technique: surface selection for enhanced tensile strength in wound repair

    Science.gov (United States)

    Soller, Eric C.; Hoffman, Grant T.; Heintzelman, Douglas L.; Duffy, Mark T.; Bloom, Jeffrey N.; McNally-Heintzelman, Karen M.

    2004-07-01

    An ex vivo study was conducted to determine the effect of the irregularity of the scaffold surface on the tensile strength of repairs formed using our Scaffold-Enhanced Biological Adhesive (SEBA). Two different scaffold materials were investigated: (i) a synthetic biodegradable material fabricated from poly(L-lactic-co-glycolic acid); and (ii) a biological material, small intestinal submucosa, manufactured by Cook BioTech. The scaffolds were doped with protein solder composed of 50%(w/v) bovine serum albumin solder and 0.5mg/ml indocyanine green dye mixed in deionized water, and activated with an 808-nm diode laser. The tensile strength of repairs performed on bovine thoracic aorta, liver, spleen, small intestine and lung, using the smooth and irregular surfaces of the above scaffold-enhanced materials were measured and the time-to-failure was recorded. The tensile strength of repairs formed using the irregular surfaces of the scaffolds were consistently higher than those formed using the smooth surfaces of the scaffolds. The largest difference was observed on repairs formed on the aorta and small intestine, where the repairs were, on average, 50% stronger using the irregular versus the smooth scaffold surfaces. In addition, the time-to-failure of repairs formed using the irregular surfaces of the scaffolds were between 50% and 100% longer than that achieved using the smooth surfaces of the scaffolds. It has previously been shown that distributing or dispersing the adhesive forces over the increased surface area of the scaffold, either smooth or irregular, produces stronger repairs than albumin solder alone. The increase in the absolute strength and longevity of repairs seen in this new study when the irregular surfaces of the scaffolds are used is thought to be due to the distribution of forces between the many independent micro-adhesions provided by the irregular surfaces.

  2. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

    Science.gov (United States)

    Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

    2015-03-13

    Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

  3. Cografts of artificial dermis matrix and autogenetic split-thickness of repaired skin in severe hand wounds in patients with deep burns

    Directory of Open Access Journals (Sweden)

    Liu Hongqi

    2014-01-01

    Full Text Available The aim of this paper was to evaluate the effect of using artificial dermis matrix plus autologous split-thickness skin (ADM and ASTS in the treatment of deep-burns in hands of severely burned patients.We recruited a total of 58 patients with large area burns greater than 80% that were eschar-excised. Twenty-eight of them were treated with ADM and ASTS (test group; 30 were treated with autologous medium-thickness skin (AMTS (control group. The healing time of the hand wound was noted, clinical and photographic evaluations were performed, and a Jebsen-Taylor hand function test was compared and analyzed in the two groups. The wound healing time in the test group (24.22±3.34 days were longer than that of the control group (13.42±3.36 days and statistically significant. The healing time of skin graft donor sites was shorter than that of the control group (7.14±1.63 vs. 14.28±2.37 days and statistically significant (P<0.05. The 3rd and 6th month follow-up with clinical and functional evaluations revealed no differences between the two groups. In addition, there was no obvious scar formation and less pigmentation in either group. The repair of deeply burned hands with artificial dermis matrix was beneficial to both wound healing and the donor site, and was beneficial to the whole body rehabilitation of severely burned patients.

  4. PATOPHYSIOLOGY OF WOUND HEALING

    OpenAIRE

    NOVINŠČAK, TOMISLAV; FILIPOVIĆ, MARINKO

    2015-01-01

    Wound healing is a basic, highly complex, logical and well orchestrated physiologic process of interaction of various speciic molecules and cells in normal tissue function and structure restoration. In essence, genetically deined and by reined physical and chemical forces driven process, in most living beings wound healing leads to imperfect but suficient tissue repair. Some rare exceptions in wound healing, like salamander or human fetus, that can achieve complete and perfect regeneration pr...

  5. Self-Repairing Membranes for Inflatable Structures Inspired by a Rapid Wound Sealing Process of Climbing Plants

    Institute of Scientific and Technical Information of China (English)

    Markus Rampf; Olga Speck; Thomas Speck; Rolf H. Luchsinger

    2011-01-01

    A new self-repairing membrane for inflatable light weight structures such as rubber boats or Tensairity(R) constructions is presented. Inspired by rapid self-sealing processes in plants, a thin soft cellular polyurethane foam coating is applied on the inside of a fabric substrate, which closes the fissure if the membrane is punctured with a spike. Experimental tests are carried out with a purpose built setup by measuring the air mass flow through a leak in a damaged membrane sample. It is shown that the weight per unit area of the self-repairing foam as well as the curing of the two component PU-foam under an overpressure influence the repair efficiency. Curing the foam under overpressure affects the relative density as well as the microstructure of the foam coatings. Maximal median repair efficiencies of 0.999 have been obtained with 0.16 g·cm-2 foam cured at 1 bar overpressure. These results suggest that the bio-inspired technique has the potential to extend the functional integrity of injured inflatable structures dramatically.

  6. 进一步重视特殊部位与特殊原因深度烧伤创面的美容修复%Lay further emphasis on the cosmetic repair of deep burn wounds in extraordinary regions or caused by uncommon agents

    Institute of Scientific and Technical Information of China (English)

    刘毅

    2014-01-01

    Along with the vigorous development of medical science and other related subjects,a lot of new techniques,concepts,materials,and methods continuously sprung up.The techniques of plastic and cosmetic surgery have already been used to repair burn wound at the early stage,especially to those wounds in extraordinary regions or caused by uncommon agents.These advances made burn wound treatment change from simply covering wound to save the patient's life to repairing wound and reconstructing function at the same time,which might achieve the aim of cosmetic repair in the future.Because of the hard work of burn surgeons,some progresses on the cosmetic repair of deep burn wounds in extraordinaru regions or caused by uncommon agents have been achieved,but there is still a long way to go for the aim of cosmetic repair.Clinical practice has proved that as long as the basic principles of cosmetic repair are followed,the techniques and methods of plastic and cosmetic surgery are employed correctly,and the role of burn rehabilitation is highly emphasized,it is practicable to achieve cosmetic repair of deep burn wounds in extraordinary regions or caused by uncommon agents.

  7. Optimization of an ex vivo wound healing model in the adult human skin: Functional evaluation using photodynamic therapy.

    Science.gov (United States)

    Mendoza-Garcia, Jenifer; Sebastian, Anil; Alonso-Rasgado, Teresa; Bayat, Ardeshir

    2015-09-01

    Limited utility of in vitro tests and animal models of human repair, create a demand for alternative models of cutaneous healing capable of functional testing. The adult human skin Wound Healing Organ Culture (WHOC) provides a useful model, to study repair and enable evaluation of therapies such as the photodynamic therapy (PDT). Thus, the aim here was to identify the optimal WHOC model and to evaluate the role of PDT in repair. Wound geometry, system of support, and growth media, cellular and matrix biomarkers were investigated in WHOC models. Subsequently, cellular activity, extracellular matrix remodeling, and oxidative stress plus gene and protein levels of makers of wound repair measured the effect of PDT on the optimized WHOC. WHOCs embedded in collagen and supplemented DMEM were better organized showing stratified epidermis and compact dermis with developing neo-epidermis. Post-PDT, the advancing reepithelialization tongue was 3.5 folds longer, and was highly proliferative with CK-14 plus p16 increased (p < 0.05) compared to controls. The neo-epidermis was fully differentiated forming neo-collagen. Proliferating nuclear antigen, p16, COLI, COLIII, MMP3, MMP19, and α-SMA were significantly more expressed (p < 0.05) in dermis surrounding the healing wound. In conclusion, an optimal model of WHOC treated with PDT shows increased reepithelialization and extracellular matrix reconstruction and remodeling, supporting evidence toward development of an optimal ex vivo wound healing model.

  8. Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing.

    Science.gov (United States)

    Charafeddine, Rabab A; Makdisi, Joy; Schairer, David; O'Rourke, Brian P; Diaz-Valencia, Juan D; Chouake, Jason; Kutner, Allison; Krausz, Aimee; Adler, Brandon; Nacharaju, Parimala; Liang, Hongying; Mukherjee, Suranjana; Friedman, Joel M; Friedman, Adam; Nosanchuk, Joshua D; Sharp, David J

    2015-09-01

    Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.

