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Sample records for accelerated wound closure

  1. Combination Therapy Accelerates Diabetic Wound Closure

    PubMed Central

    Allen Jr., Robert J.; Soares, Marc A.; Haberman, Ilyse D.; Szpalski, Caroline; Schachar, Jeffrey; Lin, Clarence D.; Nguyen, Phuong D.; Saadeh, Pierre B.; Warren, Stephen M.

    2014-01-01

    Background Non-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis. Methods and Results Wounded mice were assigned to 1 of 5 experimental arms (n = 8/arm): saline treated wild-type, saline treated diabetic, AMD3100 treated diabetic, PDGF-BB treated diabetic, and AMD3100/PDGF-BB treated diabetic. Circulating PC number and wound vascularity were analyzed for each group (n = 8/group). Cellular function was assessed in the presence of AMD3100. Using a validated preclinical model of type II diabetic wound healing, we show that AMD3100 therapy (10 mg/kg; i.p. daily) alone can rescue diabetes-specific defects in PC mobilization, but cannot restore normal wound neovascularization. Through further investigation, we demonstrate an acquired trafficking-defect within AMD3100-treated diabetic PCs that can be rescued by PDGF-BB (2 μg; topical) supplementation within the wound environment. Finally, we determine that combination therapy restores diabetic wound neovascularization and accelerates time to wound closure by 40%. Conclusions Combination AMD3100 and PDGF-BB therapy synergistically improves BM PC mobilization and trafficking, resulting in significantly improved diabetic wound closure and neovascularization. The success of this

  2. Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis.

    PubMed

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

    2013-07-01

    Delays in wound healing often result in infection, chronic ulceration, and possible amputation of extremities. Impaired wound healing is a major complication of the 23 million people in the USA with diabetes, and financial and medical burdens are demanding new treatments for wound healing. Previous studies have demonstrated that topical application of the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in rats with streptozotocin-induced type 1 diabetes. A target of NTX's action is DNA synthesis and cell proliferation. In this study, granulation tissue was evaluated to ascertain the specific cellular targets that were impaired in diabetic wounds, as well as those that were enhanced following NTX application. Mast cell number as well as the number of new blood vessels immunoreactive to fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and alpha smooth muscle actin (α-SMA) antibodies were recorded at 3, 5, 8, 10, 15, and 20 days following creation of full-thickness dorsal cutaneous wounds in normal and type 1 diabetic rats. Diabetic rats displayed delays in wound closure as well as a reduction in the number of mast cells responding to the injury, and delays in the spatial and temporal expression of FGF-2, VEGF, and α-SMA in capillaries. Topical NTX accelerated the rate of wound closure and stimulated expression of angiogenic factors within granulation tissue of diabetic rats relative to control animals receiving saline in moisturizing cream. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be modulated by topical NTX to enhance proliferative events in wound healing.

  3. Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation

    PubMed Central

    Wang, Haifeng; Chen, Lianyu; Liu, Yang; Luo, Bangzhen; Xie, Nanzi; Tan, Tao; Song, Lige; Erli, Pei; Luo, Ming

    2016-01-01

    Background: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse. Methods and Results: By using an in vivo excisional wound healing model in Goto-Kakizaki (GK) rats, we found that injection of PMSCs accelerates wound closure. Further studies revealed that application of PMSCs can regulate inflammation associated with wound healing by controlling secretion of pro- and anti-inflammatory factors, the beneficial effects can be partially blocked by application of antibodies against interleukin-10 (IL-10). Furthermore, in vitro experiments suggested that co-culture of PMSCs with human dermal fibroblasts can significantly inhibit activation of NF-ĸB induced by lipopolysaccharides (LPS), indicating the molecular mechanism of PMSCs mediated immunomodulation. Conclusion: Taken together, our study suggested that the immunomodulation of PMSCs play an important role on diabetic dermal wound healing process, thus PMSCs might represent an attractive choice for treatment of diabetes dermal wound and DFU. PMID:27904691

  4. Accelerated Wound Closure - Differently Organized Nanofibers Affect Cell Migration and Hence the Closure of Artificial Wounds in a Cell Based In Vitro Model

    PubMed Central

    2017-01-01

    Nanofiber meshes holds great promise in wound healing applications by mimicking the topography of extracellular matrix, hence providing guidance for crucial cells involved in the regenerative processes. Here we explored the influence of nanofiber alignment on fibroblast behavior in a novel in vitro wound model. The model included electrospun poly-ε-caprolactone scaffolds with different nanofiber orientation. Fibroblasts were cultured to confluency for 24h before custom-made inserts were removed, creating cell-free zones serving as artificial wounds. Cell migration into these wounds was evaluated at 0-, 48- and 96h. Cell morphological analysis was performed using nuclei- and cytoskeleton stainings. Cell viability was assessed using a biochemical assay. This study demonstrates a novel in vitro wound assay, for exploring of the impact of nanofibers on wound healing. Additionally we show that it’s possible to affect the process of wound closure in a spatial manner using nanotopographies, resulting in faster closure on aligned fiber substrates. PMID:28060880

  5. Immediate tangential excision accelerates wound closure but does not reduce scarring of mid-dermal porcine burns.

    PubMed

    Macri, L K; Singer, A J; McClain, S A; Crawford, L; Prasad, A; Kohn, J; Clark, R A F

    2016-03-31

    Current evidence supports the use of excision to remove eschar from deep dermal and full-thickness burns. However, the role of excision of mid-dermal burns remains unclear. This study aimed to develop a porcine model that could produce reproducible middermal thermal burns that undergo tangential excision; and investigate the effects of immediate tangential excision (30 minutes postburn) on healing and scarring. An aluminum bar preheated in hot water (70°C) was applied for 20 or 30 s to produce a total of sixteen mid-dermal burns per pig on each of six pigs. Thirty minutes after burn creation, half of the burns were tangentially excised. Four partial- thickness wounds per pig were created as controls. Depth of burn injury (1 and 24 h), reepithelialization (7 and 10 d) and scar depth (28 d) were assessed microscopically. Total scar surface area was grossly evaluated on day 28. Exposure of porcine skin to a preheated aluminum bar at 70 °C for 20 or 30 sec resulted in reproducible mid-dermal burns, where immediate excision enhanced complete wound closure as judged by complete re-epithelialization, but did not reduce initial depth of injury, scar contraction and scar depth. Immediate surgical intervention is sufficient to enhance wound closure, but not to mitigate mid-dermal burn scar formation. This work provides a suitable animal model to evaluate novel therapies that may be used to inhibit burn progression, accelerate wound closure and decrease scarring, especially those therapies unable to penetrate burn eschar.

  6. Wound closure after split-thickness skin grafting is accelerated with the use of continuous direct anodal microcurrent applied to silver nylon wound contact dressings.

    PubMed

    Huckfeldt, Roger; Flick, A Bart; Mikkelson, Debbie; Lowe, Cindy; Finley, Phillip J

    2007-01-01

    Wound healing after graft closure of excised burn wounds is a critical factor in the recovery process after thermal injury. Processes that speed time to stable wound closure should lead to improved outcomes, shorter lengths of hospital stays, and decreased complications. A randomized clinical trial to test the ability of continuous direct anodal microcurrent application to silver nylon wound contact dressings was designed. Time for wound closure after split-thickness skin grafting was observed. Thirty patients with full-thickness thermal burns were randomized into two groups. The control group received postoperative dressing care using moistened silver nylon fabric covered with gauze after tangential burn wound excision and split-thickness skin grafting. The study group received an identical protocol with the addition of continuous direct anodal microcurrent application. Time to 95% wound closure was measured using digital photography. The digital photographs were evaluated by a burn surgeon blinded to the patient's randomization. An independent t-test was used to analyze the data. The study group experienced a 36% reduction in time to wound closure (mean of 4.6 days) as compared to the control group (mean of 7.2 days). This was statistically significant at a P value of <.05. The use of continuous direct anodal microcurrent decreased time to wound closure after split-thickness skin grafting.

  7. Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine

    PubMed Central

    Mehrabani, Mehrnaz; Seyyedkazemi, Seyyed Mohsen; Nematollahi, Mohammad Hadi; Jafari, Elham; Mehrabani, Mitra; Mehdipour, Mohammad; Sheikhshoaee, Zahra; Mandegary, Ali

    2016-01-01

    Background A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans. Objectives This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.) Methods Twenty-four mice were selected based on simple random sampling. Twenty-five percent of the total body surface area was burned by exposure to boiling water, according to the Walker-Mason method. NF and silver sulfadiazine (the positive control) were applied topically twice a day for 21 days. The burned area in the negative control group was left untreated. Epithelialization time and the percent of wound contraction were measured during the treatment period. The process of wound repairing was evaluated using histological (H and E and trichrome staining) and immunohistological (anti-pancytokeratin) methods. Results When compared to the controls, NF significantly improved wound contraction after day 10. Epithelialization time in the NF group was significantly faster than in the other groups (20 vs. 25.5 days) (P < 0.001). Histopathological and immunohistochemical findings confirmed the efficacy of the NF. Conclusions A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF. PMID:28191338

  8. EPIDERMAL DELETION OF HIF-2α STIMULATES WOUND CLOSURE

    PubMed Central

    Cowburn, Andrew S.; Crotty Alexander, Laura E.; Southwood, Mark; Nizet, Victor; Chilvers, Edwin R.; Johnson, Randall S.

    2013-01-01

    Wound closure requires a complex series of micro-environmentally influenced events. A key aspect of wound closure is the migration of keratinocytes across the open wound. It has been found previously that the response to hypoxia via the HIF-1α transcription factor is a key feature of wound closure. The need for hypoxic response is likely due to interrupted wound vasculature as well as infection, and in this work, we investigated the need for a highly related hypoxic response transcription factor, HIF-2α. This factor was deleted tissue-specifically in mice, and the resulting mice were found to have an accelerated rate of wound closure. This is correlated with a reduced bacterial load and inflammatory response in these mice. This indicates that manipulating or reducing the HIF-2α response in keratinocytes could be a useful means to accelerate wound healing and tissue repair. PMID:24037341

  9. 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.

  10. A homeopathic remedy from arnica, marigold, St. John’s wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts

    PubMed Central

    2012-01-01

    Background Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. Methods We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712–2), its succussed hydroalcoholic solvent (0712–1) and unsuccussed solvent (0712–3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined “wound field”. All assays were performed in three independent controlled experiments. Results None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712–2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712–1) at 1:100 dilutions (p < 0.001). Unsuccussed solvent (0712–3) had no influence on cell migration (6.3%; p > 0.05). Preparation (0712–2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712–1), which caused 22.1% wound closure. Conclusion Results of this study showed that the low potency homeopathic remedy (0712–2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis. PMID:22809174

  11. Mechanics of Wound Closure: Emerging Tape-Based Wound Closure Technology vs. Traditional Methods

    PubMed Central

    Ichiryu, Kei; Kefel, Pelin; Keller, Juergen; Grice, Jon; Belson, Ori; Storne, Eric; Safa, Bauback

    2016-01-01

    To date, there is still a lack of understanding of how wound closure methods perform comparatively under daily bodily movement during the course of healing and how they affect the mechanics of healing. The present study is a first step in understanding and objectively quantifying the gap. The study provides both a new method of metrology for noninvasive evaluation of skin mechanics at the onset of wound healing and an emerging tape-based wound closure technology. The latter shows better performance with respect to commonly used staples and sutures, holding the wound intact and providing uniform mechanical support across the incision. PMID:27882274

  12. Microwave Tissue Soldering for Immediate Wound Closure

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey; Ngo, Phong H.; Phan, Chau T.; Byerly, Diane; Dusl, John; Sognier, Marguerite A.; Carl, James

    2011-01-01

    A novel approach for the immediate sealing of traumatic wounds is under development. A portable microwave generator and handheld antenna are used to seal wounds, binding the edges of the wound together using a biodegradable protein sealant or solder. This method could be used for repairing wounds in emergency settings by restoring the wound surface to its original strength within minutes. This technique could also be utilized for surgical purposes involving solid visceral organs (i.e., liver, spleen, and kidney) that currently do not respond well to ordinary surgical procedures. A miniaturized microwave generator and a handheld antenna are used to deliver microwave energy to the protein solder, which is applied to the wound. The antenna can be of several alternative designs optimized for placement either in contact with or in proximity to the protein solder covering the wound. In either case, optimization of the design includes the matching of impedances to maximize the energy delivered to the protein solder and wound at a chosen frequency. For certain applications, an antenna could be designed that would emit power only when it is in direct contact with the wound. The optimum frequency or frequencies for a specific application would depend on the required depth of penetration of the microwave energy. In fact, a computational simulation for each specific application could be performed, which would then match the characteristics of the antenna with the protein solder and tissue to best effect wound closure. An additional area of interest with potential benefit that remains to be validated is whether microwave energy can effectively kill bacteria in and around the wound. Thus, this may be an efficient method for simultaneously sterilizing and closing wounds.

  13. Dermabond wound closure in primary hip arthroplasty.

    PubMed

    Khurana, Ashish; Parker, Salim; Goel, Vivek; Alderman, Phillip M

    2008-06-01

    Cyanoacrylate glues have been used in various surgical specialties for primary wound closure or as a supplement to other methods. We assessed the overall results and safety of this technique following primary hip arthroplasty. Ninety-three patients undergoing primary total hip replacement were studied. The surgical wound had been closed with subcuticular vicryl followed by the application of topical dermabond adhesive, without any additional dressings. The mean follow-up was 7.2 months. One patient suffered wound dehiscence on the third post operative day. Two patients had serous oozing from the wound for the initial 3-4 days. This technique provides an immediate water tight seal in a sterile operative environment and provides a barrier to micro organisms. It has good tensile strength, aesthetic value and patient satisfaction.

  14. Microwave Tissue Soldering for Immediate Wound Closure

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey; Ngo, Phong H.; Plan, Chau T.; Byerly, Diane; Dusl, John; Sognier, Marguerite A.

    2011-01-01

    A novel approach for the immediate sealing of traumatic wounds is under development. A portable microwave generator and handheld antenna are used to seal wounds, binding the edges of the wound together using a biodegradable protein sealant or solder. This method could be used for repairing wounds in emergency settings, by restoring the wound surface to its original strength within minutes. This technique could also be utilized for surgical purposes involving solid visceral organs (i.e., liver, spleen, and kidney) that currently do not respond well to ordinary surgical procedures. A miniaturized microwave generator and a handheld antenna are used to deliver microwave energy to the protein solder, which is applied to the wound. The antenna can be of several alternative designs optimized for placement either in contact with or proximity to the protein solder covering the wound. In either case, optimization of the design includes the matching of impedances to maximize the energy delivered to the protein solder and wound at a chosen frequency. For certain applications, an antenna could be designed that would emit power only when it is in direct contact with the wound. The optimum frequency or frequencies for a specific application would depend on the required depth of penetration of the microwave energy. In fact, a computational simulation for each specific application could be performed, which would then match the characteristics of the antenna with the protein solder and tissue to best effect wound closure. An additional area of interest with potential benefit that remains to be validated is whether microwave energy can effectively kill bacteria in and around the wound. Thus, this may be an efficient method for simultaneously sterilizing and closing wounds. Using microwave energy to seal wounds has a number of advantages over lasers, which are currently in experimental use in some hospitals. Laser tissue welding is unsuitable for emergency use because its large, bulky

  15. The TopClosure® 3S System, for skin stretching and a secure wound closure.

    PubMed

    Topaz, Moris; Carmel, Narin-Nard; Silberman, Adi; Li, Ming Sen; Li, Yong Zhong

    2012-07-01

    The principle of stretching wound margins for primary wound closure is commonly practiced and used for various skin defects, leading at times to excessive tension and complications during wound closure. Different surgical techniques, skin stretching devices and tissue expanders have been utilized to address this issue. Previously designed skin stretching devices resulted in considerable morbidity. They were invasive by nature and associated with relatively high localized tissue pressure, frequently leading to necrosis, damage and tearing of skin at the wound margins. To assess the clinical effectiveness and performance and, to determine the safety of TopClosure® for gradual, controlled, temporary, noninvasive and invasive applications for skin stretching and secure wound closing, the TopClosure® device was applied to 20 patients for preoperative skin lesion removal and to secure closure of a variety of wound sizes. TopClosure® was reinforced with adhesives, staples and/or surgical sutures, depending on the circumstances of the wound and the surgeon's judgment. TopClosure® was used prior to, during and/or after surgery to reduce tension across wound edges. No significant complications or adverse events were associated with its use. TopClosure® was effectively used for preoperative skin expansion in preparation for dermal resection (e.g., congenital nevi). It aided closure of large wounds involving significant loss of skin and soft tissue by mobilizing skin and subcutaneous tissue, thus avoiding the need for skin grafts or flaps. Following surgery, it was used to secure closure of wounds under tension, thus improving wound aesthetics. A sample case study will be presented. We designed TopClosure®, an innovative device, to modify the currently practiced concept of wound closure by applying minimal stress to the skin, away from damaged wound edges, with flexible force vectors and versatile methods of attachment to the skin, in a noninvasive or invasive manner.

  16. Accelerating cleanup: Paths to closure

    SciTech Connect

    Edwards, C.

    1998-06-30

    This document was previously referred to as the Draft 2006 Plan. As part of the DOE`s national strategy, the Richland Operations Office`s Paths to Closure summarizes an integrated path forward for environmental cleanup at the Hanford Site. The Hanford Site underwent a concerted effort between 1994 and 1996 to accelerate the cleanup of the Site. These efforts are reflected in the current Site Baseline. This document describes the current Site Baseline and suggests strategies for further improvements in scope, schedule and cost. The Environmental Management program decided to change the name of the draft strategy and the document describing it in response to a series of stakeholder concerns, including the practicality of achieving widespread cleanup by 2006. Also, EM was concerned that calling the document a plan could be misconstrued to be a proposal by DOE or a decision-making document. The change in name, however, does not diminish the 2006 vision. To that end, Paths to Closure retains a focus on 2006, which serves as a point in time around which objectives and goals are established.

  17. 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.

  18. Accelerating cleanup: Paths to closure

    SciTech Connect

    1998-06-01

    This report describes the status of Environmental Management`s (EM`s) cleanup program and a direction forward to complete achievement of the 2006 vision. Achieving the 2006 vision results in significant benefits related to accomplishing EM program objectives. As DOE sites accelerate cleanup activities, risks to public health, the environment, and worker safety and health are all reduced. Finding more efficient ways to conduct work can result in making compliance with applicable environmental requirements easier to achieve. Finally, as cleanup activities at sites are completed, the EM program can focus attention and resources on the small number of sites with more complex cleanup challenges. Chapter 1 describes the process by which this report has been developed and what it hopes to accomplish, its relationship to the EM decision-making process, and a general background of the EM mission and program. Chapter 2 describes how the site-by-site projections were constructed, and summarizes, for each of DOE`s 11 Operations/Field Offices, the projected costs and schedules for completing the cleanup mission. Chapter 3 presents summaries of the detailed cleanup projections from three of the 11 Operations/Field Offices: Rocky Flats (Colorado), Richland (Washington), and Savannah River (South Carolina). The remaining eight Operations/Field Office summaries are in Appendix E. Chapter 4 reviews the cost drivers, budgetary constraints, and performance enhancements underlying the detailed analysis of the 353 projects that comprise EM`s accelerated cleanup and closure effort. Chapter 5 describes a management system to support the EM program. Chapter 6 provides responses to the general comments received on the February draft of this document.

  19. 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.

  20. Tensile strength of wound closure with cyanoacrylate glue.

    PubMed

    Shapiro, A J; Dinsmore, R C; North, J H

    2001-11-01

    2-Octyl cyanoacrylate tissue adhesive is increasingly being used for closure of traumatic lacerations. Data regarding the strength of incisions closed with 2-octyl cyanoacrylate are limited. We compared the strength of disruption of closure with glue with that of more conventional methods of wound closure. Segments of fresh porcine skin measuring 3.5 x 10 cm were approximated by one of four methods: 1) 2-octyl cyanoacrylate glue, 2) surgical staples, 3) 0.5 inch Steri-Strips, and 4) interrupted 4-0 poliglecaprone 25 sutures in a subcuticular fashion. Fifteen specimens were used to test each type of closure. The strength of closure was tested on an Instron 4502 tensionometer. The peak force required for disruption of the closure was recorded and the strength of the closure was compared. Staples provided the strongest closure. Skin glue proved superior to Steri-Strips but inferior to stapled closure. The difference between skin glue and suture closure was not statistically significant (P = 0.12). Patterns of failure differed between the groups. Skin glue failed because of disruption of the skin-glue interface. 2-Octyl cyanoacrylate glue provides a wound closure that is similar to closure with an interrupted subcuticular absorbable suture. This study validates the clinical use of skin glue for closure of surgical incisions. The technique should be used with caution in areas of the body that are subject to tension.

  1. A Novel Option of Uninterrupted Closure of Surgical Wounds

    PubMed Central

    Sulamanidze, Marlen A; Sulamanidze, George M

    2009-01-01

    Background: A cosmetically pleasing postoperative scar is an important aim of all aesthetic surgeries. Use of proper suture materials for delicate and gentle suturing of the operative injury is an important requirement for achieving satisfactory scars. However, closure of the edges of wounds by means of conventional suture materials does not always meet the requirements to achieve this objective. Aim: To simplify and facilitate the process of surgical wound closure, to improve the quality of scar, and to achieve a good cosmetic effect through the introduction of a new type of suture material. Materials and Methods: We have introduced a new surgical suturing material—a nontraumatic, barbed thread connected with the suture needle—APTOS SUTURE (European patent 1075843 as of 1999). Presented herein is a new modification of the technique of uninterrupted subcutaneous and intracutaneous suturing of wound edges, and the details of our experience with this material. Results: Our experience shows that, with use of APTOS, wound closure is carried out easily and quickly. The wound remains stable, the time of healing is shortened, and the process of suture removal is simplified, resulting in an aesthetically pleasing scar. Conclusions: The technique of surgical wound suturing proposed herein is a simple, facilitated, and efficient option of wound-edge closure, which can successfully be used, both in general and in aesthetic surgery for wound closure, such as plasty of scars, face lift, mammoplasty, and abdominal plasty. PMID:20808595

  2. Modeling closure of circular wounds through coordinated collective motion

    NASA Astrophysics Data System (ADS)

    Li, David S.; Zimmermann, Juliane; Levine, Herbert

    2016-02-01

    Wound healing enables tissues to restore their original states, and is achieved through collective cell migration into the wound space, contraction of the wound edge via an actomyosin filament ‘purse-string,’ as well as cell division. Recently, experimental techniques have been developed to create wounds with various regular morphologies in epithelial monolayers, and these experiments of circular closed-contour wounds support coordinated lamellipodial cell crawling as the predominant driver of gap closure. Through utilizing a particle-based mechanical tissue simulation, exhibiting long-range coordination of cell motility, we computationally model these closed-contour experiments with a high level of agreement between experimentally observed and simulated wound closure dynamics and tissue velocity profiles. We also determine the sensitivity of wound closure time in the model to changes in cell motility force and division rate. Our simulation results confirm that circular wounds can close due to collective cell migration without the necessity for a purse-string mechanism or for cell division, and show that the alignment mechanism of cellular motility force with velocity, leading to collective motion in the model, may speed up wound closure.

  3. Acceleration Of Wound Healing Ny Photodynamic Therapy

    SciTech Connect

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

    2000-08-22

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

  4. Cutaneous Wound Closure Materials: An Overview and Update

    PubMed Central

    Al-Mubarak, Luluah; Al-Haddab, Mohammed

    2013-01-01

    Introduction: On a daily basis, dermasurgeons are faced with different kinds of wounds that have to be closed. With a plethora of skin closure materials currently available, choosing a solution that combines excellent and rapid cosmetic results with practicality and cost-effectiveness can be difficult, if not tricky. Objectives: We aimed to review the available skin closure materials over the past 20 years and the scientific claims behind their effectiveness in repairing various kinds of wounds. Materials and Methods: The two authors independently searched and scrutinised the literature. The search was performed electronically using Pub Med, the Cochrane Database, Google Scholar and Ovid as search engines to find articles concerning skin closure materials written since 1990. Conclusion: Many factors are involved in the choice of skin closure material, including the type and place of the wound, available materials, physician expertise and preferences, and patient age and health. Evidence-based main uses of different skin closure materials are provided to help surgeons choose the appropriate material for different wounds. PMID:24470712

  5. Cataract surgery and methods of wound closure: a review

    PubMed Central

    Matossian, Cynthia; Makari, Sarah; Potvin, Richard

    2015-01-01

    Clear corneal incisions are routinely used in cataract surgery, but watertight wound closure may not always be achieved, which can increase the risk for anterior chamber fluid egress or ocular surface fluid ingress. A new US Food and Drug Administration-approved ocular sealant appears to have good efficacy in sealing clear corneal incisions; its use may be indicated when wound integrity is in question. PMID:26045656

  6. Ozone mediators effect on "in vitro" scratch wound closure.

    PubMed

    Valacchi, Giuseppe; Sticozzi, Claudia; Zanardi, Iacopo; Belmonte, Giuseppe; Cervellati, Franco; Bocci, Velio; Travagli, Valter

    2016-09-01

    The beneficial effect of low doses of ozone on wound healing has been well documented and attributed mainly to its bactericidal and pro-oxidant properties. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects are the results of oxidative mediators. Among the molecule produces by the interaction of ozone with biological systems, there are HNE and H2O2. At today, the cellular mechanisms accounting for the positive effects of mild ozonization on wound closure are still largely unexplored. The aim of the present study was to evaluate the effect of different non-toxic doses of ozonated saline ranging from 2 to 300 μM, in an in vitro wound scratch model by the use of human keratinocytes. The results showed that ozonated saline is able to improve in vitro wound healing by stimulating cell proliferation as measured by BrdU assay and PCNA protein levels. In order to better elucidate the molecules that play the main role in the beneficial effect of ozonated saline in wound healing, HNE and H2O2 were used alone or in combination to mimic ozonated saline effect. Surprisingly, keratinocytes treated with different doses of HNE and H2O2 did not significantly improve the wound closure, while the combination of the two compounds was able to improve wound closure. In addition, Nrf2 pathways were also activated as determined by its translocation to the nucleus and the increased HO1 gene expression. The present work suggests that ozonated saline effect on wound closure is the results of the combination of more molecules among which HNE and H2O2 play a key role.

  7. Effects of wound closure on wound healing in gynecologic surgery: a systematic literature review.

    PubMed

    Boesch, Cedric E; Umek, Wolfgang

    2009-03-01

    A systematic review was undertaken using the Cochrane and PubMed databases to answer the question of how wound closure affects wound healing after gynecologic surgery. Leaving the vaginal vault open after vaginal and abdominal hysterectomy is as safe as closing it. When closing the vaginal vault, there is no difference between sutures and staples. Nonclosure of the peritoneum is a safe method after vaginal and abdominal hysterectomy. After laparotomy there is no difference between continuous and interrupted sutures regarding wound infection and/or dehiscence. After vertical midline incisions it is possible to close Camper's fascia, use drainage or close the skin only. The overall wound complication rate after laparoscopic surgery is lower when using transcutaneous as compared to subcuticular sutures. Adhesive paper tapes save time when closing smaller skin incisions. In conclusion, specific wound closure techniques improve wound healing after gynecologic operations.

  8. Modulation of inflammation by Cicaderma ointment accelerates skin wound healing.

    PubMed

    Morin, Christophe; Roumegous, Audrey; Carpentier, Gilles; Barbier-Chassefière, Véronique; Garrigue-Antar, Laure; Caredda, Stéphane; Courty, José

    2012-10-01

    Skin wound healing is a natural and intricate process that takes place after injury, involving different sequential phases such as hemostasis, inflammatory phase, proliferative phase, and remodeling that are associated with complex biochemical events. The interruption or failure of wound healing leads to chronic nonhealing wounds or fibrosis-associated diseases constituting a major health problem where, unfortunately, medicines are not very effective. The objective of this study was to evaluate the capacity of Cicaderma ointment (Boiron, Lyon, France) to accelerate ulcer closure without fibrosis and investigate wound healing dynamic processes. We used a necrotic ulcer model in mice induced by intradermal doxorubicin injection, and after 11 days, when the ulcer area was maximal, we applied Vaseline petroleum jelly or Cicaderma every 2 days. Topical application of Cicaderma allowed a rapid recovery of mature epidermal structure, a more compact and organized dermis and collagen bundles compared with the Vaseline group. Furthermore, the expression of numerous cytokines/molecules in the ulcer was increased 11 days after doxorubicin injection compared with healthy skin. Cicaderma rapidly reduced the level of proinflammatory cytokines, mainly tumor necrosis factor (TNF)-α and others of the TNF pathway, which can be correlated to a decrease of polymorphonuclear recruitment. It is noteworthy that the modulation of inflammation through TNF-α, macrophage inflammatory protein-1α, interleukin (IL)-12, IL-4, and macrophage-colony-stimulating factor was maintained 9 days after the first ointment application, facilitating the wound closure without affecting angiogenesis. These cytokines seem to be potential targets for therapeutic approaches in chronic wounds. Our results confirm the use of Cicaderma for accelerating skin wound healing and open new avenues for sequential treatments to improve healing.

  9. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  10. A novel approach to quantify the wound closure dynamic.

    PubMed

    Ascione, Flora; Guarino, Andrea Maria; Calabrò, Viola; Guido, Stefano; Caserta, Sergio

    2017-03-15

    The Wound Healing (WH) assay is widely used to investigate cell migration in vitro, in order to reach a better understanding of many physiological and pathological phenomena. Several experimental factors, such as uneven cell density among different samples, can affect the reproducibility and reliability of this assay, leading to a discrepancy in the wound closure kinetics among data sets corresponding to the same cell sample. We observed a linear relationship between the wound closure velocity and cell density, and suggested a novel methodological approach, based on transport phenomena concepts, to overcome this source of error on the analysis of the Wound Healing assay. In particular, we propose a simple scaling of the experimental data, based on the interpretation of the wound closure as a diffusion-reaction process. We applied our methodology to the MDA-MB-231 breast cancer cells, whose motility was perturbed by silencing or over-expressing genes involved in the control of cell migration. Our methodological approach leads to a significant improvement in the reproducibility and reliability in the in vitro WH assay.

  11. 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

  12. Acceleration of palatal wound healing in Smad3-deficient mice.

    PubMed

    Jinno, K; Takahashi, T; Tsuchida, K; Tanaka, E; Moriyama, K

    2009-08-01

    Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-beta/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-beta/Smad3 signaling in palatal wound healing in Smad3-deficient (Smad3(-/-)) mice. Histological examination showed that wound closure was accelerated by the proliferation of epithelium and dermal cells in Smad3(-/-) mice compared with wild-type (WT) mice. Macrophage/monocyte infiltration at wounded regions in Smad3(-/-) mice was decreased in parallel with the diminished production of TGF-beta1, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha compared with WT mice. Fibrocytes, expressing hematopoietic surface marker and fibroblast products, were recruited and produced alpha-smooth-muscle actin in WT mice, but were not observed in Smad3(-/-) mice. These results suggest that TGF-beta/Smad3 signaling may play an important role in the regulation of palatal wound healing.

  13. Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.

    PubMed

    Rabbany, Sina Y; Pastore, Joseph; Yamamoto, Masaya; Miller, Tim; Rafii, Shahin; Aras, Rahul; Penn, Marc

    2010-01-01

    Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo K(d) 0.55 days) than SDF-1 plasmid (in vivo K(d) 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein (n = 10) and plasmid (n = 6) loaded patches healed faster than sham (n = 4) or control (n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 +/- 14.3% healed) compared to nontreated controls (8.2 +/- 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

  14. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice

    PubMed Central

    Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

    2010-01-01

    Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes. PMID:21060152

  15. Primary closure of contaminated wounds in perforated appendicitis.

    PubMed

    Burnweit, C; Bilik, R; Shandling, B

    1991-12-01

    We studied the clinical course of 506 children consecutively admitted with appendicitis at The Hospital for Sick Children from 1985 to 1989. One hundred eighty-one children (35%), ranging in age from 1 to 17 years, presented with perforation verified by histological examination. Ninety-six of them (53%) had generalized peritonitis, 47 (26%) had localized peritonitis, and 38 (21%) had abscess formation. Usually, triple antibiotics were begun preoperatively if perforation was suspected; otherwise, cefoxitin was started. Triple antibiotics were used postoperatively for 5 to 7 days in almost all children in the perforated group. Neither abdominal nor subcutaneous drainage was routinely used even in cases of intraabdominal abscess. The skin was closed primarily with steri-strips (63%), staples (20%), subcutaneous Dexon (11%), or silk (4%). Postoperative wound infection arose in 20 children (11%). Wound infections were noted from 1 to 14 days postoperatively (mean, 5.9 days). Whereas 9 of these were treated with local therapy only, 11 delayed the child's discharge or necessitated readmission. No patient suffered major complications from wound infection in that there were no cases of necrotizing fasciitis, reoperation for debridement, sepsis, or death. The intraabdominal abscess rate in this group of 181 children was 6% (n = 11). The low rate of infective complications fully justifies the policy of primary closure in contaminated wounds. This policy eliminates the necessity for painful and time-consuming dressing changes, shortens hospitalization, and obviates the trauma of delayed suturing of wounds in children.

  16. Mathematical models of wound healing and closure: a comprehensive review.

    PubMed

    Jorgensen, Stephanie N; Sanders, Jonathan R

    2016-09-01

    Wound healing is a complex process comprised of overlapping phases and events that work to construct a new, functioning tissue. Mathematical models describe these events and yield understanding about the overall process of wound healing. Generally, these models are focused on only one phase (or a few phases) to explain healing for a specific system. A review of the literature reveals insights as reported on herein regarding the variety of overlapping inputs and outputs for any given type of model. Specifically, these models have been characterized with respect to the phases of healing and their mathematical/physical basis in an effort to shed light on new opportunities for model development. Though all phases of wound healing have been modeled, previous work has focused mostly on the proliferation and related contraction phases of healing with fewer results presented regarding other phases. As an example, a gap in the literature has been identified regarding models to describe facilitated wound closure techniques (e.g., suturing and its effect on resultant scarring). Thus, an opportunity exists to create models that tie the transient processes of wound healing, such as cell migration, to resultant scarring when considering tension applied to skin with given suturing techniques.

  17. PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms.

    PubMed

    Buonomo, Roberta; Giacco, Ferdinando; Vasaturo, Angela; Caserta, Sergio; Guido, Stefano; Pagliara, Valentina; Garbi, Corrado; Mansueto, Gelsomina; Cassese, Angela; Perruolo, Giuseppe; Oriente, Francesco; Miele, Claudia; Beguinot, Francesco; Formisano, Pietro

    2012-05-01

    Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts. This difference was observed both in the absence and in the presence of mytomicin C, an inhibitor of mitosis. In time-lapse experiments, TgPED fibroblasts displayed about twofold lower velocity and diffusion coefficient, as compared to controls. These changes were accompanied by reduced spreading and decreased formation of stress fibers and focal adhesion plaques. At the molecular level, TgPED fibroblasts displayed decreased RhoA activation and increased abundance of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ERK1/2 activity by PD98059 restored RhoA activation, cytoskeleton organization and cell motility, and almost completely rescued wound closure of TgPED fibroblasts. Interestingly, skin fibroblasts isolated from KO mice displayed an increased wound closure ability. In vivo, healing of dorsal wounds was delayed in TgPED and accelerated in KO mice. Thus, PED/PEA-15 may affect fibroblast motility by a mechanism, at least in part, mediated by ERK1/2.

  18. 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.

  19. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing

    PubMed Central

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-01-01

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition. PMID:25299783

  20. Skin wound healing is accelerated and scarless in the absence of commensal microbiota.

    PubMed

    Canesso, Maria C C; Vieira, Angélica T; Castro, Tiago B R; Schirmer, Brígida G A; Cisalpino, Daniel; Martins, Flaviano S; Rachid, Milene A; Nicoli, Jacques R; Teixeira, Mauro M; Barcelos, Lucíola S

    2014-11-15

    The commensal microbiota has a high impact on health and disease by modulating the development and homeostasis of host immune system. Immune cells are involved in virtually every aspect of the wound repair process; however, the impact of commensal microbiota on skin wound healing is largely unknown. In this study, we evaluated the influence of commensal microbiota on tissue repair of excisional skin wounds by using germ-free (GF) Swiss mice. We observed that macroscopic wound closure rate is accelerated in the absence of commensal microbiota. Accordantly, histologically assessed wound epithelization was accelerated in GF in comparison with conventional (CV) Swiss mice. The wounds of GF mice presented a significant decrease in neutrophil accumulation and an increase in mast cell and macrophage infiltration into wounds. Interestingly, alternatively activated healing macrophage-related genes were highly expressed in the wound tissue of GF mice. Moreover, levels of the anti-inflammatory cytokine IL-10, the angiogenic growth factor VEGF and angiogenesis were higher in the wound tissue of those mice. Conversely, scarring and levels of the profibrogenic factor TGF-β1 were greatly reduced in GF mice wounded skin when compared with CV mice. Of note, conventionalization of GF mice with CV microbiota restored wound closure rate, neutrophil and macrophage accumulation, cytokine production, and scarring to the same extent as CV mice. Overall, our findings suggest that, in the absence of any contact with microbiota, skin wound healing is accelerated and scarless, partially because of reduced accumulation of neutrophils, increased accumulation of alternatively activated healing macrophages, and better angiogenesis at wound sites.

  1. Biafine topical emulsion accelerates excisional and burn wound healing in mice.

    PubMed

    Krausz, Aimee E; Adler, Brandon L; Landriscina, Angelo; Rosen, Jamie M; Musaev, Tagai; Nosanchuk, Joshua D; Friedman, Adam J

    2015-09-01

    Macrophages play a fundamental role in wound healing; therefore, employing a strategy that enhances macrophage recruitment would be ideal. It was previously suggested that the mechanism by which Biafine topical emulsion improves wound healing is via enhanced macrophage infiltration into the wound bed. The purpose of this study was to confirm this observation through gross and histologic assessments of wound healing using murine full-thickness excisional and burn wound models, and compare to common standards, Vaseline and silver sulfadiazine (SSD). Full-thickness excisional and burn wounds were created on two groups of 60 mice. In the excisional arm, mice were divided into untreated control, Biafine, and Vaseline groups. In the burn arm, mice were divided into untreated control, Biafine, and SSD groups. Daily treatments were administered and healing was measured over time. Wound tissue was excised and stained to appropriately visualize morphology, collagen, macrophages, and neutrophils. Collagen deposition was measured and cell counts were performed. Biafine enhanced wound healing in murine full-thickness excisional and burn wounds compared to control, and surpassed Vaseline and SSD in respective wound types. Biafine treatment accelerated wound closure clinically, with greater epidermal/dermal maturity, granulation tissue formation, and collagen quality and arrangement compared to other groups histologically. Biafine application was associated with greater macrophage and lower neutrophil infiltration at earlier stages of healing when compared to other study groups. In conclusion, Biafine can be considered an alternative topical therapy for full-thickness excisional and burn wounds, owing to its advantageous biologically based wound healing properties.

  2. 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.

  3. Effect of recombinant platelet-derived growth factor (Regranex) on wound closure in genetically diabetic mice.

    PubMed

    Chan, Rodney K; Liu, Perry H; Pietramaggiori, Giorgio; Ibrahim, Shahrul I; Hechtman, Herbert B; Orgill, Dennis P

    2006-01-01

    Burns, especially those involving large surface areas, represent a complex wound healing problem. Platelet-derived growth factor (PDGF) is released by activated platelets to recruit inflammatory cells toward the wound bed. It has effects on promoting angiogenesis and granulation tissue formation. However, the effectiveness of topical PDGF on wound closure is variable, ranging from little improvement observed in pig models to dramatic improvement reported in a diabetic mouse model. Here, we sought to determine the effectiveness of commercially sold PDGF-BB (Regranex) on wound closure in genetically diabetic mice. C57BL/KsJ db+/db+ mice and its host strain bearing dorsal 1.5-cm wounds were divided into groups (n = 8 in each group) receiving topical application of either Regranex (10 microg/wound) or vehicle for 5 consecutive days after wounding. The rate of wound closure was analyzed using computerized planimetry. The amount of granulation tissue was determined histologically. Our data indicate that diabetic mice exhibit a significant delay in wound closure when compared with their host strain. Topical application of Regranex did not improve the time to wound closure but did significantly increase the amount of granulation tissue. Our current study using commercially available Regranex failed to reproduce the previously reported finding that PDGF improved wound closure in healing impaired genetically diabetic mice.

  4. Wound healing effects of noni (Morinda citrifolia L.) leaves: a mechanism involving its PDGF/A2A receptor ligand binding and promotion of wound closure.

