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Sample records for cutaneous wound healing

  1. Porcine models of cutaneous wound healing.

    PubMed

    Seaton, Max; Hocking, Anne; Gibran, Nicole S

    2015-01-01

    Cutaneous wound healing in the pig is frequently used as a model for human cutaneous wound healing. In this review, we examine the appropriateness of this model for studying normal and pathological wound healing, and describe models for chronic nonhealing wounds, diabetic wounds, burns, and hypertrophic scars. In addition, we focus on studies that have used pigs to evaluate wound-healing therapies, and discuss genetic engineering technology in the pig that may advance our knowledge of wound healing. We conclude that, although not perfect, the pig offers a versatile model that can be adjusted to mimic a wide range of clinical scenarios.

  2. 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

  3. Acceleration of cutaneous wound healing by brassinosteroids.

    PubMed

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

    2013-01-01

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

  4. Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing

    PubMed Central

    Zheng, Zhong; Jian, Jia; Velasco, Omar; Hsu, Ching-yun; Zhang, Kermit; Levin, Andrew; Murphy, Maxwell; Zhang, Xinli

    2014-01-01

    Background: Fibromodulin (FMOD) plays a critical role in the wound-healing process. Our previous studies revealed that FMOD deficiency led to marked alterations in adult wound healing characterized by delayed dermal cell migration, postponed wound closure, and increased scar formation, all accompanied by impeded angiogenesis. Therefore, the aim of this study was to reveal the effect of FMOD on angiogenesis during the wound-healing process. Methods: In vivo angiogenic effects of FMOD were assessed by a chick embryo chorioallantoic membrane assay, a Matrigel (BD Bioscience, Franklin Lakes, N.J.) plug implant assay, and rodent primary closure wound models. In vitro angiogenic effects of FMOD were recorded by cell invasion and dimensional and topological parameters of human umbilical vein endothelial cells. Results: We provided evidence that FMOD significantly enhanced vascularization: first, FMOD boosted blood vessel formation on the chorioallantoic membrane; second, FMOD markedly stimulated capillary infiltration into Matrigel plugs subcutaneously implanted in adult mice; and finally, FMOD robustly promoted angiogenesis in multiple adult rodent cutaneous wound models. Furthermore, FMOD administration restored the vascularity of fmod−/− mouse wounds. In support of this, FMOD endorsed an angiogenesis-favored microenvironment in adult rodent wounds not only by upregulating angiogenic genes but also by downregulating angiostatic genes. In addition, FMOD significantly enhanced human umbilical vein endothelial cell invasion and tube-like structure formation in vitro. Conclusions: Altogether, we demonstrated that in addition to reducing scar formation, FMOD also promotes angiogenesis. As blood vessels organize and regulate wound healing, its potent angiogenic properties will further expand the clinical application of FMOD for cutaneous healing of poorly vascularized wounds. PMID:25587509

  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. Complement deficiency promotes cutaneous wound healing in mice.

    PubMed

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

    2015-02-01

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

  8. 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

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

    PubMed Central

    Chadwick, Sarah; Heath, Rebecca; Shah, Mamta

    2012-01-01

    Abnormally pigmented scars are an undesirable consequence of cutaneous wound healing and are a complication every single individual worldwide is at risk of. They present a challenge for clinicians, as there are currently no definitive treatment options available, and render scars much more noticeable making them highly distressing for patients. Despite extensive research into both wound healing and the pigment cell, there remains a scarcity of knowledge surrounding the repigmentation of cutaneous scars. Pigment production is complex and under the control of many extrinsic and intrinsic factors and patterns of scar repigmentation are unpredictable. This article gives an overview of human skin pigmentation, repigmentation following wounding and current treatment options. PMID:23162241

  10. 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

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

    PubMed

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

    2015-01-01

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

  12. 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

  13. 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

  14. 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

    2016-08-01

    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.

  15. 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

  16. MFG-E8 regulates angiogenesis in cutaneous wound healing.

    PubMed

    Uchiyama, Akihiko; Yamada, Kazuya; Ogino, Sachiko; Yokoyama, Yoko; Takeuchi, Yuko; Udey, Mark C; Ishikawa, Osamu; Motegi, Sei-ichiro

    2014-07-01

    Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF-PDGFRβ signaling mediated by integrin-growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31(+) blood vessels, and MFG-E8 colocalized with PDGFRβ(+), αSMA(+), and NG2(+) pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. The impact of the pH value on skin integrity and cutaneous wound healing.

    PubMed

    Schreml, S; Szeimies, R-M; Karrer, S; Heinlin, J; Landthaler, M; Babilas, P

    2010-04-01

    The process of cutaneous wound healing comprises three overlapping major phases: inflammation, proliferation and tissue remodelling. However, while mechanisms are studied scientifically on the cellular and subcellular level, there is still a lack of knowledge concerning basic clinical parameters like wound pH or pO2. It could be proven that wound healing is affected by wound pH changes as they can lead to an inhibition of endogenous and therapeutically applied enzymes. Besides, the conformational structure of proteins and their functionality in wound healing is altered. Furthermore, the likelihood of bacterial colonization, which is a common problem in chronic wound pathogenesis, is affected by wound pH alterations. However, wound pH is rarely taken into account in current wound therapy strategies. A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy.

  3. TNFα is a therapeutic target for impaired cutaneous wound healing

    PubMed Central

    Ashcroft, Gillian S.; Jeong, Moon-Jin; Ashworth, Jason J.; Hardman, Matthew; Jin, Wenwen; Moutsopoulos, Niki; Wild, Teresa; McCartney-Francis, Nancy; Sim, Davis; McGrady, George; Song, Xiao-yu; Wahl, Sharon M.

    2012-01-01

    Impaired wound healing states lead to substantial morbidity and cost with treatment resulting in an expenditure of billions of dollars per annum in the USA alone. Both chronic wounds and impaired acute wounds are characterized by excessive inflammation, enhanced proteolysis, and reduced matrix deposition. These confounding factors are exacerbated in the elderly, in part, as we report here, related to increased local and systemic tumor necrosis factor alpha(TNFα) levels. Moreover, we have used a secretory leukocyte protease inhibitor(SLPI) null mouse model of severely impaired wound healing and excessive inflammation, comparable to age-related delayed human healing, to demonstrate that topical application of anti-TNFα neutralizing antibodies blunts leukocyte recruitment and NFκB activation, alters the balance between M1 and M2 macrophages, and accelerates wound healing. Following antagonism of TNFα, matrix synthesis is enhanced, associated with suppression of both inflammatory parameters and NFκB binding activity. Our data suggest that inhibiting TNFα is a critical event in reversing the severely impaired healing response associated with the absence of SLPI, and may be applicable to prophylaxis and/or treatment of impaired wound healing states in humans. PMID:22151742

  4. Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model.

    PubMed

    Schierle, Clark F; De la Garza, Mauricio; Mustoe, Thomas A; Galiano, Robert D

    2009-01-01

    Bacterial biofilms have gained increasing visibility in recent years as a ubiquitous form of survival for microorganisms in myriad environments. A number of in vivo models exist for the study of biofilms in the setting of medically relevant implanted foreign bodies. Growing evidence has demonstrated the presence of bacterial biofilms in the setting of a number of chronic wound states including pressure sores, diabetic foot ulcers, and venous stasis ulcers. Here we present a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm. We established biofilms using either Staphylococcus aureus or Staphylococcus epidermidis in splinted cutaneous punch wounds created on the backs of normal C57Bl6/J mice. Wound reepithelialization was significantly delayed by bacterial biofilms. This effect was specifically dependent on the ability of the bacteria to form biofilms as demonstrated by exogenous administration of biofilm inhibiting peptides and the use of mutant Staphylococcus spp. deficient in biofilm formation. This represents the first direct evidence for the effect of bacterial biofilms on cutaneous wound healing.

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

    PubMed

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

    2014-12-01

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

  6. 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. PMID:27429287

  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. Interactions of the Extracellular Matrix and Progenitor Cells in Cutaneous Wound Healing

    PubMed Central

    Volk, Susan W.; Iqbal, Syed Amir; Bayat, Ardeshir

    2013-01-01

    Significance Both chronic wounds and excessive scar formation after cutaneous injury create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The deposition and remodeling of extracellular matrix (ECM) components are critical processes in cutaneous healing. Understanding the role of the ECM in directing progenitor and reparative cell fate and activities during wound repair is required to improve wound-care strategies. Recent Advances In addition to providing structural integrity, the ECM is recognized to play critical roles in regulating progenitor and reparative cell behaviors such as migration, differentiation, proliferation, and survival. The ECM dictates these activities through its binding of adhesion receptors as well as its ability to regulate growth factor bioavailability and signaling. More recently, a key role for mechanical control of cell fate through interaction with the ECM has emerged. Critical Issues Despite significant advances in understanding the pathophysiology of cutaneous wound repair, problematic wounds remain a significant healthcare challenge. Regenerative medical strategies that either target endogenous stem cells or utilize applications of exogenous stem cell populations have emerged as promising approaches to pathologic wounds. However, the identification of smart biomaterials and matrices may allow for further optimization of such therapies. Future Directions An efficient and appropriate healing response in the skin postinjury is regulated by a fine balance of the quantity and quality of ECM proteins. A more complete understanding of ECM regulation of the cell fate and activities during cutaneous wound repair is vital for the development of novel treatment strategies for improvement of cutaneous healing. PMID:24527348

  9. 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

  10. IL-33-dependent group 2 innate lymphoid cells promote cutaneous wound healing

    PubMed Central

    Siracusa, Mark C; Kim, Brian S; Wang, Kelvin; Bayat, Ardeshir; Artis, David; Volk, Susan W

    2015-01-01

    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 pro-inflammatory or epithelial repair functions following 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. Additionally, 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 following injury. PMID:26802241

  11. 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.

  12. 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

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

    PubMed Central

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

    2012-01-01

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

  14. 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.

  15. 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

  16. Induction of Specific MicroRNAs Inhibits Cutaneous Wound Healing*

    PubMed Central

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

    2012-01-01

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

  17. 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.

  18. Effects of topical application of honey on cutaneous wound healing in rabbits.

    PubMed

    Oryan, A; Zaker, S R

    1998-04-01

    Although it has been known for many centuries that honey can accelerate wound healing, there have only been isolated reports of its use in the healing of burns, ulcers, infected wounds and open wounds. None of these reports developed a model to assess the changes in morphological and biochemical properties due to topical application of honey on cutaneous wounds. In the present investigation, efficacy of honey in the healing of cutaneous wounds of rabbits was studied on the basis of histopathological and biochemical changes. For this reason 40 healthy White New Zealand rabbits were randomly assigned to four equal groups. Using aseptic surgical technique, a 3 cm incision was made on the skin of the left thigh of each rabbit and the wounds of five rabbits in each group were twice daily treated with topical application of 5 ml pure unheated honey. The other half remained as untreated controls. Rabbits in groups A, B, C and D were biopsied on days 2, 7, 14 and 21 postoperatively respectively, and biopsies from the lesions of all groups were collected for histopathological studies and from groups C and D for biomechanical evaluations as well. Treated lesions showed less oedema, fewer polymorphonuclear and mononuclear cell infiltration, less necrosis, better wound contraction, improved epithelialization and lower glycosaminoglycan and proteoglycan concentration on days 2 and 7 postoperatively and better tissue organization and consequently an improved tissue ultimate strength and yield strength on days 14 and 21 postoperation. These findings suggest that honey applied topically on cutaneous wounds accelerates the healing processes and appears to have an important property that makes it ideal as a dressing for cutaneous wounds. PMID:9673575

  19. 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

  20. 17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

    PubMed

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

    2016-10-01

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

  1. 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

  2. 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

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

    PubMed

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

    2015-12-28

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

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

    PubMed

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

    2015-01-01

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

  5. 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

  6. Rotational stress-induced increase in epinephrine levels delays cutaneous wound healing in mice.

    PubMed

    Romana-Souza, Bruna; Otranto, Marcela; Vieira, Andreza M; Filgueiras, Cláudio C; Fierro, Iolanda M; Monte-Alto-Costa, Andréa

    2010-03-01

    Stress impairs wound healing of cutaneous lesions; however, the mechanism is still unclear. The aim of this study was to evaluate the effects of rotational stress on cutaneous wound healing in mice and propose a mechanism. Male mice were spun at 45 rpm for 15 min every hour beginning 3 days before wounding until euthanasia. Control animals were not subjected to stress. To confirm that catecholamines participate in stress-induced delay of wound healing, mice were treated daily with propranolol. An excisional lesion was created and measured. Seven and 14 days later, animals were killed and lesions collected. Sections were stained with hematoxylin-eosin and immunostained for alpha-smooth muscle actin and proliferating cell nuclear antigen. Matrix metalloproteinase (MMP)-2 and -9 activity, nitrite levels, and tumor necrosis factor-alpha (TNF-alpha) expression were measured in the wounds. In addition, murine skin fibroblast cultures were treated with high levels of epinephrine and fibroblast activity was evaluated. Stressed mice exhibited reduced locomotor activity and increased normetanephrine plasma levels. Rotational stress was associated with decreased wound contraction, reduced re-epithelialization, reduced MMP-2 and MMP-9 activation, but with strongly increased nitrite levels. Furthermore, inflammatory cell infiltration, TNF-alpha expression, myofibroblastic differentiation, and angiogenesis were all delayed in the stress group. Propranolol administration reversed the deleterious effects of stress on wound contraction and re-epithelialization. High epinephrine concentrations increased murine skin fibroblast proliferation and nitric oxide synthesis, and strongly inhibited skin fibroblast migration and both pro- and active MMP-2. In conclusion, rotational stress impairs cutaneous wound healing due to epinephrine increased levels.

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

    PubMed

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

    2015-11-10

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

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

    PubMed

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

    2011-02-01

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

  9. 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.

  10. 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.

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

    PubMed Central

    de Almeida, Taís Fontoura; de Castro Pires, Taiza

    2016-01-01

    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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

    2016-03-09

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

  1. Supplementation with olive oil, but not fish oil, improves cutaneous wound healing in stressed mice.

    PubMed

    Rosa, Alice dos Santos; Bandeira, Luana Graziella; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2014-01-01

    Supplementation with olive and fish oils reverses the effects of stress on behavioral activities and adrenal activation. However, previous studies have not shown whether supplementation with olive and fish oil could inhibit the effects of stress on cutaneous wound healing. Thus, this study investigated the effects of supplementation with fish or olive oil on cutaneous healing in stressed mice. Mice were subjected to rotational stress and treated with olive or fish oil daily until euthanasia. An excisional lesion was created on each mouse, and 14 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus olive oil, and fibroblast activity was evaluated. In the in vivo studies, administration of olive oil, but not fish oil, inhibited stress-induced reduction in wound contraction, reepithelialization, hydroxyproline levels, and blood vessel density. Stress-induced increases in vascular endothelial growth factor expression and the numbers of macrophages and neutrophils were reversed only by olive oil. Both oils reversed stress-induced increase in catecholamine levels and oxidative damage. In in vitro studies, olive oil treatment reversed the reduction in fibroblast migration and collagen deposition and the increase in lipid peroxidation induced by epinephrine. In conclusion, supplementation with olive oil, but not fish oil, improves cutaneous wound healing in chronically stressed mice.

  2. Molecular microbiology: new dimensions for cutaneous biology and wound healing.

    PubMed

    Martin, Jo M; Zenilman, Jonathan M; Lazarus, Gerald S

    2010-01-01

    The role of bacteria in the pathogenesis of chronic, nonhealing wounds is unclear. All wounds are colonized with bacteria, but differentiating colonizers from invading organisms is difficult, if not impossible, at the present time. Furthermore, robust new molecular genomic techniques have shown that only 1% of bacteria can be grown in culture; anaerobes are especially difficult to identify using standard culture methods. Recent studies utilizing microbial genomic methods have demonstrated that chronic wounds are host to a wide range of microorganisms. New techniques also show that microorganisms are capable of forming highly organized biofilms within the wound that differ dramatically in gene expression and phenotype from bacteria that are typically seen in planktonic conditions. The aim of this review is to present a concise description of infectious agents as defined by new molecular techniques and to summarize what is known about the microbiology of chronic wounds in order to relate them to the pathophysiology and therapy of chronic wounds.

  3. 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

  4. Infrared microscopic imaging of cutaneous wound healing: lipid conformation in the migrating epithelial tongue

    NASA Astrophysics Data System (ADS)

    Yu, Guo; Stojadinovic, Olivera; Tomic-Canic, Marjana; Flach, Carol R.; Mendelsohn, Richard

    2012-09-01

    Infrared microscopic imaging has been utilized to analyze for the first time the spatial distribution of lipid structure in an ex vivo human organ culture skin wound healing model. Infrared images were collected at zero, two, four, and six days following wounding. Analysis of lipid infrared spectral properties revealed the presence of a lipid class with disordered chains within and in the vicinity of the migrating epithelial tongue. The presence of lipid ester C=O bands colocalized with the disordered chains provided evidence for the presence of carbonyl-containing lipid species. Gene array data complemented the biophysical studies and provided a biological rationale for the generation of the disordered chain species. This is the first clear observation, to our knowledge, of disordered lipid involvement in cutaneous wound healing. Several possibilities are discussed for the biological relevance of these observations.

  5. 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

  6. Evaluation of Effects of Topical Estradiol Benzoate Application on Cutaneous Wound Healing in Ovariectomized Female Mice

    PubMed Central

    Mukai, Kanae; Urai, Tamae; Asano, Kimi; Nakajima, Yukari; Nakatani, Toshio

    2016-01-01

    Estrogen promotes cutaneous wound healing in ovariectomized (OVX) female mice. However, the effects of topical estrogen application on wounds remain unclear. Therefore, the aim of this study was to compare the effects of topical estrogen application on wounds with standard treatment methods. Eight-week-old C57BL/6J female mice underwent OVX and received two full-thickness wounds four weeks later. Mice were divided into three groups: topical estradiol benzoate (EB) (0.75 μg/g/day) wound treatment, subcutaneous estradiol (E2) pellets (0.05 mg, 21 days), and topical E2 (0.01 g/day) skin application. Wound healing was observed until day 14. Wound area ratios were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet group on days 1–14 (p < 0.05) and topical E2 skin application group on days 1–9 (p < 0.05). Neutrophil and macrophage numbers were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 skin application groups on day 7 (p < 0.05). Moreover, the number of new blood vessels and ratio of myofibroblasts were significantly larger in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 application skin groups on day 7 (p < 0.05). These results demonstrate that the application of estrogen to wounds reduced inflammatory responses and promoted angiogenesis and wound contraction more than the two other standard treatment methods. PMID:27658263

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

    PubMed

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

    2014-01-01

    Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

  8. 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.

  9. 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

  10. 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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  14. 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

    2016-09-12

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

  15. 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

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

    PubMed Central

    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

  17. 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

  18. 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

  19. 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

  20. 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.

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

    PubMed

    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.

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

    PubMed

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

    2014-06-01

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

  3. How wounds heal

    MedlinePlus

    ... How scrapes heal; How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... from germs. Not all wounds bleed. For example, burns, some puncture wounds, and pressure sores do not ...

  4. Effect of a topical formulation containing Calophyllum brasiliense Camb. extract on cutaneous wound healing in rats.

    PubMed

    Lordani, T V A; Brenzan, M A; Cortez, L E R; Lordani, C R F; Honda, P A; Lonardoni, M V C; Cortez, D A G

    2015-01-01

    This study evaluated the wound healing effects of topical application of an emulsion containing the HPLC-standardised extract from Calophyllum brasiliense Cambess (Clusiaceae) leaves in rats. The macroscopic analysis demonstrated that the wounds treated with the C. brasiliense emulsion healed earlier than the wounds treated with emulsion base and Dersani®. The percentage of wound healing in the group treated with the C. brasiliense emulsion was significantly higher than in the other groups at 7 and 14 days. On day 14, the animals treated with the C. brasiliense emulsion exhibited a 90.67% reduction of the wound areas. The histological evaluation revealed that on day 21, the group treated with the C. brasiliense emulsion exhibited a significant increase in fibroblasts compared with the other groups. Thus, the C. brasiliense emulsion had healing properties in the topical treatment of wounds and accelerated the healing process.

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

    PubMed

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

    2013-01-01

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

  6. Activin B promotes BMSC-mediated cutaneous wound healing by regulating cell migration via the JNK-ERK signaling pathway.

    PubMed

    Zhang, Min; Sun, Li; Wang, Xueer; Chen, Shixuan; Kong, Yanan; Liu, Nuyun; Chen, Yinghua; Jia, Qin; Zhang, Lu; Zhang, Lin

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are able to differentiate into various types of skin cells and participate in skin regeneration and repair. Activin signaling can regulate wound healing and reepithelialization. The present study assessed the impact of activin B on BMSC-mediated cutaneous wound healing in rats and explored the possible mechanism involved. We found that CFSE-labeled BMSCs participated in wound healing in vivo, and compared to administration with PBS, activin B, or BMSCs, activin B plus BMSCs significantly promoted wound healing and hair follicle regeneration. Activin B induced actin stress fiber formation and cell migration in BMSCs in vitro. Activation of JNK and ERK, but not p38, was required for activin B-induced actin stress fiber formation and BMSC migration. These results show that activin B may promote BMSC-mediated wound healing by inducing actin stress fiber formation and BMSC migration via the ERK and JNK signal pathways. Combined administration of BMSCs and cytokines may be a promising therapeutic strategy for the management of skin wounds.

  7. Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

    PubMed

    Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

    2016-02-01

    The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation.

  8. 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.

  9. 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

  10. 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.

  11. Human Umbilical Cord Mesenchymal Stem Cells Transplantation Promotes Cutaneous Wound Healing of Severe Burned Rats

    PubMed Central

    Chai, Jiake; Duan, Hongjie; Chu, Wanli; Zhang, Haijun; Hu, Quan; Du, Jundong

    2014-01-01

    Background Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism. Methods Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI), and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. Results We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. Conclusion The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas. PMID:24586314

  12. 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.

  13. 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

  14. 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

  15. 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

  16. The Role of the Extracellular Matrix Components in Cutaneous Wound Healing

    PubMed Central

    Mencner, Łukasz; Komosinska-Vassev, Katarzyna

    2014-01-01

    Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors' action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed. PMID:24772435

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

    PubMed

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

    2015-06-16

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

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

    PubMed

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

    2014-10-01

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

  19. 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

  20. Development of a novel, highly quantitative in vivo model for the study of biofilm-impaired cutaneous wound healing.

    PubMed

    Gurjala, Anandev N; Geringer, Matthew R; Seth, Akhil K; Hong, Seok J; Smeltzer, Mark S; Galiano, Robert D; Leung, Kai P; Mustoe, Thomas A

    2011-01-01

    A growing body of evidence suggests that in addition to hypoxia, ischemia-reperfusion injury, and intrinsic host factors, bacterial biofilms represent a fourth major pillar in chronic wound pathogenesis. Given that most studies to date rely on in vitro or observational clinical data, our aim was to develop a novel, quantitative animal model enabling further investigation of the biofilm hypothesis in vivo. Dermal punch wounds were created in New Zealand rabbit ears, and used as uninfected controls, or inoculated with green fluorescent protein-labeled Staphylococcus aureus to form wounds with bacteria predominantly in the planktonic or biofilm phase. Epifluorescence and scanning electron microscopy revealed that S. aureus rapidly forms mature biofilm in wounds within 24 hours of inoculation, with persistence of biofilm viability over time seen through serial bacterial count measurement and laser scanning confocal imaging at different time points postwounding and inoculation. Inflammatory markers confirmed that the biofilm phenotype creates a characteristic, sustained, low-grade inflammatory response, and that over time biofilm impairs epithelial migration and granulation tissue in-growth, as shown histologically. We have established and validated a highly quantitative, reproducible in vivo biofilm model, while providing evidence that the biofilm phenotype specifically contributes to profound cutaneous wound healing impairment. Our model highlights the importance of bacterial biofilms in chronic wound pathogenesis, providing an in vivo platform for further inquiry into the basic biology of bacterial biofilm-host interaction and high-throughput testing of antibiofilm therapeutics.

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

    PubMed Central

    Lodhi, Santram; Jain, Avijeet; Jain, Alok Pal; Pawar, Rajesh Singh; Singhai, Abhay Kumar

    2016-01-01

    Objective: Martynia annua L. (M. annua), (Martyniaccae) has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea), (Fabaceae) has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M. annua leaves and aerial parts of T. purpurea. Materials and Methods: Methanol fraction of M. annua (MAF-C) and ethyl acetate fraction of T. purpurea (TPF-A) were evaluated for healing potential in dead-space and burn wound models. An ointment (5% w/w) of MAF-C and TPF-A, pongamol (0.2 and 0.5% w/w) and luteolin (0.2 and 0.5% w/w) was applied topically twice a day. The effects were compared with Povidone Iodine ointment with respect to protein, collagen content, enzymatic assay and histopathological finding of granuloma tissues. Results: Ethanol extracts of M. annua and T. purpureawere exhibited total flavonoid contents of 126.2 ± 4.69 and 171.6 ± 6.38 mg (quercetin equivalent), respectively. HPLC fingerprinting confirmed the presence of luteolin in M. annua and quercetin in T. purpurea. TPF-A and MAF-C ointments (5% w/w) significantly increases the hydroxyproline and protein contents. Luteolin and pongamol ointments were also found to be effective in both wound models. Conclusion: Our findings suggested that 5% w/w ointment of TPF-A and MAF-C fractions were more effective than isolated flavonoids in wound healing which may be due to synergistic interactions between the flavonoids and other constituents. PMID:27761428

  2. 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

  3. Effects of cerium oxide nanoparticles on the growth of keratinocytes, fibroblasts and vascular endothelial cells in cutaneous wound healing.

    PubMed

    Chigurupati, Srinivasulu; Mughal, Mohamed R; Okun, Eitan; Das, Soumen; Kumar, Amit; McCaffery, Michael; Seal, Sudipta; Mattson, Mark P

    2013-03-01

    Rapid and effective wound healing requires a coordinated cellular response involving fibroblasts, keratinocytes and vascular endothelial cells (VECs). Impaired wound healing can result in multiple adverse health outcomes and, although antibiotics can forestall infection, treatments that accelerate wound healing are lacking. We now report that topical application of water soluble cerium oxide nanoparticles (Nanoceria) accelerates the healing of full-thickness dermal wounds in mice by a mechanism that involves enhancement of the proliferation and migration of fibroblasts, keratinocytes and VECs. The Nanoceria penetrated into the wound tissue and reduced oxidative damage to cellular membranes and proteins, suggesting a therapeutic potential for topical treatment of wounds with antioxidant nanoparticles.

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

    PubMed

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

    2014-01-01

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

  5. A pilot trial using topical regular crystalline insulin vs. aqueous zinc solution for uncomplicated cutaneous wound healing: Impact on quality of life.

    PubMed

    Attia, Enas A S; Belal, Dina M I; El Samahy, May H; El Hamamsy, Manal H

    2014-01-01

    When wounds are treated with regular insulin, they are also being treated with zinc; used in the formula to crystallize insulin molecules. It is not clear if regular insulin-accelerated wound healing is due to insulin, the zinc it contains, or both. Thus, we aimed to compare topical regular crystalline insulin (containing zinc) vs. aqueous zinc chloride solution to controls, on healing of open uncomplicated cutaneous wounds. In this randomized controlled pilot study, 90 nondiabetic patients were randomly assigned to one of three groups depending on the twice daily applications received; group I: regular insulin; group II: aqueous zinc chloride solution, and group III: 0.9% saline (control). A questionnaire was used to determine the effect of wounds on the quality of life. Both topical regular crystalline insulin (containing zinc) and aqueous zinc chloride solution enhanced healing of uncomplicated cutaneous wounds of nondiabetic patients, than control (p < 0.001), and hence improved patients' quality of life. However, regular insulin showed better results than aqueous zinc solution (p = 0.015), probably due to synergistic effect between insulin and zinc of its formulation. Healing rate was significantly higher in acute than chronic wounds (p < 0.001), in those ≤40 years than those >40 (p = 0.004), and in upper body wounds than lower body (p = 0.015).

  6. 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

  7. 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

  8. Nano-porous nitrocellulose liquid bandage modulates cell and cytokine response and accelerates cutaneous wound healing in a mouse model.

    PubMed

    Mu, Xiaofeng; Yu, Hao; Zhang, Caizhen; Chen, Xiufang; Cheng, Zhiyun; Bai, Ruyu; Wu, Xunxun; Yu, Qian; Wu, Chunlin; Diao, Yong

    2016-01-20

    Nitrocellulose liquid bandage (L-Bandage) is extensively used in hard-to-cover cuts and wounds management, owing to its flexibility, softness, transparency, and conformability. However, evidence supporting their mechanisms of action as wound dressing is scanty. This study introduces a novel nano-porous L-Bandage, and provides results from a mouse full-thickness wound model investigating its mechanism of action on wound healing. Different characteristics, such as porosity, mechanical properties and water vapor transmission rate (WVTR) were determined. The L-Bandage formed film had a porous network structure with mean diameter of 18 nm that could effectively prevent the bacterial invasion, and favorable properties of tensile strength, elongation, and WVTR. The L-Bandage treated wound exhibited accelerated healing, with reduced inflammations, enhanced wound re-epithelialization, contraction, granulation tissue formation, and rapid angiogenesis. Our data suggested that L-Bandage could serve as a promising wound dressing, because of its desirable properties for wound healing.

  9. A minimally invasive human in vivo cutaneous wound model for the evaluation of innate skin reactivity and healing status.

    PubMed

    Varol, Alexandra L; Anderson, Chris D

    2010-07-01

    Individual variability in skin reactivity and healing capacity after trauma are important clinical issues. The aims were to develop an in vivo, human wound model based on a standardised minimal skin injury and to demonstrate therapeutic effect of simple wound therapies in terms of morphological wound outcome with changes in skin blood perfusion as a quantified indicator of wound healing. In a series of experiments, wounds were induced on the normal forearm skin of volunteers using a blood collection lancet. This was well tolerated. Wounds were assessed by naked eye examination or laser Doppler perfusion imaging (LDPI) at baseline and at up to 6 further time points up to 96 h in control wounds and wounds treated by commonly used occlusive dressing options. Assessment by clinical observation with 10x magnification showed over 96 h a progression of erythema, surface crust, a new keratinisation layer and finally healed areas. LDPI quantifying wound erythema showed a peak at 24 h and near normal levels at 96 h. Inter-individual variability was evident but intra-individual variability was much less pronounced. Wounds treated with occlusion showed a statistically significant more rapid return to baseline blood perfusion as measured by LDPI compared to controls supported by favourable healing parameters in the clinical assessment. The paper exemplifies use of non-invasive, bioengineering technique for quantification of individual innate variability in skin reactivity, wound healing capacity and therapeutic effect in a well-tolerated in vivo, human, minimal skin trauma model. PMID:20229284

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

    PubMed

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

    2006-01-01

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

  11. 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

  12. 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

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

    PubMed

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

    PubMed

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

    2013-01-01

    Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm-impaired wounds using the TallyHo mouse, a clinically relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll-like receptor (TLR) expression were noted in unwounded skin or noninoculated wounds of diabetic and wild-type mice. However, diabetic biofilm-containing wounds had significantly less TLR 2, TLR 4, interleukin-1β, and tumor necrosis factor-α expression than wild-type wounds with biofilm (all p < 0.001). Both groups had similar bacterial burden and neutrophil infiltration after development of biofilms at 3 days postwounding, but diabetic wounds had significantly less neutrophil oxidative burst activity. This translated into a log-fold greater bacterial burden and significant delay of wound epithelization for biofilm-impaired diabetic wounds at 10 days postwounding. These results suggest that impaired recognition of bacterial infection via the TLR pathway leading to inadequate cytokine stimulation of antimicrobial host responses may represent a potential mechanism underlying diabetic susceptibility to wound infection and ulceration.