  9. MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions.

    Science.gov (United States)

    Laplante, Patrick; Brillant-Marquis, Frédéric; Brissette, Marie-Joëlle; Joannette-Pilon, Benjamin; Cayrol, Romain; Kokta, Victor; Cailhier, Jean-François

    2017-09-01

    Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation, leading to abnormal wound healing and hypertrophic scars. Our research group has shown that apoptotic endothelial and epithelial cells secrete MFG-E8, which has the ability to reprogram macrophages from an M1 (proinflammatory) to an M2 (anti-inflammatory, pro-repair) phenotype. Hence, we tested whether modulation of macrophage reprogramming would promote tissue repair. Using a mouse model of wound healing, we showed that the presence and/or addition of MFG-E8 favors wound closure associated with an increase in CD206-positive cells and basic fibroblast growth factor production in healing tissues. More importantly, adoptive transfer of ex vivo MFG-E8-treated macrophages promoted wound closure. We also observed that MFG-E8-treated macrophages produced basic fibroblast growth factor that is responsible for fibroblast migration and proliferation. Taken together, our results strongly suggest that MFG-E8 plays a key role in macrophage reprogramming in tissue healing through induction of an anti-inflammatory M2 phenotype and basic fibroblast growth factor production, leading to fibroblast migration and wound closure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Endogenous bioelectric ifelds:a putative regulator of wound repair and regeneration in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Matthew L.Baer; Raymond J.Colello

    2016-01-01

    Studies on a variety of highly regenerative tissues, including the central nervous system (CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric ifelds (EF) that are 100-fold increased in intensity over that measured for uninjured tissue.In vitro and in vivo experiments have con-vincingly demonstrated that these electric ifelds (by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Addi-tionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.

  11. Mechanical stress changes the complex interplay between HO-1, inflammation and fibrosis, during excisional wound healing

    Directory of Open Access Journals (Sweden)

    Niels A.J. Cremers

    2015-12-01

    Full Text Available Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1 is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than 3 times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epidermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower number of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, αSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1β, TNF-α, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly-formed collagen (type III was lower in 7-day wounds after splinting; whereas, VEGF and MMP-9 were increased. Summarizing, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting, may facilitate higher myofibroblast numbers and increases the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in

  12. A randomized controlled phase IIb wound healing trial of cutaneous leishmaniasis ulcers with 0.045% pharmaceutical chlorite (DAC N-055) with and without bipolar high frequency electro-cauterization versus intralesional antimony in Afghanistan.

    Science.gov (United States)

    Stahl, Hans-Christian; Ahmadi, Faridullah; Schleicher, Ulrike; Sauerborn, Rainer; Bermejo, Justo Lorenzo; Amirih, Mohammed Latif; Sakhayee, Ibrahim; Bogdan, Christian; Stahl, Kurt-Wilhelm

    2014-11-25

    A previously published proof of principle phase IIa trial with 113 patients from Kabul showed that bipolar high-frequency (HF) electro-cauterization (EC) of cutaneous leishmaniasis (CL) ulcers and subsequent moist wound treatment (MWT) closed 85% of all Leishmania (L.) tropica lesions within 60 days. A three-armed phase IIb, randomized and controlled clinical trial was performed in Mazar-e-Sharif. L. tropica- or L. major-infected CL patients received intradermal sodium stibogluconate (SSG) (Group I); HF-EC followed by MWT with 0.045% DAC N-055 (Group II); or MWT with 0.045% DAC N-055 in basic crème alone (Group III). The primary outcome was complete epithelialisation before day 75 after treatment start. 87 patients enrolled in the trial were randomized into group I (n = 24), II (n = 32) and III (n = 31). The per-protocol analysis of 69 (79%) patients revealed complete epithelialisation before day 75 in 15 (of 23; 65%) patients of Group I, in 23 (of 23; 100%) patients of Group II, and in 20 (of 23; 87%) patients of Group III (p = 0.004, Fisher's Exact Test). In the per-protocol analysis, wound closure times were significantly different between all regimens in a pair-wise comparison (p = 0.000039, Log-Rank (Mantel-Cox) test). In the intention-to-treat analysis wound survival times in Group II were significantly different from those in Group I (p = 0.000040, Log-Rank (Mantel-Cox) test). Re-ulcerations occurred in four (17%), three (13%) and seven (30%) patients of Group I, II or III, respectively (p = 0.312, Pearson Chi-Square Test). Treatment of CL ulcers with bipolar HF-EC followed by MWT with 0.045% DAC N-055 or with DAC N-055 alone showed shorter wound closure times than with the standard SSG therapy. The results merit further exploration in larger trials in the light of our current knowledge of in vitro and in vivo activities of chlorite. Clinicaltrials.gov ID: NCT00996463. Registered: 15th October 2009.

  13. Deficiency in the LIM-only protein Fhl2 impairs skin wound healing.

    Science.gov (United States)

    Wixler, Viktor; Hirner, Stephanie; Müller, Judith M; Gullotti, Lucia; Will, Carola; Kirfel, Jutta; Günther, Thomas; Schneider, Holm; Bosserhoff, Anja; Schorle, Hubert; Park, Jung; Schüle, Roland; Buettner, Reinhard

    2007-04-09

    After skin wounding, the repair process is initiated by the release of growth factors, cytokines, and bioactive lipids from injured vessels and coagulated platelets. These signal molecules induce synthesis and deposition of a provisional extracellular matrix, as well as fibroblast invasion into and contraction of the wounded area. We previously showed that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of the LIM-only protein Fhl2 in response to activation of the RhoA GTPase (Muller, J.M., U. Isele, E. Metzger, A. Rempel, M. Moser, A. Pscherer, T. Breyer, C. Holubarsch, R. Buettner, and R. Schule. 2000. EMBO J. 19:359-369; Muller, J.M., E. Metzger, H. Greschik, A.K. Bosserhoff, L. Mercep, R. Buettner, and R. Schule. 2002. EMBO J. 21:736-748.). We demonstrate impaired cutaneous wound healing in Fhl2-deficient mice rescued by transgenic expression of Fhl2. Furthermore, collagen contraction and cell migration are severely impaired in Fhl2-deficient cells. Consequently, we show that the expression of alpha-smooth muscle actin, which is regulated by Fhl2, is reduced and delayed in wounds of Fhl2-deficient mice and that the expression of p130Cas, which is essential for cell migration, is reduced in Fhl2-deficient cells. In summary, our data demonstrate a function of Fhl2 as a lipid-triggered signaling molecule in mesenchymal cells regulating their migration and contraction during cutaneous wound healing.

  14. Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Richard W.D. Gilbert

    2016-06-01

    Full Text Available Transforming growth factor beta (TGFβ signalling is essential for wound healing, including both non-specific scar formation and tissue-specific regeneration. Specific TGFβ isoforms and downstream mediators of canonical and non-canonical signalling play different roles in each of these processes. Here we review the role of TGFβ signalling during tissue repair, with a particular focus on the prototypic isoforms TGFβ1, TGFβ2, and TGFβ3. We begin by introducing TGFβ signalling and then discuss the role of these growth factors and their key downstream signalling mediators in determining the balance between scar formation and tissue regeneration. Next we discuss examples of the pleiotropic roles of TGFβ ligands during cutaneous wound healing and blastema-mediated regeneration, and how inhibition of the canonical signalling pathway (using small molecule inhibitors blocks regeneration. Finally, we review various TGFβ-targeting therapeutic strategies that hold promise for enhancing tissue repair.

  15. 缝合神经的指固有动脉背支血管链皮瓣修复指远端皮肤缺损%Repair of fingertip defect with proper digital artery lateral cutaneous branch-chain flap accompanied with dorsal digital nerve or dorsal branch of proper digital nerve coaptation

    Institute of Scientific and Technical Information of China (English)

    孙涛; 魏鹏; 周丹亚; 胡瑞斌; 滕晓峰; 陈宏

    2011-01-01

    Objective To explore the effect of using proper digital artery lateral cutaneous branch-chain flap with dorsal digital nerves or dorsal branch of proper digital nerye for repairing of fingertip defect.Methods From December 2008 to November 2009, 24 cases (26 digits) of fingertip defect were treated with proper digital artery lateral cutaneous branch-chain flap.The flap was designed on the lateral side of the proximal phalanx of the injured finger with its long axis running on the lateral midline of the finger.The vascular pedicle was 0.8 to 1.0 cm wide.The pivot point was at the distal 1/3 of the middle phalanx upon which the flap was reversed to repair the defect of the fingertip.The dorsal digital nerve or dorsal branch of proper digital nerve was included in the flap and coapted with the nerve in the wound to reconstruct sensation of the injured finger.Results All 26 flaps survived.Postoperative follow-up period was 6 to 8 months.All these flaps recovered with satisfying and quality, excellent sensation with 4 to 8 mm two-point discrimination.ROM of the interphalangeal joint of the injured finger was good.Conclusion Proper digital artery lateral cutaneous branchchain flap transfer with nerve coaptation is an ideal method for repairing fingertip defect.The surgery is simple.Reliable blood supply can be achieved without sacrificing the proper digital artery.Coaptation of the nerve restores sensation at the fingertip.There is minor donor site damage and very few complications.%目的 探讨缝合神经的指固有动脉背支血管链皮瓣修复指远端皮肤缺损的疗效.方法 2008年12月至2009年11月,对24例26指指远端皮肤缺损患者,以指固有动脉背侧支形成的血管链为血供,于近节指体侧方设计皮瓣,皮瓣轴线为指体侧方中线,皮瓣蒂宽0.8~1.0cm,皮瓣转折点为中节指体中远端,逆行转移修复指远端皮肤缺损,皮瓣携带指固有神经背侧支或指背神经与创面指神经断端进行缝合

  16. Cutaneous amebiasis.

    Science.gov (United States)

    Rimsza, M E; Berg, R A

    1983-04-01

    An infant with cutaneous amebiasis of the vulva and amebic liver abscess is described. Epidemiologic investigations and serologic studies were crucial in establishing the diagnosis. The vulvar amebic ulcers responded dramatically to metronidazole therapy. Cutaneous amebiasis is a rare complication of Entamoeba histolytica infection which should be considered in the differential diagnosis of perineovulvar or penile ulcers. Cutaneous amebiasis may also occur on the abdominal wall surrounding a draining hepatic abscess, colostomy site, or laparotomy incision.