    PubMed

    Palu, Afa; Su, Chen; Zhou, Bing-Nan; West, Brett; Jensen, Jarakae

    2010-10-01

    Morinda citrifolia L. (Rubiaceae) commonly known as noni, has been used in Polynesia by traditional healers for the treatment of cuts, bruises and wounds. Our objective was to investigate the wound-healing mechanisms of the noni leaf. The investigations of its wound-healing mechanisms were carried out using fresh noni leaf juice (NLJ), noni leaf ethanol extract (NLEE) and its methanol (MFEE) and hexane (HFEE) fractions on the PDGF and A(2A) receptors in vitro and topically in mice. Fresh noni leaf juice showed significant affinity to PDGF receptors, and displayed 166% binding inhibition of the ligand binding to its receptors, while at the same concentration, it only had 7% inhibition of the ligand binding to the A(2A) receptors. NLEE, HFEE and MFEE showed significant affinity to A(2A) receptors, concentration dependently, with IC(50) values of 34.1, 42.9 and 86.7 μg/mL, respectively. However, MFEE significantly increased wound closure and reduced the half closure time in mice with a CT(50) of 5.4 ± 0.2 days compared with control (p < 0.05). These results suggest that noni leaf significantly accelerated wound healing in mice via its ligand binding to the PDGF and A(2A) receptors as its probable mechanisms of wound-healing and also support its traditional usage for wound-healing in Polynesia.

  5. Full-Thickness Thermal Injury Delays Wound Closure in a Murine Model

    DTIC Science & Technology

    2015-01-01

    without the application of a skin graft or a skin substitute graft. Furthermore, the effect of interval burn eschar excision on wound closure is also re...primary intention with surgical closure or the application of a skin graft or skin substitute graft, or (2) healing by secondary intention through a...the closure of severe burns and chronic wounds using cultured human autologous keratinocytes in a nat- ural fibrin matrix. Cell Tissue Bank 2004;5:89

  6. A cold plasma jet accelerates wound healing in a murine model of full-thickness skin wounds.

    PubMed

    Schmidt, Anke; Bekeschus, Sander; Wende, Kristian; Vollmar, Brigitte; von Woedtke, Thomas

    2017-02-01

    Cold plasma has been successfully applied in several fields of medicine that require, for example, pathogen inactivation, implant functionalization or alteration of cellular activity. Previous studies have provided evidence that plasma supports the healing of wounds owing to its beneficial mixtures of reactive species and modulation of inflammation in cells and tissues. To investigate the wound healing activity of an atmospheric pressure plasma jet in vivo, we examined the cold plasma's efficacy on dermal regeneration in a murine model of dermal full-thickness ear wound. Over 14 days, female mice received daily plasma treatment. Quantitative analysis by transmitted light microscopy demonstrated a significantly accelerated wound re-epithelialization at days 3-9 in comparison with untreated controls. In vitro, cold plasma altered keratinocyte and fibroblast migration, while both cell types showed significant stimulation resulting in accelerated closure of gaps in scratch assays. This plasma effect correlated with the downregulation of the gap junctional protein connexin 43 which is thought to be important in the regulation of wound healing. In addition, plasma induced profound changes in adherence junctions and cytoskeletal dynamics as shown by downregulation of E-cadherin and several integrins as well as actin reorganization. Our results theorize cold plasma to be a beneficial treatment option supplementing existing wound therapies.

  7. Clinical Trial on the Incidence of Wound Infection and Patient Satisfaction After Stoma Closure: Comparison of Two Skin Closure Techniques

    PubMed Central

    Yoon, Sang Il; Bae, Sun Mi; Park, Dong Guk

    2015-01-01

    Purpose Surgical site infection (SSI) is one of the most common complications that can occur after stoma closure. Reports have described differences in the incidence of wound infection depending on the skin closure technique, but there is no consensus on the ideal closure technique for a stoma wound. The aim of this study was to compare the incidence of SSI and the patient satisfaction between a circumferential purse-string approximation (CPA) and a primary linear closure (PC) of a stoma wound. Methods This prospective nonrandomized trial enrolled 48 patients who underwent a stoma closure from February 2010 to October 2013. Patients were divided into two groups according to the stoma closing technique: the CPA group (n = 34) and the PC group (n = 14). The incidences of SSI for the two groups were compared, and the patients' satisfaction with the stoma closure was determined by using a questionnaire. Results SSI occurred in 3 of 48 patients (6.3%) and was more frequent in the PC group than in the CPA group (3/14 [21.4%] vs. 0/34 [0%], P = 0.021). Time to complete healing after stoma closure in the CPA group was 32 days (range, 14-61 days). Patients in the CPA group were more satisfied with the resulting wound scar (P = 0.043). Conclusion After stoma closure, CPA was associated with a significantly lower incidence of wound infection and greater patient satisfaction compared to PC. However, with the CPA technique, the time to heal is longer than it is with PC. PMID:25745624

  8. Diffuse lymphatic leakage after continuous vacuum-assisted closure therapy for thoracic wound infection after rib stabilization

    PubMed Central

    Dackam, Sandrine; Furrer, Katarzyna; Haug, Martin; Lardinois, D.

    2015-01-01

    Vacuum-assisted closure (VAC) therapy is a useful tool in the management of a wide spectrum of complex wounds in cardiothoracic surgery. It promotes healing through the application of a controlled and localized negative pressure on porous polyurethane absorbent foams. Known advantages of the VAC therapy are the acceleration of wound healing, stimulation of granulation tissue and reduced tissue edema. Despite its excellent properties, some related complications after and during the therapy have been reported. We report the case of a 47-year-old female with a thoracic wound infection after rib stabilization, managed with open surgery and VAC therapy, which was complicated by a diffuse lymphatic leakage. This is the first case described of diffuse lymphatic leakage followed by partial necrosis of the breast after continuous VAC therapy. We recommend the application of a lower pressure level of this device for complex wounds of the chest wall near the breast. PMID:26675995

  9. Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage: Correlation With Subsequent Postclosure Deep Wound Infection (Bioburden Study).

    PubMed

    Bosse, Michael J; Murray, Clinton K; Carlini, Anthony R; Firoozabadi, Reza; Manson, Theodore; Scharfstein, Daniel O; Wenke, Joseph C; Zadnik, Mary; Castillo, Renan C

    2017-04-01

    Infection remains the most common and significant complication after high-energy fractures. The Bioburden Study is a multicenter, prospective, observational cohort study of wound bacterial bioburden and antibiotic care in severe open lower extremity fractures. The aims of this study are to (1) characterize the contemporary extremity wound "bioburden" at the time of definitive wound closure; (2) determine the concordance between polymerase chain reaction results and hospital microbiology; (3) determine, among those who develop deep infections, the concordance between the pathogens at wound closure and at deep infection; and (4) compare the probability of deep infection between those who did and did not receive an appropriate course of antibiotics based on bioburden at the time of wound closure. To address these aims, sites collected tissue samples from severe lower extremity injuries at the time of wound closure and at first surgery for treatment of a deep infection, nonunion, flap failure, amputation, or other complications (because these surgeries may be due to undetected infection). Otherwise, if no further surgical treatment occurred, participants were followed for 12 months. The study was conducted at 38 US trauma centers and has enrolled 655 participants aged 18-64 years. This is the first large multi-institutional study evaluating the wound bioburden of severe open tibia fractures and correlating this bioburden with the risk of wound complications after definitive soft tissue closure.

  10. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    SciTech Connect

    Walter, M.N.M.; Wright, K.T.; Fuller, H.R.; MacNeil, S.; Johnson, W.E.B.

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-{beta}1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  11. Outcome of primary closure of abdominal wounds following laparotomy for peritonitis in children

    PubMed Central

    Kache, Stephen Akau; Mshelbwala, Philip M.; Ameh, Emmanuel A.

    2016-01-01

    Background: Primary wound closure following laparotomy for peritonitis is generally believed to be associated with wound complications and long hospital stay. Open wound management has long been the most common practice after laparotomy for peritonitis. Primary closure (PC), however, has recently been advocated to reduce cost and morbidity. This study determined the incidence and severity of wound complications and their impact on hospital stay and overall outcome when PC of abdominal wounds is done following laparotomy for peritonitis. Patients and Methods: A prospective review of patients who had PC of abdominal wounds following laparotomy for peritonitis over a 6-year period. Results: Fifty-six children were analysed (35 boys and 21 girls), aged 11 months to 13 years (median: 8 years). The indication for laparotomy was typhoid intestinal perforation 47 (83.9%), perforated appendicitis 4 (7.1%), complicated cholecystitis 3 (5.3%) and penetrating abdominal injury with bowel perforation and intestinal obstruction with bowel perforation, 1 (1.8%) each, respectively. Postoperatively, 34 patients had wound complications. Nine patients (16.1%) had superficial wound infection alone, 12 (21.4%) had superficial wound infection with partial wound dehiscence, 6 (10.7%) had deep wound infection, 7 (12.5%) had deep wound infection with complete wound dehiscence, whereas 22 (39.3%) had no wound complication. Overall, wound complications in 13 (23.2%) patients were considered to be severe, but none resulted in mortality. Hospital stay in patients who developed wound complications was 8–37 days (median: 25 days) and 6–22 days (median: 10 days) in patients who had no wound complications (P = 0.02). Conclusion: The rate of wound complications following PC of dirty abdominal wounds remain but PC is safe and gives good healing outcomes. PMID:28051048

  12. Purse-String Versus Linear Conventional Skin Wound Closure of an Ileostomy: A Randomized Clinical Trial

    PubMed Central

    Alvandipour, Mina; Gharedaghi, Babak; Khodabakhsh, Hamed

    2016-01-01

    Purpose Infection is one of the most frequent complications that can occur after ileostomy closure. The incidence of wound infection depends on the skin closure technique, but there is no agreement on the perfect closure method for an ileostomy wound. The aim of this study was to evaluate the incidence of infection, the patient's approval, and the patient's pain between purse-string closure (PSC) and the usual linear closure (LC) of a stoma wound. Methods This randomized clinical trial enrolled 66 patients who underwent a stoma closure from February 2015 to May 2015 in Sari Emam Khomeini Hospital. Patients were divided into 2 groups according to the stoma closing method: the PSC group (n = 34) and the LC group (n = 32). The incidences of infection for the 2 groups were compared, and the patients' satisfaction and pain with the stoma were determined by using a questionnaire. Results Infection occurred in 1 of 34 PSC patients (2.9%) and in 7 of 32 LC patients (21.8%), and this difference was statistically significant (P = 0.021). Patients in the PSC group were more satisfied with the resulting wound scar and its cosmetic appearance at one month and three months after surgery (P = 0.043). Conclusion After stoma closure, PSC was associated with a significantly lower incidence of wound infection and greater patient satisfaction compared to LC. However, the healing period for patients who underwent PSC was longer than it was for those who underwent LC. PMID:27626025

  13. A retrospective study: clinical experience using vacuum-assisted closure in the treatment of wounds.

    PubMed Central

    Antony, Suresh; Terrazas, Sandra

    2004-01-01

    We report the results of our wound care experience using the wound vac as an adjunct therapy in the treatment of sternal, spinal, and lower-extremity wounds. This is a retrospective study in which 42 patients were evaluated between 1999 and 2002 for nonhealing sternal, spinal, and lower-extremity wounds. There were 12 patients with sternal wounds with a variety of pathogens who were treated with antimicrobials along with the wound VAC. The VAC was applied for an average of 12 days, and all 12 patients went onto complete closure by the end of four weeks. There were 14 patients in the lower-extremity wound group, again, with a variety of pathogens. The VAC was placed for an average of 29.3 days to achieve closure along with the wound VAC. There were 16 spinal wound patients with a variety of pathogens. All the patients received antimicrobial therapy, with the average duration of the VAC beings 27.6 days and closure taking about eight weeks. The wound VAC, along with appropriate antimicrobial therapy and surgery, appears to help reduce the number of days to healing, along with a reduction in the number hospital days and possibly costs to the health system. Images Figure 1a Figure 1b Figure 2a Figure 2b Figure 3a Figure 3b Figure 4 Figure 5 PMID:15303413

  14. A Small Chimeric Fibronectin Fragment Accelerates Dermal Wound Repair in Diabetic Mice

    PubMed Central

    Hocking, Denise C.; Brennan, James R.; Raeman, Carol H.

    2016-01-01

    Objective: During wound repair, soluble fibronectin is converted into biologically active, insoluble fibrils via a cell-mediated process. This fibrillar, extracellular matrix (ECM) form of fibronectin stimulates cell processes critical to tissue repair. Nonhealing wounds show reduced levels of ECM fibronectin fibrils. The objective of this study was to produce a small, recombinant wound supplement with the biological activity of insoluble fibronectin fibrils. Approach: A chimeric fibronectin fragment was produced by inserting the integrin-binding Arg-Gly-Asp (RGD) loop from the tenth type III repeat of fibronectin (FNIII10) into the analogous site within the heparin-binding, bioactive fragment of the first type III repeat (FNIII1H). FNIII1HRGD was tested for its ability to support cell functions necessary for wound healing, and then evaluated for its capacity to accelerate healing of full-thickness dermal wounds in diabetic mice. Results: In vitro, FNIII1HRGD supported cell adhesion, proliferation, and ECM fibronectin deposition. Application of FNIII1HRGD to dermal wounds of diabetic mice significantly enhanced wound closure compared with controls (73.9% ±4.1% vs. 58.1% ±4.7% closure on day 9, respectively), and significantly increased granulation tissue thickness (2.88 ± 0.75-fold increase over controls on day 14). Innovation: Recombinant proteins designed to functionally mimic the ECM form of fibronectin provide a novel therapeutic approach to circumvent diminished fibronectin fibril formation by delivering ECM fibronectin signals in a soluble form to chronic wounds. Conclusion: A small, chimeric fibronectin protein was developed. FNIII1HRGD demonstrated enhanced bioactivity in vitro and stimulated wound repair in a murine model of chronic wounds. PMID:27867754

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

    PubMed

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

    2016-06-15

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

  16. Modelling wound closure in an epithelial cell sheet using the cellular Potts model.

    PubMed

    Noppe, Adrian R; Roberts, Anthony P; Yap, Alpha S; Gomez, Guillermo A; Neufeld, Zoltan

    2015-10-01

    We use a two-dimensional cellular Potts model to represent the behavior of an epithelial cell layer and describe its dynamics in response to a microscopic wound. Using an energy function to describe properties of the cells, we found that the interaction between contractile tension along cell-cell junctions and cell-cell adhesion plays an important role not only in determining the dynamics and morphology of cells in the monolayer, but also in influencing whether or not a wound in the monolayer will close. Our results suggest that, depending on the balance between cell-cell adhesion and junctional tension, mechanics of the monolayer can either correspond to a hard or a soft regime that determines cell morphology and polygonal organization in the monolayer. Moreover, the presence of a wound in a hard regime, where junctional tension is significant, can lead to two results: (1) wound closure or (2) an initial increase and expansion of the wound area towards an equilibrium value. Theoretical approximations and simulations allowed us to determine the thresholds in the values of cell-cell adhesion and initial wound size that allow the system to lead to wound closure. Overall, our results suggest that around the site of injury, changes in the balance between contraction and adhesion determine whether or not non-monotonous wound closure occurs.

  17. Low level diode laser accelerates wound healing.

    PubMed

    Dawood, Munqith S; Salman, Saif Dawood

    2013-05-01

    The effect of wound illumination time by pulsed diode laser on the wound healing process was studied in this paper. For this purpose, the original electronic drive circuit of a 650-nm wavelength CW diode laser was reconstructed to give pulsed output laser of 50 % duty cycle and 1 MHz pulse repetition frequency. Twenty male mice, 3 months old were used to follow up the laser photobiostimulation effect on the wound healing progress. They were subdivided into two groups and then the wounds were made on the bilateral back sides of each mouse. Two sessions of pulsed laser therapy were carried along 15 days. Each mice group wounds were illuminated by this pulsed laser for 12 or 18 min per session during these 12 days. The results of this study were compared with the results of our previous wound healing therapy study by using the same type of laser. The mice wounds in that study received only 5 min of illumination time therapy in the first and second days of healing process. In this study, we found that the wounds, which were illuminated for 12 min/session healed in about 3 days earlier than those which were illuminated for 18 min/session. Both of them were healed earlier in about 10-11 days than the control group did.

  18. EXPERIMENTAL-MORPHOLOGICAL SUBSTANTIATION OF EXPEDIENCY TO USE THE SKIN GLUE "DERMABOND" FOR POSTOPERATIVE WOUND CLOSURE.

    PubMed

    Avetikov, D; Loza, K; Starchenko, I; Loza, E; Marushchak, M

    2015-01-01

    We aimed to investigate the morphological features of healing of postoperative wounds in the early stages of reparative process in the experiment, depending on the used type of the wound closure. It is proved that the nature and type of the scar depends on the processes that occur in the wound at the early postoperative stage, which in turn greatly affects the form of suture material used. The experiment included 20 male rats, weighing 180-200 g. All rats were anesthetized by a single intraperitoneal injection of sodium thiopental. After the shaving operative field, 2 cm full-thickness incision wound was made on the anterior surface of the abdomen in the longitudinal direction. As suture material for wound closure in the 1st experimental group (10 rats) we used surgical filament "Polyamide 4-0». In the 2nd experimental group (10 rats) wounds were closured by using skin glue "Dermabond". According from our experiment, the usage of skin glue creates better conditions for wound healing. Thus, to achieve a more aesthetic scar, we recommend applying skin glue instead of using nodal joints.

  19. α-Gal Nanoparticles in Wound and Burn Healing Acceleration

    PubMed Central

    Galili, Uri

    2017-01-01

    Significance: Rapid recruitment and activation of macrophages may accelerate wound healing. Such accelerated healing was observed in wounds and burns of experimental animals treated with α-gal nanoparticles. Recent Advances: α-Gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). α-Gal nanoparticles applied to wounds bind anti-Gal (the most abundant antibody in humans) and generate chemotactic complement peptides, which rapidly recruit macrophages. Fc/Fc receptor interaction between anti-Gal coating the α-gal nanoparticles and recruited macrophages activates macrophages to produce cytokines that accelerate healing. α-Gal nanoparticles applied to burns and wounds in mice and pigs producing anti-Gal, decreased healing time by 40–60%. In mice, this accelerated healing avoided scar formation. α-Gal nanoparticle-treated wounds, in diabetic mice producing anti-Gal, healed within 12 days, whereas saline-treated wounds became chronic wounds. α-Gal nanoparticles are stable for years and may be applied dried, in suspension, aerosol, ointments, or within biodegradable materials. Critical Issues: α-Gal nanoparticle therapy can be evaluated only in mammalian models producing anti-Gal, including α1,3-galactosyltransferase knockout mice and pigs or Old World primates. Traditional experimental animal models synthesize α-gal epitopes and lack anti-Gal. Future Directions: Since anti-Gal is naturally produced in all humans, it is of interest to determine safety and efficacy of α-gal nanoparticles in accelerating wound and burn healing in healthy individuals and in patients with impaired wound healing such as diabetic patients and elderly individuals. In addition, efficacy of α-gal nanoparticle therapy should be studied in healing and regeneration of internal injuries such as surgical incisions, ischemic myocardium following myocardial infarction, and injured nerves. PMID:28289553

  20. UV fluorescence excitation imaging of healing of wounds in skin: Evaluation of wound closure in organ culture model

    PubMed Central

    Wang, Ying; Gutierrez‐Herrera, Enoch; Ortega‐Martinez, Antonio; Anderson, Richard Rox

    2016-01-01

    Background and Objective Molecules native to tissue that fluoresce upon light excitation can serve as reporters of cellular activity and protein structure. In skin, the fluorescence ascribed to tryptophan is a marker of cellular proliferation, whereas the fluorescence ascribed to cross‐links of collagen is a structural marker. In this work, we introduce and demonstrate a simple but robust optical method to image the functional process of epithelialization and the exposed dermal collagen in wound healing of human skin in an organ culture model. Materials and Methods Non‐closing non‐grafted, partial closing non‐grafted, and grafted wounds were created in ex vivo human skin and kept in culture. A wide‐field UV fluorescence excitation imaging system was used to visualize epithelialization of the exposed dermis and quantitate wound area, closure, and gap. Histology (H&E staining) was also used to evaluate epithelialization. Results The endogenous fluorescence excitation of cross‐links of collagen at 335 nm clearly shows the dermis missing epithelium, while the endogenous fluorescence excitation of tryptophan at 295 nm shows keratinocytes in higher proliferating state. The size of the non‐closing wound was 11.4 ± 1.8 mm and remained constant during the observation period, while the partial‐close wound reached 65.5 ± 4.9% closure by day 16. Evaluations of wound gaps using fluorescence excitation images and histology images are in agreement. Conclusions We have established a fluorescence imaging method for studying epithelialization processes, evaluating keratinocyte proliferation, and quantitating closure during wound healing of skin in an organ culture model: the dermal fluorescence of pepsin‐digestible collagen cross‐links can be used to quantitate wound size, closure extents, and gaps; and, the epidermal fluorescence ascribed to tryptophan can be used to monitor and quantitate functional states of epithelialization. UV fluorescence

  1. 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.

  2. Sandwich Wound Closure Reduces the Risk of Cerebrospinal Fluid Leaks in Posterior Fossa Surgery

    PubMed Central

    Heymanns, Verena; Oseni, Abidemi W.; Alyeldien, Ameer; Maslehaty, Homajoun; Parvin, Richard; Scholz, Martin

    2016-01-01

    Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF) leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8%) in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark), Gelfoam® (Pfizer Inc., New York, NY, USA) and polymethylmethacrylate (osteoclastic craniotomy). The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature. PMID:27478578

  3. Tilapia Piscidin 4 (TP4) Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice

    PubMed Central

    Huang, Hang-Ning; Chan, Yi-Lin; Wu, Chang-Jer; Chen, Jyh-Yih

    2015-01-01

    Antimicrobial peptides (AMPs) are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4), was isolated from Nile tilapia (Oreochromis niloticus); TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT) and fibroblast cell line (Hs-68). In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF) gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF), transforming growth factor (TGF), and vascular endothelial growth factor (VEGF). The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing. PMID:25955756

  4. Tilapia Piscidin 4 (TP4) Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice.

    PubMed

    Huang, Hang-Ning; Chan, Yi-Lin; Wu, Chang-Jer; Chen, Jyh-Yih

    2015-05-06

    Antimicrobial peptides (AMPs) are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4), was isolated from Nile tilapia (Oreochromis niloticus); TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT) and fibroblast cell line (Hs-68). In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF) gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF), transforming growth factor (TGF), and vascular endothelial growth factor (VEGF). The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.

  5. Methods and apparatus for microwave tissue welding for wound closure

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey (Inventor); Ngo, Phong H. (Inventor); Phan, Chau T. (Inventor); Byerly, Diane L. (Inventor); Dusl, John R. (Inventor); Sognier, Marguerite A. (Inventor); Carl, James R. (Inventor)

    2013-01-01

    Methods and apparatus for joining biological tissue together are provided. In at least one specific embodiment, a method for joining biological tissue together can include applying a biological solder on a wound. A barrier layer can be disposed on the biological solder. An antenna can be located in proximate spatial relationship to the barrier layer. An impedance of the antenna can be matched to an impedance of the wound. Microwaves from a signal generator can be transmitted through the antenna to weld two or more biological tissue pieces of the wound together. A power of the microwaves can be adjusted by a control circuit disposed between the antenna and the signal generator. The heating profile within the tissue may be adjusted and controlled by the placement of metallic microspheres in or around the wound.

  6. Wound Closure in the Lamellipodia of Single Cells: Mediation by Actin Polymerization in the Absence of an Actomyosin Purse String

    PubMed Central

    Henson, John H.; Nazarian, Ronniel; Schulberg, Katrina L.; Trabosh, Valerie A.; Kolnik, Sarah E.; Burns, Andrew R.; McPartland, Kenneth J.

    2002-01-01

    The actomyosin purse string is an evolutionarily conserved contractile structure that is involved in cytokinesis, morphogenesis, and wound healing. Recent studies suggested that an actomyosin purse string is crucial for the closure of wounds in single cells. In the present study, morphological and pharmacological methods were used to investigate the role of this structure in the closure of wounds in the peripheral cytoplasm of sea urchin coelomocytes. These discoidal shaped cells underwent a dramatic form of actin-based centripetal/retrograde flow and occasionally opened and closed spontaneous wounds in their lamellipodia. Fluorescent phalloidin staining indicated that a well defined fringe of actin filaments assembles from the margin of these holes, and drug studies with cytochalasin D and latrunculin A indicated that actin polymerization is required for wound closure. Additional evidence that actin polymerization is involved in wound closure was provided by the localization of components of the Arp2/3 complex to the wound margin. Significantly, myosin II immunolocalization demonstrated that it is not associated with wound margins despite being present in the perinuclear region. Pharmacological evidence for the lack of myosin II involvement in wound closure comes from experiments in which a microneedle was used to produce wounds in cells in which actomyosin contraction was inhibited by treatment with kinase inhibitors. Wounds produced in kinase inhibitor-treated cells closed in a manner similar to that seen with control cells. Taken together, our results suggest that an actomyosin purse string mechanism is not responsible for the closure of lamellar wounds in coelomocytes. We hypothesize that the wounds heal by means of a combination of the force produced by actin polymerization alone and centripetal flow. Interestingly, these cells did assemble an actomyosin structure around the margin of phagosome-like membrane invaginations, indicating that myosin is not simply

  7. Experience With Wound VAC and Delayed Primary Closure of Contaminated Soft Tissue Injuries in Iraq

    DTIC Science & Technology

    2006-11-01

    Experience With Wound VAC and Delayed Primary Closure of Contaminated Soft Tissue Injuries in Iraq Brian E. Leininger , MD, FACS, Todd E. Rasmussen...Annual Meeting, January 2006, Orlando FL (Poster). Address for reprints: Brian Leininger , MD, FACS, 2200 Bergquist Drive, Suite 1, Wilford Hall Medical

  8. Successful closure of feline axillary wounds by reconstruction of the elbow skin fold.

    PubMed

    Brinkley, C H

    2007-02-01

    This report describes the successful closure of five chronic feline axillary wounds. The aetiology was known to be forelimb entrapment in a neck collar in three cases and was suspected in the others. Each cat underwent a single surgical procedure during which the wound was debrided, the normal structure of the elbow skin fold was restored and the remaining skin defect was closed primarily. None of the cats had undergone any previous reconstruction attempts. No postoperative complications were observed and the wounds healed uneventfully. Cats have well-developed elbow skin folds, allowing a wide range of limb motion to occur. Having a forelimb trapped in a neck collar not only creates a wound in the axilla but also disrupts the normal anatomy of the skin fold. This report demonstrates that restoring the elbow skin fold before closing the wound may improve the chances of a successful reconstruction at the first surgical intervention.

  9. Accelerated endothelial wound healing on microstructured substrates under flow.

    PubMed

    Franco, Davide; Milde, Florian; Klingauf, Mirko; Orsenigo, Fabrizio; Dejana, Elisabetta; Poulikakos, Dimos; Cecchini, Marco; Koumoutsakos, Petros; Ferrari, Aldo; Kurtcuoglu, Vartan

    2013-02-01

    Understanding and accelerating the mechanisms of endothelial wound healing is of fundamental interest for biotechnology and of significant medical utility in repairing pathologic changes to the vasculature induced by invasive medical interventions. We report the fundamental mechanisms that determine the influence of substrate topography and flow on the efficiency of endothelial regeneration. We exposed endothelial monolayers, grown on topographically engineered substrates (gratings), to controlled levels of flow-induced shear stress. The wound healing dynamics were recorded and analyzed in various configurations, defined by the relative orientation of an inflicted wound, the topography and the flow direction. Under flow perpendicular to the wound, the speed of endothelial regeneration was significantly increased on substrates with gratings oriented in the direction of the flow when compared to flat substrates. This behavior is linked to the dynamic state of cell-to-cell adhesions in the monolayer. In particular, interactions with the substrate topography counteract Vascular Endothelial Cadherin phosphorylation induced by the flow and the wounding. This effect contributes to modulating the mechanical connection between migrating cells to an optimal level, increasing their coordination and resulting in coherent cell motility and preservation of the monolayer integrity, thus accelerating wound healing. We further demonstrate that the reduction of vascular endothelial cadherin phosphorylation, through specific inhibition of Src activity, enhances endothelial wound healing in flows over flat substrates.

  10. Proteomic analysis of rabbit tear fluid: Defensin levels after an experimental corneal wound are correlated to wound closure.

    PubMed

    Zhou, Lei; Beuerman, Roger W; Huang, Liqun; Barathi, Amutha; Foo, Yong Hwee; Li, Sam F Y; Chew, Fook Tim; Tan, Donald

    2007-09-01

    The cornea is the major refracting optical element of the eye and therefore critical for forming a retinal image. The exposed surface of the eye is protected from pathogens by the innate immune system whose components include defensins, naturally occurring peptides with antimicrobial properties, and the physical barrier formed by the outer epithelial layer of the cornea. The proteomic approach has revealed that tear levels of defensins are correlated with the course of healing of an experimental corneal wound. Tears were collected from New Zealand White rabbits prior to (day 0) and daily for 5 days (days 1-5) following a standard unilateral 6 mm diameter corneal epithelial abrasion. Tear protein profiles obtained from wounded and contra-lateral control eyes were compared using SELDI ProteinChip technology. Peptides and proteins of interest were purified by RP-HPLC and characterized by nanoESI-MS/MS. Mass spectra of tears on post-wound day 1, revealed 13 peaks whose level decreased and five that increased. During wound healing the tear protein profile correlated with wound closure. An important finding was that the levels of rabbit defensins (NP-1 and NP-2), which were elevated after wounding returned to normal levels by the time the corneal abrasion healed. Relative quantification of NP-2 in tear fluid prior to (day 0) and after corneal wounding (days 1- 3) was determined using iTRAQ technology. A corneal wound eliminates the barrier function of innate immunity and puts the cornea at risk from microbial attack until the epithelial cells restore the surface barrier. The increased availability of defensins in the tears during healing suggests that these peptides could protect the cornea from microbial attack during a period of increased vulnerability.

  11. Substance P enhances EPC mobilization for accelerated wound healing.

    PubMed

    Um, Jihyun; Jung, Nunggum; Chin, Sukbum; Cho, Younggil; Choi, Sanghyuk; Park, Ki-Sook

    2016-03-01

    Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α-smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell-derived factor-1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes.

  12. Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

    PubMed Central

    Lin, Audrey; Hokugo, Akishige; Choi, Jae; Nishimura, Ichiro

    2010-01-01

    Wounds created in the oral cavity heal rapidly and leave minimal scarring. We have examined a role of a previously isolated cDNA from oral wounds encoding wound inducible transcript-3.0 (wit3.0), also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2). FGFR1OP2/wit3.0 was highly expressed in oral wound fibroblasts without noticeable up-regulation of α-smooth muscle actin. In silico analyses, denaturing and nondenaturing gel Western blot, and immunocytology together demonstrated that FGFR1OP2/wit3.0 were able to dimerize and oligomerize through coiled-coil structures and appeared to associate with cytoskeleton networks in oral wound fibroblasts. Overexpression of FGFR1OP2/wit3.0 increased the floating collagen gel contraction of naïve oral fibroblasts to the level of oral wound fibroblasts, which was in turn attenuated by small-interfering RNA knockdown. The FGFR1OP2/wit3.0 synthesis did not affect the expression of collagen I as well as procontractile peptides such as α-smooth muscle actin, and transforming growth factor-β1 had no effect on FGFR1OP2/wit3.0 expression. Fibroblastic cells derived from embryonic stem cells carrying FGFR1OP2/wit3.0 (+/−) mutation showed significant retardation in cell migration. Thus, we postulate that FGFR1OP2/wit3.0 may regulate cell motility and stimulate wound closure. FGFR1OP2/wit3.0 was not up-regulated during skin wound healing; however, when treated with FGFR1OP2/wit3.0 -expression vector, the skin wound closure was significantly accelerated, resulting in the limited granulation tissue formation. Our data suggest that FGFR1OP2/wit3.0 may possess a therapeutic potential for wound management. PMID:19959814

  13. Alginate-hyaluronan composite hydrogels accelerate wound healing process.

    PubMed

    Catanzano, O; D'Esposito, V; Acierno, S; Ambrosio, M R; De Caro, C; Avagliano, C; Russo, P; Russo, R; Miro, A; Ungaro, F; Calignano, A; Formisano, P; Quaglia, F

    2015-10-20

    In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p<0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p<0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

  14. Wound complications in joint arthroplasty: comparing traditional and modern methods of skin closure.

    PubMed

    Patel, Ronak M; Cayo, Max; Patel, Arpan; Albarillo, Marie; Puri, Lalit

    2012-05-01

    Various methods of skin closure exist in joint replacement surgery. Although subcuticular skin closure techniques offer an aesthetic advantage over conventional skin stapling, no measurable differences have been reported. Furthermore, newer barbed sutures, such as the V-Loc absorbable suture (Covidien, Mansfield, Massachusetts), theoretically distribute tension evenly through the wound and help decrease knot-related complications. The purpose of this study was to evaluate whether wound complication rates were (1) lower in V-Loc closure cases as theoretically suggested, (2) lower for subcuticular closure vs staples, and (3) significantly different for knee and hip joint reconstruction.A retrospective chart review was conducted of 278 consecutive cases of primary joint reconstruction performed by a single surgeon (L.P.). The study group comprised 106 men and 161 women. Average patient age at surgery was 63 years (range, 18-92 years), and average body mass index of the cohort was 33.7 kg/m(2) (range, 25-51 kg/m(2)). Skin was closed via staple gun or subcuticular stitch (3-0 Biosyn [Covidien] vs V-Loc). Seven (3.9%) wound complications occurred in 181 cases closed with staples. Four (7.8%) wound complications occurred in 51 cases closed via subcuticular Biosyn suture. Six (13.0%) wound complications occurred in 46 cases closed with V-Loc suture. The staple group had a lower rate of complications when compared with the suture group as a whole (P=.033) and when compared specifically with the V-Loc suture group (P=.017).

  15. Systematic review and meta-analysis of published randomized controlled trials comparing purse-string vs conventional linear closure of the wound following ileostomy (stoma) closure

    PubMed Central

    Sajid, Muhammad Shafique; Bhatti, Muhammad I.; Miles, William FA.

    2015-01-01

    Objective: The objective of this article is to systematically analyse the randomized, controlled trials comparing the effectiveness of purse-string closure (PSC) of an ileostomy wound with conventional linear closure (CLC). Methods: Randomized, controlled trials comparing the effectiveness of purse-string closure vs conventional linear closure (CLC) of ileostomy wound in patients undergoing ileostomy closure were analysed using RevMan®, and the combined outcomes were expressed as risk ratio (RR) and standardized mean difference (SMD). Results: Three randomized, controlled trials, recruiting 206 patients, were retrieved from medical electronic databases. There were 105 patients in the PSC group and 101 patients in the CLC group. There was no heterogeneity among included trials. Duration of operation (SMD: −0.18; 95% CI: −0.45, 0.09; z = 1.28; P < 0.20) and length of hospital stay (SMD: 0.01; 95% CI: −0.26, 0.28; z = 0.07; P < 0.95) was statistically similar following both approaches of ileostomy wound closure. The risk of surgical site infection (OR, 0.10; 95% CI: 0.03, 0.33; z = 3.78; P < 0.0001) was significantly reduced when ileostomy wound was closed using PSC technique. Conclusion: PSC technique for ileostomy wound is associated with a reduced risk of surgical site infection apparently without influencing the duration of operation and length of hospital stay. PMID:25011379

  16. Loss of protein kinase Cepsilon results in impaired cutaneous wound closure and myofibroblast function.

    PubMed

    Leask, Andrew; Shi-Wen, Xu; Khan, Korsa; Chen, Yunliang; Holmes, Alan; Eastwood, Mark; Denton, Christopher P; Black, Carol M; Abraham, David J

    2008-10-15

    Cutaneous wound repair requires the de novo induction of a specialized form of fibroblast, the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast, which migrates into the wound where it adheres to and contracts extracellular matrix (ECM), resulting in wound closure. Persistence of the myofibroblast results in scarring and fibrotic disease. In this report, we show that, compared with wild-type littermates, PKCepsilon-/- mice display delayed impaired cutaneous wound closure and a reduction in myofibroblasts. Moreover, both in the presence and absence of TGFbeta, dermal fibroblasts from PKCepsilon-/- mice cultured on fibronectin show impaired abilities to form ;supermature' focal adhesions and alpha-SMA stress fibers, and reduced pro-fibrotic gene expression. Smad3 phosphorylation in response to TGFbeta1 was impaired in PKCepsilon-/- fibroblasts. PKCepsilon-/- fibroblasts show reduced FAK and Rac activation, and adhesive, contractile and migratory abilities. Overexpressing constitutively active Rac1 rescues the defective FAK phosphorylation, cell migration, adhesion and stress fiber formation of these PKCepsilon-/- fibroblasts, indicating that Rac1 operates downstream of PKCepsilon, yet upstream of FAK. These results suggest that loss of PKCepsilon severely impairs myofibroblast formation and function, and that targeting PKCepsilon may be beneficial in selectively modulating wound healing and fibrotic responses in vivo.

  17. Wound Closure in Smoking Peripheral Arterial Disease Patients With Treatment-Refractory Ulcerations

    PubMed Central

    Smedley, Jonathan; Michael, Georgina M.; Tamire, Yeabsera G.

    2016-01-01

    Despite ongoing smoking cessation efforts and optimized perfusion, failed wound closure in the presence of peripheral arterial disease (PAD) and diabetes are common. A clinical effectiveness review was conducted in actively smoking diabetic patients diagnosed with PAD, treated with serial applications of a viable intact cryopreserved human placental membrane (vCPM) (Grafix, Osiris Therapeutics Inc, Columbia, MD) for recalcitrant lower extremity ulcerations (n = 6). More than half of the patients were not candidates for revascularization. Baseline vascular status in 5 of 6 lower-extremity wounds remained unchanged throughout the entire course of vCPM treatment. Daily cigarette consumption averaged 18 cigarettes per patient. Mean wound duration and mean surface area was 53 weeks and 4.6 cm2, respectively. Mean number of vCPM applications and time to closure was 7.0 grafts in 7.8 weeks. There were no wound-related infections or amputations and no vCPM-related adverse events. All 6 wounds remained closed at the 12-month follow-up visit. In conclusion, vCPM demonstrated clinically effective outcomes in 6 previously nonhealing ulcerations despite ongoing smoking habits in the presence of PAD and diabetes. PMID:27852883

  18. Sternal bands for closure of midline sternotomy leads to better wound healing.

    PubMed

    Bhattacharya, Susmit; Sau, Indrajit; Mohan, Man; Hazari, Kunal; Basu, Rajarshi; Kaul, Ajay

    2007-01-01

    Midline sternotomy is the most common incision for cardiac surgery, but problems of wound healing and sternal instability are still matters of concern. The use of stainless steel wires only was compared with the use of wires plus sternal bands for closure of midline sternotomy wounds in a 2-year period. Of 370 patients in whom only stainless steel wires were used, 14 (3.78%) required re-operation for dehiscence. Only 3 (0.76%) of 395 patients in whom sternal bands were also used, required re-operation for dehiscence. The difference was highly significant. It was concluded that use of sternal bands leads to a more stable union.

  19. LXA{sub 4} actions direct fibroblast function and wound closure

    SciTech Connect

    Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Leung, Kai P.; Van Dyke, Thomas E.

    2015-09-04

    Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

  20. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  1. An Inexpensive Modified Primary Closure Technique for Class IV (Dirty) Wounds Significantly Decreases Superficial and Deep Surgical Site Infection.

    PubMed

    Kim, Bradford J; Aloia, Thomas A

    2016-11-01

    Despite the creation of several programs to decrease the incidence of surgical site infection, it remains a common complication that has a significant impact on patient recovery and medical costs. The following is a description and brief outcome report of a modified primary closure technique used for dirty (Class IV) wounds. There were 14 consecutive patients who had a laparotomy with Class IV wounds treated by a single surgeon (TAA) from 2011 to 2015. All patients had a history of cancer and either showed signs suggestive for an acute abdomen and required an emergent exploratory laparotomy or were found to have purulent intraabdominal infection at the time of elective surgery. The operation and "modified primary closure" technique (subcutaneous wound wicks with stapled skin closure) were performed in every case. The modified primary closure technique was utilized in 14 patients with a Class IV wound. There were no 30-day mortalities or readmissions. Wound wicks were slowly advanced out over a 7-day period, and only one patient required subsequent wound packing of a single-wicked area. There were no superficial or deep surgical site infections, or wound dehiscence during the hospital course, or 30-day postoperative period. The modified primary closure technique is efficient and inexpensive and was effective in a series of 14 patients with wounds classified as dirty.

  2. The use of dermabond® as an adjunct to wound closure after total knee arthroplasty: examining immediate post-operative wound drainage.

    PubMed

    El-Gazzar, Yaser; Smith, Daniel C; Kim, Sun Jin; Hirsh, David M; Blum, Yossef; Cobelli, Marcie; Cohen, Hillel W

    2013-04-01

    Wound drainage after total knee arthroplasty (TKA) can be detrimental to surgical outcome. This IRB-approved randomized, prospective, blinded study examined the use of Dermabond® as an adjunct to wound closure after TKA. We proposed that Dermabond® supplementation to wound closure would result in a significant decrease in wound drainage after TKA. After standardized closure, patients were randomized into experimental or control groups with the experimental group receiving Dermabond® supplementation. Standardized dressings were evaluated postoperatively and drainage units were compared using a Mann-Whitney U Test. The median drainage for the Dermabond group (153) was lower than the drainage for the control group (657) at a statistically significant level (P<0.001).

