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Sample records for cutaneous wound healing

  1. Stem Cells for Cutaneous Wound Healing

    PubMed Central

    Kirby, Giles T. S.; Mills, Stuart J.; Cowin, Allison J.; Smith, Louise E.

    2015-01-01

    Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials. PMID:26137471

  2. Acceleration of cutaneous wound healing by brassinosteroids

    PubMed Central

    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 the anabolic properties of brassinosteroids possibly mediated through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Here we examined biological activity of homobrassinolide (HB) and its synthetic analogues on 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 d alongside 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 TGF-β and ICAM-1 were significantly lower, while TNF-α was nearly suppressed in the wounds from treated mice. Our data suggest that topical brassinosteroids accelerate wound healing by positively modulating inflammatory and re-epithelialization phases of the wound-repair process, in partby enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in a wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing. PMID:23937635

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

    PubMed

    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. PMID:26676806

  4. Platelet gel for healing cutaneous chronic wounds.

    PubMed

    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

  5. Wound Healing of Cutaneous Sulfur Mustard Injuries

    PubMed Central

    Graham, John S.; Chilcott, Robert P.; Rice, Paul; Milner, Stephen M.; Hurst, Charles G.; Maliner, Beverly I.

    2005-01-01

    Sulfur mustard is an alkylating chemical warfare agent that primarily affects the eyes, skin, and airways. Sulfur mustard injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Historically, blister aspiration and/or deroofing (epidermal removal), physical debridement, irrigation, topical antibiotics, and sterile dressings have been the main courses of action in the medical management of cutaneous sulfur mustard injuries. Current treatment strategy consists of symptomatic management and is designed to relieve symptoms, prevent infections, and promote healing. There are currently no standardized or optimized methods of casualty management that prevent or minimize deficits and provide for speedy wound healing. Several laboratories are actively searching for improved therapies for cutaneous vesicant injury, with the aim of returning damaged skin to optimal appearance and normal function in the shortest time. Improved treatment will result in a better cosmetic and functional outcome for the patient, and will enable the casualty to return to normal activities sooner. This editorial gives brief overviews of sulfur mustard use, its toxicity, concepts for medical countermeasures, current treatments, and strategies for the development of improved therapies. PMID:16921406

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

    PubMed Central

    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

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

    PubMed Central

    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

  8. Temporal effects of topical morphine application on cutaneous wound healing

    PubMed Central

    Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.

    2008-01-01

    Background Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Methods Full-thickness 4mm diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mM morphine sulfate on days 0–3 or 4–10 post-wounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 post-wounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Results Delays in wound closure observed during morphine application on days 0–3 post-wounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 post-wounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. Additionally, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. Conclusions These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds. PMID:18580183

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

    SciTech Connect

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

    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

  10. Stem cells in cutaneous wound healing.

    PubMed

    Cha, Jisun; Falanga, Vincent

    2007-01-01

    Treatment of chronic wounds remains difficult, in spite of better understanding of pathophysiologic principles and greater adherence to recognized standards of care. Even with recent advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, up to almost 50% of chronic wounds that have been present for more than a year remain resistant to treatment. Because of these realities, there is excitement in the use of stem cells to offset impaired healing. Early data appear encouraging, but much work remains to be done. Although pilot studies suggest that multipotent adult stem cells can accelerate wound repair or even reconstitute the wound bed, the answers will need to come from randomized clinical trials. Thus far, considerable focus has been placed on bone marrow-derived mesenchymal stem cells, and there are now promising approaches for introducing them into the wound. It might turn out, however, that other types of stem cells will be more effective, including those derived from hair follicles or, perhaps, subsets of bone marrow-derived cultured cells. Still, proper wound care and adherence to basic principles cannot be bypassed, even by the most sophisticated approaches. PMID:17276204

  11. Phototherapy promotes healing of cutaneous wounds in undernourished rats*

    PubMed Central

    Leite, Saulo Nani; de Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela dos Santos; Leite, Marcel Nani; Enwemeka, Chukuka S.; Frade, Marco Andrey Cipriani

    2014-01-01

    BACKGROUND Various studies have shown that phototherapy promotes the healing of cutaneous wounds. OBJECTIVE To investigate the effect of phototherapy on healing of cutaneous wounds in nourished and undernourished rats. METHODS Forty rats, 20 nourished plus 20 others rendered marasmus with undernourishment, were assigned to four equal groups: nourished sham, nourished Light Emitting Diode treated, undernourished sham and undernourished Light Emitting Diode treated. In the two treated groups, two 8-mm punch wounds made on the dorsum of each rat were irradiated three times per week with 3 J/cm2 sq cm of combined 660 and 890nm light; wounds in the other groups were not irradiated. Wounds were evaluated with digital photography and image analysis, either on day 7 or day 14, with biopsies obtained on day 14 for histological studies. RESULTS Undernourishment retarded the mean healing rate of the undernourished sham wounds (p < 0.01), but not the undernourished Light emission diode treated wounds, which healed significantly faster (p < 0.001) and as fast as the two nourished groups. Histological analysis showed a smaller percentage of collagen in the undernourished sham group compared with the three other groups, thus confirming our photographic image analysis data. CONCLUSION Phototherapy reverses the adverse healing effects of undernourishment. Similar beneficial effects may be achieved in patients with poor nutritional status. PMID:25387494

  12. Wnt signaling induces epithelial differentiation during cutaneous wound healing

    PubMed Central

    Houschyar, Khosrow S; Momeni, Arash; Pyles, Malcolm N; Maan, Zeshaan N; Whittam, Alexander J; Siemers, Frank

    2015-01-01

    ABSTRACT Cutaneous wound repair in adult mammals typically does not regenerate original dermal architecture. Skin that has undergone repair following injury is not identical to intact uninjured skin. This disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development and thus we seek a deeper understanding of the role that Wnt signaling plays in the mechanisms of skin repair in both fetal and adult wounds. The influence of secreted Wnt signaling proteins in tissue homeostasis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. Endogenous Wnt signaling augmentation represents an attractive option to aid in the restoration of cutaneous wounds, as the complex mechanisms of the Wnt pathway have been increasingly investigated over the years. In this review, we summarize recent data elucidating the roles that Wnt signaling plays in cutaneous wound healing process. PMID:26309090

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

    PubMed

    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 BRAF(V600)-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

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

    PubMed Central

    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. Hyaluronidase modulates inflammatory response and accelerates the cutaneous wound healing.

    PubMed

    Fronza, Marcio; Caetano, Guilherme F; Leite, Marcel N; Bitencourt, Claudia S; Paula-Silva, Francisco W G; Andrade, Thiago A M; Frade, Marco A C; Merfort, Irmgard; Faccioli, Lúcia H

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

  16. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

    PubMed Central

    Fronza, Marcio; Caetano, Guilherme F.; Leite, Marcel N.; Bitencourt, Claudia S.; Paula-Silva, Francisco W. G.; Andrade, Thiago A. M.; Frade, Marco A. C.; Merfort, Irmgard; Faccioli, Lúcia H.

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

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

    PubMed

    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. PMID:26360824

  18. Variation of intensity on the healing of cutaneous wounds

    NASA Astrophysics Data System (ADS)

    do Nascimento, Patrícia M.; Barbosa Pinheiro, Antônio L.; Castillo Salgado, Miguel A.; Pedreira Ramalho, Luciana M.

    2003-06-01

    Tissue repair is an integration of dynamic interactive processes that involves soluble mediators, blood components, production of extra-cellular matrix and mesenchymal cells. Many studies involving the use of LLLT shows that the healing process is favored by such therapy. The aim of this work was to evaluate, through histological analysis, the tissue effects of cutaneous wounds submitted to different intensities and a same irradiation dose with lasers in λ670 or λ685nm. Eighteen animals were divided in two experimental groups according to wavelength used (λ670 or λ685nm). Each one of these groups was divided still in three subgroups of three animals each, related to the intensity of applied irradiation (2, 15 or 25mW). Twelve animals acted as untreated controls and were not irradiated. The irradiation was carried out during seven days. The animals were sacrificed eight days after surgery. The specimens were removed, kept in 4% formaldehyde for 24 hours, routinely prepared to wax, stained with H&E and analyzed under light microscopy. The histological characteristics observed, so much in the irradiated animals, as in the control, they are indicative of a substitution repair process, however, the LLLT modulatory positive effect was observed, in the healing process, mainly associate to the use of the shorter wavelength and low power. The results of the present study indicate that LLLT improves cutaneous wound repair and best results are achieved when higher potencies associated to short wavelengths or lower potencies associated to higher wavelengths are used.

  19. The effects of ageing on cutaneous wound healing in mammals.

    PubMed Central

    Ashcroft, G S; Horan, M A; Ferguson, M W

    1995-01-01

    The dogma that cutaneous wound healing is impaired as a function of age is largely unsubstantiated. This can be attributed to poor experimental design of human studies, the lack of subject characterisation with the exclusion of disease processes, and the study of inappropriate animal models. Structural and functional changes in skin with age have been reported, such as a decrease in dermal thickness, decline in collagen content, a subtle alteration in the glycosaminoglycan profile, and a loss of elasticity, but these reports are subject to the above criticisms in addition to the often-neglected requirement for site specificity. Wound repair can be thought of as a culmination of three major overlapping phases: inflammation, proliferation and remodelling. The inflammatory process has not been studied systematically with respect to age, and despite a reported decline in cellular function and number, there is a confounding increase in the production of specific cytokines involved in the process of repair. The proliferative phase is associated with a loss of cellular responsiveness to specific cytokines with a decline in motility and proliferation; however caution in interpreting these findings is important as, for example, the definition of 'ageing' is used rather loosely with the result that neonatal versus young adult cells are compared instead of young versus old adults. During remodelling, fibronectin and collagen production may increase with age, as may wound contraction; the deposition of elastin has not been assessed and the resulting mechanical properties of the scar are controversial, not least because human in vivo studies have been ignored. The absence of a critical review on the effects of advancing age on wound healing has conspired to permit the perpetuation of the belief that well defined tenets exist. This review aims to redress this imbalance and to highlight the need for well designed research into an increasingly important field. Images Fig. 1 Fig. 2

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    Castellucci, Léa; Jamieson, Sarra E; Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Lessa, Marcus; Fakiola, Michaela; de Jesus, Amélia Ribeiro; Miller, E. Nancy; Carvalho, Edgar 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 the TGF beta pathway. Haplotype tagging single nucleotide polymorphisms (tag-SNPs) were genotyped using Taqman technology in 325 nuclear families (652 CL cases; 126 ML cases) from Brazil. Robust case-pseudocontrol (CPC) conditional logistic regression analysis showed associations between CL and SNPs at CTGF (SNP rs6918698; CC genotype; OR 1.67; 95%CI 1.10–2.54; P=0.016), TGFBR2 (rs1962859; OR 1.50; 95%CI 1.12–1.99; P=0.005), SMAD2 (rs1792658; OR 1.57; 95%CI 1.04–2.38; P=0.03), SMAD7 (rs4464148; AA genotype; OR 2.80; 95%CI 1.00–7.87; P=0.05) and FLII (rs2071242; OR 1.60; 95%CI 1.14–2.24; P=0.005), and between ML and SNPs at SMAD3 (rs1465841; OR 2.15; 95%CI 1.13–4.07; P=0.018) and SMAD7 (rs2337107; TT genotype; OR 3.70; 95%CI 1.27–10.7; P=0.016). Stepwise logistic regression analysis showed that all SNPs associated with CL at FLI1, CTGF, TGFBR2, and FLII showed independent effects from each other, but SNPs at SMAD2 and SMAD7 did not add independent effects to SNPs from other genes. These results suggest that TGFβ signalling via SMAD2 is important in directing events that contribute to CL, whereas signalling via SMAD3 is important in ML. Both are modulated by the inhibitory SMAD7 that acts upstream of SMAD2 and SMAD3 in this signalling pathway. Along with the published FLI1 association, these data further contribute to the hypothesis that wound healing processes are important determinants of pathology associated with cutaneous forms of leishmaniasis. PMID:22554650

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

    PubMed

    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

    2016-05-01

    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. PMID:26791370

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

    PubMed Central

    Ud-Din, Sara; Bayat, Ardeshir

    2014-01-01

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

    PubMed Central

    WU, XUE; YANG, LONGLONG; ZHENG, ZHAO; LI, ZHENZHEN; SHI, JIHONG; LI, YAN; HAN, SHICHAO; GAO, JIANXIN; TANG, CHAOWU; SU, LINLIN; HU, DAHAI

    2016-01-01

    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 metallopro-teinase-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. PMID:26821191

  6. Mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs): potential role in healing cutaneous chronic wounds.

    PubMed

    Zou, Ji-Ping; Huang, Sha; Peng, Yan; Liu, Hong-Wei; Cheng, Biao; Fu, Xiao-Bing; Xiang, Xiao-Fei

    2012-12-01

    Chronic wounds remain a major challenge in modern medicine and represent a significant health care burden. Several treatments have been suggested, but without a full understanding of the exact mechanism by which chronic wound occurs. Numerous studies have shown that mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) may have therapeutic potential in healing cutaneous chronic wounds through various mechanisms. So far, a series of hypotheses have been proposed, but a holistic image of them is lacking. This review provides a systematic analysis of recent research in animal models and preclinical or clinic trails to evaluate the potential role of MSCs in chronic cutaneous wound healing. Most important, we highlight how mesenchymal stem cells could potentially revolutionize our approach to treating cutaneous chronic wounds. Special attention should be focused on ongoing research regarding the challenges in using and prospects of MSCs in clinical settings. PMID:23222159

  7. The role of iron in the skin and cutaneous wound healing

    PubMed Central

    Wright, Josephine A.; Richards, Toby; Srai, Surjit K. S.

    2014-01-01

    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 UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. 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. PMID:25071575

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

    PubMed Central

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

    PubMed

    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. PMID:26056233

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

    PubMed

    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. PMID:25068282

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

    PubMed Central

    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. PMID:25068282

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

    PubMed

    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. PMID:26802241

  13. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing.

    PubMed

    Gong, ChangYang; Wu, QinJie; Wang, YuJun; Zhang, DouDou; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong

    2013-09-01

    A biodegradable in situ gel-forming controlled drug delivery system composed of curcumin loaded micelles and thermosensitive hydrogel was prepared and applied for cutaneous wound repair. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent. Due to its high hydrophobicity, curcumin was encapsulated in polymeric micelles (Cur-M) with high drug loading and encapsulation efficiency. Cur-M loaded thermosensitive hydrogel (Cur-M-H) was prepared and applied as wound dressing to enhance the cutaneous wound healing. Cur-M-H was a free-flowing sol at ambient temperature and instantly converted into a non-flowing gel at body temperature. In vitro studies suggested that Cur-M-H exhibited well tissue adhesiveness and could release curcumin in an extended period. Furthermore, linear incision and full-thickness excision wound models were employed to evaluate the in vivo wound healing activity of Cur-M-H. In incision model, Cur-M-H-treated group showed higher tensile strength and thicker epidermis. In excision model, Cur-M-H group exhibited enhancement of wound closure. Besides, in both models, Cur-M-H-treated groups showed higher collagen content, better granulation, higher wound maturity, dramatic decrease in superoxide dismutase, and slight increase in catalase. Histopathologic examination also implied that Cur-M-H could enhance cutaneous wound repair. In conclusion, biodegradable Cur-M-H composite might have great application for wound healing. PMID:23726229

  14. Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice.

    PubMed

    Hardman, Matthew J; Emmerson, Elaine; Campbell, Laura; Ashcroft, Gillian S

    2008-02-01

    A lack of systemic hormones in elderly postmenopausal women leads to delayed cutaneous wound healing. This effect can be reversed by systemic or topical estrogen replacement in both humans and rodent models. Over recent years selective estrogen receptor modulators have been developed in an attempt to achieve the beneficial effects of estrogen clinically, while minimizing the detrimental side effects. The effects of selective estrogen receptor modulators on the skin are poorly understood, and the effects on wound healing have not been assessed. In this study we treated 10-wk-old ovariectomized mice with estradiol, tamoxifen (TAM), raloxifene (RAL), or vehicle and examined the effect on healing of full-thickness incisional wounds. Both TAM and RAL substantially accelerate healing, associated with a dampened inflammatory response and altered inflammatory cytokine profile. In vitro TAM and RAL demonstrate antiinflammatory activity comparable to estrogen. These results have significant implications for the clinical modulation of wound healing. PMID:17974625

  15. Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

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

    2009-06-01

    Sympathetic nerve failure has been proposed as a contributing factor in impaired cutaneous wound healing in diabetes mellitus. Nevertheless, no studies have shown whether beta-adrenoceptor blockade through beta-blocker (e.g., propranolol) administration may alter healing of diabetic cutaneous lesions. This study evaluated macro- and microscopically the effects of propranolol administration on cutaneous wound healing in streptozotocin-induced diabetic rats. Acute diabetes was induced by a single intraperitoneal injection of streptozotocin 14 days before wounding. Animals were treated with propranolol (50 mg/kg) dissolved in drinking water; controls received water only. Administration of beta-receptor antagonist began 1 day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion (1 cm(2)) was created. The wound area was measured weekly and the animals were killed 14 days after wounding. Lesions and adjacent skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and immunostained for CD-68, alpha-smooth muscle actin and proliferating cell nuclear antigen. The wound area was significantly smaller in the propranolol-treated group than in the control group 7 and 14 days after wounding. Inflammatory cell numbers and metalloproteinase-9 levels were reduced in the propranolol-treated group compared to the control group 14 days after wounding. Cell proliferation, mast cell number, collagen deposition, blood vessel density, and nitric oxide levels were increased in the propranolol-treated group compared to the control group 14 days after wounding. Propranolol administration improves cutaneous wound healing of hyperglycemic diabetic rats by reducing the local inflammatory response and improving subsequent phases of the repair process. PMID:19344703

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:27187186

  18. Therapeutic potential of bone marrow-derived mesenchymal stem cells for cutaneous wound healing.

    PubMed

    Chen, Jerry S; Wong, Victor W; Gurtner, Geoffrey C

    2012-01-01

    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. PMID:22787462

  19. Diminished Type III Collagen Promotes Myofibroblast Differentiation and Increases Scar Deposition in Cutaneous Wound Healing

    PubMed Central

    Volk, Susan W.; Wang, Yanjian; Mauldin, Elizabeth A.; Liechty, Kenneth W.; Adams, Sherrill L.

    2011-01-01

    The repair of cutaneous wounds in the postnatal animal is associated with the development of scar tissue. Directing cell activities to efficiently heal wounds while minimizing the development of scar tissue is a major goal of wound management and the focus of intensive research efforts. Type III collagen (Col3), expressed in early granulation tissue, has been proposed to play a prominent role in cutaneous wound repair, although little is known about its role in this process. To establish the role of Col3 in cutaneous wound repair, we examined the healing of excisional wounds in a previously described murine model of Col3 deficiency. Col3 deficiency (Col3+/–) in aged mice resulted in accelerated wound closure with increased wound contraction. In addition, Col3-deficient mice had increased myofibroblast density in the wound granulation tissue as evidenced by an increased expression of the myofibroblast marker, α-smooth muscle actin. In vitro, dermal fibroblasts obtained from Col3-deficient embryos (Col3+/– and –/–) were more efficient at collagen gel contraction and also displayed increased myofibroblast differentiation compared to those harvested from wild-type (Col3+/+) embryos. Finally, wounds from Col3-deficient mice also had significantly more scar tissue area on day 21 postwounding compared to wild-type mice. The effect of Col3 expression on myofibroblast differentiation and scar formation in this model suggests a previously undefined role for this ECM protein in tissue regeneration and repair. PMID:21252470

  20. Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

    PubMed Central

    Ji, Yuanyuan; Zhang, Aijun; Chen, Xiaobin; Che, Xiaoxia; Zhou, Kai; Wang, Zhidong

    2016-01-01

    Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague–Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. PMID:27006897

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

    PubMed

    Idrovo, Juan-Pablo; Yang, Weng-Lang; Jacob, Asha; Ajakaiye, Michael A; Cheyuo, Cletus; Wang, Zhimin; Prince, Jose M; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    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. PMID:25781901

  2. ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

    PubMed

    Chang, Hsiao-Min; Huang, Wen-Yen; Lin, Sung-Jan; Huang, Wei-Chao; Shen, Chia-Rui; Mao, Wan-Yu; Shen, Chia-Ning

    2016-05-01

    The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing. PMID:26739701

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed Central

    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

  8. Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel.

    PubMed

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

    2013-07-01

    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

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

    PubMed Central

    2010-01-01

    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. PMID:20211009

  10. Anti-Angiogenic Drugs: Involvement in Cutaneous Side Effects and Wound-Healing Complication

    PubMed Central

    Bodnar, Richard J.

    2014-01-01

    Significance: The uses of anti-angiogenic drugs have not only made an impact on the battle to eliminate cancer but are also responsible for a number of medical complications. The long-term use of these drugs has increased the spectrum and incidence of cutaneous side effects and wound-healing complications. It is, therefore, necessary to understand the overall impact that these drugs have on patient care. Recent Advances: This review highlights the role of vascular endothelial growth factor and fibroblast growth factor in angiogenesis and wound healing and looks at how angiogenic inhibitors promote wound-healing complications. Critical Issues: With an increased use of anti-angiogenic drugs for the treatment of various cancers and ocular diseases, there is an increased need for clinicians to define the risks and to optimize the usage of these drugs to reduce the incidence of cutaneous side effects and wound-healing complications. In addition, awareness is needed when treating patients on anti-angiogenic drugs so as not to exacerbate potential wound-healing complications when performing surgical procedures. Future Directions: Clinicians and surgeons will need to develop management guidelines to optimize patient care to reduce the risk of morbidity. When performing a surgical procedure, the impact of adverse effects from the use of anti-angiogenic drugs should be considered to ensure the welfare of the patient. In addition, the development of more specific inhibitors is necessary to reduce target effects to reduce the occurrence of adverse effects. PMID:25302138

  11. Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing.