  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.

  16. 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

  17. 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

  18. 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.

  19. Wet wound healing.

    PubMed

    Vranckx, Jan J; Slama, Jaromir; Preuss, Stefan; Perez, Norvin; Svensjö, Tor; Visovatti, Scott; Breuing, Karl; Bartlett, Richard; Pribaz, Julian; Weiss, Denton; Eriksson, Elof

    2002-12-01

    Wound treatment in a flexible transparent chamber attached to the perimeter of the wound and containing a liquid has been extensively tested in preclinical experiments in pigs and found to offer several advantages. It protects the wound; the liquid medium or saline in the chamber provides in vivo tissue culture-like conditions; and antibiotics, analgesics, and various molecules can be delivered to the wound through the chamber. The wound chamber causes no injury to the wound itself or to the surrounding intact skin. Topical delivery of, for instance, antibiotics can provide very high concentrations at the wound site and with a favorable direction of the concentration gradient. A series of 28 wounds in 20 patients were treated with a wound chamber containing saline and antibiotics. Most patients had significant comorbidity and had not responded to conservative or surgical management with débridement and delayed primary closure or skin grafts. Six wounds had foreign bodies present; four of these were joint prostheses. Seven patients were on corticosteroids for rheumatoid arthritis, lupus, or chronic obstructive pulmonary disease, and four patients had diabetes. Most patients were treated with the wound chamber in preparation for a delayed skin graft or flap procedure, but one was treated with a wound chamber until the wound healed. Twenty-five of the wounds (89 percent) healed, and five wounds (18 percent) required additional conservative management after the initial chamber treatment and grafting procedure. Of the three wounds that did not heal, one healed after additional chamber treatment, one had a skin graft that did not take, and one required reamputation at a higher level. Antibiotic delivery was less than one intravenous dose daily, which avoided the potential for systemic absorption to toxic levels. Antibiotics such as vancomycin and gentamicin could be used in concentrations of up to 10,000 times the minimal inhibitory concentration. Forty-eight hours

  20. [Saliva and wound healing].

    PubMed

    Veerman, E C I; Oudhoff, M J; Brand, H S

    2011-05-01

    The oral mucosa is frequently exposed to mechanical forces, which may result in tissue damage. Saliva contributes to the repair of the oral mucosa in several ways. In the first place, it creates a humid environment to improve the function of inflammatory cells. During the last few years, it has been shown that saliva also contains a large number of proteins with a role in wound healing. Saliva contains growth factors, especially Epidermal Growth FACTOR, which promotes the proliferation of epithelial cells. Trefoil factor 3 and histatin promote the process of wound closure. The importance of Secretory Leucocyte Protease Inhibitor is demonstrated by the fact that in the absence of this salivary protein, oral wound healing is considerably delayed. Understanding these salivary proteins opens the way for the development of new wound healing medications.

  1. 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

  2. Innovation and wound healing.

    PubMed

    Harding, Keith

    2015-04-01

    Innovation in medicine requires unique partnerships between academic research, biotech or pharmaceutical companies, and health-care providers. While innovation in medicine has greatly increased over the past 100 years, innovation in wound care has been slow, despite the fact that chronic wounds are a global health challenge where there is a need for technical, process and social innovation. While novel partnerships between research and the health-care system have been created, we still have much to learn about wound care and the wound-healing processes.

  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. Stress and Wound Healing

    PubMed Central

    Christian, Lisa M.; Graham, Jennifer E.; Padgett, David A.; Glaser, Ronald; Kiecolt-Glaser, Janice K.

    2009-01-01

    Over the past decade it has become clear that stress can significantly slow wound healing: stressors ranging in magnitude and duration impair healing in humans and animals. For example, in humans, the chronic stress of caregiving as well as the relatively brief stress of academic examinations impedes healing. Similarly, restraint stress slows healing in mice. The interactive effects of glucocorticoids (e.g. cortisol and corticosterone) and proinflammatory cytokines [e.g. interleukin-1β (IL-1β), IL-lα, IL-6, IL-8, and tumor necrosis factor-α] are primary physiological mechanisms underlying the stress and healing connection. The effects of stress on healing have important implications in the context of surgery and naturally occurring wounds, particularly among at-risk and chronically ill populations. In research with clinical populations, greater attention to measurement of health behaviors is needed to better separate behavioral versus direct physiological effects of stress on healing. Recent evidence suggests that interventions designed to reduce stress and its concomitants (e.g., exercise, social support) can prevent stress-induced impairments in healing. Moreover, specific physiological mechanisms are associated with certain types of interventions. In future research, an increased focus on mechanisms will help to more clearly elucidate pathways linking stress and healing processes. PMID:17709956

  5. 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.

  6. Functionalized Silk Biomaterials for Wound Healing

    PubMed Central

    Gil, Eun Seok; Panilaitis, Bruce; Bellas, Evangelia

    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 (silk films, lamellar porous silk films, electrospun silk nanofibers) and two different drug functionalization techniques (drug coatings or drug loading into the materials) were studied to compare wound healing responses. Changes in wound size and histological assessments of wound tissues over time confirmed that functionalized silk biomaterial wound dressings increased wound healing rate, including reepithelialization, dermis proliferation, collagen synthesis, epidermal differentiation into hair follicles and sebaceous glands, and reduced scar formation, when compared to air-permeable Tegaderm™ tape (3M) (− control) and a commercially sold wound dressing (Tegaderm™ Hydrocolloid dressing) (+ control). All silk biomaterials studied were effective for wound healing, while the porous features of the silk biomaterials (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 evaluate 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. 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

  8. 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.

  9. 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

  10. Gingival Wound Healing

    PubMed Central

    Cáceres, M.; Martínez, C.; Oyarzún, A.; Martínez, J.

    2015-01-01

    Gingival wound healing comprises a series of sequential responses that allow the closure of breaches in the masticatory mucosa. This process is of critical importance to prevent the invasion of microbes or other agents into tissues, avoiding the establishment of a chronic infection. Wound healing may also play an important role during cell and tissue reaction to long-term injury, as it may occur during inflammatory responses and cancer. Recent experimental data have shown that gingival wound healing is severely affected by the aging process. These defects may alter distinct phases of the wound-healing process, including epithelial migration, granulation tissue formation, and tissue remodeling. The cellular and molecular defects that may explain these deficiencies include several biological responses such as an increased inflammatory response, altered integrin signaling, reduced growth factor activity, decreased cell proliferation, diminished angiogenesis, reduced collagen synthesis, augmented collagen remodeling, and deterioration of the proliferative and differentiation potential of stem cells. In this review, we explore the cellular and molecular basis of these defects and their possible clinical implications. PMID:25527254

  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. 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

  13. 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

  14. [Physiology of wound healing. Modern approach to wound care].

    PubMed

    Juhász, István

    2006-11-26

    The wound healing cascade is based on the programmed, reproducible cooperation of the cells involved in reparation, their products, further humoral factors and the intercellular stroma. The author describes the physiological events during the phases of cutaneous acute wound healing by second intention, such as coagulation, inflammation, proliferation, remodelling, takes into account the local pathophysiological processes found in chronic wounds. The author reviews the recent scientific literature on wound healing as well. Information is rapidly growing about the communication between cells and factors involved in cutaneous wound repair. Parallel control of the same step is common among physiological processes, with redundant safety mechanisms. The failure of therapeutic approaches based on single factor substitution is predictable for the clinician, because it is yet impossible to properly orchestrate the introduction of these factors to the system. In case of chronic wounds sofar the most effective intervention into the course of wound healing can be achieved by adding complex live structures, such as in case of biotechnologically derived materials or skin transplantation.

  15. Platelets Regulate the Migration of Keratinocytes via Podoplanin/CLEC-2 Signaling during Cutaneous Wound Healing in Mice.

    PubMed

    Asai, Jun; Hirakawa, Satoshi; Sakabe, Jun-ichi; Kishida, Tsunao; Wada, Makoto; Nakamura, Naomi; Takenaka, Hideya; Mazda, Osam; Urano, Tetsumei; Suzuki-Inoue, Katsue; Tokura, Yoshiki; Katoh, Norito

    2016-01-01

    Podoplanin is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), which is expressed on platelets. Recent evidence indicates that this specific marker of lymphatic endothelial cells is also expressed by keratinocytes at the edge of wounds. However, whether podoplanin or platelets play a role in keratinocyte activity during wound healing remains unknown. We evaluated the effect of podoplanin expression levels on keratinocyte motility using cultured primary normal human epidermal keratinocytes (NHEKs). Down-regulation of podoplanin in NHEKs via transfection with podoplanin siRNA inhibited their migration, indicating that podoplanin plays a mandatory role in this process. In addition, down-regulation of podoplanin was correlated with up-regulation of E-cadherin, suggesting that podoplanin-mediated stimulation of keratinocyte migration is associated with a loss of E-cadherin. Both the addition of platelets and treatment with CLEC-2 inhibited the migration of NHEKs. The down-regulation of RhoA activity and the up-regulation of E-cadherin in keratinocytes were also induced by CLEC-2. In conclusion, these results suggest that podoplanin/CLEC-2 signaling regulates keratinocyte migration via modulating E-cadherin expression through RhoA signaling. Altering the regulation of keratinocyte migration by podoplanin might be a novel therapeutic approach to improve wound healing. PMID:26597882

  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.

  17. Effect of laser and LED phototherapies on the healing of cutaneous wound on healthy and iron-deficient Wistar rats and their impact on fibroblastic activity during wound healing.

    PubMed

    Oliveira Sampaio, Susana C P; de C Monteiro, Juliana S; Cangussú, Maria Cristina T; Pires Santos, Gustavo M; dos Santos, Marcos André Vannier; dos Santos, Jean Nunes; Pinheiro, Antonio L B

    2013-05-01

    Iron deficiency impairs the formation of hemoglobin, red blood cells, as well the transport of oxygen. The wound healing process involves numerous functions, many of which are dependent on the presence of oxygen. Laser has been shown to improve angiogenesis, increases blood supply, cell proliferation and function. We aimed to study the effect of λ660 nm laser and λ700 nm light-emitting diode (LED) on fibroblastic proliferation on cutaneous wounds on iron-deficient rodents. Induction of iron anemia was carried out by feeding 105 newborn rats with a special iron-free diet. A 1 × 1 cm wound was created on the dorsum of each animal that were randomly distributed into seven groups: I, control anemic; II, anemic no treatment; III, anemic+L; IV, anemic+LED; V, healthy no treatment; VI, healthy+laser; VII, healthy+LED (n=15 each). Phototherapy was carried out using either a diode laser (λ660 nm, 40 mW, 10 J/cm(2)) or a prototype LED device (λ700 ± 20 nm, 15 mW, 10 J/cm(2)). Treatment started immediately after surgery and was repeated at 48-h interval during 7, 14, and 21 days. After animal death, specimens were taken, routinely processed, cut, stained with hematoxylin-eosin, and underwent histological analysis and fibroblast counting. Significant difference between healthy and anemic subjects on regards the number of fibroblast between treatments was seen (p<0.008, p<0.001). On healthy animals, significant higher count was seen when laser was used (p<0.008). Anemic subjects irradiated with LED showed significantly higher count (p<0.001). It is concluded that the use of LED light caused a significant positive biomodulation of fibroblastic proliferation on anemic animals and laser was more effective on increasing proliferation on non-anemics.

  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. Cell therapy for wound healing.

    PubMed

    You, Hi-Jin; Han, Seung-Kyu

    2014-03-01

    In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.

  20. 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.

  1. 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.

  2. 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

  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. Attempts to accelerate wound healing.

    PubMed

    Kasuya, Akira; Tokura, Yoshiki

    2014-12-01

    Wound healing is a well-orchestrated process, where numerous factors are activated or inhibited in a sequence of steps. Immediately after the infliction of damage, the repair of wound stars. The initial step is an inflammatory change with activation of innate immunity, which is followed by proliferation phase, including fibroplasia, angiogenesis and re-epithelialization. Pathological impairment of wound healing process may lead to persistent ulceration as seen in diabetic patients. Various signaling pathways are involved in wound healing. TGFβ/Smad pathway is a representative and well known to participate in fibroplasia, however, its comprehensive effect on wound healing is controversial. Experimental and clinical remedies have been being tried to promote wound healing. Advancement of cell engineering allows us to use stem cells and living skin equivalents.

  5. 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

  6. YAP and TAZ regulate skin wound healing.

    PubMed

    Lee, Min-Jung; Ran Byun, Mi; Furutani-Seiki, Makoto; Hong, Jeong-Ho; Jung, Han-Sung

    2014-02-01

    The Hippo signaling pathway regulates organ size, tissue regeneration, and stem cell self-renewal. The two key downstream transcription coactivators in this pathway, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), mediate the major gene regulation and biological functions of the Hippo pathway. The biological functions of YAP and TAZ in many tissues are known; however, their roles in skin wound healing remain unclear. To analyze whether YAP and/or TAZ are required for cutaneous wound healing, we performed small interfering RNA (siRNA)-mediated knockdown of YAP/TAZ in full-thickness skin wounds. YAP is strongly expressed in the nucleus and cytoplasm in the epidermis and hair follicle. Interestingly, YAP is expressed in the nucleus in the dermis at 2 and 7 days after wounding. TAZ normally localizes to the cytoplasm in the dermis but is distributed in both the nucleus and cytoplasm at 1 day after wounding. The knockdown of YAP and TAZ markedly delayed the rate of wound closure and reduced the transforming growth factor-β1 (TGF-β1) expression in the wound. YAP and TAZ also modulate the expression of TGF-β1 signaling pathway components such as Smad-2, p21, and Smad-7. These results suggest that YAP and TAZ localization to the nucleus is required for skin wound healing.

  7. 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 ...

  8. Murine models of human wound healing.

    PubMed

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  9. In Vivo Wound Healing Studies.

    PubMed

    2016-01-01

    Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions.

  10. In Vivo Wound Healing Studies.

    PubMed

    2016-01-01

    Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions. PMID:26939282

  11. Effect of gallium-arsenide laser, gallium-aluminum-arsenide laser and healing ointment on cutaneous wound healing in Wistar rats.

    PubMed

    Gonçalves, R V; Mezêncio, J M S; Benevides, G P; Matta, S L P; Neves, C A; Sarandy, M M; Vilela, E F

    2010-04-01

    This study determined the effects of gallium-aluminum-arsenide laser (GaAlAs), gallium-arsenide laser (GaAs) and Dersani healing ointment on skin wounds in Wistar rats. The parameters analyzed were: type I and III collagen fiber concentrations as well as the rate of wound closure. Five wounds, 12 mm in diameter, were made on the animals' backs. The depth of the surgical incision was controlled by removing the epithelial tissue until the dorsal muscular fascia was exposed. The animals were anesthetized with ketamine and xylazine via intraperitoneal injection. The rats were randomly divided into five groups of 6 animals each, according to the treatment received. Group 1 (L4): GaAs laser (4 J/cm(2)); group 2 (L30): GaAlAs laser (30 J/cm(2)); group 3 (L60): GaAlAs laser (60 J/cm(2)); group 4 (D): Dersani ointment; group 5 (control): 0.9% saline. The applications were made daily over a period of 20 days. Tissue fragments were stained with picrosirius to distinguish type I collagen from type III collagen. The collagen fibers were photo-documented and analyzed using the Quantum software based on the primary color spectrum (red, yellow and blue). Significant results for wound closing rate were obtained for group 1 (L4), 7.37 mm/day. The highest concentration of type III collagen fibers was observed in group 2 (L30; 37.80 + or - 7.10%), which differed from control (29.86 + or - 5.15%) on the 20th day of treatment. The type I collagen fibers of group 1 (L4; 2.67 + or - 2.23%) and group 2 (L30; 2.87 + or - 2.40%) differed significantly from control (1.77 + or - 2.97%) on the 20th day of the experiment.

  12. Murine model of wound healing.

    PubMed

    Dunn, Louise; Prosser, Hamish C G; Tan, Joanne T M; Vanags, Laura Z; Ng, Martin K C; Bursill, Christina A

    2013-05-28

    Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

  13. Wound healing: part II. Clinical applications.

    PubMed

    Janis, Jeffrey; Harrison, Bridget

    2014-03-01

    Treatment of all wounds requires adequate wound bed preparation, beginning with irrigation and débridement. Complicated or chronic wounds may also require treatment adjuncts or specialized wound healing products. An extensive body of research and development has introduced novel wound healing therapies and scar management options. In this second of a two-part continuing medical education series on wound healing, the reader is offered an update on current wound healing technologies and recommendations for obtaining optimal outcomes.

  14. Comparative wound healing--are the small animal veterinarian's clinical patients an improved translational model for human wound healing research?

    PubMed

    Volk, Susan W; Bohling, Mark W

    2013-01-01

    Despite intensive research efforts into understanding the pathophysiology of both chronic wounds and scar formation, and the development of wound care strategies to target both healing extremes, problematic wounds in human health care remain a formidable challenge. Although valuable fundamental information regarding the pathophysiology of problematic wounds can be gained from in vitro investigations and in vivo studies performed in laboratory animal models, the lack of concordance with human pathophysiology has been cited as a major impediment to translational research in human wound care. Therefore, the identification of superior clinical models for both chronic wounds and scarring disorders should be a high priority for scientists who work in the field of human wound healing research. To be successful, translational wound healing research should function as an intellectual ecosystem in which information flows from basic science researchers using in vitro and in vivo models to clinicians and back again from the clinical investigators to the basic scientists. Integral to the efficiency of this process is the incorporation of models which can accurately predict clinical success. The aim of this review is to describe the potential advantages and limitations of using clinical companion animals (primarily dogs and cats) as translational models for cutaneous wound healing research by describing comparative aspects of wound healing in these species, common acute and chronic cutaneous wounds in clinical canine and feline patients, and the infrastructure that currently exists in veterinary medicine which may facilitate translational studies and simultaneously benefit both veterinary and human wound care patients.

  15. 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

  16. 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.

  17. 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

  18. Factors That Impair Wound Healing.

    PubMed

    Anderson, Kristin; Hamm, Rose L

    2012-12-01

    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.

  19. 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.

  20. 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.

  1. Redox Signals in Wound Healing

    PubMed Central

    Sen, Chandan K.; Roy, Sashwati

    2008-01-01

    Physical trauma represents one of the most primitive challenges that threatened survival. Healing a problem wound requires a multi-faceted comprehensive approach. First and foremost, the wound environment will have to be made receptive to therapies. Second, the appropriate therapeutic regimen needs to be identified and provided while managing systemic limitations that could secondarily limit the healing response. Unfortunately, most current solutions seem to aim at designing therapeutic regimen with little or no consideration of the specific details of the wound environment and systemic limitations. One factor that is centrally important in making the wound environment receptive is correction of wound hypoxia. Recent work have identified that oxygen is not only required to disinfect wounds and fuel healing but that oxygen-dependent redox-sensitive signaling processes represent an integral component of the healing cascade. Over a decade ago, it was proposed that in biological systems oxidants are not necessarily always the triggers for oxidative damage and that oxidants such as H2O2 could actually serve as signaling messengers and drive several aspects of cellular signaling. Today, that concept is much more developed and mature. Evidence supporting the role of oxidants such as H2O2 as signaling messenger is compelling. A complete understanding of the continuum between the classical and emergent roles of oxygen requires a thorough consideration of current concepts in redox biology. The objective of this review is to describe our current understanding of how redox-sensitive processes may drive dermal tissue repair. PMID:18249195

  2. 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

  3. Chitosan-alginate membranes accelerate wound healing.

    PubMed

    Caetano, Guilherme Ferreira; Frade, Marco Andrey Cipriani; Andrade, Thiago Antônio Moretti; Leite, Marcel Nani; Bueno, Cecilia Zorzi; Moraes, Ângela Maria; Ribeiro-Paes, João Tadeu

    2015-07-01

    The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

  4. 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.

  5. 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.

  6. [Physiology and pathophysiology of wound healing of wound defects].

    PubMed

    Mutschler, W

    2012-09-01

    Understanding wound healing involves more than simply stating that there are the three phases of inflammation, proliferation and maturation. Wound healing is a complex series of actions, reactions and interactions among cells and mediators in a sequential and simultaneously ongoing temporal process within a spatial frame. At first this article will attempt to provide a concise summary of the events, cellular components and main influential mediators of wound healing over time. Secondly, the pathophysiology of chronic non-healing wounds is described where an imbalance of stimulating and inhibiting factors causes failure of healing. The most relevant extrinsic and intrinsic determinants are described and related to the cellular and molecular level of disturbed wound healing. A basic understanding of wound healing is a prerequisite for any prophylactic or therapeutic maneuver to maintain or re-establish wound equilibrium to give a satisfactory healing trajectory.

  7. 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.

  8. Electrical Stimulation Technologies for Wound Healing

    PubMed Central

    Kloth, Luther C.

    2014-01-01

    Objective: To discuss the physiological bases for using exogenously applied electric field (EF) energy to enhance wound healing with conductive electrical stimulation (ES) devices. Approach: To describe the types of electrical currents that have been reported to enhance chronic wound-healing rate and closure. Results: Commercial ES devices that generate direct current (DC), and mono and biphasic pulsed current waveforms represent the principal ES technologies which are reported to enhance wound healing. Innovation: Wafer-thin, disposable ES technologies (wound dressings) that utilize mini or micro-batteries to deliver low-level DC for wound healing and antibacterial wound-treatment purposes are commercially available. Microfluidic wound-healing chips are currently being used with greater accuracy to investigate the EF effects on cellular electrotaxis. Conclusion: Numerous clinical trials described in subsequent sections of this issue have demonstrated that ES used adjunctively with standard wound care (SWC), enhances wound healing rate faster than SWC alone. PMID:24761348

  9. WOUND HEALING AND COLLAGEN FORMATION

    PubMed Central

    Ross, Russell; Everett, Newton B.; Tyler, Ruth

    1970-01-01

    Healing skin wounds were studied in a series of parabiotic rats. The femurs of one parabiont of each pair were shielded whilst both animals were given 800 r from a Co60 source. The animals were wounded 3 days after irradiation. Each animal with partially shielded marrow was then given tritiated thymidine intraperitoneally daily while the cross-circulation was arrested by clamping. After the thymidine-3H had cleared the blood, the clamp was released. Animals were sacrificed, and wounds were prepared for radioautography 1, 2, and 6 days after wounding. In the wounds of the shielded animals thymidine-3H was observed in epidermis, endothelium, leukocytes, fibroblasts, and mast cells. Only neutrophilic leukocytes, monocytes, and lymphocytes were labeled, as determined by light and electron microscope radioautography, in the wounds of each nonshielded parabiont. None of the many fibroblasts present were found to contain label in the wounds of the nonshielded parabionts through the 6 day period. These observations provide further evidence that wound fibroblasts do not arise from hematogenous precursors and, therefore, must arise from adjacent connective tissue cells. PMID:5415241

  10. 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.

  11. 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

  12. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

    PubMed

    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

  13. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

    PubMed

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

    2015-04-14

    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.

  14. Influence of oxygen on wound healing.

    PubMed

    Yip, Wai Lam

    2015-12-01

    Oxygen has an important role in normal wound healing. This article reviews the evidence concerning the role of oxygen in wound healing and its influence on the different stages of wound healing. The evidence reviewed has demonstrated that improving oxygenation may be helpful in limiting wound infection, although there is a lack of good quality studies on the role of oxygen in the proliferative phase and in reepithelialisation. Overall, the relationship between oxygen and wound healing is complex. Knowledge of this aspect is important as many treatment modalities for refractory wounds are based on these principles.

  15. 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

  16. Phases of the wound healing process.

    PubMed

    Brown, Annemarie

    This is the first in a six-part series on wound management. It describes the stages of the wound healing process and explains how they relate to nursing practice. Nurses need to know how to recognise and understand the different phases so they can identify whether wounds are healing normally and apply the appropriate treatments to remove the barriers to healing. Part 2 (page 14) focuses on wound assessment.

  17. 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.

  18. Delayed Wound Healing in CXCR2 Knockout Mice

    PubMed Central

    Devalaraja, Radhika M.; Nanney, Lillian B.; Qian, Qinghua; Du, Jianguo; Yu, Yingchun; Devalaraja, Madhav N.; Richmond, Ann

    2009-01-01

    Previous studies demonstrated that the CXC chemokine, MGSA/GRO-α and its receptor, CXCR2, are expressed during wound healing by keratinocytes and endothelial cells at areas where epithelialization and neovascularization occur. The process of wound healing is dependent on leukocyte recruitment, keratinocyte proliferation and migration, and angiogenesis. These processes may be mediated in part by CXC chemokines, such as interleukin-8 and MGSA/GRO-α. To examine further the significance of CXC chemokines in wound healing, full excisional wounds were created on CXCR2 wild-type (+/+), heterozygous (+/−), or knockout (−/−) mice. Wounds were histologically analyzed for neutrophil and monocyte infiltration, neovascularization and epithelialization at days 3, 5, 7, and 10 postwounding. The CXCR2−/− mice exhibited defective neutrophil recruitment, an altered temporal pattern of monocyte recruitment, and altered secretion of interleukin-1β. Significant delays in wound healing parameters, including epithelialization and decreased neovascularization, were also observed in CXCR2−/− mice. In vitro wounding experiments with cultures of keratinocytes established from −/− and +/+ mice revealed a retardation in wound closure in CXCR2−/− keratinocytes, suggesting a role for this receptor on keratinocytes in epithelial resurfacing that is independent of neutrophil recruitment. These in vitro and in vivo studies further establish a pathophysiologic role for CXCR2 during cutaneous wound repair. PMID:10951241

  19. WOUND HEALING AND COLLAGEN FORMATION

    PubMed Central

    Ross, Russell; Benditt, Earl P.

    1961-01-01

    The regular sequence encountered in healing guinea pig skin wounds has been examined by methods of light and electron microscopy. Observations on cell populations, their fine structure, and fibril formation in the connective tissue have been made. Linear incisions in the skin of normal female guinea pigs weighing 300 to 350 grams were allowed to heal. The wounds were then excised, fixed with buffered 2 per cent osmium tetroxide, and postfixed in neutral buffered formalin, at 16 and 24 hours and at 3, 5, 9, and 14 days after wounding. They were then embedded in epoxy resin. In the inflammatory phase the exudate observed in the early wounds consists largely of polymorphonuclear neutrophilic leukocytes, macrophages, fibrin, and free extracellular organelles from the disrupted inflammatory cells. These organelles later appear in vacuoles in the cytoplasm of the macrophages. Fibroblasts first appear at 24 hours, and show extensive development and dilatation of the endoplasmic reticulum, which sometimes contains moderately dense flocculent material. In addition, these fibroblasts have enlarged mitochondria and condensations of filamentous material within the cytoplasm near the cell surface. Occasional myelin figures and moderately dense, 0.5 to 1.0 micron bodies are found within the cytoplasm of the early fibroblasts. Collagen fibrils are first seen at 3 days extracellularly near the cell surfaces. They appear at the later times in two populations of sizes. With increasing wound age the fibroblasts retain their morphology and the wounds decrease in cellularity concomitantly with the formation of increasing amounts of collagen. Several proposed mechanisms of collagen fibril formation are discussed in relation to the observed phenomena. The problem of correlating fibril diameter with the appearance of the periodic structure of collagen in relation to the minimal size fibril which would be anticipated to display this appearance is discussed. PMID:14494202

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Wound healing: translating theory into clinical practice.

    PubMed

    Cuzzell, J

    1995-04-01

    Skin care clinicians must accurately assess progress towards wound healing and identify appropriate therapies to hasten wound closure. Perhaps the most practical method for facilitating assessment and guiding intervention is the red, yellow, black (RYB) classification system.

  5. Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

    PubMed

    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

  6. 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

  7. Current management of wound healing.

    PubMed

    Gottrup, F; Karlsmark, T

    2009-06-01

    While the understanding of wound pathophysiology has progressed considerably over the past decades the improvements in clinical treatment has occurred to a minor degree. During the last years, however, new trends and initiatives have been launched, and we will continue to attain new information in the next decade. It is the hope that increasing parts of the new knowledge from basic wound healing research will be implemented in daily clinical practice. The development of new treatment products will also continue, and especially new technologies with combined types of dressing materials or dressing containing active substances will be accentuated. Further developments in the management structure and education will also continue and consensus of treatment guidelines, recommendations and organization models will hopefully be achieved.

  8. Cachexia - an intrinsic factor in wound healing.

    PubMed

    Ng, Michael F Y

    2010-04-01

    Systemic diseases are intrinsic factors that alter and may impair the wound healing process. Cachexia is a manifestation of systemic, often chronic, diseases and is characterised by systemic inflammation, appetite suppression and skeletal muscle wasting. Anorexia in cachectic states is commonly associated with malnutrition. Malnutrition may cause impaired healing. Therefore, it would follow that cachexia could influence wound healing because of reduced food intake. However, the lack of response to measures to reverse cachexia, such as supported nutrition, would suggest that a direct causal link between anorexia and weight loss in cachexia is too simple a model. To date, there is no published literature that examines the role of cachexia in human wound healing specifically. This article aims to demonstrate that cachexia is an intrinsic factor in wound healing. The role of the common mediators in wound healing and in cachexia are compared - specifically inflammation, including the nitric oxide synthase pathway, collagen deposition and reepithelialisation.

  9. 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

  10. Biofilms: do they affect wound healing?

    PubMed

    Thomson, Collette H

    2011-02-01

    Biofilms are known to exist in wounds, and it is suspected that their presence may delay wound healing, especially in chronic wounds; however, the evidence to support or refute this is not yet conclusive. This literature review has found that there is some evidence, both in vitro and in vivo, that the extracellular polysaccharide (EPS) matrix protects the biofilm from some inflammatory processes key to wound healing. The mechanisms of these effects and how this translates into clinical practice are still unknown. Strategies to manage biofilms within wounds are being investigated and may include use of silver, surgical debridedment, antibiotics and quorum-sensing inhibitors but no firm conclusions can yet be drawn from these studies. In conclusion, while there is a growing body of evidence to suggest that biofilms do indeed influence aspects of wound healing, there is still a large gap in our understanding of how this affects the wounds of clinical patients or how to improve rates of healing.

  11. Current wound healing procedures and potential care.

    PubMed

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

    2015-03-01

    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 microRNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage microenvironment 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.

  12. Acceleration Of Wound Healing Ny Photodynamic Therapy

    DOEpatents

    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.