  3. Syneture stainless STEEL suture. A collective review of its performance in surgical wound closure.

    PubMed

    Edlich, Richard F; Drake, David B; Rodeheaver, George T; Winters, Kathryne L; Greene, Jill A; Gubler, K Dean; Long, William B; Britt, L D; Winters, Samuel P; Scott, Christine C; Lin, Kant Y

    2006-01-01

    Syneture (division of U.S. Surgical, division of Tyco Healthcare, Norwalk, Connecticut, USA) STEEL sutures are monofilament stainless steel sutures composed of 316L stainless steel conforming to ASTM Standard F138 grade 2 (" Stainless steel bar and wire for surgical implant"). STEEL sutures meet all requirements established by the United States Pharmacopeia (USP) for nonabsorbable surgical sutures. Steel sutures are for use in abdominal wound closure, intestinal anastomosis, hernia repair, sternal closure, and skin closure. They are attached to the following types of surgical needles: Roto-Grip Needles and SCC Needle. The sutures and needles are packaged in a Mylar/Tyvek outer envelope. The purposes of this clinical review are two fold. First, we will report the performance of the Syneture STEEL suture product in the largest studies of suture performance ever reported in the literature. In addition, we will provide comprehensive information from the surgical literature that highlights the unique benefits of stainless steel sutures for the following wound closure techniques: sternal fixation, abdominal wound repair, inguinal hernia repair, and skin wound closure. Consorta Inc. (Rolling Meadows, Illinois), a leading healthcare resource management group purchasing organization, and Syneture, jointly with a clinician task force, designed a reproducible surgical evaluation program for needles and sutures in a large cooperative of healthcare systems. Because of the subjective nature of the more commonly used suture selection techniques, a nonexperimental observational study approach was designed to replace perception of performance characteristics with actual clinical experience. In a report involving 19 Consorta shareholder hospitals, they discussed the preliminary part (Phase I) of a large nonexperimental observational study of the clinical performance of surgical needles and sutures. Performance characteristics of the sutures and needles produced by Syneture that were

  4. Epidermal Graft Accelerates the Healing of Acute Wound: A Self-controlled Case Report

    PubMed Central

    Bystrzonowski, Nicola; Hachach-Haram, Nadine; Richards, Toby; Mosahebi, Afshin

    2016-01-01

    Summary: Wound care represents a significant socioeconomic burden, with over half of chronic wounds taking up to a year to heal. Measures to accelerate wound healing are beneficial to patients and also reduce the cost and burden of wound management. Epidermal grafting (EG) is an emerging option for autologous skin grafting in the outpatient setting to improve wound healing. Although several case series have previously reported good clinical outcome with EG, the healing rate in comparison to conservative wound management is not known. In this report, we compare the weekly healing rate of 2 separate wounds in the same patient, one treated with EG and the other with dressings. The treated wound showed accelerated healing, with the healing rate being the highest at the first 2 weeks after EG. The average healing time of the treated wound was 40% faster compared with the control wound. EG accelerates healing of acute wounds, potentially reducing the healthcare cost and surgical burden. PMID:27975024

  5. Safety and utility of a PMMA-based tissue adhesive for closure of surgical incision wounds.

    PubMed

    Suzuki, Ryusuke; Kuroyanagi, Yoshimitsu

    2013-01-01

    This study aimed to investigate the safety and utility of the polymethylmethacrylate (PMMA)-based tissue adhesive (PMMA-ta) for wound closure. This product is composed of 4-methacryloyloxyethyl trimellitate anhydride and methylmethacrylate as monomers, tri-n-butylborane as initiator, and PMMA powder as filler. These components are mixed at the time of use. This resulting paste hardens within several minutes. The safety of PMMA-ta was evaluated in an internal wound model using a cultured dermal substitute (CDS), i.e. a fibroblast-embedded collagen gel sheet. PMMA-ta was applied to one CDS, covered with a second CDS, and then cultured for 1 week (group II). A commercially available 2-octyl cyanoacrylate-based tissue adhesive (OCA) was used for comparative purposes (group I). No tissue adhesive was applied to the CDSs in the control group. Fibroblast viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell viability in the group I was 36%, and cell viability in the group II was 84%, of that in the control group. These results indicate that PMMA-ta has lower cytotoxicity than OCA. Next, the usefulness of PMMA-ta as a tissue adhesive was evaluated in three different wound models using Sprague-Dawley rats: (1) a thin skin incision wound, (2) a thick skin incision wound, and (3) a full-thickness incision wound through the abdominal wall. The third experiment is the surgical incision model with the most severe condition. The comparative study using OCA was conducted only in the third experiment. Each wound healing process was evaluated macroscopically and histologically after 1 week, 2 weeks, and 3 months. An excellent macroscopic wound appearance was observed with both PMMA-ta and OCA, with only a slightly visible fine-line scar. Histologically, a typical primary healing was observed for both adhesives. Considering its safety and utility, PMMA-ta is therefore promising for use as a tissue adhesive in wound closure.

  6. Stress Signals, Mediated by Membranous Glucocorticoid Receptor, Activate PLC/PKC/GSK-3β/β-catenin Pathway to Inhibit Wound Closure.

    PubMed

    Jozic, Ivan; Vukelic, Sasa; Stojadinovic, Olivera; Liang, Liang; Ramirez, Horacio A; Pastar, Irena; Tomic Canic, Marjana

    2016-12-23

    Glucocorticoids (GCs), key mediators of stress signals, are also potent wound healing inhibitors. To understand how stress signals inhibit wound healing, we investigated the role of membranous glucocorticoid receptor (mbGR) by using cell-impermeable BSA-conjugated dexamethasone. We found that mbGR inhibits keratinocyte migration and wound closure by activating a Wnt-like phospholipase (PLC)/ protein kinase C (PKC) signaling cascade. Rapid activation of mbGR/PLC/PKC further leads to activation of known biomarkers of nonhealing found in patients, β-catenin and c-myc. Conversely, a selective inhibitor of PKC, calphostin C, blocks mbGR/PKC pathway, and rescues GC-mediated inhibition of keratinocyte migration in vitro and accelerates wound epithelialization of human wounds ex vivo. This novel signaling mechanism may have a major impact on understanding how stress response via GC signaling regulates homeostasis and its role in development and treatments of skin diseases, including wound healing. To test tissue specificity of this nongenomic signaling mechanism, we tested retinal and bronchial human epithelial cells and fibroblasts. We found that mbGR/PLC/PKC signaling cascade exists in all cell types tested, suggesting a more general role. The discovery of this nongenomic signaling pathway, in which glucocorticoids activate Wnt pathway via mbGR, provides new insights into how stress-mediated signals may activate growth signals in various epithelial and mesenchymal tissues.

  7. Evaluation of Wound Closure Activity of Nigella sativa, Melastoma malabathricum, Pluchea indica, and Piper sarmentosum Extracts on Scratched Monolayer of Human Gingival Fibroblasts

    PubMed Central

    Ab Rahman, Mas Rizal; Mohd Bakri, Marina

    2014-01-01

    Nigella sativa, Melastoma malabathricum, Pluchea indica, and Piper sarmentosum are common Asian traditional medicines to treat minor wounds. This study aimed to investigate the in vitro wound healing properties of aqueous extracts of these plants using human gingival fibroblast (HGF) monolayer as study model. DPPH scavenging activity of the extracts was evaluated and effect on HGF proliferation was determined. Their effect on HGF's function to synthesize collagen was indicated by the level of hydroxyproline produced and effect on wound healing activity was assessed using an in vitro scratch assay. The influence of the extracts on expression of bFGF and TGF-β was also determined. Results revealed all four extracts to exhibit low free radical scavenging activity. The extract from N. sativa (NSSE) compared to the others showed favourable enhancement of HGF proliferation with EC50 of 22.67 ± 3.06 µg/mL (P < 0.05) with accelerated wound closure activity despite its nonsignificant effect on collagen synthesis. In addition to the elevated level of bFGF by up to 15% at 100 µg/mL of NSSE, a slightly better effect was observed on the expression of TGF-β. NSSE thus showed that promising wound healing properties and data obtained may contribute towards validation of its traditional use for the healing of oral wounds. PMID:25371695

  8. LiquiBand® Surgical S topical adhesive versus sutures for the closure of laparoscopic wounds. A randomized controlled trial.

    PubMed

    Jan, Haider; Waters, Natasha; Haines, Pat; Kent, Andrew

    2013-01-01

    Cyanoacrylate adhesives offer the surgeon and patient an alternative to subcuticular suturing. LiquiBand® Surgical S (LBSS) is a new formulation with a blend of monomeric n-butyl and 2-octyl cyanoacrylates. In this study, the effectiveness, safety, and clinical utility of LBSS was compared to Vicryl(™) sutures for the closure of laparoscopic incisions. This was a prospective randomized study of LBSS skin adhesive versus Vicryl(™) sutures for the topical closure of laparoscopic surgical incisions. Subjects were asked to return at 2 weeks postsurgery to report complications and adverse events. Wounds were evaluated for apposition and cosmesis using a modified Hollander Wound Evaluation Scale (HWES). The Shapiro-Wilk test of normality was done. Independent-samples T test, Mann Whitney U test, and chi-square test were used to compare variables between the two wound closure methods. A total of 114 subjects participated in this trial completing all aspects of the study. Fifty-five subjects received sutures for topical wound closure, with 59 subjects receiving LBSS. Surgeons were found to be satisfied with 100 % of all applications using the LBSS device. One hundred percent of wounds closed with sutures and 98.9 % wounds closed with LBSS achieving an optimal HWES of 0. There was no statistical difference in cosmesis or complications for either method. Closure with LBSS was significantly faster by a mean of 2 min. LiquiBand® Surgical S is as good as sutures for the closure of laparoscopic wounds in terms of cosmesis and complications with the added benefit of being significantly faster.

  9. Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin.

    PubMed

    Rittié, Laure; Farr, Elyssa A; Orringer, Jeffrey S; Voorhees, John J; Fisher, Gary J

    2016-10-01

    Human skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re-epithelialization of partial-thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound-induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell-cell cohesiveness was most obvious in ESG-derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell-cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re-epithelialization in aging and further support the importance of ESGs for the repair of human wounds.

  10. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

    Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  11. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

    PubMed

    Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

    2016-11-01

    There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation.

  12. Recombinant growth factor mixtures induce cell cycle progression and the upregulation of type I collagen in human skin fibroblasts, resulting in the acceleration of wound healing processes.

    PubMed

    Lee, Do Hyun; Choi, Kyung-Ha; Cho, Jae-We; Kim, So Young; Kwon, Tae Rin; Choi, Sun Young; Choi, Yoo Mi; Lee, Jay; Yoon, Ho Sang; Kim, Beom Joon

    2014-05-01

    Application of growth factor mixtures has been used for wound healing and anti-wrinkles agents. The aim of this study was to evaluate the effect of recombinant growth factor mixtures (RGFM) on the expression of cell cycle regulatory proteins, type I collagen, and wound healing processes of acute animal wound models. The results showed that RGFM induced increased rates of cell proliferation and cell migration of human skin fibroblasts (HSF). In addition, expression of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)4, and Cdk2 proteins was markedly increased with a growth factor mixtures treatment in fibroblasts. Expression of type I collagen was also increased in growth factor mixtures-treated HSF. Moreover, growth factor mixtures-induced the upregulation of type I collagen was associated with the activation of Smad2/3. In the animal model, RGFM-treated mice showed accelerated wound closure, with the closure rate increasing as early as on day 7, as well as re-epithelization and reduced inflammatory cell infiltration than phosphate-buffered saline (PBS)-treated mice. In conclusion, the results indicated that RGFM has the potential to accelerate wound healing through the upregulation of type I collagen, which is partly mediated by activation of Smad2/3-dependent signaling pathway as well as cell cycle progression in HSF. The topical application of growth factor mixtures to acute and chronic skin wound may accelerate the epithelization process through these molecular mechanisms.

  13. Acceleration of wound repair by curcumin in the excision wound of mice exposed to different doses of fractionated γ radiation.

    PubMed

    Jagetia, Ganesh Chandra; Rajanikant, Golgod Krishnamurthy

    2012-02-01

    Fractionated irradiation (IR) before or after surgery of malignant tumours causes a high frequency of wound healing complications. Our aim was to investigate the effect of curcumin (CUM) on the healing of deep excision wound of mice exposed to fractionated IR by mimicking clinical conditions. A full-thickness dermal excision wound was created on the shaved dorsum of mice that were orally administered or not with 100 mg of CUM per kilogram body weight before partial body exposure to 10, 20 or 40 Gy given as 2 Gy/day for 5, 10 or 20 days. The wound contraction was determined periodically by capturing video images of the wound from day 1 until complete healing of wounds. Fractionated IR caused a dose-dependent delay in the wound contraction and prolonged wound healing time, whereas CUM administration before fractionated IR caused a significant elevation in the wound contraction and reduced mean wound healing time. Fractionated IR reduced the synthesis of collagen, deoxyribonucleic acid (DNA) and nitric oxide (NO) at different post-IR times and treatment of mice with CUM before IR elevated the synthesis of collagen, DNA and NO significantly. Histological examination showed a reduction in the collagen deposition, fibroblast and vascular densities after fractionated IR, whereas CUM pre-treatment inhibited this decline significantly. Our study shows that CUM pre-treatment accelerated healing of irradiated wound and could be a substantial therapeutic strategy in the management of irradiated wounds.

  14. Acanthus ebracteatus Vahl. Ethanol Extract Enhancement of the Efficacy of the Collagen Scaffold in Wound Closure: A Study in a Full-Thickness-Wound Mouse Model

    PubMed Central

    Somchaichana, Jutamas; Bunaprasert, Tanom; Patumraj, Suthiluk

    2012-01-01

    Acanthus ebracteatus Vahl. is a Thai herb that is effective in wound healing. We sought to quantitatively determine whether or not the combined application of Acanthus ebracteatus Vahl. and a collagen scaffold will increase wound closure and angiogenesis. Balb/c mice (body weight: 22–25 g) were anesthetized with sodium thiopental. The dorsal skin incision measuring 1.5 × 1.5 cm was made and then deepened using scissors to produce a full-thickness incision down to the level of the panniculus carnosus. The size of the wound was approximately 10% of the total body surface area. The collagen sheet was implanted onto the wound. Animals were divided into 4 major groups as follows: wound with normal saline (W-NSS), wound treated with 0.3 g/kg BW of Acanthus ebracteatus Vahl. extract (W-AE (0.3 g/kg.bw)), wound implanted with collagen scaffold (W-Coll), and wound implanted with collagen scaffold and treated with 0.3 g/kg BW of Acanthus ebracteatus Vahl. (W-Coll-AE combination). On day 14, the W-Coll-AE group showed decreased wound areas and increased capillary vascularity (CV) when compared to the other 3 groups, W-NSS, W-AE0.3, and W-Coll. In the present study, the combination of AE0.3 with collagen showed the best effect on skin angiogenesis and promoted wound closure with less neutrophil infiltration. PMID:23093862

  15. [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.

  16. Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats.

    PubMed

    Immonen, Jessica A; Zagon, Ian S; Lewis, Gregory S; McLaughlin, Patricia J

    2013-10-01

    Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound

  17. Same admission colostomy closure (SACC). A new approach to rectal wounds: a prospective study.

    PubMed Central

    Renz, B M; Feliciano, D V; Sherman, R

    1993-01-01

    OBJECTIVE: The purposes of this project were to study the healing of protected rectal wounds (RWs) using contrast enemas (CEs) and to establish the safety of same admission colostomy closure (SACC) in terms of colostomy closure (CC) and rectal wound-related outcomes, for selected patients with radiologically healed RWs. SUMMARY BACKGROUND DATA: Traditional treatment of RWs has included a diverting colostomy that is closed 2 or more months later during a readmission. METHODS: All patients admitted with a rectal injury were entered into this prospective study, treated with a diverting colostomy and presacral drainage, and managed according to a postoperative protocol that included a CE per anus to detect healing of the RW. Patients with no leaking on their first CE, no infection, and anal continence underwent SACC. RESULTS: From 1990 to 1993, 30 consecutive patients had rectal injuries, 90% of which resulted from gunshot wounds. The first CE was performed in 29 patients 5 to 10 days after injury. In this group, 21 patients did not and 8 did have leakage from their RWs. The proportions of RWs radiologically healed at 7 and 10 days after injury were 55.2% and 75%, respectively. Sixteen patients with a normal CE underwent SACC 9 to 19 days after injury (mean, 12.4 days). There were two fecal fistulas (2 of 7; 28.6%) after simple suture closure, none (0 of 9) after resection of the stoma with end-to-end anastomosis, and no RW-related complications after SACC. The mean hospitalization time was 17.4 days. CONCLUSIONS: The following conclusions were drawn: (1) CE confirmed healing of RWs in 75% of patients by 10 days after injury; (2) 60% of patients with RWs were candidates for SACC, and 53% were discharged with their colostomies closed; (3) SACC was performed without complications in 87.5% of patients with radiologically healed RWs; and (4) there were no RW-related complications after SACC. Images Figure 6. Figure 7. Figure 8. Figure 9. PMID:8373271

  18. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice.

    PubMed

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers.

  19. Supplementation with undenatured whey protein during diabetes mellitus improves the healing and closure of diabetic wounds through the rescue of functional long-lived wound macrophages.

    PubMed

    Badr, Gamal

    2012-01-01

    Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic patients. A serious complication of diabetes is impaired healing, which diminishes physical activity and, in some cases, leads to chronic wounds and limb amputation. Whey proteins (WPs) enhance immunity during early development and have a protective role in some immune disorders. The effect of camel WPs on wound healing in a streptozotocin-induced type 1 diabetic mice model was investigated. Sixty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice that were orally supplemented with undenatured WP (100 mg/kg body weight/day for 1 month through oral gavage). We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF-κB and greatly improved the closure of diabetic wounds compared with the control mice. Most important, the supplementation of diabetic mice with WP rescued functional, long-lived wound-resident macrophages. Our data reveal the benefits of WP supplementation in improving the healing and closure of diabetic wounds.

  20. G-CSF Administration after the Intraosseous Infusion of Hypertonic Hydroxyethyl Starches Accelerating Wound Healing Combined with Hemorrhagic Shock

    PubMed Central

    Huang, Hong; Liu, Jiejie; Hao, Haojie; Tong, Chuan; Ti, Dongdong; Liu, Huiling; Song, Haijing; Jiang, Chaoguang; Fu, Xiaobing; Han, Weidong

    2016-01-01

    Objective. To evaluate the therapeutic effects of G-CSF administration after intraosseous (IO) resuscitation in hemorrhagic shock (HS) combined with cutaneous injury rats. Methods. The rats were randomly divided into four groups: (1) HS with resuscitation (blank), (2) HS with resuscitation + G-CSF (G-CSF, 200 μg/kg body weight, subcutaneous injection), (3) HS with resuscitation + normal saline solution injection (normal saline), and (4) HS + G-CSF injection without resuscitation (Unres/G-CSF). To estimate the treatment effects, the vital signs of alteration were first evaluated, and then wound closure rates and homing of MSCs and EPCs to the wound skins and vasculogenesis were measured. Besides, inflammation and vasculogenesis related mRNA expressions were also examined. Results. IO infusion hypertonic hydroxyethyl starch (HHES) exhibited beneficial volume expansion roles and G-CSF administration accelerated wound healing 3 days ahead of other groups under hemorrhagic shock. Circulating and the homing of MSCs and EPCs at wound skins were significantly elevated at 6 h after G-CSF treatment. Inflammation was declined since 3 d while angiogenesis was more obvious in G-CSF treated group on day 9. Conclusions. These results suggested that the synergistical application of HHES and G-CSF has life-saving effects and is beneficial for improving wound healing in HS combined with cutaneous injury rats. PMID:26989687

  1. 5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization.

    PubMed

    Gilliver, S C; Ruckshanthi, J P D; Hardman, M J; Zeef, L A H; Ashcroft, G S

    2009-01-01

    The ongoing search for explanations as to why elderly males heal acute skin wounds more slowly than do their female counterparts (and are more strongly disposed to conditions of chronic ulceration) has identified endogenous oestrogens and androgens as being respectively enhancers and inhibitors of repair. We previously demonstrated that blocking the conversion of testosterone to 5alpha-dihydrotestosterone (DHT) limits its ability to impair healing, suggesting that DHT is a more potent inhibitor of repair than is testosterone. The present study aimed to delineate the central mechanisms by which androgens delay repair. Whilst the contractile properties of neither rat wounds in vivo nor fibroblast-impregnated collagenous discs in vitro appeared to be influenced by androgen manipulations, the global blockade of DHT biosynthesis markedly accelerated re-epithelialization of incisional and excisional wounds and reduced local expression of beta-catenin, a key inhibitor of repair. Moreover, DHT retarded the in vitro migration of epidermal keratinocytes following scratch wounding. By contrast, it failed to influence the migratory and proliferative properties of dermal fibroblasts, suggesting that its primary inhibitory effect is upon re-epithelialization. These novel findings may be of particular significance in the context of chronic ulceration, for which being male is a key risk factor.

  2. A Randomized Study Comparing Skin Staples with Subcuticular Sutures for Wound Closure at Caesarean Section in Black-Skinned Women

    PubMed Central

    Abdus-Salam, Rukiyat Adeola; Bello, Folasade Adenike; Olayemi, Oladapo

    2014-01-01

    This study aimed to compare patients' satisfaction and outcome of caesarean section wound closure by skin staples and subcuticular suture at discharge and 6 weeks of postoperation. It was a randomized controlled trial of pregnant women scheduled for caesarean section at the University College Hospital, Ibadan, Nigeria, allocating them to wound closure by skin staples or subcuticular suture. Pain was assessed using the box numeric pain scale. Scar assessments were by patient, research nurse, and independent observers using the visual analogue scale, modified patient observer scar assessment scale, and patient satisfaction scale. Operation time (minutes) was significantly shorter in the staple group, 40.26 (±16.53) compared to 47.55 (±14.55) in the suture group (P = 0.025). Skin closure time (seconds) was significantly less in the staple group, 118.62 (±69.68) versus 388.70 (±170.40) in the suture group (P ≤ 0.001). There was no difference in pain experienced, wound assessment by the participants, and patients' satisfaction. Participants in the staple group scored higher on both scar assessment scales by the nurse (P = 0.044). Cost comparison analysis showed that staple use costs significantly more than suture use (P < 0.001). The perceived benefit of subcuticular suture over skin staples was not observed and participants were satisfied with both wound closure techniques. PMID:27437457

  3. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  4. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  5. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  6. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  7. Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.

    PubMed

    Mittermayr, Rainer; Branski, Ludwik; Moritz, Martina; Jeschke, Marc G; Herndon, David N; Traber, Daniel; Schense, Jason; Gampfer, Jörg; Goppelt, Andreas; Redl, Heinz

    2016-05-01

    Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Inhibition of Prostaglandin Transporter (PGT) Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-Diabetic and Diabetic Rats

    PubMed Central

    Liu, Zhongbo; Benard, Outhiriaradjou; Syeda, Mahrukh M.; Schuster, Victor L.; Chi, Yuling

    2015-01-01

    Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs), including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT) (SLCO2A1), which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells), and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs) either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs) and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs. PMID:26230411

  9. mTOR Inhibition by Everolimus Does Not Impair Closure of Punch Biopsy Wounds in Renal Transplant Patients

    PubMed Central

    Dutt, Shelley B.; Gonzales, Josephine; Boyett, Megan; Costanzo, Anne; Han, Peggy P.; Steinberg, Steven; McKay, Dianne B.; Jameson, Julie M.

    2017-01-01

    Background Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. Methods Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region. Homeostatic gene expression was examined in the skin obtained from the biopsy and wound surface area was examined on day 7. Peripheral blood mononuclear cells were examined for cytokine production. Results There are no significant changes in autophagy related 13, epidermal growth factor, insulin-like growth factor binding protein 3, IL-2, kruppel-like factor 4, and TGFB1 gene expression in the skin suggesting that there is little impact of everolimus on these genes within nonwounded skin. Peripheral blood T cells are more sensitive to cell death in everolimus-treated patients, but they retain the ability to produce proinflammatory cytokines required for efficient wound repair. Importantly, there is no delay in the closure of biopsy wounds in patients receiving everolimus as compared to those not receiving mTOR inhibition. Conclusions Everolimus treatment is not associated with impaired closure of skin biopsy wounds in kidney transplant recipients. These data highlight the importance of exploring whether larger surgical wounds would show a similar result and how other factors, such as diabetes, impact wound healing complications associated with mTOR suppression.

  10. 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.

  11. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

    PubMed Central

    Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

    2012-01-01

    Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

  12. Acceleration of diabetic wound healing using a novel protease-anti-protease combination therapy.

    PubMed

    Gao, Ming; Nguyen, Trung T; Suckow, Mark A; Wolter, William R; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-12-08

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body's response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9-knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.

  13. Acceleration of diabetic wound healing using a novel protease–anti-protease combination therapy

    PubMed Central

    Gao, Ming; Nguyen, Trung T.; Suckow, Mark A.; Wolter, William R.; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-01-01

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9–knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. PMID:26598687

  14. Emergency treatment on facial laceration of dog bite wounds with immediate primary closure: a prospective randomized trial study

    PubMed Central

    2013-01-01

    Background To investigate the emergency treatment on facial laceration of dog bite wounds and identify whether immediate primary closure is feasible. Methods Six hundred cases with facial laceration attacked by dog were divided into two groups randomly and evenly. After thorough debridement, the facial lacerations of group A were left open, while the lacerations of group B were undertaken immediate primary closure. Antibiotics use was administrated only after wound infected, not prophylactically given. The infection rate, infection time and healing time were analyzed. Results The infection rate of group A and B was 8.3% and 6.3% respectively (P>0.05); the infection time was 26.3±11.6h and 24.9±13.8h respectively (P>0.05), the healing time was 9.12±1.30d and 6.57±0.49d respectively (P<0.05) in taintless cases, 14.24±2.63d and 10.65±1.69d respectively (P<0.05) in infected cases. Compared with group A, there was no evident tendency in increasing infection rate (8.3% in group A and 6.3% in group B respectively) and infection period (26.3±11.6h in group A and 24.9±13.8h in group B respectively) in group B. Meanwhile, in group B, the wound healing time was shorter than group A statistically in both taintless cases (9.12±1.30d in group A and 6.57±0.49d in group B respectively) and infected cases (14.24±2.63d in group A and 10.65±1.69d in group B respectively). Conclusion The facial laceration of dog bite wounds should be primary closed immediately after formal and thoroughly debridement. And the primary closure would shorten the healing time of the dog bite wounds without increasing the rate and period of infection. There is no potentiality of increasing infection incidence and infection speed, compared immediate primary closure with the wounds left open. On the contrary, primary closure the wounds can promote its primary healing. Prophylactic antibiotics administration was not recommended. and the important facial organ or tissue injuries should be secondary

  15. ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell–Derived Retinal Pigmented Epithelium

    PubMed Central

    Croze, Roxanne H.; Thi, William J.; Clegg, Dennis O.

    2016-01-01

    Purpose Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell–derived RPE (hESC-RPE) attachment, proliferation, and wound closure. Methods H9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined. Results Pharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition. Conclusions ROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing. Translational Relevance Modulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies. PMID:27917311

  16. Circadian rhythms accelerate wound healing in female Siberian hamsters.

    PubMed

    Cable, Erin J; Onishi, Kenneth G; Prendergast, Brian J

    2017-03-15

    Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are impaired in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3h after light onset (ZT03) or 2h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing.

  17. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

    PubMed Central

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification. PMID:26347154

  18. The immediate use of a silicone sheet wound closure device in scar reduction and prevention.

    PubMed

    Parry, James R; Stupak, Howard D; Johnson, Calvin M

    2016-02-01

    Silicone has been used successfully postoperatively in the prevention of hypertrophic and other types of adverse scars. The Silicone Suture Plate (SSP) is a new, minimally invasive, sterile wound closure device that is applied intraoperatively to prevent adverse scarring. The SSP device permits immediate application of silicone while concurrently allowing for wound-edge tension redistribution. In this prospective, controlled, single-blinded clinical study, 8 consecutive patients undergoing deep-plane rhytidectomy were selected. SSP devices were placed on the patients' posterior rhytidectomy hairline incision; the mirror-image control site underwent standard suturing techniques. Three blinded, independent raters assessed the treatment and control sides at 6-week and 4-month follow-up visits, using the Objective Scar Assessment Scale (OSAS), a validated scar assessment tool. The 6-week OSAS scores revealed an 18.4% improvement on the side with the SSP device (13.3) when compared to the control side (16.3). The 4-month OSAS scores showed a 27.3% improvement on the treatment side from 12.7 (control) to 9.2 (SSP). These OSAS results were found to be statistically significant when taken as an aggregate of the observers' scores, but not when observers' scores were measured individually (p < 0.05). In our series of patients, we showed promising results with the use of the SSP device. Early silicone application and tissue tension distribution contributed to an overall more aesthetically pleasing scar compared to those seen with standard suturing techniques, although more testing is required.

  19. Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

    PubMed Central

    Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Sokabe, Masahiro

    2017-01-01

    Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin. PMID:28210627

  20. Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications.

    PubMed

    Xie, Jingwei; Macewan, Matthew R; Ray, Wilson Z; Liu, Wenying; Siewe, Daku Y; Xia, Younan

    2010-09-28

    This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The type I collagen exhibited a high degree of organization on the scaffolds of radially aligned fibers and a haphazard distribution on the scaffolds of random fibers. Taken together, the scaffolds based on radially aligned, electrospun nanofibers show great potential as artificial dural substitutes and may be particularly useful as biomedical patches or grafts to induce wound closure and/or tissue regeneration.

  1. Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations

    PubMed Central

    Ayello, Elizabeth A.; Woo, Kevin; Nitzki-George, Diane; Sibbald, R. Gary

    2010-01-01

    Background As millions of emergency department (ED) visits each year include wound care, emergency care providers must remain experts in acute wound management. The variety of acute wounds presenting to the ED challenge the physician to select the most appropriate management to facilitate healing. A complete wound history along with anatomic and specific medical considerations for each patient provides the basis of decision making for wound management. It is essential to apply an evidence‐based approach and consider each wound individually in order to create the optimal conditions for wound healing. Aims A comprehensive evidence‐based approach to acute wound management is an essential skill set for any emergency physician or acute care practitioner. This review provides an overview of current evidence and addresses frequent pitfalls. Methods A systematic review of the literature for acute wound management was performed. Results A structured MEDLINE search was performed regarding acute wound management including established wound care guidelines. The data obtained provided the framework for evidence‐based recommendations and current best practices for wound care. Conclusion Acute wound management varies based on the wound location and characteristics. No single approach can be applied to all wounds; however, a systematic approach to acute wound care integrated with current best practices provides the framework for exceptional wound management. PMID:21373312

  2. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    PubMed

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

    2016-10-14

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P < 0.05). The mean unhealed wound area was significantly smaller, and the mean percentage of total wound healing was significantly higher in ASI-treated wounds than in the control wounds. Hydroxyproline, collagen, and matrix metalloproteinases were measured in the granulated tissue and found to be affected. Inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  3. Accelerated wound healing with combined NPWT and IPC: a case series.

    PubMed

    Arvesen, Kristian; Nielsen, Camilla Bak; Fogh, Karsten

    2017-03-01

    Negative pressure wound therapy (NPWT) and intermittent pneumatic compression (IPC) have traditionally been used in patients with chronic complicated non-healing wounds. The aim of this study (retrospective case series) was to describe the use of NPWT in combination with IPC in patients with a relatively short history (2-6 months) of ulcers. All wounds showed improved healing during the treatment period with marked or moderate reduction in ulcer size, and granulation tissue formation was markedly stimulated. Oedema was markedly reduced due to IPC. Treatment was generally well tolerated. The results of this study indicate that combined NPWT and IPC can accelerate wound healing and reduce oedema, thus shortening the treatment period. Therefore, patients may have a shorter healing period and may avoid entering a chronic wound phase. However, controlled studies of longer duration are needed in order to show the long-term effect of a more accelerated treatment course.

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

    PubMed

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

    2016-09-01

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

  5. Combined vacuum-assisted closure treatment with laparoscopic mobilization of an omental flap and meshed skin grafts for reconstruction of infected sternotomy wounds: two cases.

    PubMed

    Veir, Zoran; Smud, Sanda; Bogdanić, Branko; Cvjeticanin, Bruno; Bagatin, Dinko; Dujmović, Anto; Duduković, Mladen; Ivrlac, Radojko; Bulić, Kresimir; Mijatović, Davor

    2009-12-01

    In cardiac surgery, poststernotomy wounds are life threatening complications, with mortality up to 50%. We described two patients, who underwent coronary artery bypass grafting and postoperatively developed a deep sternal wound infection. Reconstruction was combined with vacuum-assisted closure treatment, laparoscopic mobilization of an omental flap and split thickens skin grafts. The omental flap is a well-vascularized local flap with a large surface area and has excellent immunologic and angiogenic properties. Both patients recovered completely. In our opinion, vacuum-assisted closure treatment and laparoscopic mobilization of great omentum is suitable option for treating deep sternal wounds.

  6. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2012-02-01

    consisting of the proteins Rsu1, Integrin Linked Kinase (ILK), PINCH, and Parvin. The correct association of these proteins in a functional complex...impacting integrin function and actin polymerization. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C, protein kinase A 16. SECURITY...epithelial cell migration in wound healing. In addition, the correct association of these proteins in a functional complex depends on their phosphorylation

  7. Matrix Metalloproteinase-3 Accelerates Wound Healing following Dental Pulp Injury

    PubMed Central

    Zheng, Li; Amano, Kazuharu; Iohara, Koichiro; Ito, Masataka; Imabayashi, Kiyomi; Into, Takeshi; Matsushita, Kenji; Nakamura, Hiroshi; Nakashima, Misako

    2009-01-01

    Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. Angiogenesis is essential for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that certain MMPs expressed during pulp wound healing may support recovery processes. To address this issue, a rat pulp injury model was established to investigate expression of MMPs during wound healing. Real-time RT-PCR analysis showed that expression MMP-3 and MMP-9 (albeit lower extent) was up-regulated at 24 and 12 hours after pulp injury, respectively, whereas expression of MMP-2 and MMP-14 was not changed. MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. In addition, MMP-3 enhanced proliferation, migration, and survival of human umbilical vein endothelial cells in vitro. Furthermore, the topical application of MMP-3 protein on the rat-injured pulp tissue in vivo induced angiogenesis and reparative dentin formation at significantly higher levels compared with controls at 24 and 72 hours after treatment, respectively. Inhibition of endogenous MMP-3 by N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid resulted in untoward wound healing. These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and pulp wound healing. PMID:19834065

  8. Loss of epithelial hypoxia-inducible factor prolyl hydroxylase 2 accelerates skin wound healing in mice.

    PubMed

    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; Wielockx, Ben

    2013-09-01

    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.

  9. 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

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

    PubMed

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

    2013-12-01

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

  11. Silver Toxicity With the Use of Silver-Impregnated Dressing and Wound Vacuum-Assisted Closure in an Immunocompromised Patient

    PubMed Central

    LaRiviere, Cabrini A.; Goldin, Adam B.; Avansino, Jeffrey

    2011-01-01

    Silver-containing topical agents are used to help prevent infectious complications in wound therapy. Toxicity from topical silver agent exposure was initially reported in 1975 and was clinically characterized by granulocytopenia. Currently, the data regarding potential toxicity associated with silver-impregnated devices are limited. A 23-year-old patient receiving chemotherapy for acute lymphoblastic leukemia presented with necrotizing fasciitis of the abdominal wall and scrotum from a Crohn disease–related psoas-enteric fistula. Surgical debridement of the soft-tissue and abdominal musculature was performed to the peritoneum. Silver-containing foam sponges and wound vacuum-assisted closure were applied directly to the peritoneum 2 weeks after initial debridement. Subsequently, the patient developed leukopenia, and workup revealed the serum silver level was 4 times normal level. Silver-impregnated sponges were discontinued and silver-free sponges and wound vacuum-assisted closure therapy resumed, followed by leukopenia resolution. Silver toxicity associated with routine application of silver-impregnated sponges has not been previously reported. PMID:24527160

  12. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  13. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cheng, Poh-Guat; Phan, Chia-Wei; Sabaratnam, Vikineswary; Abdullah, Noorlidah; Abdulla, Mahmood Ameen; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.

  14. Surgical amputation of a digit and vacuum-assisted-closure (V.A.C.) management in a case of osteomyelitis and wound care in an eastern black rhinoceros (Diceros bicornis michaeli).

    PubMed

    Harrison, Tara M; Stanley, Bryden J; Sikarskie, James G; Bohart, George; Ames, N Kent; Tomlian, Janice; Marquardt, Mark; Marcum, Annabel; Kiupel, Matti; Sledge, Dodd; Agnew, Dalen

    2011-06-01

    A 14-yr-old female eastern black rhinoceros (Diceros bicornis michaeli) presented with progressive suppurative osteomyelitis in her left hind lateral toe. beta-Hemolytic Streptococcus sp. was isolated. The animal was treated with multiple systemic antibiotics, and topical wound cleansing. Repeated debridements and nail trimmings were performed for 5 mo prior to electing amputation. The toe was surgically amputated under general anesthesia between the first and second phalanges. Analgesia was diffused into the wound topically via a catheter and elastomeric pump. The open amputation site was covered with adherent drapes and a negative-pressure wound therapy device provided vacuum-assisted closure (V.A.C.) for 72 hr. Three months later this animal developed a deep dermal ulcer on the lateral aspect of the right hind limb, at the level of the stifle. Methicillin-resistant Staphylococcus aureus was isolated. The wound was managed by initial daily lavage, followed by 1 mo of V.A.C. therapy, with 72 hr between dressing changes. Clinically, this therapy expedited the formation of healthy granulation tissue and overall healing was accelerated. The animal tolerated the machine and bandage changes well via operant conditioning. The use of negative-pressure wound therapy appeared to shorten time to resolution of slow-healing wounds in black rhinoceros.

  15. Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin-based coacervate delivery system that provides controlled release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB-EGF coacervate to overcome the deficiencies of diabetic wound healing. In full-thickness excisional wounds on NONcNZO10 diabetic mice, HB-EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB-EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB-EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds.

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

    PubMed

    Chigurupati, Srinivasulu; Mughal, Mohamed R; Chan, Sic L; Arumugam, Thiruma V; Baharani, Akanksha; Tang, Sung-Chun; Yu, Qian-Sheng; Holloway, Harold W; Wheeler, Ross; Poosala, Suresh; Greig, Nigel H; Mattson, Mark P

    2010-04-06

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

  17. The effect of sutureless wound closure on postoperative pain and swelling after impacted mandibular third molar surgery.

    PubMed

    Hashemi, Hamid Mahmood; Beshkar, Majid; Aghajani, Reihaneh

    2012-04-01

    Our aim was to assess the influence of sutureless and multiple-suture closure of wounds on postoperative complications after extraction of bilateral, impacted, mandibular third molars in 30 patients in a split mouth study. After the teeth had been removed, on one side the flap was replaced but with no suture to hold it in place (study side), and on the other side the wound was closed primarily with three sutures (control side). Recorded complications included pain, swelling, bleeding, and formation of periodontal pockets. The results showed that patients had significantly less postoperative pain and swelling when no sutures were used (p=0.005). There were no signs of excessive bleeding or oozing postoperatively on either side. Six months postoperatively there was no significant difference in the depth of the periodontal pocket around the second molar.

  18. Wound management in a juvenile tiger (Panthera tigris) with vacuum-assisted closure (V.A.C. Therapy).

    PubMed

    Lafortune, Maud; Fleming, Gregory J; Wheeler, Jason L; Göbel, Thomas; Mozingo, David W

    2007-06-01

    A 6-wk-old tiger (Panthera tigris) was evaluated for severe skin lacerations from an adult tiger attack. A caudal superficial epigastric skin flap was surgically placed to cover a defect that could not be closed over the hind limb; however, the skin flap did not adhere well to the granulation tissue over a period of 1 mo. The granulation bed matured and deteriorated. A subatmospheric pressure technique (vacuum-assisted closure, V.A.C. Therapy, Kinetic Concepts Inc., San Antonio, Texas 78219, USA) was utilized, and flap adherence occurred after 4 wk. This technique should be considered when dealing with severe or chronic wounds in tractable animals.

  19. [Vacuum assisted closure therapy in dehiscence of abdominal wound after cesarean section treated in a hospital-at-home].

    PubMed

    Sánchez-Cabezón, Carmen; Montes-Olangua, Maria Isabel; García-Suarez, Sara; García-Carretero, Rafael

    2013-01-01

    The Hospital at Home is a range of hospital care provided to patients in the comfort of their own homes, so patient and family can actively participate in the process. Cesarean section is a surgical procedure that requires a short hospital stay. However if complications arise during the process, such as a dehiscence of surgical wound, the hospital stay is prolonged, delaying mother-child bonding, which is very important for the growth of the child. Nursing care in wound healing by secondary intention is a priority for the patient's recovery. VAC therapy (vacuum assisted closure) promotes a rapid recovery, although it requires dressings and active medical surveillance, as well as training by the nursing staff for carrying it out at home. We describe the outcome and the process of the healing of a surgical wound after cesarean section, not only because of a complex wound, but the previously mentioned factors that make us consider the Hospital at Home as the best alternative care.