  17. Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue in Experimental Type I Diabetes

    Directory of Open Access Journals (Sweden)

    Mariáurea M. Sarandy

    2017-01-01

    Full Text Available The effect of topical application of ointment based on Strychnos pseudoquina hydroethanolic extract in the cutaneous wounds healing in diabetic rats was evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups: Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of lanolin cream (vehicle; SS-wounds treated with silver sulfadiazine cream (10 mg/g; ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract, 5% and 10%, respectively. Fragments of wounds were removed for histological and biochemical analysis every 7 days during 21 days. ES showed equivalent levels per gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and 0.60 mg for RE. The chlorogenic acid was one of the major constituents. S. pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10 showed higher wound healing rate and higher amount of cells, blood vessels, and type III and I collagen. The oxidative stress markers were lower in the ES5 and ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic rats.

  18. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.

    Science.gov (United States)

    De Jesus, Aribet M; Aghvami, Maziar; Sander, Edward A

    2016-01-01

    Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical

  19. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.

    Directory of Open Access Journals (Sweden)

    Aribet M De Jesus

    Full Text Available Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours, structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient

  20. Animal models of chronic wound care: the application of biofilms in clinical research

    Directory of Open Access Journals (Sweden)

    Trøstrup H

    2016-11-01

    Full Text Available Hannah Trøstrup,1 Kim Thomsen,1 Henrik Calum,2 Niels Høiby,1,3 Claus Moser1 1Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, 3Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark Abstract: Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s, and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should

  1. An automated image processing method to quantify collagen fibre organization within cutaneous scar tissue.

    Science.gov (United States)

    Quinn, Kyle P; Golberg, Alexander; Broelsch, G Felix; Khan, Saiqa; Villiger, Martin; Bouma, Brett; Austen, William G; Sheridan, Robert L; Mihm, Martin C; Yarmush, Martin L; Georgakoudi, Irene

    2015-01-01

    Standard approaches to evaluate scar formation within histological sections rely on qualitative evaluations and scoring, which limits our understanding of the remodelling process. We have recently developed an image analysis technique for the rapid quantification of fibre alignment at each pixel location. The goal of this study was to evaluate its application for quantitatively mapping scar formation in histological sections of cutaneous burns. To this end, we utilized directional statistics to define maps of fibre density and directional variance from Masson's trichrome-stained sections for quantifying changes in collagen organization during scar remodelling. Significant increases in collagen fibre density are detectable soon after burn injury in a rat model. Decreased fibre directional variance in the scar was also detectable between 3 weeks and 6 months after injury, indicating increasing fibre alignment. This automated analysis of fibre organization can provide objective surrogate endpoints for evaluating cutaneous wound repair and regeneration.

  2. A influência da calcitonina sintética de salmão na cicatrização cutânea de ratos Influence of the synthetic salmon calcitonin in cutaneous wound healing of the rats

    Directory of Open Access Journals (Sweden)

    José Neiva Eulálio

    2007-08-01

    . Biochemical, biomechanical, and histological parameters were analyzed as well as possible relationships between them. METHODS: Seventy-two male rats were randomly assigned to control and experimental groups. Surgical procedure comprised the creation of incisional cutaneous wound, which was subsequently sutured. Experimental group was treated with synthetic salmon calcitonin postoperatively. The animals were sacrificed in the 5th, 10th, 15th and 20th postoperative days for wounded skin specimens removal for biochemical, biomechanical, and histological studies. RESULTS: In comparison to non-treated animals, a significant increase in hydroxyproline and collagen contents was observed in early and late proliferation phases of wound healing. Additionally, a significant increase in maximum rupture load in the late proliferation phase was observed. Histological findings corroborated biochemical and biomechanical results. CONCLUSION: Synthetic salmon calcitonin improved the wound healing process, but not in a linear constant fashion.

  3. Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells

    OpenAIRE

    Pollok, Simone; Pfeiffer, Ann-Catherine; Lobmann, Ralf; Wright, Catherine S; Moll, Ingrid; Martin, Patricia E M; Johanna M Brandner

    2010-01-01

    Abstract During early wound healing (WH) events Connexin 43 (Cx43) is down-regulated at wound margins. In chronic wound margins, including diabetic wounds, Cx43 expression is enhanced suggesting that down-regulation is important for WH. We previously reported that the Cx43 mimetic peptide Gap27 blocks Cx43 mediated intercellular communication and promotes skin cell migration of infant cells in vitro. In the present work we further investigated the molecular mechanism of Gap27 action and its t...

  4. β1 integrin signaling in asymmetric migration of keratinocytes under mechanical stretch in a co-cultured wound repair model.

    Science.gov (United States)

    Lü, Dongyuan; Li, Zhan; Gao, Yuxin; Luo, Chunhua; Zhang, Fan; Zheng, Lu; Wang, Jiawen; Sun, Shujin; Long, Mian

    2016-12-28

    Keratinocyte (KC) migration in re-epithelization is crucial in repairing injured skin. But the mechanisms of how mechanical stimuli regulate the migration of keratinocytes have been poorly understood. Human immortalized keratinocyte HaCaT cells were co-cultured with skin fibroblasts on PDMS membranes and transferred to the static stretch device developed in-house for additional 6 day culture under mechanical stretch to mimic surface tension in skin. To detect the expression of proteins on different position at different time points and the effect of β1 integrin mechanotransduction on HaCaT migration, Immunofluorescence, Reverse transcription-polymerase chain reaction, Flow cytometry, Western blotting assays were applied. Mechanical receptor of β1 integrin that recognizes its ligand of collagen I was found to be strongly associated with migration of HaCaT cells since the knockdown of β1 integrin via RNA silence eliminated the key protein expression dynamically. Here the expression of vinculin was lower but that of Cdc42 was higher for the cells at outward edge than those at inward edge, respectively, supporting that the migration capability of keratinocytes is inversely correlated with the formation of focal adhesion complexes but positively related to the lamellipodia formation. This asymmetric expression feature was further confirmed by high or low expression of PI3K for outward- or inward-migrating cells. And ERK1/2 phosphorylation was up-regulated by mechanical stretch. We reported here, a novel mechanotransduction signaling pathways were β1 integrin-dependent pattern of keratinocytes migration under static stretch in an in vitro co-culture model. These results provided an insight into underlying molecular mechanisms of keratinocyte migration under mechanical stimuli.

  5. β-Catenin-regulated myeloid cell adhesion and migration determine wound healing.

    Science.gov (United States)

    Amini-Nik, Saeid; Cambridge, Elizabeth; Yu, Winston; Guo, Anne; Whetstone, Heather; Nadesan, Puviindran; Poon, Raymond; Hinz, Boris; Alman, Benjamin A

    2014-06-01

    A β-catenin/T cell factor-dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin-mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury.

  6. Puncture Wounds

    Science.gov (United States)

    ... page. Please enable Javascript in your browser. Puncture Wounds What Is a Puncture Wound? Puncture wounds are not the same as cuts. ... professional treatment right away. Foreign Bodies in Puncture Wounds A variety of foreign bodies can become embedded ...

  7. A Primer on Wound Bed Preparation

    OpenAIRE

    Gokoo, Chuck

    2009-01-01

    Successful wound closure and healing are a major concern for today's clinician. Determining if the wound will progress or not relies on a comprehensive assessment, recognition of wound characteristics that will promote or impede the healing process and preparing the wound bed such that pathological features are removed allowing the healing cascade to occur. When complications are no longer a roadblock the wound will achieve a stable microenvironment and progress through the normal repairative...

  8. Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair.