    PubMed

    Jackson, Christopher J; Xue, Meilang; Thompson, Patrick; Davey, Ross A; Whitmont, Kaley; Smith, Susan; Buisson-Legendre, Nathalie; Sztynda, Tamara; Furphy, Louise J; Cooper, Alan; Sambrook, Philip; March, Lyn

    2005-01-01

    Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinase, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds. PMID:15953048

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

    PubMed Central

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

    2016-01-01

    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. PMID:27051343

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

    PubMed

    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. PMID:27051343

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:26515142

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

    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. PMID:19907077

  19. The effect of topical ethanol extract of Cotinus coggygria Scop. on cutaneous wound healing in rats.

    PubMed

    Aksoy, Halil; Sancar, Mesut; Sen, Ali; Okuyan, Betul; Bitis, Leyla; Uras, Fikriye; Akakin, Dilek; Cevik, Ozge; Kultur, Sukran; İzzettin, Fikret Vehbi

    2016-01-01

    The aim of this study is to determine the cutaneous wound healing effects of the ethanol extract of Cotinus coggygria leaves in rats by excision wound model to provide scientific evidence for the traditional use of C. coggygria Scop. The levels of malondialdehyde, catalase, superoxide dismutase, glutathione and hydroxyproline were investigated in wound tissues. Histopathological examination was also performed. The hydroxyproline content of the granulation tissue and the glutathione levels were both significantly higher in the treatment group than in the control group (p < 0.05 for both); while the malondialdehyde levels were significantly lower in the treatment group (p < 0.05). These results were supported with histological results. The ethanol extract of C. coggygria Scop could be considered as an effective agent in wound healing in accordance with its traditional use. PMID:25775378

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

    PubMed

    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 (P<0.05) and 7 (P<0.01 and P<0.05) after wound surgery, respectively. Both hematoxylin-eosin staining and Masson-trichrome staining revealed an increased intensity of collagen fibers and a greater number of fibroblasts in the ozone 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. PMID:19543419

  1. Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing

    PubMed Central

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

    2009-01-01

    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 (P<0.05) and 7 (P<0.01 and P<0.05) after wound surgery, respectively. Both hematoxylin-eosin staining and Masson-trichrome staining revealed an increased intensity of collagen fibers and a greater number of fibroblasts in the ozone group than that in the oil group on day 7. Immunohistochemical staining demonstrated upregulation of platelet derived growth factor (PDGF), transforming growth factor-β (TGF-β) 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-β, and VEGF. PMID:19543419

  2. Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring

    PubMed Central

    Rees, Peter Adam; Greaves, Nicholas Stuart; Baguneid, Mohamed; Bayat, Ardeshir

    2015-01-01

    Significance: Cutaneous scarring is an almost inevitable end point of adult human wound healing. It is associated with significant morbidity, both physical and psychological. Pathological scarring, including hypertrophic and keloid scars, can be particularly debilitating. Manipulation of the chemokine system may lead to effective therapies for problematic lesions. Recent Advances: Rapid advancement in the understanding of chemokines and their receptors has led to exciting developments in the world of therapeutics. Modulation of their function has led to clinically effective treatments for conditions as diverse as human immunodeficiency virus and inflammatory bowel disease. Potential methods of targeting chemokines include monoclonal antibodies, small-molecule antagonists, interference with glycosaminoglycan binding and the use of synthetic truncated chemokines. Early work has shown promising results on scar development and appearance when the chemokine system is manipulated. Critical Issues: Chemokines are implicated in all stages of wound healing leading to the development of a cutaneous scar. An understanding of entirely regenerative wound healing in the developing fetus and how the expression of chemokines and their receptors change during the transition to the adult phenotype is central to addressing pathological scarring in adults. Future Directions: As our understanding of chemokine/receptor interactions and scar formation evolves it has become apparent that effective therapies will need to mirror the complexities in these diverse biological processes. It is likely that sophisticated treatments that sequentially influence multiple ligand/receptor interactions throughout all stages of wound healing will be required to deliver viable treatment options. PMID:26543682

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

    PubMed

    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. PMID:25036212

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

    NASA Astrophysics Data System (ADS)

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

    PubMed Central

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

    2014-01-01

    Abstract. 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. PMID:25036212

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

    PubMed

    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. PMID:26679676

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

    PubMed

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

    2016-01-01

    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. PMID:26960535

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

    PubMed

    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. PMID:21134039

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

    PubMed Central

    2012-01-01

    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. PMID:23234369

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

    PubMed Central

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

    2008-01-01

    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. PMID:19145704

  11. Evaluation of cutaneous wound healing activity of Malva sylvestris aqueous extract in BALB/c mice

    PubMed Central

    Afshar, Mohammad; Ravarian, Behdad; Zardast, Mahmoud; Moallem, Seyed Adel; Fard, Mohammad Hasanpour; Valavi, Masoomeh

    2015-01-01

    Objective(s): The aim of this study was to evaluate the effects of Malva sylvestris aqueous extract on cutaneous wound healing in BALB/c mice. Materials and Methods: Twenty seven male BALB/c mice (2.5 months of age) were used. A cut wound (superficial fascia depth) was made locally. The mice were then divided into three groups: the first, second and third groups received topical administration of M. sylvestris 1% aqueous extract, silver sulfadiazine topical cream and cold cream (positive and negative control groups), respectively. On days 4, 7 and 10 excisional biopsies were performed and wound healing was evaluated histopathologically. The data were analyzed by the ANOVA and Tukey statistical tests. Results: On days 4 and 7, the numbers of inflammatory cells in the silver sulfadiazine and M. sylvestris-treated groups were significantly lower than the control group and keratinization at the edges of the wound in both groups was significantly higher than the control group. On the tenth day of the study, the Malva-treated mice showed better healing features and less fibrosis and scar formation, and also fewer hair follicles were damaged in this group. On the tenth day of the study, the numbers of inflammatory cells in M. sylvestris and silver sulfadiazine-treated groups were significantly lower than the control group. Conclusion: The present study supports the beneficial effects of M. sylvestris on the wound healing process and suggests a potential clinical application. PMID:26221487

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

    PubMed

    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. PMID:24321012

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

    PubMed Central

    Moreira, Eduarda Antunes; de Morais, Gutierrez Rodrigues; Pacheco, Isabela Almeida

    2016-01-01

    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 healing. PMID

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

    PubMed

    Bueno, Fernanda Giacomini; Moreira, Eduarda Antunes; Morais, Gutierrez Rodrigues de; Pacheco, Isabela Almeida; Baesso, Mauro Luciano; Leite-Mello, Eneri Vieira de Souza; Mello, João Carlos Palazzo de

    2016-01-01

    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 healing. PMID

  15. Factors Affecting Wound Healing

    PubMed Central

    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

  16. Acute Cutaneous Wounds Treated with Human Decellularised Dermis Show Enhanced Angiogenesis during Healing

    PubMed Central

    Greaves, Nicholas S.; Morris, Julie; Benatar, Brian; Alonso-Rasgado, Teresa; Baguneid, Mohamed; Bayat, Ardeshir

    2015-01-01

    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. PMID:25602294

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

    PubMed Central

    Ashkani-Esfahani, Soheil; Zarifi, Fariba; Asgari, Qasem; Samadnejad, Asal Zargari; Rafiee, Shima; Noorafshan, Ali

    2014-01-01

    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. PMID:25337534

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

    PubMed

    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. PMID:27060469

  19. Female, but not male, mice show delayed cutaneous wound healing following aspirin administration.

    PubMed

    dos Santos, Jeanine S; Monte-Alto-Costa, Andréa

    2013-02-01

    Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and thus COX inhibition, distinctly affects cutaneous wound healing in female and male mice. Female and male BALB/c mice were treated with aspirin (25 mg/kg per day) for 16 days until they were killed. The control group received vehicle (saline) only. A full-thickness excisional lesion was made on the back, 2 days after aspirin administration started, and macroscopic, histological and biochemical parameters were evaluated. Sections were stained and immunostained for microscopic analysis. Myeloperoxidase (MPO) activity, hydroxyproline quantity and the protein expression of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) were also determined. Female control and aspirin-treated groups exhibited delayed wound closure and re-epithelization compared with the male control and aspirin-treated groups, respectively. The female control group exhibited reduced MPO activity and a decreased number of macrophage inhibitory factor-positive cells compared with the male control group. In the female aspirin-treated group, MPO activity and the number of F4/80-positive macrophages was higher than in the control group. Collagen was reduced only in the female aspirin-treated group. The expression of vWF and VEGF protein was increased in the female aspirin-treated group. In conclusion, aspirin administration impaired the wound healing process in BALB/c female, but not male, mice. PMID:23240590

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

    PubMed

    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

  1. Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

    PubMed Central

    Henshaw, F. R.; Boughton, P.; Lo, L.; McLennan, S. V.; Twigg, S. M.

    2015-01-01

    Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P < 0.001). Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers. PMID:25789327

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

    PubMed

    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. PMID:27412288

  3. Engineered Pullulan–Collagen Composite Dermal Hydrogels Improve Early Cutaneous Wound Healing

    PubMed Central

    Wong, Victor W.; Rustad, Kristine C.; Galvez, Michael G.; Neofytou, Evgenios; Glotzbach, Jason P.; Januszyk, Michael; Major, Melanie R.; Sorkin, Michael; Longaker, Michael T.; Rajadas, Jayakumar

    2011-01-01

    New strategies for skin regeneration are needed to address the significant medical burden caused by cutaneous wounds and disease. In this study, pullulan–collagen composite hydrogel matrices were fabricated using a salt-induced phase inversion technique, resulting in a structured yet soft scaffold for skin engineering. Salt crystallization induced interconnected pore formation, and modification of collagen concentration permitted regulation of scaffold pore size. Hydrogel architecture recapitulated the reticular distribution of human dermal matrix while maintaining flexible properties essential for skin applications. In vitro, collagen hydrogel scaffolds retained their open porous architecture and viably sustained human fibroblasts and murine mesenchymal stem cells and endothelial cells. In vivo, hydrogel-treated murine excisional wounds demonstrated improved wound closure, which was associated with increased recruitment of stromal cells and formation of vascularized granulation tissue. In conclusion, salt-induced phase inversion techniques can be used to create modifiable pullulan–collagen composite dermal scaffolds that augment early wound healing. These novel biomatrices can potentially serve as a structured delivery template for cells and biomolecules in regenerative skin applications. PMID:20919949

  4. Effects of transplanted mesenchymal stem cells isolated from Wharton's jelly of caprine umbilical cord on cutaneous wound healing; histopathological evaluation.

    PubMed

    Azari, Omid; Babaei, Homayoon; Derakhshanfar, Amin; Nematollahi-Mahani, Seyed Noureddin; Poursahebi, Raheleh; Moshrefi, Mojgan

    2011-04-01

    The aim of this study was to investigate the effects of transplanted Wharton's jelly mesenchymal stem cells (WJMSCs) of caprine umbilical cord on cutaneous wound healing process in goat. After collection of caprine pregnant uterus of mixed breed goats from abattoir, the Wharton's jelly (WJ) of umbilical cord was harvested. The tissues were minced in ventilated flasks and explant culture method was used for separating mesenchymal stem cells (MSCs). The isolated cells were immunostained for Actin protein, histochemically assayed for the presence of alkaline phosphatase activity, and analyzed for detection of matrix receptors (CD44) and hematopoetic lineage markers (CD34), using flow cytometery. After The isolated cells, 3×10(6) MSCs were stained with BrdU and prepared for transplantation to each wound. Four 3-cm linear full thickness skin incisions were made on both sides of thoracic vertebrate of four Raeini goats (two wounds on each side). The left wounds were implanted with MSCs in 0.6 ml of Phosphate buffer saline (PBS), and the right wounds considered as control group that received 0.6 ml of PBS. The samples were taken from the wounds 7 and 12 days after the wounding, and healing process was compared histologically between the two groups. Anti-BrdU staining showed that the transplanted cells were still alive in the wound bed during the study. The histopathological study revealed that re-epithelialization was complete at days 7 in treated wounds with WJMSCs, whereas in control wound the wounds still showed incomplete epithelialization 12 days after wounding. Also, microscopic evaluation showed less inflammation, thinner granulation tissue formation with minimum scar in the treated wounds in comparison with control wounds. In conclusion, this study demonstrates the beneficial effect of caprine WJMSCs in cutaneous wound healing in goat. PMID:21340694

  5. Zebrafish keratocyte explants to study collective cell migration and reepithelialization in cutaneous wound healing.

    PubMed

    Rapanan, Jose L; Pascual, Agnes S; Uppalapati, Chandana K; Cooper, Kimbal E; Leyva, Kathryn J; Hull, Elizabeth E

    2015-01-01

    Due to their unique motile properties, fish keratocytes dissociated from explant cultures have long been used to study the mechanisms of single cell migration. However, when explants are established, these cells also move collectively, maintaining many of the features which make individual keratocytes an attractive model to study migration: rapid rates of motility, extensive actin-rich lamellae with a perpendicular actin cable, and relatively constant speed and direction of migration. In early explants, the rapid interconversion of cells migrating individually with those migrating collectively allows the study of the role of cell-cell adhesions in determining the mode of migration, and emphasizes the molecular links between the two modes of migration. Cells in later explants lose their ability to migrate rapidly and collectively as an epithelial to mesenchymal transition occurs and genes associated with wound healing and inflammation are differentially expressed. Thus, keratocyte explants can serve as an in vitro model for the reepithelialization that occurs during cutaneous wound healing and can represent a unique system to study mechanisms of collective cell migration in the context of a defined program of gene expression changes. A variety of mutant and transgenic zebrafish lines are available, which allows explants to be established from fish with different genetic backgrounds. This allows the role of different proteins within these processes to be uniquely addressed. The protocols outlined here describe an easy and effective method for establishing these explant cultures for use in a variety of assays related to collective cell migration. PMID:25742068

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

    NASA Astrophysics Data System (ADS)

    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. The effect of certain topical medications on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis).

    PubMed Central

    Smith, D A; Barker, I K; Allen, O B

    1988-01-01

    The effects of four topical medications on the rate and character of healing of cutaneous wounds were studied in six common garter snakes (Thamnophis sirtalis) held at an ambient temperature of 30 degrees C. Two sets of five 6 to 8 mm round excisional wounds, four test and one control site in each set, were created on the dorsolateral body wall of each snake. Wounds were examined daily and treated for ten days, then the snakes were killed and sections of all wounds were examined by light microscopy. Composite scores, derived by ranking each treatment group in relation to the control group (control score = 0) for each of 22 characteristics associated with wound healing, were used to compare the overall effects of each treatment. Statistical comparisons were made between groups for 20 characteristics. Wounds treated with a polyurethane film merited a score of +12 and had significantly more advanced healing than untreated controls for three characteristics. Wounds treated with an ointment containing scarlet red scored +6 but healing was not significantly greater than controls. Wounds treated with an antibacterial spray powder and an antibacterial ointment healed more slowly than controls and had scores of -6 and -12 respectively. PMID:3349391

  8. Local blockade of glucocorticoid activation reverses stress- and glucocorticoid-induced delays in cutaneous wound healing

    PubMed Central

    Youm, Jong-Kyung; Park, Kyungho; Uchida, Yoshikazu; Chan, Aegean; Mauro, Theodora M.; Holleran, Walter M.; Elias, Peter M.

    2015-01-01

    Stress slows cutaneous wound healing (WH) in an endogenous glucocorticoid (GC)-dependent fashion. We investigated whether stress/GC-induced delays in WH require further intracutaneous activation of endogenous GC; and whether blockade or down-regulation of peripheral activation normalizes WH in the face of stress. Delayed WH in our motion-restricted murine model of stress could be attributed to elevated systemic GC, because blockade of GC production (using corticotropin-releasing factor inhibitor, antalarmin), or of peripheral binding to the GC receptor [GCr], with an antagonist, Ru-486, normalized WH. We next investigated whether local blockade or down-regulation of the peripheral GC-activating enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), accelerates cutaneous WH. Topical applications of nonspecific (carbenoxolone) as well as an isoform-specific 11β-HSD1 inhibitor overcame stress and exogenous GC-induced delays in WH. Moreover, two liver X receptor ligands, TO901317 and GW3695, down-regulated expression of 11β-HSD1, attenuating stress-induced delays in WH. Combined inhibitor and liver X receptor ligand applications accelerated WH in the face of stress/systemic GC. Thus: (1) intracutaneous conversion of inactive-to-active GC accounts for stress (GC)-induced delays in WH; and (2) blockade or down-regulation of 11β-HSD1 and/or GCr normalize cutaneous WH in the face of stress/GC. Local blockade or down-regulation of cutaneous GC activation could help enhance WH in various clinical settings. PMID:23927023

  9. Augmentation of cutaneous wound healing by pharmacologic mobilization of endogenous bone marrow stem cells.

    PubMed

    Tolar, Jakub; McGrath, John A

    2014-09-01

    Novel therapeutic tools to accelerate wound healing would have a major impact on the overall burden of skin disease. Lin et al. demonstrate in mice that endogenous bone marrow stem cell mobilization, produced by a pharmacologic combination of AMD3100 and tacrolimus, leads to faster and better-quality wound healing, findings that have exciting potential for clinical translation. PMID:25120149

  10. Sodium pentaborate pentahydrate and pluronic containing hydrogel increases cutaneous wound healing in vitro and in vivo.

    PubMed

    Doğan, Ayşegül; Demirci, Selami; Cağlayan, Ahmet B; Kılıç, Ertuğrul; Günal, Mehmet Y; Uslu, Unal; Cumbul, Alev; Sahin, Fikrettin

    2014-12-01

    After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds. PMID:25129136

  11. The integrin αv-TGFβ signaling axis is necessary for epidermal proliferation during cutaneous wound healing.

    PubMed

    Duperret, Elizabeth K; Natale, Christopher A; Monteleon, Christine; Dahal, Ankit; Ridky, Todd W

    2016-08-01

    Proliferation and migration of epidermal keratinocytes are essential for proper cutaneous wound closure after injury. αv integrins and several of their ligands-vitronectin, TGFβ and thrombospondin-are up-regulated in healing wounds. However, the role of αv integrins in wound re-epithelialization is unknown. Here, we show that genetic depletion or antibody-mediated blockade of pan-integrin αv, or the specific heterodimer αvβ6, in keratinocytes limited epidermal proliferation at the wound edge and prevented re-epithelialization of wounded human organotypic skin both in vivo and in vitro. While we did not observe a migration defect upon αv blockade in vivo, αv was necessary for keratinocyte migration over longer distances in organotypic skin. Integrin αv is required for local activation of latent TGFβ, and the wound healing defect in the setting of integrin αv loss was rescued by exogenous, active TGFβ, indicating that the αv-TGFβ signaling axis is a critical component of the normal epidermal wound healing program. As chronic wounds are associated with decreased TGFβ signaling, restoration of TGFβ activity may have therapeutic utility in some clinical settings. PMID:27295308

  12. Evaluation of the effects of a combination of Japanese honey and hydrocolloid dressing on cutaneous wound healing in male mice.

    PubMed

    Mukai, Kanae; Koike, Miki; Nakamura, Saki; Kawaguchi, Yuka; Katagiri, Fumika; Nojiri, Saki; Yamada, Yuki; Miyajima, Eri; Matsumoto, Mayuko; Komatsu, Emi; Nakajima, Yukari; Urai, Tamae; Murakado, Naoko; Nakatani, Toshio

    2015-01-01

    The aim of this study was to evaluate the effect of the combined use of Japanese honey and hydrocolloid dressing (HCD) on cutaneous wound healing. Mice were divided into four groups: the Acacia (Japan) + HCD, Manuka (New Zealand) + HCD, Chinese milk vetch (Japan) + HCD, and HCD (control) groups. The mice received two full-thickness wounds. The wounds of the HCD group were covered with HCD, whereas those of the other groups were treated with 0.1 mL of the relevant type of honey, before being covered with HCD. Wound area was significantly smaller in the HCD group than in the Acacia + HCD and Manuka + HCD groups on day 13 and days 8-14, respectively. Moreover, compared with the HCD group, reepithelialization was delayed in the Acacia + HCD group and reepithelialization and collagen deposition were delayed in the Chinese milk vetch + HCD and Manuka + HCD groups. These results indicate that the combined use of Japanese honey and HCD does not promote cutaneous wound healing compared with the use of HCD alone. Thus, this method is probably not useful for promoting healing. PMID:25945118

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

    PubMed

    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 (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect. PMID:27309263

  14. How wounds heal

    MedlinePlus

    ... How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... bleed. For example, burns, some puncture wounds, and pressure sores don't bleed. Once the scab forms, your ...

  15. Combined Mulberry Leaf and Fruit Extract Improved Early Stage of Cutaneous Wound Healing in High-Fat Diet-Induced Obese Mice.