  13. Wound cleaning and wound healing: a concise review.

    PubMed

    Wilkins, Robert G; Unverdorben, Martin

    2013-04-01

    Chronic wounds present a significant societal burden in their cost of care, and they reduce patient quality of life. Key components of wound care include such measures as debridement, irrigation, and wound cleaning. Appropriate care removes necrotic tissue and reduces wound bioburden to enhance wound healing. Physical cleaning with debridement and irrigation is of documented efficacy. Wounds may be washed with water, saline, or Ringer's solution or cleaned with active ingredients, such as hydrogen peroxide, sodium hypochlorite, acetic acid, alcohol, ionized silver preparations, chlorhexidine, polyhexanide/betaine solution, or povidone-iodine--the majority of which are locally toxic and of limited or no proven efficacy in enhancing wound healing. Although the consensus opinion is that these topical cleaning agents should not be routinely used, recent clinical evidence suggests that polyhexanide/betaine may be nontoxic and effective in enhancing wound healing. Further well-designed studies are needed. PMID:23507692

  14. Wound cleaning and wound healing: a concise review.

    PubMed

    Wilkins, Robert G; Unverdorben, Martin

    2013-04-01

    Chronic wounds present a significant societal burden in their cost of care, and they reduce patient quality of life. Key components of wound care include such measures as debridement, irrigation, and wound cleaning. Appropriate care removes necrotic tissue and reduces wound bioburden to enhance wound healing. Physical cleaning with debridement and irrigation is of documented efficacy. Wounds may be washed with water, saline, or Ringer's solution or cleaned with active ingredients, such as hydrogen peroxide, sodium hypochlorite, acetic acid, alcohol, ionized silver preparations, chlorhexidine, polyhexanide/betaine solution, or povidone-iodine--the majority of which are locally toxic and of limited or no proven efficacy in enhancing wound healing. Although the consensus opinion is that these topical cleaning agents should not be routinely used, recent clinical evidence suggests that polyhexanide/betaine may be nontoxic and effective in enhancing wound healing. Further well-designed studies are needed.

  15. 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

  16. 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

  17. 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

  18. "Inert" vehicles do affect wound healing.

    PubMed

    Eaglstein, W H; Mertz, P M

    1980-02-01

    The effect of a single daily application of U.S.P. petrolatum, an oil-in-water vanishing cream or a lotion on the rate of epidermal wound healing was determined in domestic white pigs. The superficial wounds were made with a dermatome and were not infected. In these studies, applications of U.S.P. white petrolatum retarded the rate of epidermal healing by 17% compared to untreated control wounds. Applications of an oil-in-water vanishing cream increased the rate of epidermal healing by 24% and a lotion increased the rate 15% compared to untreated control wounds.

  19. Advances in Wound Healing: A Review of Current Wound Healing Products

    PubMed Central

    Murphy, Patrick S.; Evans, Gregory R. D.

    2012-01-01

    Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing. PMID:22567251

  20. Wound Healing Activity of Silibinin in Mice

    PubMed Central

    Samanta, Rojalini; Pattnaik, Ashok K.; Pradhan, Kishanta K.; Mehta, Beena K.; Pattanayak, Shakti P.; Banerjee, Sugato

    2016-01-01

    Background: Silibinin is a semi-purified fraction of silymarin contained in milk thistle (Silybum marianum Asteraceae). Primarily known for its hepatoprotective actions, silymarin may also stimulate epithelialization and reduce inflammation in excision wound. Previous studies show antioxidant, anti-inflammatory, and antimicrobial actions of silibinin. However, wound healing property of silibinin is not well studied. Objective: This study investigates wound healing activity of silibinin topical formulation. Materials and Methods: Wound healing activity of 0.2% silibinin gel was assessed by incision and excision wound models in mice. Animals were divided into gel base, silibinin gel, and Mega Heal gel® treated groups with six animals in each group. Wound contraction, wound tissue tensile strength, and hydroxyproline content were measured, and histopathological evaluation of wound tissue of all the above treatment groups was carried out. Results: Application of 0.2% silibinin hydrogel for 8 days led to 56.3% wound contraction compared to 64.6% using standard Mega Heal gel with a subsequent increase in hydroxyproline content, which was significantly higher (P < 0.001) over control animals showing 33.2% contraction. After 14 days, percentage of contraction reached 96.1%, 97.6%, and 86.7%, respectively. Wound tissue tensile strength with silibinin (223.55 ± 3.82 g) and standard (241.38 ± 2.49 g) was significantly higher (P < 0.001) than control (174.06 ± 5.75 g). Histopathology of silibinin and standard gel treated wound tissue showed more fibroblasts, fewer macrophage infiltration, and well-formed collagen fibers. Conclusion: Here, we show potent wound healing activity of silibinin hydrogel formulation. SUMMARY 0.2% silibinin hydrogel showed potent wound healing activity in incision and excision wound models in mice. Abbreviations Used: ROS: Reactive oxygen species PMID:27695272

  1. Wound Healing Activity of Silibinin in Mice

    PubMed Central

    Samanta, Rojalini; Pattnaik, Ashok K.; Pradhan, Kishanta K.; Mehta, Beena K.; Pattanayak, Shakti P.; Banerjee, Sugato

    2016-01-01

    Background: Silibinin is a semi-purified fraction of silymarin contained in milk thistle (Silybum marianum Asteraceae). Primarily known for its hepatoprotective actions, silymarin may also stimulate epithelialization and reduce inflammation in excision wound. Previous studies show antioxidant, anti-inflammatory, and antimicrobial actions of silibinin. However, wound healing property of silibinin is not well studied. Objective: This study investigates wound healing activity of silibinin topical formulation. Materials and Methods: Wound healing activity of 0.2% silibinin gel was assessed by incision and excision wound models in mice. Animals were divided into gel base, silibinin gel, and Mega Heal gel® treated groups with six animals in each group. Wound contraction, wound tissue tensile strength, and hydroxyproline content were measured, and histopathological evaluation of wound tissue of all the above treatment groups was carried out. Results: Application of 0.2% silibinin hydrogel for 8 days led to 56.3% wound contraction compared to 64.6% using standard Mega Heal gel with a subsequent increase in hydroxyproline content, which was significantly higher (P < 0.001) over control animals showing 33.2% contraction. After 14 days, percentage of contraction reached 96.1%, 97.6%, and 86.7%, respectively. Wound tissue tensile strength with silibinin (223.55 ± 3.82 g) and standard (241.38 ± 2.49 g) was significantly higher (P < 0.001) than control (174.06 ± 5.75 g). Histopathology of silibinin and standard gel treated wound tissue showed more fibroblasts, fewer macrophage infiltration, and well-formed collagen fibers. Conclusion: Here, we show potent wound healing activity of silibinin hydrogel formulation. SUMMARY 0.2% silibinin hydrogel showed potent wound healing activity in incision and excision wound models in mice. Abbreviations Used: ROS: Reactive oxygen species

  2. 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

  3. 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.

  4. Wound healing properties of Artocarpus heterophyllus Lam.

    PubMed

    Gupta, Nilesh; Jain, U K; Pathak, A K

    2009-04-01

    The studies on excision wound healing model reveals significant wound healing activity of the methanolic leaf extract (simple ointment 5%) of "Artocarpus heterophyllus" ham which is comparable with standard (Betadine). In the excision model, the period of epithelization, of the extract treated group was found to be higher than the controlgroup and slightly lesser than standard treated group of animals on the up to 16(th) post wounding day.

  5. Wound healing properties of Artocarpus heterophyllus Lam

    PubMed Central

    Gupta, Nilesh; Jain, U.K.; Pathak, A.K.

    2009-01-01

    The studies on excision wound healing model reveals significant wound healing activity of the methanolic leaf extract (simple ointment 5%) of “Artocarpus heterophyllus” ham which is comparable with standard (Betadine). In the excision model, the period of epithelization, of the extract treated group was found to be higher than the controlgroup and slightly lesser than standard treated group of animals on the up to 16th post wounding day. PMID:22557331

  6. Wound healing properties of Artocarpus heterophyllus Lam.

    PubMed

    Gupta, Nilesh; Jain, U K; Pathak, A K

    2009-04-01

    The studies on excision wound healing model reveals significant wound healing activity of the methanolic leaf extract (simple ointment 5%) of "Artocarpus heterophyllus" ham which is comparable with standard (Betadine). In the excision model, the period of epithelization, of the extract treated group was found to be higher than the controlgroup and slightly lesser than standard treated group of animals on the up to 16(th) post wounding day. PMID:22557331

  7. [Modification of postoperative wound healing by showering].

    PubMed

    Neues, C; Haas, E

    2000-02-01

    Usually postoperative wounds are kept dry until the stitches are removed. In a prospective randomized study early water contact was allowed in order to test postoperative wound healing in 817 patients operated on for varicose veins. Regardless of whether the wounds were kept dry or had water contact with or without shower foam from the second postoperative day, no infection was registered.

  8. 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.

  9. Loss of innervation and axon plasticity accompanies impaired diabetic wound healing.

    PubMed

    Cheng, Chu; Singh, Vandana; Krishnan, Anand; 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.

  10. Low-intensity vibration improves angiogenesis and wound healing in diabetic mice.

    PubMed

    Weinheimer-Haus, Eileen M; Judex, Stefan; Ennis, William J; Koh, Timothy J

    2014-01-01

    Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing--whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b- cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors.

  11. 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

  12. Wound healing of intestinal epithelial cells

    PubMed Central

    Iizuka, Masahiro; Konno, Shiho

    2011-01-01

    The intestinal epithelial cells (IECs) form a selective permeability barrier separating luminal content from underlying tissues. Upon injury, the intestinal epithelium undergoes a wound healing process. Intestinal wound healing is dependent on the balance of three cellular events; restitution, proliferation, and differentiation of epithelial cells adjacent to the wounded area. Previous studies have shown that various regulatory peptides, including growth factors and cytokines, modulate intestinal epithelial wound healing. Recent studies have revealed that novel factors, which include toll-like receptors (TLRs), regulatory peptides, particular dietary factors, and some gastroprotective agents, also modulate intestinal epithelial wound repair. Among these factors, the activation of TLRs by commensal bacteria is suggested to play an essential role in the maintenance of gut homeostasis. Recent studies suggest that mutations and dysregulation of TLRs could be major contributing factors in the predisposition and perpetuation of inflammatory bowel disease. Additionally, studies have shown that specific signaling pathways are involved in IEC wound repair. In this review, we summarize the function of IECs, the process of intestinal epithelial wound healing, and the functions and mechanisms of the various factors that contribute to gut homeostasis and intestinal epithelial wound healing. PMID:21633524

  13. Practices in wound healing studies of plants.

    PubMed

    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

  14. 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

  15. Honey: an immunomodulator in wound healing.

    PubMed

    Majtan, Juraj

    2014-01-01

    Honey is a popular natural product that is used in the treatment of burns and a broad spectrum of injuries, in particular chronic wounds. The antibacterial potential of honey has been considered the exclusive criterion for its wound healing properties. The antibacterial activity of honey has recently been fully characterized in medical-grade honeys. Recently, the multifunctional immunomodulatory properties of honey have attracted much attention. The aim of this review is to provide closer insight into the potential immunomodulatory effects of honey in wound healing. Honey and its components are able to either stimulate or inhibit the release of certain cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) from human monocytes and macrophages, depending on wound condition. Similarly, honey seems to either reduce or activate the production of reactive oxygen species from neutrophils, also depending on the wound microenvironment. The honey-induced activation of both types of immune cells could promote debridement of a wound and speed up the repair process. Similarly, human keratinocytes, fibroblasts, and endothelial cell responses (e.g., cell migration and proliferation, collagen matrix production, chemotaxis) are positively affected in the presence of honey; thus, honey may accelerate reepithelization and wound closure. The immunomodulatory activity of honey is highly complex because of the involvement of multiple quantitatively variable compounds among honeys of different origins. The identification of these individual compounds and their contributions to wound healing is crucial for a better understanding of the mechanisms behind honey-mediated healing of chronic wounds.

  16. Effect of negative pressure wound therapy on wound healing.

    PubMed

    Huang, Chenyu; Leavitt, Tripp; Bayer, Lauren R; Orgill, Dennis P

    2014-07-01

    The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is small and much more can be learned about the mechanisms of action. In the future, hopefully we will have the data to assist clinicians in selecting optimal parameters for specific wounds including interface material, waveform of suction application, and the amount of suction to be applied. Further investigation into specific interface coatings and instillation therapy are also needed. We believe that advances in mechanobiology, the science of wound healing, the understanding of biofilms, and advances in cell therapy will lead to better care for our patients.

  17. 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

  18. Antioxidant status in delayed healing type of wounds

    PubMed Central

    Rasik, Anamika M; Shukla, Arti

    2000-01-01

    This investigation studied the contribution of antioxidants in delaying healing in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and vitamin E in streptozotocin-induced diabetic rat were lower as compared to nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E level along with depleted GSH content. In aged rats (18 months old), higher levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and GSH were found as compared to their values in young rats (3–4 months old). The levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged rats were significantly lower in comparison to those in young rats. However, TBARS were elevated in these wound tissues. The non-wounded skin of immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS and higher GSH and GPx levels in comparison to those present in normal mouse skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD, catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the wound tissue of normal mice. Thus low levels of antioxidants accompanied by raised levels of markers of free radical damage play a significant role in delaying wound healing in aged rats. In diabetic rats reduced glutathione levels may have a contributory role in delaying the healing process. However, in immunocompromised mice the antioxidant status following injury showed an adapted response. PMID:10971747

  19. 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

  20. Mechanoregulation of Wound Healing and Skin Homeostasis.

    PubMed

    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

  1. 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

  2. [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

  3. Cellular senescence controls fibrosis in wound healing.

    PubMed

    Jun, Joon-Il; Lau, Lester F

    2010-09-01

    Mammalian wound healing involves the rapid synthesis and deposition of extracellular matrix (ECM) to maintain tissue integrity during repair. This process must be tightly controlled, as its deregulation may result in fibrosis, scarring, and loss of tissue function. Recent studies have uncovered an efficient and parsimonious mechanism for rendering fibrogenesis self-limiting in wound healing: in such diverse organs as the liver and skin, the myofibroblasts that initially proliferate and produce ECM are themselves eventually driven into senescence, blocking their further proliferation and converting them into matrix-degrading cells. Myofibroblast senescence in skin wounds is triggered by a dynamically expressed matricellular protein, CCN1/CYR61, which acts through integrin-mediated induction of oxidative stress. We propose that the onset of myofibroblast senescence is a programmed wound healing response that functions as a self-limiting mechanism for fibrogenesis, and this process may be regulated by the ECM microenvironment through the expression of CCN1/CYR61.

  4. Dietary peptides improve wound healing following surgery.

    PubMed

    Roberts, P R; Black, K W; Santamauro, J T; Zaloga, G P

    1998-03-01

    To determine if peptide-based enteral diets improve wound healing when compared to amino acid-based diets, a prospective randomized study was conducted using 38 male Sprague-Dawley rats. Following placement of a standardized abdominal wound, 20 animals were randomized to an isonitrogenous peptide-based (PEP) versus amino acid-based diet (AA) for 10 d. In addition, 18 animals were randomized to an amino acid-based diet supplemented with the peptide carnosine (CARN) or its constituent amino acids (Control). Diets were administered through small bowel feeding tubes. Wound bursting pressure was significantly higher in the PEP animals compared to the AA animals (179+/-9 versus 138+/-12 mmHg; P=0.02). In addition, wound bursting pressure was significantly greater in the CARN animals compared to the Control animals (143+/-10 versus 116+/-8 mmHg; P=0.005). Peptide-based enteral diets improve wound healing when compared to nonpeptide generating amino acid-based diets. We also conclude that the dietary peptide carnosine represents a dietary peptide that improves wound healing when administered as part of a complete enteral formula. This effect on wound healing may be clinically relevant because carnosine is not found in most enteral formulas.

  5. 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

  6. 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

  7. Efficacy of Jasminum grandiflorum L. leaf extract on dermal wound healing in rats.

    PubMed

    Chaturvedi, Adya P; Kumar, Mohan; Tripathi, Yamini B

    2013-12-01

    Wound healing is a fundamental response to tissue injury and natural products accelerate the healing process. Here, we have explored the efficacy of topical administration of an ointment, prepared by methanolic extract of Jasminum grandiflorum L. (Oleaceae) leaves, on cutaneous wound healing in rats. The topical application of the Jasminum ointment on full thickness excision wounds accelerated the healing process. Tissue growth and collagen synthesis were significantly higher determined by total hydroxyl proline, hexosamine, protein and DNA content. The response was concentration- and time-dependent, when observed on days 4, 8 and 12 after wound creation. The rate of wound healing was faster as determined by wound contraction, tensile strength and other histopathological changes. In addition, this ointment also raised the activity of superoxide dismutase (SOD) and catalase (CAT) with high GSH content and low lipid peroxidation products in wound tissue. Thus, it could be suggested that the ointment from the methanolic extract of J. grandiflorum leaf improves the rate of wound healing by enhancing the rate of collagen synthesis and also by improving the antioxidant status in the newly synthesised healing wound tissue.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. A wound healing model with sonographic monitoring.

    PubMed

    Hoffmann, K; Winkler, K; el-Gammal, S; Altmeyer, P

    1993-05-01

    The methods used hitherto for quantification of skin repair processes only allow an examiner a two-dimensional assessment of superficial wound healing. With the recent advent of high frequency B-scan ultrasonography in dermatology it has become possible to follow the course of healing and evaluate the healing processes in deeper layers of the skin. In this investigation 80 patients received cryosurgery for treatment of basal cell carcinomas on the face or neck region. As the size of cryosurgical defects can be precisely controlled they are potentially useful as standardized wound healing models. The course of wound healing after cryosurgery using a digital ultrasound scanner (DUB 20, Taberna pro medicum, Lüneburg, Germany) was monitored. The usable depth of penetration of the echo signal is approximately 7 mm. The lateral resolution is approximately 200 microns, the axial resolution approximately 80 microns. The cryolesion and the repair processes were examined ultrasonographically and clinically over a period of at least 3 weeks or until the wound had completely healed. The depth of invasion and lateral extent of the basal cell carcinoma as well as the size of the induced cryolesion can be determined by ultrasound. The exudative phase after cryosurgery, with developing oedema and necrosis, can be quantified on the basis of the reduced reflectivity in the corium. The repair processes taking place in the region of necrosis can be visualized in the ultrasound scan. The ultrasonically monitored wound healing model which we have demonstrated is particularly suitable for investigating the efficacy of drugs which promote healing.

  13. 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

  14. Effects of psychological stress and housing conditions on the delay of wound healing.

    PubMed

    Vegas, Óscar; VanBuskirk, JoAnne; Richardson, Steven; Parfitt, David; Helmreich, Dana; Rempel, Max; Moynihan, Jan; Tausk, Francisco

    2012-11-01

    This study explores the effects of stress and housing conditions on the healing of cutaneous wounds and its relationship with circulating levels of corticosterone. Specifically, we set out to examine the effect of combined physical (restraint stress and ultrasound) and psychological (predator scent) stressors on the cutaneous wound healing of female mice that had been housed either in groups (with social support; n= 16) or individually (without social support; n= 16). In contrast with other studies, the model of multiple ethological mild stressors utilized in this study significantly increased the levels of corticosterone, but failed to dramatically alter the healing of skin wounds. However, the results of this study provide evidence of the importance of housing conditions, suggesting that positive social interactions in females accelerate the rate of wound healing, and reduce levels of anxiety and circulating corticosterone. The level of anxiety, as well as the basal levels of corticosterone, proved to be valid predictors of the healing rates during different stages of cutaneous wound healing.

  15. Laser Biostimulation Of Wound Healing In Arteriopatic Patients

    NASA Astrophysics Data System (ADS)

    Tallarida, G.; Baldoni, F.; Raimondi, G.; Massaro, M.; Peruzzi, G.; Bertolotti, M.; Ferrari, A.; Scudieri, F.

    1981-05-01

    Low-power laser irradiation has been employed in the attempt to accelerate the wound-healing of ischemic cutaneous ulcerations with threatening or manifest gangrene due to arteriosclerosis obliterans of the lower limbs. Irradiation was performed by using a low-power He-Ne gas laser of 6328 Å wavelength and was concentrated at the peripheral zone of the lesions. The preliminary results of the study indicate that laser stimulation might be new approach in the conservative menagement of the ischemic ulcers in patients with severe peripheral obstructive arteriopaties not suited for arterial reconstruction.

  16. The effects of caffeine on wound healing.

    PubMed

    Ojeh, Nkemcho; Stojadinovic, Olivera; Pastar, Irena; Sawaya, Andrew; Yin, Natalie; Tomic-Canic, Marjana

    2016-10-01

    The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing.

  17. 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

  18. 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

  19. [Maggots in the wound, debridement, disinfection and wound healing].

    PubMed

    Schouten, Helga W; Knippels, Marion C J; Franken, Ralph J P M

    2009-01-01

    An 87-year-old man had a longstanding untreated large basosquamous carcinoma on his right ear. He was admitted to the emergency department at our hospital. A large portion of the auricle had perished, together with part of the tumour. Surgery was planned but two days before, the patient complained of an irritating loud noise in his ear. We discovered this was caused by maggots in his external acoustic meatus: myiasis. Dozens of maggots were removed. A striking finding was that the smell of the wound had disappeared and that the wound was much cleaner, with a reddish aspect and less necrosis. The surgical procedure was uneventful. Larval therapy has been known for centuries. In recent years it has gained renewed interest as it may enhance wound debridement, wound disinfection, and may promote wound healing.

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

    PubMed Central

    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

  1. 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

  2. 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

  3. 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

  4. Effects of skin-derived precursors on wound healing of denervated skin in a nude mouse model.

    PubMed

    Shu, Bin; Xie, Ju-Lin; Xu, Ying-Bin; Lai, Wen; Huang, Yong; Mao, Ren-Xiang; Liu, Xu-Sheng; Qi, Shao-Hai

    2015-01-01

    Denervated skin could result in impaired healing of wounds, such as decubitus ulcers and diabetic foot ulcers. Other studies indicated that cutaneous fiber density is reduced after inner nerve transection and that neuropeptide level depletes after denervation, leading to reduced cell proliferation around the wound and thus wound healing problems. Recent studies have revealed that skin-derived precursors (SKPs), which form a neural crest-related stem cell population in the dermis of skin, participate in cutaneous nerve regeneration. We hypothesized that injecting SKPs into denervated wound promotes healing. A bilateral denervation wound model was established followed by SKP transplantation. The wound healing rate was determined at 7, 14, and 21 d after injury. Cell proliferation activity during wound healing was analyzed by proliferating cell nuclear antigen immunohistochemistry (IHC). Nerve fiber density was measured by S-100 IHC. The contents of nerve growth factor, substance P, and calcitonin gene-related peptide were examined by enzyme-linked immunosorbent assay. The rate of epithelization in the SKP-treated group was faster than that in the control group. Wound cell proliferation and nerve fiber density were obviously higher in the SKP-treated group than in the control group. In addition, the content of neuropeptides was higher in the SKP-treated group than in the control group during wound healing. In conclusion, SKPs can promote denervated wound healing through cell proliferation and nerve fiber regeneration, and can facilitate the release of neuropeptides.

  5. Effects of skin-derived precursors on wound healing of denervated skin in a nude mouse model

    PubMed Central

    Shu, Bin; Xie, Ju-Lin; Xu, Ying-Bin; Lai, Wen; Huang, Yong; Mao, Ren-Xiang; Liu, Xu-Sheng; Qi, Shao-Hai

    2015-01-01

    Denervated skin could result in impaired healing of wounds, such as decubitus ulcers and diabetic foot ulcers. Other studies indicated that cutaneous fiber density is reduced after inner nerve transection and that neuropeptide level depletes after denervation, leading to reduced cell proliferation around the wound and thus wound healing problems. Recent studies have revealed that skin-derived precursors (SKPs), which form a neural crest-related stem cell population in the dermis of skin, participate in cutaneous nerve regeneration. We hypothesized that injecting SKPs into denervated wound promotes healing. A bilateral denervation wound model was established followed by SKP transplantation. The wound healing rate was determined at 7, 14, and 21 d after injury. Cell proliferation activity during wound healing was analyzed by proliferating cell nuclear antigen immunohistochemistry (IHC). Nerve fiber density was measured by S-100 IHC. The contents of nerve growth factor, substance P, and calcitonin gene-related peptide were examined by enzyme-linked immunosorbent assay. The rate of epithelization in the SKP-treated group was faster than that in the control group. Wound cell proliferation and nerve fiber density were obviously higher in the SKP-treated group than in the control group. In addition, the content of neuropeptides was higher in the SKP-treated group than in the control group during wound healing. In conclusion, SKPs can promote denervated wound healing through cell proliferation and nerve fiber regeneration, and can facilitate the release of neuropeptides. PMID:26045771

  6. [3-dimensional documentation of wound-healing].

    PubMed

    Körber, A; Grabbe, S; Dissemond, J

    2006-04-01

    The objective evaluation of the course of wound-healing represents a substantial parameter for the quality assurance of a modern wound management in chronic wounds. Established procedures exclusively based on a two-dimensional measurement of the wound surface with planimetry or digital photo documentation in combination with a metric statement of size. Thus so far an objective method is missing for the evaluation of the volumes of chronic wounds. By the linkage of digital photography, optical grid by means of digital scanner and an image processing software in co-operation with the company RSI we were able to do an accurate 3-dimensional documentation of chronic wounds (DigiSkin). The generated scatter-plots allow a visual, computer-assisted 3-dimensional measurement and documentation of chronic wounds. In comparison with available systems it is now possible for the first time to objectify the volume changes of a chronic wound. On the basis of a case report of a female patient with an venous leg ulcer, which has been treated with a vacuum closure therapy before and after performing a mesh-graft transplantation, we would like to describe the advantages and the resulting scientific use of this new, objective wound documentation system in the clinical employment. PMID:16575675

  7. 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...

  8. Use of Platelet-Rich Fibrin over Skin Wounds: Modified Secondary Intention Healing

    PubMed Central

    Desai, Chirag B; Mahindra, Uma R; Kini, Yogesh K; Bakshi, Makarand K

    2013-01-01

    The healing process after any surgical intervention has always posed a challenge for the surgeons. In spite of the advances in wound closure techniques and devices, there is a crucial need for newer methods of enhancing the healing process to achieve optimal outcomes. Fibrin adhesives and platelet concentrates have proven useful in various treatment modalities in the fields of microvascular and plastic surgery. This case report shows its unique use in the field of maxillofacial and cutaneous surgery. It shows an innovative technique of enhancement of skin wound healing by local application of platelet-rich fibrin. PMID:23723604

  9. 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

  10. 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

  11. 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

  12. Mathematical model for wound healing following autologous keratinocyte transplantation.

    PubMed

    Renner, Regina; Teuwen, Isabell; Gebhardt, Carl; Simon, Jan C

    2008-06-01

    In times of increasing economical pressure on the health care systems, it is important to optimise the outpatient treatment of chronic wounds. Another aim of wound healing research is to discover agents to accelerate healing. Wound healing trajectories or healing velocities can provide information to demonstrate the endpoints for wound healing. A great problem in clinical trials is to specify these parameters. Therefore, we developed a mathematical model for more transparency. In this initial project, we observed 19 wounds to construct the wound healing trajectories after transplantation of autologous keratinocytes, and the results are so encouraging that investigation in this area will continue. The developed mathematical model describes the clinical observed healing process. It was possible to find parameters to distinguish between old and young patients, retrospectively or prospectively calculate the healing rates and to determine exactly the endpoint of healing. Therefore, our model might be very useful in practices or for studies.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Fibrin sealant combined with fibroblasts and platelet-derived growth factor enhance wound healing in excisional wounds.

    PubMed

    Mogford, Jon E; Tawil, Bill; Jia, Shengxian; Mustoe, Thomas A

    2009-01-01

    We test the hypothesis that the fibrinogen-thrombin formulation of fibrin sealant combined with fibroblasts and PDGF-BB enhance cutaneous wound healing. Four formulations varying in fibrinogen and thrombin concentration were applied to full-thickness biopsy wounds in the rabbit ear cutaneous wound healing model with or without cultured rabbit dermal fibroblasts (RDFs; 3 x 10(5) cells/wound) embedded in the fibrinogen component. At post-wounding day 7, there was no difference in the diluted vs. non-diluted formulations for either the promotion of granulation tissue coverage of the open wounds or total granulation tissue area when tested without embedded cells. Including the RDFs, the highest degree of wound coverage by granulation tissue was observed in the combined dilution formulation (17.3 mg/mL fibrinogen, 167 U/mL thrombin; n=10 wounds) that was 167% (p<0.05) of the nondiluted FS containing cells (50 mg/mL fibrinogen, 250 U/mL thrombin; n=10 wounds). Inclusion of fibroblasts increased granulation tissue area within the wounds vs. FS alone (p<0.05) for each diluted formulation although no differences in this parameter were observed within each group (FS alone or with embedded cells). However, addition of the vulnerary growth factor PDGF-BB (3 mg; n=4) with the embedded RDFs in the combined dilution formulation increased granulation tissue area over two-fold (p<0.01) over FS alone. Additionally, the presence of the RDFs promoted incorporation of the granulation tissue with and epithelial migration over the FS suggesting an active interaction between cells delivered to the wound by FS and the host repair cells. The findings suggest the progress of cutaneous defect repair can be enhanced by ex vivo cell delivery in fibrin sealant.

  20. 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

  1. 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).

  2. 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

  3. 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

  4. Low-output carbon dioxide laser for cutaneous wound closure of scalpel incisions: comparative tensile strength studies of the laser to the suture and staple for wound closure

    SciTech Connect

    Garden, J.M.; Robinson, J.K.; Taute, P.M.; Lautenschlager, E.P.; Leibovich, S.J.; Hartz, R.S.

    1986-01-01

    The low-output carbon dioxide (CO/sub 2/) laser was used for cutaneous wound closure of scalpel incisions. Cutaneous scalpel incisions were placed over the dorsum of three minipigs and were then closed by either the laser, sutures, or staples. At multiple time points after wound closure, up to day 90, the tensile strengths of these wounds were comparatively evaluated. All wounds, including those closed with the laser, clinically appeared to heal similarly with no evidence of wound dehiscence or infection. Tensile strength studies revealed similar sigmoid curves for all wound closure modalities with low initial tensile strengths up to days 14 to 21, which afterwards increased rapidly, with a plateau toward day 90. From our study, it appears that the CO/sub 2/ laser, in the low-output mode, can be used for cutaneous wound closure and that similar clinical healing and tensile strength measurements are obtained relative to the conventional cutaneous wound closure modalities of the suture or staple.

  5. Effects of glutamine on wound healing.

    PubMed

    Kesici, Ugur; Kesici, Sevgi; Ulusoy, Hulya; Yucesan, Fulya; Turkmen, Aygen U; Besir, Ahmet; Tuna, Verda

    2015-06-01

    Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.

  6. 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

  7. Wound healing and treating wounds: Differential diagnosis and evaluation of chronic wounds.

    PubMed

    Morton, Laurel M; Phillips, Tania J

    2016-04-01

    Wounds are an excellent example of how the field of dermatology represents a cross-section of many medical disciplines. For instance, wounds may be caused by trauma, vascular insufficiency, and underlying medical conditions, such as diabetes, hypertension, and rheumatologic and inflammatory disease. This continuing medical education article provides an overview of wound healing and the pathophysiology of chronic wounds and reviews the broad differential diagnosis of chronic wounds. It also describes the initial steps necessary in evaluating a chronic wound and determining its underlying etiology.

  8. Angiogenesis Is Induced and Wound Size Is Reduced by Electrical Stimulation in an Acute Wound Healing Model in Human Skin

    PubMed Central

    Ud-Din, Sara; Sebastian, Anil; Giddings, Pamela; Colthurst, James; Whiteside, Sigrid; Morris, Julie; Nuccitelli, Richard; Pullar, Christine; Baguneid, Mo; Bayat, Ardeshir

    2015-01-01

    Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up

  9. Wound healing - A literature review*

    PubMed Central

    Gonzalez, Ana Cristina de Oliveira; Costa, Tila Fortuna; Andrade, Zilton de Araújo; Medrado, Alena Ribeiro Alves Peixoto

    2016-01-01

    Regeneration and tissue repair processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. The exsudative, proliferative, and extracellular matrix remodeling phases are sequential events that occur through the integration of dynamic processes involving soluble mediators, blood cells, and parenchymal cells. Exsudative phenomena that take place after injury contribute to the development of tissue edema. The proliferative stage seeks to reduce the area of tissue injury by contracting myofibroblasts and fibroplasia. At this stage, angiogenesis and reepithelialization processes can still be observed. Endothelial cells are able to differentiate into mesenchymal components, and this difference appears to be finely orchestrated by a set of signaling proteins that have been studied in the literature. This pathway is known as Hedgehog. The purpose of this review is to describe the various cellular and molecular aspects involved in the skin healing process.