    Science.gov (United States)

    Dang, Catherine M; Beanes, Steven R; Soo, Chia; Ting, Kang; Benhaim, Prosper; Hedrick, Marc H; Lorenz, H Peter

    2003-05-01

    Fibroblast growth factors (FGFs) are a family of 21 cytokines with a broad spectrum of activities, including regulation of cell proliferation, differentiation, and migration. The various FGFs bind to one or more of four different tyrosine kinase receptor types. FGFs 1, 2, 5, 7, and 10 are up-regulated during adult cutaneous wound healing. However, the expression of FGFs during fetal skin development and scarless wound healing has not been characterized. It was hypothesized that differential expression of FGF isoforms and receptors occurs during fetal skin development and that this differential expression pattern may regulate the transition from scarless repair to healing with scar formation. Excisional wounds (2 mm) were created on fetal rats at gestational days 16.5 (scarless) (one wound per fetus, n = 36 fetuses) and 19.5 (scarring) (one wound per fetus, n = 36 fetuses). Wounds were harvested at 24, 48, and 72 hours. Survival until wound harvest ranged from 66 to 75 percent for the gestational day 16 fetuses, and from 83 to 92 percent for the gestational day 19 fetuses. Nonwounded fetal skin from littermates (n = 12 fetuses per wound harvest time point) was used as the control. Wounds/skins were pooled by harvest time point, and RNA was isolated from pooled wounds/skins. Reduced-cycle, specific-primer reverse transcriptase-polymerase chain reaction was performed to determine the expression of FGF isoforms 2, 5, 7, 9, and 10 and FGF receptors 1, 2, and 4 in wounds relative to unwounded skin.In unwounded fetal skin, FGF isoform 5 expression more than doubled at birth. FGF 10 expression doubled during the transition period. FGF 7 expression increased more than sevenfold at birth. Expression of FGF isoforms 2 and 9 did not change during late fetal skin development. The expression of FGF receptors 1, 2, and 4 increased at birth. After wounding, expression of FGF isoforms 7 and 10 was down-regulated in scarless wounds, whereas FGF receptor 2 expression decreased in

  9. Wound Care.

    Science.gov (United States)

    Balsa, Ingrid M; Culp, William T N

    2015-09-01

    Wound care requires an understanding of normal wound healing, causes of delays of wound healing, and the management of wounds. Every wound must be treated as an individual with regard to cause, chronicity, location, and level of microbial contamination, as well as patient factors that affect wound healing. Knowledge of wound care products available and when negative pressure wound therapy and drain placement is appropriate can improve outcomes with wound healing. Inappropriate product use can cause delays in healing. As a wound healing progresses, management of a wound and the bandage material used must evolve.

  10. 面部皮肤挫裂伤伴灰粒嵌入的急诊美容修复%The aesthetic repair of facial lacerating wound associated with dust embedded

    Institute of Scientific and Technical Information of China (English)

    李开梓; 王晓川; 高吕静; 李志鹏; 颜如珍

    2013-01-01

    Objective To observe the methods and technique of plastic surgical repair in facial soft tissue trauma with dust embedded.Methods We repaired 62 wounds of emergency traumatic cases with aesthetic surgery methods and technique.Results The 62 wounds of emergency traumatic cases healed perfectly except the 2 cases with serious bruise and coloboma of skin were grafted skin on the granulation burn wounds.Conclusion Injury of facial superficial soft tissue might be repaired with cosmetic surgical operation on emergency and we applied aesthetic surgery methods and technique to repair the facial trauma can reduce traumatic tattoo,postoperative scar abnormality and iatrogenic disfigure effectively.%目的:探讨颜面部软组织外伤伴灰尘颗粒嵌入的急诊美容修复技术和方法.方法:根据伤情,分别对62例灰尘颗粒创面进行急诊清创及美容外科修复.结果:本组62例灰尘颗粒创面,除2例因皮肤挫伤严重并缺损行肉芽创面植皮外,余均达到Ⅰ期修复并愈合,外伤性文身不明显.结论:遵循美容整形外科原则修复颜面部灰尘颗粒嵌入创面,可有效地减少伤后颜面部的外伤性文身、瘢痕畸形和医源性毁容.

  11. Scarless wound healing: finding the right cells and signals.

    Science.gov (United States)

    Leavitt, Tripp; Hu, Michael S; Marshall, Clement D; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

    2016-09-01

    From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal

  12. Cloning, expression and functional analyses of human platelet-derived growth factor-B chain peptide for wound repair of cat corneal endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LUO Wen-juan; ZHAO Gui-qiu; WANG Chuan-fu; WANG Li-mei; WANG Xiao-ji

    2009-01-01

    Objective: To investigate the biological function of platelet-derived growth factor B (PDGF-B) on the survival and proliferation of cat corneal endothelial cells so as to provide bases for further studies of its role in wound repair and its clinical application.Methods: Total RNA was extracted from the placenta tissues of healthy pregnant women undergoing hysterotokotomy and PDGF eDNA was obtained with re-verse transcription-polymerase chain reaction (RT-PCR). The prokaryotic expression vector pET-PDGF-B was constructed and expressed the recombinant PDGF-B in Escherichia coli (E.coli) BL21 (DE3). After purification and refolding on Ni2+-chelation affinity chromatography (NTA) column, it was used to culture cat corneal endothelial cells. Cell proliferation was tested by modified tertrazolium salt (MTT) and flow cytometer. And the morphologic change and the ultrastructure were ob-served under an inverted phase contrast microscope, a scan-ning electron microscope and a transmission electon microscope, respectively.Results: PDGF-B chain peptide (PDGF-BB) gene was successfully inserted into the prokaryotic expression vector, pET-28a(+). The purified recombined protein pET-PDGF-B showed a single band on sodium dodecyl sulfate polyacry-lamide gel electropheresis (SDS-PAGE) with the molecular weight of about 27 u, which was in agreement with the de-duced value. MTT and flow cytometry showed that PDGF-BB promoted the survival and proliferation of cat corneal en-dothelial cells.Conclusions: The construction of recombinant prokary-otic expression vector pET-PDGF-B and the preparation of PDGF-BB protein provide a foundation for further study of the function of PDGF-BB and producing biological PDGF-BB protein. The expressed PDGF-BB promotes the prolif-eration of cultured cat corneal endothelial cells.

  13. Cutaneous loxoscelism

    Directory of Open Access Journals (Sweden)

    Purohit S

    1995-01-01

    Full Text Available A case of spider bitea presenting as cutaneous loxoscelism is reported. The clinical features and management of spider bite are highlighted and the relevant literature has been reviewed

  14. Molecular pathology of wound healing.

    Science.gov (United States)

    Kondo, Toshikazu; Ishida, Yuko

    2010-12-15

    Skin-wound healing is an orchestrated biological phenomena consisting of three sequential phases, inflammation, proliferation, and maturation. Many biological substances are involved in the process of wound repair, and this short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. With the development of genetically engineered animals, essential molecules for skin-wound healing have been identified. Especially, cytokines, and growth factors are useful candidates and markers for the determination of wound vitality or age. Moreover, bone marrow-derived progenitor cells would give significant information to wound age determination. In this review article, some interesting observations are presented, possibly contributing to the future practice of forensic pathologists. Copyright © 2010. Published by Elsevier Ireland Ltd.

  15. Clinical analysis of vacuum sealing drainage combined with artificial dermis in repairing chronic wounds%封闭负压引流技术联合人工真皮修复慢性创面的临床研究

    Institute of Scientific and Technical Information of China (English)

    陈柏秋; 彭文要; 邱加崇; 余继超; 刘冰峰; 招伟峰

    2014-01-01

    目的 观察封闭负压引流技术(VSD)联合人工真皮修复慢性创面的临床疗效.方法 66例慢性创面患者随机分成两组.对照组33例:予抗感染,改善微循环,聚维酮纱外敷,经换药治疗创面未愈者行植皮或皮瓣修复术.观察组33例:予抗感染,改善微循环,早期应用VSD处理创面,创面有新鲜肉芽组织后植入人工真皮(皮耐克),待其肉芽生长满意后行植皮术.结果 对照组平均住院天数(55.3±1.2)天,其中植皮或皮瓣修复术修复30例,创面换药愈合者3例,创面愈合后疤痕增生明显.观察组平均住院天数(31.6±1.2)天,其中20例患者创面较大,经外敷人工真皮,肉芽生长满意后予植皮手术,其余患者经植入人工真皮换药,创面治愈后外观满意,疤痕增生轻或不明显.结论 VSD联合人工真皮修复慢性创面可以有效的促进慢性创面愈合,减少疤痕增生,缩短住院时间.%Objective To observe the clinical efficacy of vacuum sealing drainage (VSD) combined with artificial dermis in repairing chronic wounds.Methods 66 cases of chronic wounds were randomly divided into control group and observation group,33 cases in each group.Control group was treated by antiinfection,microcirculation improvement,and wounds were covered by gauze soaked with povidone iodine cream with regular dressing change.Observation group was treated by anti-infection,microcirculation improvement and early vacuum sealing drainage (VSD),wounds were covered by artificial dermis (PELNAC) to induce dermal reconstruction after granulation tissue grew.Some bigger wounds were treated by skin grafting on base of satisfying growth of granulation tissue.Results In control group,the average hospital stay was (55.3 ± 1.2) days,30 cases received skin grafting or skin flap transplantation,wounds in 3 cases healed by wound dressing with remarkable scar formation.In observation group,the average hospital stay was (31.6 ± 1.2) days,bigger wounds in 20 cases