    PubMed

    Eo, Hyeyoon; Lim, Yunsook

    2016-02-01

    Obesity is a pandemic that causes many health challenges, including difficulties in achieving proper wound healing without complications. The current study investigated the role of NLRP3 inflammasome in the early stages of cutaneous wound healing and the effect of combined mulberry leaf and fruit extract (MLFE) on cutaneous NLRP inflammasome involvement in delayed wound healing mice with high-fat diet (HFD)-induced obesity. After obesity was induced by HFD for 10 weeks, the mice were supplemented with MLFE (at a dose of 500 mg/kg containing 333.3 mg/kg of mulberry leaf extract and 166.7 mg/kg of mulberry fruit extract) by gavage, 5 days/week for 12 weeks. MLFE supplementation ameliorated delayed wound closure in obese mice. While wound size was positively correlated with fasting blood glucose level during the early stage of wound healing, it was strongly correlated with body weight gain and body fat mass during the later stage of wound healing. Under obese conditions, the levels of NLRP3 inflammasome and its related markers (pro-caspase-1 and precursor/mature interleukin 1 beta) were increased at a basal level, but the NLRP3 inflammasome was suppressed during the inflammatory stage of cutaneous wound healing. However, MLFE supplementation stimulated cutaneous NLRP3 inflammasome in HFD-induced obese mice (day 3). Taken together, stimulating the NLRP3 inflammasome might be beneficial in the early inflammatory stage of cutaneous wound healing and MLFE could be a potential therapeutic intervention in delayed wound healing through activation of the NLRP3 inflammasome in obesity. PMID:26491791

  16. Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.

    PubMed

    Das, Amitava; Ghatak, Subhadip; Sinha, Mithun; Chaffee, Scott; Ahmed, Noha S; Parinandi, Narasimham L; Wohleb, Eric S; Sheridan, John F; Sen, Chandan K; Roy, Sashwati

    2016-06-15

    Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care. PMID:27194784

  17. Effect of recombinant human epidermal growth factor against cutaneous scar formation in murine full-thickness wound healing.

    PubMed

    Kim, Young Seok; Lew, Dae Hyun; Tark, Kwan Chul; Rah, Dong Kyun; Hong, Joon Pio

    2010-04-01

    A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta(1) in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta(1), and mediating the formation of collagen. PMID:20358003

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

    NASA Astrophysics Data System (ADS)

    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 (p<0.05). At the 14th day, the longitudinal measurement was significantly higher in euthyroids (control and irradiated with laser) when compared to the hypothyroid group (p <0.05). This study has shown that hypothyroidism delays wound healing and Laser and LED photobiomodulation using 24 J/cm2 per session improved cutaneous wound healing in hypothyroid rats.

  19. The Matricellular Protein CCN1/CYR61 Induces Fibroblast Senescence and Restricts Fibrosis in Cutaneous Wound Healing

    PubMed Central

    Jun, Joon-Il; Lau, Lester F.

    2010-01-01

    Cellular senescence is a recognised mechanism of tumor suppression; however, its contribution to other pathologies is not well understood. We show that the matricellular protein CCN1/CYR61, which is dynamically expressed at sites of wound repair, can induce fibroblast senescence through its cell adhesion receptors, integrin α6β1 and heparan sulfate proteoglycans. CCN1 induces DNA damage response and p53 activation, and activates the RAC1-NOX1 complex to induce reactive oxygen species (ROS) generation and ROS-dependent activation of the p16INK4a/pRb pathway, leading to senescence and concomitant expression of antifibrotic genes. Senescent fibroblasts accumulate in granulation tissues of healing cutaneous wounds and express antifibrotic genes in wild type mice. These processes are obliterated in knockin mice that express a senescence-defective CCN1 mutant, resulting in exacerbated fibrosis. Topical application of CCN1 protein to wounds reverses these defects. Thus, fibroblast senescence is a CCN1-dependent wound healing response in cutaneous injury, functioning to curb fibrosis during tissue repair. PMID:20526329

  20. The effect of low-intensity laser therapy (LILT) on cutaneous wound healing and pain relief in rats.

    PubMed

    Koo, Hyun-Mo; Yong, Min-Sik; Na, Sang-Su

    2015-11-01

    [Purpose] This study examined the impact of low-intensity laser therapy on wound healing and pain control using a rat cutaneous wound model. [Subjects and Methods] Twenty-four adult male Sprague-Dawley rats (between 220-240 g, 7 weeks) were used in this study. The rats were anesthetized and a circular fragment of skin was removed from the dorsal region of the back by a punch with an 8-mm diameter. The animals were randomly divided into 6 groups, Groups C 1, C 3, and C 5, control groups, received no laser treatment. Groups T 1, T 3, and T 5 received laser treatment for 20 min per day for 1, 3 and 5 days, respectively. Lumbar spine and dorsal skin were extracted and processed using western blot analysis. [Results] Periodical observation showed increases in NGF expression on the skin, and decreases in c-fos expression by the spinal cord in the treatment groups compared to the control group. [Conclusion] The present findings suggest that low-intensity laser therapy could be used as an effective therapy for wound healing and pain relief, and could be further used as a clinical approach for treating cutaneous wounds. PMID:26696711

  1. 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".

    PubMed

    Li, Hongling; Cao, Cong; Huang, Ai; Man, Yi

    2015-01-01

    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. PMID:26457307

  2. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

    PubMed Central

    Isakson, M.; de Blacam, C.; Whelan, D.; McArdle, A.; Clover, A. J. P.

    2015-01-01

    Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review. PMID:26106431

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

    PubMed

    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. PMID:25186490

  4. The Matricellular Protein CCN1 Mediates Neutrophil Efferocytosis in Cutaneous Wound Healing

    PubMed Central

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

    2015-01-01

    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 Leprdb/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. PMID:26077348

  5. The Efficacy of Sodium Aescinate on Cutaneous Wound Healing in Diabetic Rats.

    PubMed

    Zhang, Zonglin; Cao, Guangchao; Sha, Liying; Wang, Dazhi; Liu, Min

    2015-10-01

    This study is aimed to evaluate the potential effects of sodium aescinate (SA, the sodium salt of aescin) on wound healing in streptozotocin-induced diabetic rats. An excision skin wound was created in diabetic rats, and the wounded rats were divided into three groups: I) control group, II) gel-treated group, and III) SA-treated group. The control group wounds received topically normal saline once daily for 19 days. The gel-treated and SA-treated wounds received topically 400 μl of pluronic F-127 gel (25%) and 400 μl of SA (0.3%) in pluronic gel, respectively, once daily for 19 days. SA application in diabetic rats increased the wound contraction and significantly decreased the level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in comparison to the gel-treated group and control group. SA application in diabetic rats also resulted in a marked increase in the level of anti-inflammatory cytokine interleukin-10 (IL-10) and activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) compared to the other groups. Histopathologically, SA-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation, and wounds were covered by thick regenerated epithelial layer. Additionally, the application of only pluronic gel produced some beneficial effects in some parameters in comparison to control group, but most of them were not significantly different. These findings demonstrated that SA may effectively control and improve wound healing in diabetic rats via its anti-inflammatory and antioxidant activities. PMID:25903967

  6. Multifunctional Skin-like Electronics for Quantitative, Clinical Monitoring of Cutaneous Wound Healing

    PubMed Central

    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

    2014-01-01

    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 we report a skin-like electronics 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. 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. PMID:24668927

  7. Pentoxifylline improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Babaei, Saeed; Bayat, Mohammad; Nouruzian, Mohsen; Bayat, Mehrnoush

    2013-01-30

    Worldwide, 15% of the 200 million diabetics suffer from diabetic wounds. In 1997, the cost for amputation of toes and limbs that resulted from infected diabetic foot ulcers ranged from $25,000-$40,000 per incident. Increasing numbers of research have shown the positive influence of pentoxifylline (PTX) on healing skin wounds. In this study, we evaluate the effect of systemic PTX (25mg/kg bid) on wound healing in 80 diabetic rats (DB) by secondary intention. Wounds (20 mm × 5 mm) were identically inflicted on the skin area of the backs of all rats. On day 15 following surgery, a band of skin (4 mm × 60 mm) that contained wound was extracted for biomechanical testing. For histologic analysis, both experimental (DB+PTX) and control, receiving distilled water (DB+DW) groups were further subdivided into day 3 and 7 groups. Rats were sacrificed three and seven days after surgery, and a sample from each wound was taken. All specimens were sectioned stereologically and stained with H&E. Cell counts were performed by stereological methods. Semi-quantitative evaluation of matrix metalloproteinases (MMPs) and inhibitor-1 was performed by Reversed Transcription-PCR and UVI TEC software. For statistical analysis we used student's t-test. Collectively, the results of this study demonstrate that there was significant improvement with PTX in all biomechanical parameters. Histologically, PTX reduced inflammation by day seven. Quantitatively, by day five, PTX reduced expression of MMPs and increased TIMP-1 expression. These findings revealed that PTX significantly improved wound healing indices in streptozotocin-induced DB. PMID:23220163

  8. Imaging Mass Spectrometry for Assessing Cutaneous Wound Healing: Analysis of Pressure Ulcers

    PubMed Central

    2015-01-01

    Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing. PMID:25488653

  9. Translational Lessons from Scarless Healing of Cutaneous Wounds and Regenerative Repair of the Myocardium

    PubMed Central

    Palatinus, Joseph A.; Rhett, J. Matthew; Gourdie, Robert G.

    2009-01-01

    Regenerative healing is the process by which injured tissues are restored to their original structure and function. Many species are capable of healing in this manner. However, in mammals the healing response in most tissues is marked by fibroblast proliferation and scar tissue deposition. While scarring contributes to efficient resolution of mammalian wounds and restoration of at least partial structural and functional support, the final result of scar formation can be more deleterious than the initial insult. This is especially true in the heart, which is sensitive to electrical heterogeneities and altered mechanical properties produced by scarring. Several therapeutic modalities promoting regeneration in skin wounds have been developed that modulate various aspects of the healing process. Targets include cytokine stimulation, control of fibroblast activation, modulation of gap junctions, and stem cell differentiation. Here, we review and compare mechanisms of injury, repair, and scarring in the skin and heart and discuss the promise and caveats of future therapies that may translate to improving repair of myocardial tissues. PMID:19560469

  10. Thyroid Hormone and Wound Healing

    PubMed Central

    Safer, Joshua D.

    2013-01-01

    Although thyroid hormone is one of the most potent stimulators of growth and metabolic rate, the potential to use thyroid hormone to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated intriguing therapeutic potential for topical thyroid hormone. Topical T3 has accelerated wound healing and hair growth in rodents. Topical T4 has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along with skin manifestations of thyroid disease. The paper is intended to provide a context for recent findings of direct thyroid hormone action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing. PMID:23577275

  11. Controlled release of thymosin beta 4 using a collagen-chitosan sponge scaffold augments cutaneous wound healing and increases angiogenesis in diabetic rats with hindlimb ischemia.

    PubMed

    Ti, Dongdong; Hao, Haojie; Xia, Lei; Tong, Chuan; Liu, Jiejie; Dong, Liang; Xu, Shenjun; Zhao, Yali; Liu, Huiling; Fu, Xiaobing; Han, Weidong

    2015-02-01

    It is important to establish an efficient vascularization for the long-term acceptance of bioengineered skin equivalents treating the cutaneous wounds of diabetic rats with hindlimb ischemia. This study investigates the possible use of a collagen-chitosan sponge scaffold encapsulated with thymosin beta 4 (CCSS-eTβ4), an angiogenic factor, to accelerate cutaneous wound healing in streptozotocin (STZ)-induced diabetic rats with hindlimb ischemia. CCSSs-eTβ4 was fabricated using a freeze-drying method. The scaffolds were analyzed by scanning electron microscopy, swelling and degradation assays, mechanical properties, and scaffolds of 50:50 collagen-chitosan were selected and applied. The controlled release of Tβ4 from the scaffolds elicited localized and prolonged effects over 12 days, as shown by an enzyme-linked immunosorbent assay (ELISA). In vivo, CCSSs-eTβ4 improved diabetic cutaneous wound healing, with faster wound reepithelialization, better dermal reorganization, and higher wound vascularization. Furthermore, CCSSs-eTβ4 downregulated inflammatory genes and upregulated angiogenic genes in the wound tissue. Significant increases in CD31-positive endothelial cells and new vessel density were also observed. In vitro, Tβ4 increased the migratory and proliferative activity of high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). Meanwhile, we found that Tβ4 could promote HG-treated HUVECs migration and improve angiogenesis by activation of the VEGF/AKT pathway. Overall, these findings demonstrated the promising potential of CCSSs-eTβ4 to promote more effective wound healing and suggest its possible application for diabetic cutaneous wound treatment. PMID:25204972

  12. Dietary supplementation of N-acetylcysteine enhances early inflammatory responses during cutaneous wound healing in protein malnourished mice.

    PubMed

    Lim, Yunsook; Levy, Mark A; Bray, Tammy M

    2006-05-01

    Prolonged wound healing is a complication that contributes to the morbidity and mortality of protein malnutrition (PM). The molecular mechanisms that underlie impaired wound healing in PM may begin in the early inflammatory stage of the process. We hypothesized that the impaired wound healing observed in PM occurs as a consequence of excessive reactive oxygen species (ROS) production that impairs the wound healing process by depressing nuclear factor kappa B (NFkappaB) activation and the subsequent synthesis and release of proinflammatory cytokines that are critical mediators of the inflammatory response. In this study, we showed that the time to wound closure was significantly prolonged in PM mice. During the early wound healing in PM, inhibitory kappa B alpha (IkappaBalpha), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) expression and neutrophil infiltration were significantly decreased in PM mice. The role of excess ROS in PM was demonstrated by using transgenic mice with overexpression of copper zinc superoxide dismutase and with dietary supplementation of N-acetylcysteine (NAC). Both interventions improved the extent of wound closure in PM mice. Moreover, NAC supplementation in PM mice restored the expression of IkappaBalpha, IL-1beta and TNF-alpha and infiltration of neutrophils to levels observed in control animals. These findings support the notion that wound healing defects in PM may result from dysregulation of ROS-mediated and NFkappaB-regulated signaling pathways. PMID:16214328

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

    PubMed Central

    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 <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. PMID:27486319

  14. Metalloproteinases and Wound Healing

    PubMed Central

    Caley, Matthew P.; Martins, Vera L.C.; O'Toole, Edel A.

    2015-01-01

    Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. PMID:25945285

  15. Saliva and wound healing.

    PubMed

    Brand, Henk S; Veerman, Enno C I

    2013-01-01

    Wounds in the oral cavity heal faster and with less scarring than wounds in other parts of the body. One of the factors implicated in this phenomenon is the presence of saliva, which promotes the healing of oral wounds in several ways. Saliva creates a humid environment, which improves the survival and functioning of inflammatory cells that are crucial for wound healing. Furthermore, saliva contains a variety of proteins that play a role in the various stages of the intraoral wound healing. Tissue factor, present in salivary exosomes, accelerates the clotting of blood dramatically. The subsequent proliferation of epithelial cells is promoted by growth factors in saliva, especially epidermal growth factor. The importance of secretory leucocyte protease inhibitor is demonstrated by the observation that in the absence of this salivary protein, oral wound healing is considerably delayed. Members of the salivary histatin family promote wound closure in vitro by enhancing cell spreading and cell migration. Cell proliferation is not enhanced by histatin. Cyclization of histatin increased its biological activity approximately 1,000-fold compared to linear histatin. These studies suggest that histatins could potentially be used for the development of new wound healing medications. PMID:23878824

  16. Wound healing in urology.

    PubMed

    Ninan, Neethu; Thomas, Sabu; Grohens, Yves

    2015-03-01

    Wound healing is a dynamic and complex phenomenon of replacing devitalized tissues in the body. Urethral healing takes place in four phases namely inflammation, proliferation, maturation and remodelling, similar to dermal healing. However, the duration of each phase of wound healing in urology is extended for a longer period when compared to that of dermatology. An ideal wound dressing material removes exudate, creates a moist environment, offers protection from foreign substances and promotes tissue regeneration. A single wound dressing material shall not be sufficient to treat all kinds of wounds as each wound is distinct. This review includes the recent attempts to explore the hidden potential of growth factors, stem cells, siRNA, miRNA and drugs for promoting wound healing in urology. The review also discusses the different technologies used in hospitals to treat wounds in urology, which make use of innovative biomaterials synthesised in regenerative medicines like hydrogels, hydrocolloids, foams, films etc., incorporated with growth factors, drug molecules or nanoparticles. These include surgical zippers, laser tissue welding, negative pressure wound therapy, and hyperbaric oxygen treatment. PMID:25500273

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Result 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. Conclusions 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. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196 PMID:23866960

  18. The effect of ambient temperature and type of wound on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis).

    PubMed Central

    Smith, D A; Barker, I K; Allen, O B

    1988-01-01

    The effects of ambient temperature (13.5 degrees C, 21 degrees C, 30 degrees C) and type of wound on healing of skin wounds were evaluated in common garter snakes (Thamnophis sirtalis). Linear unsutured incisions and circular excisional wounds were evaluated grossly and microscopically in three snakes held at each temperature at each of two, five and ten days after surgery. Linear sutured and unsutured incisions and circular and square excisional wounds were similarly evaluated three and six weeks after wound production in groups of six snakes held at each temperature. The rates of stabilization of wound margins, scab formation, migration and maturation of the regenerating epithelium, resolution of dermal inflammation, and fibroplasia varied directly with temperature. The inflammatory reaction to wounding was similar in character and intensity in snakes held at all three temperatures two days after surgery. Unsutured linear incisions, compared to sutured incisions, tended to have more rapid epithelial maturation and a less intense inflammatory response. Healing of square and circular excisional wounds was similar; contraction of round wounds was slightly more irregular and, at a few observations, dermal maturation was slower and inflammation more widespread. It was concluded that healing of skin wounds can be accelerated by holding reptiles at the upper end of their voluntary temperature range. Wounds, if possible, should be created along the axis of lines of skin tension. Suturing small incisional wounds may not be advantageous. PMID:3349390

  19. Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor.

    PubMed

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mitra Mazumder, Papiya; Veer, Vijay

    2014-01-01

    Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. PMID:24624303

  20. Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor

    PubMed Central

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mitra Mazumder, Papiya; Veer, Vijay

    2014-01-01

    Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. PMID:24624303

  1. Local delivery of allogeneic bone marrow and adipose tissue-derived mesenchymal stromal cells for cutaneous wound healing in a porcine model.

    PubMed

    Hanson, Summer E; Kleinbeck, Kyle R; Cantu, David; Kim, Jaeyhup; Bentz, Michael L; Faucher, Lee D; Kao, W John; Hematti, Peiman

    2016-02-01

    Wound healing remains a major challenge in modern medicine. Bone marrow- (BM) and adipose tissue- (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT-MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM- or AT-MSCs were administered intradermally (1 x 10(6) cells) into partial-thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC-injected wounds were associated with improved appearance and faster re-epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM- and AT-MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM- and AT-MSC for treatment of cutaneous wounds through modulation of healing and epithelialization. PMID:23418160

  2. Comparative study of the effects of the use of the CO2 laser and of cholorhexidine on the healing of cutaneous wounds infected by the staphylococcus aureus

    NASA Astrophysics Data System (ADS)

    Matos de Oliveira, Marcos A.; Barbosa Pinheiro, Antonio L.; Azevedo Moreira, Ana C.; Pedreira Ramalho, Luciana M.; Brugnera, Aldo, Jr.; Zanin, Fatima A. A.; Costa Lima, Taciano L.

    2003-06-01

    The aim of this study was to compare histologic and microbiogically the use of the CO2 Laser and Chlorohexidine Gluconate (0.5% and 2%) on cutaneous wounds infected by Staphylococcus aureus. Wound infection constitutes a risk for the patients and it is usually associated to increase morbidity, mortality and hospital costs. It is accepted that local treatment of these infections is effective. Standardised wounds created on the dorsum of Wistar rats were infected with Staphylococcus aureus and treated as follows: Group 1: control; Group 2: Chlorohexidien Gluconate (0.5%), 1 min, six days; Group 3: Chlorohexidine Gluconate (2%), 1 min, six days; Group 4: CO2 Laser, CW, RSP, 8W, 10s, single application, maintaining surface debris; Group 5: CO2 Laser, CW, RSP, 8W, 10s, single application, removing surface debris. Eight days after wounding material from the surface of the wound was collected for microbiology and the animals were sacrificed and specimens taken for light microscopy. Microbiological examinations showed that on group 2 the bacteria were not found on 50% of the animals. On group 3 83% were germ-free, on group 4 50% and on group 5 66%. Histological examination showed a better result for CO2 laser treated wounds compared to others. It is concluded that the use of a 2% Cholohexidine solution was more effective on decontaminating the wounds. However, wounds treated with the CO2 laer and with the removal of surface debris healed better than the others.

  3. Phytochemicals in Wound Healing

    PubMed Central

    Thangapazham, Rajesh L.; Sharad, Shashwat; Maheshwari, Radha K.