  10. In-vivo monitoring rat skin wound healing using nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Guo, Chungen; Zhang, Fan; Xu, Yahao; Zhu, Xiaoqin; Xiong, Shuyuan; Chen, Jianxin

    2014-11-01

    Nonlinear optical microscopy (NLOM) was employed for imaging and evaluating the wound healing process on rat skin in vivo. From the high-resolution nonlinear optical images, the morphology and distribution of specific biological markers in cutaneous wound healing such as fibrin clot, collagens, blood capillaries, and hairs were clearly observed at 1, 5 and 14 days post injury. We found that the disordered collagen in the fibrin clot at day 1 was replaced by regenerative collagen at day 5. By day 14, the thick collagen with well-network appeared at the original margin of the wound. These findings suggested that NLOM is ideal for noninvasively monitoring the progress of wound healing in vivo.

  11. Effect of fibroblast-seeded artificial dermis on wound healing.

    PubMed

    Jang, Joon Chul; Choi, Rak-Jun; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2015-04-01

    In covering wounds, efforts should include use of the safest and least invasive methods with a goal of achieving optimal functional and cosmetic outcome. The recent development of advanced technology in wound healing has triggered the use of cells and/or biological dermis to improve wound healing conditions. The purpose of the study was to evaluate the effects of fibroblast-seeded artificial dermis on wound healing efficacy.Ten nude mice were used in this study. Four full-thickness 6-mm punch wounds were created on the dorsal surface of each mouse (total, 40 wounds). The wounds were randomly assigned to one of the following 4 treatments: topical application of Dulbecco phosphate-buffered saline (control), human fibroblasts (FB), artificial dermis (AD), and human fibroblast-seeded artificial dermis (AD with FB). On the 14th day after treatment, wound healing rate and wound contraction, which are the 2 main factors determining wound healing efficacy, were evaluated using a stereoimage optical topometer system, histomorphological analysis, and immunohistochemistry.The results of the stereoimage optical topometer system demonstrated that the FB group did not have significant influence on wound healing rate and wound contraction. The AD group showed reduced wound contraction, but wound healing was delayed. The AD with FB group showed decreased wound contraction without significantly delayed wound healing. Histomorphological analysis exhibited that more normal skin structure was regenerated in the AD with FB group. Immunohistochemistry demonstrated that the AD group and the AD with FB group produced less α-smooth muscle actin than the control group, but this was not shown in the FB group.Fibroblast-seeded artificial dermis may minimize wound contraction without significantly delaying wound healing in the treatment of skin and soft tissue defects.

  12. Wound Healing Activity of Elaeis guineensis Leaf Extract Ointment

    PubMed Central

    Sasidharan, Sreenivasan; Logeswaran, Selvarasoo; Latha, Lachimanan Yoga

    2012-01-01

    Elaeis guineensis of the Arecaceae family is widely used in the traditional medicine of societies in West Africa for treating various ailments. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied. The results showed that E. guineensis leaf extract had potent wound healing capacity as evident from the better wound closure (P < 0.05), improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Matrix metalloproteinases expression correlated well with the results thus confirming efficacy of E. guineensis in the treatment of the wound. E. guineensis accelerated wound healing in rats, thus supporting its traditional use. The result of this study suggested that, used efficiently, oil palm leaf extract is a renewable resource with wound healing properties. PMID:22312255

  13. Wound healing activity of Elaeis guineensis leaf extract ointment.

    PubMed

    Sasidharan, Sreenivasan; Logeswaran, Selvarasoo; Latha, Lachimanan Yoga

    2012-01-01

    Elaeis guineensis of the Arecaceae family is widely used in the traditional medicine of societies in West Africa for treating various ailments. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied. The results showed that E. guineensis leaf extract had potent wound healing capacity as evident from the better wound closure (P < 0.05), improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Matrix metalloproteinases expression correlated well with the results thus confirming efficacy of E. guineensis in the treatment of the wound. E. guineensis accelerated wound healing in rats, thus supporting its traditional use. The result of this study suggested that, used efficiently, oil palm leaf extract is a renewable resource with wound healing properties.

  14. A potential wound-healing-promoting peptide from salamander skin.

    PubMed

    Mu, Lixian; Tang, Jing; Liu, Han; Shen, Chuanbin; Rong, Mingqiang; Zhang, Zhiye; Lai, Ren

    2014-09-01

    Although it is well known that wound healing proceeds incredibly quickly in urodele amphibians, such as newts and salamanders, little is known about skin-wound healing, and no bioactive/effector substance that contributes to wound healing has been identified from these animals. As a step toward understanding salamander wound healing and skin regeneration, a potential wound-healing-promoting peptide (tylotoin; KCVRQNNKRVCK) was identified from salamander skin of Tylototriton verrucosus. It shows comparable wound-healing-promoting ability (EC50=11.14 μg/ml) with epidermal growth factor (EGF; NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR) in a murine model of full-thickness dermal wound. Tylotoin directly enhances the motility and proliferation of keratinocytes, vascular endothelial cells, and fibroblasts, resulting in accelerated reepithelialization and granulation tissue formation in the wound site. Tylotoin also promotes the release of transforming growth factor β1 (TGF-β1) and interleukin 6 (IL-6), which are essential in the wound healing response. Gene-encoded tylotoin secreted in salamander skin is possibly an effector molecule for skin wound healing. This study may facilitate understanding of the cellular and molecular events that underlie quick wound healing in salamanders.

  15. Elements affecting wound healing time: An evidence based analysis.

    PubMed

    Khalil, Hanan; Cullen, Marianne; Chambers, Helen; Carroll, Matthew; Walker, Judi

    2015-01-01

    The purpose of this study was to identify the predominant client factors and comorbidities that affected the time taken for wounds to heal. A prospective study design used the Mobile Wound Care (MWC) database to capture and collate detailed medical histories, comorbidities, healing times and consumable costs for clients with wounds in Gippsland, Victoria. There were 3,726 wounds documented from 2,350 clients, so an average of 1.6 wounds per client. Half (49.6%) of all clients were females, indicating that there were no gender differences in terms of wound prevalence. The clients were primarily older people, with an average age of 64.3 years (ranging between 0.7 and 102.9 years). The majority of the wounds (56%) were acute and described as surgical, crush and trauma. The MWC database categorized the elements that influenced wound healing into 3 groups--factors affecting healing (FAH), comorbidities, and medications known to affect wound healing. While there were a multitude of significant associations, multiple linear regression identified the following key elements: age over 65 years, obesity, nonadherence to treatment plan, peripheral vascular disease, specific wounds associated with pressure/friction/shear, confirmed infection, and cerebrovascular accident (stroke). Wound healing is a complex process that requires a thorough understanding of influencing elements to improve healing times.© 2015 by the Wound Healing Society.

  16. Endothelial Antioxidant-1: a Key Mediator of Copper-dependent Wound Healing in vivo

    PubMed Central

    Das, Archita; Sudhahar, Varadarajan; Chen, Gin-Fu; Kim, Ha Won; Youn, Seock-Won; Finney, Lydia; Vogt, Stefan; Yang, Jay; Kweon, Junghun; Surenkhuu, Bayasgalan; Ushio-Fukai, Masuko; Fukai, Tohru

    2016-01-01

    Copper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1−/− mice. Endothelial cell (EC)-specific Atox1−/− mice and gene transfer of nuclear-target Atox1 in Atox1−/− mice reveal that Atox1 in ECs as well as transcription factor function of Atox1 are required for wound healing. Mechanistically, Atox1−/− mice show reduced Atox1 target proteins such as p47phox NADPH oxidase and cyclin D1 as well as extracellular matrix Cu enzyme LOX activity in wound tissues. This in turn results in reducing O2− production in ECs, NFkB activity, cell proliferation and collagen formation, thereby inhibiting angiogenesis, macrophage recruitment and extracellular matrix maturation. Our findings suggest that Cu-dependent transcription factor/Cu chaperone Atox1 in ECs plays an important role to sense Cu to accelerate wound angiogenesis and healing. PMID:27666810

  17. Excisional Wound Healing Is Delayed in a Murine Model of Chronic Kidney Disease

    PubMed Central

    Seth, Akhil K.; De la Garza, Mauricio; Fang, Robert C.; Hong, Seok J.; Galiano, Robert D.

    2013-01-01

    Background Approximately 15% of the United States population suffers from chronic kidney disease (CKD), often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. Methods CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD) 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR). Results CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU) and angiogenesis (CD31), with a concurrent increase in inflammation (CD45) as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS) on qPCR. Conclusions These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes. PMID:23536900

  18. A primer on wound healing in colorectal surgery in the age of bioprosthetic materials.

    PubMed

    Lundy, Jonathan B

    2014-12-01

    Wound healing is a complex, dynamic process that is vital for closure of cutaneous injuries, restoration of abdominal wall integrity after laparotomy closure, and to prevent anastomotic dehiscence after bowel surgery. Derangements in healing have been described in multiple processes including diabetes mellitus, corticosteroid use, irradiation for malignancy, and inflammatory bowel disease. A thorough understanding of the process of healing is necessary for clinical decision making and knowledge of the current state of the science may lead future researchers in developing methods to enable our ability to modulate healing, ultimately improving outcomes. An exciting example of this ability is the use of bioprosthetic materials used for abdominal wall surgery (hernia repair/reconstruction). These bioprosthetic meshes are able to regenerate and remodel from an allograft or xenograft collagen matrix into site-specific tissue; ultimately being degraded and minimizing the risk of long-term complications seen with synthetic materials. The purpose of this article is to review healing as it relates to cutaneous and intestinal trauma and surgery, factors that impact wound healing, and wound healing as it pertains to bioprosthetic materials.

  19. Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds.

    PubMed

    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 lead 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 the 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 2 days postwounding, and covered with semiocclusive dressings for 2 weeks. Most of the control wounds were epithelialized by 28 days postwounding. 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 nonhealing 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 a 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.

  20. [Stem cells and growth factors in wound healing].

    PubMed

    Pikuła, Michał; Langa, Paulina; Kosikowska, Paulina; Trzonkowski, Piotr

    2015-01-02

    Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF). Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included.

  1. A short peptide from frog skin accelerates diabetic wound healing.

    PubMed

    Liu, Han; Duan, Zilei; Tang, Jing; Lv, Qiumin; Rong, Mingqiang; Lai, Ren

    2014-10-01

    Delayed wound healing will result in the development of chronic wounds in some diseases, such as diabetes. Amphibian skins possess excellent wound-healing ability and represent a resource for prospective wound-healing promoting compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes wound healing in a murine model with a full-thickness dermal wound in both normal and diabetic animals. In addition to its strong angiogenic ability with respect to the upregulation of some angiogenic proteins, CW49 also showed a significant anti-inflammatory effect in diabetic wounds, which was very important for healing chronic wounds. CW49 had little effect on re-epithelialization, resulting in no significant effect on wound closure rate compared to a vehicle control. Altogether, this indicated that CW49 might accelerate diabetic wound healing by promoting angiogenesis and preventing any excessive inflammatory response. Considering its favorable traits as a small peptide that significantly promotes angiogenesis, CW49 might be an excellent candidate or template for the development of a drug for use in the treatment of diabetic wounds.

  2. New insights into microRNAs in skin wound healing.

    PubMed

    Fahs, Fatima; Bi, Xinling; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng

    2015-12-01

    Chronic wounds are a major burden to overall healthcare cost and patient morbidity. Chronic wounds affect a large portion of the US, and billions of healthcare dollars are spent in their treatment and management. microRNAs (miRNAs) are small, noncoding double-stranded RNAs that post-transcriptionally downregulate the expression of protein-coding genes. Studies have identified miRNAs involved in all three phases of wound healing including inflammation, proliferation, and remodeling. Some miRNAs have been demonstrated in vitro with primary keratinocyte wound healing model and in vivo with mouse wound healing model through regulation of miRNA expression to affect the wound healing process. This review updates the current miRNAs involved in wound healing and discusses the future therapeutic implications and research directions.

  3. Case 5: non-healing traumatic wound colonised with MRSA.

    PubMed

    Simon, Deborah

    2016-03-01

    A traumatic wound colonised with MRSA failed to respond to topical antimicrobial dressings. Following the combined use of octenilin Wound Gel and octenilin Wound Irrigation Solution, the MRSA was removed in 4 weeks, the necrotic tissue was debrided and the wound started healing. PMID:26949849

  4. Wound duration and healing rates: cause or effect?

    PubMed

    Bosanquet, David C; Harding, Keith G

    2014-01-01

    Multiple factors affect the likelihood of a wound healing. One of these factors, wound duration, is well known to be related to healing rates, with numerous publications showing that older wounds are less likely to heal. However, disentangling the effect of this factor on wound healing rates is complex. Is this simply an observation of the obvious; wounds of longer duration will by definition be harder to heal? Or does time represent an independent factor, implying that should treatments be given earlier in the disease process, better outcomes may result? This review summarizes the available evidence of the effects of wound duration on healing rates and examines potential biological aberrations identified in chronic wounds, which may be significant in making chronic wounds difficult to heal. Wounds of longer duration are associated with excessive inflammation, fibroblast senescence, and alterations in wound bed flora, which appears to have a temporal relationship. Early and aggressive treatment of ulcers that fail to respond to standard care may well aid in reducing the burden of wounds that become chronic.

  5. Collagen-Based Biomaterials for Wound Healing

    PubMed Central

    Chattopadhyay, Sayani; Raines, Ronald T.

    2014-01-01

    With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, non-toxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on-going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds. PMID:24633807

  6. Chronic wounds: management of healing and wellbeing.

    PubMed

    Grothier, Lorraine; Pardoe, Ann

    This article discusses the impact of living with a chronic wound including the individual's wellbeing and the need for clinicians to consider the complex and often challenging factors that can help or hinder the patient experience. Patient engagement in the care planning process is an important consideration in promoting concordance (Gray et al, 2011). When choosing a dressing regimen, clinical decision-making should be based on holistic assessment and include the patient's perspective, expectations and attitudes (Dowsett, 2008). Living with a chronic wound can have a significant impact on both the physical and psychological health of an individual and patients may suffer from multiple effects including reduced mobility, pain, poor nutrition and depression. Management plans that have been informed by patient feedback and are sensitive to their concerns can only serve to promote concordance and partnership and achieve a positive experience even when healing is not the endpoint.

  7. Evaluation of wound healing activity of some herbal formulations.

    PubMed

    Mukherjee, Pulok K; Mukherjee, Kakali; Rajesh Kumar, M; Pal, M; Saha, B P

    2003-03-01

    The wound healing activity of two herbal formulations (Himax ointment and lotion) containing Indradaru extract, i.e. Arjuna bark (Terminalia arjuna, Family-Combretaceae), extract was evaluated for its wound healing potential in two types of wound models in rats (i) excision wound model and (ii) incision wound model. Both the formulations responded significantly in both the wound models tested. The results were also comparable to that of the standard drug nitrofurazone used as a standard drug for comparison in this present investigation. The results were also comparable in terms of wound contracting ability, epithelization period, tensile strength and regeneration of tissues at the wound area. Thus, this investigation con fi rms the use of the Himax ointment and lotion containing Terminalia arjuna extract as a wound-healing agent as known from folklore medicine.

  8. Incisional wound healing in transforming growth factor-beta1 null mice.

    PubMed

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B

    2000-01-01

    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  9. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring. PMID:23746929

  10. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring.

  11. The wound healing, chronic fibrosis, and cancer progression triad

    PubMed Central

    Rybinski, Brad; Franco-Barraza, Janusz

    2014-01-01

    For decades tumors have been recognized as “wounds that do not heal.” Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing. PMID:24520152

  12. Adenosine receptor agonists for promotion of dermal wound healing

    PubMed Central

    Valls, María D.; Cronstein, Bruce N.; Montesinos, M. Carmen

    2009-01-01

    Wound healing is a dynamic and complex process that involves a well coordinated, highly regulated series of events including inflammation, tissue formation, revascularization and tissue remodeling. However, this orderly sequence is impaired in certain pathophysiological conditions such as diabetes mellitus, venous insufficiency, chronic glucocorticoid use, aging and malnutrition. Together with proper wound care, promotion of the healing process is the primary objective in the management of chronic poorly healing wounds. Recent studies have demonstrated that A2A adenosine receptor agonists promote wound healing in normal and diabetic animals and one such agonist, Sonedenoson, is currently being evaluated as a prospective new therapy of diabetic foot ulcers. We will review the mechanisms by which adenosine receptor activation affects the function of the cells and tissues that participate in wound healing, emphasizing the potential beneficial impact of adenosine receptor agonists in diabetic impaired healing. PMID:19041853

  13. Perceived stress and cortisol levels predict speed of wound healing in healthy male adults.

    PubMed

    Ebrecht, Marcel; Hextall, Justine; Kirtley, Lauren-Grace; Taylor, Alice; Dyson, Mary; Weinman, John

    2004-07-01

    The main purpose of the present study was to investigate the association between perceived stress and impaired cutaneous wound healing in humans using a novel wound assessment technique, and taking into account putative mediating factors such as cortisol levels, health behaviours, and personality factors. The study made use of a prospective, within-subjects design in which 24 male non-smokers participated. Every subject received a standard 4mm-punch biopsy, and the healing progress was monitored via high-resolution ultrasound scanning. Participants completed questionnaires on perceived stress, health behaviours, and personality factors, and sampled saliva for cortisol assessment after awakening at 2 weeks prior, directly after, and 2 weeks after the biopsy. The overall results showed a significant negative correlation between speed of wound healing, and both Perceived Stress scale (PSS) scores (r=-.59; p<.01), and General Health Questionnaire (GHQ) scores (r=-.59; p<.01) at the time of the biopsy. The area under the morning cortisol response curve was negatively correlated with speed of wound healing (r=-.55; p<.05), indicating a clear elevation in the morning cortisol slope of those whose wounds were slowest to heal. A median split of the complete sample yielded that the 'slow healing' group showed higher stress levels (PSS t=3.93, p<.01, GHQ t=2.50, p<.05), lower trait optimism (t=3.25, p<.05), and higher cortisol levels to awakening (F=5.60, p<.05) compared with the 'fast healing' group. None of the health behaviours investigated (i.e. alcohol consumption, exercise, healthy eating, and sleep) were correlated with healing speed at any time point. Our data hint at a considerable influence of stress on wound healing, and suggests that elevated cortisol levels, rather than altered health behaviours, play a role in this effect.

  14. Traditional Therapies for Skin Wound Healing

    PubMed Central

    Pereira, Rúben F.; Bártolo, Paulo J.

    2016-01-01

    Significance: The regeneration of healthy and functional skin remains a huge challenge due to its multilayer structure and the presence of different cell types within the extracellular matrix in an organized way. Despite recent advances in wound care products, traditional therapies based on natural origin compounds, such as plant extracts, honey, and larvae, are interesting alternatives. These therapies offer new possibilities for the treatment of skin diseases, enhancing the access to the healthcare, and allowing overcoming some limitations associated to the modern products and therapies, such as the high costs, the long manufacturing times, and the increase in the bacterial resistance. This article gives a general overview about the recent advances in traditional therapies for skin wound healing, focusing on the therapeutic activity, action mechanisms, and clinical trials of the most commonly used natural compounds. New insights in the combination of traditional products with modern treatments and future challenges in the field are also highlighted. Recent Advances: Natural compounds have been used in skin wound care for many years due to their therapeutic activities, including anti-inflammatory, antimicrobial, and cell-stimulating properties. The clinical efficacy of these compounds has been investigated through in vitro and in vivo trials using both animal models and humans. Besides the important progress regarding the development of novel extraction methods, purification procedures, quality control assessment, and treatment protocols, the exact mechanisms of action, side effects, and safety of these compounds need further research. Critical Issues: The repair of skin lesions is one of the most complex biological processes in humans, occurring throughout an orchestrated cascade of overlapping biochemical and cellular events. To stimulate the regeneration process and prevent the wound to fail the healing, traditional therapies and natural products have been used

  15. Application of hyaluronic acid in the healing of non-experimental open wounds: A pilot study on 12 wounds in 10 client-owned dogs

    PubMed Central

    Ferrari, Roberta; Boracchi, Patrizia; Romussi, Stefano; Ravasio, Giuliano; Stefanello, Damiano

    2015-01-01

    Aim: Veterinarians have frequently to deal with wounds to the skin, subcutis, and underlying muscle. The aim was to explore the application of hyaluronic acid (HA)-containing dressing on open skin wounds in dogs. The progress of healing was assessed by wound area reduction and two scoring scales applied in human medicine. Materials and Methods: Ten client-owned dogs with 12 cutaneous open wounds healed by the second intention were included. All wounds were treated using available in commerce HA-containing wound dressing from admission to complete re-epithelialization. At every clinical examination, wound area and scale scoring assessments were performed. Results: After debridement, an increased wound size was obtained while an improvement was determined by both grading systems. The median numbers of return to the clinic for bandage change were 5 times. The median time to complete wound healing was 34.5 days. The mean wound area at day 7, 14, 21, and 28 were, respectively, 90.4%, 47.7%, 22.4%, and 14.8% of the original size (for linear measurement) and 95.5%, 54.4%, 23.10%, and 14.8% of the original size (for software measurement). Regarding wound healing assessment tools, the agreement between two operators was considered high for both scales. Conclusions: HA-containing dressing may be a possible wound treatment for cutaneous open wounds in dogs. The assessment of wound quality using scale scoring system could be useful especially in the 1st week and to direct clinical decision-making process. PMID:27047026

  16. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

    PubMed Central

    Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

    2015-01-01

    Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction

  17. Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing

    PubMed Central

    Kalan, Lindsay; Loesche, Michael; Hodkinson, Brendan P.; Heilmann, Kristopher; Ruthel, Gordon

    2016-01-01

    ABSTRACT Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater (P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes. PMID:27601572

  18. Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.

    PubMed

    Boink, Mireille A; van den Broek, Lenie J; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan

    2016-01-01

    Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. PMID:26542883

  19. Advanced Therapeutic Dressings for Effective Wound Healing--A Review.

    PubMed

    Boateng, Joshua; Catanzano, Ovidio

    2015-11-01

    Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing because of the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer-reviewed literature and other publicly available sources such as the US FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic wounds (e.g., accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue-engineered substitutes, biomaterials-based biological dressings, biological and naturally derived dressings, medicated sutures, and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging physical approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care.

  20. Wound healing and all-cause mortality in 958 wound patients treated in home care.

    PubMed

    Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B E

    2015-09-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.

  1. [Wound healing after laser and red light irradiation].

    PubMed

    Hutschenreiter, G; Haina, D; Paulini, K; Schumacher, G

    1980-04-01

    Laser irradiation and red light irradiation, daily 2 respectively 4 J/cm2, do not bring any acceleration of wound healing in rats. No significant effect was evident in the cell pattern of wounds during various phases of healing through the irradiation. The tensile strength of cicatrices increased by laser irradiation, but not by red light irradiation (monochromatic lambda = 633 nm).

  2. Potato tuber wounding induces responses associated with various healing processes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wounding induces an avalanche of biological responses involved in the healing and protection of internal tuber tissues exposed by mechanical damage and seed cutting. Collectively, our studies have framed a portrait of the mechanisms and regulation of potato tuber wound-healing, but much more is req...

  3. [To ponder the key issues in achieving wound healing].

    PubMed

    Lu, Shuliang

    2014-04-01

    The understanding of the mechanism of wound healing is deepening. Key issues in the process of wound healing need to be seriously considered, i.e. how to establish the concept of application of phasic and selective means to promote wound healing according to the characteristics of a network and sequential process; to correctly assess the function and status of macrophages in wound healing and to explore the conditions of regulating timely infiltration of macrophages, as well as the phasic and orderly expression of type Iand type II macrophages; to properly understand the role and status of extracellular matrix components or the three-dimensional structure and morphology in wound healing; to elucidate the effects of wound microenvironment on the proliferation and differentiation of stem cells; to find out the intrinsic mechanism of negative pressure in the process of wound healing. The understanding of the above problems are of great value for us to grasp the intrinsic mechanism of wound healing in order to establish a more effective and rational treatment of wound.

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

    PubMed

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

    2014-05-01

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

  5. In vivo wound-healing effects of novel benzalkonium chloride-loaded hydrocolloid wound dressing.

    PubMed

    Jin, Sung Giu; Yousaf, Abid Mehmood; Jang, Sun Woo; Son, Mi-Won; Kim, Kyung Soo; Kim, Dong-Wuk; Li, Dong Xun; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2015-05-01

    The purpose of this study was to evaluate the wound-healing effects of a novel benzalkonium chloride (BC)-loaded hydrocolloid wound dressing (HCD). A BC-loaded HCD was prepared with various constituents using a hot melting method, and its mechanical properties and antimicrobial activities were assessed. The in vivo wound healings of the BC-loaded HCD in various would models were evaluated in rats compared with a commercial wound dressing, Duoderm™. This BC-loaded HCD gave better skin adhesion, swelling, mechanical strength, and flexibility compared with the commercial wound dressing. It showed excellent antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In addition, as compared with the commercial wound dressing, it showed more improved wound healings and tissue restoration effect on the excision, infection, and abrasion wounds in rats. Thus, this novel BC-loaded HCD would be an excellent alternative to the commercial wound dressing for treatment of various wounds.

  6. Wound healing activity of the inflorescence of Typha elephantina (Cattail).

    PubMed

    Panda, Vandana; Thakur, Tejas

    2014-03-01

    Methanolic extracts of Typha elephantina inflorescence (TE) and its bandage were screened for wound healing by incision and excision wound models in Wistar rats. In the incision wound model, incision wounds were topically treated with TE gel (2.0% [w/w], 3.0% [w/w], and 5.0% [w/w]), Typha elephantina inflorescence bandage, and the reference standard 5.0% w/w povidone iodine for a period of 10 days. When the wounds healed thoroughly, sutures were removed on the 8th postwounding day, and the tensile strength of the skin was measured on the 10th day. In the excision wound model, excision wounds were treated with TE gel (3.0% [w/w] and 5.0% [w/w]), inflorescence bandage, and 5.0% w/w povidone iodine till the wounds completely healed. Epithelization time, wound contraction, hydroxyproline and hexosamine content of the scab, and ascorbic acid and malondialdehyde content of the plasma were determined in this model. In the incision wound model, high tensile strength of the skin of the healed wound was observed in rats treated with the TE gels and the inflorescence bandage when compared with wounded control rats. The increase in tensile strength indicates a promotion of collagen fibers and a firm knitting of the disrupted wound surfaces by collagen. In the excision wound model, higher rate of wound contraction, decreased period of epithelization, elevated hydroxyproline, hexosamine, and ascorbic acid levels, and a significant decrease in malondialdehyde content was observed in treated groups when compared with the wounded control animals. It may be concluded that the inflorescence of Typha elephantina possesses a potent wound healing activity, which may be due to an underlying antioxidant mechanism.

  7. Enhanced healing of full-thickness burn wounds using di-rhamnolipid

    PubMed Central

    Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

    2006-01-01

    The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213

  8. Nod-like receptor protein-3 inflammasome plays an important role during early stages of wound healing.

    PubMed

    Weinheimer-Haus, Eileen M; Mirza, Rita E; Koh, Timothy J

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing.

  9. Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

    PubMed Central

    Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

  10. Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.

    PubMed

    Zimny, S; Pfohl, M

    2005-02-01

    Time line of wound healing and prediction of healing times in diabetic foot ulcers is an important issue. Usually, the percentage of wounds healed within a defined period is used for characterization of wound healing. R=sqrtA/pi (R, radius; A, planimetric wound area; pi, constant 3.14), and the wound radius reduction was 0.39 mm/week which was previously established. The initial average wound area was 96.9+/-13.1 mm2 (mean+/-SEM), and 3.61+/-1.6 mm 2 after ten weeks with an average healing time of 75.9 (95 %-CI 71-81) days. Using the equation mentioned above and the calculated weekly wound radius reduction, the predicted healing time in the test group was 86.9 (95 %-CI 73-101) days. The predicted and the observed healing times were significantly correlated with each other (r=0.55, p=0.0002). Providing standard care, the time needed for wound healing can reliably be predicted in neuropathic diabetic foot ulcers. This may be a useful tool in daily clinical practice to predict wound healing and recognize ulcers who do not respond adequately to the treatment. PMID:15772900

  11. Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study.

    PubMed

    Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

    2015-10-01

    It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we determined which patient- and wound-related characteristics best predict time to complete wound healing and derived a prediction formula to estimate how long this may take. We selected 563 patients with acute wounds, documented in the WEC registry between 2007 and 2012. Wounds had existed for a median of 19 days (range 6-46 days). The majority of these were located on the leg (52%). Five significant independent predictors of prolonged wound healing were identified: wound location on the trunk [hazard ratio (HR) 0·565, 95% confidence interval (CI) 0·405-0·788; P = 0·001], wound infection (HR 0·728, 95% CI 0·534-0·991; P = 0·044), wound size (HR 0·993, 95% CI 0·988-0·997; P = 0·001), wound duration (HR 0·998, 95% CI 0·996-0·999; P = 0·005) and patient's age (HR 1·009, 95% CI 1·001-1·018; P = 0·020), but not diabetes. Awareness of the five factors predicting the healing of complex acute wounds, particularly wound infection and location on the trunk, may help caregivers to predict wound healing time and to detect, refer and focus on patients who need additional attention.

  12. Promising role of ANGPTL4 gene in diabetic wound healing.

    PubMed

    Arya, Awadhesh K; Tripathi, Kamlakar; Das, Parimal

    2014-03-01

    Diabetes mellitus (DM) is one of the severe metabolic disorders of carbohydrate metabolism worldwide. Developing countries are at higher risk of DM, and there is significant evidence that it is epidemic in many economically developing and newly industrialized countries. Among all other complications associated with DM, delayed wound healing is a major concern in diabetic patients. Wound healing is a natural healing process that starts immediately after injury. This involves interaction of a complex cascade of cellular events that generates resurfacing, reconstitution, and restoration of the tensile strength of injured skin. There are multiple factors responsible for delayed wound healing among which the contribution of DM has been well documented. The wound healing process is also delayed by the metabolic, vascular, neurological, and inflammatory alterations, which are well known in both type 1 and type 2 diabetes. Keratinocytes are crucial for wound re-epithelialization, and defects in directed migration of keratinocytes due to DM are associated with the delayed wound healing process. Many factors responsible for re-epithelialization have been identified, characterized, and well described; however, the genes responsible for the healing process have only partially been illustrated. This article will therefore focus on the efficacy of ANGPTL4 (angiopoietin-like 4) gene, which plays a novel role in keratinocyte migration during wound healing.