  16. 轴型肌皮瓣移植修复颈胸部难愈性创面%Axial myocutaneous flap transplantation for repair of refractory wound in the cervico-thoracic region

    Institute of Scientific and Technical Information of China (English)

    黎洪棉; 高建华; 姜平; 黎小间

    2011-01-01

    BACKGROUND: Axial myocutaneous flap transplantation is the common method for repair of various refractory. Thir method had certain blindness in judgment of the main arteiies in flaps before surgery in the past. Therefore, it is importantto develop a more accurate method.OBJECTIVE: To introduce the application experiences of axial myocutaneous flap in repair of refractory wound in the cervico-thoracic region.METHODS: Color dopplerflow imaging was used to examine the starting point, branching point, exterior diameter, vessel trend, vessel length and hemodynamic parameters of the main arteries of 4 types flaps from 62 cases. The axial myocutaneous flaps were designed according to the detection. The sizes of the axial myocutaneous flaps ranged from(£cfTK7cm)to(18cnft13cm;L RESULTS AND CONCLUSION: According to color dopplerflow imaging, one case of thoracodorsal artery had slow blood flow, rough vascular wall and obvious arteriosclerosis, and the other cases were with smooth blood flew and vascular wall, and without embolism, arteriosclerosis or absence of blood vessel. The starting point, branching point, exterior diameter, vessel trend and anatomic layers of the detected arteries were displayed clearly, in consistency with the results of operation; the flap completely survived in 60 cases with primary healing; distal partial necrosis occurred in 2 cases and was cured by symptomatic treatment. All the cases were followed up for4weeks to 6 years. 24 months in average, and the flaps were with a normal color, good texture and satisfactory appearance. Choosing a suitable pedicled musculo cutaneous flap for refractory wound in cervico-thoracic region according to specific conditions can achieve satisfactoryfunction and appearance. Color dopplerfloAi imaging e asimple, inturtri/e and and non-invashse method to judge blood vessel of axial myocutaneous flaps, and can guide the axial myocutaneous flap transplantation.%背景:轴型肌皮瓣移植是当前修复各种难愈

  17. Peripheral blood fibrocytes: enhancement of wound healing by cell proliferation, re-epithelialization, contraction, and angiogenesis.

    Science.gov (United States)

    Kao, Huang-Kai; Chen, Bin; Murphy, George F; Li, Qin; Orgill, Dennis P; Guo, Lifei

    2011-12-01

    To identify the in vitro characteristics and functional properties of fibrocytes and investigate the in vivo mechanism of action of fibrocytes injection in accelerating the cutaneous healing process in diabetic mice. Fibrocytes are hematopoietic derived stem cells that may have a role in tissue repair, perhaps as the precursors of fibroblast- or myofibroblast-like cells. In vitro, the time-dependent phenotypic expression of peripheral blood (PB) fibrocytes was stained with anti-CD11b, anti-CD45, anti-Col-I, and anti-α-SMA antibodies. The functional properties of fibrocytes and dermal fibroblasts were tested by using reverse-transcriptase polymerase chain reaction. In vivo, full thickness wounds in diabetic mice were treated either with fibrocytes, dermal fibroblasts, or phosphate buffered saline (PBS) through tail vein injection. Wound healing kinetics, including wound contraction, re-epithelialization, and microscopic metrics such as cell proliferation, angiogenesis, and granulation growth were investigated. Expression of proinflammatory factors, profibrotic factors, growth factors, and extracellular matrix components were measured in wound tissues. Fibrocytes gradually lose their hematopoietic cell markers and increase mesenchymal cell markers during differentiation in vitro. Fibrocytes stimulate wound healing by dermal cell proliferation, keratinocyte proliferation with re-epithelialization, and angiogenesis compared with dermal fibroblast and PBS treated wounds. Expression of angiogenesis markers (VEGF and b-FGF), growth factors (TGF-β, PDGF-A, and FGF-7), chemokines (MCP-1 and MIP-1α), and extracellular matrix (collagen-I and α-SMA) were upregulated in fibrocyte-treated wounds. Peripheral blood fibrocytes can accelerate wound healing by stimulating cell proliferation, re-epithelialization, and angiogenesis in a diabetic mice experimental model. The application of fibrocytes may represent a potential clinical solution for the treatment of chronic wounds

  18. 股前内侧穿支皮瓣游离移植修复手部创面%Clinical application of anteromedial thigh perforator flap transplantation for repairing wounds in the hand

    Institute of Scientific and Technical Information of China (English)

    杨晓东; 刘杨武; 杨锦; 陈逸民; 付尚俊; 周阳; 丁建波; 楼旭鹏

    2012-01-01

    Objective To investigate the clinical effects of repairing wounds in the hand with free anteromedial thigh perforator flap transplantation. Methods From June 2008 to June 2011,15 cases were treated with free anteromedial thigh perforator flap transplantation for repairing the wound in the hand.There were 5 cases of volar defects,4 cases of defects on the ulnar aspect of the hand,1case of first web space wound and 5 cases of dorsal defects.Wound sizes ranged from 6 cm × 4 cm to 13 cm × 9 cm.Flap pedicles were anastomosed to the radial artery and cephalic vein of the recipient site in 11cases,and to the ulnar artery and basilic vein in 4 cases.Direct closure of the donor rite was possible in 9 cases,while skin graft was necessary in 6 cases. Results All the transplants survived.There was no vascular crisis.Postoperative follow-up ranged from 3 to 12 months.Satisfactory clinical results were recorded. Conclusion Anteromedial thigh perforator flap transfer is an effective method of repairing wounds in the hand.%目的 探讨应用股前内侧穿支皮瓣游离移植修复手部创面的临床疗效.方法 2008年6月至2011年6月,应用股前内侧穿支皮瓣游离移植修复手部创面共15例,其中手掌侧创面5例,尺侧创面4例,虎口区创面1例,手背创面5例;缺损面积:6 cm×4cm~13cm×9 cm;其中11例与受区桡动脉、头静脉吻合,4例与尺动脉、贵要静脉吻合.供区直接缝合9例,部分植皮6例.结果 本组15例皮瓣全部存活,未出现血管危象.随访3~ 12个月,临床效果满意.结论 应用股前内侧穿支皮瓣游离移植修复手部(正)面,临床效果满意,值得推广应用.

  19. Connective tissue growth factor promoter activity in normal and wounded skin

    Directory of Open Access Journals (Sweden)

    Kapoor Mohit

    2008-10-01

    Full Text Available Abstract In skin, connective tissue growth factor (CTGF/CCN2 is induced during tissue repair. However, what the exact cell types are that express CTGF in normal and wounded skin remain controversial. In this report, we use transgenic knock-in mice in which the Pacific jellyfish Aequorea victoria enhanced green fluorescent protein (E-GFP gene has been inserted between the endogenous CTGF promoter and gene. Unwounded (day 0 and wounded (days 3 and 7 skin was examined for GFP to detect cells in which the CTGF promoter was active, α-smooth muscle actin (α-SMA to detect myofibroblasts, and NG2 expression to detect pericytes. In unwounded mice, CTGF expression was absent in epidermis and was present in a few cells in the dermis. Upon wounding, CTGF expression was induced in the dermis. Double immunolabeling revealed that CTGF-expressing cells also expressed α-SMA, indicating the CTGF was expressed in myofibroblasts. A subset (~30% of myofibroblasts were also NG2 positive, indicating that pericytes significantly contributed to the number of myofibroblasts in the wound. Pericytes also expressed CTGF. Collectively, these results indicate that CTGF expression in skin correlates with myofibroblast induction, and that CTGF-expressing pericytes are significant contributors to myofibroblast activity during cutaneous tissue repair.

  20. Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair

    NARCIS (Netherlands)

    Caskey, Robert C.; Allukian, Myron; Lind, Robert C.; Herdrich, Benjamin J.; Xu, Junwang; Radu, Antoneta; Mitchell, Marc E.; Liechty, Kenneth W.