    2016-01-01

    Significance: Traditional therapies, including the use of dietary components for wound healing and skin regeneration, are very common in Asian countries such as China and India. The increasing evidence of health-protective benefits of phytochemicals, components derived from plants is generating a lot of interest, warranting further scientific evaluation and mechanistic studies. Recent Advances: Phytochemicals are non-nutritive substances present in plants, and some of them have the potential to provide better tissue remodeling when applied on wounds and to also act as proangiogenic agents during wound healing. Critical Issues: In this review, we briefly discuss the current understanding, important molecular targets, and mechanism of action(s) of some of the phytochemicals such as curcumin, picroliv, and arnebin-1. We also broadly review the multiple pathways that these phytochemicals regulate to enhance wound repair and skin regeneration. Future Directions: Recent experimental data on the effects of phytochemicals on wound healing and skin regeneration establish the potential clinical utility of plant-based compounds. Additional research in order to better understand the exact mechanism and potential targets of phytochemicals in skin regeneration is needed. Human studies a2nd clinical trials are pivotal to fully understand the benefits of phytochemicals in wound healing and skin regeneration. PMID:27134766

  4. An experimental study of the effects of Matricaria chamomilla extract on cutaneous burn wound healing in albino rats.

    PubMed

    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. PMID:18404562

  5. Epidemiology of chronic cutaneous wounds in China.

    PubMed

    Jiang, Yufeng; Huang, Sha; Fu, Xiaobing; Liu, Hongwei; Ran, Xingwu; Lu, Shuliang; Hu, Dahai; Li, Qiang; Zhang, Hongwei; Li, Ying; Wang, Runxiu; Xie, Ting; Cheng, Biao; Wang, Lingfeng; Liu, Yi; Ye, Xiangbai; Han, Chunmao; Chen, Huade

    2011-01-01

    Chronic cutaneous wounds represent a major health care burden in China. However, limited information exists regarding the epidemiologic changes associated with recent social and economic development. We designed a cross-sectional survey in 2,513 patients who underwent treatment of chronic cutaneous wounds from a nationally representative sample in 17 hospitals between 2007 and 2008. Results revealed the prevalence of chronic cutaneous wounds among hospitalized patients was 1.7‰. Patient ages ranged from 18 days to 96 years (median, 58 years). The highest ratios were among 40-60 and 60-80-year-old patients (31% and 38%, respectively). The leading causes of chronic cutaneous wounds were diabetes (31.3% men, 35.3% women) trauma (26.4% men, 19.2% women). Manual workers (38.5% men, 29.3% women) and retirees (27.9% men, 23.5% women) accounted for over half the chronic cutaneous wound patients. Regarding treatments, only 22.4% were treated with modern dressings or other novel technologies and more patients received antibiotics (77.8%). Treatment was paid for by the patients in 42.3% of cases, by social medical insurance in 25.0%, by commercial medical insurance in 4.8%, while 27.9% received free medical care. Approximately half the patients' wounds were completely healed at discharge (1,345/2,513). In conclusion, diabetes has recently become the leading cause of chronic cutaneous wounds in China. The large population and considerable financial burden mean that serious attention should be paid to the early detection, prevention and diagnosis of chronic cutaneous wounds, and suggest that an overall health insurance system should be established, especially for the elderly. PMID:21362085

  6. Functionalized silk biomaterials for wound healing.

    PubMed

    Gil, Eun Seok; Panilaitis, Bruce; Bellas, Evangelia; Kaplan, David L

    2013-01-01

    Silk protein-biomaterial wound dressings with epidermal growth factor (EGF) and silver sulfadiazine were studied with a cutaneous excisional mouse wound model. Three different material designs and two different drug incorporation techniques were studied to compare wound healing responses. Material formats included silk films, lamellar porous silk films and electrospun silk nanofibers, each studied with the silk matrix alone and with drug loading or drug coatings on the silk matrices. Changes in wound size and histological assessments of wound tissues showed that the functionalized silk biomaterial wound dressings increased wound healing rate, including reepithelialization, dermis proliferation, collagen synthesis and reduced scar formation, when compared to air-permeable Tegaderm tape (3M) (- control) and a commercial wound dressing, Tegaderm Hydrocolloid dressing (3M) (+ control). All silk biomaterials were effective for wound healing, while the lamellar porous films and electrospun nanofibers and the incorporation of EGF/silver sulfadiazine, via drug loading or coating, provided the most rapid wound healing responses. This systematic approach to evaluating functionalized silk biomaterial wound dressings demonstrates a useful strategy to select formulations for further study towards new treatment options for chronic wounds. PMID:23184644

  7. Image-guided plasma therapy of cutaneous wound

    NASA Astrophysics Data System (ADS)

    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.

  8. Integrins in Wound Healing

    PubMed Central

    Koivisto, Leeni; Heino, Jyrki; Häkkinen, Lari; Larjava, Hannu

    2014-01-01

    Significance: Regulation of cell adhesions during tissue repair is fundamentally important for cell migration, proliferation, and protein production. All cells interact with extracellular matrix proteins with cell surface integrin receptors that convey signals from the environment into the nucleus, regulating gene expression and cell behavior. Integrins also interact with a variety of other proteins, such as growth factors, their receptors, and proteolytic enzymes. Re-epithelialization and granulation tissue formation are crucially dependent on the temporospatial function of multiple integrins. This review explains how integrins function in wound repair. Recent Advances: Certain integrins can activate latent transforming growth factor beta-1 (TGF-β1) that modulates wound inflammation and granulation tissue formation. Dysregulation of TGF-β1 function is associated with scarring and fibrotic disorders. Therefore, these integrins represent targets for therapeutic intervention in fibrosis. Critical Issues: Integrins have multifaceted functions and extensive crosstalk with other cell surface receptors and molecules. Moreover, in aberrant healing, integrins may assume different functions, further increasing the complexity of their functionality. Discovering and understanding the role that integrins play in wound healing provides an opportunity to identify the mechanisms for medical conditions, such as excessive scarring, chronic wounds, and even cancer. Future Directions: Integrin functions in acute and chronic wounds should be further addressed in models better mimicking human wounds. Application of any products in acute or chronic wounds will potentially alter integrin functions that need to be carefully considered in the design. PMID:25493210

  9. Electrical stimulation to accelerate wound healing

    PubMed Central

    Thakral, Gaurav; LaFontaine, Javier; Najafi, Bijan; Talal, Talal K.; Kim, Paul; Lavery, Lawrence A.

    2013-01-01

    Background There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. PMID:24049559

  10. Nutritional aspects of wound healing.

    PubMed

    Ayello, E A; Thomas, D R; Litchford, M A

    1999-01-01

    Proper nutrition is essential to prevent the development of pressure ulcers and to support adequate and timely wound healing. Additionally, research and clinical observation suggest nutrients play a major role in wound healing. How the nutrients Vitamin A, Vitamin C, zinc, calories, protein, and fluids are used in wound healing and recommendations regarding use of supplements are discussed in this article. PMID:10855131

  11. Healing Invisible Wounds

    ERIC Educational Resources Information Center

    Adams, Erica J.

    2010-01-01

    As many as 9 in 10 justice-involved youth are affected by traumatic childhood experiences. According to "Healing Invisible Wounds: Why Investing in Trauma-Informed Care for Children Makes Sense," between 75 and 93 percent of youth currently incarcerated in the justice system have had at least one traumatic experience, including sexual abuse, war,…

  12. Placenta Growth Factor in Diabetic Wound Healing

    PubMed Central

    Cianfarani, Francesca; Zambruno, Giovanna; Brogelli, Laura; Sera, Francesco; Lacal, Pedro Miguel; Pesce, Maurizio; Capogrossi, Maurizio C.; Failla, Cristina Maria; Napolitano, Monica; Odorisio, Teresa

    2006-01-01

    Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process. PMID:17003476

  13. Potential benefits of pentoxifylline on wound healing.

    PubMed

    Ahmadi, Motahareh; Khalili, Hossein

    2016-01-01

    In this review, potential benefits of pentoxifylline (PTX) on wound healing have been evaluated. All available experimental and clinical studies examined effects of PTX on wound healing have been included. No time limitation was considered and all studies up to writing the manuscript were included. Administration of oral or parenteral PTX showed beneficial effects on the healing of colorectal anastomosis, post burn scar, radiation-induced skin/soft tissue injury, venous ulcers, recurrent aphthous stomatitis and cutaneous/mucocutaneous leishmaniasis. Data regarding effect of PTX on skin flap survival are conflicting. Only few evidences support promising effects of PTX in pressure ulcer, skin developing injury and burn. PMID:26558813

  14. Wound healing for the clinician.

    PubMed

    Zitelli, J

    1987-01-01

    Wound healing is a complex sequence of events, beginning with tissue injury, mediated by inflammation, and ending long after reepithelialization is complete. Research and controlled clinical experience have provided a better understanding so that clinicians can influence the events of healing to decrease pain, control bleeding, infection, and cosmetic result as well as speed the time for complete healing. The following is a summary of guidelines for the management of wound healing: (1) wound creation; wounds should be created with minimal necrosis of tissue in order to prevent delays in healing. Electrosurgical, cryosurgical, and laser surgical wounds heal more slowly than wounds created by scalpel excision or curettage. Electro-coagulation should be used sparingly in sutured wounds. Large lesions are best treated in a single stage rather than in divided treatments since the rate of wound healing is not proportional to the area but instead to the logarithm of the area. Thus, the total healing time is much shorter if done in a single treatment session. (2) use of drugs; corticosteroids given before or within three days of wounding in dose of prednisone 40 mg or greater will inhibit wound healing. Vitamin A topically or systemically may reverse this inhibition. Aspirin and other nonsteroidal anti-inflammatory agents are more important for their effects on platelet function and bleeding than on wound healing. (3) wound dressings; the use of occlusive dressings to promote moist wound healing is the most significant advance in wound management. Occlusive dressings shorten the time for healing, decrease pain, reduce wound contamination, and improve the cosmetic result. (4) control of wound contraction and scar formation; at the time of wound formation, guiding sutures may be helpful in wound healing by secondary intention in order to control the direction of wound contraction and prevent distortion. Intralesional steroids may be useful for hypertrophic scars and keloids

  15. Multimodal imaging of cutaneous wound tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Shiwu; Gnyawali, Surya; Huang, Jiwei; Ren, Wenqi; Gordillo, Gayle; Sen, Chandan K.; Xu, Ronald

    2015-01-01

    Quantitative assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate detection, staging, and treatment of chronic wounds. However, few methods are available for simultaneous assessment of these tissue parameters in a noninvasive and quantitative fashion. We integrated hyperspectral, laser speckle, and thermographic imaging modalities in a single-experimental setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation characteristics. Algorithms were developed for appropriate coregistration between wound images acquired by different imaging modalities at different times. The multimodal wound imaging system was validated in an occlusion experiment, where oxygenation and perfusion maps of a healthy subject's upper extremity were continuously monitored during a postocclusive reactive hyperemia procedure and compared with standard measurements. The system was also tested in a clinical trial where a wound of three millimeters in diameter was introduced on a healthy subject's lower extremity and the healing process was continuously monitored. Our in vivo experiments demonstrated the clinical feasibility of multimodal cutaneous wound imaging.

  16. Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing.

    PubMed

    Phan, T T; Wang, L; See, P; Grayer, R J; Chan, S Y; Lee, S T

    2001-12-01

    Extracts from the leaves of Chromolaena odorata have been shown to be beneficial for treatment of wounds. The crude ethanol extract of the plant had been demonstrated to be a powerful antioxidant to protect fibroblasts and keratinocytes in vitro. In this study, the most active compounds were fractionated and identified from the crude extract using liquid chromatography coupled with UV spectroscopy and mass spectrometry. The antioxidant effects of purified fractions on cultured fibroblasts and keratinocytes were investigated using colorimetric and lactate hydrogenase release assay. The results showed that the phenolic acids present (protocatechuic, p-hydroxybenzoic, p-coumaric, ferulic and vanillic acids) and complex mixtures of lipophilic flavonoid aglycones (flavanones, flavonols, flavones and chalcones) were major and powerful antioxidants to protect cultured skin cells against oxidative damage. In conclusion, the extract from C odorata contains a mixture of powerful antioxidant compounds that may be one of potential mechanism contributing to enhanced wound healing. PMID:11767105

  17. Radiotherapy and wound healing.

    PubMed

    Devalia, Haresh L; Mansfield, Lucy

    2008-03-01

    This review article discusses basic radiation physics and effects of radiation on wounds. It examines various postulated hypothesis on the role of circulatory decrease and radiation-induced direct cellular damage. The new concept related to the radiation pathogenesis proposes that there is a cascade of cytokines initiated immediately after the radiation. Sustained activation of myofibroblasts in the wound accounts for its chronicity. Recent advances highlight that transforming growth factor beta1 is the master switch in pathogenesis of radiation fibrosis. This articles overviews its role and summarises the available evidences related to radiation damage. The goal of this article was to provide its modern understanding, as future research will concentrate on antagonising the effects of cytokines to promote wound healing. PMID:18081782

  18. Cellular and molecular facets of keratinocyte reepithelization during wound healing

    SciTech Connect

    Santoro, Massimo M. . E-mail: msantoro@unipmn.it; Gaudino, Giovanni

    2005-03-10

    Cutaneous wound healing is a highly coordinated physiological process that rapidly and efficiently restores skin integrity. Reepithelization is a crucial step during wound healing, which involves migration and proliferation of keratinocytes to cover the denuded dermal surface. Recent advances in wound biology clarified the molecular pathways governing keratinocyte reepithelization at wound sites. These new findings point towards novel therapeutic targets and provide suitable methods to promote faster tissue regeneration in vivo.

  19. Curcumin as a wound healing agent.

    PubMed

    Akbik, Dania; Ghadiri, Maliheh; Chrzanowski, Wojciech; Rohanizadeh, Ramin

    2014-10-22

    Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarizes and discusses recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds. PMID:25200875

  20. Skin wound healing and phytomedicine: a review.

    PubMed

    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. PMID:24993834

  1. Wound Healing Devices Brief Vignettes

    PubMed Central

    Anderson, Caesar A.; Hare, Marc A.; Perdrizet, George A.

    2016-01-01

    Significance: The demand for wound care therapies is increasing. New wound care products and devices are marketed at a dizzying rate. Practitioners must make informed decisions about the use of medical devices for wound healing therapy. This paper provides updated evidence and recommendations based on a review of recent publications. Recent Advances: The published literature on the use of medical devices for wound healing continues to support the use of hyperbaric oxygen therapy, negative pressure wound therapy, and most recently electrical stimulation. Critical Issue: To inform wound healing practitioners of the evidence for or against the use of medical devices for wound healing. This information will aid the practitioner in deciding which technology should be accepted or rejected for clinical use. Future Directions: To produce high quality, randomized controlled trials or acquire outcome-based registry databases to further test and improve the knowledge base as it relates to the use of medical devices in wound care. PMID:27076996

  2. Wound healing activity of honey: A pilot study

    PubMed Central

    Vijaya, Kumari K.; Nishteswar, K.

    2012-01-01

    Vrana (wound) and its sequels play a major concern in the field of surgery as Vrana Ropana (wound healing) requires uneventful healing. The aim of the study was to evaluate the changes in physical and morphological properties due to topical application of Madhu (honey) on fresh traumatic wounds or cutaneous wounds. Ten patients of wounds of either sex were randomly selected. Site of the wound, shape, size, floor, and margin were recorded on day 0 and observed on day 7, 15, 20, and till the end of the healing for the progression of granulation, scar type, shape, size, and clinical symptoms. There was significant improvement in the healing process as Madhu possesses antibacterial, wound cleansing, wound healing properties and showed beneficiary effects. PMID:23723644

  3. Wound healing in plants

    PubMed Central

    Tisi, Alessandra; Angelini, Riccardo

    2008-01-01

    Copper amine oxidases (CuAO) and flavin-containing amine oxidases (PAO) are hydrogen peroxide (H2O2)-producing enzymes responsible for the oxidative de-amination of polyamines. Currently, a key role has been ascribed to apoplastic amine oxidases in plants, i.e., to behave as H2O2-delivering systems in the cell wall during cell growth and differentiation as well as in the context of host-pathogen interactions. Indeed, H2O2 is the co-substrate for the peroxidase-driven reactions during cell-wall maturation and a key signalling molecule in defence mechanisms. We recently demonstrated the involvement of an apoplastic PAO in the wound-healing process of the Zea mays mesocotyl. Experimental evidence indicated a similar role for an apoplastic PAO in Nicotiana tabacum. In this addendum we suggest that a CuAO activity is also involved in this healing event. PMID:19704660

  4. 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

    PubMed Central

    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

  5. Nutritional support for wound healing.

    PubMed

    MacKay, Douglas; Miller, Alan L

    2003-11-01

    Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome. PMID:14653765

  6. Wound Healing and Care

    MedlinePlus

    ... heal through natural scar formation. continue The Healing Process Before healing begins, the body gears up to ... dry at all times to help the healing process. As the body does its healing work on ...

  7. Myeloid Cells in Cutaneous Wound Repair.

    PubMed

    Cash, Jenna L; Martin, Paul

    2016-06-01

    Cutaneous wound repair is a complex, dynamic process with the goal of rapidly sealing any breach in the skin's protective barrier. Myeloid cells compose a significant proportion of the inflammatory cells recruited to a wound site and play important roles in decontaminating the injured tissue of any invading microorganisms. Subsequently, myeloid cells are able to influence many aspects of the healing response, in part through their capacity to release a large array of signaling molecules that allow them to communicate with and regulate the behavior of other wound cells and in turn, be themselves exquisitely regulated by the wound microenvironment. Macrophages, for example, appear to play important, temporally changing roles in the initiation of scarring and subsequently in matrix remodeling to resolve fibrosis. In this way, myeloid cells seem to play both positive (e.g., pathogen killing and matrix remodeling) and negative (e.g., scarring) roles in wound repair. Further research is of course needed to elucidate the precise temporal and spatial myeloid cell phenotypes and behaviors and ultimately to design effective strategies to optimize the beneficial functions of these cells while minimizing their detrimental contributions to improve wound healing in the clinic. PMID:27337466

  8. Chemokines and diabetic wound healing.

    PubMed

    Ochoa, Oscar; Torres, Francis M; Shireman, Paula K

    2007-01-01

    Chemokines are critical for white blood cell recruitment to injured tissues and play an important role in normal wound healing processes. In contrast, impaired wound healing in diabetic patients is accompanied by decreased early inflammatory cell infiltration but persistence of neutrophils and macrophages in the chronic, nonhealing wounds. These changes in inflammatory cell recruitment occur in conjunction with alterations in chemokine and growth factor expression. In addition to leukocyte trafficking, many different cell types, including endothelial cells, fibroblasts, and keratinocytes, produce and respond to chemokines, and these interactions are altered in diabetic wounds. Thus, the chemokine system may have both direct and inflammatory-mediated effects on many different aspects of diabetic wound healing. The potential roles of chemokines and inflammatory or immune cells in nonhealing diabetic wounds, including impairments in growth factor expression, angiogenesis, extracellular matrix formation, and reepithelialization, are examined. PMID:18053419

  9. Neutrophil depletion in the early inflammatory phase delayed cutaneous wound healing in older rats: improvements due to the use of un-denatured camel whey protein

    PubMed Central

    2014-01-01

    Background While it is known that advanced age alters the recruitment of neutrophils during wound healing, thereby delaying the wound healing process, little is known about prolonged wound healing in advanced ages. Thus, we investigated the correlation of neutrophil recruitment with healing events, and the impact of whey protein (WP) on neutrophil activation. Methods The animals were allocated into wounded young group, wounded older group and wounded older rats with daily treatment of WP at a dose of 100 mg/kg of body weight. Results Our results pointed to a marked deficiency in the number of neutrophils in the wounds of older rats, which was accompanied with impairment of the healing process. In the group of older rats, phagocytic activity, as tested by fluorescence microscopy, declined throughout the first 24 hours after wounding. Both the neutrophil number and the phagocytic activity recovered in older rats which received WP supplementation. Interestingly, WP was found to significantly up-regulate the MIP-1α and CINC-1 mRNA expression in old rats. On the other hand, the wound size in older rats was significantly higher than that in younger ones. Blood angiogenesis was also significantly delayed in the older group as opposed to the young rats. WP, however, was found to return these indices to normal levels in the older rats. Proliferation and epidermal migration of the keratinocytes and the collagen deposition were also returned to the normal rates. Conclusions This data confirms the critical role of neutrophil recruitment in the early inflammatory phase of wound healing in older rats. In addition, WP protein was used to improve neutrophil function in older rats, healing events returned to a more normal profile. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2100966986117779. PMID:24593823

  10. Inflammation and Neuropeptides: The Connection in Diabetic Wound Healing

    PubMed Central

    Pradhan, Leena; Nabzdyk, Christoph; Andersen, Nicholas D; LoGerfo, Frank W; Veves, Aristidis

    2013-01-01

    This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization are essential phases of wound healing. The link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. The bidirectional connection between the nervous and the immune systems and the role it plays in wound healing has emerged as one of the focal features of the wound healing dogma. The mediators of this connection include neuropeptides and the cytokines released from different cells including immune and cutaneous cells. Therefore, to develop successful wound healing therapies, it is vital to understand in depth the signaling pathways in the neuro-immune axis and their implication in diabetic wound healing. PMID:19138453

  11. Multimodal imaging of cutaneous wound tissue

    PubMed Central

    Zhang, Shiwu; Gnyawali, Surya; Huang, Jiwei; Ren, Wenqi; Gordillo, Gayle; Sen, Chandan K.; Xu, Ronald

    2015-01-01

    Abstract. Quantitative assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate detection, staging, and treatment of chronic wounds. However, few methods are available for simultaneous assessment of these tissue parameters in a noninvasive and quantitative fashion. We integrated hyperspectral, laser speckle, and thermographic imaging modalities in a single-experimental setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation characteristics. Algorithms were developed for appropriate coregistration between wound images acquired by different imaging modalities at different times. The multimodal wound imaging system was validated in an occlusion experiment, where oxygenation and perfusion maps of a healthy subject’s upper extremity were continuously monitored during a postocclusive reactive hyperemia procedure and compared with standard measurements. The system was also tested in a clinical trial where a wound of three millimeters in diameter was introduced on a healthy subject’s lower extremity and the healing process was continuously monitored. Our in vivo experiments demonstrated the clinical feasibility of multimodal cutaneous wound imaging. PMID:25604545

  12. Histological evaluation of the healing properties of Dead Sea black mud on full-thickness excision cutaneous wounds in BALB/c mice.