  13. HoxD3 accelerates wound healing in diabetic mice

    SciTech Connect

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

    2003-12-01

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

  14. Wound Healing Effects of Curcumin: A Short Review.

    PubMed

    Tejada, Silvia; Manayi, Azadeh; Daglia, Maria; Nabavi, Seyed F; Sureda, Antoni; Hajheydari, Zohreh; Gortzi, Olga; Pazoki-Toroudi, Hamidreza; Nabavi, Seyed M

    2016-01-01

    Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed. PMID:27640646

  15. Benzoyl peroxide and epidermal wound healing.

    PubMed

    Alvarez, O M; Mertz, P M; Eaglstein, W H

    1983-03-01

    The effectiveness of 10%, 20%, and 50% benzoyl peroxide in a lotion, 20% benzoyl peroxide in a gel, and the effect of the vehicles alone on wound reepithelialization were evaluated in young domestic pigs. Twenty percent benzoyl peroxide suspension in a lotion base substantially increased the rate of reepithelialization by 33% over a seven-day evaluation period. Twenty percent benzoyl peroxide suspension in a gel base and 10% benzoyl peroxide suspension in a lotion base slightly enhanced epidermal resurfacing, while 50% benzoyl peroxide suspension in a lotion base and the vehicle gel retarded healing. Variations in the rate of reepithelialization were observed when different lots of 20% benzoyl peroxide lotions were compared. Chemical analysis of each of the 20% benzoyl peroxide preparations tested disclosed great differences in zinc, magnesium, and sodium content.

  16. Wound healing in glaucoma filtering surgery.

    PubMed

    Skuta, G L; Parrish, R K

    1987-01-01

    Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success.

  17. Electrospun nitric oxide releasing bandage with enhanced wound healing.

    PubMed

    Lowe, A; Bills, J; Verma, R; Lavery, L; Davis, K; Balkus, K J

    2015-02-01

    Research has shown that nitric oxide (NO) enhances wound healing. The incorporation of NO into polymers for medical materials and surgical devices has potential benefits for many wound healing applications. In this work, acrylonitrile (AN)-based terpolymers were electrospun to form non-woven sheets of bandage or wound dressing type materials. NO is bound to the polymer backbone via the formation of a diazeniumdiolate group. In a 14 day NO release study, the dressings released 79 μmol NO g(-1) polymer. The NO-loaded dressings were tested for NO release in vivo, which demonstrate upregulation of NO-inducible genes with dressing application compared to empty dressings. Studies were also conducted to evaluate healing progression in wounds with dressing application performed weekly and daily. In two separate studies, excisional wounds were created on the dorsa of 10 mice. Dressings with NO loaded on the fibers or empty controls were applied to the wounds and measurements of the wound area were taken at each dressing change. The data show significantly enhanced healing progression in the wounds with weekly NO application, which is more dramatic with daily application. Further, the application of daily NO bandages results in improved wound vascularity. These data demonstrate the potential for this novel NO-releasing dressing as a valid wound healing therapy. PMID:25463501

  18. Wound Healing and Anti-Inflammatory Effect in Animal Models of Calendula officinalis L. Growing in Brazil.

    PubMed

    Parente, Leila Maria Leal; Lino Júnior, Ruy de Souza; Tresvenzol, Leonice Manrique Faustino; Vinaud, Marina Clare; de Paula, José Realino; Paulo, Neusa Margarida

    2012-01-01

    Calendula officinalis is an annual herb from Mediterranean origin which is popularly used in wound healing and as an anti-inflammatory agent. In this study, the ethanolic extract, the dichloromethane, and hexanic fractions of the flowers from plants growing in Brazil were produced. The angiogenic activity of the extract and fractions was evaluated through the chorioallantoic membrane and cutaneous wounds in rat models. The healing activity of the extract was evaluated by the same cutaneous wounds model through macroscopic, morphometric, histopathologic, and immunohistochemical analysis. The antibacterial activity of the extract and fractions was also evaluated. This experimental study revealed that C. officinalis presented anti-inflammatory and antibacterial activities as well as angiogenic and fibroplastic properties acting in a positive way on the inflammatory and proliferative phases of the healing process. PMID:22315631

  19. An Assessment of Wound Healing Potential of Argyreia speciosa Leaves

    PubMed Central

    Yadav, Narayan Prasad; Rawat, Bindu; Rai, Vineet Kumar; Shanker, Karuna; Venkateswara Rao, Chandana

    2014-01-01

    In North India, poultice of young unfolded leaves of Argyreia speciosa Linn. (Convolvulaceae) is used for healing wounds. In order to find scientific evidence for the traditional utilization of leaves of A. speciosa in wound healing, this investigation was carried out. A linear incision wound of about 3 cm in length and 2 mm in depth and circular excision wound of 177 mm2 full thickness were made on the dorsal region of separate groups (n = 5) of anesthetized Swiss albino mice. A simple ointment, developed by including ethanol, ethanol-water, and water extracts (10% each, separately) of A. speciosa, was applied topically to mice once daily for 14 days after wounding. To evaluate the effect of each extract, wound contraction, epithelization period, wound breaking strength, and hydroxyproline content were determined. The water extract of A. speciosa showed accelerated wound healing activity as evidenced by fast wound contraction (96.30 ± 0.52%; P < 0.01), rapid epithelization period (11.40 ± 0.60 days; P < 0.001), greater wound breaking strength (376.56 ± 21.16 g; P < 0.001), and higher hydroxyproline content (16.49 ± 1.12 mg/g; P < 0.05) of granulation tissue. The present report supports the traditional use of Argyreia speciosa leaves for wound healing and signify its relevant therapeutic potential. PMID:24688387

  20. Fibroblast-loaded cholecyst-derived scaffold induces faster healing of full thickness burn wound in rabbit.

    PubMed

    Revi, Deepa; Geetha, C; Thekkuveettil, Anoopkumar; Anilkumar, Thapasimuthu V

    2016-02-01

    Graft-assisted healing is often proposed for clinical management of large-sized third-degree cutaneous burn wounds. Skin-graft substitutes prepared by loading appropriate cell types on suitable scaffolds have been found successful. We have previously shown that cholecyst-derived scaffold prepared by a non-detergent/enzymatic method can be used as skin-graft substitute for promoting healing of full thickness excision wounds in rabbit. This article examines the use of this scaffold for preparing bio-artificial grafts by loading homologous fibroblasts. The healing potential was evaluated in a rabbit model of full thickness skin-burn wound. The healing process was evaluated by gross morphology evaluation and histomorphology evaluation at 7, 14 and 28 days of healing. Ex vivo imaging of the wounded tissue was performed and it was found that the loaded fibroblasts remained viable at least for 14 days in the healing wound. By the first week, re-epithelialisation was evident in all animals treated with the cell-loaded graft. Histomorphological wound healing parameters such as the quickness of re-epithelialisation, the nature of collagen deposition and the extent of neo-vascularisation indicated that cell-loaded grafts promoted faster healing of the wounds. Results of immunohistochemistry indicated a parallel change in the number of proliferating cells and myofibroblast in the healing tissue. Although the pathophysiology of the healing reaction was not established, the observations suggested that homologus fibroblast-loaded cholecyst-derived scaffold promoted faster healing of third-degree wounds in rabbit model by modulating myofibroblast response. It was concluded that cholecyst-derived scaffold prepared by the non-detergent/enzymatic method is a potential scaffold for fabricating bioartificial skin grafts. PMID:26589297

  1. Silver-based wound dressings reduce bacterial burden and promote wound healing.

    PubMed

    Lin, Yu-Hsin; Hsu, Wei-Shan; Chung, Wan-Yu; Ko, Tse-Hao; Lin, Jui-Hsiang

    2016-08-01

    Various types of wound dressings have been designed for different purposes and functions. Controlling bacterial burden in a wound during the early phase is important for successful wound repair. Once bacterial burden is under control, the active promotion of wound healing is another important factor for efficient wound healing. This study investigated the potential of three silver-containing dressings, namely KoCarbonAg(®) , Aquacel(®) Ag and Acticoat 7, in reducing bacterial survival and promoting wound healing. The ability of these dressings to block the entry of bacteria from external environment and retain intrinsic bacteria was studied in vitro. In addition, the study used a rat model to compare the healing efficiencies of the three dressings and investigate the quantity of collagen synthesis in vivo. In vitro results indicated that the silver-containing dressings prevented bacterial growth in wounds by blocking the entry of external bacteria and by retaining the bacteria in the dressing. In vivo study indicated that reduction in bacterial burden accelerated wound healing. Wounds treated by the silver-containing dressings showed better healing than those treated with gauze. Moreover, KoCarbonAg(®) further accelerated wound healing by promoting collagen synthesis and arrangement.

  2. Development of a wound healing index for patients with chronic wounds.

    PubMed

    Horn, Susan D; Fife, Caroline E; Smout, Randall J; Barrett, Ryan S; Thomson, Brett

    2013-01-01

    Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p < 0.05) were determined and subsequently tested on a holdout sample of data. A different model predicted healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics.

  3. Effects of topical oxygen therapy on ischemic wound healing.

    PubMed

    Rao, Congqiang; Xiao, Liling; Liu, Hongwei; Li, Shenghong; Lu, Jinqiang; Li, Jiangxuan; Gu, Shixing

    2016-01-01

    [Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing.

  4. Role of adipose-derived stem cells in wound healing.

    PubMed

    Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

    2014-01-01

    Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration.

  5. Potential of oncostatin M to accelerate diabetic wound healing.

    PubMed

    Shin, Soo Hye; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2014-08-01

    Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.

  6. Wounding the cornea to learn how it heals.

    PubMed

    Stepp, Mary Ann; Zieske, James D; Trinkaus-Randall, Vickery; Kyne, Briana M; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Pajoohesh-Ganji, Ahdeah

    2014-04-01

    Corneal wound healing studies have a long history and rich literature that describes the data obtained over the past 70 years using many different species of animals and methods of injury. These studies have lead to reduced suffering and provided clues to treatments that are now helping patients live more productive lives. In spite of the progress made, further research is required since blindness and reduced quality of life due to corneal scarring still happens. The purpose of this review is to summarize what is known about different types of wound and animal models used to study corneal wound healing. The subject of corneal wound healing is broad and includes chemical and mechanical wound models. This review focuses on mechanical injury models involving debridement and keratectomy wounds to reflect the authors' expertise.

  7. Wounding the Cornea to Learn How it Heals

    PubMed Central

    Stepp, Mary Ann; Zieske, James D.; Trinkaus-Randall, Vickery; Kyne, Briana; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Pajoohesh-Ganji, Ahdeah

    2014-01-01

    Corneal wound healing studies have a long history and rich literature that describes the data obtained over the past 70 years using many different species of animals and methods of injury. These studies have lead to reduced suffering and provided clues to treatments that are now helping patients live more productive lives. In spite of the progress made, further research is required since blindness and reduced quality of life due to corneal scarring still happens. The purpose of this review is to summarize what is known about different types of wound and animal models used to study corneal wound healing. The subject of corneal wound healing is broad and includes chemical and mechanical wound models. This review focuses on mechanical injury models involving debridement and keratectomy wounds to reflect the authors’ expertise. PMID:24607489

  8. An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing.

    PubMed

    Kanokpanont, Sorada; Damrongsakkul, Siriporn; Ratanavaraporn, Juthamas; Aramwit, Pornanong

    2012-10-15

    In this study, the novel silk fibroin-based bi-layered wound dressing was developed. Wax-coated silk fibroin woven fabric was introduced as a non-adhesive layer while the sponge made of sericin and glutaraldehyde-crosslinked silk fibroin/gelatin was fabricated as a bioactive layer. Wax-coated silk fibroin fabrics showed improved mechanical properties compared with the non-coated fabrics, but less adhesive than the commercial wound dressing mesh. This confirmed by results of peel test on both the partial- and full-thickness wounds. The sericin-silk fibroin/gelatin spongy bioactive layers showed homogeneous porous structure and controllable biodegradation depending on the degree of crosslinking. The bi-layered wound dressings supported the attachment and proliferation of L929 mouse fibroblasts, particularly for the silk fibroin/gelatin ratio of 20/80 and 0.02% GA crosslinked. Furthermore, we proved that the bi-layered wound dressings promoted wound healing in full-thickness wounds, comparing with the clinically used wound dressing. The wounds treated with the bi-layered wound dressings showed the greater extent of wound size reduction, epithelialization, and collagen formation. The superior properties of the silk fibroin-based bi-layered wound dressings compared with those of the clinically used wound dressings were less adhesive and had improved biological functions to promote cell activities and wound healing. This novel bi-layered wound dressing should be a good candidate for the healing of full-thickness wounds.

  9. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications

    PubMed Central

    Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

    2015-01-01

    The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration. PMID:26512657

  10. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications.

    PubMed

    Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

    2015-10-23

    The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

  11. Chitosan as a starting material for wound healing applications.

    PubMed

    Patrulea, V; Ostafe, V; Borchard, G; Jordan, O

    2015-11-01

    Chitosan and its derivatives have attracted great attention due to their properties beneficial for application to wound healing. The main focus of the present review is to summarize studies involving chitosan and its derivatives, especially N,N,N-trimethyl-chitosan (TMC), N,O-carboxymethyl-chitosan (CMC) and O-carboxymethyl-N,N,N-trimethyl-chitosan (CMTMC), used to accelerate wound healing. Moreover, formulation strategies for chitosan and its derivatives, as well as their in vitro, in vivo and clinical applications in wound healing are described.

  12. Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice

    PubMed Central

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M.; Huttner, Wieland; Weidemann, Alexander

    2013-01-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds. PMID:23798557

  13. Healing of Chronic Wounds through Systemic Effects of Electromagnetic Fields

    NASA Astrophysics Data System (ADS)

    Cañedo, L.; Trigos, I.; García-Cantú, R.; Godina-Nava, J. J.; Serrano, G.

    2002-08-01

    Extremely low frequency electromagnetic fields (ELF) were configured to interact with peripheral blood mononuclear cells (PBMC). These ELF were applied in the arm to five patients with chronic wounds resistant to medical and surgical treatment. Wound healing began in all patients during the first two weeks after ELF exposure permiting their previously unresponsive chronic wounds to function as internal controls. All lesions were cured or healed >70% in less than four months. Systemic effects were explained by ELF activation of PBMC and their transportation through the blood to the affected site. This therapy is effective in selected patients with chronic wounds.

  14. Potency of umbilical cord blood- and Wharton’s jelly-derived mesenchymal stem cells for scarless wound healing

    PubMed Central

    Doi, Hanako; Kitajima, Yuriko; Luo, Lan; Yan, Chan; Tateishi, Seiko; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Mori, Ryoichi; Masuzaki, Hideaki; Shimokawa, Isao; Hirano, Akiyoshi; Li, Tao-Sheng

    2016-01-01

    Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton’s jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 105 UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation. PMID:26728342

  15. Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

    PubMed

    Doi, Hanako; Kitajima, Yuriko; Luo, Lan; Yan, Chan; Tateishi, Seiko; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Mori, Ryoichi; Masuzaki, Hideaki; Shimokawa, Isao; Hirano, Akiyoshi; Li, Tao-Sheng

    2016-01-01

    Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation. PMID:26728342

  16. Immunonutrition: Role in Wound Healing and Tissue Regeneration.

    PubMed

    Chow, Oliver; Barbul, Adrian

    2014-01-01

    Significance: The role of immunonutrition in wound healing has been an area of both interest and controversy for many years. Although deficiencies in certain nutrients have long been known to impair healing, supplementation of specific immune modulating nutrients has not consistently yielded improvements in wound healing. Still, the prospect of optimizing nutrition to assist the immune system in wound repair bears great significance in both medical and surgical fields, as the costs of wound care and repair cannot be ignored. Recent Advances: Recent studies have rekindled efforts to elucidate the roles of specific immunonutrients, and we now have a better understanding of the conditionally essential role of various nutrients such as arginine, which becomes essential in certain clinical situations such as for the trauma patient or patients at high risk for malnutrition. Immunonutrition in its current formulation usually includes supplementation with arginine, glutamine, omega-3 fatty acids, vitamins, and trace minerals, and its use has often been associated with decreased infectious complications and sometimes with improvements in wound healing. Critical Issues: A key to understanding the role of immunonutrition in wound healing is recognizing the distinct contributions and importance of the various elements utilized. Future Directions: Critical areas for future study include identifying the specific populations, timing, and ideal composition of immunomodulating diets in order to optimize the wound healing process.

  17. Wound Healing Potential of Formulated Extract from Hibiscus Sabdariffa Calyx

    PubMed Central

    Builders, P. F.; Kabele-Toge, B.; Builders, M.; Chindo, B. A.; Anwunobi, Patricia A.; Isimi, Yetunde C.

    2013-01-01

    Wound healing agents support the natural healing process, reduce trauma and likelihood of secondary infections and hasten wound closure. The wound healing activities of water in oil cream of the methanol extract of Hibiscus sabdariffa L. (Malvaceae) was evaluated in rats with superficial skin excision wounds. Antibacterial activities against Pseudomonas aeroginosa, Staphylococcus aureus and Echerichia coli were determined. The total flavonoid content, antioxidant properties and thin layer chromatographic fingerprints of the extract were also evaluated. The extract demonstrated antioxidant properties with a total flavonoid content of 12.30±0.09 mg/g. Six reproducible spots were obtained using methanol:water (95:5) as the mobile phase. The extract showed no antimicrobial activity on the selected microorganisms, which are known to infect and retard wound healing. Creams containing H. sabdariffa extract showed significant (P<0.05) and concentration dependent wound healing activities. There was also evidence of synergism with creams containing a combination of gentamicin and H. sabdariffa extract. This study, thus, provides evidence of the wound healing potentials of the formulated extract of the calyces of H. sabdariffa and synergism when co-formulated with gentamicin. PMID:23901160

  18. Immunonutrition: Role in Wound Healing and Tissue Regeneration

    PubMed Central

    Chow, Oliver; Barbul, Adrian

    2014-01-01

    Significance: The role of immunonutrition in wound healing has been an area of both interest and controversy for many years. Although deficiencies in certain nutrients have long been known to impair healing, supplementation of specific immune modulating nutrients has not consistently yielded improvements in wound healing. Still, the prospect of optimizing nutrition to assist the immune system in wound repair bears great significance in both medical and surgical fields, as the costs of wound care and repair cannot be ignored. Recent Advances: Recent studies have rekindled efforts to elucidate the roles of specific immunonutrients, and we now have a better understanding of the conditionally essential role of various nutrients such as arginine, which becomes essential in certain clinical situations such as for the trauma patient or patients at high risk for malnutrition. Immunonutrition in its current formulation usually includes supplementation with arginine, glutamine, omega-3 fatty acids, vitamins, and trace minerals, and its use has often been associated with decreased infectious complications and sometimes with improvements in wound healing. Critical Issues: A key to understanding the role of immunonutrition in wound healing is recognizing the distinct contributions and importance of the various elements utilized. Future Directions: Critical areas for future study include identifying the specific populations, timing, and ideal composition of immunomodulating diets in order to optimize the wound healing process. PMID:24761344

  19. Fibroblast-specific upregulation of Flightless I impairs wound healing.

    PubMed

    Turner, Christopher T; Waters, James M; Jackson, Jessica E; Arkell, Ruth M; Cowin, Allison J

    2015-09-01

    The cytoskeletal protein Flightless (Flii) is a negative regulator of wound healing. Upregulation of Flii is associated with impaired migration, proliferation and adhesion of both fibroblasts and keratinocytes. Importantly, Flii translocates from the cytoplasm to the nucleus in response to wounding in fibroblasts but not keratinocytes. This cell-specific nuclear translocation of Flii suggests that Flii may directly regulate gene expression in fibroblasts, providing one potential mechanism of action for Flii in the wound healing response. To determine whether the tissue-specific upregulation of Flii in fibroblasts was important for the observed inhibitory effects of Flii on wound healing, an inducible fibroblast-specific Flii overexpressing mouse model was generated. The inducible ROSA26 system allowed the overexpression of Flii in a temporal and tissue-specific manner in response to tamoxifen treatment. Wound healing in the inducible mice was impaired, with wounds at day 7 postwounding significantly larger than those from non-inducible controls. There was also reduced collagen maturation, increased myofibroblast infiltration and elevated inflammation. The impaired healing response was similar in magnitude to that observed in mice with non-tissue-specific upregulation of Flii suggesting that fibroblast-derived Flii may have an important role in the wound healing response.

  20. New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications

    PubMed Central

    Abdullah, Md Farooque; Das, Suvadra; Roy, Partha; Datta, Sriparna; Mukherjee, Arup

    2013-01-01

    Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (P < 0.05). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation. PMID:24175306

  1. Muscle wound healing in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Schmidt, J G; Andersen, E W; Ersbøll, B K; Nielsen, M E

    2016-01-01

    We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β1 and -β3, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least partially due to the low temperature of about 8.5 °C during the first 100 days. The inflammation phase lasted more than 14 days, and the genes relating to production and remodeling of new extracellular matrix (ECM) exhibited a delayed but prolonged upregulation starting 1-2 weeks post-wounding and lasting until at least 100 days post-wounding. The gene expression patterns and histology reveal limited capacity for muscle regeneration in rainbow trout, and muscle texture analyses one year after wound infliction confirm that wounds heal with fibrosis. At 100 dpw epidermis had fully regenerated, and dermis partially regenerated. Scales had not regenerated even after one year. CD163 is a marker of "wound healing"-type M2c macrophages in mammals. M2 macrophage markers are as yet poorly described in fish. The pattern of CD163 expression in the present study is consistent with the expected timing of presence of M2c macrophages in the wound. CD163 may thus potentially prove a valuable marker of M2 macrophages - or a subset hereof - in fish. We subjected a group of fish to

  2. Orientation and shape dependence of embryonic wound healing

    NASA Astrophysics Data System (ADS)

    Lynch, Holley; Ma, Xiaoyan; Hutson, M. Shane

    2007-11-01

    Wounds in embryonic epithelia heal without scarring. They do so via the combined action of two cytoskeletal structures: an actin-rich supracellular purse-string at the wound margin; and actin-based projections like filopodia. Neither structure is absolutely required for wound closure and their relative importance depends strongly on wound shape. To further investigate this dependence, we have followed the healing process in fruit fly embryos using confocal microscopy after precise laser incisions. The wound shape and rate of healing depend on the orientation of the incision. Cuts along the long axis of the embryo initially expand to greater areas and round up. Cuts along the short axis expand less and remain elliptical. These short-axis wounds heal more quickly and in a different manner. For such cuts, cellular projections tend to bridge across the ends of the wound. After such bridges are formed, the smaller holes (towards the ends of the wound) close quickly. On the other hand, for cuts along the long axis, the cellular projections tend to bridge across the middle of the wound -- often leaving two to three holes of similar size that then close independently at similar rates.

  3. [Poorly healing periorbital wounds. Therapeutic use of maggots].

    PubMed

    Pitz, S; Renieri, G; Gericke, A

    2012-05-01

    The treatment of poorly healing wounds, although not a typical problem in the periorbital area, has been enriched by the option of biosurgery, the therapeutic application of larvae of the blow fly (Lucilia sericata).

  4. Wound-healing error model for radon carcinogenesis

    SciTech Connect

    Kondo, Sohei

    1995-12-31

    Epidemiological studies of lung cancer in uranium miners exposed to radon suggest that radon is a tumor promoter. I will refine this notion by applying the wound-healing error model proposed for radiation carcinogenesis in general.

  5. Investigating Wound Healing in Plant Cells: This Spud's for You!

    ERIC Educational Resources Information Center

    Thomson, Norm

    2000-01-01

    Presents classroom inquiry-based investigations to investigate wound healing in plant tissues and cells. Students create their own research problems and the investigations can be related to the National Science Standards. (SAH)

  6. Negative pressure wound therapy promotes vessel destabilization and maturation at various stages of wound healing and thus influences wound prognosis

    PubMed Central

    MA, ZHANJUN; SHOU, KANGQUAN; LI, ZONGHUAN; JIAN, CHAO; QI, BAIWEN; YU, AIXI

    2016-01-01

    Negative pressure wound therapy (NPWT) has been observed to accelerate the wound healing process in humans through promoting angiogenesis. However, the potential biological effect and relevant molecular mechanisms, including microvessel destabilization, regression and endothelial cell proliferation in the early stage (1–3 days), and the neovascular stabilization and maturation in the later stage (7–15 days), have yet to be fully elucidated. The current study aimed to research the potential effect of NPWT on angiogenesis and vessel maturation, and investigate relevant association between mature microvessels and wound prognosis, as well as the regulatory mechanisms in human wound healing. Patients in the present study (n=48) were treated with NPWT or a petrolatum gauze, and relevant growth factors and vessel changes were detected using various experimental methods. NPWT increased the expression levels of angiogenin-2 (Ang-2), and decreased the expression levels of Ang-1 and ratios of Ang-1/Ang-2 in the initial stages of wound healing. However, in the latter stages of wound healing, NPWT increased the expression levels of Ang-1 and ratios of Ang-1/Ang-2, as well as the phosphorylation level of tyrosine kinase receptor-2. Consequently, microvessel pericyte coverage was gradually elevated, and the basement membrane was gradually supplied with new blood at the later stage of wound healing. In conclusion, NPWT may preferentially stimulate microvessel destabilization and regression in the early stage of wound healing, and as a consequence, increase angiogenesis. Subsequently, in the later stage of wound healing, NPWT may preferentially promote microvessel stabilization, thereby promoting microvessel maturation in human wounds through the angiogenin/tyrosine kinase receptor-2 signaling pathway. The results of the present study results demonstrated that NPWT was able to accelerate wound healing speed, and thus influence wound prognosis, as a result of an abundance of

  7. Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing.

    PubMed

    Pradhan, Leena; Cai, Xuemei; Wu, Szuhuei; Andersen, Nicholas D; Martin, Michelle; Malek, Junaid; Guthrie, Patrick; Veves, Aristidis; Logerfo, Frank W

    2011-05-15

    The interaction between neuropeptides and cytokines and its role in cutaneous wound healing is becoming evident. The goal of the present study is to investigate the impact of diabetes on peripheral cytokine and neuropeptide expression and its role in diabetic wound healing. To achieve this goal, the effect of diabetes on wound healing, along with the role of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) secreted in the wound microenvironment, and neuropeptides such as substance P (SP) and neuropeptide Y (NPY), secreted from peripheral nerves is monitored in non-diabetic and diabetic rabbits. Rabbits in the diabetic group received alloxan monohydrate (100mg/kg i.v.). Ten days after diabetic induction, four full thickness circular wounds were created in both ears using a 6mm punch biopsy. Wound healing was monitored over 10 d and gene expression of cytokines and neuropeptides was assessed in the wounds. Compared with the non-diabetic rabbits, wounds of diabetic rabbits heal significantly slower. Diabetic rabbits show significantly increased baseline gene expression of IL-6 and IL-8, their receptors, CXCR1, CXCR2, GP-130, and a decrease of prepro tachykinin-A (PP-TA), the precursor of SP, whereas the expression of prepro-NPY (PP-NPY), the precursor of NPY is not different. Similarly, baseline protein expression of CXCR1 is higher in diabetic rabbit skin. Post-injury, the increase over baseline gene expression of IL-6, IL-8, CXCR1, CXCR2, and GP-130 is significantly less in diabetic wounds compared with non-diabetic wounds. Although there is no difference in PP-TA gene expression between non-diabetic and diabetic rabbits post-injury, the gene expression of PP-NPY is reduced in diabetic rabbits. In conclusion, diabetes causes dysregulation in the neuropeptide expression in the skin along with a suppressed focused inflammatory response to injury. This suggests that the chronic inflammation in the skin of diabetic rabbits inhibits the acute

  8. [A telemedicine consultation in the framework of a wound and wound healing network].

    PubMed

    Perrier-Bonnet, Sabine

    2016-01-01

    I: n Languedoc-Roussillon, the Domoplaies telemedicine project provides support to nurses experiencing difficulties with the treatment of a wound at home or in a health institute. Thanks to new communication and information technologies, doctors and nurses with expertise in wounds and wound healing can offer individualised care management. PMID:27633698

  9. Wound healing after radiation therapy: Review of the literature

    PubMed Central

    2012-01-01

    Radiation therapy is an established modality in the treatment of head and neck cancer patients. Compromised wound healing in irradiated tissues is a common and challenging clinical problem. The pathophysiology and underlying cellular mechanisms including the complex interaction of cytokines and growth factors are still not understood completely. In this review, the current state of research regarding the pathomechanisms of compromised wound healing in irradiated tissues is presented. Current and possible future treatment strategies are critically reviewed. PMID:23006548

  10. Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model.

    PubMed

    Lin, Li-Xin; Wang, Peng; Wang, Yu-Ting; Huang, Yong; Jiang, Lei; Wang, Xue-Ming

    2016-02-01

    Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1β in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing. PMID:26677006

  11. Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model.

    PubMed

    Lin, Li-Xin; Wang, Peng; Wang, Yu-Ting; Huang, Yong; Jiang, Lei; Wang, Xue-Ming

    2016-02-01

    Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1β in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing.

  12. The Impact of Lipoproteins on Wound Healing: Topical HDL Therapy Corrects Delayed Wound Healing in Apolipoprotein E Deficient Mice

    PubMed Central

    Gordts, Stephanie C.; Muthuramu, Ilayaraja; Amin, Ruhul; Jacobs, Frank; Geest, Bart De

    2014-01-01

    Chronic non-healing wounds lead to considerable morbidity and mortality. Pleiotropic effects of high density lipoproteins (HDL) may beneficially affect wound healing. The objectives of this murine study were: (1) to investigate the hypothesis that hypercholesterolemia induces impaired wound healing and (2) to study the effect of topical HDL administration in a model of delayed wound healing. A circular full thickness wound was created on the back of each mouse. A silicone splint was used to counteract wound contraction. Coverage of the wound by granulation tissue and by epithelium was quantified every 2 days. Re-epithelialization from day 0 till day 10 was unexpectedly increased by 21.3% (p < 0.05) in C57BL/6 low density lipoprotein (LDLr) deficient mice with severe hypercholesterolemia (489 ± 14 mg/dL) compared to C57BL/6 mice and this effect was entirely abrogated following cholesterol lowering adenoviral LDLr gene transfer. In contrast, re-epithelialization in hypercholesterolemic (434 ± 16 mg/dL) C57BL/6 apolipoprotein (apo) E−/− mice was 22.6% (p < 0.0001) lower than in C57BL/6 mice. Topical HDL gel administered every 2 days increased re-epithelialization by 25.7% (p < 0.01) in apo E−/− mice. In conclusion, topical HDL application is an innovative therapeutic strategy that corrects impaired wound healing in apo E−/− mice. PMID:24705596

  13. Intracellular Adenosine Triphosphate Delivery Enhanced Skin Wound Healing in Rabbits

    PubMed Central

    Wang, Jianpu; Zhang, Qunwei; Wan, Rong; Mo, Yiqun; Li, Ming; Tseng, Michael T.; Chien, Sufan

    2016-01-01

    Small unilamellar lipid vesicles were used to encapsulate adenosine triphosphate (ATP-vesicles) for intracellular energy delivery. This technique was tested in full-thickness skin wounds in 16 adult rabbits. One ear was rendered ischemic by using a minimally invasive surgery. The other ear served as a normal control. Four circular full-thickness wounds were created on the ventral side of each ear. ATP-vesicles or saline was used and the wounds were covered with Tegaderm (3M, St. Paul, MN). Dressing was changed and digital photos were taken daily until all the wounds were healed. The mean healing times of ATP-vesicles–treated wounds were significantly shorter than that of saline-treated wounds on ischemic and nonischemic ears. Histologic study indicated better-developed granular tissue and reepithelial-ization in the ATP-vesicles–treated wounds. The wounds treated by ATP-vesicles exhibited extremely fast granular tissue growth. More CD31 positive cells were seen in the ATP-vesicles–treated wounds. This preliminary study shows that direct intracellular delivery of ATP can accelerate the healing process of skin wounds on ischemic and nonischemic rabbit ears. The extremely fast granular tissue growth was something never seen or reported in the past. PMID:19158531

  14. Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

    SciTech Connect

    Kioka, Noriyuki; Ito, Takuya; Yamashita, Hiroshi; Uekawa, Natsuko; Umemoto, Tsutomu; Motoyoshi, Soh; Imai, Hiroshi; Takahashi, Kenzo; Watanabe, Hideto; Yamada, Masayasu; Ueda, Kazumitsu

    2010-06-10

    In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.