  20. Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

    PubMed

    Aramwit, Pornanong; Siritienthong, Tippawan; Srichana, Teerapol; Ratanavaraporn, Juthamas

    2013-01-01

    Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds.

  1. Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration.

    PubMed

    Mori, Ryoichi; Kondo, Toshikazu; Ohshima, Tohru; Ishida, Yuko; Mukaida, Naofumi

    2002-07-01

    To clarify biological roles of tumor necrosis factor receptor p55 (TNF-Rp55) -mediated signals in wound healing, skin excisions were prepared in BALB/c (WT) and TNF-Rp55-deficient (KO) mice. In WT mice, the wound area was reduced to 50% of the original area 6 days after injury, with angiogenesis and collagen accumulation. Histopathologically, reepithelialization rate was approximately 80% 6 days. Myeloperoxidase activity and macrophage recruitment were the most evident 1 and 6 days after injury, respectively. Gene expression of adhesion molecules, interleukin 1alpha (IL-1alpha), IL-1beta, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-2, transforming growth factor beta1 (TGF-beta1) connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), Flt-1, and Flk-1 was enhanced at the wound site. In KO mice, an enhancement in angiogenesis, collagen content, and reepithelialization was accelerated with the increased gene expression of TGF-beta1, CTGF, VEGF, Flt-1, and Flk-1 at the wound sites, resulting in accelerated wound healing compared with WT mice. In contrast, leukocyte infiltration, mRNA expression of adhesion molecules, and cytokines were significantly reduced in KO mice. These observations suggest that TNF-Rp55-mediated signals have some role in promoting leukocyte infiltration at the wound site and negatively affect wound healing, probably by reducing angiogenesis and collagen accumulation.

  2. Use of Adipose-Derived Stem Cells to Support Topical Skin Adhesive for Wound Closure: A Preliminary Report from Animal In Vivo Study

    PubMed Central

    Pietkun, Katarzyna; Jundziłł, Arkadiusz; Grzanka, Dariusz; Skopinska-Wisniewska, Joanna; Scibior, Kinga; Pokrywczyńska, Marta; Grzanka, Alina; Zegarski, Wojciech

    2016-01-01

    The aim of this study was to determine the local and systemic effects of adipose-derived stem cells (ADSCs) as a component of topical skin adhesive in an animal artificial wound closure model. In presented study the cosmetic effects, histological analysis, mechanical properties, and cell migration have been assessed to evaluate the usefulness of ADSCs as supporting factor for octyl blend cyanoacrylate adhesive. The total of 40 rats were used and divided into six groups. In the Study Group, ADSCs were administered by multipoint injection of the six surrounding intrawound areas with additional freely leaving procedure of the cells between the skin flaps just before applying adhesive to close the wound. Five control groups without using ADSCs, utilizing different types of standard wound closure, were created in order to check efficiency of experimental stem cell therapy. In our study, we proved that ADSCs could be used effectively also as a supportive tool in topical skin adhesive for wound closure. However we did not achieve any spectacular differences related to such aspects as better mechanical properties or special biological breakthroughs in wound healing properties. The use of stem cells, especially ADSCs for wound closure can provide an inspiring development in plastic and dermatologic surgery. PMID:27803921

  3. Risk-Based Decision Process for Accelerated Closure of a Nuclear Weapons Facility

    SciTech Connect

    Butler, L.; Norland, R. L.; DiSalvo, R.; Anderson, M.

    2003-02-25

    Nearly 40 years of nuclear weapons production at the Rocky Flats Environmental Technology Site (RFETS or Site) resulted in contamination of soil and underground systems and structures with hazardous substances, including plutonium, uranium and hazardous waste constituents. The Site was placed on the National Priority List in 1989. There are more than 370 Individual Hazardous Substance Sites (IHSSs) at RFETS. Accelerated cleanup and closure of RFETS is being achieved through implementation and refinement of a regulatory framework that fosters programmatic and technical innovations: (1) extensive use of ''accelerated actions'' to remediate IHSSs, (2) development of a risk-based screening process that triggers and helps define the scope of accelerated actions consistent with the final remedial action objectives for the Site, (3) use of field instrumentation for real time data collection, (4) a data management system that renders near real time field data assessment, and (5) a regulatory agency consultative process to facilitate timely decisions. This paper presents the process and interim results for these aspects of the accelerated closure program applied to Environmental Restoration activities at the Site.

  4. 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

  5. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis.

    PubMed

    Asai, Jun; Takenaka, Hideya; Hirakawa, Satoshi; Sakabe, Jun-ichi; Hagura, Asami; Kishimoto, Saburo; Maruyama, Kazuichi; Kajiya, Kentaro; Kinoshita, Shigeru; Tokura, Yoshiki; Katoh, Norito

    2012-12-01

    Impaired wound healing is a major complication of diabetes. Recent studies have reported reduced lymphangiogenesis and angiogenesis during diabetic wound healing, which are thought to be new therapeutic targets. Statins have effects beyond cholesterol reduction and can stimulate angiogenesis when used systemically. However, the effects of topically applied statins on wound healing have not been well investigated. The present study tested the hypothesis that topical application of simvastatin would promote lymphangiogenesis and angiogenesis during wound healing in genetically diabetic mice. A full-thickness skin wound was generated on the back of the diabetic mice and treated with simvastatin or vehicle topically. Simvastatin administration resulted in significant acceleration of wound recovery, which was notable for increases in both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted infiltration of macrophages, which produced vascular endothelial growth factor C in granulation tissues. In vitro, simvastatin directly promoted capillary morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells. These results suggest that the favorable effects of simvastatin on lymphangiogenesis are due to both a direct influence on lymphatics and indirect effects via macrophages homing to the wound. In conclusion, a simple strategy of topically applied simvastatin may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.

  6. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2010-12-01

    the protein kinase C (PKC) family and the process can be enhanced or inhibited by modulating the levels of the RIPP complex proteins as well by...HACAT cells indicates that PKC may modulate migration on two-dimensional surface. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C ...ABSTRACT U c . THIS PAGE U UU 11 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18

  7. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    PubMed

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  8. Accelerated healing of excisional skin wounds by PL 14736 in alloxan-hyperglycemic rats.

    PubMed

    Seveljević-Jaran, D; Cuzić, S; Dominis-Kramarić, M; Glojnarić, I; Ivetić, V; Radosević, S; Parnham, M J

    2006-01-01

    PL 14736 is a synthetic peptide, originally isolated from human gastric juice, that has anti-inflammatory and tissue-protective actions in experimental models of gastrointestinal inflammation. To investigate its possible benefit in poorly healing skin wounds, the effects of the topical application of PL 14736 in a gel formulation have been studied on full-thickness excisional wounds in rats, either healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex, a standard therapy for diabetic foot ulcers, were investigated for comparison. Healing was evaluated for up to 7 days after wounding, using digital planimetry analysis, macroscopic scoring and histology. While healing was too rapid in healthy rats to observe enhancement by either treatment, in the hyperglycemic rats which exhibited delayed healing, PL 14736 (10-1,000 microg/wound) produced a dose-dependent acceleration of wound healing (determined by macroscopic scoring) equivalent at the highest doses to that observed with becaplermin. The beneficial effect on healing was associated with increased deposition of organized granulation tissue by day 7 for both PL 14736 and becaplermin, as determined histologically. PL 14736 tended to have a greater effect than becaplermin on the formation of granulation tissue containing mature collagen. Wound contraction, as measured by planimetry, was not significantly affected. In conclusion, topical PL 14736 produces a dose-dependent acceleration of deficient skin wound healing in hyperglycemic rats by facilitating granulation tissue formation, similar to the response seen with topical becaplermin, the standard therapy for diabetic skin wounds. PL 14736 may represent an alternative therapy for delayed wound healing, such as that seen with diabetic foot ulcers, without the proliferative concerns or immunogenicity associated with growth factors.

  9. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

    PubMed Central

    Smout, Michael J.; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N.; Chan, Lai Yue; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Giacomin, Paul R.; Moran, Corey S.; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P.

    2015-01-01

    Abstract Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

  10. Potential use of blood bank platelet concentrates to accelerate wound healing of diabetic ulcers.

    PubMed

    Han, Seung-Kyu; Kim, Deok-Woo; Jeong, Seong-Ho; Hong, Yong-Taek; Woo, Hong-Suh; Kim, Woo-Kyung; Gottrup, Finn

    2007-11-01

    Many clinical trials have shown the effectiveness of platelet releasates on diabetic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. This study was undertaken to investigate the potential of blood bank platelet concentrate (BBPC) for accelerating diabetic wound healing. Platelet-derived growth factor-BB (PDGF-BB) contents in BBPC were determined by enzyme-linked immunosorbent assay in vitro, and the in vivo study involved comparing extents of wound healing in BBPC-treated and control groups using diabetic mouse wound models. In the in vitro study, 5.2 +/- 1.2 pg of PDGF-BB was found to be released by 1 million platelets in fresh BBPC, and adding thrombin to BBPC significantly increased the levels of PDGF-BB released. Our in vivo study in diabetic mice revealed that BBPC treatment greatly accelerated wound healing. Our results suggest that BBPC has potential to accelerate the healing of diabetic ulcers.

  11. Successes and lessons learned: How to accelerate the base closure process

    SciTech Connect

    Larkin, V.C.; Stoll, R.

    1994-12-31

    Naval Station Puget Sound, Seattle, was nominated for closure by the Base Closure Commission in 1991 (BRAC II) and will be transferred in September of 1995. Historic activities have resulted in petroleum-related environmental issues. Unlike many bases being closed, the politically sensitive issues are not the economics of job losses. Because homeless housing is expected to be included in the selected reuse plan, the primary concerns of the public are reduced real estate values and public safety. In addition to a reuse plan adopted by the Seattle City Council, the Muckleshoot Indian tribe has also submitted an alternative reuse plan to the Navy. Acceleration methods described in this paper include methods for beginning the environmental impact statement (EIS) process before reuse plans are finalized; tracking development of engineering alternatives in parallel with environmental investigations; using field screening data to begin developing plans and specifications for remediation, instead of waiting 6 weeks for analytical results and data validation; using efficient communication techniques to facilitate accelerated review of technical documents by the BCT; expediting removal actions and performing ``cleanups incidental to investigation``; and effectively facilitating members of the Restoration Advisory Board with divergent points of view. This paper will describe acceleration methods that proved to be effective and methods that could be modified to be more effective at other sites.

  12. Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

    PubMed

    Mori, Ryoichi; Tanaka, Katsuya; de Kerckhove, Maiko; Okamoto, Momoko; Kashiyama, Kazuya; Tanaka, Katsumi; Kim, Sangeun; Kawata, Takuya; Komatsu, Toshimitsu; Park, Seongjoon; Ikematsu, Kazuya; Hirano, Akiyoshi; Martin, Paul; Shimokawa, Isao

    2014-09-01

    The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

  13. Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration.

    PubMed

    Dunn, Louise L; de Valence, Sarra; Tille, Jean-Christophe; Hammel, Philippe; Walpoth, Beat H; Stocker, Roland; Imhof, Beat A; Miljkovic-Licina, Marijana

    2016-11-01

    Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds.

  14. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

    PubMed

    Falanga, Vincent; Iwamoto, Satori; Chartier, Molly; Yufit, Tatyana; Butmarc, Janet; Kouttab, Nicholas; Shrayer, David; Carson, Polly

    2007-06-01

    The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db

  15. Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Ortega-Martinez, Antonio; Farinelli, Bill; Anderson, R. R.; Franco, Walfre

    2016-02-01

    Wound size is a key parameter in monitoring healing. Current methods to measure wound size are often subjective, time-consuming and marginally invasive. Recently, we developed a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds. This method exploits the fluorescence of native molecules to tissue as functional and structural markers. The objective of the present study is to demonstrate the feasibility of using variations in the fluorescence intensity of tryptophan and cross-links of collagen to evaluate proliferation of keratinocyte cells and quantitate size of wound during healing, respectively. Circular dermal wounds were created in ex vivo human skin and cultured in different media. Two serial fluorescence images of tryptophan and collagen cross-links were acquired every two days. Histology and immunohistology were used to validate correlation between fluorescence and epithelialization. Images of collagen cross-links show fluorescence of the exposed dermis and, hence, are a measure of wound area. Images of tryptophan show higher fluorescence intensity of proliferating keratinocytes forming new epithelium, as compared to surrounding keratinocytes not involved in epithelialization. These images are complementary since collagen cross-links report on structure while tryptophan reports on function. HE and immunohistology show that tryptophan fluorescence correlates with newly formed epidermis. We have established a fluorescence imaging method for studying epithelialization processes during wound healing in a skin organ culture model, our approach has the potential to provide a non-invasive, non-contact, quick, objective and direct method for quantitative measurements in wound healing in vivo.

  16. Use of the wound healing trajectory as an outcome determinant for acute wound healing.

    PubMed

    Franz, M G; Kuhn, M A; Wright, T E; Wachtel, T L; Robson, M C

    2000-01-01

    Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.

  17. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    NASA Astrophysics Data System (ADS)

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

  18. Umbilical Cord Mesenchymal Stem Cells Combined With a Collagenfibrin Double-layered Membrane Accelerates Wound Healing.

    PubMed

    Nan, Wenbin; Liu, Rui; Chen, Hongli; Xu, Zhihao; Chen, Jiannan; Wang, Manman; Yuan, Zhiqing

    2015-05-01

    The aim of this study was to examine the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) in combination with a collagen-fibrin double-layered membrane on wound healing in mice. A collagen-fibrin double-layered membrane was prepared, and the surface properties of the support material were investigated using a scanning electron microscope. Twenty-four mice were prepared for use as full-thickness skin wound models and randomly divided into 3 groups: group A, a control group in which the wounds were bound using a conventional method; group B, a group treated with hUCMSCs combined with a collagen membrane; and group C, a group treated with hUCMSCs combined with a collagen-fibrin double-layered membrane. The postoperative concrescence of the wounds was observed daily to evaluate the effects of the different treatments. Scanning electron microscope observation showed the collagen-fibrin scaffolds exhibited a highly porous and interconnected structure, and wound healing in the double-layered membrane group was better than in groups A or B. Treatment with hUCMSCs combined with a collagen-fibrin double-layered membrane accelerated wound healing.

  19. Novel hemostatic patch achieves sutureless epicardial wound closure during complex cardiac surgery, a case report.

    PubMed

    Jainandunsing, Jayant S; Al-Ansari, Sali; Woltersom, Bozena D; Scheeren, Thomas W L; Natour, Ehsan

    2015-01-27

    Treatment of damaged cardiac tissue in patients with high bleeding tendency can be very challenging, damaged myocardial tissue has a high rupture risk when being sutured subsequently on-going bleeding is a major risk factor for poor clinical outcome. We present a case demonstrating the feasibility in using a novel haemostatic collagen sponge for the management of a myocardial wound. This report is the first description in cardiac surgery where Hemopatch sponges are used to successfully seal a left ventricle wound. Our patient was diagnosed with endocarditis, had a low pre-operative haemoglobin count and underwent cardiac surgery for multiple valve repairs. The procedure was performed on cardiopulmonary bypass, which meant our patient had to be heparinized. Despite these major risk factors for bleeding Hemopatch managed to contain bleeding and seal the wound, no sutures were needed.

  20. 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

  1. Temporary intentional leg shortening and deformation to facilitate wound closure using the Ilizarov/Taylor spatial frame.

    PubMed

    Nho, Shane J; Helfet, David L; Rozbruch, S Robert

    2006-07-01

    Infected tibial nonunions with bone loss pose an extremely challenging problem for the orthopaedic surgeon. A comprehensive approach that addresses the infection, bone quality, and overlying soft-tissue integrity must be considered for a successful outcome. Acute shortening with an Ilizarov frame has been shown to be helpful in the treatment of open tibia fractures with simultaneous bone and soft-tissue loss. Cases in which the soft-tissue defect considerably exceeds bone loss may require an Ilizarov frame along with a concomitant soft-tissue procedure; however, there are a number of potential difficulties with vascularized pedicle flaps and free tissue flaps, including anastomotic complications, partial flap necrosis, and flap failure. The technique described in this report involves acute shortening and temporary bony deformation with the Ilizarov apparatus to facilitate wound closure and does not require a concomitant soft-tissue reconstructive procedure. Once the wound is healed, osseous deformity and length are gradually corrected by distraction osteogenesis with the Ilizarov/Taylor Spatial frame.

  2. Knockout of Endothelial Cell-Derived Endothelin-1 Attenuates Skin Fibrosis but Accelerates Cutaneous Wound Healing

    PubMed Central

    Makino, Katsunari; Jinnin, Masatoshi; Aoi, Jun; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Sakai, Keisuke; Nakayama, Kazuhiko; Emoto, Noriaki; Yanagisawa, Masashi; Ihn, Hironobu

    2014-01-01

    Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach. PMID:24853267

  3. Platelet lysate promotes in vitro wound scratch closure of human dermal fibroblasts: different roles of cell calcium, P38, ERK and PI3K/AKT.

    PubMed

    Ranzato, Elia; Mazzucco, Laura; Patrone, Mauro; Burlando, Bruno

    2009-08-01

    There is a growing interest for the clinical use of platelet derivates in wound dressing. Platelet beneficial effect is attributed to the release of growth factors and other bioactive substances, though mechanisms are mostly unknown. We studied wound-healing processes of human primary fibroblasts, by exposing cells to a platelet lysate (PL) obtained from blood samples. Crystal violet and tetrazolium salt (MTS) assays showed dose-response increase of cell proliferation and metabolism. In scratch wound and transwell assays, a dose of 20% PL induced a significant increase of wound closure rate at 6 and 24 hrs, and had a strong chemotactic effect. BAPTA-AM, SB203580 and PD98059 caused 100% inhibition of PL effects, whereas wortmannin reduced to about one third the effect of PL on wound healing and abolished the chemotactic response. Confocal imaging showed the induction by PL of serial Ca2(+) oscillations in fibroblasts. Data indicate that cell Ca2(+) plays a fundamental role in wound healing even without PL, p38 and ERK1/2 are essential for PL effects but are also activated by wounding per se, PI3K is essential for PL effects and its downstream effector Akt is activated only in the presence of PL. In conclusion, PL stimulates fibroblast wound healing through the activation of cell proliferation and motility with different patterns of involvement of different signalling pathways.

  4. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers.

  5. Quercetin accelerated cutaneous wound healing in rats by increasing levels of VEGF and TGF-β1.

    PubMed

    Gopalakrishnan, A; Ram, M; Kumawat, S; Tandan, Sk; Kumar, D

    2016-03-01

    Quercetin (3,3',4',5,7-penthydroxyflavone)-induced biological effects have been beneficial in various disease conditions. In this study, wound healing potential of quercetin was evaluated in a time-dependent manner in open excision wounds in adult Wistar rats. Experimentally-wounded rats were divided into two groups namely, control and quercetin-treated. Wounds were photographed and the area was measured on the day of wounding and on days 3, 7, 11 and 14 post-wounding. The granulation/healing tissue was collected on days 3, 7, 11 and 14 post-wounding for cytokine/growth factor measurements and histology/immunohistochemistry studies. There was significant time-dependent increase in wound closure in quercetin-treated rats. Vascular endothelial growth factor and transforming growth factor-β1 expressions were significantly upregulated in quercetin-treated rats, whereas tumor necrosis factor-α level was markedly reduced. Interleukin- 10 levels and CD31 stained vessels were markedly higher on day 3 and on day 7, respectively, in quercetin-treated rats. In H & E stained sections, quercetin-treated group showed less inflammatory cells, more fibroblast proliferation, increased microvessel density, better reepithelialization and more regular collagen deposition, as compared to control. The results suggest that topical application of quercetin promotes wound healing by effectively modulating the cytokines, growth factors and cells involved in inflammatory and proliferative phases of healing.

  6. Transplantation of endothelial progenitor cells accelerates dermal wound healing with increased recruitment of monocytes/macrophages and neovascularization.

    PubMed

    Suh, Wonhee; Kim, Koung Li; Kim, Jeong-Min; Shin, In-Soon; Lee, Young-Sam; Lee, Jae-Young; Jang, Hyung-Suk; Lee, Jung-Sun; Byun, Jonghoe; Choi, Jin-Ho; Jeon, Eun-Seok; Kim, Duk-Kyung

    2005-01-01

    Endothelial progenitor cells (EPCs) act as endothelial precursors that promote new blood vessel formation and increase angiogenesis by secreting growth factors and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC transplantation should accelerate the wound-repair process by facilitating neovascularization and the production of various molecules related to wound healing. In a murine dermal excisional wound model, EPC transplantation accelerated wound re-epithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPC-transplanted group exhibited significantly more monocytes/macrophages in the wound at day 5 after injury than did the EC-transplanted group. This observation is consistent with enzyme-linked immunosorbent assay results showing that EPCs produced in abundance several chemoattractants of monocytes and macrophages that are known to play a pivotal role in the early phase of wound healing. At day 14 after injury, the EPC-transplanted group showed a statistically significant increase in vascular density in the granulation tissue relative to that of the EC-transplanted group. Fluorescence microscopy revealed that EPCs preferentially moved into the wound and were directly incorporated into newly formed capillaries in the granulation tissue. These results suggest that EPC transplantation will be useful in dermal wound repair and skin regeneration, because EPCs both promote the recruitment of monocytes/macrophages into the wound and increase neovascularization.

  7. N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells

    PubMed Central

    Kwon, Yang Woo; Heo, Soon Chul; Lee, Tae Wook; Park, Gyu Tae; Yoon, Jung Won; Jang, Il Ho; Kim, Seung-Chul; Ko, Hyun-Chang; Ryu, Youngjae; Kang, Hyeona; Ha, Chang Man; Lee, Sang Chul; Kim, Jae Ho

    2017-01-01

    Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro. Knockdown of CXCR2 expression in hEPCs abrogated the stimulatory effects of Ac-PGP on migration and tube formation. In a cutaneous wound healing model of rats and mice, topical application of Ac-PGP accelerated cutaneous wound healing with promotion of neovascularization. The positive effects of Ac-PGP on wound healing and neovascularization were blocked in CXCR2 knockout mice. In nude mice, the individual application of Ac-PGP treatment or hEPC injection accelerated wound healing by increasing neovascularization. Moreover, the combination of Ac-PGP treatment and hEPC injection further stimulated wound healing and neovascularization. Topical administration of Ac-PGP onto wound bed stimulated migration and engraftment of transplanted hEPCs into cutaneous dermal wounds. Therefore, these results suggest novel applications of Ac-PGP in promoting wound healing and augmenting the therapeutic efficacy of hEPCs. PMID:28230162

  8. 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

  9. Is skin closure with cyanoacrylate glue effective for the prevention of sternal wound infections?

    PubMed

    Chambers, Anthony; Scarci, Marco

    2010-05-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed whether cyanoacrylate glue was effective at preventing wound infection following sternotomy incision. Altogether more than 108 papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that applying cyanoacrylate glue to a sternal wound has superior outcomes in terms of infection rates, both if applied preoperatively (decreasing from 10.8% to 2.7% or 7.8% to 1.1%, according to two studies) and postoperatively (4.9%-2.1%). This trend is true of both deep surgical site infections (0.6%-0%) and superficial site infections (4.3%-2.1%). Furthermore, in patients who had developed mediastinitis following cardiac surgery rates of recurrent sternal detachment and osteomyelitis were significantly reduced in cases where sealant was applied compared to controls (35.3% vs. 0%). In all studies examining hospital stay, duration was reduced in cases where cyanoacrylate glue was used, both in patients treated for recurrent mediastinitis (24.06 vs. 14.16 days) and those with uncomplicated recovery following cardiac surgery (13 vs. 9 days). In addition, two studies examining the use of cyanoacrylate glue to secure the sternum in complicated cases of recurrent detachment report success rates of 86% and 100%.

  10. Composites containing albumin protein or cyanoacrylate adhesives and biodegradable scaffolds: I. Acute wound closure study in a rat model

    NASA Astrophysics Data System (ADS)

    Hoffman, Grant T.; Soller, Eric C.; Heintzelman, Douglas L.; Duffy, Mark T.; Bloom, Jeffrey N.; Gilmour, Travis M.; Gonnerman, Krista N.; McNally-Heintzelman, Karen M.

    2004-07-01

    Composite adhesives composed of biodegradable scaffolds impregnated with a biological or synthetic adhesive were investigated for use in wound closure as an alternative to using either one of the adhesives alone. Two different scaffold materials were investigated: (i) a synthetic biodegradable material fabricated from poly(L-lactic-co-glycolic acid); and (ii) a biological material, small intestinal sub mucosa, manufactured by Cook BioTech. The biological adhesive was composed of 50%(w/v) bovine serum albumin solder and 0.5mg/ml indocyanine green dye mixed in deionized water, and activated with an 808-nm diode laser. The synthetic adhesive was Ethicon's Dermabond, a 2-octyl-cyanoacrylate. The tensile strength of skin incisions repaired ex vivo in a rat model, by adhesive alone or in combination with a scaffold, as well as the time-to-failure, were measured and compared. The tensile strength of repairs formed using the scaffold-enhanced biological adhesives were on average, 80% stronger than their non-enhanced counterparts, with an accompanying increase in the time-to-failure of the repairs. These results support the theory that a scaffold material with an irregular surface that bridges the wound provides a stronger, more durable and consistent adhesion, due to the distribution of the tensile stress forces over the many micro-adhesions provided by the irregular surface, rather than the one large continuous adhesive contact. This theory is also supported by several previous ex vivo experiments demonstrating enhanced tensile strength of irregular versus smooth scaffold surfaces in identical tissue repairs performed on bovine thoracic aorta, liver, spleen, small intestine and lung tissue.

  11. Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing.

    PubMed

    Rabbani, Piul S; Zhou, Anna; Borab, Zachary M; Frezzo, Joseph A; Srivastava, Nikita; More, Haresh T; Rifkin, William J; David, Joshua A; Berens, Samuel J; Chen, Raymond; Hameedi, Sophia; Junejo, Muhammad H; Kim, Camille; Sartor, Rita A; Liu, Che F; Saadeh, Pierre B; Montclare, Jin K; Ceradini, Daniel J

    2017-04-03

    Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

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

    PubMed

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

    2009-01-01

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

  13. Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation.

    PubMed

    Zhou, Tian; Wang, Nanping; Xue, Yang; Ding, Tingting; Liu, Xin; Mo, Xiumei; Sun, Jiao

    2016-07-01

    The development of biomaterials with the ability to induce skin wound healing is a great challenge in biomedicine. In this study, tilapia skin collagen sponge and electrospun nanofibers were developed for wound dressing. The collagen sponge was composed of at least two α-peptides. It did not change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of CD4(+)/CD8(+) lymphocytes, and the level of IgG or IgM in Sprague-Dawley rats. The tensile strength and contact angle of collagen nanofibers were 6.72±0.44MPa and 26.71±4.88°, respectively. They also had good thermal stability and swelling property. Furthermore, the nanofibers could significantly promote the proliferation of human keratinocytes (HaCaTs) and stimulate epidermal differentiation through the up-regulated gene expression of involucrin, filaggrin, and type I transglutaminase in HaCaTs. The collagen nanofibers could also facilitate rat skin regeneration. In the present study, electrospun biomimetic tilapia skin collagen nanofibers were succesfully prepared, were proved to have good bioactivity and could accelerate rat wound healing rapidly and effectively. These biological effects might be attributed to the biomimic extracellular matrix structure and the multiple amino acids of the collagen nanofibers. Therefore, the cost-efficient tilapia collagen nanofibers could be used as novel wound dressing, meanwhile effectively avoiding the risk of transmitting animal disease in the future clinical apllication.

  14. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

    PubMed

    Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

    2014-12-10

    Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6-7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05). Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05). At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

  15. Combined nitric oxide-releasing poly(vinyl alcohol) film/F127 hydrogel for accelerating wound healing.

    PubMed

    Schanuel, Fernanda Seabra; Raggio Santos, Karen Slis; Monte-Alto-Costa, Andréa; de Oliveira, Marcelo G

    2015-06-01

    Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing.

  16. Clippers or the knife? The reform of surgical practice and the difficulty of early wound closure.

    PubMed

    Stephens-Borg, Keith

    2009-09-01

    Salt, vinegar and wine sounds more like a recipe from the Saturday kitchen, but in 1667 it was all a surgeon could use to close wounds, along with silk and linen strips. In providing this service, barbers and surgeons found themselves confused and intertwined, struggling for professional recognition that was about to experience reform. Allegations of neglect in the aftermath of a major seafaring battle on the very shores of our capital city required the court of King Charles II to search for a solution of supreme magnitude to accommodate the hundreds of maimed sailors who were littering the streets of London. A campaign to conceal the horrors of warfare began which lead to the implementation of the Greenwich charter and the construction of a hospital which the architect Christopher Wren helped to design.

  17. Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with bevacizumab (Avastin®) and radiation.

    PubMed

    Golas, Alyssa Reiffel; Boyko, Tatiana; Schwartz, Theodore H; Stieg, Philip E; Boockvar, John A; Spector, Jason A

    2014-09-01

    Neurosurgical craniotomy, craniectomy, or other trans-galeal interventions are performed for a variety of indications, including the resection of benign or malignant tumors, hematoma evacuation, and for the management of intractable seizure disorders. Despite an overall low complication rate of intervention, wound healing complications such as dehiscence, surgical site infection, and cerebrospinal fluid leak are not uncommon. A retrospective review was performed of all patients who underwent scalp incision closure at a single institution by a single plastic surgeon between 2006 and 2013. Sixty patients (83 procedures) were included in the study. Fifty-seven patients (95.0 %) underwent previous craniotomy, craniectomy, or other trans-galeal procedure. Of the total 60 patients, 35 patients received preoperative radiation. Sixteen patients received bevacizumab prior to their index case, while 12 received bevacizumab postoperatively. Ten patients (16.7 %) required additional plastic surgical intervention for wound complications after their index plastic surgery procedure. Plastic surgery was consulted prophylactically in 34 patients (38 procedures). When plastic surgery was consulted prophylactically, 4 patients (11.8 %) required further wound revision. None of the 14 patients who underwent prophylactic plastic surgery closure for previous scalp incision, preoperative bevacizumab, and XRT administration required re-intervention. Plastic surgery closure of complex scalp incisions reduces the incidence of wound complications among patients who underwent previous neurosurgical intervention, XRT administration, and preoperative bevacizumab administration. This is particularly true when plastic surgery closure is performed "prophylactically." Further collaboration between the neurosurgical and plastic surgery teams is therefore warranted, particularly in the setting of these high-risk cases.

  18. Closure of an Open Wound Associated with Bisphosphonate-Related Osteonecrosis of the Jaw in a Breast Cancer Patient

    PubMed Central

    Soolari, Nafiseh; Soolari, Ahmad

    2011-01-01

    Background and Objective: Many clinicians will not treat patients presenting with bisphosphonate-related osteonecrosis of the jaw following long-term use of bisphosphonates because of the lack of predictable outcomes. Materical and Methods: The patient presented with pain from a nonhealing lesion in the posterior maxilla following extraction of the maxillary right third molar. The lesion had not responded to any conventional dental treatment. The patient had suffered from breast cancer, and her treatment included several years of therapy with Zometa (zoledronic acid), a bisphosphonate. Results: The patient stopped taking Zometa and commenced rinsing with phosphate buffer–stabilized 0.1% chlorine dioxide–containing mouthwash. After 5 months, changes in the morphology of the lesion were noted and the soft tissue had closed over the open wound. Conclusion: Cessation of bisphosphonate therapy and usage of a phosphate buffer–stabilized 0.1% chlorine dioxide–containing mouthwash lessened the patient’s pain and resulted in closure of the soft tissue lesion. PMID:22135700

  19. Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites

    PubMed Central

    Li, Yunyuan; Jalili, Reza Baradar; Ghahary, Aziz

    2016-01-01

    Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells. PMID:27363517

  20. Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process.

    PubMed

    Tepedelen, Burcu Erbaykent; Soya, Elif; Korkmaz, Mehmet

    2016-12-01

    Boron is absorbed by the digestive and respiratory system, and it was considered that it is converted to boric acid (BA), which was distributed to all tissues above 90 %. The biochemical essentiality of boron element is caused by boric acid because it affects the activity of several enzymes involved in the metabolism. DNA damage repair mechanisms and oxidative stress regulation is quite important in the transition stage from normal to cancerous cells; thus, this study was conducted to investigate the protective effect of boric acid on DNA damage and wound healing in human epithelial cell line. For this purpose, the amount of DNA damage occurred with irinotecan (CPT-11), etoposide (ETP), doxorubicin (Doxo), and H2O2 was determined by immunofluorescence through phosphorylation of H2AX((Ser139)) and pATM((Ser1981)) in the absence and presence of BA. Moreover, the effect of BA on wound healing has been investigated in epithelial cells treated with these agents. Our results demonstrated that H2AX((Ser139)) foci numbers were significantly decreased in the presence of BA while wound healing was accelerated by BA compared to that in the control and only drug-treated cells. Eventually, the results indicate that BA reduced the formation of DNA double strand breaks caused by agents as well as improving the wound healing process. Therefore, we suggest that boric acid has important therapeutical effectiveness and may be used in the treatment of inflammatory diseases where oxidative stress and wound healing process plays an important role.

  1. Remediation of the Melton Valley Watershed at Oak Ridge National Lab: An Accelerated Closure Success Story

    SciTech Connect

    Johnson, Ch.; Cange, J.; Skinner, R.; Adams, V.

    2008-07-01

    The Melton Valley (MV) Watershed at the U. S. Department of Energy's (DOE's) Oak Ridge National Laboratory (ORNL) encompasses approximately 430 hectares (1062 acres). Historic operations at ORNL produced a diverse legacy of contaminated facilities and waste disposal areas in the valley. In addition, from 1955 to 1963, ORNL served as a major disposal site for wastes from over 50 off-site government-sponsored installations, research institutions, and other isotope users. Contaminated areas in the watershed included burial grounds, landfills, underground tanks, surface impoundments, liquid disposal pits/trenches, hydro-fracture wells, leak and spill sites, inactive surface structures, and contaminated soil and sediment. Remediation of the watershed in accordance with the requirements specified in the Melton Valley Record of Decision (ROD) for Interim Actions in Melton Valley, which estimated that remedial actions specified in the ROD would occur over a period of 14 years, with completion by FY 2014. Under the terms of the Accelerated Closure Contract between DOE and its contractor, Bechtel Jacobs Company, LLC, the work was subdivided into 14 separate sub-projects which were completed between August 2001 and September 2006, 8 years ahead of the original schedule. (authors)

  2. Clinical and Histologic Evaluation of Platelet-Rich Fibrin Accelerated Epithelization of Gingival Wound

    PubMed Central

    Bansal, Mansi; Kumar, Ashish; Puri, Komal; Khatri, Manish; Gupta, Geeti; Vij, Hitesh

    2016-01-01

    The foremost indication for gingival depigmentation is patient demand for improved aesthetics. In most cases after the removal of pigmented layer, the area is covered with periodontal packs. These dressings have no curative properties. They only minimise the likelihood of surface trauma during mastication. However, platelet-rich fibrin (PRF) accelerates wound healing by effective neovascularisation and promoting fast cicatricial tissue remodelling. In the present split mouth study, PRF membrane was applied in the first quadrant and non-eugenol dressing (Coe-Pack) in the second quadrant after depigmentation. Clinical evaluation of epithelization with toluidine blue revealed that PRF treated sites stained substantially less indicating better wound healing as compared to Coe-Pack sites, which appeared more erythematous after 5 days. The histologic evaluation also revealed greater inflammatory cell infiltrate on Coe-Pack sites as compared to PRF. Thus, PRF membrane as a periodontal dressing is a successful approach to protect the raw wound area of the depigmented site to reduce healing time and patient discomfort. PMID:27761092

  3. Acceleration of wound healing by α-gal nanoparticles interacting with the natural anti-Gal antibody.

    PubMed

    Galili, Uri

    2015-01-01

    Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40-60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries.

  4. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice

    PubMed Central

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  5. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

    PubMed

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  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. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

    PubMed Central

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Purpose Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Materials and methods Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Results Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. Conclusion These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis

  8. Rapid recruitment and activation of macrophages by anti-Gal/α-Gal liposome interaction accelerates wound healing.

    PubMed

    Wigglesworth, Kim M; Racki, Waldemar J; Mishra, Rabinarayan; Szomolanyi-Tsuda, Eva; Greiner, Dale L; Galili, Uri

    2011-04-01

    Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95-100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.

  9. Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate the Oral Wound Healing in Rats.

    PubMed

    Coelho, Fernanda Hack; Salvadori, Gabriela; Rados, Pantelis Varvaki; Magnusson, Alessandra; Danilevicz, Chris Krebs; Meurer, Luise; Martins, Manoela Domingues

    2015-07-01

    The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats.

  10. Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure.

    PubMed

    Kim, Yang-Hee; Tabata, Yasuhiko

    2016-04-01

    In this study, the wound closure of mouse skin defects was examined in terms of recruitment of mesenchymal stem cells (MSC) and macrophages. For the cells recruitment, stromal derived factor-1 (SDF-1) of a MSC recruitment agent and sphingosine-1 phosphate agonist (SEW2871) of a macrophages recruitment agent were incorporated into gelatin hydrogels, and then released in a controlled fashion. When applied to a skin wound defect of mice, gelatin hydrogels incorporating mixed 500 ng SDF-1 and 0.4, 0.8, or 1.6 mg SEW2871-micelles recruited a higher number of both MSC and macrophages than those incorporating SDF-1 or phosphate buffered saline. However, the number of M1 phenotype macrophages for the hydrogel incorporating mixed SDF-1 and SEW2871-micelles recruited was remarkably low to a significant extent compared with that for those hydrogel incorporating 0.4, 0.8, or 1.6 mg SEW2871-micelles. On the other hand, the number of M2 macrophages 3 days after the implantation of the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles significantly increased compared with that for other hydrogels. In vivo experiments revealed the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles promoted the wound closure of skin defect to a significant stronger extent than those incorporating SEW2871-micelles, SDF-1, and a mixture of SDF-1 and higher doses of SEW2871-micelles. It is concluded that the in vivo recruitment of MSC and macrophages to the defects may contribute to the tissue regeneration of skin wound.

  11. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    PubMed

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2016-05-24

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  12. Comparison of laser and diode sources for acceleration of in vitro wound healing by low-level light therapy.

    PubMed

    Spitler, Ryan; Berns, Michael W

    2014-03-01

    Low-level light therapy has been shown to improve in vitro wound healing. However, well-defined parameters of different light sources for this therapy are lacking. The goal of this study was (1) to determine if the wavelengths tested are effective for in vitro wound healing and (2) to compare a laser and a light-emitting diode (LED) source at similar wavelengths. We show four wavelengths, delivered by either a laser or LED array, improved in vitro wound healing in A549, U2OS, and PtK2 cells. Improved wound healing occurred through increased cell migration demonstrated through scratch wound and transwell assays. Cell proliferation was tested by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-car-boxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay and was found generally not to be involved in the wound healing process. The laser and LED sources were found to be comparable when equal doses of light were applied. The biological response measured was similar in most cases. We conclude that the laser at 652 (5.57  mW/cm2, 10.02  J/cm2) and 806 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 5 nm), and LED at 637 (5.57  mW/cm2, 10.02  J/cm2) and 901 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 17 and 69 nm respectively) induce comparable levels of cell migration and wound closure.

  13. The effect of B vitamin supplementation on wound healing in type 2 diabetic mice

    PubMed Central

    Mochizuki, Saeka; Takano, Mayuko; Sugano, Naoyuki; Ohtsu, Mariko; Tsunoda, Kou; Koshi, Ryosuke; Yoshinuma, Naoto

    2016-01-01

    The aim of this study was to test the effects of B-group vitamin supplements on wound healing in diabetic mice. The mice in the experimental group were treated daily with 1 g/L B6, 1.25 mg/L B12, and 62.5 mg/L folic acid in their drinking water. Full-thickness excision wounds were created with 6-mm skin biopsy punches. Each wound closure was digitally photographed. Beginning on day 3 after wounding, the wound area in the diabetic mice was statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 42.8 ± 11.3%, p<0.05). On day 9 after wounding, the wound area in the diabetic mice was also statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 13.2 ± 16.8%, p<0.05). In addition, the high glucose level in the diabetic animals decreased significantly in response to B vitamin treatment. In conclusion, the results of this study indicate that B vitamin supplementation may improve wound healing in diabetic mice. PMID:26798199

  14. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing.