    PubMed

    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. PMID:24163956

  13. Tissue Engineering and Regenerative Repair in Wound Healing

    PubMed Central

    Hu, Michael S.; Maan, Zeshaan N.; Wu, Jen-Chieh; Rennert, Robert C.; Hong, Wan Xing; Lai, Tiffany S.; Cheung, Alexander T. M.; Walmsley, Graham G.; Chung, Michael T.; McArdle, Adrian; Longaker, Michael T.; Lorenz, H. Peter

    2014-01-01

    Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration. PMID:24788648

  14. Heparin-Based Coacervate of FGF2 Improves Dermal Regeneration by Asserting a Synergistic Role with Cell Proliferation and Endogenous Facilitated VEGF for Cutaneous Wound Healing.

    PubMed

    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. PMID:27196997

  15. [Wound healing in the elderly].

    PubMed

    Eming, S A; Wlaschek, M; Scharffetter-Kochanek, K

    2016-02-01

    Restoration of tissue integrity is essential for host defense and protection of the organism. The efficacy and quality of skin repair varies significantly over a person's lifetime. Whereas prenatal wound healing is characterized by regeneration and scarless healing, scarring, fibrosis, and loss of function are features of postnatal repair. In fact, aging is the prominent risk factor for chronic wounds, skin fragility, infections, comorbidities, and decreased quality of life. Current strategies for restoration of tissue integrity and wound therapy are not sufficient and require further investigation of the underlying pathomechanisms and the development of causal-based concepts. PMID:26728073

  16. Extracellular matrix and wound healing.

    PubMed

    Maquart, F X; Monboisse, J C

    2014-04-01

    Extracellular matrix has been known for a long time as an architectural support for the tissues. Many recent data, however, have shown that extracellular matrix macromolecules (collagens, elastin, glycosaminoglycans, proteoglycans and connective tissue glycoproteins) are able to regulate many important cell functions, such as proliferation, migration, protein synthesis or degradation, apoptosis, etc., making them able to play an important role in the wound repair process. Not only the intact macromolecules but some of their specific domains, that we called "Matrikines", are also able to regulate many cell activities. In this article, we will summarize main findings showing the effects of extracellular matrix macromolecules and matrikines on connective tissue and epithelial cells, particularly in skin, and their potential implication in the wound healing process. These examples show that extracellular matrix macromolecules or some of their specific domains may play a major role in wound healing. Better knowledge of these interactions may suggest new therapeutic targets in wound healing defects. PMID:24650524

  17. Factors That Impair Wound Healing

    PubMed Central

    Anderson, Kristin; Hamm, Rose L.

    2014-01-01

    The body's response to tissue injury in a healthy individual is an intricate, sequential physiologic process that results in timely healing with full re-epithelialization, resolution of drainage, and return of function to the affected tissue. Chronic wounds, however, do not follow this sequence of events and can challenge the most experienced clinician if the underlying factors that are impairing wound healing are not identified. The purpose of this article is to present recent information about factors that impair wound healing with the underlying pathophysiological mechanism that interferes with the response to tissue injury. These factors include co-morbidities (diabetes, obesity, protein energy malnutrition), medications (steroids, non-steroidal anti-inflammatory drugs or NSAIDs, anti-rejection medications), oncology interventions (radiation, chemotherapy), and life style habits (smoking, alcohol abuse). Successful treatment of any chronic wound depends upon identification and management of the factors for each individual. PMID:26199879

  18. Healing in the irradiated wound

    SciTech Connect

    Miller, S.H.; Rudolph, R. )

    1990-07-01

    Poor or nonhealing of irradiated wounds has been attributed to progressive obliterative endarteritis. Permanently damaged fibroblasts may also play an important part in poor healing. Regardless of the cause, the key to management of irradiated skin is careful attention to prevent its breakdown and conservative, but adequate, treatment when wounds are minor. When wounds become larger and are painful, complete excision of the wound or ulcer is called for and coverage should be provided by a well-vascularized nonparasitic distant flap.16 references.

  19. Current concepts in wound management and wound healing products.

    PubMed

    Davidson, Jacqueline R

    2015-05-01

    Current concepts in wound management are summarized. The emphasis is on selection of the contact layer of the bandage to promote a moist wound environment. Selection of an appropriate contact layer is based on the stage of wound healing and the amount of wound exudate. The contact layer can be used to promote autolytic debridement and enhance wound healing. PMID:25744144

  20. Progress in corneal wound healing.

    PubMed

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  1. Modeling of anisotropic wound healing

    NASA Astrophysics Data System (ADS)

    Valero, C.; Javierre, E.; García-Aznar, J. M.; Gómez-Benito, M. J.; Menzel, A.

    2015-06-01

    Biological soft tissues exhibit non-linear complex properties, the quantification of which presents a challenge. Nevertheless, these properties, such as skin anisotropy, highly influence different processes that occur in soft tissues, for instance wound healing, and thus its correct identification and quantification is crucial to understand them. Experimental and computational works are required in order to find the most precise model to replicate the tissues' properties. In this work, we present a wound healing model focused on the proliferative stage that includes angiogenesis and wound contraction in three dimensions and which relies on the accurate representation of the mechanical behavior of the skin. Thus, an anisotropic hyperelastic model has been considered to analyze the effect of collagen fibers on the healing evolution of an ellipsoidal wound. The implemented model accounts for the contribution of the ground matrix and two mechanically equivalent families of fibers. Simulation results show the evolution of the cellular and chemical species in the wound and the wound volume evolution. Moreover, the local strain directions depend on the relative wound orientation with respect to the fibers.

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

    PubMed Central

    Lundvig, Ditte M S; Scharstuhl, Alwin; Cremers, Niels A J; Pennings, Sebastiaan W C; te Paske, Jeroen; van Rheden, René; van Run-van Breda, Coby; Regan, Raymond F; Russel, Frans G M; Carels, Carine E; Maltha, Jaap C; Wagener, Frank 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 wound healing in HO-2 deficient mice is impaired with exorbitant inflammation and absence of HO-1 expression. This study addresses the role of HO-2 in cutaneous excisional wound healing using HO-2 knockout (KO) mice. Here, we show that HO-2 deficiency also delays cutaneous wound closure compared to WT controls. In addition, we detected reduced collagen deposition and vessel density in the wounds of HO-2 KO mice compared to WT controls. Surprisingly, wound closure in HO-2 KO mice was accompanied by an inflammatory response comparable to WT mice. HO-1 induction in HO-2 deficient skin was also similar to WT controls and may explain this protection against exaggerated cutaneous inflammation but not the delayed wound closure. Proliferation and myofibroblast differentiation were similar in both two genotypes. Next, we screened for candidate genes to explain the observed delayed wound closure, and detected delayed gene and protein expression profiles of the chemokine (C-X-C) ligand-11 (CXCL-11) in wounds of HO-2 KO mice. Abnormal regulation of CXCL-11 has been linked to delayed wound healing and disturbed angiogenesis. However, whether aberrant CXCL-11 expression in HO-2 KO mice is caused by or is causing delayed wound healing needs to be further investigated. PMID:25224969

  3. [Phlebology and wound healing].

    PubMed

    Hafner, Jürg; Läuchli, Severin; French, Lars E

    2010-04-01

    Venous diseases are highly prevalent and chronic wounds cause high morbidity and costs. Prevalence of severe forms of chronic venous insufficiency is on the decline. This is due to improved diagnosis and treatment of venous thromboembolism, and to improved surgery of varicose veins and their sequelae. The spectrum of chronic wounds has shifted from venous ulcers towards more complex pathologies. At the same time, new treatment options are available. Modern phlebology effectively treats varicose veins, prevents sequelae of varicosis and deep venous thrombosis, and offers help to the great majority of patients with chronic wounds. PMID:20336620

  4. [Fascial healing and wound failure].

    PubMed

    Fackeldey, V; Höer, J; Klinge, U

    2004-05-01

    The difficulties of acute or delayed failure of fascial healing after laparotomies are of great socioeconomic relevance. Despite a plurality of publications in the last decades, the incidence of burst abdomen (1-3%) and incisional hernia (10-15%) remained unchanged. The generally accepted cause is a multifactorial event with a large number of influencing factors. Therefore, only interdisciplinary cooperations are a match for the scientific complexity of this topic. A still underestimated problem is the description of wound healing factors influencing the microclimate in fascial healing. New aspects of pharmacotherapy and better understanding of collagen synthesis and dynamics of closure tension might improve the clinical situation in the future. PMID:15071734

  5. Skin substitutes and wound healing.

    PubMed

    Auger, F A; Lacroix, D; Germain, L

    2009-01-01

    Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are not life threatening. Nowadays, more than 20 products are commercially available, more are undergoing clinical trials and a large number of new models are being investigated in various research laboratories worldwide. Many of the current products do not contain any living cells and vary in their capacity to harness the innate capacity of the body to heal itself. Others include living cells, of allogeneic or autologous origin, and are often referred to as 'cellular therapy' or 'tissue-engineered' products. Modifications and improvements are currently investigated that aim at improving the healing potential of those products through the use of recombinant growth factors and additional features such as microvascularization. Fundamental research into wound healing and scar-free regeneration raises the hope that we will eventually be able to restore almost completely the appearance and function of skin after the healing of wounds. PMID:19188757

  6. Hyperbaric oxygen and wound healing

    PubMed Central

    Bhutani, Sourabh; Vishwanath, Guruswamy

    2012-01-01

    Hyperbaric oxygen therapy (HBOT) is the use of 100% oxygen at pressures greater than atmospheric pressure. Today several approved applications and indications exist for HBOT. HBOT has been successfully used as adjunctive therapy for wound healing. Non-healing wounds such as diabetic and vascular insufficiency ulcers have been one major area of study for hyperbaric physicians where use of HBOT as an adjunct has been approved for use by way of various studies and trials. HBOT is also indicated for infected wounds like clostridial myonecrosis, necrotising soft tissue infections, Fournier's gangrene, as also for traumatic wounds, crush injury, compartment syndrome, compromised skin grafts and flaps and thermal burns. Another major area of application of HBOT is radiation-induced wounds, specifically osteoradionecrosis of mandible, radiation cystitis and radiation proctitis. With the increase in availability of chambers across the country, and with increasing number of studies proving the benefits of adjunctive use for various kinds of wounds and other indications, HBOT should be considered in these situations as an essential part of the overall management strategy for the treating surgeon. PMID:23162231

  7. Hyperbaric oxygen and wound healing.

    PubMed

    Bhutani, Sourabh; Vishwanath, Guruswamy

    2012-05-01

    Hyperbaric oxygen therapy (HBOT) is the use of 100% oxygen at pressures greater than atmospheric pressure. Today several approved applications and indications exist for HBOT. HBOT has been successfully used as adjunctive therapy for wound healing. Non-healing wounds such as diabetic and vascular insufficiency ulcers have been one major area of study for hyperbaric physicians where use of HBOT as an adjunct has been approved for use by way of various studies and trials. HBOT is also indicated for infected wounds like clostridial myonecrosis, necrotising soft tissue infections, Fournier's gangrene, as also for traumatic wounds, crush injury, compartment syndrome, compromised skin grafts and flaps and thermal burns. Another major area of application of HBOT is radiation-induced wounds, specifically osteoradionecrosis of mandible, radiation cystitis and radiation proctitis. With the increase in availability of chambers across the country, and with increasing number of studies proving the benefits of adjunctive use for various kinds of wounds and other indications, HBOT should be considered in these situations as an essential part of the overall management strategy for the treating surgeon. PMID:23162231

  8. Principles of Wound Management and Wound Healing in Exotic Pets.

    PubMed

    Mickelson, Megan A; Mans, Christoph; Colopy, Sara A

    2016-01-01

    The care of wounds in exotic animal species can be a challenging endeavor. Special considerations must be made in regard to the animal's temperament and behavior, unique anatomy and small size, and tendency toward secondary stress-related health problems. It is important to assess the entire patient with adequate systemic evaluation and consideration of proper nutrition and husbandry, which could ultimately affect wound healing. This article summarizes the general phases of wound healing, factors that affect healing, and principles of wound management. Emphasis is placed on novel methods of treating wounds and species differences in wound management and healing. PMID:26611923

  9. Efficacy of Butea monosperma on dermal wound healing in rats.

    PubMed

    Sumitra, Miriyala; Manikandan, Panchatcharam; Suguna, Lochin

    2005-03-01

    Wound healing occurs as a fundamental response to tissue injury. Several natural products have been shown to accelerate the healing process. The present investigation was undertaken to determine the efficacy of topical administration of an alcoholic bark extract of Butea monosperma (B. monosperma) on cutaneous wound healing in rats. Full-thickness excision wounds were made on the back of rat and B. monosperma extract was administered topically. The granulation tissue formed on days 4, 8, 12 and 16 (post-wound) was used to estimate total collagen, hexosamine, protein, DNA and uronic acid. The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and total collagen content of granulation tissues. The extract treated wounds were found to heal much faster as indicated by improved rates of epithelialization and wound contraction, also confirmed by histopathological examinations. Also, the tensile strength of drug-treated wounds was increased significantly. In addition, we show that B. monosperma possesses antioxidant properties, by its ability to reduce lipid peroxidation. The results clearly substantiate the beneficial effects of the topical application of B. monosperma in the acceleration of wound healing. PMID:15618014

  10. 635nm diode laser biostimulation on cutaneous wounds

    NASA Astrophysics Data System (ADS)

    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.

  11. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

    PubMed Central

    Madigan, Michael C; McEnaney, Ryan M; Shukla, Ankur J; Hong, Guiying; Kelley, Eric E; Tarpey, Margaret M; Gladwin, Mark; Zuckerbraun, Brian S; Tzeng, Edith

    2015-01-01

    Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 μg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production. PMID:25879627

  12. Gene Therapy and Wound Healing

    PubMed Central

    Eming, Sabine A.; Krieg, Thomas; Davidson, Jeffrey M

    2007-01-01

    Wound repair involves the sequential interaction of various cell types, extracellular matrix molecules, and soluble mediators. During the past 10 years, much new information on signals controlling wound cell behavior has emerged. This knowledge has led to a number of novel_therapeutic strategies. In particular, the local delivery of pluripotent growth factor molecules to the injured tissue has been intensively investigated over the past decade. Limited success of clinical trails indicates that a crucial aspect of the growth factor wound-healing strategy is the effective delivery of these polypeptides to the wound site. A molecular approach in which genetically modified cells synthesize and deliver the desired growth factor in regulated fashion has been used to overcome the limitations associated with the (topical) application of recombinant growth factor proteins. We have summarized the molecular and cellular basis of repair mechanisms and their failure, and we give an overview of techniques and studies applied to gene transfer in tissue repair. PMID:17276205

  13. Wound healing and treating wounds: Chronic wound care and management.

    PubMed

    Powers, Jennifer G; Higham, Catherine; Broussard, Karen; Phillips, Tania J

    2016-04-01

    In the United States, chronic ulcers--including decubitus, vascular, inflammatory, and rheumatologic subtypes--affect >6 million people, with increasing numbers anticipated in our growing elderly and diabetic populations. These wounds cause significant morbidity and mortality and lead to significant medical costs. Preventative and treatment measures include disease-specific approaches and the use of moisture retentive dressings and adjunctive topical therapies to promote healing. In this article, we discuss recent advances in wound care technology and current management guidelines for the treatment of wounds and ulcers. PMID:26979353

  14. Amyloidogenesis in Healing Wound

    PubMed Central

    Hashimoto, Ken; Brownstein, Martin H.

    1972-01-01

    Clinically and histologically typical skin lesions of macular and lichenoid amyloidoses were biopsied. Rebiopsies were performed after 2 to 16 weeks, and the sequence of amyloid reproduction in granulation tissue was followed. Initially, medium electron-dense proteinaceous substance with fine filaments was produced within or in close relation to the rough-surfaced endoplasmic reticulum of fibroblasts and subsequently discharged. Typical amyloid filaments emerged within and in the vicinity of this substance. A significant number of collagen fibrils were admixed in the centers of some amyloid islands. Predominantly amorphous amyloid substance was seen in contact with the basal laminae. No plasma cells were observed in foci of amyloid. Nonepithelialized wounds did not contain amyloid. It was suggested that, in the primary skin amyloidoses, abnormal dermal fibroblasts produce amyloid precursors under the influence of the epidermis. ImagesFig 9Fig 10Fig 4Fig 5Fig 11Fig 6Fig 7Fig 12Fig 1Fig 2Fig 8Fig 3 PMID:5049430

  15. Therapeutic utility of antibacterial peptides in wound healing.

    PubMed

    Otvos, Laszlo; Ostorhazi, Eszter

    2015-07-01

    Cationic antimicrobial peptides were first thought to fight infection in animal models by disintegrating bacterial peptides and later by inhibiting bacteria-specific intracellular processes. However, ever increasing evidences indicate that cationic peptides accumulate around and modulate the immune system both systemically and in cutaneous and mucosal surfaces where injuries and infections occur. Native and designer antibacterial peptides as well as cationic peptides, never considered as antibiotics, promote wound healing at every step of cutaneous tissue regeneration. This article provides an introductory list of examples of how cationic peptides are involved in immunostimulation and epithelial tissue repair, eliminating wound infections and promoting wound healing in potential therapeutic utility in sight. Although a few antimicrobial peptides reached the Phase II clinical trial stage, toxicity concerns limit the potential administration routes. Resistance induction to both microbiology actions and the integrity of the innate immune system has to be carefully monitored. PMID:25835521

  16. Effect of age and caloric restriction on cutaneous wound closure in rats and monkeys.

    PubMed

    Roth, G S; Kowatch, M A; Hengemihle, J; Ingram, D K; Spangler, E L; Johnson, L K; Lane, M A

    1997-03-01

    Cutaneous wounds close more slowly in rats and monkeys as age increases. Caloric restriction of 40% in rats and 30% in monkeys did not significantly affect healing rates, although it did exert a trend toward faster closure. Similarly, voluntary exercise did not significantly alter healing rates in rats. Thus, impaired wound healing appears to be a generalized physiological manifestation of aging, but its possible amelioration by "anti-aging" interventions remains to be established. PMID:9060966

  17. Photobiomodulation in promoting wound healing: a review.

    PubMed

    Kuffler, Damien P

    2016-01-01

    Despite diverse methods being applied to induce wound healing, many wounds remain recalcitrant to all treatments. Photobiomodulation involves inducing wound healing by illuminating wounds with light emitting diodes or lasers. While used on different animal models, in vitro, and clinically, wound healing is induced by many different wavelengths and powers with no optimal set of parameters yet being identified. While data suggest that simultaneous multiple wavelength illumination is more efficacious than single wavelengths, the optimal single and multiple wavelengths must be better defined to induce more reliable and extensive healing of different wound types. This review focuses on studies in which specific wavelengths induce wound healing and on their mechanisms of action. PMID:26681143

  18. The role of nuclear hormone receptors in cutaneous wound repair

    PubMed Central

    Rieger, Sandra; Zhao, Hengguang; Martin, Paige; Abe, Koichiro; Lisse, Thomas S.

    2015-01-01

    The cutaneous wound repair process involves balancing a dynamic series of events ranging from inflammation, oxidative stress, cell migration, proliferation, survival and differentiation. A complex series of secreted trophic factors, cytokines, surface and intracellular proteins are expressed in a temporospatial manner to restore skin integrity after wounding. Impaired initiation, maintenance or termination of the tissue repair processes can lead to perturbed healing, necrosis, fibrosis or even cancer. Nuclear hormone receptors (NHRs) in the cutaneous environment regulate tissue repair processes such as fibroplasia and angiogenesis. Defects in functional NHRs and their ligands are associated with the clinical phenotypes of chronic non-healing wounds and skin endocrine disorders. The functional relationship between NHRs and skin niche cells such as epidermal keratinocytes and dermal fibroblasts is pivotal for successful wound closure and permanent repair. The aim of this review is to delineate the cutaneous effects and cross-talk of various nuclear receptors upon injury towards functional tissue restoration. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25529612

  19. Topical Naltrexone as Treatment for Type 2 Diabetic Cutaneous Wounds

    PubMed Central

    Immonen, Jessica A.; Zagon, Ian S.; McLaughlin, Patricia J.

    2014-01-01

    Objective: Type 2 diabetes (T2D) is associated with impaired cutaneous wound healing and can result in ulceration, infection, and/or amputation. More than 25 million people in the United States have T2D and are vulnerable to epithelial-related complications. Current therapies are limited in their efficacy. New treatments for full-thickness cutaneous wounds that focus on underlying diabetic pathways are needed. Approach: Topical application of the opioid receptor antagonist naltrexone (NTX) dissolved in cream reverses delayed wound closure in type 1 diabetic rat by the acceleration of reepithelialization and enhancement of angiogenesis and remodeling. NTX blocks the opioid growth factor (OGF)–OGF receptor (OGFr) axis and upregulates DNA synthesis and cell proliferation. To investigate whether NTX is an effective therapy for T2D wound closure, genetically obese mice (db/db) and normal C57Bl/6J mice received full-thickness cutaneous wounds. Wounds (5 mm in diameter) were treated topically three times daily with 10−5 M NTX or sterile saline dissolved in cream and photographed every 2 days. Results: Wounds in db/db mice treated with saline were 11–92% larger than those in normal mice throughout the 2-week observation. Topical NTX therapy in T2D mice reduced the residual wound size by 13–30% between days 8 and 14 relative to diabetic mice receiving saline. Reepithelialization and DNA synthesis, as analyzed by epithelial thickness and BrdU labeling indexes, respectively, were accelerated in NTX-treated wounds. Innovation and Conclusion: These data suggest that the OGF-OGFr axis plays a role in epithelial-related complications of T2D and that blockade of this pathway by NTX may be an effective treatment for wound repair. PMID:24940556

  20. Polygonum aviculare L. and its active compounds, quercitrin hydrate, caffeic acid, and rutin, activate the Wnt/β-catenin pathway and induce cutaneous wound healing.