  15. In vivo wound healing and antiulcer properties of white sweet potato (Ipomoea batatas).

    PubMed

    Hermes, Daniele; Dudek, Débora N; Maria, Mariana D; Horta, Lívia P; Lima, Eliete N; de Fátima, Ângelo; Sanches, Andréia C C; Modolo, Luzia V

    2013-07-01

    The potential of tuber flour of Ipomoea batatas (L.) Lam. cv. Brazlândia Branca (white sweet potato) as wound healing and antiulcerogenic agent was investigated in vivo in animal model. Excision on the back of Wistar rats was performed to induce wounds that were topically treated with Beeler's base containing tuber flour of white sweet potato at 2.5%. Number of cells undergoing metaphase and the degree of tissue re-epithelialization were investigated 4, 7 and 10 days post-treatment. The protective effect of aqueous suspension of tuber flour (75 and 100 mg/kg animal weight) on gastric mucosa of Wistar rats was also studied by using the ethanol-induced ulceration model. Ointment based on white sweet potato at 2.5% effectively triggered the healing of cutaneous wound as attested by the increased number of cells undergoing metaphase and tissue re-epithelialization regardless the time of wound treatment. Tuber flour potentially prevented ethanol-induced gastric ulceration by suppressing edema formation and partly protecting gastric mucosa wrinkles. Crude extracts also exhibited potential as free radical scavengers. The results from animal model experiments indicate the potential of tuber flour of white sweet potato to heal wounds.

  16. In vivo wound healing and antiulcer properties of white sweet potato (Ipomoea batatas)

    PubMed Central

    Hermes, Daniele; Dudek, Débora N.; Maria, Mariana D.; Horta, Lívia P.; Lima, Eliete N.; de Fátima, Ângelo; Sanches, Andréia C.C.; Modolo, Luzia V.

    2012-01-01

    The potential of tuber flour of Ipomoea batatas (L.) Lam. cv. Brazlândia Branca (white sweet potato) as wound healing and antiulcerogenic agent was investigated in vivo in animal model. Excision on the back of Wistar rats was performed to induce wounds that were topically treated with Beeler’s base containing tuber flour of white sweet potato at 2.5%. Number of cells undergoing metaphase and the degree of tissue re-epithelialization were investigated 4, 7 and 10 days post-treatment. The protective effect of aqueous suspension of tuber flour (75 and 100 mg/kg animal weight) on gastric mucosa of Wistar rats was also studied by using the ethanol-induced ulceration model. Ointment based on white sweet potato at 2.5% effectively triggered the healing of cutaneous wound as attested by the increased number of cells undergoing metaphase and tissue re-epithelialization regardless the time of wound treatment. Tuber flour potentially prevented ethanol-induced gastric ulceration by suppressing edema formation and partly protecting gastric mucosa wrinkles. Crude extracts also exhibited potential as free radical scavengers. The results from animal model experiments indicate the potential of tuber flour of white sweet potato to heal wounds. PMID:25685447

  17. Effect of 15-hydroxyprostaglandin dehydrogenase inhibitor on wound healing.

    PubMed

    Seo, Seung Yong; Han, Song-Iy; Bae, Chun Sik; Cho, Hoon; Lim, Sung Chul

    2015-06-01

    PGE2 is an important mediator of wound healing. It is degraded and inactivated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Various growth factors, type IV collagen, TIMP-2 and PGE2 are important mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring. If we make the condition downregulating growth factors and upregulating PGE2, the wound will have a positive effect which results in little scar formation after healing. TD88 is a 15-PGDH inhibitor based on thiazolinedione structure. We evaluated the effect of TD88 on wound healing. In 10 guinea pigs (4 control and 6 experimental groups), we made four 1cm diameter-sized circular skin defects on each back. TD88 and vehicle were applicated on the wound twice a day for 4 days in the experimental and control groups, respectively. Tissue samples were harvested for qPCR and histomorphometric analyses on the 2nd and 4th day after treatment. Histomorphometric analysis showed significant reepithelization in the experimental group. qPCR analysis showed significant decrease of PDGF, CTGF and TIMP-2, but significant increase of type IV collagen in the experimental group. Taken together TD88 could be a good effector on wound healing, especially in the aspects of prevention of scarring.

  18. Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing.

    PubMed

    Yu, Hongfei; Peng, Jinliang; Xu, Yuhong; Chang, Jiang; Li, Haiyan

    2016-01-13

    Wound healing is a complicated process, and fibroblast is a major cell type that participates in the process. Recent studies have shown that bioglass (BG) can stimulate fibroblasts to secrete a multitude of growth factors that are critical for wound healing. Therefore, we hypothesize that BG can stimulate fibroblasts to have a higher bioactivity by secreting more bioactive growth factors and proteins as compared to untreated fibroblasts, and we aim to construct a bioactive skin tissue engineering graft for wound healing by using BG activated fibroblast sheet. Thus, the effects of BG on fibroblast behaviors were studied, and the bioactive skin tissue engineering grafts containing BG activated fibroblasts were applied to repair the full skin lesions on nude mouse. Results showed that BG stimulated fibroblasts to express some critical growth factors and important proteins including vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, collagen I, and fibronectin. In vivo results revealed that fibroblasts in the bioactive skin tissue engineering grafts migrated into wound bed, and the migration ability of fibroblasts was stimulated by BG. In addition, the bioactive BG activated fibroblast skin tissue engineering grafts could largely increase the blood vessel formation, enhance the production of collagen I, and stimulate the differentiation of fibroblasts into myofibroblasts in the wound site, which would finally accelerate wound healing. This study demonstrates that the BG activated skin tissue engineering grafts contain more critical growth factors and extracellular matrix proteins that are beneficial for wound healing as compared to untreated fibroblast cell sheets.

  19. Wound healing and hyper-hydration: a counterintuitive model.

    PubMed

    Rippon, M G; Ousey, K; Cutting, K F

    2016-02-01

    Winter's seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle, confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model 'hyper-hydration' of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration. Declaration of interest: K. Cutting is a Clinical Research Consultant to the medical device and biotechnology industry. M. Rippon is Visiting Clinical Research Fellow, University of Huddersfield and K. Ousey provides consultancy for a range of companies through the University of Huddersfield including consultancy services for Paul Hartmann Ltd on HydroTherapy products. PMID:26878298

  20. NeutroPhase(®) in chronic non-healing wounds.

    PubMed

    Crew, John; Varilla, Randell; Rocas, Thomas Allandale; Debabov, Dmitri; Wang, Lu; Najafi, Azar; Rani, Suriani Abdul; Najafi, Ramin Ron; Anderson, Mark

    2012-01-01

    Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient's morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase(®) as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase(®) is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase(®) with and without NPWT. NeutroPhase(®) was non-toxic to living tissues.

  1. Wound healing and hyper-hydration: a counterintuitive model.

    PubMed

    Rippon, M G; Ousey, K; Cutting, K F

    2016-02-01

    Winter's seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle, confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model 'hyper-hydration' of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration. Declaration of interest: K. Cutting is a Clinical Research Consultant to the medical device and biotechnology industry. M. Rippon is Visiting Clinical Research Fellow, University of Huddersfield and K. Ousey provides consultancy for a range of companies through the University of Huddersfield including consultancy services for Paul Hartmann Ltd on HydroTherapy products.

  2. Evaluation of LED photobiomodulation on wound healing in hypothyroid and euthyroid rats

    NASA Astrophysics Data System (ADS)

    Paraguassú, Gardênia Matos; Xavier, Flávia Calo Aquino; Rodriguez, Tânia Tavares; Ramalho, Maria José Pedreira; Pinheiro, Antônio Luiz Barbosa; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Thyroid hormone deficiency has been associated to disruption of the body's metabolism, including healing process. LED phototherapy has been shown to be effective in improving healing in many situations, but their usefulness in the improvement of hypothyroidism wound healing remains unknown. The aim of this study was to assess histologically the effect of LED (λ630 ± 20nm, 150mW, CW, φ=0.5 cm2, 24J/cm2 per session) on wounds healing in hypothyroid and euthyroid Wistar rats. Standard cutaneous wound (1cm2) was created on the dorsum of 24 animals divided into four groups of 6 animals each: G1: Euthyroid; G2: Euthyroid + LED; G3: Hypothyroid; G4: 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. The irradiation started immediately after surgery and was repeated every other day for 7 days. Animals were killed 8 days after surgery. The specimens were removed, routinely processed and stained with H&E and Sirius red. Statistical analysis was performed using the Fisher's Test and significance level was 5%. The results of the present investigation showed delayed wounds healing process in hypothyroid rats characterized by incomplete reepithelialization and formation of disorganized collagen fibers (p<0.05) when compared to the euthyroid group, and that in the irradiated groups the reepithelialization was statistically higher when compared with non-irradiated ones (p<0.05). There was improved collagen fibers deposition on irradiated animals (euthyroid and hypothyroid) when compared to non-irradiated ones, but no statistically significant difference (p>0.05). It is concluded that LED light has a positive biomodulative effect on the wound healing process, even when hipothyroidism was present.

  3. Stromal cell-derived factor-1 promotes human adipose tissue-derived stem cell survival and chronic wound healing

    PubMed Central

    LI, QIANG; GUO, YANPING; CHEN, FEIFEI; LIU, JING; JIN, PEISHENG

    2016-01-01

    Adipose tissue-derived stem cells (ADSCs) hold great potential for the stem cell-based therapy of cutaneous wound healing. Stromal cell-derived factor-1 (SDF-1) activates CXC chemokine receptor (CXCR)4+ and CXCR7+ cells and plays an important role in wound healing. Increasing evidence suggests a critical role for SDF-1 in cell apoptosis and the survival of mesenchymal stem cells. However, the function of SDF-1 in the apoptosis and wound healing ability of ADSCs is not well understood. The aim of this study was to analyze the effect of SDF-1 on the apoptosis and therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivos. By flow cytometric analysis, it was found that hypoxia and serum free promoted the apoptosis of ADSCs. When pretreated with SDF-1, the apoptosis of ADSCs induced by hypoxia and serum depletion was partly recovered. Furthermore, in vivo experiments established that the post-implantation cell survival and chronic wound healing ability of ADSCs were increased following pretreatment with SDF-1 in a diabetic mouse model of chronic wound healing. To explore the potential mechanism underlying the effect of SDF-1 on ADSC apoptosis, western blot analysis was employed and the results indicate that SDF-1 may protect against cell apoptosis in hypoxic and serum-free conditions through activation of the caspase signaling pathway in ADSCs. This study provides evidence that SDF-1 pretreatment can increase the therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivo. PMID:27347016

  4. Effect of novel blend nanofibrous scaffolds on diabetic wounds healing.

    PubMed

    Gholipour-Kanani, Adeleh; Bahrami, S Hajir; Rabbani, Shahram

    2016-02-01

    Chitosan-poly (vinyl alcohol) (Cs: PVA) (2:3) and poly (caprolactone)-chitosan-poly (vinyl alcohol) (PCL: Cs: PVA) (2:1:1.5) nanofibrous blend scaffolds were fabricated using the electrospinning technique in the authors' previous studies. The results of the previous studies confirmed the high biological properties of the scaffolds and their ability in healing of burn and excision wounds on rat model. In the present study, the biological scaffolds were applied on diabetic dorsum skin wounds and diabetic foot wound on rat models (n = 16). Macroscopic and microscopic investigations were carried out using digital images and haematoxylin and eosin (H&E) staining respectively, to measure the wound areas and to track wound healing rate. It was found that at all time points the areas of wounds treated with nanofibrous scaffolds were smaller compared with the controls. Pathological results showed much better healing efficacy for the test samples compared with the control ones. Pathological investigations proved the presence of more pronounced granulation tissues in the scaffold-treated wounds compared with the control ones. At 20 days post excision, the scaffold-treated groups achieved complete repair. The results indicated that Cs: PVA and PCL: Cs: PVA nanofibrous webs could be considered to be promising materials for burn, excision and diabetic wounds healing. PMID:26766866

  5. Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

    PubMed Central

    Tracy, Lauren E.; Minasian, Raquel A.; Caterson, E.J.

    2016-01-01

    Significance: Fibroblasts play a critical role in normal wound healing. Various extracellular matrix (ECM) components, including collagens, fibrin, fibronectin, proteoglycans, glycosaminoglycans, and matricellular proteins, can be considered potent protagonists of fibroblast survival, migration, and metabolism. Recent Advances: Advances in tissue culture, tissue engineering, and ex vivo models have made the examination and precise measurements of ECM components in wound healing possible. Likewise, the development of specific transgenic animal models has created the opportunity to characterize the role of various ECM molecules in healing wounds. In addition, the recent characterization of new ECM molecules, including matricellular proteins, dermatopontin, and FACIT collagens (Fibril-Associated Collagens with Interrupted Triple helices), further demonstrates our cursory knowledge of the ECM in coordinated wound healing. Critical Issues: The manipulation and augmentation of ECM components in the healing wound is emerging in patient care, as demonstrated by the use of acellular dermal matrices, tissue scaffolds, and wound dressings or topical products bearing ECM proteins such as collagen, hyaluronan (HA), or elastin. Once thought of as neutral structural proteins, these molecules are now known to directly influence many aspects of cellular wound healing. Future Directions: The role that ECM molecules, such as CCN2, osteopontin, and secreted protein, acidic and rich in cysteine, play in signaling homing of fibroblast progenitor cells to sites of injury invites future research as we continue investigating the heterotopic origin of certain populations of fibroblasts in a healing wound. Likewise, research into differently sized fragments of the same polymeric ECM molecule is warranted as we learn that fragments of molecules such as HA and tenascin-C can have opposing effects on dermal fibroblasts. PMID:26989578

  6. Effects of tretinoin on wound healing in aged skin.

    PubMed

    de Campos Peseto, Danielle; Carmona, Erica Vilaça; Silva, Kellyn Cristina da; Guedes, Flavia Roberta Valente; Hummel Filho, Fernando; Martinez, Natalia Peres; Pereira, José Aires; Rocha, Thalita; Priolli, Denise Gonçalves

    2016-03-01

    Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid-Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing. PMID:26834030

  7. Secretome of peripheral blood mononuclear cells enhances wound healing.

    PubMed

    Mildner, Michael; Hacker, Stefan; Haider, Thomas; Gschwandtner, Maria; Werba, Gregor; Barresi, Caterina; Zimmermann, Matthias; Golabi, Bahar; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2013-01-01

    Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SEC(PBMC)). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SEC(PBMC) containing emulsion or controls were applied daily for three days. Morphology and neo-angiogenesis were analyzed by H&E-staining and CD31 immuno-staining, respectively. In vitro effects on diverse skin cells were investigated by migration assays, cell cycle analysis, and tube formation assay. Signaling pathways were analyzed by Western blot analysis. Application of SEC(PBMC) on 6 mm punch biopsy wounds significantly enhanced wound closure. H&E staining of the wounds after 6 days revealed that wound healing was more advanced after application of SEC(PBMC) containing emulsion. Furthermore, there was a massive increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was induced. In endothelial cells (EC) SEC(PBMC) induced proliferation and tube-formation in a matrigel-assay. In addition, SEC(PBMC) treatment of skin cells led to the induction of multiple signaling pathways involved in cell migration, proliferation and survival. In summary, we could show that emulsions containing the secretome of PBMC derived from healthy individuals accelerates wound healing in a mouse model and induce wound healing associated mechanisms in human primary skin cells. The formulation and use of such emulsions might therefore represent a possible novel option for the treatment of non-healing skin ulcers.

  8. Wound healing evaluation of sodium fucidate-loaded polyvinylalcohol/sodium carboxymethylcellulose-based wound dressing.

    PubMed

    Lee, Jeong Hoon; Lim, Soo-Jeong; Oh, Dong Hoon; Ku, Sae Kwang; Li, Dong Xun; Yong, Chul Soon; Choi, Han-Gon

    2010-07-01

    The cross-linked hydrogel films containing sodium fucidate were previously reported to be prepared polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method and their physicochemical property was investigated. For the development of novel sodium fucidate-loaded wound dressing, here its in vivo wound healing test and histopathology were performed compared with the conventional ointment product. In wound healing test, the sodium fucidate-loaded composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug showed faster healing of the wound made in rat dorsum than the hydrogel without drug, indicating the potential healing effect of sodium fucidate. Furthermore, from the histological examination, the healing effect of sodium fucidate-loaded hydrogel was greater than that of the conventional ointment product and hydrogel without drug, since it might gave an adequate level of moisture and build up the exudates on the wound area. Thus, the sodium fucidate-loaded wound dressing composed of 5% PVA, 1.125% Na-CMC and 0.2% drug is a potential wound dressing with excellent wound healing.

  9. Effect of aged garlic extract on wound healing: a new frontier in wound management.

    PubMed

    Ejaz, Sohail; Chekarova, Irina; Cho, Jae Woo; Lee, Seung Yeon; Ashraf, Shoaib; Lim, Chae Woong

    2009-01-01

    Successful wound healing depends upon angiogenesis, and impaired angiogenesis is a hallmark of the chronic wounds encountered with diabetes and venous or arterial insufficiency. To intervene and improve wound closure, it is essential to investigate the effects of different natural remedies in wound healing. The chicken dorsum skin excisional wound assay was used to investigate the influence of different concentrations of aged garlic solution (AGS) on wound healing. Gross, histopathology, scanning electron microscopy (SEM) and computer-based three-dimensional (3D) image-probing techniques were utilized to determine the effects of AGS on wound closure, re-epithelialization, dermal matrix regeneration, and angiogenesis. Ninety chicks, aged 1 week and divided in 6 groups, were topically exposed to different concentrations of AGS for 6 days: control (group A), 1% (group B), 5% (group C), 10% (group D), 15% (group E), and skin lotion (group F). Different patterns, ranging from incomplete to almost complete wound closure, were observed among different groups with highly significant results (P < 0.001) in group E. Histological investigations revealed a positive augment in the re-epithelialization of all AGS exposed wounds. An increase in the number of new loosely packed collagen and maturation of collagen bundles was observed in all treated wounds at days 4 and 6 post-wounding, respectively. Similar results were achieved through SEM of treated wounds. Histological investigations revealed the profuse dose-dependent neovascularization among AGS-treated wounds. Abbott curve, angular spectrum, and different parameters of 3D surface roughness of wounds were also measured for the precise quantification of angiogenesis. A very highly significant (P < 0.001) increase in angiogenesis was observed among all treated groups. No significant change was observed among control and skin lotion-treated groups. These observations substantiate the beneficial use of AGS in the treatment of

  10. Antimicrobial peptides and wound healing: biological and therapeutic considerations.

    PubMed

    Mangoni, Maria Luisa; McDermott, Alison M; Zasloff, Michael

    2016-03-01

    Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defense molecules, including antimicrobial peptides (AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review, we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for the treatment of non-life-threatening skin and other epithelial injuries. PMID:26738772

  11. [Searching for new wound healing strategies--problems and pitfalls].

    PubMed

    Waniczek, Dariusz A; Rudzki, Marek K; Buda, Krzysztof K; Arendt, Jerzy

    2011-01-01

    Authors present the most recent and prospective trends in wound healing procedures, which are expected to solve problems with acute and chronic wounds management. While searching for new strategies to optimize the would healing process, reduce the complication probability, and support or replace the classical treatment procedures, researchers are faced with many diagnostic and therapeutic problems and pitfalls. That leads to creating highly complicated and expensive treatment procedures which, however, have not yet been proven to exceed the effectiveness of the moist wound therapy.

  12. Silver Nanoparticles as Real Topical Bullets for Wound Healing

    PubMed Central

    Gunasekaran, Thirumurugan; Nigusse, Tadele; Dhanaraju, Magharla Dasaratha

    2012-01-01

    Nanotechnology is on the threshold of providing a host of new materials and approaches, revolutionizing the medical and pharmaceutical fields. Several areas of medical care are already profiting from the advantage that nanotechnology offers. Recently, silver nanoparticles are attracting interest for a clinical application because of its potential biological properties such as antibacterial activity, anti-inflammatory effects, and wound healing efficacy, which could be exploited in developing better dressings for wounds and ulcers. This article reviews the role of silver nanoparticles in wound healing. PMID:24527370

  13. Peroxide-based oxygen generating topical wound dressing for enhancing healing of dermal wounds.

    PubMed

    Chandra, Prafulla K; Ross, Christina L; Smith, Leona C; Jeong, Seon S; Kim, Jaehyun; Yoo, James J; Harrison, Benjamin S

    2015-01-01

    Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds.

  14. State-of-the-art wound healing: skin substitutes for chronic wounds.

    PubMed

    Han, George

    2014-01-01

    The care of chronic wounds represents an important and evolving area of dermatology. With a rising prevalence of chronic wounds bearing notable effects on patient morbidity including amputations, appropriate and effective intervention to treat these debilitating wounds can make a significant clinical impact. In recent years, several advanced bioactive wound dressings have been developed to specifically treat chronic nonhealing wounds. These wound dressings encompass a wide range of products containing synthetic matrix scaffolds, animal-derived matrices, and human tissue. With several of these wound dressings, randomized controlled trials (RCTs) have demonstrated improvement in wound healing; furthermore, cost-effectiveness studies have suggested that these products may reduce the overall cost of treating a chronic wound. Familiarity with these products and their appropriate use may be helpful to dermatologists treating chronic wounds.

  15. Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice.

    PubMed

    Eo, Hyeyoon; Lee, Hea-Ji; Lim, Yunsook

    2016-09-23

    Among the diabetic complications, diabetic foot ulcer due to delayed wound healing is one of the most significant clinical problems. Early inflammatory stage is important for better prognosis during wound healing. Thus, regulation of inflammatory response during early stage of wound healing is main target for complete cutaneous recovery. This study investigated the role of genistein supplementation in inflammation and oxidative stress, which are related to NLRP3 inflammasome, NFκB and Nrf2 activation, during cutaneous wound healing in alloxan-induced diabetic mice. Mice with diabetes with fasting blood glucose (FBG) levels > 250 mg/dl were fed diets with AIN-93G rodent diet containing 0%, 0.025% (LG) or 0.1% (HG) genistein. After 2 weeks of genistein supplementation, excisional wounds were made by biopsy punches (4 mm). Genistein supplementation improved fasting glucose levels and wound closure rate. Moreover, genistein supplementation restored NLRP3 inflammasome (NLRP3, ASC and caspase-1) at the basal level and ameliorated both inflammation (TNFα, iNOS, COX2 and NFκB) and antioxidant defense system (Nrf2, HO-1, GPx, and catalase) during early stage of wound healing in diabetic mice. Taken together, genistein supplementation would be a potential therapeutic nutrient in prevention and treatment of delayed wound healing by modulation of inflammation and oxidative stress during inflammatory stage.

  16. Spontaneous skin erosions and reduced skin and corneal wound healing characterize CLIC4(NULL) mice.

    PubMed

    Padmakumar, V C; Speer, Kelsey; Pal-Ghosh, Sonali; Masiuk, Katelyn E; Ryscavage, Andrew; Dengler, Samuel L; Hwang, Shelly; Edwards, John C; Coppola, Vincenzo; Tessarollo, Lino; Stepp, Mary Ann; Yuspa, Stuart H

    2012-07-01

    Cutaneous wound healing is a complex process involving blood clotting, inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue remodeling and wound closure. Many of these processes involve transforming growth factor-β (TGF-β) signaling, and mice lacking components of the TGF-β signaling pathway are defective in wound healing. We show herein that CLIC4, an integral component of the TGF-β pathway, is highly up-regulated in skin wounds. We genetically deleted murine CLIC4 and generated a colony on a C57Bl/6 background. CLIC4(NULL) mice were viable and fertile but had smaller litters than did wild-type mice. After 6 months of age, up to 40% of null mice developed spontaneous skin erosions. Reepithelialization of induced full-thickness skin wounds and superficial corneal wounds was delayed in CLIC4(NULL) mice, resolution of inflammation was delayed, and expression of β4 integrin and p21 was reduced in lysates of constitutive and wounded CLIC4(NULL) skin. The induced level of phosphorylated Smad2 in response to TGF-β was reduced in cultured CLIC4(NULL) keratinocytes relative to in wild-type cells, and CLIC4(NULL) keratinocytes migrated slower than did wild-type keratinocytes and did not increase migration in response to TGF-β. CLIC4(NULL) keratinocytes were also less adherent on plates coated with matrix secreted by wild-type keratinocytes. These results indicate that CLIC4 participates in skin healing and corneal wound reepithelialization through enhancement of epithelial migration by a mechanism that may involve a compromised TGF-β pathway.

  17. Spontaneous Skin Erosions and Reduced Skin and Corneal Wound Healing Characterize CLIC4NULL Mice

    PubMed Central

    Padmakumar, V.C.; Speer, Kelsey; Pal-Ghosh, Sonali; Masiuk, Katelyn E.; Ryscavage, Andrew; Dengler, Samuel L.; Hwang, Shelly; Edwards, John C.; Coppola, Vincenzo; Tessarollo, Lino; Stepp, Mary Ann; Yuspa, Stuart H.

    2013-01-01

    Cutaneous wound healing is a complex process involving blood clotting, inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue remodeling and wound closure. Many of these processes involve transforming growth factor-β (TGF-β) signaling, and mice lacking components of the TGF-β signaling pathway are defective in wound healing. We show herein that CLIC4, an integral component of the TGF-β pathway, is highly up-regulated in skin wounds. We genetically deleted murine CLIC4 and generated a colony on a C57Bl/6 background. CLIC4NULL mice were viable and fertile but had smaller litters than did wild-type mice. After 6 months of age, up to 40% of null mice developed spontaneous skin erosions. Reepithelialization of induced full-thickness skin wounds and superficial corneal wounds was delayed in CLIC4NULL mice, resolution of inflammation was delayed, and expression of β4 integrin and p21 was reduced in lysates of constitutive and wounded CLIC4NULL skin. The induced level of phosphorylated Smad2 in response to TGF-β was reduced in cultured CLIC4NULL keratinocytes relative to in wild-type cells, and CLIC4NULL keratinocytes migrated slower than did wild-type keratinocytes and did not increase migration in response to TGF-β. CLIC4NULL keratinocytes were also less adherent on plates coated with matrix secreted by wild-type keratinocytes. These results indicate that CLIC4 participates in skin healing and corneal wound reepithelialization through enhancement of epithelial migration by a mechanism that may involve a compromised TGF-β pathway. PMID:22613027

  18. Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing.

    PubMed

    Charafeddine, Rabab A; Makdisi, Joy; Schairer, David; O'Rourke, Brian P; Diaz-Valencia, Juan D; Chouake, Jason; Kutner, Allison; Krausz, Aimee; Adler, Brandon; Nacharaju, Parimala; Liang, Hongying; Mukherjee, Suranjana; Friedman, Joel M; Friedman, Adam; Nosanchuk, Joshua D; Sharp, David J

    2015-09-01

    Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.

  19. Multimodal noninvasive monitoring of soft tissue wound healing.

    PubMed

    Bodo, Michael; Settle, Timothy; Royal, Joseph; Lombardini, Eric; Sawyer, Evelyn; Rothwell, Stephen W

    2013-12-01

    Here we report results of non-invasive measurements of indirect markers of soft tissue healing of traumatic wounds in an observational swine study and describe the quantification of analog physiological signals. The primary purpose of the study was to measure bone healing of fractures with four different wound treatments. A second purpose was to quantify soft tissue wound healing by measuring the following indirect markers: (1) tissue oxygenation, (2) fluid content, and (3) blood flow, which were all measured by non-invasive modalities, measured with available devices. Tissue oxygenation was measured by near infrared spectroscopy; fluid content was measured by bipolar bio-impedance; and blood flow was measured by Doppler ultrasound. Immediately after comminuted femur fractures were produced in the right hind legs of thirty anesthetized female Yorkshire swine, one of four wound treatments was instilled into each wound. The four wound treatments were as follows: salmon fibrinogen/thrombin-n = 8; commercial bone filler matrix-n = 7; bovine collagen-n = 8; porcine fibrinogen/thrombin-n = 7. Fractures were stabilized with an external fixation device. Immediately following wound treatments, measurements were made of tissue oxygenation, fluid content and blood flow; these measurements were repeated weekly for 3 weeks after surgery. Analog signals of each modality were recorded on both the wounded (right) hind leg and the healthy (left) hind leg, for comparison purposes. Data were processed off-line. The mean values of 10-s periods were calculated for right-left leg comparison. ANOVA was applied for statistical analysis. Results of the bone healing studies are published separately (Rothwell et al. in J Spec Oper Med 13:7-18, 2013). For soft tissue wounds, healing did not differ significantly among the four wound treatments; however, regional oxygenation of wounds treated with salmon fibrinogen/thrombin showed slightly different time trends. Further studies are

  20. Application of stems cells in wound healing--an update.

    PubMed

    Teng, Miao; Huang, Yuesheng; Zhang, Hengshu

    2014-01-01

    Wound healing is a complex but well-orchestrated tissue repair process composed of a series of molecular and cellular events conducted by various types of cells and extracellular matrix. Despite a variety of therapeutic strategies proposed to accelerate the healing of acute and/or chronic wounds over the past few decades, effective treatment of chronic nonhealing wounds still remains a challenge. Due to the recent advances in stem cell research, a dramatic enthusiasm has been drawn to the application of stem cells in regenerative medicine. Both embryonic and adult stem cells have prolonged self-renewal capacity and are able to differentiate into various tissue types. Nevertheless, use of embryonic stem cells is limited, owing to ethical concerns and legal restrictions. Adult stem cells, which could be isolated from bone marrow, umbilical cord blood, adipose tissue, skin and hair follicles,are being explored extensively to facilitate the healing of both acute and chronic wounds. The current article summarizes recent research on various types of stem cell-based strategies applied to improve wound healing. In addition, future directions of stem cell-based therapy in wound healing have also been discussed. Finally, despite its apparent advantages, limitations and challenges of stem cell therapy are discussed.

  1. Electrical stimulation for pressure sore prevention and wound healing.

    PubMed

    Bogie, K M; Reger, S I; Levine, S P; Sahgal, V

    2000-01-01

    This paper reviews applications of therapeutic electrical stimulation (ES) specific to wound healing and pressure sore prevention. The application of ES for wound healing has been found to increase the rate of healing by more than 50%. Furthermore, the total number of wounds healed is also increased. However, optimal delivery techniques for ES therapy have not been established to date. A study of stimulation current effects on wound healing in a pig model has shown that direct current (DC) stimulation is most effective in wound area reduction and alternating current (AC) stimulation for wound volume reduction at current densities of 127 microA/cm2 and 1,125 microA/cm2, respectively. Preliminary studies have been carried out at two research centers to assess the role of ES in pressure sore prevention. Surface stimulation studies have shown that ES can produce positive short-term changes in tissue health variables such as regional blood flow and pressure distribution. The use of an implanted stimulation system consisting of intramuscular electrodes with percutaneous leads has been found to produce additional long-term changes. Specifically, gluteal muscle thickness increased by 50% with regular long-term ES application concurrent with a 20% decrease in regional interface pressures and increased tissue oxygen levels. These findings indicate that an implantable ES system may have great potential for pressure sore prevention, particularly for individuals who lack sensation or who are physically unable to perform regular independent pressure relief.