    2013-01-01

    Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decr

  1. 皮能快愈敷料在深度烧伤创面治疗中的改良应用%The improved application of artificial dermaiin repairing depth of burn wounds

    Institute of Scientific and Technical Information of China (English)

    李钢; 陈智勇; 刘中文; 张杨; 胡鹏; 陈强

    2012-01-01

    Objective To explore the therapeutic efficacy of artificial dermal in repairing depth of burn wounds.Methods Twenty-two cases of patients with depth bum who were admitted to our hospital during August of 2008 to August of 2010 were enrolled in this trial for retrospective study.The style of management was evaluated in these patients.Burn wound depth and severity was assessed immediately after patients admission,wound treatment was performed after patients with stable vital signs and wound edema peak period vanished.Artificial dermal was grafted onto the wound tissue after the primary debridement. Then,transplantation of artificial dermal was performed,with moist dressingonto it.After two weeks,the razor thick autoskin was grafted onto the surface of the artificial dermal after the removing of its silicon membrane during the secondary operation.Results The wound healed completely with the survival of skin grafting and satisfactory appearance in all 22 patients. Furthermore,the scar in the donor site exhibited unconspicuous. Conclusion It's an optimal choice to repair deep burn with artificial dermal and thick autoskin.%目的 探讨皮能快愈敷料对深度烧伤患者的治疗效果.方法 2008年8月至2010年8月我们收治深度烧伤患者22例.患者入院后立即进行创面深度及烧伤严重程度评估,待生命体征稳定,创面水肿高峰期结束后行创面治疗,1期清创手术,行皮能快愈敷料移植术,皮能快愈敷料外加湿性敷料(德湿威);2周后Ⅱ期手术,去除皮能快愈敷料硅胶膜行自身刃厚皮移植.结果 22例深度烧伤创面均愈合,皮能快愈敷料无感染及溶解.皮片移植存活,创面外观满意,供皮区瘢痕增生轻.结论 改良皮能快愈敷料与自体刃厚皮复合修复深度烧伤创面具有较好的临床应用价值.

  2. Cutaneous zygomycosis.

    Science.gov (United States)

    Bonifaz, Alexandro; Vázquez-González, Denisse; Tirado-Sánchez, Andrés; Ponce-Olivera, Rosa María

    2012-01-01

    Cutaneous zygomycosis is a fungal infection caused by zygomycetes that affects the skin. It occurs in uncontrolled diabetic patients and immunosuppressed individuals. It has 2 clinical forms: primary cutaneous zygomycosis and secondary cutaneous zygomycosis. The first is characterized by necrotic lesions and the fungus is usually inoculated by trauma. If diagnosed early, it generally has a good prognosis. Secondary zygomycosis is usually a complication and extension of the rhinocerebral variety that starts as a palpebral fistula and progresses to a necrotic lesion with a poor prognosis. The diagnosis is made by identification of the fungus by direct KOH examination, culture, and biopsy. Treatment for the primary disease is surgical debridement plus amphotericin B. The secondary type is treated with amphotericin B and/or posaconazole.

  3. Clinical observation of ankle cutaneous defect repaired by flap prosthetics%皮瓣修复踝关节周围软组织缺损的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王道明; 曾荣铭; 余榕

    2016-01-01

    Objective To investigate the repair of ankle cutaneous defect with flap prosthetics. Methods There were 30 cases ankle cutaneous defect, who had been repaired with 6 kinds of skin flaps. Local gyral flap in 7 cases, distal sural neurocutaneous flap in 5 cases, distal perforators peroneal artery flap in 6 cases, posterior tibial artery perforators flap in 6 cases, reverse lateral supramalleolar island flap in 1 case, and free anterolateral femoral cutaneous flap in 5 cases. The dimensions of the flap ranged from 3 cm ×3 cm to 19 cm ×9 cm. Results 26 cases were one-stage survival, 2 cases of distal sural neurocutaneous flap partly necrosised and healed after change dressings, 1 case of posterior tibial artery perforators flap distal 1/4 portion necrosised and healed after two stage skin-grafting, 1 case of distal perforators peroneal artery flap venous crisis occurred and healing under-scab after distal portion bleeding therapy. Conclusion The application of flap prothesis can cure kinds of ankle cutaneous defect nicely.%目的:探讨应用外科皮瓣技术修复常见的踝关节周围软组织缺损的临床疗效。方法对2007-2014年收治的踝关节周围软组织缺损30例,行6种外科皮瓣技术修复,其中局部转移皮瓣7例,远端蒂腓肠神经皮瓣5例,远端蒂腓动脉皮穿支皮瓣6例,胫后动脉皮穿支皮瓣6例,逆行外踝上岛状皮瓣1例,游离股前外侧穿支皮瓣5例。切取皮瓣最小3 cm×3 cm,最大19 cm×9 cm。结果30例皮瓣中26例Ⅰ期全部成活;2例远端蒂腓肠神经岛状皮瓣远端部分坏死,经局部换药治疗后创面愈合;1例胫后动脉皮穿支皮瓣远端1/4部分坏死,经Ⅱ期植皮后闭合创面;1例远端蒂腓动脉皮穿支皮瓣术后出现静脉危象,行远端放血处理后,后期皮瓣皮肤脱痂愈合。随访3个月~5年,皮瓣质地好。结论应用皮瓣修复技术,可使骨科各类常见的踝关节周围软组

  4. Social facilitation of wound healing.

    Science.gov (United States)

    Detillion, Courtney E; Craft, Tara K S; Glasper, Erica R; Prendergast, Brian J; DeVries, A Courtney

    2004-09-01

    It is well documented that psychological stress impairs wound healing in humans and rodents. However, most research effort into influences on wound healing has focused on factors that compromise, rather than promote, healing. In the present study, we determined if positive social interaction, which influences hypothalamic-pituitary-adrenal (HPA) axis activity in social rodents, promotes wound healing. Siberian hamsters received a cutaneous wound and then were exposed to immobilization stress. Stress increased cortisol concentrations and impaired wound healing in isolated, but not socially housed, hamsters. Removal of endogenous cortisol via adrenalectomy eliminated the effects of stress on wound healing in isolated hamsters. Treatment of isolated hamsters with oxytocin (OT), a hormone released during social contact and associated with social bonding, also blocked stress-induced increases in cortisol concentrations and facilitated wound healing. In contrast, treating socially housed hamsters with an OT antagonist delayed wound healing. Taken together, these data suggest that social interactions buffer against stress and promote wound healing through a mechanism that involves OT-induced suppression of the HPA axis. The data imply that social isolation impairs wound healing, whereas OT treatment may ameliorate some effects of social isolation on health.

  5. Cutaneous sarcoidosis.

    Science.gov (United States)

    Wilson, N J; King, C M

    1998-11-01

    Sarcoidosis is a multi-organ granulomatous disorder of unknown cause. Skin sarcoidosis occurs in about 25% of patients with systemic disease and may also arise in isolation. A wide range of clinical presentations of cutaneous sarcoidosis is recognised. The diagnosis rests on the presence of non-caseating granulomas on skin biopsy and the exclusion of other granulomatous skin disease. The treatment and overall prognosis of cutaneous sarcoidosis is primarily dependent on the degree of systemic involvement. In patients with aggressive disease limited to the skin immunosuppressive therapy may be indicated.

  6. Repair of lower extremity soft tissue defect with free musculo-cutaneous flaps bridging with healthy contralateral posterior tibial vessel%游离肌皮瓣桥接胫后血管修复对侧下肢软组织缺损

    Institute of Scientific and Technical Information of China (English)

    夏成德; 狄海萍; 薛继东; 赵耀华; 李晓亮; 李强; 牛希华; 李永林; 连鸿凯

    2015-01-01

    Objective To observe the clinical effects of free musculo-cutaneous flap bridging with contralateral posterior tibial vessel on repair of lower extremity soft tissue defect.Methods From February 2006 to June 2013,10 patients with soft tissue defect on lower shank and foot were included.The posterior tibial vessel on healthy lower extremity was chosen as recipient vessel and anastomosed with free latissimus dorsi musculo-cutaneous flap,or free latissimus dorsi musculo-cutaneous flap combined with thoracic-umbilical skin flap or anterolateral femoral musculo-cutaneous flap.The retrograde bridged flap was transposed to repair defect on contralateral lower shank and foot.The wound area ranged from 40 cm × 21 cm to 22 cm×15 cm,with flap size from 48 cm×26 cm to 25 cm×18 cm.Meanwhile the defects on donor sites were covered with skin graft and both lower extremities were fixed with kirschner wires at middle tibia and calcaneus.The kirschner wires were removed at 4 weeks and pedicles were cut off 5 ~ 8 weeks postoperatively.Six patients received posterior tibial vessel reanastomosis at the same time of pedicle cutting.Results All the 10 flaps survived and 3 patients received thinning of flaps due to excessive thickness.During the follow-up period of 3 months to 2 years follow up,the ambulatory function of injured legs recovered gradually with satisfactory appearance.The reanastomosed posterior tibial vessel on the healthy side was recovered.Conclusions Appropriate bridged musculo-cutaneous flaps is suitable for extensive soft tissue defect of lower shank and foot.It is a safe and effective method for limb salvage.%目的 观察游离肌皮瓣与健肢胫后血管桥接修复对侧下肢软组织缺损的临床效果.方法 2006年2月至2013年6月,对10例小腿下段及足部软组织缺损患者,应用健肢胫后血管与游离背阔肌肌皮瓣、背阔肌肌皮瓣联合胸脐皮瓣、股前外侧肌肌皮瓣的血管吻合,形成以健肢

  7. Wound repair in Montipora capitata

    Science.gov (United States)

    Work, T.M.; Aeby, G.S.