    PubMed

    Seo, Seol Hwa; Lee, Soung-Hoon; Cha, Pu-Hyeon; Kim, Mi-Yeon; Min, Do Sik; Choi, Kang-Yell

    2016-05-01

    Polygonum aviculare L. is a member of the Polygonaceae family of plants, which has been known for its antioxidant and anti-obesity effects. However, the wound healing function of P. aviculare extract has not been assessed. In this study, we identified a novel property of P. aviculare extract as a Wnt/β-catenin pathway activator based on a screen of 350 plant extracts using HEK293-TOP cells retaining the Wnt/β-catenin signaling reporter gene. P. aviculare extract accelerated the migration of HaCaT keratinocytes without showing significant cytotoxicity. Moreover, P. aviculare extract efficiently re-epithelized wounds generated on mice. Additionally, ingredients of P. aviculare extract, such as quercitrin hydrate, caffeic acid, and rutin, also accelerated the motility of HaCaT keratinocytes with the activation of Wnt/β-catenin signaling. Therefore, based on our findings, P. aviculare extract and its active ingredients could be potential therapeutic agents for wound healing. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26929003

  1. Topical tacrolimus does not negatively impact acute skin wound healing.

    PubMed

    Namkoong, Sun; Chung, Jimin; Yoo, Jiyeon; Jung, Minyoung; Gye, Jiwon; Kim, Ji Seok; Kim, Jee Young; Ahn, Sung Ku; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2013-05-01

    Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two full-thickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimus- and topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semi-quantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-β, TNF-α and IL-1α. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1α and TGF-β were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model. PMID:23614749

  2. The Role of Chemokines in Fibrotic Wound Healing

    PubMed Central

    Ding, Jie; Tredget, Edward E.

    2015-01-01

    Significance: Main dermal forms of fibroproliferative disorders are hypertrophic scars (HTS) and keloids. They often occur after cutaneous wound healing after skin injury, or keloids even form spontaneously in the absence of any known injury. HTS and keloids are different in clinical performance, morphology, and histology, but they all lead to physical and psychological problems for survivors. Recent Advances: Although the mechanism of wound healing at cellular and tissue levels has been well described, the molecular pathways involved in wound healing, especially fibrotic healing, is incompletely understood. Critical Issues: Abnormal scars not only lead to increased health-care costs but also cause significant psychological problems for survivors. A plethora of therapeutic strategies have been used to prevent or attenuate excessive scar formation; however, most therapeutic approaches remain clinically unsatisfactory. Future Directions: Effective care depends on an improved understanding of the mechanisms that cause abnormal scars in patients. A thorough understanding of the roles of chemokines in cutaneous wound healing and abnormal scar formation will help provide more effective preventive and therapeutic strategies for dermal fibrosis as well as for other proliferative disorders. PMID:26543681

  3. Engineered Biopolymeric Scaffolds for Chronic Wound Healing

    PubMed Central

    Dickinson, Laura E.; Gerecht, Sharon

    2016-01-01

    Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use. However, it is presently hypothesized that no treatment significantly outperforms the others. To address this unmet challenge, recent research has focused on developing innovative acellular biopolymeric scaffolds as more efficacious wound healing therapies. These biomaterial-based skin substitutes are precisely engineered and fine-tuned to recapitulate aspects of the wound healing milieu and target specific events in the wound healing cascade to facilitate complete skin repair with restored function and tissue integrity. This mini-review will provide a brief overview of chronic wound healing and current skin substitute treatment strategies while focusing on recent engineering approaches that regenerate skin using synthetic, biopolymeric scaffolds. We discuss key polymeric scaffold design criteria, including degradation, biocompatibility, and microstructure, and how they translate to inductive microenvironments that stimulate cell infiltration and vascularization to enhance chronic wound healing. As healthcare moves toward precision medicine-based strategies, the potential and therapeutic implications of synthetic, biopolymeric scaffolds as tunable treatment modalities for chronic wounds will be considered. PMID:27547189

  4. Bioelectrical impedance assessment of wound healing.

    PubMed

    Lukaski, Henry C; Moore, Micheal

    2012-01-01

    Objective assessment of wound healing is fundamental to evaluate therapeutic and nutritional interventions and to identify complications. Despite availability of many techniques to monitor wounds, there is a need for a safe, practical, accurate, and effective method. A new method is localized bioelectrical impedance analysis (BIA) that noninvasively provides information describing cellular changes that occur during healing and signal complications to wound healing. This article describes the theory and application of localized BIA and provides examples of its use among patients with lower leg wounds. This promising method may afford clinicians a novel technique for routine monitoring of interventions and surveillance of wounds. PMID:22401341

  5. UVC Light Prophylaxis for Cutaneous Wound Infections in Mice

    PubMed Central

    Dai, Tianhong; Garcia, Barbara; Murray, Clinton K.; Vrahas, Mark S.

    2012-01-01

    UVC light has long been known to be highly germicidal but has not been much developed as a therapy for infections. This study investigated the potential of UVC light for the prophylaxis of infections developing in highly contaminated superficial cutaneous wounds. In vitro studies demonstrated that the pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus were inactivated at UVC light exposures much lower than those needed for a similar effect on mammalian keratinocytes. Mouse models of partial-thickness skin abrasions infected with bioluminescent P. aeruginosa and S. aureus were developed. Approximately 107 bacterial cells were inoculated onto wounds measuring 1.2 by1.2 cm on the dorsal surfaces of mice. UVC light was delivered at 30 min after bacterial inoculation. It was found that for both bacterial infections, UVC light at a single radiant exposure of 2.59 J/cm2 reduced the bacterial burden in the infected mouse wounds by approximately 10-fold in comparison to those in untreated mouse wounds (P < 0.00001). Furthermore, UVC light increased the survival rate of mice infected with P. aeruginosa by 58.3% (P = 0.0023) and increased the wound healing rate in mice infected with S. aureus by 31.2% (P < 0.00001). DNA lesions were observed in the UVC light-treated mouse wounds; however, the lesions were extensively repaired by 48 h after UVC light exposure. These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections. PMID:22564833

  6. Current wound healing procedures and potential care

    PubMed Central

    Dreifke, Michael B.; Jayasuriya, Amil A.; Jayasuriya, Ambalangodage C.

    2015-01-01

    In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting micro RNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage micro environment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection – all in the hopes of early detection of complications. PMID:25579968

  7. Acceleration Of Wound Healing Ny Photodynamic Therapy

    SciTech Connect

    Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

    2000-08-22

    Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

  8. A physiologically active polysaccharide hydrogel promotes wound healing.

    PubMed

    Luo, Yi; Diao, Huajia; Xia, Suhua; Dong, Lei; Chen, Jiangning; Zhang, Junfeng

    2010-07-01

    When the skin is injured, the subcutaneous tissues and organs are threatened by pathogens and excessive water loss. Wound dressings are, therefore, needed to protect the wound site from infection and improve the wound closure. Natural polysaccharides have been applied for various biomaterials including wound dressings, which show their advantages in biocompatibility, low toxicity, and pharmaceutical biomedical activity. In this study, a natural polysaccharide Bletilla striata polysaccharide (BSP) hydrogel is prepared by an oxidation and crosslinking methods. This BSP hydrogel represents preferable swelling ability and appropriate water vapor transmission rate. Using a full-thickness trauma mouse model, the hydrogel is applied on the in vivo cutaneous wound healing. Compared with the control groups, the BSP hydrogel achieves the much better healing results. The quantification of the infiltrating inflammatory cells and the level of tumor necrosis factor alpha (TNF-alpha) in the BSP group are attenuated, whereas the secretion of the epidermal growth factor (EGF) is highly elevated. On the 11th day after surgery, the wound area in the BSP hydrogel group is only 1/5-1/3 of those in the control groups. This new BSP hydrogel is proved to control the inflammatory responses and accelerate the wound closure and has potential application in wound healing. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID:20128009

  9. Epidermal Wound Healing in the Nematode Caenorhabditis elegans

    PubMed Central

    Chisholm, Andrew D.

    2015-01-01

    Significance: Healing of epidermal wounds is a fundamentally conserved process found in essentially all multicellular organisms. Studies of anatomically simple and genetically tractable model invertebrates can illuminate the roles of key genes and mechanisms in wound healing. Recent Advances: The nematode skin is composed of a simple epithelium, the epidermis (also known as hypodermis), and an associated extracellular cuticle. Nematodes likely have a robust capacity for epidermal repair; yet until recently, relatively few studies have directly analyzed wound healing. Here we review epidermal wound responses and repair in the model nematode Caenorhabditis elegans. Critical Issues: Wounding the epidermis triggers a cutaneous innate immune response and wound closure. The innate immune response involves upregulation of a suite of antimicrobial peptides. Wound closure involves a Ca2+-triggered rearrangement of the actin cytoskeleton. These processes appear to be initiated independently, yet, their coordinated activity allows the animal to survive otherwise fatal skin wounds. Future Directions: Unanswered questions include the nature of the damage-associated molecular patterns sensed by the epidermis, the signaling pathways relaying Ca2+ to the cytoskeleton, and the mechanisms of permeability barrier repair. PMID:25945288

  10. Wound Healing in PatientsWith Cancer

    PubMed Central

    Payne, Wyatt G.; Naidu, Deepak K.; Wheeler, Chad K.; Barkoe, David; Mentis, Marni; Salas, R. Emerick; Smith, David J.; Robson, Martin C.

    2008-01-01

    Objective: The treatment of patients with cancer has advanced into a complex, multimodal approach incorporating surgery, radiation, and chemotherapy. Managing wounds in this population is complicated by tumor biology, the patient's disease state, and additional comorbidities, some of which may be iatrogenic. Radiation therapy, frequently employed for local-regional control of disease following surgical resection, has quantifiable negative healing effects due to local tissue fibrosis and vascular effects. Chemotherapeutic agents, either administered alone or as combination therapy with surgery and radiation, may have detrimental effects on the rapidly dividing tissues of healing wounds. Overall nutritional status, often diminished in patients with cancer, is an important aspect to the ability of patients to heal after surgical procedures and/or treatment regimens. Methods: An extensive literature search was performed to gather pertinent information on the topic of wound healing in patients with cancer. The effects that surgical procedures, radiation therapy, chemotherapy, and nutritional deficits play in wound healing in these patients were reviewed and collated. Results: The current knowledge and treatment of these aspects of wound healing in cancer patients are discussed, and observations and recommendations for optimal wound healing results are considered. Conclusion: Although wound healing may proceed in a relatively unimpeded manner for many patients with cancer, there is a potential for wound failure due to the nature and effects of the oncologic disease process and its treatments. PMID:18264518

  11. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.

    PubMed

    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

  12. A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing

    PubMed Central

    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

  13. Stem Cells in Skin Wound Healing: Are We There Yet?

    PubMed Central

    Cerqueira, Mariana Teixeira; Pirraco, Rogério Pedro; Marques, Alexandra Pinto

    2016-01-01

    Significance: Cutaneous wound healing is a serious problem worldwide that affects patients with various wound types, resulting from burns, traumatic injuries, and diabetes. Despite the wide range of clinically available skin substitutes and the different therapeutic alternatives, delayed healing and scarring are often observed. Recent Advances: Stem cells have arisen as powerful tools to improve skin wound healing, due to features such as effective secretome, self-renewal, low immunogenicity, and differentiation capacity. They represent potentially readily available biological material that can particularly target distinct wound-healing phases. In this context, mesenchymal stem cells have been shown to promote cell migration, angiogenesis, and a possible regenerative rather than fibrotic microenvironment at the wound site, mainly through paracrine signaling with the surrounding cells/tissues. Critical Issues: Despite the current insights, there are still major hurdles to be overcome to achieve effective therapeutic effects. Limited engraftment and survival at the wound site are still major concerns, and alternative approaches to maximize stem cell potential are a major demand. Future Directions: This review emphasizes two main strategies that have been explored in this context. These comprise the exploration of hypoxic conditions to modulate stem cell secretome, and the use of adipose tissue stromal vascular fraction as a source of multiple cells, including stem cells and factors requiring minimal manipulation. Nonetheless, the attainment of these approaches to target successfully skin regeneration will be only evident after a significant number of in vivo works in relevant pre-clinical models. PMID:27076994

  14. Calcium-Based Nanoparticles Accelerate Skin Wound Healing

    PubMed Central

    Ishise, Hisako; Carre, Antoine Lyonel; Nishimoto, Soh; Longaker, Michael; Lorenz, H. Peter

    2011-01-01

    Introduction Nanoparticles (NPs) are small entities that consist of a hydroxyapatite core, which can bind ions, proteins, and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calcium levels and have the potential to modulate calcium homeostasis in vivo. Nanoparticles have been associated with various calcium-mediated disease processes, such as atherosclerosis and kidney stone formation. We hypothesized that nanoparticles could have an effect on other calcium-regulated processes, such as wound healing. In the present study, we synthesized pH-sensitive calcium-based nanoparticles and investigated their ability to enhance cutaneous wound repair. Methods Different populations of nanoparticles were synthesized on collagen-coated plates under various growth conditions. Bilateral dorsal cutaneous wounds were made on 8-week-old female Balb/c mice. Nanoparticles were then either administered intravenously or applied topically to the wound bed. The rate of wound closure was quantified. Intravenously injected nanoparticles were tracked using a FLAG detection system. The effect of nanoparticles on fibroblast contraction and proliferation was assessed. Results A population of pH-sensitive calcium-based nanoparticles was identified. When intravenously administered, these nanoparticles acutely increased the rate of wound healing. Intravenously administered nanoparticles were localized to the wound site, as evidenced by FLAG staining. Nanoparticles increased fibroblast calcium uptake in vitro and caused contracture of a fibroblast populated collagen lattice in a dose-dependent manner. Nanoparticles also increased the rate of fibroblast proliferation. Conclusion Intravenously administered, calcium-based nanoparticles can acutely decrease open wound size via contracture. We hypothesize that their contraction effect is mediated by the release of ionized calcium into the wound bed, which occurs when the p

  15. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis.

    PubMed

    Wu, Yaojiong; Chen, Liwen; Scott, Paul G; Tredget, Edward E

    2007-10-01

    Although chronic wounds are common, treatment for these disabling conditions remains limited and largely ineffective. In this study, we examined the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing. Using an excisional wound splinting model, we showed that injection around the wound and application to the wound bed of green fluorescence protein (GFP)(+) allogeneic BM-MSCs significantly enhanced wound healing in normal and diabetic mice compared with that of allogeneic neonatal dermal fibroblasts or vehicle control medium. Fluorescence-activated cell sorting analysis of cells derived from the wound for GFP-expressing BM-MSCs indicated engraftments of 27% at 7 days, 7.6% at 14 days, and 2.5% at 28 days of total BM-MSCs administered. BM-MSC-treated wounds exhibited significantly accelerated wound closure, with increased re-epithelialization, cellularity, and angiogenesis. Notably, BM-MSCs, but not CD34(+) bone marrow cells in the wound, expressed the keratinocyte-specific protein keratin and formed glandular structures, suggesting a direct contribution of BM-MSCs to cutaneous regeneration. Moreover, BM-MSC-conditioned medium promoted endothelial cell tube formation. Real-time polymerase chain reaction and Western blot analysis revealed high levels of vascular endothelial growth factor and angiopoietin-1 in BM-MSCs and significantly greater amounts of the proteins in BM-MSC-treated wounds. Thus, our data suggest that BM-MSCs promote wound healing through differentiation and release of proangiogenic factors. Disclosure of potential conflicts of interest is found at the end of this article. PMID:17615264

  16. Ultraviolet light and hyperpigmentation in healing wounds

    SciTech Connect

    Wiemer, D.R.; Spira, M.

    1983-10-01

    The concept of permanent hyperpigmentation in wounds following ultraviolet light exposure during the postoperative period has found a place in plastic surgical literature but has not been documented. This study evaluates the effect of ultraviolet light on healing wounds in paraplegics. It failed to confirm permanent alteration in pigmentation response to ultraviolet exposure and suggests that other factors are of greater importance in the development of hyperpigmentation in the healing wound.

  17. Rapid identification of slow healing wounds.

    PubMed

    Jung, Kenneth; Covington, Scott; Sen, Chandan K; Januszyk, Michael; Kirsner, Robert S; Gurtner, Geoffrey C; Shah, Nigam H

    2016-01-01

    Chronic nonhealing wounds have a prevalence of 2% in the United States, and cost an estimated $50 billion annually. Accurate stratification of wounds for risk of slow healing may help guide treatment and referral decisions. We have applied modern machine learning methods and feature engineering to develop a predictive model for delayed wound healing that uses information collected during routine care in outpatient wound care centers. Patient and wound data was collected at 68 outpatient wound care centers operated by Healogics Inc. in 26 states between 2009 and 2013. The dataset included basic demographic information on 59,953 patients, as well as both quantitative and categorical information on 180,696 wounds. Wounds were split into training and test sets by randomly assigning patients to training and test sets. Wounds were considered delayed with respect to healing time if they took more than 15 weeks to heal after presentation at a wound care center. Eleven percent of wounds in this dataset met this criterion. Prognostic models were developed on training data available in the first week of care to predict delayed healing wounds. A held out subset of the training set was used for model selection, and the final model was evaluated on the test set to evaluate discriminative power and calibration. The model achieved an area under the curve of 0.842 (95% confidence interval 0.834-0.847) for the delayed healing outcome and a Brier reliability score of 0.00018. Early, accurate prediction of delayed healing wounds can improve patient care by allowing clinicians to increase the aggressiveness of intervention in patients most at risk. PMID:26606167

  18. Biomarkers for wound healing and their evaluation.

    PubMed

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing. PMID:26762498

  19. Regenerative materials that facilitate wound healing.

    PubMed

    Mulder, Gerit; Wallin, Kelly; Tenenhaus, Mayer

    2012-07-01

    Wounds and damaged tissue become problematic when the tissue repair process does not proceed in a normal manner. Standard treatment of wounds entails topical dressings and devices in conjunction with good wound care practices. Good practices adequately support healing in most patients. Difficult, chronic, or recalcitrant wounds may require the use of more advanced technologies. Wounds that are full thickness or present with the absence of a matrix, may particularly benefit from regenerative materials. This article focuses on the use of cellular and acellular materials as well as chemical constructs to support granulation, tissue repair, and wound closure. PMID:22732374

  20. Regulation of wound healing by growth factors and cytokines.

    PubMed

    Werner, Sabine; Grose, Richard

    2003-07-01

    Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process. PMID:12843410

  1. Loss of Innervation and Axon Plasticity Accompanies Impaired Diabetic Wound Healing

    PubMed Central

    Cheng, Chu; Kan, Michelle; Martinez, Jose A.; Zochodne, Douglas W.

    2013-01-01

    Loss of cutaneous innervation from sensory neuropathy is included among mechanisms for impaired healing of diabetic skin wounds. The relationships between cutaneous axons and their local microenvironment during wound healing are challenged in diabetes. Here, we show that secondary wound closure of the hairy dorsal skin of mice is delayed by diabetes and is associated with not only a pre-existing loss of cutaneous axons but substantial retraction of axons around the wound. At 7d following a 3mm punch wound, a critical period of healing and reinnervation, both intact skin nearby the wound and skin directly at the wound margins had over 30-50% fewer axons and a larger deficit of ingrowing axons in diabetics. These findings contrasted with a pre-existing 10-15% deficit in axons. Moreover, new diabetic ingrowing axons had less evidence of plasticity. Unexpectedly, hair follicles adjacent to the wounds had a 70% reduction in their innervation associated with depleted expression of hair follicular stem cell markers. These impairments were associated with the local upregulation of two established axon regenerative ‘roadblocks’: PTEN and RHOA, potential but thus far unexplored mediators of these changes. The overall findings identify striking and unexpected superimposed cutaneous axon loss or retraction beyond that expected of diabetic neuropathy alone, associated with experimental diabetic skin wounding, a finding that prompts new considerations in diabetic wounds. PMID:24098736

  2. microRNA and Wound Healing.