  2. Identification of gunpowder in healed wounds.

    PubMed

    Smith, O C; Berryman, H E; Symes, S A; LeVaughn, M M

    1993-05-01

    A woman received a contact gunshot wound to the abdomen from a .22 caliber revolver. She recovered only to succumb to another gunshot wound six months later. The initial wound was dissected and multiple intact granules of round flake gunpowder were recovered. Cross sections of granules were clearly identifiable in histologic slides. Recovery of intact powder in remote wounds has not been previously described and may help classify the ammunition and weapon used to produce the injury.

  3. The role of endogenous and exogenous enzymes in chronic wounds: a focus on the implications of aberrant levels of both host and bacterial proteases in wound healing.

    PubMed

    McCarty, Sara M; Cochrane, Christine A; Clegg, Peter D; Percival, Steven L

    2012-01-01

    Cutaneous wound healing is orchestrated by a number of physiological pathways that ultimately lead to reformation of skin integrity and the production of functional scar tissue. The remodeling of a wound is significantly affected by matrix metalloproteinases (MMPs), which act to control the degradation of the extracellular matrix (ECM). Regulation of MMPs is imperative for wound healing as excessive levels of MMPs can lead to disproportionate destruction of the wound ECM compared to ECM deposition. In addition to human MMPs, bacterial proteases have been found to be influential in tissue breakdown and, as such, have a role to play in the healing of infected wounds. For example, the zinc-metalloproteinase, elastase, produced by Pseudomonas aeruginosa, induces degradation of fibroblast proteins and proteoglycans in chronic wounds and has also been shown to degrade host immune cell mediators. Microbial extracellular enzymes have also been shown to degrade human wound fluid and inhibit fibroblast cell growth. It is now being acknowledged that host and bacterial MMPs may act synergistically to cause tissue breakdown within the wound bed. Several studies have suggested that bacterial-derived secreted proteases may act to up-regulate the levels of MMPs produced by the host cells. Together, these findings indicate that bacterial phenotype in terms of protease producing potential of bacteria should be taken into consideration during diagnostic and clinical intervention of infected wound management. Furthermore, both host MMPs and those derived from infecting bacteria need to be targeted in order to increase the healing capacity of the injured tissue. The aim of this review is to investigate the evidence suggestive of a relationship between unregulated levels of both host and bacterial proteases and delayed wound healing. PMID:22380687

  4. The role of endogenous and exogenous enzymes in chronic wounds: a focus on the implications of aberrant levels of both host and bacterial proteases in wound healing.

    PubMed

    McCarty, Sara M; Cochrane, Christine A; Clegg, Peter D; Percival, Steven L

    2012-01-01

    Cutaneous wound healing is orchestrated by a number of physiological pathways that ultimately lead to reformation of skin integrity and the production of functional scar tissue. The remodeling of a wound is significantly affected by matrix metalloproteinases (MMPs), which act to control the degradation of the extracellular matrix (ECM). Regulation of MMPs is imperative for wound healing as excessive levels of MMPs can lead to disproportionate destruction of the wound ECM compared to ECM deposition. In addition to human MMPs, bacterial proteases have been found to be influential in tissue breakdown and, as such, have a role to play in the healing of infected wounds. For example, the zinc-metalloproteinase, elastase, produced by Pseudomonas aeruginosa, induces degradation of fibroblast proteins and proteoglycans in chronic wounds and has also been shown to degrade host immune cell mediators. Microbial extracellular enzymes have also been shown to degrade human wound fluid and inhibit fibroblast cell growth. It is now being acknowledged that host and bacterial MMPs may act synergistically to cause tissue breakdown within the wound bed. Several studies have suggested that bacterial-derived secreted proteases may act to up-regulate the levels of MMPs produced by the host cells. Together, these findings indicate that bacterial phenotype in terms of protease producing potential of bacteria should be taken into consideration during diagnostic and clinical intervention of infected wound management. Furthermore, both host MMPs and those derived from infecting bacteria need to be targeted in order to increase the healing capacity of the injured tissue. The aim of this review is to investigate the evidence suggestive of a relationship between unregulated levels of both host and bacterial proteases and delayed wound healing.

  5. The effects of cancer and cancer therapies on wound healing

    SciTech Connect

    McCaw, D.L.

    1989-11-01

    Based on experimental evidence in rodents, most of the antineoplastic agents will affect wound healing. With most of the agents, this impairment is not sufficient to produce increased morbidity based on the clinical reports in humans. Radiation therapy appears to inhibit healing in both experimental animals and during clinical trials. In spite of this, it is reported that wounds in animals will heal when they are receiving radiation therapy after surgery. Based on the information presented here and experience at the University of Missouri, the decision to use adjuvant therapy should depend on the surgery performed. With a single incision that had no increased tension, there should be no hesitation to use adjuvant therapy. If removal of the tumor required reconstructive surgery, no radiation or chemotherapy should be used until the wound has healed. 30 references.

  6. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    PubMed Central

    Bhatia, Ayesha; O’Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

  7. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

    PubMed

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  8. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

    PubMed

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

  9. Wound healing stimulation in mice by low-level light

    NASA Astrophysics Data System (ADS)

    Demidova, Tatiana N.; Herman, Ira M.; Salomatina, Elena V.; Yaroslavsky, Anna N.; Hamblin, Michael R.

    2006-02-01

    It has been known for many years that low levels of laser or non-coherent light (LLLT) accelerate some phases of wound healing. LLLT can stimulate fibroblast and keratinocyte proliferation and migration. It is thought to work via light absorption by mitochondrial chromophores leading to an increase in ATP, reactive oxygen species and consequent gene transcription. However, despite many reports about the positive effects of LLLT on wound healing, its use remains controversial. Our laboratory has developed a model of a full thickness excisional wound in mice that allows quantitative and reproducible light dose healing response curves to be generated. We have found a biphasic dose response curve with a maximum positive effect at 2 J/cm2 of 635-nm light and successively lower beneficial effects from 3-25 J/cm2, the effect is diminished at doses below 2J/cm2 and gradually reaches control healing levels. At light doses above 25 J/cm2 healing is actually worse than controls. The two most effective wavelengths of light were found to be 635 and 820-nm. We found no difference between filtered 635+/-15-nm light from a lamp and 633-nm light from a HeNe laser. The strain and age of the mouse affected the magnitude of the effect. Light treated wounds start to contract after illumination while control wounds initially expand for the first 24 hours. Our hypothesis is that a single brief light exposure soon after wounding affects fibroblast cells in the margins of the wound. Cells may be induced to proliferate, migrate and assume a myofibroblast phenotype. Our future work will be focused on understanding the mechanisms underlying effects of light on wound healing processes.

  10. Effect of Zoledronate on Oral Wound Healing in Rats

    PubMed Central

    Yamashita, Junro; Koi, Kiyono; Yang, Dong-Ye; McCauley, Laurie K.

    2010-01-01

    Purpose Osteonecrosis of the jaw (ONJ) is a growing concern in patients who receive bisphosphonates which target osteoclasts. Since osteoclasts play multifunctional roles in the bone marrow, their suppression likely affects bone homeostasis and alters wound healing of the jaw. The objective was to delineate the impact of osteoclast suppression in the bone marrow and wound healing of the jaw. Experimental Design Zoledronate was administered to senile rats for 14 weeks. A portion of the gingiva was removed to denude the palatal bone. Gene expression in the bone marrow was assessed and histologic sections analyzed to determine the wound healing status. Results Angiogenesis-related genes, CD31 and VEGF-A, were not altered by zoledronate. VEGF-C, which plays a role in lymphangiogenesis, was suppressed. There was a decrease in gene expression of Tcirg1 and MMP-13. Bone denudation caused extensive osteocyte death indicative of bone necrosis. In zoledronate-treated rats, the necrotic bone was retained in the wound while, in controls, osteoclastic resorption of the necrotic bone was prominent. Even though large necrotic bone areas existed in zoledronate-treated rats, overlaying soft tissue healed clinically. Immunohistochemical staining showed rich vascularity in the overlaying soft tissue. Conclusions Zoledronate therapy impacts bone marrow by suppressing genes associated with lymphoangiogenesis and tissue remodeling, such as VEGF-C and MMP-13. Zoledronate was associated with impaired osseous wound healing but had no effect on angiogenic markers in the bone marrow or soft tissue wound healing. Zoledronate selectively blunts healing in bone but does not effect soft tissue healing in the oral cavity. PMID:21149614

  11. Wound healing. New modalities for a new millennium.

    PubMed

    Williams, R L; Armstrong, D G

    1998-01-01

    Common to all studies of wound healing modalities is the need to convert the chronic wound into an acute wound and to maintain the wound in an acute state while subsequently using adjunctive therapy. Hence, precise control and documentation of wound care is extremely important in order to avoid contamination of the effects of a specific modality with the effects of good wound care. Falanga has noted that neuropathy of diabetes has been given wide support as the primary pathogenic component of diabetic ulcers, whereas less recognition has been made of the wound-healing failure component. The therapies discussed in this article considered the wound-healing failure component. Oxygen is a drug. The use of oxygen under normobaric conditions at higher than normal inspired partial pressures is standard operating procedure when clinicians are faced with patients with respiratory embarrassment or heart failure. The use of oxygen under hyperbaric conditions, however, remains estranged from the mainstream thoughts of most clinicians. Abnormally hypoxic wounds may benefit from specific oxygen therapy in hyperbaric dosage ranges. However, correction of abnormal wound oxygen tension alone does not guarantee healing. Hyperbaric studies have been criticized for the lack of well-defined wound care protocols, the absence of precise wound healing measures, and poorly defined wound healing endpoints. Studies with growth factors and human skin equivalents exclude patients typically referred for hyperbaric therapy. Patients referred for hyperbaric therapy often have larger wounds with greater severity of peripheral vascular disease with ABIs < 0.7 and TcPO2 < 30 to 40 mm Hg, are often on medications known to inhibit wound healing (e.g., steroids), or have concomitant medical disorders (collagen vascular disease, renal failure) associated with poor healing. No hyperbaric study has controlled stringently for all of these factors. Nevertheless, HBO2 is more specific and successful for the

  12. Evaluation of wound healing property of Terminalia catappa on excision wound models in Wistar rats.

    PubMed

    Khan, A A; Kumar, V; Singh, B K; Singh, R

    2014-05-01

    Wound is defined as the loss of breaking cellular and functional continuity of the living tissues. Management of wounds is frequently encountered with different problems. Drug resistance and toxicity hindered the development of synthetic antimicrobial agents with wound healing activity. Many plants with potent pharmacological activities may offer better treatment options viz. Terminalia chebula, Terminalia bellirica and Phyllanthus emblica formulations have shown healing activities on wounds.The present study was planned to investigate the wound healing activity of Terminalia catappa on excision wound model in rats. Ointment was prepared by using bark extract of Terminalia catappa in soft paraffin and preservative. Wistar albino rats (200-250 gm) of either sex were used in the present study. A circular wound of 2 cm in diameter was made on the depilated dorsal thoracic region of the rats under ether anesthesia in aseptic conditions. The ointment was applied for 18 days and percent wound closure observed along with the parameters viz. Epithelization, granuloma weight and scar formation. Animals were observed on 3rd, 6th, 9th, 12th, 15th and 18th post-wounding day.Wound healing activity was compared with that of control and Betadine ointment as standard drug. Animals treated with Terminalia catappa ointment exhibited 97% reduction in wound area as compared to the control animals (81%). Ointment treated wounds were found to induce epithelization faster compared to the control. In conclusion, Terminalia catappa ointment promotes significant wound healing in rats and further evaluation of this activity in humans is suggested.

  13. In silico design of treatment strategies in wound healing and bone fracture healing.

    PubMed

    Geris, L; Schugart, R; Van Oosterwyck, H

    2010-06-13

    Wound and bone fracture healing are natural repair processes initiated by trauma. Over the last decade, many mathematical models have been established to investigate the healing processes in silico, in addition to ongoing experimental work. In recent days, the focus of the mathematical models has shifted from simulation of the healing process towards simulation of the impaired healing process and the in silico design of treatment strategies. This review describes the most important causes of failure of the wound and bone fracture healing processes and the experimental models and methods used to investigate and treat these impaired healing cases. Furthermore, the mathematical models that are described address these impaired healing cases and investigate various therapeutic scenarios in silico. Examples are provided to illustrate the potential of these in silico experiments. Finally, limitations of the models and the need for and ability of these models to capture patient specificity and variability are discussed.

  14. Biosurgery in wound healing--the renaissance of maggot therapy.

    PubMed

    Wollina, U; Karte, K; Herold, C; Looks, A

    2000-07-01

    Chronic wounds are a challenge for modern health care. A basic principle of treatment is the removal of sloughy, necrotic, devitalized tissue to prevent wound infection and delayed healing. Biosurgery (syn. maggot or larval therapy) is a promising adjunct to the whole spectrum of topical treatment methods, in particular for debridement. The term 'biosurgery' describes the use of living maggots on wounds to remove devitalized tissue, decrease the risk of infection and improve wound healing. The present paper gives a brief review of history, entomology, biochemistry and medical indications of biosurgery and the practical handling of maggots. We also provide some clinical data from the literature and our own experience in a wound care unit. Biosurgery is an effective and safe treatment option for debridement and disinfection. PMID:11204517

  15. Burn wound healing property of Cocos nucifera: An appraisal

    PubMed Central

    Srivastava, Pallavi; Durgaprasad, S.

    2008-01-01

    Objectives: The study was undertaken to evaluate the burn wound healing property of oil of Cocos nucifera and to compare the effect of the combination of oil of Cocos nucifera and silver sulphadiazine with silver sulphadiazine alone. Materials and Methods: Partial thickness burn wounds were inflicted upon four groups of six rats each. Group I was assigned as control, Group II received the standard silver sulphadiazine. Group III was given pure oil of Cocos nucifera , and Group IV received the combination of the oil and the standard. The parameters observed were epithelialization period and percentage of wound contraction. Results: It was noted that there was significant improvement in burn wound contraction in the group treated with the combination of Cocos nucifera and silver sulphadiazine. The period of epithelialization also decreased significantly in groups III and IV. Conclusion: It is concluded that oil of Cocos nucifera is an effective burn wound healing agent. PMID:20040946

  16. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

    PubMed

    Yang, Peilang; Pei, Qing; Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

  17. Wound healing complications in brain tumor patients on Bevacizumab.

    PubMed

    Ladha, Harshad; Pawar, Tushar; Gilbert, Mark R; Mandel, Jacob; O-Brien, Barbara; Conrad, Charles; Fields, Margaret; Hanna, Teresa; Loch, Carolyn; Armstrong, Terri S

    2015-09-01

    Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation. PMID:26298437

  18. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

    PubMed Central

    Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds. PMID:27028201

  19. Irradiation at 660 nm modulates different genes central to wound healing in wounded and diabetic wounded cell models

    NASA Astrophysics Data System (ADS)

    Houreld, Nicolette N.

    2014-02-01

    Wound healing is a highly orchestrated process and involves a wide variety of cellular components, chemokines and growth factors. Laser irradiation has influenced gene expression and release of various growth factors, cytokines and extracellular matrix proteins involved in wound healing. This study aimed to determine the expression profile of genes involved in wound healing in wounded and diabetic wounded fibroblast cells in response to irradiation at a wavelength of 660 nm. Human skin fibroblast cells (WS1) were irradiated with a diode laser (wavelength 660 nm; fluence 5 J/cm2; power output 100 mW; power density 11 mW/cm2; spot size 9.1 cm2; exposure duration 7 min 35 s). Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used as a template in real-time qualitative polymerase chain reaction (qPCR). Eighty four genes involved in wound healing (extracellular matrix and cell adhesion; inflammatory cytokines and chemokines; growth factors; and signal transduction) were evaluated in wounded and diabetic wounded cell models. Forty eight hours post-irradiation, 6 genes were significantly upregulated and 8 genes were down-regulated in irradiated wounded cells, whereas 1 gene was up-regulated and 33 genes down-regulated in irradiated diabetic wounded cells. Irradiation of stressed fibroblast cells to a wavelength of 660 nm and a fluence of 5 J/cm2 modulated the expression of different genes involved in wound healing in different cell models. Modulation of these genes leads to the effects of laser irradiation seen both in vivo and in vitro, and facilitates the wound healing process.

  20. Ultrasound accelerates healing of normal wounds but not of ischemic ones.

    PubMed

    Altomare, Mariane; Nascimento, Adriana P; Romana-Souza, Bruna; Amadeu, Thaís P; Monte-Alto-Costa, Andréa

    2009-01-01

    To examine the influence of therapeutic ultrasound (US) on repair of standard and ischemic cutaneous lesions, full-thickness excisional wounds were made in rats and treated with a US 3 MHz, 0.5 W/cm(2) pulsed duty cycle. We used five experimental groups: control (received US powered off on the day of surgery, and on the second and fourth day), control US (received US on the day of surgery, and on the second and fourth day), ischemic (received US powered off on the day of surgery, and on the second and fourth day), ischemic US 3X (received US on the day of surgery, and on the second and fourth day) and ischemic US 5X (received US in the day of surgery, first, second, third and fourth day). The control US group showed acceleration in wound contraction 7 days after wounding, an increase in collagen density, and only focal inflammatory areas. Neo-epidermis formation was more advanced in the control US group than in the control one. Wound contraction was delayed in the ischemic group when compared with the control group as well as the ischemic US 3X group, was but slightly accelerated in the ischemic US 5X group when compared with the ischemic group 7 days after wounding. Reepithelialization was delayed in both ischemic US groups when compared with the ischemic group. The number of inflammatory cells was higher in both US ischemic groups. We conclude that US therapy accelerates wound healing in normal wounds and delays wound healing in ischemic wounds.

  1. Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management.

    PubMed

    Lee, Woosik; Kwon, Ohjin; Lee, Dong Sup; Yeo, Woon-Hong

    2015-09-02

    Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of cutaneous wound healing on the skin. Existing methods, however, still rely on visual inspections through various microscopic tools and devices that normally include high-cost, sophisticated systems and require well trained personnel for operation and data analysis. Here, we describe methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination to the skin surface near the wound tissues, which provides recording of high fidelity electrical signals such as skin temperature and thermal conductivity. The methods of device fabrication provide details of step-by-step preparation of the microelectronic system that is completely enclosed with elastomeric silicone materials to offer electrical isolation. The experimental study presents multifunctional, biocompatible, waterproof, reusable, and flexible/stretchable characteristics of the device for clinical applications. Protocols of clinical testing provide an overview and sequential process of cleaning, testing setup, system operation, and data acquisition with the skin-like electronics, gently mounted on hypersensitive, cutaneous wound and contralateral tissues on patients.

  2. Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management.

    PubMed

    Lee, Woosik; Kwon, Ohjin; Lee, Dong Sup; Yeo, Woon-Hong

    2015-01-01

    Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of cutaneous wound healing on the skin. Existing methods, however, still rely on visual inspections through various microscopic tools and devices that normally include high-cost, sophisticated systems and require well trained personnel for operation and data analysis. Here, we describe methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination to the skin surface near the wound tissues, which provides recording of high fidelity electrical signals such as skin temperature and thermal conductivity. The methods of device fabrication provide details of step-by-step preparation of the microelectronic system that is completely enclosed with elastomeric silicone materials to offer electrical isolation. The experimental study presents multifunctional, biocompatible, waterproof, reusable, and flexible/stretchable characteristics of the device for clinical applications. Protocols of clinical testing provide an overview and sequential process of cleaning, testing setup, system operation, and data acquisition with the skin-like electronics, gently mounted on hypersensitive, cutaneous wound and contralateral tissues on patients. PMID:26381652

  3. Anthocyanins from black soybean seed coat enhance wound healing.

    PubMed

    Xu, Lianji; Choi, Tae Hyun; Kim, Sukwha; Kim, Sang-Hyon; Chang, Hyuk Won; Choe, Misun; Kwon, Sun Young; Hur, Ji An; Shin, Sung Chul; Chung, Jong Il; Kang, Dawon; Zhang, Duo

    2013-10-01

    Anthocyanins are known to have antioxidant and antiinflammatory effects. We hypothesized that anthocyanins would enhance wound healing in Sprague-Dawley rats. The purpose of this study was to evaluate our hypothesis and investigate the mechanism of wound healing enhancement. The cytoprotective effect of an immortalized epidermal keratinocyte cell line (HaCaT) and human neonatal dermal fibroblasts in response to various concentrations of anthocyanins was determined. Vascular endothelial growth factor (VEGF) and thrombospondin 1 (TSP1) of HaCaT were measured by Western blot analysis. Anthocyanins were applied to the wounds in rats, and the healing ratio was calculated. Tissue VEGF, TSP1, CD31, nuclear factor-κB, and phosphorylation of IκBα were measured. The viability of the HaCaT cell line and human neonatal dermal fibroblasts increased under cytotoxicity by H2O2 in the anthocyanin-treated groups. The VEGF in the anthocyanin-treated groups increased, whereas TSP1 decreased. Wounds in the experimental groups healed faster, and VEGF and CD31 increased in the experimental groups, whereas TSP1 decreased. Anthocyanins inhibited the translocation of nuclear factor-κB (p65) from cytosol to nucleus and also prevented the phosphorylation of IκBα. Anthocyanins enhance wound healing through a cytoprotective effect, enhancement of angiogenesis, and an antiinflammatory effect.

  4. A multifunctional in situ-forming hydrogel for wound healing.

    PubMed

    Du, Lina; Tong, Li; Jin, Yiguang; Jia, Junwei; Liu, Yangpu; Su, Chang; Yu, Shanjiang; Li, Xin

    2012-01-01

    In this study, a multifunctional in situ-forming hydrogel (MISG) was prepared as a wound dressing designed to stop bleeding, inhibit inflammation, relieve pain, and improve healing. A mixture of poloxamers 407 and 188 was used for the matrix of the MISG. Other ingredients include aminocaproic acid (to stop bleeding), povidone iodine (anti-infective), lidocaine (pain relief), and chitosan (to enhance wound healing and regeneration). The incipient gelation temperature of the MISG was modified by varying the poloxamer concentration. Poloxamer cytotoxicity was evaluated in addition to the effect of the MISG on hemostasis in rabbits, pain relief in mice, bacteriostasis in vitro, and wound healing. The optimal MISG matrix consisted of 30% (w/v) poloxamer (407/188, 1 : 1, w/w) solution and was able to change to a gel within 10 minutes at 37 °C. The poloxamer solution had no cytotoxicity in fibroblasts. Compared to sterile gauze alone, the MISG significantly shortened average hemostasis time and decreased bleeding. The hydrogel showed strong bacteriostatic action similar to povidone iodine solution. It markedly increased the pain threshold and accelerated wound healing compared to the gauze. The MISG is a promising formulation for wound healing in emergency situations. PMID:23110551

  5. Lumican binds ALK5 to promote epithelium wound healing.

    PubMed

    Yamanaka, Osamu; Yuan, Yong; Coulson-Thomas, Vivien Jane; Gesteira, Tarsis Ferreira; Call, Mindy K; Zhang, Yujin; Zhang, Jianhua; Chang, Shao-Hsuan; Xie, Changchun; Liu, Chia-Yang; Saika, Shizuya; Jester, James V; Kao, Winston W-Y

    2013-01-01

    Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-β receptor 1 (ALK5) was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo.

  6. Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions.

    PubMed

    Yang, Dong Joo; Moh, Sang Hyun; Son, Dong Hwee; You, Seunghoon; Kinyua, Ann W; Ko, Chang Mann; Song, Miyoung; Yeo, Jinhee; Choi, Yun-Hee; Kim, Ki Woo

    2016-01-01

    Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications. PMID:27399667

  7. [The incidence of wound healing disorders in heart surgery].

    PubMed

    Fritzsche, D; Krakor, R; Widera, R; Lindenau, K F

    1992-01-01

    In a five-year retrospective study we investigated the wound infection rate after median sternotomy in 2805 adult patients on whom elective surgery had been performed with extracorporeal circulation. On the basis of 14,700 apparently relevant data from 101 patients with wound healing disturbances at the sternotomy site, both the significance of predisposing risk profiles and the prevalence of nosocomial pathogens were evaluated. The control group was formed by 100 patients selected at random. The results were checked for statistical significance using the X2 test for alternative characters; the significance level was set at alpha = 5%. The infection rate observed in our group was 3.6%, which was assigned to 5 internally defined degrees of severity. Cases of healing by second intention were caused to 93% by coagulase-negative staphylococci and staphylococcus aureus. Factors leading to a decrease in oxygenation of the wound area (low-output syndrome, rethoracotomy), diabetes, obesity and the duration of wound drainage were accompanied by a significantly more frequent occurrence of wound healing disturbances. On the other hand, perfusion-technical parameters, operation duration, revascularisation techniques (IMA/ACVB), pulmonary conditioned hypoxemias and the end-of-year desinfection usual in our clinic had no influence on wound healing. Seasonal fluctuation of the epidermal microclimate appear to be responsible for the prevalence and virulence of the pathogen strains in the clinic environment. The preventive measures used in cardiosurgical clinics do not yet represent a fully developed prophylaxis against exposure to nosocomial pathogens.

  8. Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration.

    PubMed

    An, Yulin; wei, Wei; Jing, Huan; Ming, Leiguo; Liu, Shiyu; Jin, Yan

    2015-11-23

    Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP(+)) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP(+)-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous.

  9. Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration

    PubMed Central

    An, Yulin; wei, Wei; Jing, Huan; Ming, Leiguo; Liu, Shiyu; Jin, Yan

    2015-01-01

    Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP+) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP+-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous. PMID:26594024

  10. Comparison of a liquid and a powder insecticidal dressing to aid healing and prevent flystrike of mulesing wounds in lambs.

    PubMed

    Pearse, B H; Peucker, S K

    1991-05-01

    A proprietary insecticidal mulesing powder containing diazinon and an experimental liquid dressing based on eucalyptus oil, naphthalene, cresylic acid and chlorfenvinphos in a carrier of liquid hydrocarbons and petroleum oil were compared for their ability to promote wound healing and reduce the incidence of fly strike in freshly mulesed lambs. Throughout the trial period of 4 weeks, fly trapping confirmed the presence of Lucilia cuprina in the paddock where the ewes and lambs were grazing At inspection one month after mulesing, no deaths had occurred since mulesing and no lambs showed evidence of cutaneous myiasis, although a number of their dams (with 8 months wool) were struck. At 4 weeks after mulesing, the wounds of the lambs treated with the experimental liquid dressing showed better healing than those treated with the powder dressing. It was concluded that both mulesing preparations were effective in inhibiting flystrike, but the liquid dressing promoted faster wound healing than did the powder.

  11. Comparison of a liquid and a powder insecticidal dressing to aid healing and prevent flystrike of mulesing wounds in lambs.

    PubMed

    Pearse, B H; Peucker, S K

    1991-05-01

    A proprietary insecticidal mulesing powder containing diazinon and an experimental liquid dressing based on eucalyptus oil, naphthalene, cresylic acid and chlorfenvinphos in a carrier of liquid hydrocarbons and petroleum oil were compared for their ability to promote wound healing and reduce the incidence of fly strike in freshly mulesed lambs. Throughout the trial period of 4 weeks, fly trapping confirmed the presence of Lucilia cuprina in the paddock where the ewes and lambs were grazing At inspection one month after mulesing, no deaths had occurred since mulesing and no lambs showed evidence of cutaneous myiasis, although a number of their dams (with 8 months wool) were struck. At 4 weeks after mulesing, the wounds of the lambs treated with the experimental liquid dressing showed better healing than those treated with the powder dressing. It was concluded that both mulesing preparations were effective in inhibiting flystrike, but the liquid dressing promoted faster wound healing than did the powder. PMID:1883292

  12. Stem Cell-Based Therapeutics to Improve Wound Healing

    PubMed Central

    Hu, Michael S.; Leavitt, Tripp; Malhotra, Samir; Duscher, Dominik; Pollhammer, Michael S.; Walmsley, Graham G.; Maan, Zeshaan N.; Cheung, Alexander T. M.; Schmidt, Manfred; Huemer, Georg M.; Longaker, Michael T.; Lorenz, H. Peter

    2015-01-01

    Issues surrounding wound healing have garnered deep scientific interest as well as booming financial markets invested in novel wound therapies. Much progress has been made in the field, but it is unsurprising to find that recent successes reveal new challenges to be addressed. With regard to wound healing, large tissue deficits, recalcitrant wounds, and pathological scar formation remain but a few of our most pressing challenges. Stem cell-based therapies have been heralded as a promising means by which to surpass current limitations in wound management. The wide differentiation potential of stem cells allows for the possibility of restoring lost or damaged tissue, while their ability to immunomodulate the wound bed from afar suggests that their clinical applications need not be restricted to direct tissue formation. The clinical utility of stem cells has been demonstrated across dozens of clinical trials in chronic wound therapy, but there is hope that other aspects of wound care will inherit similar benefit. Scientific inquiry into stem cell-based wound therapy abounds in research labs around the world. While their clinical applications remain in their infancy, the heavy investment in their potential makes it a worthwhile subject to review for plastic surgeons, in terms of both their current and future applications. PMID:26649195

  13. Raman spectroscopy and the spectral correlation index for predicting wound healing outcome: towards in vivo application

    NASA Astrophysics Data System (ADS)

    Berger, Adam G.; Crane, Nicole J.; Elster, Eric A.

    2016-03-01

    Combat wounds are sometimes confounded by healing complications that are not as prevalent in civilian wounds due to their high energy etiology. One complication of wound healing is dehiscence, where a surgically closed wound reopens after closure. This complication can have serious consequences for the patient, but knowledge about the molecular composition of the wound bed beyond what is readily visible may help clinicians mitigate these complications. It is necessary to develop techniques that can be used in vivo to assess and predict wound healing pointof- care so that care-takers can decide the best way to make informed clinical decisions regarding their patient's healing. Raman spectroscopy is a perfect candidate for predicting wound healing due to its ability to provide a detailed molecular fingerprint of the wound bed noninvasively. Here, we study the spectral correlation index, a measure of orthogonality, with ten reference tissue components to stratify wounds based on how they heal. We analyze these indexes over time to show the modulation of these tissue components over the wound healing process. Results show that qualitative observation of the spectra cannot reveal major differences between the dehisced and normal healing wounds, but the spectral correlation index can. Analysis of the spectral correlations across the wound healing process demonstrates the changes throughout the wound healing process, showing that early differences in tissue components may portend wound healing. Furthermore, Raman spectroscopy coupled with the spectral correlation index presents as a possible point-of-care tool for enabling discrimination of wounds with impaired healing.

  14. Comparative effect of human and Trypanosoma cruzi calreticulin in wound healing.

    PubMed

    Ignacio Arias, J; Sepulveda, Caroll; Bravo, Patricia; Hamilton-West, Christopher; Maldonado, Ismael; Ferreira, Arturo

    2015-01-01

    In orthopaedics, the use of factors that enhance granulation tissue formation and prevent or delay new bone regeneration is sometimes desirable. Calreticulin (CRT), a unique endoplasmic reticulum luminal Ca(2+) -binding chaperone widely distributed in eukaryotic cells, is involved in many cellular functions. Among them, CRT has an important influence in cutaneous wound healing and diverse processes associated with cutaneous repair, inhibition of angiogenesis, promotion of cell adhesion and antitumour effect. One of the molecules involved in several aspects of the host-parasite interplay is Trypanosoma cruzi calreticulin (TcCRT), which is highly homologous to human calreticulin (HuCRT). Here, recombinant (r)HuCRT and rTcCRT are compared on their abilities to affect fibroblast behaviour in a scratch plate assay, and wound healing in in vivo skin rat models. In molar terms, rTcCRT is three orders of magnitude more efficient than rHuCRT in increasing proliferation and migration of human fibroblasts in vitro. A similar effect was observed in vivo on rat skin wounds and inhibition of bone gap bridging in rabbit unicortical bone osteotomies.