    PubMed

    Idrovo, Juan Pablo; Jacob, Asha; Yang, Weng Lang; Wang, Zhimin; Yen, Hao Ting; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2016-02-01

    Chronic or non-healing wounds are a major concern in clinical practice and these wounds are mostly associated with diabetes, and venous and pressure ulcers. Wound healing is a complex process involving overlapping phases and the primary phase in this complex cascade is the inflammatory state. While inflammation is necessary for wound healing, a prolonged inflammatory phase leads to impaired healing. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that are expressed in high levels under stress conditions. Recently, we demonstrated that a deficiency in CIRP led to decreased inflammation and mortality in an experimental model of hemorrhagic shock. Thus, we hypothesized that a deficiency in CIRP would accelerate the inflammatory phase and lead to an improvement in cutaneous wound healing. In this study, to examine this hypothesis, a full-thickness wound was created on the dorsum of wild-type (WT) and CIRP-/- mice. The wound size was measured every other day for 14 days. The wound area was significantly decreased in the CIRP-/- mice by day 9 and continued to decrease until day 14 compared to the WT mice. In a separate cohort, mice were sacrificed on days 3 and 7 after wounding and the skin tissues were harvested for histological analysis and RNA measurements. On day 3, the mRNA expression of tumor necrossis factor (TNF)-α in the skin tissues was increased by 16-fold in the WT mice, whereas these levels were increased by 65-fold in the CIRP-/- mice. Of note on day 7, while the levels of TNF-α remained high in the WT mice, these levels were significantly decreased in the CIRP-/- mice. The histological analysis of the wounded skin tissue indicated an improvement as early as day 3 in the CIRP-/- mice, whereas in the WT mice, infiltrated immune cells were still present on day 7. On day 7 in the CIRP-/- mice, Gr-1 expression was low and CD31 expression was high, whereas in the WT mice, Gr-1 expression was high and CD31 expression was low

  15. 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

  16. Surgical wound infection - treatment

    MedlinePlus

    ... wounds heal, you may have a wound VAC (vacuum-assisted closure) dressing. It increases blood flow in ... helps with healing. This is a negative pressure (vacuum) dressing. There is a vacuum pump, a foam ...

  17. Development of ethyl alcohol-precipitated silk sericin/polyvinyl alcohol scaffolds for accelerated healing of full-thickness wounds.

    PubMed

    Siritienthong, Tippawan; Ratanavaraporn, Juthamas; Aramwit, Pornanong

    2012-12-15

    Silk sericin has been recently reported for its advantageous biological properties to promote wound healing. In this study, we established that the ethyl alcohol (EtOH) could be used to precipitate sericin and form the stable sericin/polyvinyl alcohol (PVA) scaffolds without the crosslinking. The sericin/PVA scaffolds were fabricated via freeze-drying and subsequently precipitating in various concentrations of EtOH. The EtOH-precipitated sericin/PVA scaffolds showed denser structure, higher compressive modulus, but lower water swelling ability than the non-precipitated scaffolds. Sericin could be released from the EtOH-precipitated sericin/PVA scaffolds in a sustained manner. After cultured with L929 mouse fibroblasts, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed the highest potential to promote cell proliferation. After applied to the full-thickness wounds of rats, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed significantly higher percentage of wound size reduction and higher extent of type III collagen formation and epithelialization, compared with the control scaffolds without sericin. The accelerated wound healing by the 70 vol% EtOH-precipitated sericin/PVA scaffolds was possibly due to (1) the bioactivity of sericin itself to promote wound healing, (2) the sustained release of precipitated sericin from the scaffolds, and (3) the activation and recruitment of wound healing-macrophages by sericin to the wounds. This finding suggested that the EtOH-precipitated sericin/PVA scaffolds were more effective for the wound healing, comparing with the EtOH-precipitated PVA scaffolds without sericin.

  18. Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats.

    PubMed

    Kwon, David S; Gao, Xiaohua; Liu, Yong Bo; Dulchavsky, Deborah S; Danyluk, Andrew L; Bansal, Mona; Chopp, Michael; McIntosh, Kevin; Arbab, Ali S; Dulchavsky, Scott A; Gautam, Subhash C

    2008-06-01

    Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.

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

    PubMed

    Plichta, Jennifer K; Radek, Katherine A

    2012-01-01

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

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

    PubMed

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

    2010-09-01

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

  1. 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

  2. Effectiveness of indonesian honey on the acceleration of cutaneous wound healing: an experimental study in mice.

    PubMed

    Haryanto, Haryanto; Urai, Tamae; Mukai, Kanae; Gontijo Filho, Paulo P; Suriadi, Suriadi; Sugama, Junko; Nakatani, Toshio

    2012-04-01

    The purpose of this study was to investigate the effectiveness of Indonesian honey in wound healing compared to Tegaderm hydrocolloid dressing and Manuka honey. Three groups of male mice were treated to produce 2 circular, full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Manuka honey, or hydrocolloid (control). Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic findings on days 3, 7, 11, and 14 after wounding were obtained. The ratios of wound areas for honey groups on day 3 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the control group wound area peaked on day 5 and rapidly decreased until day 14. On day 3, myofibroblasts and new blood capillaries in wound tissue of honey groups were observed, but were not seen in the control group. After day 7, microscopic findings were almost the same among the 3 groups. These results indicate that Indonesian honey is almost as effective for wound healing as Manuka honey and hydrocolloid dressing. .

  3. A silicone-nylon laminated dressing (IP-758) for closure of excised or débrided burn wounds.

    PubMed

    Nathan, P; Robb, E C; Dressler, D; MacMillan, B G

    1982-05-01

    A synthetic dressing (IP-758) consisting of a silicone membrane with a laminated layer of nylon fabric was evaluated in patients as a substitute for biological materials to cover excised areas of burn wounds. During a 3-day interval, the tissue developed a tightly adherent bond to the synthetic dressing. The IP-758 conformed to irregularly-shaped regions and stretched with the movements of the wound surface. Seventeen burned children from 3 to 12 years of age and 1 adult are included in this study. In 12 cases, the mean area covered with the synthetic ranged from approximately 39 to 118 cm2. The average dressing remained in place for 3 days and was replaced once. Microbiological sampling (wet swab technique) of the area under the IP-758 after application of second dressing was compared with open control sites treated with topical antibiotics. The results with Staphylococcus aureus, a frequent contaminant, were similar for the two test areas. The IP-758 site in 6 patients contained an average of 10 3 S. aureus per swab test. Immediately following removal of the adherent IP-758 and control of local bleeding, the wounds in most patients provided excellent sites for autografts. The IP-758 dressing is well-tolerated, elastic and adherent to the burn wound permitting maturation of the wound to readily accept autografts.

  4. Evaluation of an Oxygen-Diffusion Dressing for Accelerated Healing of Donor-Site Wounds

    DTIC Science & Technology

    2014-06-01

    of their wounds, compared with a similar occlusive dressing without oxygen.7 Hyperbaric oxy- gen therapy is thought to improve healing of chronic...wounds in humans,8 but requires visits to facilities with trained personnel and is limited by oxygen toxicity issues. Compared with hyperbaric oxygen...3rd, Fife CE, Gesell LB, Bennett M. Undersea Hyperbaric Medicine Society (UHMS) position statement: topical oxygen for chronic wounds. Undersea

  5. Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis

    PubMed Central

    Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

    2017-01-01

    Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor “35K” could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing. PMID:28098795

  6. Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.

    PubMed

    Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

    2017-01-13

    Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor "35K" could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing.

  7. Healing of experimentally induced wounds of mammary papilla (teat) of the cow: comparison of closure with tissue adhesive versus nonsutured wounds.

    PubMed

    Grymer, J; Watson, G L; Coy, C H; Prindle, L V

    1984-10-01

    Lacerations were surgically produced on the mammary papillae (teats) in 11 healthy dairy cows (10 Holstein and 1 Guernsey). Chemical restraint and local anesthesia were used before the lacerations were done. Twenty-one lacerations (10 front and 11 rear papillae) were apposed with synthetic adhesives. Eight lacerated papillae (6 front and 2 rear) were allowed to heal without tissue apposition. Healing was evaluated daily by palpation and visual inspection. Histologic and subgross photomycrographies were done at the time of slaughter (13 to 20 days). Of the 21 lacerated wounds apposed with adhesive materials, 17 healed by primary intention (81%). One papillary laceration dehisced on the second day and developed a milk fistula. The remaining 3 wounds which were initially repaired with adhesives were injured during the cows' anesthetic recovery and were reapposed with adhesives. The latter healed, but not as well as did the 17. Clinically, there was no detectable differences between adhesives as concerns healing. Of the 8 controls (papillary lacerations that were not apposed), 3 healed by 1st intention (37.5%). The remaining five (62.6%) healed by 2nd and 3rd intention with fistula formation. When evaluated by subgross photomycrography, 20 wounds (18 glued; 2 controls) were bridged by connective tissue and showed no change in wall thickness. Three papillary lacerations (2 glued; 1 control) showed different stages of bridging with connective tissue and wall thickness. Histopathologic evaluation revealed a marked foreign body response evidenced by giant cell and epithelial macrophages adjacent to all lacerations apposed with adhesives. Tissue alteration varied widely depending on the method of tissue apposition and the tissue adhesive used.

  8. Topical Estrogen Accelerates Cutaneous Wound Healing in Aged Humans Associated with an Altered Inflammatory Response

    PubMed Central

    Ashcroft, Gillian S.; Greenwell-Wild, Teresa; Horan, Michael A.; Wahl, Sharon M.; Ferguson, Mark W. J.

    1999-01-01

    The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects. PMID:10514397

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

    PubMed Central

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

    2014-01-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. PMID:25186490

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

    PubMed

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

    2014-10-01

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

  11. Application of Antrodia camphorata Promotes Rat's Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro.

    PubMed

    Amin, Zahra A; Ali, Hapipah M; Alshawsh, Mohammed A; Darvish, Pouya H; Abdulla, Mahmood A

    2015-01-01

    Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson's trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation.

  12. Application of Antrodia camphorata Promotes Rat's Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro

    PubMed Central

    Amin, Zahra A.; Ali, Hapipah M.; Alshawsh, Mohammed A.; Darvish, Pouya H.; Abdulla, Mahmood A.

    2015-01-01

    Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson's trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation. PMID:26557855

  13. Leaching of antioxidants and vulcanization accelerators from rubber closures into drug preparations.

    PubMed

    Airaudo, C B; Gayte-Sorbier, A; Momburg, R; Laurent, P

    1990-01-01

    A thin-layer chromatographic method was used to highlight the leaching into drug preparations of several constituents of elastomeric closures. Among the 150 preparations analysed, the twenty-eight local anaesthetics presented in single-dose delivery syringe-cartridges, one Epinephrine injection in prefilled syringes, eight insulin preparations and two Prednisolone acetate suspensions in the form of small volume flasks (less than or equal to 20 ml) were contaminated by one or more of the following: 2-mercaptobenzothiazole (MBT), 2-mercaptobenzothiazole disulphide and 2-mercaptobenzimidazole (MBI). Prednisolone acetate suspensions also contained 2,2'-methylene-bis(4-methyl-6-alpha-methylcyclohexylphenol). No contamination was found in drug preparations presented in large volume flasks (250-1000 ml). 2-(2-Hydroxyethylthio)-benzothiazole was not present, which indicated that the rubbers had not been sterilized with ethylene oxide. Elastomeric parts of drug closures analysed in the same way contained the same compounds as those found in drugs, one case excepted, which confirms the origin of the contamination. The lowest and the highest concentrations were found in syringe-cartridges; they ranged from 8.3 to 13.8 micrograms ml-1 for MBT, from 2.9 to 9.3 micrograms ml-1 for MBTS and from 2.8 to 11.1 micrograms ml-1 for MBI. Variable results were obtained, for a same preparation, depending upon the batches analysed, which indicates that rubber formulations and/or vulcanization conditions differed. The allergenic, toxic, embryotoxic and mutagenic properties of the compounds leached are discussed.

  14. Novel Anti-Microbial Peptide SR-0379 Accelerates Wound Healing via the PI3 Kinase/Akt/mTOR Pathway

    PubMed Central

    Tomioka, Hideki; Nakagami, Hironori; Tenma, Akiko; Saito, Yoshimi; Kaga, Toshihiro; Kanamori, Toshihide; Tamura, Nao; Tomono, Kazunori; Kaneda, Yasufumi; Morishita, Ryuichi

    2014-01-01

    We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions. PMID:24675668

  15. Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model.

    PubMed

    Mohamad, Najwa; Mohd Amin, Mohd Cairul Iqbal; Pandey, Manisha; Ahmad, Naveed; Rajab, Nor Fadilah

    2014-12-19

    Natural polymer-based hydrogels are of interest to health care professionals as wound dressings owing to their ability to absorb exudates and provide hydration for healing. The aims of this study were to develop and characterize bacterial cellulose/acrylic acid (BC/AA) hydrogels synthesized by electron beam irradiation and investigate its wound healing potential in an animal model. The BC/AA hydrogels were characterized by SEM, tensile strength, water absorptivity, and water vapor transmission rate (WVTR). The cytotoxicity of the hydrogels was investigated in L929 cells. Skin irritation and wound healing properties were evaluated in Sprague-Dawley rats. BC/AA hydrogels had a macroporous network structure, high swelling ratio (4000-6000% at 24h), and high WVTR (2175-2280 g/m(2)/day). The hydrogels were non-toxic in the cell viability assay. In vivo experiments indicated that hydrogels promoted faster wound-healing, enhanced epithelialization, and accelerated fibroblast proliferation compared to that in the control group. These results suggest that BC/AA hydrogels are promising materials for burn dressings.

  16. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    PubMed Central

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-01-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing. PMID:27600999

  17. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    NASA Astrophysics Data System (ADS)

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-09-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

  18. Skin-derived precursors possess the ability of differentiation into the epidermal progeny and accelerate burn wound healing.

    PubMed

    Bayati, Vahid; Abbaspour, Mohammad Reza; Neisi, Niloofar; Hashemitabar, Mahmoud

    2017-02-01

    Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte-like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte-like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte-like cells on tissue culture plate and collagen-chitosan scaffold prepared by freeze-drying. Their differentiation capability was detected by real-time RT-PCR and immunofluorescence. Thereafter, they were cultured on scaffold and implanted in a rat model of burn wound. Histopathological and immunohistochemical analyses were employed to examine the reconstituted skin. The research findings revealed that SKPs were able to differentiate along the epidermal lineage and this ability can be enhanced on a suitable scaffold. Additionally, the results indicated that SKPs apparently promoted wound healing process and accelerate its transition from proliferating stage to maturational phase, especially if they were differentiated into keratinocyte-like cells. Regarding the results, it is concluded that SKPs are able to differentiate into keratinocyte-like cells, particularly when they are cultured on collagen-chitosan scaffold. Moreover, they can regenerate epidermal and dermal layers including thick collagen bundles, possibly through differentiation into keratinocyte-like cells.

  19. Stromal cell-derived factor-1 receptor CXCR4-overexpressing bone marrow mesenchymal stem cells accelerate wound healing by migrating into skin injury areas.

    PubMed

    Yang, Dazhi; Sun, Shijin; Wang, Zhengguo; Zhu, Peifang; Yang, Zailiang; Zhang, Bo

    2013-06-01

    Stromal cell-derived factor-1 (SDF-1) and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. This study investigated the hypothesis that bone marrow-derived mesenchymal stem cells (BMSCs) accelerate skin wound healing in the mouse model by overexpression of CXCR4 in BMSCs. We compared SDF-1 expression and skin wound healing times of BALB/c mice, severe combined immunodeficiency (SCID) mice, and immune system-deficient nude mice after (60)Co radiation-induced injury of their bone marrow. The occurrence of transplanted adenovirus-transfected CXCR4-overexpressing male BMSCs in the wound area was compared with the occurrence of untransfected male BALB/c BMSCs in (60)Co-irradiated female mice skin wound healing areas by Y chromosome marker analyses. The wound healing time of BALB/c mice was 14.00±1.41 days, whereas for the nude and SCID mice it was 17.16±1.17 days and 19.83±0.76 days, respectively. Male BMSCs could be detected in the surrounding areas of (60)Co-irradiated female BALB/c mice wounds, and CXCR4-overexpressing BMSCs accelerated the wound healing time. CXCR4-overexpressing BMSCs migrate in an enhanced manner to skin wounds in a SDF-1-expression-dependent manner, thereby reducing the skin wound healing time.

  20. Conditional knockout of N-WASP in mouse fibroblast caused keratinocyte hyper proliferation and enhanced wound closure

    PubMed Central

    Jain, Neeraj; Kalailingam, Pazhanichamy; Tan, Kai Wei; Tan, Hui Bing; Sng, Ming Keat; Chan, Jeremy Soon Kiat; Tan, Nguan Soon; Thanabalu, Thirumaran

    2016-01-01

    Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). N-WASPFKO (N-WASPfl/fl; Fsp-cre) were born following Mendelian genetics, survived without any visible abnormalities for more than 1 year and were sexually reproductive, suggesting that expression of N-WASP in fibroblast is not critical for survival under laboratory conditions. Histological sections of N-WASPFKO mice skin (13 weeks old) showed thicker epidermis with higher percentage of cells staining for proliferation marker (PCNA), suggesting that N-WASP deficient fibroblasts promote keratinocyte proliferation. N-WASPFKO mice skin had elevated collagen content, elevated expression of FGF7 (keratinocyte growth factor) and TGFβ signaling proteins. Wound healing was faster in N-WASPFKO mice compared to control mice and N-WASP deficient fibroblasts were found to have enhanced collagen gel contraction properties. These results suggest that N-WASP deficiency in fibroblasts improves wound healing by growth factor-mediated enhancement of keratinocyte proliferation and increased wound contraction in mice. PMID:27909303

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

    PubMed Central

    Park, Na-Young; Valacchi, Giuseppe; Lim, Yunsook

    2010-01-01

    Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses. PMID:20871865

  2. 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.

  3. Composites containing albumin protein or cyanoacrylate adhesives and biodegradable scaffolds: II. In vivo wound closure study in a rat model

    NASA Astrophysics Data System (ADS)

    McNally-Heintzelman, Karen M.; Heintzelman, Douglas L.; Duffy, Mark T.; Bloom, Jeffrey N.; Soller, Eric C.; Gilmour, Travis M.; Hoffman, Grant T.; Edward, Deepak

    2004-07-01

    Our Scaffold-Enhanced Biological Adhesive (SEBA) system was investigated as an alternative to sutures or adhesives alone for repair of wounds. Two scaffold materials were investigated: (i) a synthetic biodegradable material fabricated from poly(L-lactic-co-glycolic acid); and (ii) a biologic material, small intestinal submucosa, manufactured by Cook BioTech. Two adhesive materials were also investigated: (i) a biologic adhesive composed of 50%(w/v) bovine serum albumin solder and 0.5mg/ml indocyanine green dye mixed in deionized water, and activated with an 808-nm diode laser; and (ii) Ethicon"s Dermabond, a 2-octyl-cyanoacrylate. The tensile strength and time-to-failure of skin incisions repaired in vivo in a rat model were measured at seven days postoperative. Incisions closed by protein solder alone, by Dermabond alone, or by suture, were also tested for comparison. The tensile strength of repairs formed using the SEBA system were 50% to 65% stronger than repairs formed by suture or either adhesive alone, with significantly less variations within each experimental group (average standard deviations of 15% for SEBA versus 38% for suture and 28% for adhesive alone). In addition, the time-to-failure curves showed a longevity not previously seen with the suture or adhesive alone techniques. The SEBA system acts to keep the dermis in tight apposition during the critical early phase of wound healing when tissue gaps are bridged by scar and granulation tissue. It has the property of being more flexible than either of the adhesives alone and may allow the apposed edges to move in conjunction with each other as a unit for a longer period of time and over a greater range of stresses than adhesives alone. This permits more rapid healing and establishment of integrity since the microgaps between the dermis edges are significantly reduced. By the time the scaffolds are sloughed from the wound site, there is greater strength and healing than that produced by adhesive alone or

  4. Injectable Citrate-Based Mussel-Inspired Tissue Bioadhesives With High Wet Strength for Sutureless Wound Closure

    PubMed Central

    Mehdizadeh, M. Reza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian

    2012-01-01

    The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:22902057

  5. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation.

    PubMed

    Zhao, Bin; Zhang, Yijie; Han, Shichao; Zhang, Wei; Zhou, Qin; Guan, Hao; Liu, Jiaqi; Shi, Jihong; Su, Linlin; Hu, Dahai

    2017-04-01

    Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

  6. 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.

  7. Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice

    PubMed Central

    Yu, Jiawen; Sun, Yuannan; Ren, Guofei; Zhu, Jianjun

    2017-01-01

    Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway. PMID:28373902

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

    PubMed

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

    2014-06-01

    The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar-Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P < 0.05). In the TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P < 0.05). Distinctive decreases of pro-inflammatory cytokines observed in the dermis in the TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.

  9. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic rats.

    PubMed

    Amin, Mohamed A; Abdel-Raheem, Ihab T

    2014-08-01

    Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze-thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same previous composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.

  10. Mechanisms and clinical applications of the vacuum-assisted closure (VAC) Device: a review.

    PubMed

    Venturi, Mark L; Attinger, Christopher E; Mesbahi, Ali N; Hess, Christopher L; Graw, Katherine S

    2005-01-01

    The use of sub-atmospheric pressure dressings, available commercially as the vacuum-assisted closure (VAC) device, has been shown to be an effective way to accelerate healing of various wounds. The optimal sub-atmospheric pressure for wound healing appears to be approximately 125 mm Hg utilizing an alternating pressure cycle of 5 minutes of suction followed by 2 minutes off suction. Animal studies have demonstrated that this technique optimizes blood flow, decreases local tissue edema, and removes excessive fluid from the wound bed. These physiologic changes facilitate the removal of bacteria from the wound. Additionally, the cyclical application of sub-atmospheric pressure alters the cytoskeleton of the cells in the wound bed, triggering a cascade of intracellular signals that increases the rate of cell division and subsequent formation of granulation tissue. The combination of these mechanisms makes the VAC device an extremely versatile tool in the armamentarium of wound healing. This is evident in the VAC device's wide range of clinical applications, including treatment of infected surgical wounds, traumatic wounds, pressure ulcers, wounds with exposed bone and hardware, diabetic foot ulcers, and venous stasis ulcers. VAC has also proven useful in reconstruction of wounds by allowing elective planning of the definitive reconstructive surgery without jeopardizing the wound or outcome. Furthermore, VAC has significantly increased the skin graft success rate when used as a bolster over the freshly skin-grafted wound. VAC is generally well tolerated and, with few contraindications or complications, is fast becoming a mainstay of current wound care.

  11. Primary and secondary closure of the surgical wound after removal of impacted mandibular third molars: a comparative study.

    PubMed

    Pasqualini, D; Cocero, N; Castella, A; Mela, L; Bracco, P

    2005-01-01

    Primary and secondary closure techniques after removal of impacted third molars were compared in terms of post-operative pain and swelling. Two hundred patients with impacted third molars were randomly divided into two groups of 100. Panoramic radiographs were taken to assess degree of eruption and angulation of third molars. Teeth were extracted, and in Group 1 the socket was closed by hermetically suturing the flap. In Group 2 a 5-6 mm wedge of mucosa adjacent to the second molar was removed to obtain secondary healing. Swelling and pain were evaluated for 7 days after surgery with the VAS scale. The statistical analysis (*analysis of variance for repeated measures, P < 0.05) showed that pain was greater in Group 1, although it decreased over time similarly in the two groups (P = 0.081, F(6,198) = 3.073*). Swelling was significantly worse in Group 1 (P < 0.001, F(6,198) = 44.30*). In Group 1, dehiscence of the mucosa was present in 33% of patients at day 7, and 2% showed signs of re-infection with suppurative alveolitis at 30 days. Pain and swelling were less severe with secondary healing than with primary healing.

  12. A unique combination of infrared and microwave radiation accelerates wound healing.

    PubMed

    Schramm, J Mark; Warner, Dave; Hardesty, Robert A; Oberg, Kerby C

    2003-01-01

    Light or electromagnetic radiation has been reported to enhance wound healing. The use of selected spectra, including infrared and microwave, has been described; however, no studies to date have examined the potential benefit of combining these spectra. In this study, a device that emits electromagnetic radiation across both the infrared and microwave ranges was used. To test the effects of this unique electromagnetic radiation spectrum on wound healing, two clinically relevant wound-healing models (i.e., tensile strength of simple incisions and survival of McFarlane flaps) were selected. After the creation of a simple full-thickness incision (n = 35 rats) or a caudally based McFarlane flap (n = 33 rats), animals were randomly assigned to one of three treatment groups: untreated control, infrared, or combined electromagnetic radiation. Treatment was administered for 30 minutes, twice daily for 18 days in animals with simple incisions, and 15 days in animals with McFarlane flaps. The wound area or flap was harvested and analyzed, blinded to the treatment regimens. A p value of less than 0.05 obtained by analysis of variance was considered to be statistically significant. Animals receiving combined electromagnetic radiation demonstrated increased tensile strength (2.62 N/mm2) compared with animals receiving infrared radiation (2.36 N/mm2) or untreated controls (1.73 N/mm2, p < 0.001). Animals with McFarlane flaps receiving combined electromagnetic radiation had increased flap survival (78.0 percent) compared with animals receiving infrared radiation (69.7 percent) and untreated controls (63.1 percent, p < 0.01). Thus, combined electromagnetic radiation provided a distinct advantage in wound healing that might augment current treatment regimens.

  13. Benefit of Leukocyte- and Platelet-Rich Plasma in Operative Wound Closure in Oral and Maxillofacial Surgery

    PubMed Central

    Glik, Justyna; Skowroński, Rafał

    2016-01-01

    This article reports the influence of an autologous leukocyte- and platelet-rich plasma (L-PRP) injection as a minimally invasive method on supporting wound healing processes after a mandibular odontogenic cystectomy and double mandibular fracture fixation. 113 patients were enrolled into a control group (received no L-PRP injection) and 102 patients were enrolled into an L-PRP group with an oral mucosa incision. 18 patients after a double mandibular fracture were operated on using 2 external submandibular approaches receiving no fluids in the right site (a control group) and an L-PRP injection in the left incision (L-PRP group). Clinical observations showed that the oral mucosa healed faster in patients treated with L-PRP, in comparison to cases where inductive biomaterial was not added. Pain at the L-PRP injection site was relieved within few hours after an operation in patients with double mandibular fractures. However, there were no differences observed in the progression of the healing process. L-PRP possesses inductive properties that could stimulate healing processes and it seems to be one of the most promising methods in the future for the treatment of soft tissue defects. PMID:28097149

  14. 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.

  15. Proangiogenic activity of plant extracts in accelerating wound healing - a new face of old phytomedicines.

    PubMed

    Majewska, Iwona; Gendaszewska-Darmach, Edyta

    2011-01-01

    Angiogenesis, the formation of new capillaries from pre-existing vascular network, plays an important role in physiological and pathological processes such as embryonic development, wound healing, and development of atherosclerosis. Extension of the circulatory network is also considered to be one the most important factors during cancerogenesis. Inhibition of angiogenesis may lead to inhibition of tumor growth whereas stimulation may improve wound healing. Research achievements suggest the use of plants and their extracts as potential therapeutic agents with pro- or antiangiogenic activity. Since the anticancer and antiangiogenic properties of many phytomedicines have been amply reviewed elsewhere this paper will focus on the treatment of vascular insufficiency in wound healing. Globally accepted herbal drugs are thought to be safe and effective, however, there is a need for more evidence-based confirmation in controlled and validated trials. Among the most frequently studied proangiogenic phytochemicals are ginsenosides from Panax ginseng, beta-sitosterol from Aloe vera, calycosin from Radix Astragali, and extracts from Hippophae rhamnoides L. and Angelica sinensis.

  16. Thiolated Carboxymethyl-Hyaluronic-Acid-Based Biomaterials Enhance Wound Healing in Rats, Dogs, and Horses

    PubMed Central

    Yang, Guanghui; Prestwich, Glenn D.; Mann, Brenda K.

    2011-01-01

    The progression of wound healing is a complicated but well-known process involving many factors, yet there are few products on the market that enhance and accelerate wound healing. This is particularly problematic in veterinary medicine where multiple species must be treated and large animals heal slower, oftentimes with complicating factors such as the development of exuberant granulation tissue. In this study a crosslinked-hyaluronic-acid (HA-) based biomaterial was used to treat wounds on multiple species: rats, dogs, and horses. The base molecule, thiolated carboxymethyl HA, was first found to increase keratinocyte proliferation in vitro. Crosslinked gels and films were then both found to enhance the rate of wound healing in rats and resulted in thicker epidermis than untreated controls. Crosslinked films were used to treat wounds on forelimbs of dogs and horses. Although wounds healed slower compared to rats, the films again enhanced wound healing compared to untreated controls, both in terms of wound closure and quality of tissue. This study indicates that these crosslinked HA-based biomaterials enhance wound healing across multiple species and therefore may prove particularly useful in veterinary medicine. Reduced wound closure times and better quality of healed tissue would decrease risk of infection and pain associated with open wounds. PMID:23738117

  17. Enhanced growth of endothelial precursor cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: a diabetic mouse model.

    PubMed

    Kanitkar, Meghana; Jaiswal, Amit; Deshpande, Rucha; Bellare, Jayesh; Kale, Vaijayanti P

    2013-01-01

    Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.

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

    PubMed

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-25

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

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

    PubMed Central

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-01

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID:26804208

  20. PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing.

    PubMed

    Ho, Tsung-Chuan; Chen, Show-Li; Wu, Ju-Yun; Ho, Mei-Ying; Chen, Lee-Jen; Hsieh, Jui-Wen; Cheng, Huey-Chuan; Tsao, Yeou-Ping

    2013-09-01

    Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.

  1. Maltodextrin/ascorbic acid stimulates wound closure by increasing collagen turnover and TGF-β1 expression in vitro and changing the stage of inflammation from chronic to acute in vivo.

    PubMed

    Salgado, Rosa M; Cruz-Castañeda, Otilia; Elizondo-Vázquez, Francisco; Pat, Lucia; De la Garza, Anabel; Cano-Colín, Saúl; Baena-Ocampo, Leticia; Krötzsch, Edgar

    2017-02-01

    It has been reported that carbohydrates confer physicochemical properties to the wound environment that improves tissue repair. We evaluated in vitro and in vivo wound healing during maltodextrin/ascorbic acid treatment. In a fibroblast monolayer scratch assay, we demonstrated that maltodextrin/ascorbic acid stimulated monolayer repair by increasing collagen turnover coordinately with TGF-β1 expression (rising TGF-β1 and MMP-1 expression, as well as gelatinase activity, while TIMP-1 was diminished), similar to in vivo trends. On the other hand, we observed that venous leg ulcers treated with maltodextrin/ascorbic acid diminished microorganism population and improved wound repair during a 12 week period. When maltodextrin/ascorbic acid treatment was compared with zinc oxide, almost four fold wound closure was evidenced. Tissue architecture and granulation were improved after the carbohydrate treatment also, since patients that received maltodextrin/ascorbic acid showed lower type I collagen fiber levels and increased extracellular alkaline phosphatase activity and blood vessels than those treated with zinc oxide. We hypothesize that maltodextrin/ascorbic acid treatment stimulated tissue repair of chronic wounds by changing the stage of inflammation and modifying collagen turnover directly through fibroblast response.

  2. The use of honey as a topical dressing to treat a large, devitalized wound in a stumptail macaque (Macaca arctoides).

    PubMed

    Staunton, Christine J; Halliday, Lisa C; Garcia, Kelly D

    2005-07-01

    There are many reasons wounds are managed as open wounds rather than by primary closure. Indications include gross contamination, infection, and skin loss leading to insufficient adjacent tissue for wound closure. The most common method of managing an open wound is with wet-to-dry dressings. Wet-to-dry dressings provide mechanical debridement and promote the movement of viscous exudates away from the wound. Wet-to-dry bandages ideally are changed every 12 to 24 h. For nonhuman primates, it is desirable to develop wound management techniques that limit animal handling for bandage changes and thus the frequency of sedation. Anecdotal reports on the use of honey to treat wounds date back to 2000 B.C. Recently, scientific inquiries have found merit to these reports. Honey accelerates healing because of its direct effects on tissue and antibacterial properties. In addition, dressings with honey can be changed relatively infrequently. Honey decreases inflammatory edema, hastens sloughing of devitalized tissue, attracts macrophages which cleanse the wound, provides a local cellular energy source, and protectively covers the wound. A high osmolarity, acidity, and hydrogen peroxide content confer honey with antibacterial properties. Here we describe the use of honey to manage a bite wound in a stumptail macaque (Macaca arctoides). The wound healed rapidly: after 2 weeks of treatment, there was markedly less exudate and no necrotic tissue. This report describes how honey may be helpful in the management of open wounds in nonhuman primates by minimizing the need for sedation for bandage changes.

  3. Acceleration of wound healing in gastric ulcers by local injection of neutralising antibody to transforming growth factor beta 1.

    PubMed Central

    Ernst, H; Konturek, P; Hahn, E G; Brzozowski, T; Konturek, S J

    1996-01-01

    BACKGROUND: Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1. METHOD: Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed. RESULTS: The application of NAs to TGF beta 1 led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in the TGF beta 1 treated group. CONCLUSION: Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing. Images Figure 2 Figure 3 PMID:8991853

  4. Pfannenstiel incision closure: a review of current skin closure techniques.

    PubMed

    Altman, Alon D; Allen, Victoria M; McNeil, Shelly A; Dempster, Jeffrey

    2009-06-01

    The goal of any skin closure technique is to produce appropriate skin approximation and adequate healing while minimizing pain, wound complications, cost, and scarring; the technique should be quick, cost-effective, and simple, while maximizing wound cosmesis and patient satisfaction. Although many studies have shown the superiority of staples for speed of closure, it is unclear if staples give a superior cosmetic result or reduce pain. Several randomized controlled trials have found that sutures are superior for cosmesis and that they decrease postoperative pain and are more cost-effective. There remains a paucity of data on wound infections and complications associated with closure technique. This review summarizes studies to date evaluating outcomes associated with wound closure using staples and sutures in repairing abdominal incisions and, in particular, assesses outcomes in the obstetric population with a Pfannenstiel incision.

  5. Erythropoietin improves skin wound healing and activates the TGF-β signaling pathway.

    PubMed

    Siebert, Nikolai; Xu, Weiguo; Grambow, Eberhard; Zechner, Dietmar; Vollmar, Brigitte

    2011-12-01

    We could recently report that erythropoietin (EPO) accelerates skin wound healing in mice. Now, we provide insight into the molecular mechanisms of this non-hematopoietic property of EPO analyzing the transforming growth factor (TGF)-β signaling pathway. EPO receptor was found expressed in both non-wounded and wounded skin tissue as well as in fibroblasts and keratinocytes. In saline-treated control animals, wounds exhibited a significant upregulation of TGF-β1 and of α-smooth muscle actin (α-SMA) compared with non-wounded skin. EPO treatment accelerated wound epithelialization and induced mRNA expression of TGF-β1 and α-SMA. In addition, EPO significantly enhanced phosphorylation of Smad2 and Smad3 in fibroblasts and also elevated phosphorylation of Smad3 in wound tissue. Blockade of TGF-β using a neutralizing anti-TGF-β antibody attenuated EPO-induced acceleration of wound epithelialization in vivo and markedly reversed EPO effects on mRNA expression of TGF-β1 and α-SMA. In conclusion, EPO caused activation of the Smad-dependent TGF-β signaling pathway, enhanced differentiation of myofibroblasts, and accelerated skin wound closure.

  6. 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.

  7. Importance of wound stabilization in early wound healing of laser skin welds

    NASA Astrophysics Data System (ADS)

    Thomsen, Sharon L.; Chan, Eric K.; Stubig, Ingrid M.; Menovsky, Thomas; Welch, Ashley J.

    1995-05-01

    Photothermal coagulation of indocyanine/fibrinogen/hyaluronate `glue' with diode laser irradiation (ICG) produces mechanically more stable wound closures in rat skin incisions when compared to wounds closed by CW HoYAG laser irradiation alone. However, neither laser- medicated technique produced wound closures as stabile as the sutured wounds. The predominant advantages of photothermal closure of skin wounds are short operating times and formation of fluid tight bonds with minimal tissue manipulation. The added stability of ICG/laser closed wounds demonstrated in this study suggests the possible usefulness of this technique to close skin wounds in areas of low skin tension.

  8. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

    PubMed Central

    Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses. PMID:26798423

  9. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model.

    PubMed

    Tamaki, Naofumi; Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.

  10. Acceleration of dermal wound healing by using electrospun curcumin-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) fibrous mats.

    PubMed

    Fu, Shao-Zhi; Meng, Xiao-Hang; Fan, Juan; Yang, Ling-Lin; Wen, Qing-Lian; Ye, Su-Juan; Lin, Sheng; Wang, Bi-Qiong; Chen, Lan-Lan; Wu, Jing-Bo; Chen, Yue; Fan, Jun-Ming; Li, Zhi

    2014-04-01

    This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.

  11. Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.

    PubMed

    Chen, Jialin; Lan, Jie; Liu, Dongle; Backman, Ludvig J; Zhang, Wei; Zhou, Qingjun; Danielson, Patrik

    2017-03-09

    High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. © Stem Cells Translational Medicine 2017.

  12. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    PubMed

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

    2014-02-01

    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

  13. An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA

    PubMed Central

    Demaria, Marco; Ohtani, Naoko; Youssef, Sameh A.; Rodier, Francis; Toussaint, Wendy; Mitchell, James R.; Laberge, Remi-Martin; Vijg, Jan; Van Steeg, Harry; Dollé, Martijn E.T.; Hoeijmakers, Jan H.J.; de Bruin, Alain; Hara, Eiji; Campisi, Judith

    2015-01-01

    SUMMARY Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved. PMID:25499914

  14. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.

    PubMed

    Demaria, Marco; Ohtani, Naoko; Youssef, Sameh A; Rodier, Francis; Toussaint, Wendy; Mitchell, James R; Laberge, Remi-Martin; Vijg, Jan; Van Steeg, Harry; Dollé, Martijn E T; Hoeijmakers, Jan H J; de Bruin, Alain; Hara, Eiji; Campisi, Judith

    2014-12-22

    Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

  15. Stimulation of Skin and Wound Fibroblast Migration by Mesenchymal Stem Cells Derived from Normal Donors and Chronic Wound Patients

    PubMed Central

    Rodriguez-Menocal, Luis; Salgado, Marcela; Ford, Dwayne

    2012-01-01

    Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow-derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose-dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow-derived MSCs in wound healing and may provide insight into why some wounds do not heal. PMID:23197781

  16. Clinical Usage and Economic Effectiveness of a Recently Developed Epidermal Autograft Harvesting System in 13 Chronic Wound Patients in a University-Based Wound Center

    PubMed Central

    Hulsey, Angela; Linneman, Paul

    2016-01-01

    Introduction: Chronic wounds are a significant healthcare problem in the United States. Their costs approach 25 billion dollars in the United States. Current wound-care treatments of local wound care, moist dressings, and source control, while necessary for wound healing, are frequently not enough to ensure complete wound closure. The current surgical technique of split-thickness skin grafting is an operative procedure, painful, time-consuming, and leaves significant donor site wounds. A recently developed and marketed epidermal autograft harvester was tested at our university hospital wound center on 13 patients with wounds of various etiologies. Their clinical outcomes were evaluated, as were the costs associated with its usage compared with the potential costs of continued wound care without autograft placement. Methods: Thirteen patients whose wounds appeared to have "stalled" or reached a plateau in healing by measurement data and visual evidence were chosen to receive an epidermal autograft to accelerate wound closure. Wound-types included diabetic ulcers, venous or lymphedema-related ulcers, surgical site wounds, and traumatic wounds. Time-to-healing in days, when applicable, was captured. Wound center billing and charges were available and evaluated for nine of the 13 patients. Costs of standard care continuation compared with the cost of epidermal autograft technology usage were compared. Results: Healing rates were 62%; eight of the 13 patients had healed within four months, two were lost to follow-up, and three have wounds that remain open. Four of the patients healed in less than one month. The comparatively rapid closure of the open wound(s) post-epidermal autograft placement potentially reduced healthcare costs based on charges at an average of $1,153 per patient and yielded an average of $650 to the wound center, not applying the routine costs of dressings applied in the center.  Conclusion: The epidermal autograft harvester accelerated

  17. Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice.

    PubMed

    Koppel, Aaron C; Kiss, Alexi; Hindes, Anna; Burns, Carole J; Marmer, Barry L; Goldberg, Gregory; Blumenberg, Miroslav; Efimova, Tatiana

    2014-05-15

    Proline-rich protein tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family. We used Pyk2 knockout (Pyk2-KO) mice to study the role of Pyk2 in cutaneous wound repair. We report that the rate of wound closure was delayed in Pyk2-KO compared with control mice. To examine whether impaired wound healing of Pyk2-KO mice was caused by a keratinocyte cell-autonomous defect, the capacities of primary keratinocytes from Pyk2-KO and wild-type (WT) littermates to heal scratch wounds in vitro were compared. The rate of scratch wound repair was decreased in Pyk2-KO keratinocytes compared with WT cells. Moreover, cultured human epidermal keratinocytes overexpressing the dominant-negative mutant of Pyk2 failed to heal scratch wounds. Conversely, stimulation of Pyk2-dependent signaling via WT Pyk2 overexpression induced accelerated scratch wound closure and was associated with increased expression of matrix metalloproteinase (MMP)-1, MMP-9, and MMP-10. The Pyk2-stimulated increase in the rate of scratch wound repair was abolished by coexpression of the dominant-negative mutant of PKCδ and by GM-6001, a broad-spectrum inhibitor of MMP activity. These results suggest that Pyk2 is essential for skin wound reepithelialization in vivo and in vitro and that it regulates epidermal keratinocyte migration via a pathway that requires PKCδ and MMP functions.