    PubMed

    Banerjee, Jaideep; Sen, Chandan K

    2015-01-01

    microRNAs (miRNAs) are small noncoding RNA molecules which play pivotal roles in wound healing. The increased expression of certain genes and expression of some others represent a key component of the wound biology and are largely under the regulation of naturally occurring miRNAs. Understanding the dysregulated miRNAs in chronic wound biology will therefore enable the development of newer therapies. This chapter focuses on the miRNAs that can be potentially targeted for improving skin wound healing and the challenges in miRNA therapy, including considerations in miRNA target identification and delivery. PMID:26663189

  3. Thrombomodulin Promotes Corneal Epithelial Wound Healing

    PubMed Central

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    Purpose To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing. Methods TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays. Results TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing. Conclusions TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury. PMID:25816372

  4. Systems-based approaches toward wound healing

    PubMed Central

    Buganza-Tepole, Adrian; Kuhl, Ellen

    2013-01-01

    Wound healing in the pediatric patient is of utmost clinical and social importance, since hypertrophic scarring can have aesthetic and psychological sequelae, from early childhood to late adolescence. Wound healing is a well-orchestrated reparative response affecting the damaged tissue at the cellular, tissue, organ, and system scales. While tremendous progress has been made towards understanding wound healing at the individual temporal and spatial scales, its effects across the scales remain severely understudied and poorly understood. Here we discuss the critical need for systems-based computational modeling of wound healing across the scales, from short-term to long-term and from small to large. We illustrate the state of the art in systems modeling by means of three key signaling mechanisms: oxygen tension regulating angiogenesis and revascularization; TGF-β kinetics controlling collagen deposition; and mechanical stretch stimulating cellular mitosis and extracellular matrix remodeling. The complex network of biochemical and biomechanical signaling mechanisms and the multi-scale character of the healing process make systems modeling an integral tool in exploring personalized strategies for wound repair. A better mechanistic understanding of wound healing in the pediatric patient could open new avenues in treating children with skin disorders such as birth defects, skin cancer, wounds, and burn injuries. PMID:23314298

  5. Mast Cells Regulate Wound Healing in Diabetes.

    PubMed

    Tellechea, Ana; Leal, Ermelindo C; Kafanas, Antonios; Auster, Michael E; Kuchibhotla, Sarada; Ostrovsky, Yana; Tecilazich, Francesco; Baltzis, Dimitrios; Zheng, Yongjun; Carvalho, Eugénia; Zabolotny, Janice M; Weng, Zuyi; Petra, Anastasia; Patel, Arti; Panagiotidou, Smaro; Pradhan-Nabzdyk, Leena; Theoharides, Theoharis C; Veves, Aristidis

    2016-07-01

    Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P < 0.05). Conversely, postwounding MC degranulation increases in nondiabetic mice, but not in diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P < 0.05). Nevertheless, nondiabetic and diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes. PMID:27207516

  6. Wound-healing properties of nut oil from Pouteria lucuma

    PubMed Central

    Rojo, Leonel E; Villano, Caren M; Joseph, Gili; Schmidt, Barbara; Shulaev, Vladimir; Shuman, Joel L; Lila, Mary Ann; Raskin, Ilya

    2014-01-01

    Summary Background Cell migration, angiogenesis, inflammation, and extracellular matrix remodeling are key events in wound healing. Natural products, including fatty acids (FAs), can accelerate wound healing by modulating the aforementioned events. Aims This study aims to evaluate the effect of lucuma (Pouteria lucuma O Kezte) nut oil (LNO) on fibroblasts migration, angiogenesis, inflammation, bacterial and fungal growth, and wound healing. Methods GC–MS analysis of FAs methyl esters (FAMES) was used for chemical characterization of LNO. In vitro studies were carried out with LNO investigating the induction of cell migration, cytoskeleton remodeling of human fibroblasts, inhibition of LPS-induced nitric oxide production in macrophages, and antibacterial and antifungal effects. Two in vivo studies were carried out to study LNO’s effect on angiogenesis and wound healing: (i) tail fin regeneration in transgenic zebrafish larvae expressing enhanced green fluorescent protein (EGFP) in vascular endothelial cells was used to study vessel sprouting and wound healing and (ii) the closure of wounds was evaluated in CD-1 mice after topical applications of LNO-containing formulations. Results Lucuma nut oil is a mixture of FAs, 99.7% of which were characterized. Major components of LNO (w/w) are linoleic acid (38.9%), oleic acid (27.9%), palmitic acid (18.6%), stearic acid (8.9%), and γ linolenic acid (2.9%). In vitro studies showed that LNO significantly promoted migration and vinculin expression in human fibroblasts. LNO decreased LPS-induced nitric oxide production and did not display significant antibacterial or antifungal effects. LNO induced tail fin regeneration in transgenic zebrafish larvae 48 h after tail fin amputation and significantly accelerated cutaneous wound closure in CD-1 mice. Conclusions Natural FAs from P. lucuma nut promote skin regeneration and, thus, may have applications in medicine and skin care. PMID:20883291

  7. Cellular events and biomarkers of wound healing

    PubMed Central

    Shah, Jumaat Mohd. Yussof; Omar, Effat; Pai, Dinker R.; Sood, Suneet

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds. PMID:23162220

  8. Practices in Wound Healing Studies of Plants

    PubMed Central

    Thakur, Rupesh; Jain, Nitika; Pathak, Raghvendra; Sandhu, Sardul Singh

    2011-01-01

    Wounds are the result of injuries to the skin that disrupt the other soft tissue. Healing of a wound is a complex and protracted process of tissue repair and remodeling in response to injury. Various plant products have been used in treatment of wounds over the years. Wound healing herbal extracts promote blood clotting, fight infection, and accelerate the healing of wounds. Phytoconstituents derived from plants need to be identified and screened for antimicrobial activity for management of wounds. The in vitro assays are useful, quick, and relatively inexpensive. Small animals provide a multitude of model choices for various human wound conditions. The study must be conducted after obtaining approval of the Ethics Committee and according to the guidelines for care and use of animals. The prepared formulations of herbal extract can be evaluated by various physicopharmaceutical parameters. The wound healing efficacies of various herbal extracts have been evaluated in excision, incision, dead space, and burn wound models. In vitro and in vivo assays are stepping stones to well-controlled clinical trials of herbal extracts. PMID:21716711

  9. Wound Healing Essentials: Let There Be Oxygen

    PubMed Central

    Sen, Chandan K.

    2009-01-01

    The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O2 in the peri-operative period reduces the incidence of post-operative infections. Correction of wound pO2 may, by itself, trigger some healing responses. Importantly, approaches to correct wound pO2 favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near-anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising. PMID:19152646

  10. Mechanoregulation of Wound Healing and Skin Homeostasis

    PubMed Central

    Rosińczuk, Joanna; Taradaj, Jakub; Dymarek, Robert; Sopel, Mirosław

    2016-01-01

    Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study. PMID:27413744

  11. [Actin in the wound healing process].

    PubMed

    Nowak, Dorota; Popow-Woźniak, Agnieszka; Raźnikiewicz, Linda; Malicka-Błaszkiewicz, Maria

    2009-01-01

    Wound healing is an important biological process of crucial value for organisms survival and retention of its proper functions. The recognition of molecular mechanisms of these phenomenon is still under investigation. The transition of mesenchymal fibroblasts to myofibroblasts is a key point in wound healing. The contraction ability of myofibroblast enables the shrinkage of a wound and closes its edges. Alpha smooth muscle actin (alpha-SMA), one of six actin isoforms, is a marker of compeletely differentiated myofibroblast. The regulation of differentiation process depends on many growth factors (especially TGF beta 1), the level of active thymosin beta 4, extracellular matrix proteins--including fibronectin, and also on specificity of microenvironment. Thymosin beta 4 is responsible for maintenance of pool of monomeric actin and actin filaments depolymerization. It can also act as a transcription factor, migration stimulator and immunomodulator, so this protein deserves for more attention in wound healing research field. PMID:19824469

  12. Scarless wound healing: chasing the holy grail.

    PubMed

    Walmsley, Graham G; Maan, Zeshaan N; Wong, Victor W; Duscher, Dominik; Hu, Michael S; Zielins, Elizabeth R; Wearda, Taylor; Muhonen, Ethan; McArdle, Adrian; Tevlin, Ruth; Atashroo, David A; Senarath-Yapa, Kshemendra; Lorenz, H Peter; Gurtner, Geoffrey C; Longaker, Michael T

    2015-03-01

    Over 100 million patients acquire scars in the industrialized world each year, primarily as a result of elective operations. Although undefined, the global incidence of scarring is even larger, extending to significant numbers of burn and other trauma-related wounds. Scars have the potential to exert a profound psychological and physical impact on the individual. Beyond aesthetic considerations and potential disfigurement, scarring can result in restriction of movement and reduced quality of life. The formation of a scar following skin injury is a consequence of wound healing occurring through reparative rather than regenerative mechanisms. In this article, the authors review the basic stages of wound healing; differences between adult and fetal wound healing; various mechanical, genetic, and pharmacologic strategies to reduce scarring; and the biology of skin stem/progenitor cells that may hold the key to scarless regeneration. PMID:25719706

  13. Complement Activation and Inhibition in Wound Healing

    PubMed Central

    Cazander, Gwendolyn; Jukema, Gerrolt N.; Nibbering, Peter H.

    2012-01-01

    Complement activation is needed to restore tissue injury; however, inappropriate activation of complement, as seen in chronic wounds can cause cell death and enhance inflammation, thus contributing to further injury and impaired wound healing. Therefore, attenuation of complement activation by specific inhibitors is considered as an innovative wound care strategy. Currently, the effects of several complement inhibitors, for example, the C3 inhibitor compstatin and several C1 and C5 inhibitors, are under investigation in patients with complement-mediated diseases. Although (pre)clinical research into the effects of these complement inhibitors on wound healing is limited, available data indicate that reduction of complement activation can improve wound healing. Moreover, medicine may take advantage of safe and effective agents that are produced by various microorganisms, symbionts, for example, medicinal maggots, and plants to attenuate complement activation. To conclude, for the development of new wound care strategies, (pre)clinical studies into the roles of complement and the effects of application of complement inhibitors in wound healing are required. PMID:23346185

  14. Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species.

    PubMed

    Panchatcharam, Manikandan; Miriyala, Sumitra; Gayathri, Vinaya Subramani; Suguna, Lonchin

    2006-10-01

    Wound healing consists of an orderly progression of events that re-establish the integrity of the damaged tissue. Several natural products have been shown to accelerate the healing process. The present investigation was undertaken to determine the role of curcumin on changes in collagen characteristics and antioxidant property during cutaneous wound healing in rats. Full-thickness excision wounds were made on the back of rat and curcumin was administered topically. The wound tissues removed on 4th, 8th and 12th day (post-wound) were used to analyse biochemical and pathological changes. Curcumin increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and type III collagen content of wound tissues. Curcumin treated wounds were found to heal much faster as indicated by improved rates of epithelialisation, wound contraction and increased tensile strength which were also confirmed by histopathological examinations. Curcumin treatment was shown to decrease the levels of lipid peroxides (LPs), while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), activities were significantly increased exhibiting the antioxidant properties of curcumin in accelerating wound healing. Better maturation and cross linking of collagen were observed in the curcumin treated rats, by increased stability of acid-soluble collagen, aldehyde content, shrinkage temperature and tensile strength. The results clearly substantiate the beneficial effects of the topical application of curcumin in the acceleration of wound healing and its antioxidant effect. PMID:16770527

  15. Curbing Inflammation in Skin Wound Healing: A Review

    PubMed Central

    Rosique, Rodrigo G.; Rosique, Marina J.; Farina Junior, Jayme A.

    2015-01-01

    Wound healing is a complex regulated process that results in skin scar formation in postnatal mammals. Chronic wounds are major medical problems that can confer devastating consequences. Currently, there are no treatments to prevent scarring. In the early fetus wounds heal without scarring and the healing process is characterized by relatively less inflammation compared to adults; therefore, research aimed at reducing the inflammatory process related to wound healing might speed healing and improve the final scar appearance. PMID:26356299

  16. Nutrient support of the healing wound.

    PubMed

    Meyer, N A; Muller, M J; Herndon, D N

    1994-05-01

    Wound healing is a series of complex physicochemical interactions that require various micronutrients at every step. In the critically ill or severely injured patient, wound healing is impaired by the protein-catabolic, hypermetabolic response to stress. The hypothalamus responds to cytokine stimulation by increasing the thermoregulatory set-point and by augmenting elaboration of stress hormones (catecholamines, cortisol, and glucagon). In turn, the stress hormones induce thermogenic futile substrate cycling, lipolysis, and proteolysis. Increased glucose production results at the expense of skeletal muscle degradation, producing amino acid substrate for hepatic gluconeogenesis. Nutritional support of the hypermetabolic state is an essential part of ensuring efficient wound healing in these patients. Protein catabolism cannot be reversed by increased amino acid availability alone, due partly to a defect in amino acid transport. This defect can be reversed by anabolic agents, such as growth hormone and insulin-like growth factor-1. Growth hormone treatment dramatically improves wound healing in severely burned children. Supplementation with protein and vitamins, specifically arginine and vitamins A, B, and C, provides optimum nutrient support of the healing wound. PMID:7922445

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

    PubMed

    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. PMID:26218128

  18. Wound Healing and the Dressing*

    PubMed Central

    Scales, John T.

    1963-01-01

    The evolution of surgical dressings is traced from 1600 b.c. to a.d. 1944. The availability of an increasing variety of man-made fibres and films from 1944 onwards has stimulated work on wound dressings, and some of the more important contributions, both clinical and experimental, are discussed. The functions of a wound dressing and the properties which the ideal wound dressing should possess are given. The necessity for both histological and clinical evaluation of wound dressings in animals and in man is stressed. Wound dressings are the most commonly used therapeutic agents, but there is no means whereby their performance can be assessed. An attempt should be made either nationally or internationally to establish a standard method of assessing the performance of wound dressings. For this it is necessary to have an internationally agreed standard dressing which could be used as a reference or control dressing in all animal and human work. The only animal with skin morphologically similar to that of man is the domestic pig. Three types of wounds could be used: (1) partial-thickness wounds; (2) full-thickness excisions; and (3) third-degree burns. The development of standard techniques for the assessment of the efficiency of wound dressings would be of considerable benefit to the research worker, the medical profession, the patient, and the surgical dressings industry. PMID:13976490

  19. Pulsed electromagnetic fields (PEMF) promote early wound healing and myofibroblast proliferation in diabetic rats.

    PubMed

    Cheing, Gladys Lai-Ying; Li, Xiaohui; Huang, Lin; Kwan, Rachel Lai-Chu; Cheung, Kwok-Kuen

    2014-04-01

    Reduced collagen deposition possibly leads to slow recovery of tensile strength in the healing process of diabetic cutaneous wounds. Myofibroblasts are transiently present during wound healing and play a key role in wound closure and collagen synthesis. Pulsed electromagnetic fields (PEMF) have been shown to enhance the tensile strength of diabetic wounds. In this study, we examined the effect of PEMF on wound closure and the presence of myofibroblasts in Sprague-Dawley rats after diabetic induction using streptozotocin. A full-thickness square-shaped dermal wound (2 cm × 2 cm) was excised aseptically on the shaved dorsum. The rats were randomly divided into PEMF-treated (5 mT, 25 Hz, 1 h daily) and control groups. The results indicated that there were no significant differences between the groups in blood glucose level and body weight. However, PEMF treatment significantly enhanced wound closure (days 10 and 14 post-wounding) and re-epithelialization (day 10 post-wounding), although these improvements were no longer observed at later stages of the wound healing process. Using immunohistochemistry against α-smooth muscle actin (α-SMA), we demonstrated that significantly more myofibroblasts were detected on days 7 and 10 post-wounding in the PEMF group when compared to the control group. We hypothesized that PEMF would increase the myofibroblast population, contributing to wound closure during diabetic wound healing. PMID:24395219

  20. 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

    PubMed Central

    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. PMID:27057551

  1. Dynamic Regulation of Integrin α6β4 During Angiogenesis: Potential Implications for Pathogenic Wound Healing

    PubMed Central

    Desai, Diana; Singh, Purva; Van De Water, Livingston; LaFlamme, Susan E.

    2013-01-01

    Objective Angiogenesis is an essential component of normal cutaneous wound repair, but is altered in pathogenic forms of wound healing, such as chronic wounds and fibrosis. We previously reported that endothelial expression of integrin α6β4 is developmentally regulated, with α6β4 expression correlating with tissue maturation and further showed that endothelial α6β4 is downregulated in explant angiogenesis assays. These data support the hypothesis that dynamic regulation of α6β4 may play an important role during new vessel formation in healing wounds. Approach To test this hypothesis, we examined the endothelial expression of α6β4 using a murine model of cutaneous wound healing and in vitro cultures of primary human dermal microvascular endothelial cells (HDMECs). Results Expression of α6β4 is downregulated during early stages of wound healing; angiogenic vessels in day 7 wounds do not express α6β4. Endothelial expression of α6β4 is resumed in day 14 wounds. Moreover, explanted HDMECs do not express α6β4, but expression is induced by treatment with histone deacetylase inhibitors. Innovation We provide in vivo data supporting a role for the dynamic regulation of α6β4 during vessel formation and remodeling during cutaneous wound repair and in vitro findings that suggest endothelial β4 expression is regulated transcriptionally, providing an important foundation for future studies to understand the transcriptional mechanisms involved in endothelial cell maturation during normal wound repair. Conclusion Our data indicate that α6β4 is dynamically regulated during angiogenesis and vessel maturation and suggest that disruption of this regulation may contribute to defective angiogenesis associated with diabetic wounds or cutaneous fibrosis. PMID:24527356

  2. Forces driving epithelial wound healing

    NASA Astrophysics Data System (ADS)

    Brugués, Agustí; Anon, Ester; Conte, Vito; Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2014-09-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and `purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.

  3. Forces driving epithelial wound healing

    PubMed Central

    Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2015-01-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and “purse-string” contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423

  4. Boundary crossing in epithelial wound healing

    PubMed Central

    Fong, Eileen; Tzlil, Shelly; Tirrell, David A.

    2010-01-01

    The processes of wound healing and collective cell migration have been studied for decades. Intensive research has been devoted to understanding the mechanisms involved in wound healing, but the role of cell-substrate interactions is still not thoroughly understood. Here we probe the role of cell-substrate interactions by examining in vitro the healing of monolayers of human corneal epithelial (HCE) cells cultured on artificial extracellular matrix (aECM) proteins. We find that the rate of wound healing is dependent on the concentration of fibronectin-derived (RGD) cell-adhesion ligands in the aECM substrate. The wound closure rate varies nearly sixfold on the substrates examined, despite the fact that the rates of migration and proliferation of individual cells show little sensitivity to the RGD concentration (which varies 40-fold). To explain this apparent contradiction, we study collective migration by means of a dynamic Monte Carlo simulation. The cells in the simulation spread, retract, and proliferate with probabilities obtained from a simple phenomenological model. The results indicate that the overall wound closure rate is determined primarily by the rate at which cells cross the boundary between the aECM protein and the matrix deposited under the cell sheet. PMID:20974917

  5. Epithelialization in Wound Healing: A Comprehensive Review

    PubMed Central

    Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana

    2014-01-01

    Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064

  6. The Presence of Oxygen in Wound Healing.

    PubMed

    Kimmel, Howard M; Grant, Anthony; Ditata, James

    2016-08-01

    Oxygen must be tightly governed in all phases of wound healing to produce viable granulation tissue. This idea of tight regulation has yet to be disputed; however, the role of oxygen at the cellular and molecular levels still is not fully understood as it pertains to its place in healing wounds. In an attempt to better understand the dynamics of oxygen on living tissue and its potential role as a therapy in wound healing, a substantial literature review of the role of oxygen in wound healing was performed and the following key points were extrapolated: 1) During energy metabolism, oxygen is needed for mitochondrial cytochrome oxidase as it produces high-energy phosphates that are needed for many cellular functions, 2) oxygen is also involved in the hydroxylation of proline and lysine into procollagen, which leads to collagen maturation, 3) in angiogenesis, hypoxia is required to start the process of wound healing, but it has been shown that if oxygen is administered it can accelerate and sustain vessel growth, 4) the antimicrobial action of oxygen occurs when nicotinamide adenine dinucleotide phosphate (NADPH)-linked oxygenase acts as a catalyst for the production of reactive oxygen species (ROS), a superoxide ion which kills bacteria, and 5) the level of evidence is moderate for the use of hyperbaric oxygen therapy (HBOT) for diabetic foot ulcers, crush injuries, and soft-tissue infections. The authors hypothesized that HBOT would be beneficial to arterial insufficiency wounds and other ailments, but at this time further study is needed before HBOT would be indicated. PMID:27560469

  7. The phytoestrogen genistein promotes wound healing by multiple independent mechanisms.

    PubMed

    Emmerson, Elaine; Campbell, Laura; Ashcroft, Gillian S; Hardman, Matthew J

    2010-06-10

    Genistein has been implicated in the beneficial effects of soy on human health, particularly in the context of ageing. In post-menopausal women reduced systemic estrogen leads to a range of age-associated pathologies, including delayed cutaneous wound healing. We have previously shown that this can be reversed by estrogen replacement. However, the effect of genistein on the skin is poorly understood and crucially the influence of genistein on wound healing has not been assessed. 10-week-old ovariectomised mice were systemically treated with 17beta-estradiol or genistein. Genistein substantially accelerated wound repair, associated with a dampened inflammatory response. Unexpectedly, co-treatment with the ER antagonist ICI had little impact on the anti-inflammatory, healing promoting effects of genistein. Thus genistein's actions are only partially mediated via classical estrogen receptor-dependent signalling pathways. Indeed, we report that alternative (cell-type specific) signalling mechanisms are activated in the skin in response to genistein treatment. PMID:20193736

  8. Delayed Wound Healing in Diabetic (db/db) Mice with Pseudomonas aeruginosa Biofilm Challenge – A Model for the Study of Chronic Wounds

    PubMed Central

    Zhao, Ge; Hochwalt, Phillip C.; Usui, Marcia L.; Underwood, Robert A.; Singh, Pradeep K.; James, Garth A.; Stewart, Philip S.; Fleckman, Philip; Olerud, John E.

    2010-01-01

    Chronic wounds are a major clinical problem that leads to considerable morbidity and mortality. We hypothesized that an important factor in the failure of chronic wounds to heal was the presence of microbial biofilm resistant to antibiotics and protected from host defenses. A major difficulty in studying chronic wounds is the absence of suitable animal models. The goal of this study was to create a reproducible chronic wound model in diabetic mice by application of bacterial biofilm. Six millimeter punch biopsy wounds were created on the dorsal surface of diabetic (db/db) mice, subsequently challenged with Pseudomonas aeruginosa (PAO1) biofilms two days post-wounding, and covered with semi-occlusive dressings for two weeks. Most of the control wounds were epithelialized by 28 days post-wounding. In contrast, none of biofilm challenged wounds were closed. Histological analysis showed extensive inflammatory cell infiltration, tissue necrosis and epidermal hyperplasia adjacent to challenged wounds- all indicators of an inflammatory non-healing wound. Quantitative cultures and transmission electron microscopy demonstrated that the majority of bacteria were in the scab above the wound bed rather than in the wound tissue. The model was reproducible, allowed localized cutaneous wound infections without high mortality and demonstrated delayed wound healing following biofilm challenge. This model may provide an approach to study the role of microbial biofilms in chronic wounds as well as the effect of specific biofilm therapy on wound healing. PMID:20731798

  9. Wound Healing in Potato Tuber Tissue

    PubMed Central

    Borchert, R.; McChesney, J. D.; Watson, D.