    2010-01-01

    We documented the microscopic morphology of tissue healing in Montipora capitata. Fragments from two healthy coral colonies were traumatized by scraping tissue and skeleton and monitored in flow-through seawater tables every 2-4. days for 40. days for gross and cellular changes. Grossly, corals appeared healed and repigmented by Day 40. Histologically, traumatized issues were undistinguishable from intact untraumatized tissues by Day 12. We suspect that the calicoblastic epidermis of basal body wall is pluripotential and can develop into surface epidermis when needed. ?? 2010.

  8. Application of novel vacuum sealing drainage in repairing wound following operation of breast cancer%新型负压封闭引流技术在乳腺癌术后创面修复中的应用

    Institute of Scientific and Technical Information of China (English)

    鲍琼; 曹东升; 李红红; 谢娟

    2015-01-01

    目的:探讨新型负压封闭引流(VSD-D型)技术联合游离皮片移植在修复乳腺癌术后皮瓣坏死创面中的应用价值。方法对2014年3月至2014年8月处理的16例乳腺癌术后皮瓣存活不良局部创面坏死的病例,在创面封闭前期治疗中使用VSD-D型引流观察创面肉芽的生长情况,根据创面条件,Ⅱ期采用皮片移植修复创面。结果本组全部病例在使用VSD-D型后创面肉芽生长良好,结合后期游离皮片移植修复,全部病例创面均被修复,效果满意。结论 VSD-D型在修复乳腺癌术后残留创面上具有操作方便、缩短病程、促进肉芽生长的疗效,为Ⅱ期手术创造了良好条件。%Objective To investigate the clinical efficacy of novel vacuum sealing drainage (Type VSD-D),together with free skin grafting,in repairing wound due to skin flap necrosis following operation of breast cancer.Methods From Mar 2014 to Aug 2014,a novel vacuum sealing drainage (Type VSD-D)was used,in early stage of wound sealing treatment,to treat 16 patients with local skin flap necrosis following operation of breast cancer in our hospital.Five to seven days later,the device was removed and the situation of wounds and granula-tion tissues were observed.Free skin grafting was performed to repair the wound surface according to the wound situation.Results All gran-ulation tissues of the wounds due to skin flap necrosis grew and developed well when dealt with this type VSD-D technique.All 16 cases re-covered satisfactorily after skin grafting and wound healing.Conclusion The novel vacuum sealing drainage (Type VSD-D)is a technique simple to use,with the clinical efficacy of course shortening and granulation promoting in repairing wound due to skin flap necrosis following operation of breast cancer,and might make good preparation for subsequent operation.

  9. Vasculogenic Cytokines in Wound Healing

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    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  10. Cell therapy for wound healing.

    Science.gov (United States)

    You, Hi-Jin; Han, Seung-Kyu

    2014-03-01

    In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.

  11. Estudo comparativo do tratamento de ferimento de colon de coelho com reparo seroso da parede de jejunum e sutura primária Comparative study of colon wound repair using jejunal serosal wall and primary suture, in rabbits

    Directory of Open Access Journals (Sweden)

    Carlos Edmundo Fontes

    2000-03-01

    Full Text Available Os animais foram submetidos a procedimento operatório sob anestesia geral para a produção de dois ferimentos padronizados em colo não preparado, usando instrumento desenvolvido para esta finalidade. O primeiro ferimento foi produzido a 2 cm do ceco e o segundo 20 cm eqüidistante deste, no sentido caudal. Estes ferimentos foram reparados obedecendo a resultado de sorteio que determinou a técnica a ser usada, se com o lado seroso da parede de jejuno ou por sutura primária. Nas duas técnicas foram usados pontos separados de fio monofilamentar de poliglecaprone 4-0 , sendo que o animal serviu de controle para si mesmo. Realizou-se eutanásia no 7º P.O. para os animais do sub-grupo A e no 30º P.O. para os animais do sub-grupo B para avaliação macroscópica e microscópica. O experimento demonstrou que é viável o uso do lado seroso da parede de jejuno para reparar ferimento em colo não preparado e apresentou resultados com tendências a serem superiores aos da sutura primária , não dual de MaringáThe present research aimed to compare the repair of colon wound using both the jejunal wall and the primary suture . Thirty young rabbits white New Zeland were used, weighing about 3,2 Kg. and were born and raised at the University of Maringá's Experimental farm. The animals were deeply anaesthetized and then submited to a surgery during wich two similar wounds were made in unprepared colon . An instrument created for this purpose was used. The first wound was made 2 cm away from the ceco , and the second one was made 20 cm from the first wound in the caudal location. The wounds were repaired using either the jejunal serosal wall or the primary suture. In both techniques were used separated stitches , made by monofilament poliglecaprone 4-0. The animal was used to control itself. The animals were submited to euthanasia either in the 7th or in 30th day after surgery, at random.Then a macroscopic and microscopic study was made. This research

  12. Effect of polysaccharides from Opuntia ficus-indica (L.) cladodes on the healing of dermal wounds in the rat.

    Science.gov (United States)

    Trombetta, D; Puglia, C; Perri, D; Licata, A; Pergolizzi, S; Lauriano, E R; De Pasquale, A; Saija, A; Bonina, F P

    2006-05-01

    In traditional medicine extracts of polysaccharide-containing plants are widely employed for the treatment of skin and epithelium wounds and of mucous membrane irritation. The extracts of Opuntia ficus-indica cladodes are used in folk medicine for their antiulcer and wound-healing activities. The present study describes the wound-healing potential of two lyophilized polysaccharide extracts obtained from O. ficus-indica (L.) cladodes applied on large full-thickness wounds in the rat. When topically applied for 6 days, polysaccharides with a molecular weight (MW)>10(4)Da from O. ficus-indica cladodes induce a beneficial effect on cutaneous repair in this experimental model; in particular the topical application of O. ficus-indica extracts on skin lesions accelerates the reepithelization and remodelling phases, also by affecting cell-matrix interactions and by modulating laminin deposition. Furthermore, the wound-healing effect is more marked for polysaccharides with a MW ranging 10(4)-10(6)Da than for those with MW>10(6)Da, leading us to suppose that the fine structure of these polysaccharides and thus their particular hygroscopic, rheologic and viscoelastic properties may be essential for the wound-healing promoter activity observed.

  13. Wound healing in the 21st century.

    Science.gov (United States)

    Schreml, Stephan; Szeimies, Rolf-Markus; Prantl, Lukas; Landthaler, Michael; Babilas, Philipp

    2010-11-01

    Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.

  14. The clinical experience of repairing forefoot wound with perforator flap of free peroneal artery%游离腓动脉穿支皮瓣修复前足创面的临床体会

    Institute of Scientific and Technical Information of China (English)

    梁献丹; 王雨露; 周浩; 严威; 朱玉辉

    2016-01-01

    目的:探讨游离腓动脉穿支皮瓣修复前足创面的临床效果。方法2012年5月-2014年5月,收治前足皮肤软组织缺损7例,均采用游离腓动脉穿支皮瓣修复。结果7例皮瓣全部成活,无血管危象发生。随访6~12个月,皮瓣质地优良,颜色及外形满意,踝足部功能正常。结论采用游离腓动脉穿支皮瓣修复前足创面手术简单,疗效满意。%Objective To study the clinical effect of repairing forefoot wound with perforator flap of free peroneal artery. Methods From May 2012 to May 2014, 7 patiens were treated, whose forefoot skin and soft tissue was defected and were repaired with perforator flap of free peroneal artery. Results All flap of the 7 cases survived, and no blood vessel crisis appeared. By follow-up for 6 months, flap character was better, color and appearance was satisfied, the function of ankle and foot was normal. Conclusion The operation of repairing forefoot wound with perforator flap of free peroneal artery is a simple and the curative method, which can obtain satisfactory effect.

  15. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis.

    Science.gov (United States)

    Zhang, Xiao-Na; Ma, Ze-Jun; Wang, Ying; Li, Yu-Zhu; Sun, Bei; Guo, Xin; Pan, Cong-Qing; Chen, Li-Ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing.