  15. Effects of mouse genotype on bone wound healing and irradiation-induced delay of healing.

    PubMed

    Glowacki, Julie; Mizuno, Shuichi; Kung, Jason; Goff, Julie; Epperly, Michael; Dixon, Tracy; Wang, Hong; Greenberger, Joel S

    2014-01-01

    We tested the effects of mouse genotype (C57BL/6NHsd, NOD/SCID, SAMR1, and SAMP6) and ionizing irradiation on bone wound healing. Unicortical wounds were made in the proximal tibiae, and the time course of spontaneous healing and effects of irradiation were monitored radiographically and histologically. There was reproducible healing beginning with intramedullary osteogenesis, subsequent bone resorption by osteoclasts, gradual bridging of the cortical wound, and re-population of medullary hematopoietic cells. The most rapid wound closure was noted in SAMR1 mice, followed by SAMP6, C57BL/6NHsd, and NOD/SCID. Ionizing irradiation (20 Gy) to the leg significantly delayed bone wound healing in mice of all four genotypes. Mice with genetically-determined predisposition to early osteopenia (SAMP6) or with immune deficiency (NOD/SCID) had impairments in bone wound healing. These mouse models should be valuable for determining the effects of irradiation on bone healing and also for the design and testing of novel bone growth-enhancing drugs and mitigators of ionizing irradiation.

  16. Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats.

    PubMed

    de Oliveira, Ana Paula; Franco, Eryvelton de Souza; Rodrigues Barreto, Rafaella; Cordeiro, Daniele Pires; de Melo, Rebeca Gonçalves; de Aquino, Camila Maria Ferreira; E Silva, Antonio Alfredo Rodrigues; de Medeiros, Paloma Lys; da Silva, Teresinha Gonçalves; Góes, Alexandre José da Silva; Maia, Maria Bernadete de Sousa

    2013-01-01

    The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds. PMID:23573130

  17. Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats.

    PubMed

    de Oliveira, Ana Paula; Franco, Eryvelton de Souza; Rodrigues Barreto, Rafaella; Cordeiro, Daniele Pires; de Melo, Rebeca Gonçalves; de Aquino, Camila Maria Ferreira; E Silva, Antonio Alfredo Rodrigues; de Medeiros, Paloma Lys; da Silva, Teresinha Gonçalves; Góes, Alexandre José da Silva; Maia, Maria Bernadete de Sousa

    2013-01-01

    The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

  18. Effect of Semisolid Formulation of Persea Americana Mill (Avocado) Oil on Wound Healing in Rats

    PubMed Central

    de Oliveira, Ana Paula; Franco, Eryvelton de Souza; Rodrigues Barreto, Rafaella; Cordeiro, Daniele Pires; de Melo, Rebeca Gonçalves; de Aquino, Camila Maria Ferreira; e Silva, Antonio Alfredo Rodrigues; de Medeiros, Paloma Lys; da Silva, Teresinha Gonçalves; Góes, Alexandre José da Silva; Maia, Maria Bernadete de Sousa

    2013-01-01

    The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds. PMID:23573130

  19. [Advances in the effects of pH value of micro-environment on wound healing].

    PubMed

    Tian, Ruirui; Li, Na; Wei, Li

    2016-04-01

    Wound healing is a complex regeneration process, which is affected by lots of endogenous and exogenous factors. Researches have confirmed that acid environment could prevent wound infection and accelerate wound healing by inhibiting bacteria proliferation, promoting oxygen release, affecting keratinocyte proliferation and migration, etc. In this article, we review the literature to identify the potential relationship between the pH value of wound micro-environment and the progress of wound healing, and summarize the clinical application of variation of pH value of micro-environment in wound healing, thereby to provide new treatment strategy for wound healing.

  20. Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

    PubMed

    Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

    2014-04-01

    Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

  1. The quantitative and qualitative impairment of wound healing by adriamycin.

    PubMed

    Devereux, D F; Thibault, L; Boretos, J; Brennan, M F

    1979-03-01

    Clinical impression suggests that Adriamycin (ADR) interferes with wound healing. To examine the effects of ADR on wound healing, male Fischer rats were subjected to a dorsal, midline, full-thickness longitudinal incision (day 0). Wound clips were removed on day +7. Twenty animals per group were given intravenous ADR on day -7, day 0, day +3 and day +7. Twenty animals served as non-treated, wounded controls (C). Five animals/group were sacrificed on days +7, +14 and +21, at which time two 9.5 mm wide strips were taken from each animal perpendicular to the wound axis and submitted for wound breaking strength (WBS) measurements and load-extension curve analysis. WBS differed most markedly at Day 21 between C(1671 +/- 59g) and ADR day -7(1360 + 71 g) p less than 0.01; C and ADR day 0 (1051 +/- 108 g) p less than 0.001; C and ADR day + 3(1134 +/- 176 g) p less than 0.02. No difference existed between C and day +7 (1790 +/- 153 g). A point of inflection always occurred between 55-60% elongation in ADR treated animals only. This portion of the curve has been previously shown to represent collagen content. It is concluded that perioperative ADR administration (day -7 through day +3) significantly and substantially impairs skin wound healing in the rat. A form of collagen yielding underlies and may contribute to this defect. PMID:427732

  2. Effects of Topically Applied Vitamin D during Corneal Wound Healing

    PubMed Central

    Reins, Rose Y.; Hanlon, Samuel D.; Magadi, Sri; McDermott, Alison M.

    2016-01-01

    Vitamin D is an important regulator of immune function and largely acts to dampen chronic inflammatory events in a variety of tissues. There is also accumulating evidence that vitamin D acts to enhance initial inflammation, beneficial during both infection and wound healing, and then promotes resolution and prevention of chronic, damaging inflammation. The current study examines the effect of topical vitamin D in a mouse of model of corneal epithelial wound healing, where acute inflammation is necessary for efficient wound closure. At 12 and 18 hours post-wounding, vitamin D treatment significantly delayed wound closure by ~17% and increased infiltration of neutrophils into the central cornea. Basal epithelial cell division, corneal nerve density, and levels of VEGF, TGFβ, IL-1β, and TNFα were unchanged. However, vitamin D increased the production of the anti-microbial peptide CRAMP 12 hours after wounding. These data suggest a possible role for vitamin D in modulating corneal wound healing and have important implications for therapeutic use of vitamin D at the ocular surface. PMID:27035345

  3. Vitamin C promotes wound healing through novel pleiotropic mechanisms.

    PubMed

    Mohammed, Bassem M; Fisher, Bernard J; Kraskauskas, Donatas; Ward, Susan; Wayne, Jennifer S; Brophy, Donald F; Fowler, Alpha A; Yager, Dorne R; Natarajan, Ramesh

    2016-08-01

    Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.

  4. The effect of monochromatic infrared energy on diabetic wound healing.

    PubMed

    He, Yayi; Yip, Selina Ly; Cheung, Kwok-Kuen; Huang, Lin; Wang, Shijie; Cheing, Gladys Ly

    2013-12-01

    This study examined the effect of monochromatic infrared energy (MIRE) on diabetic wound healing. Fifteen diabetic rats were given MIRE intervention on their skin wounds located on the dorsum and compared with 15 control diabetic rats. Assessments were conducted for each group at weeks 1, 2 and 4 post wounding (five rats at each time point) by calculating the percentage of wound closures (WCs) and performing histological and immunohistochemical staining on sections of wound tissue. Evaluations of WCs and histological examinations of reepithelialisation, cellular content and granulation tissue formation showed no significant difference between the MIRE and the control group at each time point. Through semi-quantitative immunohistochemical staining, the deposition of type I collagen in the MIRE group was found to have improved when compared with the control group at the end of week 2 (P = 0.05). No significant differences in the myofibroblast population were detected between the two groups. In conclusion, MIRE appeared to promote collagen deposition in the early stage of wound healing in diabetic rats, but the overall wound healing in the MIRE group was not significantly different from that of the control group.

  5. Profiling wound healing with wound effluent: Raman spectroscopic indicators of infection

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; Elster, Eric A.

    2012-01-01

    The care of modern traumatic war wounds remains a significant challenge for clinicians. Many of the extremity wounds inflicted during Operation Enduring Freedom and Operation Iraqi Freedom are colonized or infected with multi-drug resistant organisms, particularly Acinetobacter baumannii. Biofilm formation and resistance to current treatments can significantly confound the wound healing process. Accurate strain identification and targeted drug administration for the treatment of wound bioburden has become a priority for combat casualty care. In this study, we use vibrational spectroscopy to examine wound exudates for bacterial load. Inherent chemical differences in different bacterial species and strains make possible the high specificity of vibrational spectroscopy.

  6. 14S,21R-dihydroxydocosahexaenoic acid remedies impaired healing and mesenchymal stem cell functions in diabetic wounds.

    PubMed

    Tian, Haibin; Lu, Yan; Shah, Shraddha P; Hong, Song

    2011-02-11

    Treatment of diabetes-impaired wound healing remains a major unresolved medical challenge. Here, we identified suppressed formation of a novel reparative lipid mediator 14S,21R-dihydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA) in cutaneous wounds of diabetic db/db mice. These results indicate that diabetes impedes the biosynthetic pathways of 14S,21R-diHDHA in skin wounds. Administration of exogenous 14S,21R-diHDHA to wounds in diabetic animals rescued healing and angiogenesis. When db/db mesenchymal stem cells (MSCs) were administered together with 14S,21R-diHDHA to wounds in diabetic animals, they coacted to accelerate wound re-epithelialization, granulation tissue formation, and synergistically improved vascularization. In the pivotal cellular processes of angiogenesis, 14S,21R-diHDHA enhanced VEGF release, vasculature formation, and migration of db/db dermal microvascular endothelial cells (DMVECs), as well as remedied paracrine angiogenic functions of db/db MSCs, including VEGF secretion and the promotion of DMVEC migration and vasculature formation. Our results show that 14S,21R-diHDHA activates the p38 MAPK pathway in wounds, db/db MSCs, and DMVECs. Overall, the impeded formation of 14S,21R-diHDHA described in this study suggests that diabetes could affect the generation of pro-healing lipid mediators in wound healing. By restoring wound healing and MSC functions, 14S,21R-diHDHA is a new lead for the development of better therapeutics used in treating wounds of diabetics.

  7. [New directions of research related to chronic wound healing].

    PubMed

    Rusak, Agnieszka; Rybak, Zbigniew

    2013-01-01

    Optimal nutrition, immunological state and psychological condition play an important role in the process of chronic wound healing. Infections caused by pathogens resistant to commonly used antibiotics additionally complicate and disturb regeneration of wounds. As part of the treatment, modern wound dressings are used, for example designed on the basis of alginates, dextranomers, hydrogels, hydrofiber, polyurethanes foams, hydrocolloids and liquids for wound debridement such us 0.9% NaCl, the PWE liquid, Ringer's liquid, octenidine. Owing to their features, treatment in accordance with TIME concept could be realized, because they provide moisture wound bed, protection against contamination, gas exchange, protection of wound edges and infection control. Repairing process in chronic wounds is dependent on blood flow in tissues, which may be insufficient. The result is a permanent hypoxia. Natural occurring antioxidants are becoming more crucial in chronic wound treatment. They decrease oxygen radical concentration, increase angiogenesis, reduce inflammatory response, stimulate fibroblasts and keratinocytes proliferation, possess antibacterial properties against chemotherapeutic resistant strains. There are a lot of antioxidants in honey, papaya fruit (Carrica papaia L.), transgenic flax (Linum usitatissimum), and in orange oil (Citrus sinensis), stem of acanthus (Acanthus ebracteatus), leafs of tea (Camellia sinensis). Application of biologically active, natural derived compounds is nowadays a direction of intense in vitro and in vivo research focused on the chronic wound treatment. Results suggest beneficial influence of antioxidant on wound repairing process. Clinical research are needed to state effective influence of natural compound in the chronic wound treatment.

  8. [New directions of research related to chronic wound healing].

    PubMed

    Rusak, Agnieszka; Rybak, Zbigniew

    2013-01-01

    Optimal nutrition, immunological state and psychological condition play an important role in the process of chronic wound healing. Infections caused by pathogens resistant to commonly used antibiotics additionally complicate and disturb regeneration of wounds. As part of the treatment, modern wound dressings are used, for example designed on the basis of alginates, dextranomers, hydrogels, hydrofiber, polyurethanes foams, hydrocolloids and liquids for wound debridement such us 0.9% NaCl, the PWE liquid, Ringer's liquid, octenidine. Owing to their features, treatment in accordance with TIME concept could be realized, because they provide moisture wound bed, protection against contamination, gas exchange, protection of wound edges and infection control. Repairing process in chronic wounds is dependent on blood flow in tissues, which may be insufficient. The result is a permanent hypoxia. Natural occurring antioxidants are becoming more crucial in chronic wound treatment. They decrease oxygen radical concentration, increase angiogenesis, reduce inflammatory response, stimulate fibroblasts and keratinocytes proliferation, possess antibacterial properties against chemotherapeutic resistant strains. There are a lot of antioxidants in honey, papaya fruit (Carrica papaia L.), transgenic flax (Linum usitatissimum), and in orange oil (Citrus sinensis), stem of acanthus (Acanthus ebracteatus), leafs of tea (Camellia sinensis). Application of biologically active, natural derived compounds is nowadays a direction of intense in vitro and in vivo research focused on the chronic wound treatment. Results suggest beneficial influence of antioxidant on wound repairing process. Clinical research are needed to state effective influence of natural compound in the chronic wound treatment. PMID:24377187

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

    PubMed

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

    2015-01-01

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

  10. Biofilm delays wound healing: A review of the evidence.

    PubMed

    Metcalf, Daniel G; Bowler, Philip G

    2013-01-01

    Biofilm is the predominant mode of life for bacteria and today it is implicated in numerous human diseases. A growing body of scientific and clinical evidence now exists regarding the presence of biofilm in wounds. This review summarizes the clinical experiences and in vivo evidence that implicate biofilm in delayed wound healing. The various mechanisms by which biofilm may impede healing are highlighted, including impaired epithelialization and granulation tissue formation, and reduced susceptibilities to antimicrobial agents and host defenses. Strategies to manage biofilm and encourage progression to wound healing are discussed; these include debridement and appropriate antimicrobial therapies which may be improved upon in the future with the emergence of anti-biofilm technologies.

  11. Wound healing activity of flower extract of Calendula officinalis.

    PubMed

    Preethi, Korengath C; Kuttan, Ramadasan

    2009-01-01

    The effects of oral and topical application of Calendula officinalis flower extract on excision wounds made in rats were checked. The parameters assessed were the days needed for re-epithelization and percentage of wound closure. The hydroxy proline and hexosamine content in the granuloma tissue of the wound was also measured. The percentage of wound closure was 90.0% in the extract-treated group, whereas the control group showed only 51.1% on the eighth day of wounding (p < .01). The days needed for re-epithelization were 17.7 for the control animals; extract treatment at a dose of 20 or 100 mg/kg b.wt reduced the period to 14 and 13 days, respectively. A significant increase was observed in the hydroxy proline and hexosamine content in the extract-treated group compared with the untreated animals. The data indicate potent wound healing activity ofC. officinalis extract. PMID:19601397

  12. Integration of silver nanoparticle-impregnated polyelectrolyte multilayers into murine-splinted cutaneous wound beds.

    PubMed

    Guthrie, Kathleen M; Agarwal, Ankit; Teixeira, Leandro B C; Dubielzig, Richard R; Abbott, Nicholas L; Murphy, Christopher J; Singh, Harpreet; McAnulty, Jonathan F; Schurr, Michael J

    2013-01-01

    Silver is a commonly used topical antimicrobial. However, technologies to immobilize silver at the wound surface are lacking, while currently available silver-containing wound dressings release excess silver that can be cytotoxic and impair wound healing. We have shown that precise concentrations of silver at lower levels can be immobilized into a wound bed using a polyelectrolyte multilayer attachment technology. These silver nanoparticle-impregnated polyelectrolyte multilayers are noncytotoxic yet bactericidal in vitro, but their effect on wound healing in vivo was previously unknown. The purpose of this study was to determine the effect on wound healing of integrating silver nanoparticle/polyelectrolyte multilayers into the wound bed. A full-thickness, splinted, excisional murine wound healing model was employed in both phenotypically normal mice and spontaneously diabetic mice (healing impaired model). Gross image measurements showed an initial small lag in healing in the silver-treated wounds in diabetic mice, but no difference in time to complete wound closure in either normal or diabetic mice. Histological analysis showed modest differences between silver-treated and control groups on day 9, but no difference between groups at the time of wound closure. We conclude that silver nanoparticle/polyelectrolyte multilayers can be safely integrated into the wound beds of both normal and diabetic mice without delaying wound closure, and with transient histological effects. The results of this study suggest the feasibility of this technology for use as a platform to affect nanoscale wound engineering approaches to microbial prophylaxis or to augment wound healing. PMID:23511285

  13. Cutaneous Melioidosis Cluster Caused by Contaminated Wound Irrigation Fluid

    PubMed Central

    Merritt, Adam J.; Peck, Mariani; Gayle, Dionne; Levy, Avram; Ler, Yi-Horng; Raby, Edward; Gibbs, Tristan M.

    2016-01-01

    Melioidosis usually occurs after environmental exposure to Burkholderia pseudomallei in the tropics. A cluster of 5 cutaneous melioidosis cases occurred in suburban southwest Australia after an earlier case in January 2012. We collected environmental samples at the first patient’s home in January 2012 and from a nearby health center in December 2013 after 2 new cases occurred in the same postal district. We isolated genotypically identical B. pseudomallei from the first patient and 5 other patients in the district. Environmental sampling implicated an opened bottle of saline wound irrigation fluid containing >106 B. pseudomallei/mL. The bottle included instructions to discard within 24 hours of opening. No further cases of B. pseudomallei infection occurred after removing the contaminated bottle. This cutaneous melioidosis cluster demonstrates that B. pseudomallei can survive and disseminate in widely used medical fluids beyond its known geographic distribution, highlighting a need to use these products according to manufacturers’ instructions. PMID:27438887

  14. Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots

    PubMed Central

    Fugate, Karen K.; Ribeiro, Wellington S.; Lulai, Edward C.; Deckard, Edward L.; Finger, Fernando L.

    2016-01-01

    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 stored at 6 and 12°C for 28 days. Surface abrasions are common injuries of stored roots, and the storage temperatures used are typical of freshly harvested or rapidly cooled roots. Transpiration rate from the wounded surface and root weight loss were used to quantify wound healing. At 12°C, transpiration rate from the wounded surface declined within 14 days and wounded roots lost weight at a rate similar to unwounded controls. At 6°C, transpiration rate from the wounded surface did not decline in the 28 days after injury, and wounded roots lost 44% more weight than controls after 28 days storage. Melanin formation, lignification, and suberization occurred more rapidly at 12°C than at 6°C, and a continuous layer of lignified and suberized cells developed at 12°C, but not at 6°C. Examination of enzyme activities involved in melanin, lignin, and suberin formation indicated that differences in melanin formation at 6 and 12°C were related to differences in polyphenol oxidase activity, although no relationships between suberin or lignin formation and phenylalanine ammonia lyase or peroxidase activity were evident. Wound-induced respiration was initially greater at 12°C than at 6°C. However, with continued storage, respiration rate of wounded roots declined more rapidly at 12°C, and over 28 days, the increase in respiration due to injury was 52% greater in roots stored at 6°C than in roots stored at 12°C. The data indicate that storage at 6°C severely slowed and impaired wound-healing of surface-abraded sugarbeet roots relative to roots stored at 12°C and suggest that postharvest losses may be accelerated if freshly harvested roots are cooled too quickly. PMID

  15. Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots.

    PubMed

    Fugate, Karen K; Ribeiro, Wellington S; Lulai, Edward C; Deckard, Edward L; Finger, Fernando L

    2016-01-01

    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 stored at 6 and 12°C for 28 days. Surface abrasions are common injuries of stored roots, and the storage temperatures used are typical of freshly harvested or rapidly cooled roots. Transpiration rate from the wounded surface and root weight loss were used to quantify wound healing. At 12°C, transpiration rate from the wounded surface declined within 14 days and wounded roots lost weight at a rate similar to unwounded controls. At 6°C, transpiration rate from the wounded surface did not decline in the 28 days after injury, and wounded roots lost 44% more weight than controls after 28 days storage. Melanin formation, lignification, and suberization occurred more rapidly at 12°C than at 6°C, and a continuous layer of lignified and suberized cells developed at 12°C, but not at 6°C. Examination of enzyme activities involved in melanin, lignin, and suberin formation indicated that differences in melanin formation at 6 and 12°C were related to differences in polyphenol oxidase activity, although no relationships between suberin or lignin formation and phenylalanine ammonia lyase or peroxidase activity were evident. Wound-induced respiration was initially greater at 12°C than at 6°C. However, with continued storage, respiration rate of wounded roots declined more rapidly at 12°C, and over 28 days, the increase in respiration due to injury was 52% greater in roots stored at 6°C than in roots stored at 12°C. The data indicate that storage at 6°C severely slowed and impaired wound-healing of surface-abraded sugarbeet roots relative to roots stored at 12°C and suggest that postharvest losses may be accelerated if freshly harvested roots are cooled too quickly. PMID

  16. Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots.

    PubMed

    Fugate, Karen K; Ribeiro, Wellington S; Lulai, Edward C; Deckard, Edward L; Finger, Fernando L

    2016-01-01

    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 stored at 6 and 12°C for 28 days. Surface abrasions are common injuries of stored roots, and the storage temperatures used are typical of freshly harvested or rapidly cooled roots. Transpiration rate from the wounded surface and root weight loss were used to quantify wound healing. At 12°C, transpiration rate from the wounded surface declined within 14 days and wounded roots lost weight at a rate similar to unwounded controls. At 6°C, transpiration rate from the wounded surface did not decline in the 28 days after injury, and wounded roots lost 44% more weight than controls after 28 days storage. Melanin formation, lignification, and suberization occurred more rapidly at 12°C than at 6°C, and a continuous layer of lignified and suberized cells developed at 12°C, but not at 6°C. Examination of enzyme activities involved in melanin, lignin, and suberin formation indicated that differences in melanin formation at 6 and 12°C were related to differences in polyphenol oxidase activity, although no relationships between suberin or lignin formation and phenylalanine ammonia lyase or peroxidase activity were evident. Wound-induced respiration was initially greater at 12°C than at 6°C. However, with continued storage, respiration rate of wounded roots declined more rapidly at 12°C, and over 28 days, the increase in respiration due to injury was 52% greater in roots stored at 6°C than in roots stored at 12°C. The data indicate that storage at 6°C severely slowed and impaired wound-healing of surface-abraded sugarbeet roots relative to roots stored at 12°C and suggest that postharvest losses may be accelerated if freshly harvested roots are cooled too quickly.

  17. Microbial biofilms and wound healing: an ecological hypothesis.

    PubMed

    Krom, Bastiaan P; Oskam, Jacques

    2014-05-19

    Man has lived together with microbes for so long that we have become completely dependent on their presence. Most microbes reside in biofilms; structured communities encased in a protective matrix of biopolymers. Under healthy conditions, the microbial biofilm is in balance with itself (endo-balance) and with the host (exo-balance). Integrity of the skin is an important immunological function. Wounds go through a well-orchestrated series of healing steps. However, if for some reason healing times are extended, serious problems related to infection and homeostasis can develop. Based on recent advances in biofilm research and microbiological identification we discuss two hypotheses describing the role of microbial biofilms in chronic wound biology. The first hypothesis describes microbial biofilms as the cause of extended healing times. The second hypothesis is based on the host as cause of extended healing times and basically treats microbial biofilms as a logical consequence of failure to re-build the integrity of the skin.

  18. Ultrasonographic assessment of standing laparotomy wound healing in dairy cows.

    PubMed

    Buczinski, S; Bourel, C; Bélanger, A M

    2012-08-01

    The surgical wounds of 40 cows with a standing clean laparotomy were assessed 10-15 days after surgery. The abdominal wall thickness on the upper (w1), the middle (w2) and the lower (w3) third of the wound (and the contralateral flank n1, n2, and n3), the presence of edema, cavitary lesion, capsulated lesion, or visualization of shadow artifact in the wound were assessed ultrasonographically. On day 30, wound healing status (normal or surgical site infection (SSI)) was determined. Five out of 39 cows (12.8%) had SSI. A significant positive correlation was found between w3 and edema (p<0.01; r=0.44), w3/n3 and edema (p<0.05; r=0.32), w3 and pain on wound palpation (p<0.01; r=0.41); w3/n3 and the presence of pain (p<0.002; r=0.49) and w2/n2 and pain when palpating the wound (p<0.05; r=0.33). No association was found between the ultrasonographic evidence of edema and SSI (p=0.10), cavitary lesion and SSI (p=0.65), encapsulated lesion and SSI (p=1), and shadow artefact and SSI (p=1). The wound ultrasonography 10-15 days after surgery was not predictive of abnormal wound healing.

  19. An Essential Role of NRF2 in Diabetic Wound Healing.

    PubMed

    Long, Min; Rojo de la Vega, Montserrat; Wen, Qing; Bharara, Manish; Jiang, Tao; Zhang, Rui; Zhou, Shiwen; Wong, Pak K; Wondrak, Georg T; Zheng, Hongting; Zhang, Donna D

    2016-03-01

    The high mortality and disability of diabetic nonhealing skin ulcers create an urgent need for the development of more efficacious strategies targeting diabetic wound healing. In the current study, using human clinical specimens, we show that perilesional skin tissues from patients with diabetes are under more severe oxidative stress and display higher activation of the nuclear factor-E2-related factor 2 (NRF2)-mediated antioxidant response than perilesional skin tissues from normoglycemic patients. In a streptozotocin-induced diabetes mouse model, Nrf2(-/-) mice have delayed wound closure rates compared with Nrf2(+/+) mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis. More importantly, pharmacological activation of the NRF2 pathway significantly improves diabetic wound healing. In vitro experiments in human immortalized keratinocyte cells confirm that NRF2 contributes to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, and increasing the expression of TGF-β1 and lowering MMP9 under high-glucose conditions. This study indicates an essential role for NRF2 in diabetic wound healing and the therapeutic benefits of activating NRF2 in this disease, laying the foundation for future clinical trials using NRF2 activators in treating diabetic skin ulcers. PMID:26718502

  20. Wound healing: a new perspective on glucosylated tetrahydrocurcumin

    PubMed Central

    Bhaskar Rao, Adari; Prasad, Ernala; Deepthi, Seelam Siva; Haritha, Vennapusa; Ramakrishna, Sistla; Madhusudan, Kuncha; Surekha, Mullapudi Venkata; Venkata Rao, Yerramilli Sri Rama

    2015-01-01

    Wound healing represents a dynamic set of coordinated physiological processes observed in response to tissue injury. Several natural products are known to accelerate the process of wound healing. Tetrahydrocurcumin (THC), an in vivo biotransformed product/metabolite of curcumin, is known to exhibit a wide spectrum of biological activities similar to those of native curcuminoids. The poor bioavailability of these curcuminoids limits their clinical applications. The present study highlights the percutaneous absorption and wound healing activity of glucosyl-conjugated THC (glucosyl-THC) in male Wistar rats. A high plasma concentration of glucosyl-THC (4.35 μg/mL) was found in rats 3 hours after application. A significant enhanced wound healing activity and reduced epithelialization time were observed in rats that received glucosyl-THC. This may have been due to the improved bioavailability of the glucosyl compound. The nonstaining and lack of skin-sensitive side effects render the bioconjugated glucosyl-THC a promising therapeutic compound in the management of excision wounds and in cosmetic applications, in the near future. PMID:26203224

  1. Burn wound healing properties of asiaticoside and madecassoside

    PubMed Central

    Hou, Qiang; Li, Ming; Lu, Yan-Hua; Liu, Dong-Hong; Li, Cheng-Cun

    2016-01-01

    The healing of burn wounds has been widely characterized to be highly intricate, involving processes such as neo-vascularization, granulation, re-epithelialization, inflammation and wound contraction. Various therapies are available for the management of burn wounds; however, a truly effective therapeutic strategy has yet to be identified due to safety issues. The aim of the present study was to assess and confirm the burn wound healing properties of the compounds asiaticoside (AE) and madecassoside (MA), which are found in the herb Centella asiatica. The cytotoxic nature of the AE and MA were inspected and were confirmed to be non-toxic up to 500 ppm. The compounds AE and MA increased monocyte chemoattractant protein-1 production, but caused no significant effect on vascular endothelial growth factor production. In addition, an in vivo animal burn model was employed to represent the features of burn wound healing. Hence, the present results warrant the further investigation of C. asiatica extracts for use in burn healing. PMID:27588048

  2. Nutrition, Anabolism, and the Wound Healing Process: An Overview

    PubMed Central

    Demling, Robert H.

    2009-01-01

    Objective: To develop a clear, concise, and up-to-date treatise on the role of anabolism from nutrition in wound healing. Special emphasis was to be placed on the effect of the stress response to wounding and its effect. Methods: A compilation of both the most important and most recent reports in the literature was used to also develop the review. The review was divided into sections to emphasize specific nutrition concepts of importance. Results: General and specific concepts were developed from this material. Topics included body composition and lean body mass, principles of macronutritional utilization, the stress response to wounding, nutritional assessment, nutritional support, and use of anabolic agents. Conclusions: We found that nutrition is a critical component in all the wound healing processes. The stress response to injury and any preexistent protein-energy malnutrition will alter this response, impeding healing and leading to potential severe morbidity. A decrease in lean body mass is of particular concern as this component is responsible for all protein synthesis necessary for healing. Nutritional assessment and support needs to be well orchestrated and precise. The use of anabolic agents can significantly increase overall lean mass synthesis and directly or indirectly improves healing by increasing protein synthesis. PMID:19274069

  3. Neurolaena lobata L. promotes wound healing in Sprague Dawley rats

    PubMed Central

    Nayak, Bijoor Shivananda; Ramlogan, Surrin; Chalapathi Rao, AV; Maharaj, Sandeep

    2014-01-01

    Background: The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. Aim: The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Materials and Methods: Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group animals were treated with mupirocin and petroleum jelly, respectively. Treatment was given for 13 days and the wound area was measured on alternate days. Parameters of healing assessed were the rate of wound contraction, period of epithelialization and hydroxyproline content. Antimicrobial activity of the extract was observed against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Results: Phytochemical analysis of the extract showed the presence of saponins, tannins, alkaloids and flavanoids. Extract-treated animals exhibited 87% reduction in the wound area over 13 days when compared with the control (78%) and standard (83%) groups (P < 0.05). A significant decrease in the epithelialization period was noticed with the extract-treated test group animals compared with the controls and the standard group animals (P < 0.008). The hydroxyproline content of the extract-treated animals was higher (230.5 ± 42.1) when evaluated against the control and (79.0 ± 32.2) and the standard (115.0 ± 44.5) groups (P < 0.05). Conclusion: Increase in the rate of wound contraction and hydroxyproline content with decrease in epithelialization time in extract-treated animals support further evaluation of N. lobata as a pharmacotherapy for wound healing. PMID:25143886

  4. Endocytosis-dependent coordination of multiple actin regulators is required for wound healing.

    PubMed

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla; Millard, Tom H

    2015-08-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form "signaling centers" along the wound edge that control actin assembly. We conclud