    1974-01-01

    Several aspects of wound healing in tuber tissue of potato (Solanum tuberosum var. Kennebec), known to require protein synthesis, are inhibited by 2,4-dichlorobenzyltributylphosphonium chloride (Phosphon D). Cell division was completely blocked by 60 μm Phosphon and markedly reduced by concentrations as low as 3 μm. When applied at the time of wounding, 0.25mm Phosphon completely prevented the wound-induced respiratory increase. Application at 15 hours after wounding arrested respiration at the rate present at that time. The same concentrations of Phosphon inhibited auxin-induced cell expansion of the tissue, protein synthesis as measured by the incorporation of leucine-14C into the trichloroacetic acid-insoluble fraction of tissue disks, and the appearance of wound-induced peroxidase isozymes. None of these inhibitory effects of Phosphon could be prevented or reversed by the application of gibberellic acid. All wound-induced processes inhibited by Phosphon are also inhibited by cycloheximide. It is suggested that inhibitory effects of Phosphon on wound healing in potato and on other developmental processes in excised plant tissues which cannot be reversed by gibberellin are due to interference with protein synthesis. PMID:16658674

  10. Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

    PubMed Central

    Xue, Meilang; Jackson, Christopher J.

    2015-01-01

    Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. PMID:25785236

  11. Cold temperature delays wound healing in postharvest sugarbeet roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Storage temperature affects the rate and extent of wound-healing in a number of root and tuber crops. The effect of storage temperature on wound-healing in sugarbeet (Beta vulgaris L.) roots, however, is largely unknown. Wound-healing of sugarbeet roots was investigated using surface-abraded roots s...

  12. Signals Involved in Tuber Wound-Healing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The induction and regulation of wound-healing (WH) processes in potato tubers and other vegetables are of great nutritional and economic importance. The rapid accumulation of waxes to restrict water vapor loss and formation of suberin barriers to block infection are crucial components of WH. Recen...

  13. Biomechanics and Wound Healing in the Cornea

    PubMed Central

    Dupps, William J.; Wilson, Steven E.

    2009-01-01

    The biomechanical and wound healing properties of the cornea undermine the predictability and stability of refractive surgery and contribute to discrepancies between attempted and achieved visual outcomes after LASIK, surface ablation and other keratorefractive procedures. Furthermore, patients predisposed to biomechanical failure or abnormal wound healing can experience serious complications such as keratectasia or clinically significant corneal haze, and more effective means for the identification of such patients prior to surgery are needed. In this review, we describe the cornea as a complex structural composite material with pronounced anisotropy and heterogeneity, summarize current understanding of major biomechanical and reparative pathways that contribute to the corneal response to laser vision correction, and review the role of these processes in ectasia, intraocular pressure measurement artifact, diffuse lamellar keratitis (DLK) and corneal haze. The current understanding of differences in the corneal response after photorefractive keratectomy (PRK), LASIK and femtosecond-assisted LASIK are reviewed. Surgical and disease models that integrate corneal geometric data, substructural anatomy, elastic and viscoelastic material properties and wound healing behavior have the potential to improve clinical outcomes and minimize complications but depend on the identification of preoperative predictors of biomechanical and wound healing responses in individual patients. PMID:16720023

  14. Mucopolysaccharides from psyllium involved in wound healing.

    PubMed

    Westerhof, W; Das, P K; Middelkoop, E; Verschoor, J; Storey, L; Regnier, C

    2001-01-01

    Mucopolysaccharides derived from the husk of psyllium (Plantago ovata) have properties beneficial for wound cleansing and wound healing. Recent studies indicate that these mucopolysaccharides also limit scar formation. Our in vitro and in vivo studies aimed to investigate the mechanisms involved, e.g., fluid absorption, bacterial adherence and in vitro stimulatory effects on macrophages, which are pivotal in wound healing. The mucopolysaccharides contained in a sachet (Askina Cavity) or in a hydrocolloid mixture (Askina Hydro) were found to have a gradual and sustained absorbency over a period of 7 days, amounting to 4-6 times their weight in water. The swelling index was 9 mm after 312 h. Adherence of wound bacteria to the mucopolysaccharides started after 2 h and was more pronounced after 3 h. Semiquantitative measurements of bacterial adherence used centrifugation and subsequent optical density determinations of supernatant. These confirmed the strong adherence potential of psyllium particles. Lactic acid dehydrogenase staining of pretreated cultured human skin explants did not reveal toxicity of the mucopolysaccharides derived from psyllium husk. Langerhans' cell migration from the epidermis was negligible and interleukin-1 beta expression in the explants was not significant, supporting the very low allergenic potential of psyllium. The characteristics of mucopolysaccharide granulate derived from psyllium husk in Askina Cavity and Askina Hydro related to fluid absorption, bacterial adherence, biocompatibility, stimulation of macrophages, irritancy response and allergenicity showed an optimal profile, supporting the good clinical performance of wound healing products containing psyllium husk. PMID:11951574

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

    PubMed

    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. PMID:26061630

  16. Autologous Bone Marrow Aspirate Therapy in Wound Healing

    PubMed Central

    Chittoria, Ravi Kumar; Nandhagopal, Vijayaraghavan; Mohapatra, Devi Prasad; Thiruvoth, Friji Meethale; Sivakumar, Dinesh Kumar; Asokan, Arjun

    2016-01-01

    Objective: To study the role of autologous bone marrow aspirate therapy (ABMAT) in wound healing. Approach: This is a retrospective analysis of 9 patients (11 chronic nonhealing wounds) in whom ABMAT was used. Patients (wounds) were grouped into two groups. Group 1 included 4 patients (5 wounds) refusing/unfit for reconstruction and managed only with ABMAT. Group 2 included 5 patients (6 wounds) who agreed/fit for reconstruction after wound bed preparation with ABMAT. End point of the study was complete wound healing. Results: ABMAT helped in complete healing of chronic nonhealing wounds by secondary intention in group 1 patients and enhanced process of wound bed preparation for reconstruction in group 2 patients. Innovation: This study highlights the importance of ABMAT in the management of chronic nonhealing wounds. Conclusion: ABMAT helps in wound bed preparation to allow the wound to heal completely or cover by skin graft/flap. PMID:26989576

  17. In vivo analysis of wound healing by optical methods

    PubMed Central

    Alborova, Alena; Lademann, Jürgen; Kramer, Axel; Richter, Heike; Patzelt, Alexa; Sterry, Wolfram; Koch, Stefan

    2008-01-01

    The analysis of wound healing is important for the therapy control and for the development of drugs stimulating the healing process. Wounds cause damage to the skin barrier. A damaged stratum corneum leads to an increased water loss through the skin barrier. The standard measuring procedure for characterization of wound healing is the measurement of transepidermal water loss (TEWL). The disadvantage of this method is that it can be easily disturbed by the perspiration of the volunteers and by topically applied substances, for instance wound healing creams. In the study presented, in vivo laser scanning microscopy and optical coherent tomography were compared concerning the application for their analysis of wound healing processes. The laser scanning microscopy allows the analysis of the healing process on a cellular level. The course of wound healing determined by laser scanning microscopy was correlated with numerical values, allowing the numerical characterization of the wound healing process. PMID:20204112

  18. Grand challenge in Biomaterials-wound healing

    PubMed Central

    Salamone, Joseph C.; Salamone, Ann Beal; Swindle-Reilly, Katelyn; Leung, Kelly Xiaoyu-Chen; McMahon, Rebecca E.

    2016-01-01

    Providing improved health care for wound, burn and surgical patients is a major goal for enhancing patient well-being, in addition to reducing the high cost of current health care treatment. The introduction of new and novel biomaterials and biomedical devices is anticipated to have a profound effect on the future improvement of many deleterious health issues. This publication will discuss the development of novel non-stinging liquid adhesive bandages in healthcare applications developed by Rochal Industries. The scientists/engineers at Rochal have participated in commercializing products in the field of ophthalmology, including rigid gas permeable contact lenses, soft hydrogel contact lenses, silicone hydrogel contact lenses, contact lens care solutions and cleaners, intraocular lens materials, intraocular controlled drug delivery, topical/intraocular anesthesia, and in the field of wound care, as non-stinging, spray-on liquid bandages to protect skin from moisture and body fluids and medical adhesive-related skin injuries. Current areas of entrepreneurial activity at Rochal Industries pertain to the development of new classes of biomaterials for wound healing, primarily in regard to microbial infection, chronic wound care, burn injuries and surgical procedures, with emphasis on innovation in product creation, which include cell-compatible substrates/scaffolds for wound healing, antimicrobial materials for opportunistic pathogens and biofilm reduction, necrotic wound debridement, scar remediation, treatment of diabetic ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and adjuvants for skin tissue substitutes. PMID:27047680

  19. Grand challenge in Biomaterials-wound healing.

    PubMed

    Salamone, Joseph C; Salamone, Ann Beal; Swindle-Reilly, Katelyn; Leung, Kelly Xiaoyu-Chen; McMahon, Rebecca E

    2016-06-01

    Providing improved health care for wound, burn and surgical patients is a major goal for enhancing patient well-being, in addition to reducing the high cost of current health care treatment. The introduction of new and novel biomaterials and biomedical devices is anticipated to have a profound effect on the future improvement of many deleterious health issues. This publication will discuss the development of novel non-stinging liquid adhesive bandages in healthcare applications developed by Rochal Industries. The scientists/engineers at Rochal have participated in commercializing products in the field of ophthalmology, including rigid gas permeable contact lenses, soft hydrogel contact lenses, silicone hydrogel contact lenses, contact lens care solutions and cleaners, intraocular lens materials, intraocular controlled drug delivery, topical/intraocular anesthesia, and in the field of wound care, as non-stinging, spray-on liquid bandages to protect skin from moisture and body fluids and medical adhesive-related skin injuries. Current areas of entrepreneurial activity at Rochal Industries pertain to the development of new classes of biomaterials for wound healing, primarily in regard to microbial infection, chronic wound care, burn injuries and surgical procedures, with emphasis on innovation in product creation, which include cell-compatible substrates/scaffolds for wound healing, antimicrobial materials for opportunistic pathogens and biofilm reduction, necrotic wound debridement, scar remediation, treatment of diabetic ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and adjuvants for skin tissue substitutes. PMID:27047680

  20. Effect of medicinal plants on wound healing.

    PubMed

    Budovsky, Arie; Yarmolinsky, Ludmila; Ben-Shabat, Shimon

    2015-01-01

    In the United States alone, chronic wounds affect 6.5 million patients. It is expected that the number of chronic wounds will increase worldwide due to the increase in age-related conditions and pathologies such as diabetes, obesity, and cardiovascular diseases. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds, and the burden is rapidly growing due to increasing healthcare costs, an aging population, and a sharp rise in the incidence of diabetes and obesity worldwide. While current therapeutic agents have generally inadequate efficacy and number of serious adverse effects, the medicinal plants have been used in medicine since ancient times and are well known for their abilities to promote wound healing and prevent infection without grave side effects. Thus, herbal therapy may be an alternative strategy for treatment of wounds. The purpose of this review is to provide the verified data on the medicinal plants of the world flora with wound healing activity including the biologically active substances belonging to these herbal preparations and describe in detail the various cellular and molecular mechanisms of their actions. PMID:25703533

  1. A comprehensive review of advanced biopolymeric wound healing systems.

    PubMed

    Mayet, Naeema; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; Du Toit, Lisa C; Pillay, Viness

    2014-08-01

    Wound healing is a complex and dynamic process that involves the mediation of many initiators effective during the healing process such as cytokines, macrophages and fibroblasts. In addition, the defence mechanism of the body undergoes a step-by-step but continuous process known as the wound healing cascade to ensure optimal healing. Thus, when designing a wound healing system or dressing, it is pivotal that key factors such as optimal gaseous exchange, a moist wound environment, prevention of microbial activity and absorption of exudates are considered. A variety of wound dressings are available, however, not all meet the specific requirements of an ideal wound healing system to consider every aspect within the wound healing cascade. Recent research has focussed on the development of smart polymeric materials. Combining biopolymers that are crucial for wound healing may provide opportunities to synthesise matrices that are inductive to cells and that stimulate and trigger target cell responses crucial to the wound healing process. This review therefore outlines the processes involved in skin regeneration, optimal management and care required for wound treatment. It also assimilates, explores and discusses wound healing drug-delivery systems and nanotechnologies utilised for enhanced wound healing applications. PMID:24985412

  2. Epidermal Development and Wound Healing in Matrix Metalloproteinase 13-Deficient Mice

    PubMed Central

    Hartenstein, Bettina; Dittrich, Bernd Thilo; Stickens, Dominique; Heyer, Babette; Vu, Thiennu H.; Teurich, Sibylle; Schorpp-Kistner, Marina; Werb, Zena; Angel, Peter

    2009-01-01

    Degradation of the extracellular matrix, which is an indispensable step in tissue remodelling processes such as embryonic development and wound healing of the skin, has been attributed to collagenolytic activity of members of the matrix metalloproteinase family (MMPs). Here, we employed mmp13 knockout mice to elucidate the function of MMP13 in embryonic skin development, skin homeostasis, and cutaneous wound healing. Overall epidermal architecture and dermal composition of non-injured skin were indistinguishable from wild-type mice. Despite robust expression of MMP13 in the early phase of wound healing, wild-type and mmp13 knockout animals did not differ in their efficiency of re-epithelialization, inflammatory response, granulation tissue formation, angiogenesis, and restoration of basement membrane. Yet, among other MMPs also expressed during wound healing, MMP8 was found to be enhanced in wounds of MMP13-deficient mice. In summary, skin homeostasis and also tissue remodelling processes like embryonic skin development and cutaneous wound healing are independent of MMP13 either owing to MMP13 dispensability or owing to functional substitution by other collagenolytic proteinases such as MMP8. PMID:16374453

  3. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

    PubMed Central

    Reid, Brian; Zhao, Min

    2014-01-01

    Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds. PMID:24761358

  4. Scar tissue orientation in unsutured and sutured corneal wound healing.

    PubMed Central

    Melles, G R; Binder, P S; Beekhuis, W H; Wijdh, R H; Moore, M N; Anderson, J A; SundarRaj, N

    1995-01-01

    AIMS--This study aimed to evaluate stromal wound healing morphology in short term unsutured compared with sutured corneal wounds, to define regional variation in healing within radial keratotomy wounds. METHODS--Stromal scar tissue orientation (fibroblast and collagen fibre orientation) was analysed in unsutured and adjacent sutured keratotomy wounds in monkeys, 2 to 9 weeks after surgery, using light and transmission electron microscopy. RESULTS--At 2 to 4 weeks, scar tissue orientation was transverse to the wound edge in unsutured wounds, but sagittal in sutured wounds. At 5 to 9 weeks, a reorientation of scar tissue sagittal to the wound was seen in the unsutured wounds, proceeding from the posterior to anterior wound regions. In sutured wounds, a scar tissue reorientation transverse to the wound was seen, proceeding from the anterior wound region in a posterior direction. CONCLUSIONS--Within the same cornea, sutured and unsutured wounds showed opposite patterns of healing. Sutured wounds initially healed more slowly, but obtained pseudolamellar continuity over time. In contrast, healing of unsutured wounds was characterised by an early approximation towards lamellar repair that was followed by an ineffective reorganisation of the scar. This latter pattern of healing, that may be associated with a variable weakening of the wound, may relate to the clinical findings of unpredictability and/or progression of refractive effect following radial keratotomy. Images PMID:7547789

  5. Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals.

    PubMed

    Richardson, Rebecca; Metzger, Manuel; Knyphausen, Philipp; Ramezani, Thomas; Slanchev, Krasimir; Kraus, Christopher; Schmelzer, Elmon; Hammerschmidt, Matthias

    2016-06-15

    Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial- or full-thickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-β- and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells - processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make re-epithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization. PMID:27122176

  6. Quantifying cell behaviors during embryonic wound healing

    NASA Astrophysics Data System (ADS)

    Mashburn, David; Ma, Xiaoyan; Crews, Sarah; Lynch, Holley; McCleery, W. Tyler; Hutson, M. Shane

    2011-03-01

    During embryogenesis, internal forces induce motions in cells leading to widespread motion in tissues. We previously developed laser hole-drilling as a consistent, repeatable way to probe such epithelial mechanics. The initial recoil (less than 30s) gives information about physical properties (elasticity, force) of cells surrounding the wound, but the long-term healing process (tens of minutes) shows how cells adjust their behavior in response to stimuli. To study this biofeedback in many cells through time, we developed tools to quantify statistics of individual cells. By combining watershed segmentation with a powerful and efficient user interaction system, we overcome problems that arise in any automatic segmentation from poor image quality. We analyzed cell area, perimeter, aspect ratio, and orientation relative to wound for a wide variety of laser cuts in dorsal closure. We quantified statistics for different regions as well, i.e. cells near to and distant from the wound. Regional differences give a distribution of wound-induced changes, whose spatial localization provides clues into the physical/chemical signals that modulate the wound healing response. Supported by the Human Frontier Science Program (RGP0021/2007 C).

  7. Mechanoregulation of Angiogenesis in Wound Healing

    PubMed Central

    Lancerotto, Luca; Orgill, Dennis P.

    2014-01-01

    Significance: Mechanical forces are important regulators of cell and tissue function. Endothelial cells proliferate in response to tissue stretch and the mechanical properties of the environment direct capillary sprouting and growth. As the vascular network is a key factor in physiology and disease, control of the vascularity by means of mechanical forces could lead to the development of innovative therapeutic strategies. Recent Advances: Increased understanding of mechanobiology has stimulated translational research and allowed the development and optimization of clinical devices that exploit mechanical forces for the treatment of diseases, in particular in the field of wound healing. Stretching in distraction osteogenesis and tissue expansion induces neogenesis of well-vascularized tissues. In micro-deformational wound therapy, micro-mechanical distortions of the wound bed stimulate cell proliferation and angiogenesis by stretching resident cells to improve healing of difficult wounds. Relief from tension antagonizes proliferation and angiogenesis in primarily closed wounds allowing for better scar quality. Critical Issues: The integration of mechanobiology into traditional cell biology and pathophysiology in general is not yet complete and further research is needed to fill existing gaps, in particular in the complexity of in vivo conditions. Future Directions: Still largely unexplored approaches based on mechanical perturbation of the micro-/macro-environment can be devised to overcome the limits of current strategies in a broad spectrum of clinical conditions. PMID:25302137

  8. Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats.

    PubMed

    Gopal, Anu; Kant, Vinay; Gopalakrishnan, Anu; Tandan, Surendra K; Kumar, Dinesh

    2014-05-15

    Copper possesses efficacy in wound healing which is a complex phenomenon involving various cells, cytokines and growth factors. Copper nanoparticles modulate cells, cytokines and growth factors involved in wound healing in a better way than copper ions. Chitosan has been shown to be beneficial in healing because of its antibacterial, antifungal, biocompatible and biodegradable polymeric nature. In the present study, chitosan-based copper nanocomposite (CCNC) was prepared by mixing chitosan and copper nanoparticles. CCNC was applied topically to evaluate its wound healing potential and to study its effects on some important components of healing process in open excision wound model in adult Wistar rats. Significant increase in wound contraction was observed in the CCNC-treated rats. The up-regulation of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1(TGF-β1) by CCNC-treatment revealed its role in facilitating angiogenesis, fibroblast proliferation and collagen deposition. The tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were significantly decreased and increased, respectively, in CCNC-treated rats. Histological evaluation showed more fibroblast proliferation, collagen deposition and intact re-epithelialization in CCNC-treated rats. Immunohistochemistry of CD31 revealed marked increase in angiogenesis. Thus, we concluded that chitosan-based copper nanocomposite efficiently enhanced cutaneous wound healing by modulation of various cells, cytokines and growth factors during different phases of healing process. PMID:24632085

  9. Pro-healing effects of bilirubin in open excision wound model in rats.

    PubMed

    Ahanger, Azad A; Leo, Marie D; Gopal, Anu; Kant, Vinay; Tandan, Surendra K; Kumar, Dinesh

    2016-06-01

    Bilirubin, a by-product of heme degradation, has an important role in cellular protection. Therefore, we speculated that bilirubin could be of potential therapeutic value in wound healing. To validate the hypothesis, we used a full-thickness cutaneous wound model in rats. Bilirubin (30 mg/kg) was administered intraperitoneally every day for 9 days. The surface area of the wound was measured on days 0, 2, 4, 7 and 10 after the creation of the wound. The granulation tissue was collected on day 10 post-wounding for analysing various parameters of wound healing. Bilirubin treatment accelerated wound contraction and increased hydroxyproline and glucosamine contents. mRNA expression of pro-inflammatory factors such as intercellular cell adhesion molecule-1 (ICAM-1) and tumour necrosis factor-α (TNF-α) were down-regulated and that of anti-inflammatory cytokine interleukin-10 (IL-10) was up-regulated. The findings suggest that bilirubin could be a new agent for enhancing cutaneous wound healing. PMID:24947136

  10. Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds

    PubMed Central

    Marfia, Giovanni; Navone, Stefania Elena; Di Vito, Clara; Ughi, Nicola; Tabano, Silvia; Miozzo, Monica; Tremolada, Carlo; Bolla, Gianni; Crotti, Chiara; Ingegnoli, Francesca; Rampini, Paolo; Riboni, Laura; Gualtierotti, Roberta; Campanella, Rolando

    2015-01-01

    abstract Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances. PMID:26652928