  18. Re-Epithelialization of Pathological Cutaneous Wounds Is Improved by Local Mineralocorticoid Receptor Antagonism.

    PubMed

    Nguyen, Van Tuan; Farman, Nicolette; Maubec, Eve; Nassar, Dany; Desposito, Dorinne; Waeckel, Ludovic; Aractingi, Sélim; Jaisser, Frederic

    2016-10-01

    Impaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the glucocorticoid receptor, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) might be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re-epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC-impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology.

  19. The Golden Spiral Flap: A New Flap Design that Allows for Closure of Larger Wounds under Reduced Tension – How Studying Nature’s Own Design Led to the Development of a New Surgical Technique

    PubMed Central

    Paul, Sharad P.

    2016-01-01

    This paper details the study of biodynamic excisional skin tension lines on the scalp and the development of a new flap technique for closure of scalp wounds. Recently, a study by this author, on pigskin, replicated whorls by placing tissue under rapid stretch using saline tissue expanders, by recreating rapid dermo-epidermal shear of skin – thereby concluding that the golden spiral pattern is nature’s own pattern for rapid expansion. Given the relationship between tissue expansion and stretch has been shown to cause deformation gradients that have both elastic and growth factors, the author set out to test the hypothesis that a golden spiral pattern therefore would be more efficient at closing wounds under less tension when compared with standard semicircular rotational flap patterns. The author conducted a series of experiments, both on pigskin (to first confirm the hypothesis, using a recently developed computerized tensiometer) and later a clinical study. This paper presents a new random pivotal flap technique for skin closures on the head and neck: the golden spiral flap. Biomechanics, planning, and advantages of this new flap are described in this paper. PMID:27900320

  20. The Golden Spiral Flap: A New Flap Design that Allows for Closure of Larger Wounds under Reduced Tension - How Studying Nature's Own Design Led to the Development of a New Surgical Technique.

    PubMed

    Paul, Sharad P

    2016-01-01

    This paper details the study of biodynamic excisional skin tension lines on the scalp and the development of a new flap technique for closure of scalp wounds. Recently, a study by this author, on pigskin, replicated whorls by placing tissue under rapid stretch using saline tissue expanders, by recreating rapid dermo-epidermal shear of skin - thereby concluding that the golden spiral pattern is nature's own pattern for rapid expansion. Given the relationship between tissue expansion and stretch has been shown to cause deformation gradients that have both elastic and growth factors, the author set out to test the hypothesis that a golden spiral pattern therefore would be more efficient at closing wounds under less tension when compared with standard semicircular rotational flap patterns. The author conducted a series of experiments, both on pigskin (to first confirm the hypothesis, using a recently developed computerized tensiometer) and later a clinical study. This paper presents a new random pivotal flap technique for skin closures on the head and neck: the golden spiral flap. Biomechanics, planning, and advantages of this new flap are described in this paper.

  1. The Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl) homoserine lactone can accelerate cutaneous wound healing through myofibroblast differentiation in rats.

    PubMed

    Nakagami, Gojiro; Minematsu, Takeo; Asada, Mayumi; Nagase, Takashi; Akase, Tomoko; Huang, Lijuan; Morohoshi, Tomohiro; Ikeda, Tsukasa; Ohta, Yasunori; Sanada, Hiromi

    2011-07-01

    Quorum sensing is a cell density-dependent gene regulation system in bacteria. N-(3-oxododecanoyl) homoserine lactone (3-oxo-C12-HSL) is used in the las quorum-sensing system in Pseudomonas aeruginosa, which is an opportunistic pathogen that causes many human diseases. Although many studies have investigated the sole effects of quorum sensing on several types of mammalian cells, including lung cells, little is known about the effects of quorum sensing on the cells associated with wound healing. To better understand the mechanism of bacterial wound infection, we investigated the effects of 3-oxo-C12-HSL on cells using a rat full-thickness wound-healing model. We found that the wound contraction was significantly increased at 24 h after the administration of 3-oxo-C12-HSL to the surface of granulation tissue. Differentiation of fibroblasts to myofibroblasts was induced in the in vivo wound-healing model and was confirmed in vitro using the rat fibroblastic cell line Rat-1. Cyclooxygenase (Cox)-2 expression was also induced in Rat-1 cells by 3-oxo-C12-HSL. This finding suggested that Cox-2 upregulation may be related to the inflammatory findings in the histological examinations, in which infiltrating polymorphonuclear neutrophils were observed at the wound site. Taken together, these results imply that mammals have a potential defense system against invading pathogens by responding to the presence of 3-oxo-C12-HSL and inducing the differentiation of fibroblasts to myofibroblasts as well as inflammation for accelerating wound healing.

  2. HDFx: a novel biologic immunomodulator accelerates wound healing and is suggestive of unique regenerative powers: potential implications for the warfighter and disaster victims.

    PubMed

    Altura, Burton M; Carella, Anthony; Gebrewold, Asefa

    2012-01-01

    Recently, we reported on the discovery of a new, conserved biologic protein (35-40 KDa), termed HDFx, that protects rats, guinea-pigs, mice, and rabbits against lethal hemorrhage, endotoxins, intestinal ischemic-shock, and traumatic injuries. It was found to stimulate several arms of the immune system. The present report demonstrates, for the first time, that HDFx accelerates wound healing in two different models (excision wound model; and incision wound model) in rats. The results shown, herein, indicate that HDFx produces greater rates of wound contraction, greater tensile strength, and more rapid healing than controls. Our new data also show that this biologic increases hydroxyproline content of granulation tissue coupled with a reduction in superoxide dismutase (SOD). In addition, we show that HDFx increases the levels of serum ascorbic acid and stimulates the mononuclear cells of the reticuloendothelial system (RES). Overall, these data suggest that HDFx may possess unique regenerative powers. We, thus, believe that HDFx can be of great potential use in diverse types of wounds which, otherwise, could result in difficult to treat infections and thus prevent sepsis and loss of body parts from amputations.

  3. Effects of erythropoietin in skin wound healing are dose related.

    PubMed

    Sorg, Heiko; Krueger, Christian; Schulz, Torsten; Menger, Michael D; Schmitz, Frank; Vollmar, Brigitte

    2009-09-01

    The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. We studied the effect of EPO on dermal regeneration using intravital microscopy in a model of full dermal thickness wounds in the skin-fold chamber of hairless mice. Animals received repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound cellularity, and induced maturation of newly formed microvascular networks. In contrast, RHD-EPO impaired the healing process, as indicated by delayed epithelialization, high wound cellularity, and lack of maturation of microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and rheological malfunction, further deteriorating vessel and tissue maturation. Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed accelerated wound scratch closure. In summary, our data show that a single application of a high dose of EPO accelerates and improves skin wound healing.

  4. Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

    PubMed Central

    Krausewitz, Philipp; Brückner, Markus; Ketelhut, Steffi; Domagk, Dirk; Kemper, Björn

    2014-01-01

    Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing. PMID:25251440

  5. Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization

    PubMed Central

    Xiao, Yun; Reis, Lewis A.; Feric, Nicole; Knee, Erica J.; Gu, Junhao; Cao, Shuwen; Laschinger, Carol; Londono, Camila; Antolovich, Julia; McGuigan, Alison P.; Radisic, Milica

    2016-01-01

    There is a clinical need for new, more effective treatments for chronic wounds in diabetic patients. Lack of epithelial cell migration is a hallmark of nonhealing wounds, and diabetes often involves endothelial dysfunction. Therefore, targeting re-epithelialization, which mainly involves keratinocytes, may improve therapeutic outcomes of current treatments. In this study, we present an integrin-binding prosurvival peptide derived from angiopoietin-1, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), as a therapeutic candidate for diabetic wound treatments by demonstrating its efficacy in promoting the attachment, survival, and collective migration of human primary keratinocytes and the activation of protein kinase B Akt and MAPKp42/44. The QHREDGS peptide, both as a soluble supplement and when immobilized in a substrate, protected keratinocytes against hydrogen peroxide stress in a dose-dependent manner. Collective migration of both normal and diabetic human keratinocytes was promoted on chitosan–collagen films with the immobilized QHREDGS peptide. The clinical relevance was demonstrated further by assessing the chitosan–collagen hydrogel with immobilized QHREDGS in full-thickness excisional wounds in a db/db diabetic mouse model; QHREDGS showed significantly accelerated and enhanced wound closure compared with a clinically approved collagen wound dressing, peptide-free hydrogel, or blank wound controls. The accelerated wound closure resulted primarily from faster re-epithelialization and increased formation of granulation tissue. There were no observable differences in blood vessel density or size within the wound; however, the total number of blood vessels was greater in the peptide-hydrogel–treated wounds. Together, these findings indicate that QHREDGS is a promising candidate for wound-healing interventions that enhance re-epithelialization and the formation of granulation tissue. PMID:27647919

  6. Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization.

    PubMed

    Xiao, Yun; Reis, Lewis A; Feric, Nicole; Knee, Erica J; Gu, Junhao; Cao, Shuwen; Laschinger, Carol; Londono, Camila; Antolovich, Julia; McGuigan, Alison P; Radisic, Milica

    2016-10-04

    There is a clinical need for new, more effective treatments for chronic wounds in diabetic patients. Lack of epithelial cell migration is a hallmark of nonhealing wounds, and diabetes often involves endothelial dysfunction. Therefore, targeting re-epithelialization, which mainly involves keratinocytes, may improve therapeutic outcomes of current treatments. In this study, we present an integrin-binding prosurvival peptide derived from angiopoietin-1, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), as a therapeutic candidate for diabetic wound treatments by demonstrating its efficacy in promoting the attachment, survival, and collective migration of human primary keratinocytes and the activation of protein kinase B Akt and MAPKp42/44 The QHREDGS peptide, both as a soluble supplement and when immobilized in a substrate, protected keratinocytes against hydrogen peroxide stress in a dose-dependent manner. Collective migration of both normal and diabetic human keratinocytes was promoted on chitosan-collagen films with the immobilized QHREDGS peptide. The clinical relevance was demonstrated further by assessing the chitosan-collagen hydrogel with immobilized QHREDGS in full-thickness excisional wounds in a db/db diabetic mouse model; QHREDGS showed significantly accelerated and enhanced wound closure compared with a clinically approved collagen wound dressing, peptide-free hydrogel, or blank wound controls. The accelerated wound closure resulted primarily from faster re-epithelialization and increased formation of granulation tissue. There were no observable differences in blood vessel density or size within the wound; however, the total number of blood vessels was greater in the peptide-hydrogel-treated wounds. Together, these findings indicate that QHREDGS is a promising candidate for wound-healing interventions that enhance re-epithelialization and the formation of granulation tissue.

  7. 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.

  8. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

    PubMed

    Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

    2014-11-28

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.

  9. RGTA OTR 4120, a heparan sulfate proteoglycan mimetic, increases wound breaking strength and vasodilatory capability in healing rat full-thickness excisional wounds.

    PubMed

    Tong, Miao; Zbinden, Mariken M; Hekking, Ineke J M; Vermeij, Marcel; Barritault, Denis; van Neck, Johan W

    2008-01-01

    ReGeneraTing Agents (RGTAs), a family of polymers engineered to protect and stabilize heparin-binding growth factors, have been shown to promote tissue repair and regeneration. In this study, the effects of one of these polymers, RGTA OTR4120, on healing of full-thickness excisional wounds in rats were investigated. Two 1.5 cm diameter circular full-thickness excisional wounds were created on the dorsum of a rat. After creation of the wounds, RGTA OTR4120 was applied. The progress of healing was assessed quantitatively by evaluating the wound closure rate, vasodilatory capability, and wound breaking strength. The results showed a triple increase of the local vascular response to heat provocation in the RGTA OTR4120-treated wounds as compared with vehicle-treated wounds. On days 14 and 79 after surgery, the wounds treated with RGTA OTR4120 gained skin strength 12% and 48% of the unwounded skin, respectively, and displayed a significantly increased gain in skin strength when compared with control animals. These results raise the possibility of efficacy of RGTA OTR4120 in accelerating surgically cutaneous wound healing by enhancing the wound breaking strength and improving the microcirculation.

  10. Secretome of Peripheral Blood Mononuclear Cells Enhances Wound Healing

    PubMed Central

    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 (SECPBMC). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SECPBMC 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 SECPBMC 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 SECPBMC 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) SECPBMC induced proliferation and tube-formation in a matrigel-assay. In addition, SECPBMC 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. PMID:23533667

  11. 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.

  12. 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

  13. From Cleanup to Stewardship. A companion report to Accelerating Cleanup: Paths to Closure and background information to support the scoping process required for the 1998 PEIS Settlement Study

    SciTech Connect

    None, None

    1999-10-01

    Long-term stewardship is expected to be needed at more than 100 DOE sites after DOE's Environmental Management program completes disposal, stabilization, and restoration operations to address waste and contamination resulting from nuclear research and nuclear weapons production conducted over the past 50 years. From Cleanup to stewardship provides background information on the Department of Energy (DOE) long-term stewardship obligations and activities. This document begins to examine the transition from cleanup to long-term stewardship, and it fulfills the Secretary's commitment to the President in the 1999 Performance Agreement to provide a companion report to the Department's Accelerating Cleanup: Paths to Closure report. It also provides background information to support the scoping process required for a study on long-term stewardship required by a 1998 Settlement Agreement.

  14. Burn-wound healing effect of gelatin/polyurethane nanofiber scaffold containing silver-sulfadiazine.

    PubMed

    Heo, Dong Nyoung; Yang, Dae Hyeok; Lee, Jung Bok; Bae, Min Soo; Kim, Jung Ho; Moon, Seong Hwan; Chun, Heoung Jae; Kim, Chun Ho; Lim, Ho-Nam; Kwon, Il Keun

    2013-03-01

    Despite the fact that advances of burn treatment have led to reduction in the morbidity caused by burns, burn infection is still a serious problem. In this study, we designed blended synthetic and natural polymers nanofiber scaffolds using polyurethane (PU) and gelatin, which were prepared by an electrospinning method. Silver-sulfadiazine (SSD) was co-mixed to the blended polymer solution for being incorporated into the nanofibers after the electrospinning, followed by examination of burn-wound healing effect. The nanofiber scaffolds containing SSD should not only serve as a substrate for skin regeneration, but may also deliver suitable drugs, within a controlled manner during healing. The SSD release was able to prevent the growth of a wide array of bacteria and accelerate the wound healing by preventing infection. Therefore it could accelerate the burn-wound closure rate. We confirmed that PU/gelatin nanofiber scaffolds containing SSD lead to enhanced regeneration of burn-wounds.

  15. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    PubMed

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.

  16. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis.

    PubMed

    Zhang, Xiao-Na; Ma, Ze-Jun; Wang, Ying; Li, Yu-Zhu; Sun, Bei; Guo, Xin; Pan, Cong-Qing; Chen, Li-Ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing.

  17. Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing

    NASA Astrophysics Data System (ADS)

    Xu, He; Lv, Fang; Zhang, Yali; Yi, Zhengfang; Ke, Qinfei; Wu, Chengtie; Liu, Mingyao; Chang, Jiang

    2015-11-01

    A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing.A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04802h

  18. Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction.

    PubMed

    Kimura, Takayuki; Sugaya, Makoto; Blauvelt, Andrew; Okochi, Hitoshi; Sato, Shinichi

    2013-07-01

    Skin wound healing is an interactive process involving soluble mediators, ECM, resident cells, and infiltrating cells. Little is known about wound healing in the presence of lymphedema. In this study, we investigated wound healing using kCYC⁺/⁻ mice, which demonstrate severe lymphatic dysfunction. Wound healing was delayed significantly in kCYC⁺/⁻ mice when compared with WT mice. In wounded skin of kCYC⁺/⁻ mice, mast cell numbers were increased compared with WT mice, whereas macrophage numbers were decreased. Moreover, IL-10 expression by mast cells was increased, and expression of bFGF, mainly produced by macrophages, was decreased in wounded skin of kCYC⁺/⁻ mice compared with WT mice. We next crossed kCYC⁺/⁻ mice with IL-10⁻/⁻ mice, which were reported to show accelerated wound closure. In kCYC⁺/⁻ IL-10⁺/⁻ mice, time course of wound healing, numbers of macrophages, and IL-10 mRNA expression levels in wounded skin were comparable with WT IL-10⁺/⁻ mice. Similar results were obtained using a different lymphedema model, in which circumferential skin excision was performed on the tails of mice to remove the superficial lymphatics. In summary, these findings suggest that IL-10 plays an important role in delayed wound healing in the setting of lymphatic dysfunction.

  19. [Current clinical applications of vacuum-assisted closure (VAC) in vascular surgery].

    PubMed

    Lejay, A; Creton, O; Thaveau, F; Bajcz, C; Stephan, D; Kretz, J-G; Chakfé, N

    2008-12-01

    The aim of the study was to evaluate the efficacy of vacuum-assisted closure (VAC) in vascular patients presenting limb ulcers or non healed amputations. The efficacy of the VAC was studied in terms of healing, walking distance, and autonomy of life. This retrospective study included 14 patients, 11 men and three women, who were treated by a VAC therapy between December 2003 and February 2007. Two patients presented critical ischemia with limb ulcers and 12 patients non healed amputations despite previous revascularisation. Vascular reconstruction was performed in all cases before the VAC therapy. The rate of wound healing with VAC therapy was 87%. After wound healing, 92% of patients were walking and 62% of them were independent. In conclusion, VAC therapy may be a useful tool to accelerate healing of lower-limb wounds or non healing wounds secondary to amputation, allowing a faster recovery with a good level of autonomy.

  20. Copper-induced vascular endothelial growth factor expression and wound healing.

    PubMed

    Sen, Chandan K; Khanna, Savita; Venojarvi, Mika; Trikha, Prashant; Ellison, E Christopher; Hunt, Thomas K; Roy, Sashwati

    2002-05-01

    Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. Whereas a direct role of copper to facilitate angiogenesis has been evident two decades ago, the specific targets of copper action remained unclear. This report presents first evidence showing that inducible VEGF expression is sensitive to copper and that the angiogenic potential of copper may be harnessed to accelerate dermal wound contraction and closure. At physiologically relevant concentrations, copper sulfate induced VEGF expression in primary as well as transformed human keratinocytes. Copper shared some of the pathways utilized by hypoxia to regulate VEGF expression. Topical copper sulfate accelerated closure of excisional murine dermal wound allowed to heal by secondary intention. Copper-sensitive pathways regulate key mediators of wound healing such as angiogenesis and extracellular matrix remodeling. Copper-based therapeutics represents a feasible approach to promote dermal wound healing.

  1. [Endoscopic vacuum-assisted closure].

    PubMed

    Wedemeyer, J; Lankisch, T

    2013-03-01

    Anastomotic leakage in the upper and lower intestinal tract is associated with high morbidity and mortality. Within the last 10 years endoscopic treatment options have been accepted as sufficient treatment option of these surgical complications. Endoscopic vacuum assisted closure (E-VAC) is a new innovative endoscopic therapeutic option in this field. E-VAC transfers the positive effects of vacuum assisted closure (VAC) on infected cutaneous wounds to infected cavities that can only be reached endoscopically. A sponge connected to a drainage tube is endoscopically placed in the leakage and a continuous vacuum is applied. Sponge and vacuum allow removal of infected fluids and promote granulation of the leakage. This results in clean wound grounds and finally allows wound closure. Meanwhile the method was also successfully used in the treatment of necrotic pancreatitis.

  2. β-Cyclodextrin-Linked Polyethylenimine Nanoparticles Facilitate Gene Transfer and Enhance the Angiogenic Capacity of Mesenchymal Stem Cells for Wound Repair and Regeneration.

    PubMed

    Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Zhang, Tian-Yuan; Zhang, Chen-Zhen; Wu, Jia-He; Yu, Lian; Lin, Jun; Liang, Wen-Quan; Khang, Gilson; Gao, Jian-Qing

    2015-04-01

    Repair of deep wounds by cell transplantation strongly depends on angiogenesis and on the regeneration of skin and appendages. In this study, plasmid DNA encoding vascular endothelial growth factor-165 (VEGF-165) was transduced into bone-marrow mesenchymal stem cells (MSCs) using a nonviral vector, β-cyclodextrin-linked polyethylenimine, to enhance angiogenic capacity. The effects of MSCs administered by intradermal injection or transplantation on wound closure were compared in a full-thickness excision wound model. The results showed that the MSC-seeded sponge had significantly stronger acceleration in wound closure than the MSC injection. The effects on wound repair and regeneration of transplanted MSCs and pDNA-VEGF1 65-transfected MSCs (TMSCs) with gelatin/β-tricalcium phosphate scaffold were also investigated. Compared with MSC transplantation, TMSC transplantation showed higher efficacy in stimulating wound closure, promoting dermal collagen synthesis and regulating the deposition of newly formed collagen. In addition, the angiogenic capacity of the TMSCs was higher than that of the MSCs. The results indicate that the nonviral genetic engineering of the MSCs is a promising strategy to enhance the angiogenic capacity of MSCs for wound repair and angiogenesis. Functional gene-activated MSCs may be used as cost-effective and accessible seed cells for skin tissue engineering and as novel carriers for wound gene therapy.

  3. Cabled butterfly closure: a novel technique for sternal closure.

    PubMed

    Jolly, Shashank; Flom, Beau; Dyke, Cornelius

    2012-10-01

    Impaired sternal wound healing remains problematic after median sternotomy and can lead to significant morbidity after cardiac surgical procedures. Although metal plating systems exist for closing the sternum, their use is limited by expense and practicality, and simple wire closure remains the most common technique to close the sternum. We describe a cabling technique for sternal closure that is secure, uses standard sternal wire, and may be used on every patient. We have used the technique routinely in 291 patients with no sternal dehiscence or wound healing problems.

  4. Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

    PubMed Central

    Zhang, Jieyuan; Chen, Chunyuan; Hu, Bin; Niu, Xin; Liu, Xiaolin; Zhang, Guowei; Zhang, Changqing; Li, Qing; Wang, Yang

    2016-01-01

    Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration. PMID:27994512

  5. Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

    PubMed

    Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang

    2016-04-01

    It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates

  6. Amniotic mesenchymal stem cells enhance wound healing in diabetic NOD/SCID mice through high angiogenic and engraftment capabilities.

    PubMed

    Kim, Sung-Whan; Zhang, Hong-Zhe; Guo, Longzhe; Kim, Jong-Min; Kim, Moo Hyun

    2012-01-01

    Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

  7. Assessment of platelet-derived growth factor using A splinted full thickness dermal wound model in bearded dragons (Pogona vitticeps).

    PubMed

    Keller, Krista A; Paul-Murphy, Joanne; Weber, E P Scott; Kass, Philip H; Guzman, Sanchez-Migallon David; Park, Shin Ae; Raghunathan, Vijay Krishna; Gustavsen, Kate A; Murphy, Christopher J

    2014-12-01

    Wounds in reptiles are a common reason for presentation to a veterinarian. At this time there is limited information on effective topical medications to aid in wound closure. The objectives of this study were to translate the splinted, full-thickness dermal wound model, validated in mice, to the bearded dragon (Pogona vitticeps) and to determine the effect of topical becaplermin (BP), a platelet-derived growth factor (0.01%), on the rate of wound closure. Ten bearded dragons were anesthetized and two full-thickness cutaneous wounds were made on the dorsum of each lizard. Encircling splints were applied surrounding each wound and subsequently covered by a semi-occlusive dressing. Five lizards had one wound treated with BP and the adjacent wound treated with a vehicle control. Five additional lizards had one wound treated with saline and the second wound treated with a vehicle control. Wounds were imaged daily, and the wound area was measured using digital image analysis. The change in percentage wound closure over 17 days and the time to 50% wound closure was compared among the four treatment groups. There was no significant difference in wound closure rates between BP-treated and saline-treated wounds or in the time to 50% wound closure between any treatments. Vehicle-treated wounds adjacent to saline-treated wounds closed significantly slower than did BP (P < 0.010), saline (P < 0.001), and vehicle-treated wounds adjacent to BP-treated wounds (P < 0.013). Our preliminary study indicates that the splinted wound model, with modifications, may be used to determine wound closure rates in bearded dragons. When compared with saline, BP did not have a significant effect on wound closure rates, while the vehicle alone delayed wound closure. Histologic analysis of experimentally created wounds throughout the wound healing process is needed to further evaluate the effects of these treatments on reptile dermal wound healing.

  8. Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

    PubMed

    Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

    2017-03-06

    Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2(cub/cub)) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2(cub/cub) mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2(cub/cub) and Rhbdf2(+/+) mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2(cub/cub) mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds.

  9. Porous microspheres as promising vehicles for the topical delivery of poorly soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro &in vivo.

    PubMed

    Zhang, Chen-Zhen; Niu, Jie; Chong, Yee-Song; Huang, Yan-Fen; Chu, Yang; Xie, Sheng-Yang; Jiang, Zhi-Hong; Peng, Li-Hua

    2016-12-01

    Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio, solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo. Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro. More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.

  10. Development of fibroblast culture in three-dimensional activated carbon fiber-based scaffold for wound healing.

    PubMed

    Huang, Wen-Ying; Yeh, Chia-Lin; Lin, Jui-Hsiang; Yang, Jai-Sing; Ko, Tse-Hao; Lin, Yu-Hsin

    2012-06-01

    This work developed a novel bi-layer wound dressing composed of 3D activated carbon fibers that allows facilitates fibroblast cell growth and migration to a wound site for tissue reconstruction, and the gentamicin is incorporated into a poly(γ-glutamic acid)/gelatin membrane to prevent bacterial infection. In an in vitro, field emission scanning electron microscopy shows that rat skin fibroblasts appeared and spread on the surface of activated carbon fibers, and penetrated the interior and exterior of the 3D activated carbon fiber construct to a depth of roughly 200 μm. An in vivo analysis shows that fibroblast cells containing the proposed 3D scaffold had the potential of a biologically functionalized dressing to accelerate wound closure. Additionally, fibroblasts migrated to the wound site in a bi-layer wound dressing containing fibroblasts, enhancing fibronectin and type I collagen expression, resulting in faster skin regeneration than that achieved with a Tegaderm™ hydrocolloid dressing or gauze.

  11. Endogenous N-acyl taurines regulate skin wound healing

    PubMed Central

    Sasso, Oscar; Pontis, Silvia; Armirotti, Andrea; Cardinali, Giorgia; Kovacs, Daniela; Migliore, Marco; Summa, Maria; Moreno-Sanz, Guillermo; Picardo, Mauro; Piomelli, Daniele

    2016-01-01

    The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two long-chain saturated NATs—N-tetracosanoyl-taurine [NAT(24:0)] and N-eicosanoyl-taurine [NAT(20:0)]—as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy. PMID:27412859

  12. Use of Equine Derived Pericardium as a Biological Cover To Promote Closure of a Complicated Wound With Associated Scleroderma and Raynaud's Disease .

    PubMed

    Mulder, Gerit; Lee, Daniel K

    2009-11-01

    A 39-year-old man with previously undiagnosed scleroderma was admitted to the UCSD Medical Center with bilateral, limb-threatening necrotic lower extremity ulcers extending to underlying fascia and muscle. Rather than amputate the extremities, the patient requested alternative treatment and underwent extensive tissue debridement followed by placement of an equine pericardium xenograft. Subsequent to treatment, the patient underwent weekly examinations and dressing changes without additional treatment. The patient was ambulating without assistance and with complete closure of all wounds in 10 weeks. The patient remained without wound recurrence at a recent 6-month follow-up visit .

  13. 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.

  14. In vivo evaluation of chitosan-PVP-titanium dioxide nanocomposite as wound dressing material.

    PubMed

    Archana, D; Singh, Brijesh K; Dutta, Joydeep; Dutta, P K

    2013-06-05

    In our present study, the blends of chitosan, poly(N-vinylpyrrolidone) (PVP) and titanium dioxide (TiO2) were investigated by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The size distribution of the TiO2 nanoparticles was measured using transmission electron microscope and scanning electron microscope. The studies on the mechanical properties of composite material indicate that the addition of TiO2 nanoparticles increases its strength. The prepared nanocomposite dressing has excellent antimicrobial efficacy and good biocompatibility against NIH3T3 and L929 fibroblast cells. Compared to conventional gauze, soframycin skin ointment and chitosan treated groups, the prepared nano dressing caused an accelerated healing of open excision type wounds in albino rat model. The synergistic effects of nanocomposite dressing material like good antibacterial ability, high swelling properties, high WVTR, excellent hydrophilic nature, biocompatibility, wound appearance and wound closure rate through in vivo test makes it a suitable candidate for wound healing applications.

  15. Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells.

    PubMed

    Syarina, Pauzi Nur Aimi; Karthivashan, Govindarajan; Abas, Faridah; Arulselvan, Palanisamy; Fakurazi, Sharida

    2015-01-01

    Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 μg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue-green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients.

  16. Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells

    PubMed Central

    Syarina, Pauzi Nur Aimi; Karthivashan, Govindarajan; Abas, Faridah; Arulselvan, Palanisamy; Fakurazi, Sharida

    2015-01-01

    Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 μg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue-green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients. PMID:27004048

  17. Hyperglycemia-Suppressed Expression of Serpine1 Contributes to Delayed Epithelial Wound Healing in Diabetic Mouse Corneas

    PubMed Central

    Sun, Haijing; Mi, Xiaofan; Gao, Nan; Yan, Chenxi; Yu, Fu-Shin

    2015-01-01

    Purpose. Patients with diabetes mellitus (DM) are at an increased risk for developing corneal complications, including delayed wound healing. The purpose of this study was to characterize the expression and the function of Serpine1 and other components of urokinase plasminogen activator (uPA)–proteolytic system in delayed epithelial wound healing in diabetic mouse corneas. Methods. Mice of the strain C57BL/6 were induced to develop diabetes by streptozotocin, and wound-healing assays were performed 10 weeks afterward. Gene expression and/or distribution were assessed by real-time PCR, Western blotting, and/or immunohistochemistry. The role of Serpine1 in mediating epithelial wound closure was determined by subconjunctival injections of neutralizing antibodies in either normal or recombinant protein in diabetic corneas. Enzyme assay for matrix metalloproteinase (MMP)-3 was also performed. Results. The expressions of Serpine1 (PAI-1), Plau (uPA), and Plaur (uPA receptor) were upregulated in response to wounding, and these upregulations were significantly suppressed by hyperglycemia. In healing epithelia, Plau and Serpine1 were abundantly expressed at the leading edge of the healing epithelia of normal and, to a lesser extent, diabetic corneas. Inhibition of Serpine1 delayed epithelial wound closure in normal corneas, whereas recombinant Serpine1 accelerated it in diabetic corneas. The Plau and MMP-3 mRNA levels and MMP-3 enzymatic activities were correlated to Serpine1 levels and/or the rates of epithelial wound closure. Conclusions. Serpine1 plays a role in mediating epithelial wound healing and its impaired expression may contribute to delayed wound healing in DM corneas. Hence, modulating uPA proteolytic pathway may represent a new approach for treating diabetic keratopathy. PMID:26024123

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

    PubMed Central

    Ko, Junghae; Jun, Haejung; Chung, Hyesook; Yoon, Changshin; Kim, Taekyoon; Kwon, Minjeong; Lee, Soonhee; Jung, Soojin; Kim, Mikyung

    2011-01-01

    Background To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds. Methods Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group. Results In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant. Conclusion Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different. PMID:21785742

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

    PubMed

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

    2009-12-01

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

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

    PubMed Central

    Rodrigues, Hosana G.; Vinolo, Marco A. R.; Sato, Fabio T.; Magdalon, Juliana; Kuhl, Carolina M. C.; Yamagata, Ana S.; Pessoa, Ana Flávia M.; Malheiros, Gabriella; dos Santos, Marinilce F.; Lima, Camila; Farsky, Sandra H.; Camara, Niels O. S.; Williner, Maria R.; Bernal, Claudio A.; Calder, Philip C.; Curi, Rui

    2016-01-01

    Introduction Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. Objectives We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. Methods Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. Results LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). Conclusions Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis. PMID:27764229

  1. Wound Care.

    PubMed

    Balsa, Ingrid M; Culp, William T N

    2015-09-01

    Wound care requires an understanding of normal wound healing, causes of delays of wound healing, and the management of wounds. Every wound must be treated as an individual with regard to cause, chronicity, location, and level of microbial contamination, as well as patient factors that affect wound healing. Knowledge of wound care products available and when negative pressure wound therapy and drain placement is appropriate can improve outcomes with wound healing. Inappropriate product use can cause delays in healing. As a wound healing progresses, management of a wound and the bandage material used must evolve.

  2. Resolution Mediator Chemerin15 Reprograms the Wound Microenvironment to Promote Repair and Reduce Scarring

    PubMed Central

    Cash, Jenna L.; Bass, Mark D.; Campbell, Jessica; Barnes, Matthew; Kubes, Paul; Martin, Paul

    2014-01-01

    Summary Disorders of cutaneous repair can cause disability or death given that skin functions as a protective barrier against the external environment. The inflammatory response triggered by tissue damage is thought to play both positive (e.g., pathogen-killing) and negative (e.g., scarring) roles in repair [1–3]. Inflammatory resolution mediators such as chemerin15 (C15) control the magnitude and duration of the inflammatory response; however, their role in wound repair and scarring is unknown [4–8]. Here, we show that the C15 precursor, chemerin, and its receptor, ChemR23, are both upregulated after skin damage and that the receptor is expressed by macrophages, neutrophils, and keratinocytes. Dynamic live-imaging studies of murine cutaneous wounds demonstrate that C15 delivery dampens the immediate intravascular inflammatory events, including platelet adhesion to neutrophils, an important event in driving leukocyte recruitment. C15 administration indirectly accelerates wound closure while altering fibroblast-mediated collagen deposition and alignment to reduce scarring. Macrophage recruitment is restricted to the immediate wound site rather than spilling extensively into the adjacent tissue as in control wounds, and macrophage phenotype in C15-treated wounds is skewed toward a less inflammatory phenotype with reduced iNOS, increased Arginase-1, and lower wound tumor necrosis factor α (TNF-α) expression. Modulation of inflammatory resolution pathways in acute and chronic wounds may therefore provide a novel therapeutic avenue to improve repair and reduce scarring. PMID:24881877

  3. Topical androgen antagonism promotes cutaneous wound healing without systemic androgen deprivation by blocking β-catenin nuclear translocation and cross-talk with TGF-β signaling in keratinocytes.

    PubMed

    Toraldo, Gianluca; Bhasin, Shalender; Bakhit, Mena; Guo, Wen; Serra, Carlo; Safer, Joshua D; Bhawan, Jag; Jasuja, Ravi

    2012-01-01

    Orchidectomy in rodents and lower testosterone levels in men are associated with improved cutaneous wound healing. However, due to the adverse effects on skeletal and sexual tissues, systemic androgen blockade is not a viable therapeutic intervention. Accordingly, we tested the hypothesis that topical application of an androgen antagonist would elicit accelerated wound healing without systemic androgen antagonism. Full-thickness cutaneous wounds were created on adult C57BL6/J mice. Daily topical application of androgen receptor antagonist, flutamide, resulted in improved gap closure similar to orchiectomized controls and faster than orchidectomized mice treated with topical testosterone. In vivo data showed that the effects of androgen antagonism on wound closure primarily accelerate keratinocytes migration without effecting wound contraction. Consequently, mechanisms of testosterone action on reepithelialization were investigated in vitro by scratch wounding assays in confluent keratinocytes. Testosterone inhibited keratinocyte migration and this effect was in part mediated through promotion of nuclear translocation of β-catenin and by attenuating transforming growth factor-β (TGF-β) signaling through β-catenin. The link between Wnt and TGF beta signaling was confirmed by blocking β-catenin and by following TGF-β-induced transcription of a luciferase reporter gene. Together, these data show that blockade of β-catenin can, as a potential target for novel therapeutic interventions, accelerate cutaneous wound healing.

  4. A modified collagen gel enhances healing outcome in a preclinical swine model of excisional wounds.

    PubMed

    Elgharably, Haytham; Roy, Sashwati; Khanna, Savita; Abas, Motaz; Dasghatak, Piya; Das, Amitava; Mohammed, Kareem; Sen, Chandan K

    2013-01-01

    Collagen-based dressings are of great interest in wound care. However, evidence supporting their mechanism of action is scanty. This work provides first results from a preclinical swine model of excisional wounds, elucidating the mechanism of action of a modified collagen gel (MCG) dressing. Following wounding, wound-edge tissue was collected at specific time intervals (3, 7, 14, and 21 days postwounding). On day 7, histological analysis showed significant increase in the length of rete ridges, suggesting improved biomechanical properties of the healing wound tissue. Rapid and transient mounting of inflammation is necessary for efficient healing. MCG significantly accelerated neutrophil and macrophage recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21. MCG induced monocyte chemotactic protein-1 expression in neutrophil-like human promyelocytic leukemia-60 cells in vitro. In vivo, MCG-treated wound tissue displayed elevated vascular endothelial growth factor expression. Consistently, MCG-treated wounds displayed significantly higher abundance of endothelial cells with increased blood flow to the wound area indicating improved vascularization. This observation was explained by the finding that MCG enhanced proliferation of wound-site endothelial cells. In MCG-treated wound tissue, Masson's trichrome and picrosirius red staining showed higher abundance of collagen and increased collagen type I:III ratio. This work presents first evidence from a preclinical setting explaining how a collagen-based dressing may improve wound closure by targeting multiple key mechanisms. The current findings warrant additional studies to determine whether the responses to the MCG are different from other collagen-based products used in clinical setting.

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

    PubMed Central

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

    2017-01-01

    Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair. PMID:28337222

  6. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review

    PubMed Central

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-01-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds. PMID:27679749

  7. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review.

    PubMed

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-09-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds.

  8. Silicone-coated non-woven polyester dressing enhances reepithelialisation in a sheep model of dermal wounds.

    PubMed

    Losi, Paola; Briganti, Enrica; Costa, Manolo; Sanguinetti, Elena; Soldani, Giorgio

    2012-09-01

    Negative-pressure wound therapy (NPWT) also known as V.A.C. (Vacuum-assisted closure), is widely used to manage various type of wounds and accelerate healing. NPWT has so far been delivered mainly via open-cell polyurethane (PU) foam or medical gauze. In this study an experimental setup of sheep wound model was used to evaluate, under NPWT conditions, the performance of a silicone-coated non-woven polyester (N-WPE) compared with PU foam and cotton hydrophilic gauze, used as reference materials. Animals were anesthetized with spontaneous breathing to create three 3 × 3 cm skin defects bilaterally; each animal received three different samples on each side (n = 6 in each experimental group) and was subjected to negative and continuous 125 mmHg pressure up to 16 days. Wound conditions after 1, 8 and 16 days of treatment with the wound dressings were evaluated based on gross and histological appearances. Skin defects treated with the silicone-coated N-WPE showed a significant decrease in wound size, an increase of re-epithelialization, collagen deposition and wound neovascularisation, and a minimal stickiness to the wound tissue, in comparison with gauze and PU foam. Taken all together these findings indicate that the silicone-coated N-WPE dressing enhances wound healing since stimulates higher granulation tissue formation and causes minor tissue trauma during dressing changes.

  9. Negative Pressure Wound Therapy

    PubMed Central

    2006-01-01

    follows: Randomized controlled trial (RCT) with a sample size of 20 or more Human study Published in English Summary of Findings Seven international health technology assessments on NPWT were identified. Included in this list of health technology assessments is the original health technology review on NPWT by the Medical Advisory Secretariat from 2004. The Medical Advisory Secretariat found that the health technology assessments consistently reported that NPWT may be useful for healing various types of wounds, but that its effectiveness could not be empirically quantified because the studies were poorly done, the patient populations and outcome measures could not be compared, and the sample sizes were small. Six RCTs were identified that compared NPWT to standard care. Five of the 6 studies were of low or very low quality according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. The low and very low quality RCTs were flawed owing to small sample sizes, inconsistent reporting of results, and patients lost to follow-up. The highest quality study, which forms the basis of this health technology policy assessment, found that: There was not a statistically significant difference (≥ 20%) between NPWT and standard care in the rate of complete wound closure in patients who had complete wound closure but did not undergo surgical wound closure (P = .15). The authors of this study did not report the length of time to complete wound closure between NPWT and standard care in patients who had complete wound closure but who did not undergo surgical wound closure There was no statistically significant difference (≥ 20%) in the rate of secondary amputations between the patients that received NPWT and those that had standard care (P = .06) There may be an increased risk of wound infection in patients that receive NPWT compared with those that receive standard care. Conclusion Based on the evidence to date, the clinical effectiveness of NPWT to

  10. Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats.