  16. Cutaneous leiomyosarcoma.

    Science.gov (United States)

    Porter, Christopher J W; Januszkiewicz, Janek S

    2002-03-01

    Cutaneous leiomyosarcoma is a rare soft-tissue sarcoma with negligible metastatic potential, but local recurrence rates after surgical excision have ranged from 14 percent to 42 percent. Unlike other sarcomas, guidelines for the optimal surgical excision margin of cutaneous leiomyosarcoma are not clearly defined in the existing literature. A review of local experience with this condition revealed eight patients over 12 years, none of whom developed local recurrence or distant metastases. This is despite poor prognostic factors in seven patients and excision margins ranging from 1 to 27 mm. These findings are compared with previously published data, and conclusions are drawn based on analysis of the collective results. Complete surgical excision with a narrow margin is recommended, and patients should be observed for a minimum of 5 years after surgery.

  17. Estudo do reparo do ferimento de colon com o lado seroso da parede de jejuno, utilizando cianoacrilato e cola de fibrina Study of repair of rat's colon wound whith serosal of jejunal wall using cyanoacrylate and fibrin glue

    Directory of Open Access Journals (Sweden)

    Carlos Edmundo Rodrigues Fontes

    2006-04-01

    Full Text Available OBJETIVO: Comparar o efeito do cianoacrilato e da cola de fibrina como adesivo das bordas do ferimento de cólon reparado com o lado seroso da parede de jejuno. MÉTODO: Foram utilizados 45 ratos wistar adultos jovens, machos , com peso médio de 260 gramas procedentes do Biotério Central da Universidade Estadual de Maringá.Os animais foram submetidos a procedimento operatório sob sedação com thiopental para produção de ferimento pradonizado de 0,5 cm distante caudalmente a 2 cm do ceco que foi reparado no grupo I pelo lado seroso da parede de jejuno e sutura, no grupo II, pelo lado seroso da parede de jejuno e cola de fibrina, e o grupo III pelo lado seroso da parede de jejuno e cianoacrilato. No 4º dia de pós-operatório os animais foram submetidos a um enema opaco, para estudo o de estenose. No 7º dia de pós-operatório os animais foram submetidos a laparotomia sob sedação para estudo macroscópico da cavidade , e coleta dos segmentos que foram processados para análise microscópica. RESULTADOS: A cola de fibrina teve uma tendência de ser melhor reparadora, estimulando a proliferação de fibras de colágeno a partir da borda da ferida. CONCLUSÃO: O experimento demonstrou que o ferimento em cólon de rato pode ser reparado pelo lado seroso da parede de jejuno colado às bordas da ferida por cola de fibrina ou cianoacrilato.BACKGROUND: The present experiment aimed to compare the effect of the use of cyanoacrylate and fibrine glue as adesive on repared colon's wounds with the serosal side of jejuno's wall. METHODS: Forty five male, young adult Wister rats, weighting about 260 g , from the University of Maringá were used.After having been deeply anaesthetized (thiopental was used, the animals underwent a surgery, and a pattern 0,5 cm wound was made, 2 cm away from the cecum, in the caudal location. Group one the wound was repaired by using the jejunal serosal wall and suture.On group two the jejunal serosal wall and fibrine glue

  18. 腹壁下动脉穿支皮瓣修复外阴癌根治术后创面的方法及效果%Application of DIEP to repair the wound after radical vulvectomy

    Institute of Scientific and Technical Information of China (English)

    梁锋; 章一新; 陈昴

    2016-01-01

    目的:探讨应用腹壁下动脉穿支皮瓣修复外阴癌根治术后创面的方法及效果。方法自2010年5月至2015年3月,对6例外阴癌的患者均采用广泛的外阴癌根治术,扩大切除所受累的外阴皮肤。根据切除后外阴组织缺损面积的大小,在腹壁切去相同大小的腹壁下穿支皮瓣,以一侧腹壁下动静脉为蒂,通过阴阜区皮下隧道转移至外阴,重建外阴形态。结果6例患者切取腹壁下穿支皮瓣(6~10 cm)×(12~17 cm),术后皮瓣全部成活,Ⅰ期再造尿道口、阴道口外形满意。结论采用腹壁下动脉穿支皮瓣修复外阴癌根治术后创面,皮瓣转移安全、方便,副损伤轻,术后外阴形态满意,是较好的外阴修复重建的方法之一。%Objective To study the method and effect of using the deep inferior epigastric perforator flap (DIEP) to repair the wound after radical vulvectomy. Method From May 2010 to March 2011, 5 cases of patients with carcinoma of vulva were treated by radical vulvectomy. Then DIEP was harvested from the abdominal wall and transplanted to repair the wound through subcutaneous tunnel under skin of mons pubis, using the deep inferior epigastric artery and vein on one side as vascular pedicle. The urethral orifice and vaginal orifice were also reconstructed in the same stage of operation. Results All DIEP(6~10 cm×12~17 cm)survived well after operation with satisfactory appearance of the urethral orifice and vaginal orifice. Conclusion Application of DIEP is one of the best methods to repair the wounds after radical vulvectomy for the advantages like:safety, convenience, minor injury of donor site and satisfactory appearance.

  19. The use of amniotic membrane in the repair of duodenal wounds in Wistar rats Uso da membrana amniótica no reparo de feridas duodenais em ratos Wistar

    Directory of Open Access Journals (Sweden)

    Luciano Rodrigues Schimidt

    2010-02-01

    Full Text Available Purpose: In the search of a new material to repair duodenal wounds, a trial was conducted to assess the behavior of human amniotic membrane in the repair of the duodenal wall in rats. METHODS: Fifty Wistar rats weighing between 250 and 350g, male, were submitted to duodenotomy and randomly distributed into two groups. Group A (n=8 had no treatment and was used as the control group. In Group B (n=42 the duodenal wound was treated with a patch of human amniotic membrane. RESULTS: All animals in Group A died. In Group B no changes were observed with regards to death or the formation of duodenal fistula. All animals presented peritoneal adherences in the region on the duodenal wall repair and intestinal obstruction was observed in two animals. Healing of the duodenal wall in the region of the patch took place progressively as the post-operatory period increased, with regeneration of the mucosa and of the smooth muscle layer. CONCLUSION: From the clinical standpoint, the amniotic membrane proved to be a biological tissue which served as a temporary seal and allowed the wound to heal by second-intention, with re-establishment of the duodenal wall structure.OBJETIVO: Na busca de um novo material para o reparo dos ferimentos duodenais, foi efetuado um estudo para avaliar o comportamento da membrana amniótica humana no reparo da parede duodenal em ratos. MÉTODOS: Foram utilizados 50 ratos Wistar, com peso entre 250 e 350g, machos, distribuídos, aleatoriamente, em dois grupos. Grupo A (n=8, submetido à duodenotomia sem tratamento, utilizados como controle. Grupo B (n=42, submetido a um remendo de membrana amniótica humana para tratamento de ferimento duodenal provocado. RESULTADOS: Todos os animais do grupo A foram a óbito. No grupo B não foram observadas alterações quanto a óbito ou formação de fístula duodenal. Observaram-se em todos os animais aderências peritoneais à região do reparo da parede do duodeno e obstrução intestinal em

  20. Cutaneous mucormycosis postcosmetic surgery

    Science.gov (United States)

    Al-Tarrah, Khaled; Abdelaty, Mahmoud; Behbahani, Ahmad; Mokaddas, Eman; Soliman, Helmy; Albader, Ahdi

    2016-01-01

    Abstract Background: Mucormycosis is a rare, aggressive, and life-threatening infection that is caused by organisms belonging to the order Mucorales. It is usually acquired through direct means and virtually always affects immunocompromised patients with the port of entry reflecting the site of infection, in this case, cutaneous. Unlike other mucormycoses, patients affected by Apophysomyces elegans (A elegans) are known to be immunocompetent. This locally aggressive disease penetrates through different tissue plains invading adjacent muscles, fascia, and even bone causing extensive morbidity and may prove fatal if treated inadequately. Cutaneous mucormycosis is associated with disruption of cutaneous barriers such as trauma. However, rarely, it may be iatrogenic. No cases have been previously reported postcosmetic surgery, especially one that is so commonly performed, lipofilling. Case Report: The patient is a, previously healthy, 41-year-old middle-eastern female who was admitted to the plastic surgery department 17 days after undergoing cosmetic surgery. She suffered from extensive tissue inflammation and necrosis in both gluteal regions. Following admission, she was initially started on empirical antimicrobial therapy which was changed to an antifungal agent, voriconazole, when preliminary microbiological results showed filamentous fungi. This was discontinued and liposomal amphotericin B was commenced when further mycological analysis identified A elegans. Furthermore, she underwent a total of 10 sessions of extensive debridement to the extent that portions of the sacrum and left femoral head became exposed. Her clinical status and wounds improved with the appropriate management and she remained an inpatient for 62 days. Subsequently, she had defects in both gluteal regions which required reconstructive surgery. Conclusion: A elegans is an uncommon cause of iatrogenic cutaneous mucormycosis. A high index of clinical suspicion is required, especially in the