    PubMed

    Huang, Zhifeng; Lu, Meifei; Zhu, Guanghui; Gao, Hongchang; Xie, Liyun; Zhang, Xiaoqin; Ye, Chaohui; Wang, Yan; Sun, Chuanchuan; Li, Xiaokun

    2011-01-01

    Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor (rhaFGF) was site-selectively PEGylated with 20 kDa mPEG-butyraldehyde. Mono-PEGylated rhaFGF was purified to near homogeneity by Sephadex G 25-gel filtration followed by a Heparin Sepharose TM CL-6B affinity chromatography. PEGylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half-life time in vivo was significantly extended. Then, the physiological function of PEGylated rhaFGF on diabetic-wound healing was evaluated in type 1 diabetic Sprague Dawley rats. The results showed that, compared with the group of animal treated with native rhaFGF, the group treated with PEGylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor (TGF)-β expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEGylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEGylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF.

  11. Platelet lysate induces in vitro wound healing of human keratinocytes associated with a strong proinflammatory response.

    PubMed

    El Backly, Rania; Ulivi, Valentina; Tonachini, Laura; Cancedda, Ranieri; Descalzi, Fiorella; Mastrogiacomo, Maddalena

    2011-07-01

    Platelet lysates (PL), which are derived from platelets, are cocktails of growth factors and cytokines that can promote tissue regeneration. Until today, most studies have focused on growth factor content of platelets rather than on their potential as a reservoir of mediators and cytokines. Taking advantage of an in vitro scratch assay performed under both normal and inflammatory conditions, in the present work, we report that at physiologic concentrations, PL enhanced wound closure rates of NCTC 2544 human keratinocytes. This effect was clearly detectable 6 h after wounding. Moreover, PL induced a strong cell actin cytoskeletal re-organization that persisted up to 24 h. The accelerated wound closure promoted by PL, in either presence or absence of serum, was associated with a high expression of the inflammatory cytokine interleukin-8. Further, after 24 h PL treatment, confluent keratinocytes also expressed low amounts of interleukin-8 and of the antimicrobial peptide neutrophil gelatinase-associated lipocalin, which dramatically increased under inflammatory conditions. These effects were associated with activation of the inflammatory pathways, p38 mitogen-activated protein kinase, and NF-κB. Our findings support the concept that platelet-derived preparations could accelerate regeneration of difficult-to-heal wounds by triggering an inflammatory cascade and having an antimicrobial role.

  12. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis

    PubMed Central

    Zhang, Xiao-na; Ma, Ze-jun; Wang, Ying; Li, Yu-zhu; Sun, Bei; Guo, Xin; Pan, Cong-qing; Chen, Li-ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing. PMID:27057551

  13. Transforming growth factor-beta improves healing of radiation-impaired wounds

    SciTech Connect

    Bernstein, E.F.; Harisiadis, L.; Salomon, G.; Norton, J.; Sollberg, S.; Uitto, J.; Glatstein, E.; Glass, J.; Talbot, T.; Russo, A. )

    1991-09-01

    Exogenously applied TGF-{beta} 1 has been shown to increase wound strength in incisional wounds early in the healing process. An impaired wound healing model was first established in guinea pigs by isolating flaps of skin and irradiating the flaps to 15 Gray in one fraction using a 4-MeV linear accelerator. Incisions made 2 d after irradiation were excised 7 d later, and showed decreased linear wound bursting strength (WBS) as compared to non-irradiated control wounds on the contralateral side of each animal (p = 0.001). The effect of TGF-{beta}on healing of radiation-impaired wounds was studied using this model. Skin on both left and right sides of guinea pigs was irradiated as above. A linear incision was made in each side. Collagen with either 1, 5, or 20 micrograms of TGF-{beta} was applied to one side prior to closure with staples, whereas the contralateral side received saline in collagen. Wounds given either 1 or 5 micrograms of TGF-{beta} were found to be stronger than controls at 7 d (p less than 0.05), whereas those receiving the higher 20-micrograms dose were weaker than controls (p less than 0.05). Thus, TGF-{beta} in lower doses improved healing at 7 d but very large amounts of the growth factor actually impaired healing. In situ hybridization done on wound samples showed increased type I collagen gene expression by fibroblasts in wounds treated with 1 micrograms TGF-{beta} over control wounds. These results indicate that TGF-{beta} improved wound healing as demonstrated by increased WBS. This improvement is accompanied by an up-regulation of collagen gene expression by resident fibroblasts.

  14. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.

    PubMed

    Icli, Basak; Nabzdyk, Christoph S; Lujan-Hernandez, Jorge; Cahill, Meghan; Auster, Michael E; Wara, A K M; Sun, Xinghui; Ozdemir, Denizhan; Giatsidis, Giorgio; Orgill, Dennis P; Feinberg, Mark W

    2016-02-01

    Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

  15. Subcuticular closure versus Dermabond: a prospective randomized trial.

    PubMed

    Switzer, Erin F; Dinsmore, Robert C; North, James H

    2003-05-01

    2-Octylcyanoacrylate tissue adhesive (Dermabond, Ethicon, Inc, Somerville, NJ) is being used successfully for closure of minor lacerations. To date, however, there have been no studies evaluating its use in the operating room for surgical incisions. We conducted a prospective randomized trial to compare the closure of inguinal herniorrhaphy incisions using 2-octylcyanoacrylate tissue adhesive (Dermabond) with closures using 4-0 Monocryl (Ethicon, Inc) in a running subcuticular closure. A total of 46 incisions were randomized at the time of closure. Of these incisions 24 were randomized to Dermabond closure (TA) and 22 were randomized to subcuticular closure (SC). Performance measures included: time for closure, wound complications, and cosmesis. Cosmesis was evaluated by blinded evaluation of photographs of the incisions taken 4 weeks after surgery. Closure times for the TA group were faster than in the SC group (mean of 155 vs 286 seconds; P < 0.001). Wound complications were higher in the TA group (P = 0.045). Cosmesis was also felt to be better in the SC group with a score of 4.2 versus 3.88, but this did not reach statistical significance. Although the use of Dermabond did result in faster wound cultures it also resulted in an increase in wound complications. The difference in mean cosmetic score for each group was not statistically significant but trended toward better scores in the SC group. Based on these findings we do not feel Dermabond is an acceptable alternative to subcuticular suture closure in inguinal herniorrhaphy incisions.

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

    PubMed Central

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

    2017-01-01

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

  17. VAC therapy to promote wound healing after surgical revascularisation for critical lower limb ischaemia.

    PubMed

    De Caridi, Giovanni; Massara, Mafalda; Greco, Michele; Pipitò, Narayana; Spinelli, Francesco; Grande, Raffaele; Butrico, Lucia; de Franciscis, Stefano; Serra, Raffaele

    2016-06-01

    Vacuum-assisted closure (VAC) therapy is a new emerging non-invasive system in wound care, which speeds up wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates, and facilitating the removal of bacteria from the wound. The application of sub-atmospheric pressure on the lesions seems to alter the cytoskeleton of the cells on the wound bed, triggering a cascade of intracellular signals that increase the rate of cell division and subsequent formation of granulation tissue. The aim of this study is to analyse the results of VAC therapy used as an adjuvant therapy for the treatment of foot wounds in patients affected by critical limb ischaemia (CLI) (Rutherford 6 class) after distal surgical revascularisation, to promote and accelerate the healing of ulcers. Twenty-nine patients (20 males, 9 females; mean age 68·4) affected by CLI of Rutherford 6 class, after surgical revascularisation of the lower limb, underwent VAC therapy in order to speed up wound healing. Complete wound healing was achieved in 19 patients (65·51%), in an average period of 45·4 ± 25·6 days. VAC therapy is a valid aid, after surgical revascularisation, to achieve rapid healing of foot lesions in patients with CLI.

  18. 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.

  19. [Ozone-ultrasonic therapy in the treatment of purulent wounds].

    PubMed

    Lipatov, K V; Sopromadze, M A; Shekhter, A B; Rudenko, T G; Emel'ianov, A Iu

    2002-01-01

    Based on planimetric, bacteriologic and histologic study high efficiency of local ozonotherapy of wound in combination with low-frequency ultrasound was demonstrated experimentally on rat model of infected purulent skin wound. This method was used in 45 patients with purulent wounds of soft tissues (postoperative, posttraumatic, burn, sore spot) that led to fast cleaning of wound surface, decrease of bacterial contamination and granulations. It permitted to eliminate inflammation and to create optimum conditions for wound closure.

  20. The use of keratin-based wound products on refractory wounds.

    PubMed

    Batzer, Annette T; Marsh, Clive; Kirsner, Robert S

    2016-02-01

    Keratin proteins have been shown to play a key role in wound healing. Controlled keratin gene (KRT) expression promotes cell growth, migration and differentiation, and as an example of the importance of keratin proteins, absence of KRT17 has been shown to delay wound closure. In addition, downregulation of KRT6 and KRT16 in non-healing chronic venous ulcers suggests that deregulation of keratin expression contributes to non-healing phenotype. A sample of 45 chronic wounds of mixed aetiologies presenting in 31 patients were treated with keratin-based novel topical wound healing products. Thirty-seven wounds or 82% of wounds were either healed or reduced in size of >50% during treatment, with 29 (64%) healing completely and an additional 8 wounds experiencing 50% wound size reduction or greater. Of the wounds that responded, 15 required antimicrobial treatment during their course of treatment, suggesting that keratin dressing treatment should be interrupted briefly and then restarted when wound infection occur.

  1. Noninvasive and High-Resolution Optical Monitoring of Healing of Diabetic Dermal Excisional Wounds Implanted with Biodegradable In Situ Gelable Hydrogels

    PubMed Central

    Yuan, Zhijia; Zakhaleva, Julia; Ren, Hugang; Liu, Jingxuan; Chen, Weiliam

    2010-01-01

    Closure of diabetic dermal chronic wounds remains a clinical challenge. Implant-assisted healing is emerging as a potential class of therapy for dermal wound closure; this advancement has not been paralleled by the development in complementary diagnostic techniques to objectively monitor the wound-healing process in conjunction with assessing/monitoring of implant efficacy. Biopsies provide the most objective morphological assessments of wound healing; however, they not only perpetuate the wound presence but also increase the risk of infection. A noninvasive and high-resolution imaging technique is highly desirable to provide objective longitudinal diagnosis of implant-assisted wound healing. We investigated the feasibility of deploying optical coherence tomography (OCT) for noninvasive monitoring of the healing of full-thickness excisional dermal wounds implanted with a novel in situ gelable hydrogel composed of N-carboxyethyl chitosan, oxidized dextran, and hyaluronan, in both normal and db/db mice. The results showed that OCT was able to differentiate the morphological differences (e.g., thickness of dermis) between normal and diabetic mice as validated by their corresponding histological evaluations (p < 0.05). OCT could detect essential morphological changes during wound healing, including re-epithelization, inflammatory response, and granulation tissue formation as well as impaired wound repair in diabetic mice. Importantly, by tracking specific morphological changes in hydrogel-assisted wound healing (e.g., implants' degradation and resorption, cell-mediated hydrogel degradation, and accelerated re-epithelization), OCT could also be deployed to monitor and evaluate the transformation of implanted biomaterials, thus holding the promise for noninvasive and objective monitoring of wound healing longitudinally and for objective efficacy assessment of implantable therapeutics in tissue engineering. PMID:19496703

  2. Stress and wound healing.

    PubMed

    Cohen, I

    1979-01-01

    An experiment was performed to compare the effects of stressors--cold, heat and noise--on primary wound activity (i.e., wound closure in the first 24 h after wound infliction) and on rate of healing in mice. A significant correlation was found between reduced primary wound activity and a faster rate of healing. Conversely, a correlation was found between relatively greater primary wound activity and a slower rate of healing. A possible explanation of this correlation is a compensatory mechanism inherent to the skin healing process. This mechanism is visualized as (1) stress exposure affecting the skin by (a) causing it to become thinner and tauter and (b) causing it to have less elastic recoil; therefore, (2) when a square wound is produced in stressed skin, (a) the wound does not recoil readily or gapes soon after cutting and (b) a longer wound perimeter results. Because there is evidence that rate of healing is governed by cells on the wound perimeter, the greater the perimeter, the greater the number of cells that will undergo rapid mitosis and the faster will be the rate of healing. Therefore, stressed skin will heal at a faster rate, compensating for the loss of elasticity and cellular depletion caused by stress. This study is of interest to anthropology because it deals with dynamic adaptation, trying to grasp the meaning of the elusive endocrine interface between environmental stimulation and a measurable physical entity like healing. This work may have revealed a functional complex that is common to the healing of all mammalian skin, whereby retarding effects of stress on the healing process are obviated.

  3. IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice

    PubMed Central

    Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P.; Hackney, Jason A.; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M.; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

    2017-01-01

    Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU. PMID:28125663

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

    PubMed Central

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice. PMID:26057238

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

    PubMed

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

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

  6. Reduced Il17a expression distinguishes a Ly6c(lo)MHCII(hi) macrophage population promoting wound healing.

    PubMed

    Rodero, Mathieu P; Hodgson, Samantha S; Hollier, Brett; Combadiere, Christophe; Khosrotehrani, Kiarash

    2013-03-01

    Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6c(lo)MHCII(hi) "noninflammatory" subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88-/- models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A-/- mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.

  7. Evaluation of in situ injectable hydrogels as controlled release device for ANXA1 derived peptide in wound healing.

    PubMed

    Del Gaudio, Pasquale; De Cicco, Felicetta; Aquino, Rita P; Picerno, Patrizia; Russo, Paola; Dal Piaz, Fabrizio; Bizzarro, Valentina; Belvedere, Raffaella; Parente, Luca; Petrella, Antonello

    2015-01-22

    In this paper, for the first time, hydrogels containing Annexin A1 N-terminal derived peptide, Ac2-26, as a novel dressing were successfully developed for dermal wound repair application. High mannuronic (M) content alginate and low molecular weight chitosan have been used as hydrogel carrier. Peptide recovery analyses, FTIR studies and molecular modelling highlighted chemical interactions between peptide and hydrogel polymers. Ac2-26 resulted entrapped into chitosan hydrogel matrix that prevented its release, whereas such interaction in alginate hydrogel slowed down peptide diffusion enabling its sustained release till 72 h. In vivo wound healing studies conducted on mice dorsal wounds indicate that after the 9th day of post wounding Ac2-26/alginate hydrogels could significantly accelerate wound healing, with complete closure of the wound on day 14th. Therefore, these results suggest that the developed of Ac2-26 high M content alginate hydrogel could be a promising wound dressing with potential application in dermal wound healing.

  8. Anti-inflammatory glycosylated flavonoids as therapeutic agents for treatment of diabetes-impaired wounds.

    PubMed

    Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet; Serna-Saldívar, Sergio O

    2015-01-01

    Diabetes is a chronic disease that affects more than 387 million people worldwide. About 20% of patients diagnosed with diabetes develop diabetic foot ulcerations (DFU). Standard treatment of DFU includes wound debridement, infection control, revascularization and, in general, the acceleration of the healing process. Topical ointments containing flavonoids exert beneficial effects in wound healing process. Flavonoids increase the migration and proliferation of fibroblasts and collagen synthesis. Furthermore, most flavonoids exert antibacterial and astringent activities that help in infection control. Additionally, flavonoids possess antioxidant and anti-inflammatory activities reducing the reactive oxygen species and modulating the inflammatory pathways, respectively. Bioactivity of flavonoids can vary according to source, chemical structure and glycosylation pattern. In summary, topical application of flavonoids reduces epithelialization and wound closure time of DFU in diabetic patients.

  9. Total knee arthroplasty closure with barbed sutures.

    PubMed

    Eickmann, Tom; Quane, Erika

    2010-09-01

    Bidirectional barbed sutures, which do not require the tying of knots, have the potential to reduce closure times of total knee arthroplasty (TKA) wounds without adverse effect to wound security, cosmesis, or infection risk. In this retrospective study, data were reviewed from TKAs performed between January 2007 and September 2008. For 88 of these procedures, conventional absorbable sutures were used for interrupted closure of the retinacular and subcutaneous layers and for running closure of the subcuticular layer. For 90 procedures, bidirectional barbed absorbable sutures were used for running closure of the retinacular and subcutaneous layers. Surgeries performed with barbed sutures were significantly faster than those performed with conventional sutures (mean times of 74.3 minutes and 85.8 minutes, respectively, p < 0.001) with no detrimental clinical effects.

  10. Achieving closure at Fernald

    SciTech Connect

    Bradburne, John; Patton, Tisha C.

    2001-02-25

    When Fluor Fernald took over the management of the Fernald Environmental Management Project in 1992, the estimated closure date of the site was more than 25 years into the future. Fluor Fernald, in conjunction with DOE-Fernald, introduced the Accelerated Cleanup Plan, which was designed to substantially shorten that schedule and save taxpayers more than $3 billion. The management of Fluor Fernald believes there are three fundamental concerns that must be addressed by any contractor hoping to achieve closure of a site within the DOE complex. They are relationship management, resource management and contract management. Relationship management refers to the interaction between the site and local residents, regulators, union leadership, the workforce at large, the media, and any other interested stakeholder groups. Resource management is of course related to the effective administration of the site knowledge base and the skills of the workforce, the attraction and retention of qualified a nd competent technical personnel, and the best recognition and use of appropriate new technologies. Perhaps most importantly, resource management must also include a plan for survival in a flat-funding environment. Lastly, creative and disciplined contract management will be essential to effecting the closure of any DOE site. Fluor Fernald, together with DOE-Fernald, is breaking new ground in the closure arena, and ''business as usual'' has become a thing of the past. How Fluor Fernald has managed its work at the site over the last eight years, and how it will manage the new site closure contract in the future, will be an integral part of achieving successful closure at Fernald.

  11. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing

    PubMed Central

    Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G.; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

    2015-01-01

    Background. The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. Methods. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Results. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. Conclusions. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine. PMID:26539504

  12. Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing.

    PubMed

    Nosbaum, Audrey; Prevel, Nicolas; Truong, Hong-An; Mehta, Pooja; Ettinger, Monika; Scharschmidt, Tiffany C; Ali, Niwa H; Pauli, Mariela L; Abbas, Abul K; Rosenblum, Michael D

    2016-03-01

    Foxp3-expressing regulatory T cells (Tregs) reside in tissues where they control inflammation and mediate tissue-specific functions. The skin of mice and humans contain a large number of Tregs; however, the mechanisms of how these cells function in skin remain largely unknown. In this article, we show that Tregs facilitate cutaneous wound healing. Highly activated Tregs accumulated in skin early after wounding, and specific ablation of these cells resulted in delayed wound re-epithelialization and kinetics of wound closure. Tregs in wounded skin attenuated IFN-γ production and proinflammatory macrophage accumulation. Upon wounding, Tregs induce expression of the epidermal growth factor receptor (EGFR). Lineage-specific deletion of EGFR in Tregs resulted in reduced Treg accumulation and activation in wounded skin, delayed wound closure, and increased proinflammatory macrophage accumulation. Taken together, our results reveal a novel role for Tregs in facilitating skin wound repair and suggest that they use the EGFR pathway to mediate these effects.

  13. 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

  14. Forces driving epithelial wound healing

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  15. Retained wound vacuum foam in non-healing wounds: a real possibility.

    PubMed

    Mazoch, M; Montgomery, C

    2015-06-01

    Negative pressure wound therpay (NPWT) has revolutionised the management of chronic wounds, particularly pressure ulcers (PU). Frequently, PUs are too large to close primarily, so NPWT is used to assist in management on an outpatient basis. If not closely monitored, NPWT closure foam can be accidentally left in patients. Here we describe two cases where NPWT closure foam was left in patients resulting in persistent infections. Additionally, some suggestions of how to help avoid these should be 'never' events are provided.

  16. Desmoglein 3-Dependent Signaling Regulates Keratinocyte Migration and Wound Healing.

    PubMed

    Rötzer, Vera; Hartlieb, Eva; Winkler, Julia; Walter, Elias; Schlipp, Angela; Sardy, Miklós; Spindler, Volker; Waschke, Jens

    2016-01-01

    The desmosomal transmembrane adhesion molecules desmoglein 3 (Dsg3) and desmocollin 3 (Dsc3) are required for strong keratinocyte cohesion. Recently, we have shown that Dsg3 associates with p38 mitogen-activated protein kinase (p38MAPK) and suppresses its activity. Here, we further investigated the role of Dsg3-dependent control of p38MAPK function. Dsg3-deficient mice display recurrent spontaneously healing skin erosions. In lesional and perilesional biopsies, p38MAPK activation was detectable compared with control animals. This led us to speculate that Dsg3 regulates wound repair in a p38MAPK-dependent manner. Indeed, scratch-wounded keratinocyte monolayers exhibited p38MAPK activation and loss of Dsg3 in cells lining the wound edge. Human keratinocytes after silencing of Dsg3 as well as primary cells isolated from Dsg3 knockout animals exhibited accelerated migration, which was further corroborated in an ex vivo skin outgrowth assay. Importantly, migration was efficiently blocked by inhibition of p38MAPK, indicating that p38MAPK mediates the effects observed upon loss of Dsg3. In line with this, we show that levels of active p38MAPK associated with Dsc3 are increased in Dsg3-deficient cells. These data indicate that Dsg3 controls a switch from an adhesive to a migratory keratinocyte phenotype via p38MAPK inhibition. Thus, loss of Dsg3 adhesion may foster wound closure by allowing p38MAPK-dependent migration.

  17. The Use of NPWT-i Technology in Complex Surgical Wounds

    PubMed Central

    Ochoa, Robert A; Punch, Laurie; Van Epps, Jeffrey; Gordon-Burroughs, Sherilyn; Martinez, Sylvia

    2016-01-01

    Advanced wound management of complex surgical wounds remains a significant challenge as more patients are being hospitalized with infected wounds. Reducing recurrent infections and promoting granulation tissue formation is essential to overall wound healing. Wounds with acute infection and critical colonization require advanced multimodal approaches including systemic antibiotics, surgical debridement, and primary wound care. The goal in surgical wound management is to optimize clinical outcomes such as time to wound closure and functional recovery. A review of current literature suggests that negative pressure wound therapy with instillation (NPWT-i) is a viable adjunct therapy in the management of infected wounds especially in patients with medical comorbidities. The aim of this case series is to highlight the ability of NPWT-i as adjunct to prepare the wound bed for closure on infected surgical wounds that would normally require multiple operations to obtain source control. PMID:28083464

  18. The Use of NPWT-i Technology in Complex Surgical Wounds.

    PubMed

    Rupert, Paula; Ochoa, Robert A; Punch, Laurie; Van Epps, Jeffrey; Gordon-Burroughs, Sherilyn; Martinez, Sylvia

    2016-12-08

    Advanced wound management of complex surgical wounds remains a significant challenge as more patients are being hospitalized with infected wounds. Reducing recurrent infections and promoting granulation tissue formation is essential to overall wound healing. Wounds with acute infection and critical colonization require advanced multimodal approaches including systemic antibiotics, surgical debridement, and primary wound care. The goal in surgical wound management is to optimize clinical outcomes such as time to wound closure and functional recovery. A review of current literature suggests that negative pressure wound therapy with instillation (NPWT-i) is a viable adjunct therapy in the management of infected wounds especially in patients with medical comorbidities. The aim of this case series is to highlight the ability of NPWT-i as adjunct to prepare the wound bed for closure on infected surgical wounds that would normally require multiple operations to obtain source control.

  19. Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

    PubMed Central

    Mendoza Marí, Yssel; Fernández Mayola, Maday; Aguilera Barreto, Ana; García Ojalvo, Ariana; Bermúdez Alvarez, Yilian; Mir Benítez, Ana Janet; Berlanga Acosta, Jorge

    2016-01-01

    In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6) proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ) were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit's ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit's model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic. PMID:27200188

  20. Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds.

    PubMed

    Mendoza Marí, Yssel; Fernández Mayola, Maday; Aguilera Barreto, Ana; García Ojalvo, Ariana; Bermúdez Alvarez, Yilian; Mir Benítez, Ana Janet; Berlanga Acosta, Jorge

    2016-01-01

    In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6) proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ) were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit's ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit's model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

  1. Recent advances in topical wound care.

    PubMed

    Sarabahi, Sujata

    2012-05-01

    There are a wide variety of dressing techniques and materials available for management of both acute wounds and chronic non-healing wounds. The primary objective in both the cases is to achieve a healed closed wound. However, in a chronic wound the dressing may be required for preparing the wound bed for further operative procedures such as skin grafting. An ideal dressing material should not only accelerate wound healing but also reduce loss of protein, electrolytes and fluid from the wound, and help to minimize pain and infection. The present dictum is to promote the concept of moist wound healing. This is in sharp contrast to the earlier practice of exposure method of wound management wherein the wound was allowed to dry. It can be quite a challenge for any physician to choose an appropriate dressing material when faced with a wound. Since wound care is undergoing a constant change and new products are being introduced into the market frequently, one needs to keep abreast of their effect on wound healing. This article emphasizes on the importance of assessment of the wound bed, the amount of drainage, depth of damage, presence of infection and location of wound. These characteristics will help any clinician decide on which product to use and where,in order to get optimal wound healing. However, there are no 'magical dressings'. Dressings are one important aspect that promotes wound healing apart from treating the underlying cause and other supportive measures like nutrition and systemic antibiotics need to be given equal attention.

  2. Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization

    PubMed Central

    Mirabelli, Pierfrancesco; Xeroudaki, Maria; Parekh, Mohit; Bertolin, Marina; Breda, Claudia; Cagini, Carlo; Ponzin, Diego; Lagali, Neil; Ferrari, Stefano

    2016-01-01

    Background and Purpose The connexin 43 (Cx43) mimetic peptide Gap27 was designed to transiently block the function of this gap junction. This study was undertaken to investigate the effect of Gap27 on corneal healing, inflammation and neovascularization. Experimental Approach The effect of Gap27 on wound healing, inflammation and vascularization was assessed in primary human corneal epithelial cells (HCEC) in vitro and whole human corneas ex vivo, and in an in vivo rat wound healing model. Key Results Gap27 enhanced the wound closure of HCEC in vitro and accelerated wound closure and stratification of epithelium in human corneas ex vivo, but did not suppress the corneal release of inflammatory mediators IL‐6 or TNF‐α in vivo. In human corneas ex vivo, F4/80 positive macrophages were observed around the wound site. In vivo, topical Gap27 treatment enhanced the speed and density of early granulocyte infiltration into rat corneas. After 7 days, the expressions of TNF‐α and TGFβ1 were elevated and correlated with inflammatory cell accumulation in the tissue. Additionally, Gap27 did not suppress VEGF release in organotypic culture, nor did it suppress early or late VEGFA expression or neovascularization in vivo. Conclusions and Implications Gap27 can be effective in promoting the healing of superficial epithelial wounds, but in deep stromal wounds it has the potential to promote inflammatory cell migration and accumulation in the tissue and does not suppress the subsequent neovascularization response. These results support the proposal that Gap27 acts as a healing agent in the transient, early stages of corneal epithelial wounding. PMID:27472295

  3. Effect of Powdered Shells of the Snail Megalobulimus lopesi on Secondary-Intention Wound Healing in an Animal Model

    PubMed Central

    Andrade, Paulo Henrique Muleta; Schmidt Rondon, Eric; Carollo, Carlos Alexandre; Rodrigues Macedo, Maria Lígia; Viana, Luiz Henrique; Schiaveto de Souza, Albert; Turatti Oliveira, Carolina; Cepa Matos, Maria de Fatima

    2015-01-01

    Topical administration of powdered shells of the land snail Megalobulimus lopesi was evaluated in Wistar rats for their healing activity in an excision wound model. The animals were distributed into three groups—G1 (control): no therapeutic intervention; G2 (vehicle controls): Lanette cream once daily; G3 (experimental animals): treated with powdered shells. Variables investigated were: wound area contraction, angiogenic activity, morphometric data, leukocytic inflammatory infiltrate, and total leukocyte count in peripheral blood. Thermogravimetric analysis and quantification and characterization of powdered shell proteins were also performed. Wound area on days 3, 7, and 14 was smaller in G3, besides presenting wound closure on day 21 for all these animals. Topical administration of the powdered shells also led to an increased number of vessels at the wound site, higher leukocyte counts in peripheral blood, and increased leukocytic inflammatory infiltrate. The results lend support to the southern Brazilian folk use of M. lopesi powdered shells, as shown by the enhanced secondary-intention healing achieved with their topical administration to wounds in rats. Topical administration caused inflammatory response modulation, crucial to accelerating the healing process, the chronification of which increases the risks of wound contamination by opportunistic pathogens. PMID:25821475

  4. Antibodies to wounded tissue enhance cutaneous wound healing.

    PubMed

    Nishio, Naomi; Ito, Sachiko; Suzuki, Haruhiko; Isobe, Ken-ichi

    2009-11-01

    The wound repair process is a highly ordered sequence of events that encompasses haemostasis, inflammatory cell infiltration, tissue regrowth and remodelling. Wound healing follows tissue destruction so we hypothesized that antibodies might bind to wounded tissues, which would facilitate the engulfment of damaged tissues by macrophages. Here, we show that B cells, which produce antibodies to damaged tissues, are engaged in the process of wound healing. Splenectomy delayed wound healing, and transfer of spleen cells into splenectomized mice recovered the delay in wound healing. Furthermore, wound healing in splenectomized nude mice was also delayed. Transfer of enriched B220(+) cells by magnetic beads accelerated wound healing in splenectomized mice. We detected immunoglobulin G1 (IgG1) binding to wounded tissues by using fluorescein isothiocyanate-labelled anti-IgG1 6-24 hr after wounding. Splenectomy reduced the amount of IgG1 binding to wounded tissues. Immunoblotting studies revealed several bands, which were reduced by splenectomy. Using immunoprecipitation with anti-IgG bound to protein G we found that the intensity of several bands was lower in the serum from splenectomized mice than in that from sham-operated mice. These bands were matched to myosin IIA, carbamoyl-phosphate synthase, argininosuccinate synthase, actin and alpha-actinin-4 by liquid chromatography tandem mass spectrometry analysis.

  5. Duct closure

    DOEpatents

    Vowell, Kennison L.

    1987-01-01

    A closure for an inclined duct having an open upper end and defining downwardly extending passageway. The closure includes a cap for sealing engagement with the open upper end of the duct. Associated with the cap are an array of vertically aligned plug members, each of which has a cross-sectional area substantially conforming to the cross-sectional area of the passageway at least adjacent the upper end of the passageway. The plug members are interconnected in a manner to provide for free movement only in the plane in which the duct is inclined. The uppermost plug member is attached to the cap means and the cap means is in turn connected to a hoist means which is located directly over the open end of the duct.

  6. Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells.

    PubMed

    Kim, Sung-Ae; Ryu, Han-Won; Lee, Kyu-Suk; Cho, Jae-We

    2013-02-01

    Application of autologous platelet-rich plasma (PRP) has been used for chronic wound healing. The aim of this study was to evaluate the effect of PRP on the wound healing processes of both acute and chronic ulcers and the underlying molecular mechanisms involved. We treated 16 patients affected by various acute and chronic ulcers with PRP. We performed molecular studies of cell proliferation, migration assays, immunoblotting and chloramphenicol acetyltransferase (CAT) assays in PRP-treated HaCaT keratinocyte cells. PRP treatment induced increased rates of cell proliferation and cell migration of HaCaT cells. In addition, the expression of cyclin A and cyclin dependent kinase (CDK) 4 proteins was markedly increased with a low concentration (0.5%) of PRP treatment in HaCaT cells. In 11 patients with chronic ulcers, including stasis ulcers, diabetic ulcers, venous leg ulcers, livedoid vasculitis, claw foot and traumatic ulcers, 9 patients showed 90-100% epithelization after 15.18 days. In 5 patients with acute ulcers, such as dehiscence, open wound and burn wound, 80-100% epithelization was achieved between 4 to 20 days. Topical application of PRP to acute and chronic skin ulcers significantly accelerated the epithelization process, likely through upregulation of the cell cycle regulatory proteins cyclin A and CDK4.

  7. Closure device

    SciTech Connect

    Sable, D. E.

    1985-06-11

    A closure device connectible to a well head through which the polished rod of a rod string extends into a well tubing for operating pump means for moving well fluids to a surface flow conductor, the closure device having a tubular ram provided with a packing or plug for closing an annular passage between the polished rod and a tubular body connected to the well head above a lateral port of the tubular body, the tubular ram and the tubular body having thread means for moving the plug between an operative lower position wherein it closes the annular passage when the rod string is stationary and on inoperative upper position; seal means between the ram and the polished rod spaced above the plug; and a plurality of independent seal means between the ram and the tubular body operative when the plug is in its inoperative position. The plug of the closure device is especially adapted to operate under high temperature and pressure conditions of the well, as during steam injection operations when the rod string is stationary, to protect the seal means from high pressures and temperatures as well as any fluids which may be corrosive or otherwise deleterious to the substance of which the seal means are made.

  8. Full-thickness splinted skin wound healing models in db/db and heterozygous mice: implications for wound healing impairment.

    PubMed

    Park, Shin Ae; Teixeira, Leandro B C; Raghunathan, Vijay Krishna; Covert, Jill; Dubielzig, Richard R; Isseroff, Roslyn Rivkah; Schurr, Michael; Abbott, Nicholas L; McAnulty, Jonathan; Murphy, Christopher J

    2014-01-01

    The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.

  9. Amelioration of excision wounds by topical application of green synthesized, formulated silver and gold nanoparticles in albino Wistar rats.

    PubMed

    Naraginti, Saraschandra; Kumari, P Lakshmi; Das, Raunak Kumar; Sivakumar, A; Patil, Sagar Hindurao; Andhalkar, Vaibhav Vilas

    2016-05-01

    Wound healing, a complex biological process, has attained a lot of attention as dermatologists are primarily interested in stimulated wound closure without formation of scar or a faint scar. The recent upsurgence of nanotechnology has provided novel therapeutic materials in the form of silver and gold nanoparticles which accelerate the wound healing process. The effect of formulated nanoparticles using Coleus forskohlii root extract (green synthesized) has been tried out for ameliorating full thickness excision wounds in albino Wistar male rats. The evaluation of in vivo activity of nanoparticles in wound healing was carried out on open wounds made by excision on the dorsal sides of albino Wistar rats under anesthesia, and the healing of the wounds was assessed. Histological aspects of the healing process were studied by a HE (Hematoxylin and Eosin) staining method to assess various degrees of re-epithelialization and the linear alignment of the granulation tissue whereas Van Gieson's histochemical staining was performed to observe collagen fibers. The healing action shown by the formulated nanoparticles was remarkable during the early stages of wound healing, which resulted in the substantial reduction of the whole healing period. Topical application of formulated gold nanoparticles was found to be more effective in suppressing inflammation and stimulating re-epithelialization compared to silver nanoparticles during the healing process. The results throw light on the amelioration of excision wounds using nanoparticles which could be a novel therapeutic way of improving wound healing in clinical practice. The mechanism of advanced healing action of both types of nanoparticles could be due to their antimicrobial, antioxidant and anti-inflammatory properties.

  10. Autologous platelet concentrate and vacuum-assisted closure device use in a nonhealing total knee replacement.

    PubMed

    Klayman, Myra H; Trowbridge, Cody C; Stammers, Alfred H; Wolfgang, Gary L; Zijerdi, David A; Bitterly, Thomas J

    2006-03-01

    Following a total knee replacement surgery, a 51-year-old insulin-dependent patient presented with complications of impaired healing and postoperative trauma to the wound site. The inability of this leg wound to heal placed this patient at risk of amputation. Vacuum-assisted closure therapy was initiated at postoperative day 53; after 100 days of protracted wound history a series of treatments with topical platelet concentrates were added to the vacuum assisted closure therapy and conventional wound care therapy. The previous nonhealing wound presented with good granulation and margination that enabled a skin graft with good take on postoperative day 150.

  11. Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented With Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds.

    PubMed

    Yates, Cecelia C; Nuschke, Austin; Rodrigues, Melanie; Whaley, Diana; Dechant, Jason J; Taylor, Donald P; Wells, Alan

    2017-01-24

    Mesenchymal stem cells (MSCs) remain of great interest in regenerative medicine because of their ability to home to sites of injury, differentiate into a variety of relevant lineages, and modulate inflammation and angiogenesis through paracrine activity. Many studies have found that despite the promise of MSC therapy, cell survival upon implant is highly limited and greatly reduces the therapeutic utility of MSCs. The matrikine tenascin C, a protein expressed often at the edges of a healing wound, contains unique EGF-like repeats that are able to bind EGFR at low affinities and induce downstream prosurvival signaling without inducing receptor internalization. In this study, we utilized tenascin C in a collagen/GAG-based polymer (TPolymer) that has been shown to be beneficial for skin wound healing, incorporating human MSCs into the polymer prior to application to mouse punch biopsy wound beds. We found that the TPolymer was able to promote MSC survival for 21 days in vivo, leading to associated improvements in wound healing such as dermal maturation and collagen content. This was most marked in a model of hypertrophic scarring, in which the scar formation was limited. This approach also reduced the inflammatory response in the wound bed, limiting CD3e+ cell invasion by approximately 50% in the early wound-healing process, while increasing the numbers of endothelial cells during the first week of wound healing as well. Ultimately, this matrikine-based approach to improving MSC survival may be of great use across a variety of cell therapies utilizing matrices as delivery vehicles for cells.

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

    PubMed Central

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

    2014-01-01

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

  13. Closure of the open abdomen.

    PubMed

    Björck, Martin; D'Amours, Scott K; Hamilton, A E Ricardo

    2011-07-01

    The open abdomen is a valuable tool in the management of patients with intra-abdominal hypertension and abdominal compartment syndrome. The longer an abdomen is left open, the greater the potential morbidity, however. From the very start, specific measures should be considered to increase the likelihood of definitive closure and prevent the development of visceral adhesions, lateralization, and/or loss of skin and fascia, ileus, fistulae, and malnutrition. Early definitive closure of all abdominal wall layers is the short-term goal of management once the need for the open abdomen has resolved. Several devices and strategies improve the chances for definitive closure. If a frozen abdomen develops, split-thickness skin grafting of a granulating open abdominal wound base is an alternative. Early coverage of the exposed viscera and acceptance of a large abdominal hernia permit earlier reversal of the catabolic state and lower the risk of fistula formation. When a stoma is required, sealing and separation can become problematic. If a fistula develops, a more complex situation prevails, requiring specific techniques to isolate its output and a longer-term strategy to restore intestinal continuity. Planning the closure of an open abdomen is a process that starts on the first day that the abdomen is opened. Multiple factors need to be addressed, optimized, and controlled to achieve the best outcome.

  14. Red Deer Antler Extract Accelerates Hair Growth by Stimulating Expression of Insulin-like Growth Factor I in Full-thickness Wound Healing Rat Model.

    PubMed

    Yang, ZhiHong; Gu, LiJuan; Zhang, DongLiang; Li, Zheng; Li, JingJie; Lee, MiRa; Wang, ChunYan; Wang, Zhen; Cho, JeongHee; Sung, Changkeun

    2012-05-01

    In order to investigate and evaluate the effects of red deer antlers on hair growth in the full-thickness wound healing model, Sprague-Dawley rats were given incision wounds through the full thickness of their dorsal skin and deer antler was applied for 40 days. At specified intervals thereafter (4, 8, 16, 32 and 40 days), the animals were sacrificed and the wound site skins were excised, processed, and sectioned. At post-injury days 16, 32 and 40, longer and more active new hair appeared around the healing wound of antler-treated skin. Histological studies showed that the antler extract markedly increases the depth, size, and number of hair follicles. Expression of IGF-I (insulin-like growth factor) mRNA was detected by RT-PCR and real time RT-PCR. The result showed that the expression of IGF-I (days 16, 32, and 40) was obviously up-regulated in antler-treated skins compared to control skins. Similar results were seen in the ELISA analysis to quantify the IGF-I expression. These results support the notion that wound healing can cause hair growth by enhancing the expression of IGF-I. Deer antler extract appears to have the potential to promote hair growth and could be used in hair growth products.

  15. The Role of Chemokines in Mesenchymal Stem Cell Homing to Wounds

    PubMed Central

    Hocking, Anne M.

    2015-01-01

    Significance: Mesenchymal stem cells (MSCs) are being administered to cutaneous wounds with the goal of accelerating wound closure and promoting regeneration instead of scar formation. An ongoing challenge for cell-based therapies is achieving effective and optimal targeted delivery and engraftment at the site of injury. Contributing to this challenge is our incomplete understanding of endogenous MSC homing to sites of injury. Recent Advances: Chemokines and their receptors are now recognized as important mediators of stem cell homing. To date, the most studied chemokine–chemokine receptor axis in MSC homing to wounds is CXCL12-CXCR4 but recent work suggests that CCL27-CCR10 and CCL21-CCR7 may also be involved. Critical Issues: Strategies to enhance chemokine-mediated MSC homing to wounds are using a variety of approaches to amplify the chemokine signal at the wound site and/or overexpress specific chemokine receptors on the surface of the MSC. Future Directions: Harnessing chemokine signaling may enhance the therapeutic effects of stem cell therapy by increasing the number of both exogenous and endogenous stem cells recruited to the site of injury. Alternatively, chemokine-based therapies directly targeting endogenous stem cells may circumvent the need for the time-consuming and costly isolation and expansion of autologous stem cells prior to therapeutic administration. PMID:26543676

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

    PubMed

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

    2013-12-01

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

  17. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats.

    PubMed

    Zhang, Jianying; Yuan, Ting; Wang, James H-C

    2016-02-23

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients.

  18. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats

    PubMed Central

    Zhang, Jianying; Yuan, Ting; Wang, James H-C.

    2016-01-01

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients. PMID:26885754

  19. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

    PubMed

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

    2015-05-01

    Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats.

  20. Effect of low-power luminescent irradiation on surgical and burn wounds of soft tissues

    NASA Astrophysics Data System (ADS)

    Monich, Victor A.; Malinovskaya, Svetlana L.; Lokhmachova, Elvira; Vorobjev, Andrei

    1996-11-01

    It is shown, that direct, of low-intensity luminescent incoherent radiation (LUMIR) exposure on the surgery skin wound, causes the acceleration of wound healing in rats. The influence of LUMIR spectrum at the wound healing processes was found.

  1. Topical erythropoietin promotes wound repair in diabetic rats.

    PubMed

    Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

    2010-01-01

    Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

  2. Facial bite wounds: management update.

    PubMed

    Stefanopoulos, P K; Tarantzopoulou, A D

    2005-07-01

    Bite wounds are frequently located on the face; injuries inflicted by dogs are most common, especially in children. Bacteriology of infected dog and cat bite wounds includes Pasteurella multocida, Staphylococcus aureus, viridans streptococci, Capnocytophaga canimorsus, and oral anaerobes. Infected human bites yield a similar spectrum of bacteria except for Pasteurellae and C. canimorsus; instead human bites are frequently complicated by Eikenella corrodens. Antibiotic therapy against these bacteria is indicated both for infected bite wounds and fresh wounds considered at risk for infection. Amoxicillin-clavulanate (and other combinations of extended-spectrum penicillins with beta-lactamase inhibitors) and moxifloxacin offer the best in vitro coverage of the pathogenic flora. Initial wound management consisting in irrigation and debridement is at least equally important with antibiotics for prevention of infection. The need for prophylaxis against systemic infectious complications, particularly tetanus, should also be evaluated. Primary surgical repair is the treatment of choice for most clinically uninfected facial bite wounds, whereas delayed closure should be reserved for certain high risk or already infected wounds. Avulsive injuries with significant tissue loss represent the most difficult cases for definitive management and are also those most likely to require hospitalization.

  3. Electrospun Tropoelastin for Delivery of Therapeutic Adipose-Derived Stem Cells to Full-Thickness Dermal Wounds

    PubMed Central

    Machula, Hans; Ensley, Burt; Kellar, Robert

    2014-01-01

    Objective: To evaluate the physiological effects of electrospun tropoelastin scaffolds as therapeutic adipose-derived stem cell (ADSC) delivery vehicles for the treatment of full-thickness dermal wounds. Approach: Using the process of electrospinning, several prototype microfiber scaffolds were created with tropoelastin. Initial testing of scaffold biocompatibility was performed in vitro through ADSC culture, followed by scanning electron microscopy (SEM) for assessment of ADSC attachment, morphology, and new extracellular matrix (ECM) deposition. The wound healing effects of ADSC-seeded scaffolds were then evaluated in a murine dermal excisional wound model. Results: For the in vitro study, SEM revealed exceptional biocompatibility of electrospun tropoelastin for ADSCs. In the wound-healing study, ADSC-treated groups demonstrated significantly enhanced wound closure and epithelial thickness compared to controls. Innovation: This is the first report on the use of tropoelastin-based biomaterials as delivery vehicles for therapeutic ADSCs. Conclusion: We have demonstrated that tropoelastin-based ADSC delivery vehicles significantly accelerate wound healing compared to controls that represent the current clinical standard of care. Furthermore, the unique mechanical and biochemical characteristics of tropoelastin may favor its use over other biological or synthetic scaffolds for the treatment of certain pathologies due to its unique intrinsic mechanical properties. PMID:24804156

  4. CLOSURE DEVICE

    DOEpatents

    Linzell, S.M.; Dorcy, D.J.

    1958-08-26

    A quick opening type of stuffing box employing two banks of rotatable shoes, each of which has a caraming action that forces a neoprene sealing surface against a pipe or rod where it passes through a wall is presented. A ring having a handle or wrench attached is placed eccentric to and between the two banks of shoes. Head bolts from the shoes fit into slots in this ring, which are so arranged that when the ring is rotated a quarter turn in one direction the shoes are thrust inwardly to cramp the neopnrene about the pipe, malting a tight seal. Moving the ring in the reverse direction moves the shoes outwardly and frees the pipe which then may be readily removed from the stuffing box. This device has particular application as a closure for the end of a coolant tube of a neutronic reactor.

  5. [Application of modern wound dressings in the treatment of chronic wounds].

    PubMed

    Triller, Ciril; Huljev, Dubravko; Smrke, Dragica Maja

    2012-10-01

    Chronic and acute infected wounds can pose a major clinical problem because of associated complications and slow healing. In addition to classic preparations for wound treatment, an array of modern dressings for chronic wound care are currently available on the market. These dressings are intended for the wounds due to intralesional physiological, pathophysiological and pathological causes and which failed to heal as expected upon the use of standard procedures. Classic materials such as gauze and bandage are now considered obsolete and of just historical relevance because modern materials employed in wound treatment, such as moisture, warmth and appropriate pH are known to ensure optimal conditions for wound healing. Modern wound dressings absorb wound discharge, reduce bacterial contamination, while protecting wound surrounding from secondary infection and preventing transfer of infection from the surrounding area onto the wound surface. The use of modern wound dressings is only justified when the cause of wound development has been established or chronic wound due to the underlying disease has been diagnosed. Wound dressing is chosen according to wound characteristics and by experience. We believe that the main advantages of modern wound dressings versus classic materials include more efficient wound cleaning, simpler placement of the dressing, reduced pain to touch, decreased sticking to the wound surface, and increased capacity of absorbing wound exudate. Modern wound dressings accelerate the formation of granulation tissue, reduce the length of possible hospital stay and facilitate personnel work. Thus, the overall cost of treatment is reduced, although the price of modern wound dressings is higher than that of classic materials. All types of modern wound dressings, their characteristics and indications for use are described.

  6. Inhibition of Pseudomonas aeruginosa biofilm formation on wound dressings

    PubMed Central

    Brandenburg, Kenneth S.; Calderon, Diego F.; Kierski, Patricia R.; Brown, Amanda L.; Shah, Nihar M.; Abbott, Nicholas L.; Schurr, Michael J.; Murphy, Christopher J.; McAnulty, Jonathan F.; Czuprynski, Charles J.

    2016-01-01

    Chronic non-healing skin wounds often contain bacterial biofilms that prevent normal wound healing and closure and present challenges to the use of conventional wound dressings. We investigated inhibition of Pseudomonas aeruginosa biofilm formation, a common pathogen of chronic skin wounds, on a commercially available biological wound dressing. Building upon prior reports, we examined whether the amino acid tryptophan would inhibit P. aeruginosa biofilm formation on the 3-dimensional surface of the biological dressing. Bacterial biomass and biofilm polysaccharides were quantified using crystal violet staining or an enzyme linked lectin, respectively. Bacterial cells and biofilm matrix adherent to the wound dressing were visualized through scanning electron microscopy. D-/L-tryptophan inhibited P. aeruginosa biofilm formation on the wound dressing in a dose dependent manner and was not directly cytotoxic to immortalized human keratinocytes although there was some reduction in cellular metabolism or enzymatic activity. More importantly, D-/L-tryptophan did not impair wound healing in a splinted skin wound murine model. Furthermore, wound closure was improved when D-/L-tryptophan treated wound dressing with P. aeruginosa biofilms were compared with untreated dressings. These findings indicate that tryptophan may prove useful for integration into wound dressings to inhibit biofilm formation and promote wound healing. PMID:26342168

  7. Negative Pressure Wound Therapy: Experience in 45 Dogs

    PubMed Central

    Pitt, Kathryn A.; Stanley, Bryden J.

    2016-01-01

    Objective To report experience with negative pressure wound therapy (NPWT) in 45 consecutive dogs admitted with extensive cutaneous wounds and to determine if NPWT is feasible in veterinary hospital practice. Study Design Prospective descriptive study Animals Dogs (n = 45) Methods Collected data were organized into 6 categories: patient data, wound data, NPWT data, adjunctive treatments, complications, and final outcome Results Wounds (53 in 45 dogs) were largely traumatic in origin, and distributed fairly evenly to the trunk, proximal and distal aspects of the limbs. Most wounds (34 dogs, 76%) had no granulation tissue and were treated a mean of 4.2 days after wounding, whereas 11 dogs had granulating wounds that were initially treated a mean of 87 days after wounding. Median NPWT use was 3 days with a mean hospitalization of 7.8 days. Most wounds (33; 62%) were closed surgically after NPWT and were healed by 14 days. The other 18 wounds healed (mean, 21 days) by second intention after hospital discharge. Overall, 96% of the wounds healed; 2 dogs died before definitive closure could be attempted. Conclusion NPWT is applicable to a wide variety of canine wounds is well tolerated, allows for several days between dressing changes, and can used to optimize the wound bed for surgical closure or second intention healing. PMID:24512302

  8. Institution Closures.

    ERIC Educational Resources Information Center

    Hayden, Mary F., Ed.; And Others

    1995-01-01

    This newsletter theme issue focuses on the need to accelerate the closing of institutions for people with mental retardation. Articles are by both current and former residents of institutions and by professionals, and include: "The Realities of Institutions" (Tia Nelis); "I Cry Out So That I Won't Go Insane" (Mary F. Hayden); "Trends in…

  9. Camel whey protein enhances diabetic wound healing in a streptozotocin-induced diabetic mouse model: the critical role of β-Defensin-1, -2 and -3

    PubMed Central

    2013-01-01

    Background Delayed wound healing is considered one of the most serious diabetes-associated complications. The presence of replicating organisms such as bacteria within a diabetic’s wound is considered one of the most important factors that impair cutaneous wound healing and the potential cellular and/or molecular mechanisms that are involved in the healing process. Defensins, which are anti-microbial peptides, have potent bactericidal activity against a wide spectrum of the bacterial and fungal organisms that are commonly responsible for wound infections. We recently demonstrated that camel whey proteins (WPs) expedite the healing of diabetic wounds by enhancing the immune response of wounded tissue cells and by alleviating some of the diabetic complications. Methods In the present study, we investigated the effects of WP supplementation on the mRNA and protein expression levels of β-defensin-1 (BD-1), 2 and 3 and subsequently on the wound healing process in a streptozotocin (STZ)-induced diabetic mouse model. In this study, three groups of mice were used (10 mice per group): group 1, the non-diabetic mice (control); group 2, the diabetic mice; and group 3, the diabetic mice that received a daily supplement of undenatured WP (100 mg/kg of body weight) via oral gavage for 1 month. Results Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound closure that was characterized by a reduction in hydroxyproline content (indicator of collagen deposition), a marked elevation in free radical levels and a prolonged elevation in the levels of inflammatory cytokines, including interleukin-6 (IL-6), transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α). Interestingly, compared with the diabetic mice that did not receive WP supplementation, the diabetic mice with WP had an accelerated closure and healing process of their wounds. The WP supplementation also decreased their levels of free radicals and restored their

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

    PubMed

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

    2017-03-01

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

  11. Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds.

    PubMed

    Xu, Kedi; Cantu, David Antonio; Fu, Yao; Kim, Jaehyup; Zheng, Xiaoxiang; Hematti, Peiman; Kao, W John

    2013-11-01

    Mesenchymal stromal/stem cells (MSCs) are considered promising cellular therapeutics in the fields of tissue engineering and regenerative medicine. MSCs secrete high concentrations of immunomodulatory cytokines and growth factors, which exert paracrine effects on infiltrating immune and resident cells in the wound microenvironment that could favorably promote healing after acute injury. However, better spatial delivery and improved retention at the site of injury are two factors that could improve the clinical application of MSCs. In this study, we utilized thiol-ene Michael-type addition for rapid encapsulation of MSCs within a gelatin/poly(ethylene glycol) biomatrix. This biomatrix was also applied as a provisional dressing to full thickness wounds in Sprague-Dawley rats. The three-way interaction of MSCs, gelatin/poly(ethylene glycol) biomatrices, and host immune cells and adjacent resident cells in the wound microenvironment favorably modulated wound progression and host response. In this model we observed attenuated immune cell infiltration, lack of foreign giant cell (FBGC) formation, accelerated wound closure and re-epithelialization, as well as enhanced neovascularization and granulation tissue formation by 7 days. The MSC entrapped in the gelatin/poly(ethylene glycol) biomatrix localized cell presentation adjacent to the wound microenvironment and thus mediated the early resolution of inflammatory events and facilitated the proliferative phases in wound healing.

  12. Therapy of chronic wounds with water-filtered infrared-A (wIRA)

    PubMed Central

    von Felbert, Verena; Schumann, Hauke; Mercer, James B.; Strasser, Wolfgang; Daeschlein, Georg; Hoffmann, Gerd

    2008-01-01

    The central portion of chronic wounds is often hypoxic and relatively hypothermic, representing a deficient energy supply of the tissue, which impedes wound healing or even makes it impossible. Water-filtered infrared-A (wIRA) is a special form of heat radiation with a high tissue penetration and a low thermal load to the skin surface. wIRA produces a therapeutically usable field of heat and increases temperature, oxygen partial pressure and perfusion of the tissue. These three factors are decisive for a sufficient tissue supply with energy and oxygen and consequently as well for wound healing, especially in chronic wounds, and infection defense. wIRA acts both by thermal and thermic as well as by non-thermal and non-thermic effects. wIRA can advance wound healing or improve an impaired wound healing process and can especially enable wound healing in non-healing chronic wounds. wIRA can considerably alleviate the pain and diminish wound exudation and inflammation and can show positive immunomodulatory effects. In a prospective, randomized, controlled study of 40 patients with chronic venous stasis ulcers of the lower legs irradiation with wIRA and visible light (VIS) accelerated the wound healing process (on average 18 vs. 42 days until complete wound closure, residual ulcer area after 42 days 0.4 cm² vs. 2.8 cm²) and led to a reduction of the required dose of pain medication in comparison to the control group of patients treated with the same standard care (wound cleansing, wound dressing with antibacterial gauze, and compression garment therapy) without the concomitant irradiation. Another prospective study of 10 patients with non-healing chronic venous stasis ulcers of the lower legs included extensive thermographic investigation. Therapy with wIRA(+VIS) resulted in a complete or almost complete wound healing in 7 patients and a marked reduction of the ulcer size in another 2 of the 10 patients, a clear reduction of pain and required dose of pain medication

  13. Soft Tissue Wounds and Principles of Healing

    DTIC Science & Technology

    2007-01-01

    protamine’s anticoagulant properties could set the stage for impaired fibroblast synthetic activity [39]. It is to the fibro- blasts, which are the agents ...aspirin or other agents such as ticlopidine, dipyr- idamole, and clopidogrel [28]. For most of the wounds we deal with, the vessels have been cut...regulation is critical to the kinetics of normal wound closure [41]. Factors that adversely affect fibroproliferation Agents that are toxic to cells

  14. Modified Off-Midline Closure of Pilonidal Sinus Disease

    PubMed Central

    Saber, Aly

    2014-01-01

    Background: Numerous surgical procedures have been described for pilonidal sinus disease, but treatment failure and disease recurrence are frequent. Conventional off-midline flap closures have relatively favorable surgical outcomes, but relatively unfavorable cosmetic outcomes. Aim: The author reported outcomes of a new simplified off-midline technique for closure of the defect after complete excision of the sinus tracts. Patients and Methods: Two hundred patients of both sexes were enrolled for modified D-shaped excisions were used to include all sinuses and their ramifications, with a simplified procedure to close the defect. Results: The overall wound infection rate was 12%, (12.2% for males and 11.1% for females). Wound disruption was necessitating laying the whole wound open and management as open technique. The overall wound disruption rate was 6%, (6.1% for males and 5.5% for females) and the overall recurrence rate was 7%. Conclusion: Our simplified off-midline closure without flap appeared to be comparable to conventional off-midline closure with flap, in terms of wound infection, wound dehiscence, and recurrence. Advantages of the simplified procedure include potentially reduced surgery complexity, reduced surgery time, and improved cosmetic outcome. PMID:24926445

  15. 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.

  16. Tissue Responses to Postoperative Laser Therapy in Diabetic Rats Submitted to Excisional Wounds

    PubMed Central

    de Loura Santana, Cristiano; de Fátima Teixeira Silva, Daniela; Deana, Alessandro Melo; Prates, Renato Araujo; Souza, Amanda Pires; Gomes, Mariana Teixeira; de Azevedo Sampaio, Brunna Pileggi; Shibuya, Josiane Ferraretto; Bussadori, Sandra Kalil; Mesquita-Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos; França, Cristiane Miranda

    2015-01-01

    In a previous study about low-level laser therapy biomodulation on a full-thickness burn model we showed that single and fractionated dose regimens increased wound healing and leukocyte influx similarly when compared with untreated control. In order to verify if this finding would be similar in an impaired wound model, we investigated the effect of single and multiple irradiations on wound closure rate, type of inflammatory infiltrate, myofibroblasts, collagen deposition, and optical retardation of collagen in diabetic rats. Female Wistar rats in the same estrous cycle had diabetes induced with streptozotocin and an 8-mm excisional wound performed with a punch. The experimental groups were: control group – untreated ulcer; single-dose group – ulcer submitted to single dose of diode laser therapy (λ = 660 ± 2 nm; P = 30 mW; energy density: 4 J/cm2) and fractionated-dose group – ulcer submitted to 1 J/cm2 laser therapy on Days 1, 3, 8, and 10. The ulcers were photographed on the experimental days and after euthanasia tissue samples were routinely processed for histological and immunohistochemistry analyses. Independently of the energy density, laser therapy accelerated wound closure by approximately 40% in the first three days in comparison to the control group. Laser therapy increased acute inflammatory infiltrate until Day 3. Both laser groups exhibited more myofibroblasts and better collagen organization than the control group. The findings demonstrate that low-level laser therapy in the immediate postoperative period can enhance the tissue repair process in a diabetes model. Similar effects were achieved with laser therapy applied a single time with an energy density of 4 J/cm2 and applied four times with an energy density of 1 J/cm2. The application of laser therapy in the inflammatory phase was the most important factor to the enhancement of the tissue repair process. PMID:25909480

  17. Tissue responses to postoperative laser therapy in diabetic rats submitted to excisional wounds.

    PubMed

    de Loura Santana, Cristiano; Silva, Daniela de Fátima Teixeira; Deana, Alessandro Melo; Prates, Renato Araujo; Souza, Amanda Pires; Gomes, Mariana Teixeira; de Azevedo Sampaio, Brunna Pileggi; Shibuya, Josiane Ferraretto; Bussadori, Sandra Kalil; Mesquita-Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos; França, Cristiane Miranda

    2015-01-01

    In a previous study about low-level laser therapy biomodulation on a full-thickness burn model we showed that single and fractionated dose regimens increased wound healing and leukocyte influx similarly when compared with untreated control. In order to verify if this finding would be similar in an impaired wound model, we investigated the effect of single and multiple irradiations on wound closure rate, type of inflammatory infiltrate, myofibroblasts, collagen deposition, and optical retardation of collagen in diabetic rats. Female Wistar rats in the same estrous cycle had diabetes induced with streptozotocin and an 8-mm excisional wound performed with a punch. The experimental groups were: control group--untreated ulcer; single-dose group--ulcer submitted to single dose of diode laser therapy (λ = 660 ± 2 nm; P = 30 mW; energy density: 4 J/cm2) and fractionated-dose group--ulcer submitted to 1 J/cm2 laser therapy on Days 1, 3, 8, and 10. The ulcers were photographed on the experimental days and after euthanasia tissue samples were routinely processed for histological and immunohistochemistry analyses. Independently of the energy density, laser therapy accelerated wound closure by approximately 40% in the first three days in comparison to the control group. Laser therapy increased acute inflammatory infiltrate until Day 3. Both laser groups exhibited more myofibroblasts and better collagen organization than the control group. The findings demonstrate that low-level laser therapy in the immediate postoperative period can enhance the tissue repair process in a diabetes model. Similar effects were achieved with laser therapy applied a single time with an energy density of 4 J/cm2 and applied four times with an energy density of 1 J/cm2. The application of laser therapy in the inflammatory phase was the most important factor to the enhancement of the tissue repair process.

  18. 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

  19. Tracheocutaneous fistula closure using a Cartilo-musculo-cutaneous bilobed flap.

    PubMed

    Petersen, Wiebke; Amr, Amro; Held, Manuel; Werner, Jan-Ole; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin

    2014-03-01

    In general, the development of a tracheocutaneous fistula (TCF) after tracheotomy is a seldom but recurrent clinical problem in long-term ventilated patients. In cases of prolonged wound healing with no spontaneous wound closure or insufficient later closure by secondary suture, different surgical procedures have been previously described for the closure of TCFs. Nonetheless, each procedure has its individually associated complications so that definite closure of TCFs still remains a challenge. The purpose of this case report is to present a unique case of a patient with a persistent TCF that was successfully closed using a local cartilo-musculo-cutaneous bilobed flap.

  20. 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.

  1. Trehalose lyophilized platelets for wound healing.

    PubMed

    Pietramaggiori, Giorgio; Kaipainen, Arja; Ho, David; Orser, Cindy; Pebley, Walter; Rudolph, Alan; Orgill, Dennis P

    2007-01-01

    Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds.

  2. Role of endothelial selectins in wound repair.

    PubMed

    Subramaniam, M; Saffaripour, S; Van De Water, L; Frenette, P S; Mayadas, T N; Hynes, R O; Wagner, D D

    1997-05-01

    P- and E-selectins are adhesion molecules expressed on activated endothelium and platelets at sites of vascular injury and inflammation. The selectins are important for leukocyte recruitment. Because little is known about the role of selectins in wound healing, we studied cutaneous wound repair of full-thickness excisional skin wounds in mice lacking P-selectin, E-selectin, or both of these selectins. The absence of either selectin alone had no notable effect on healing, and the only deficit observed was a delay in early neutrophil extravasation in the P-selectin-deficient mice. Mice deficient in both P- and E-selectins had markedly reduced recruitment of inflammatory cells and impaired closure of the wounds. Wound sections, studied up to 3 days after wounding, showed significant impairment of neutrophil influx. Macrophage numbers were also reduced in the double mutants at 3 and 7 days after wounding as compared with wild-type mice. Additionally, a wider epithelial gap in the wounds of the P- and E-selectin-double-deficient mice 3 days after wounding indicated delayed keratinocyte migration. These results demonstrate an important combined role for P- and E-selectins in processes leading to wound healing.

  3. The Efficacy of Gelam Honey Dressing towards Excisional Wound Healing.

    PubMed

    Tan, Mui Koon; Hasan Adli, Durriyyah Sharifah; Tumiran, Mohd Amzari; Abdulla, Mahmood Ameen; Yusoff, Kamaruddin Mohd

    2012-01-01

    Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing.

  4. Allium stipitatum Extract Exhibits In Vivo Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus and Accelerates Burn Wound Healing in a Full-Thickness Murine Burn Model.

    PubMed

    Karunanidhi, Arunkumar; Ghaznavi-Rad, Ehsanollah; Jeevajothi Nathan, Jayakayatri; Abba, Yusuf; van Belkum, Alex; Neela, Vasanthakumari

    2017-01-01

    The in vivo antibacterial and burn wound healing potency of Persian shallot bulbs (Allium stipitatum) were explored in a mice burn model infected with methicillin-resistant Staphylococcus aureus (MRSA). Hexane (ASHE) and dichloromethane (ASDE) extracts were tested. Female BALB/c mice were inflicted with third-degree thermal injury followed by infection with MRSA. ASHE and ASDE formulated with simple ointment base (SOB) at concentrations of 1%, 2%, and 5% (w/w) were topically applied to burn wounds twice a day for 20 days. Silver sulfadiazine (1%) served as drug positive control. Microbiological analysis was carried out on 1, 2, 3, 4, and 5 days postwounding (dpw) and histopathological analysis at the end of the experiment (20 dpw). Both ointments demonstrated strong antibacterial activity with complete elimination of MRSA at 48-72 h after infection. The rate of wound contraction was higher (95-100%) in mice groups treated with ASHE and ASDE ointments after 15 dpw. Histological analysis revealed significant increase (p < 0.05) in epithelialization and collagenation in treated groups. The ASHE and ASDE were found to be relatively noncytotoxic and safe to Vero cell line (383.4 μg mL(-1); 390.6 μg mL(-1)), suggesting the extracts as safe topical antibacterial as well as promising alternatives in managing thermal injuries.

  5. Allium stipitatum Extract Exhibits In Vivo Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus and Accelerates Burn Wound Healing in a Full-Thickness Murine Burn Model

    PubMed Central

    Karunanidhi, Arunkumar; Jeevajothi Nathan, Jayakayatri; van Belkum, Alex

    2017-01-01

    The in vivo antibacterial and burn wound healing potency of Persian shallot bulbs (Allium stipitatum) were explored in a mice burn model infected with methicillin-resistant Staphylococcus aureus (MRSA). Hexane (ASHE) and dichloromethane (ASDE) extracts were tested. Female BALB/c mice were inflicted with third-degree thermal injury followed by infection with MRSA. ASHE and ASDE formulated with simple ointment base (SOB) at concentrations of 1%, 2%, and 5% (w/w) were topically applied to burn wounds twice a day for 20 days. Silver sulfadiazine (1%) served as drug positive control. Microbiological analysis was carried out on 1, 2, 3, 4, and 5 days postwounding (dpw) and histopathological analysis at the end of the experiment (20 dpw). Both ointments demonstrated strong antibacterial activity with complete elimination of MRSA at 48–72 h after infection. The rate of wound contraction was higher (95–100%) in mice groups treated with ASHE and ASDE ointments after 15 dpw. Histological analysis revealed significant increase (p < 0.05) in epithelialization and collagenation in treated groups. The ASHE and ASDE were found to be relatively noncytotoxic and safe to Vero cell line (383.4 μg mL−1; 390.6 μg mL−1), suggesting the extracts as safe topical antibacterial as well as promising alternatives in managing thermal injuries. PMID:28321262

  6. Wound Status Early Outcome Sensor and 3D Construct Development

    DTIC Science & Technology

    2015-03-01

    data of the outliers were checked and their data qualities were confirmed. Median normalization was chosen to apply to raw data and normalize the...Assessment, Wound Management Track, Master’s Clinical Science (MCISc) Program, School of Physical Therapy, University of Western Ontario, London, Ontario...stage IV pressure ulcer area and perimeter as healing parameters to predict wound closure. Ostomy Wound Management 2011;57(10):50-62. APPENDICES

  7. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro.

    PubMed

    Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

    2015-01-01

    Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin-eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway.

  8. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro

    PubMed Central

    Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

    2015-01-01

    Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin–eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway. PMID:25995620

  9. Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration

    PubMed Central

    Simkin, Jennifer; Sammarco, Mimi C.; Dawson, Lindsay A.; Tucker, Catherine; Taylor, Louis J.; Van Meter, Keith

    2015-01-01

    Abstract Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2‐octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled. PMID:27499872

  10. Skin grafting and wound healing-the "dermato-plastic team approach".

    PubMed

    Hierner, Robert; Degreef, Hugo; Vranckx, Jan Jerome; Garmyn, Maria; Massagé, Patrick; van Brussel, Michel

    2005-01-01

    Autologous skin grafts are successfully used to close recalcitrant chronic wounds especially at the lower leg. If wound care is done in a dermato-plastic team approach using the "integrated concept," difficulties associated with harvesting the skin graft as well as the complexities associated with inducing closure at the donor and the recipient site can be minimized. In the context of wound healing, skin transplantation can be regarded as (1) a supportive procedure for epithelialization of the wound surface and (2) mechanical stability of the wound ground. By placing skin grafts on a surface, central parts are covered much faster with keratinocytes. Skin (wound) closure is the ultimate goal, as wound closure means resistance to infection. Depending on the thickness of the skin graft, different amounts of dermis are transplanted with the overlying keratinocytes. The dermal component determines the mechanical (resistance to pressure and shear forces, graft shrinkage), functional (sensibility), and aesthetic properties of the graft. Generally speaking, the thicker the graft the better the mechanical, functional, and aesthetic properties, however, the worse the neo- and revascularization. Skin grafts do depend entirely on the re- and neovascularization coming from the wound bed. If the wound bed is seen as a recipient site for tissue graft, the classification of Lexer (Die freien Transplantationen. Stuttgart: Enke; 1924) turned out to be of extreme value. Three grades can be distinguished: "good wound conditions," "moderate wound conditions," and "insufficient wound conditions." Given good wound conditions, skin grafting is feasible. Nevertheless, skin closure alone might not be sufficient to fulfill the criteria of successful defect reconstruction. In case of moderate or insufficient wound conditions, wound bed preparation is necessary. If wound bed preparation is successful and good wound conditions can be achieved, skin grafting is possible. If, however, this

  11. Effect of chitosan acetate bandage on wound healing in infected and noninfected wounds in mice

    PubMed Central

    Burkatovskaya, Marina; Castano, Ana P.; Demidova-Rice, Tatiana N.; Tegos, George P.; Hamblin, Michael R.

    2010-01-01

    HemCon® bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important. PMID:18471261

  12. [Wound healing and wound dressing].

    PubMed

    Eitel, F; Sklarek, J

    1988-01-01

    This review article intends to discuss the clinical management of wounds in respect to a pathophysiological background. Recent results of research in the field of wound healing are demonstrated. Wound healing can be seen as aseptic inflammatory response to a traumatic stimulus. The activation of the clotting cascade by the trauma induces a sequence of humoral and cellular reactions. Platelets, granulocytes and macrophages are activated stepwisely. In the first phase of wound healing the wounded tissue area will be prepared for phagocytosis by enzymatic degradation of ground substance and depolymerisation of protein macromolecules (wound edema). Following the phagocytic microdebridement mesenchymal cells proliferate and produce matrix substance. Microcirculation within the traumatized area will be restored by angiogenesis, macroscopically observed as new formed granulation tissue. This leads to the wound healing phase of scar tissue formation. In this complexity of reactions naturally many possibilities of impairment are given. The most common complication during wound healing is the infection. It can be seen as self reinforcing process. The therapy of the impairment of wound healing consists in the disruption of the specific vicious circle, in the case of an osseus infection that would be a macrodebridement (that is necrectomy) and biomechanical stabilization. The surgical management of wounds principally consists in ensuring an undisturbed sequence of the healing process. This can be done by the wound excision that supports the phagocytic microdebridement. A further possibility is to avoid overwhelming formation of edema by eliminating the traumatic stimulus, by immobilization of the injured region and by ensuring a physiological microenvironment with a primary suture if possible. There are up to the present no drugs available to enhance cell proliferation and to regulate wound healing but it seems that experimental research is successful in characterizing

  13. Tension regulates myosin dynamics during Drosophila embryonic wound repair.

    PubMed

    Kobb, Anna B; Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

    2017-02-15

    Embryos repair epithelial wounds rapidly in a process driven by collective cell movements. Upon wounding, actin and the molecular motor non-muscle myosin II are redistributed in the cells adjacent to the wound, forming a supracellular purse string around the lesion. Purse string contraction coordinates cell movements and drives rapid wound closure. By using fluorescence recovery after photobleaching in Drosophila embryos, we found that myosin turns over as the purse string contracts. Myosin turnover at the purse string was slower than in other actomyosin networks that had a lower level of contractility. Mathematical modelling suggested that myosin assembly and disassembly rates were both reduced by tension at the wound edge. We used laser ablation to show that tension at the purse string increased as wound closure progressed, and that the increase in tension was associated with reduced myosin turnover. Reducing purse string tension by laser-mediated severing resulted in increased turnover and loss of myosin. Finally, myosin motor activity was necessary for its stabilization around the wound and for rapid wound closure. Our results indicate that mechanical forces regulate myosin dynamics during embryonic wound repair.

  14. Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin, Tazobactam, and Vancomycin During Negative Pressure Wound Therapy

    PubMed Central

    Rowan, Matthew P.; Niece, Krista L.; Rizzo, Julie A.; Akers, Kevin S.

    2017-01-01

    Objective: Negative pressure wound therapy (NPWT) uses subatmospheric pressure as a noninvasive adjunct to treat wounds and has demonstrated clinical efficacy by accelerating healing of a variety of acute and chronic wounds. NPWT may also play a role in preventing or treating wound infections, possibly by increasing wound penetration of antibiotics. However, clinical data in patients undergoing antibiotic and NPWT treatment are limited. Approach: To evaluate the wound penetration of antibiotics in NPWT patients, we conducted a prospective, observational study of burn and trauma patients treated with NPWT and systemic antibiotics. We evaluated the plasma pharmacokinetic profile of systemic vancomycin, ciprofloxacin, cefazolin, and piperacillin/tazobactam, as well as total and unbound antibiotic concentrations in wound exudate from the same patients. Results: Data from 32 patients with 37 wounds undergoing NPWT demonstrated that vancomycin, ciprofloxacin, and piperacillin/tazobactam all penetrated wounds with exudate to plasma concentration ratios more than 0.8. Cefazolin did not penetrate wounds in patients undergoing NPWT as effectively, with an average exudate to plasma concentration ratio of 0.51. Innovation: Clinical data on the wound penetration of antibiotics in patients undergoing NPWT are limited, but these data suggest that antibiotics have different capacities for wound penetration during NPWT that should be considered when making clinical decisions. Conclusion: This initial report suggests that (1) vancomycin, ciprofloxacin, and piperacillin/tazobactam effectively penetrate wounds during NPWT and (2) cefazolin as well as other antibiotics may not penetrate wounds during NPWT. PMID:28224048

  15. Gene electrotransfer into skin using noninvasive multi-electrode array for vaccination and wound healing.

    PubMed

    Kos, Spela; Vanvarenberg, Kevin; Dolinsek, Tanja; Cemazar, Maja; Jelenc, Jure; Préat, Véronique; Sersa, Gregor; Vandermeulen, Gaëlle

    2017-04-01

    Skin is an attractive target for gene electrotransfer due to its easy accessibility and its interesting immune properties. Since electrodes are often invasive and frequently induce discomfort during pulse application, there is a fundamental need for non-invasive electrodes for skin delivery. We developed circular pin non-invasive multi-electrode array (MEA), suitable for different clinical applications. MEA was first employed to deliver a luciferase reporter gene. Then, it was used to deliver a DNA vaccine coding for ovalbumin or a plasmid encoding hCAP-18/LL-37 for promoting wound healing. The results demonstrated a strong gene expression and an efficient delivery of both, DNA vaccine and wound healing agent, dependent on the pulses applied. The use of MEA to deliver the ovalbumin plasmid demonstrated a strong immune response, as evidenced by the presence of antibodies in sera, the IFN-gamma response and the delayed tumor growth when the mice were subsequently challenged with B16-OVA cells. The delivery of a plasmid encoding hCAP-18/LL-37 significantly accelerated wound closure. The easy applicability and non-invasiveness of MEA make it suitable for various clinical applications that require gene electrotransfer to skin. Specifically, by adapting electric pulses to the expected action of a transgene, non-invasive MEA can be employed either for vaccination or for wound healing.

  16. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  17. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-06-07

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways.

  18. Quantifying dorsal closure in three dimensions

    PubMed Central

    Lu, Heng; Sokolow, Adam; Kiehart, Daniel P.; Edwards, Glenn S.

    2016-01-01

    Dorsal closure is an essential stage of Drosophila embryogenesis and is a powerful model system for morphogenesis, wound healing, and tissue biomechanics. During closure, two flanks of lateral epidermis close an eye-shaped dorsal opening that is filled with amnioserosa. The two flanks of lateral epidermis are zipped together at each canthus (“corner” of the eye). Actomyosin-rich purse strings are localized at each of the two leading edges of lateral epidermis (“lids” of the eye). Here we report that each purse string indents the dorsal surface at each leading edge. The amnioserosa tissue bulges outward during the early-to-mid stages of closure to form a remarkably smooth, asymmetric dome indicative of an isotropic and uniform surface tension. Internal pressure of the embryo and tissue elastic properties help to shape the dorsal surface. PMID:27798232

  19. Use of Multiple Adjunctive Negative Pressure Wound Therapy Modalities to Manage Diabetic Lower-Extremity Wounds

    PubMed Central

    2016-01-01

    Objective: Various treatment options exist for wound healing; however, clinical assessment of the patient and the wound environment must be considered before determining an optimal wound treatment plan. Negative pressure wound therapy alone and/or with an instilled topical solution can be effective in adjunctive management of acute and chronic wounds. Hyperbaric oxygen therapy has also been shown to contribute to the wound-healing process. A pilot evaluation using a multistep approach of adjunctive negative pressure wound therapy with instillation and a dwell time, standard negative pressure wound therapy, and hyperbaric oxygen therapy was explored to manage postsurgical, diabetic lower-extremity wounds with a significant bioburden. Methods: Three diabetic patients with lower-extremity ulcers were treated after surgical intervention. Multistep wound therapy consisted of (1) negative pressure wound therapy with instillation of normal saline with a 20-minute dwell time, followed by 2 hours of negative pressure at −150 mm Hg for 3 to 4 days; (2) 1 to 3 weeks of continuous negative pressure at −150 mm Hg; and (3) multiple treatments of hyperbaric oxygen therapy. Results: After surgery, wound closure was achieved within 4 weeks postinitiation of multistep wound therapy. All patients regained limb function and recovered with no long-term sequelae. Conclusions: In these 3 cases, a multistep wound therapy approach after surgery resulted in successful outcomes; however, larger prospective studies are needed to demonstrate the potential efficacy of this approach in the postsurgical management of complex, diabetic lower-extremity wounds. PMID:28077984

  20. Stress-relaxation and tension relief system for immediate primary closure of large and huge soft tissue defects: an old-new concept: new concept for direct closure of large defects.

    PubMed

    Topaz, Moris; Carmel, Narin Nard; Topaz, Guy; Li, Mingsen; Li, Yong Zhong

    2014-12-01

    Stress-relaxation is a well-established mechanism for laboratory skin stretching, with limited clinical application in conventional suturing techniques due to the inherent, concomitant induction of ischemia, necrosis and subsequent suture failure. Skin defects that cannot be primarily closed are a common difficulty during reconstructive surgery. The TopClosure tension-relief system (TRS) is a novel device for wound closure closure, providing secured attachment to the skin through a wide area of attachment, in an adjustable manner, enabling primary closure of medium to large skin defects. The aim of this study was to evaluate the efficiency of the TopClosure TRS as a substitute for skin grafting and flaps for primary closure of large soft tissue defects by stress-relaxation. We present three demonstrative cases requiring resection of large to huge tumors customarily requiring closure by skin graft or flaps. TRS was applied during surgery serving as a tension-relief platform for tension sutures, to enable primary skin-defect closure by cycling of stress-relaxation, and following surgery as skin-secure system until complete wound closure. All skin defects ranging from 7 to 26 cm in width were manipulated by the TRS through stress-relaxation, without undermining of skin, enabling primary skin closure and eliminating the need for skin grafts and flaps. Immediate wound closure ranged 26 to 135 min. TRS was applied for 3 to 4 weeks. Complications were minimal and donor site morbidity was eliminated. Surgical time, hospital stay and costs were reduced and wound aesthetics were improved. In this case series we present a novel technology that enables the utilization of the viscoelastic properties of the skin to an extreme level, extending the limits of primary wound closure by the stress-relaxation principle. This is achieved via a simple device application that may aid immediate primary wound closure and downgrade the complexity of surgical procedures for a wide range

  1. Silk fibroin/gelatin electrospun nanofibrous dressing functionalized with astragaloside IV induces healing and anti-scar effects on burn wound.

    PubMed

    Shan, Ying-Hui; Peng, Li-Hua; Liu, Xin; Chen, Xi; Xiong, Jie; Gao, Jian-Qing

    2015-02-20

    Functional wound dressing has provided new challenges for researchers who focus on burn to improve skin graft quality, reduce scarring, and develop a pluristratified dermal or epidermal construct of a burn wound. This study aimed to investigate the effect of a silk fibroin/gelatin (SF/GT) electrospun nanofibrous dressing loaded with astragaloside IV (AS) on deep partial-thickness burn wound. AS-loaded SF/GT-blended nanofibrous dressing was prepared by electrospinning nanotechnology. The optimal ratio (25:75) of silk fibroin to gelatin was further optimized by evaluating ATR-FTIR characteristics, mechanical properties, porosity, swelling rate, degradation, and release profile of the AS-loaded SF/GT nanofibrous dressing. In contrast to the blank control, the AS-loaded SF/GT nanofibrous dressing promoted cell adhesion and proliferation with good biocompatibility in vitro (p<0.01). This dressing also accelerated wound healing and inhibited scar formation in vivo by stimulating wound closure (p<0.05), increasing angiogenesis, regulating newly formed types of collagen, and improving collagen organization. These results showed that SF/GT nanofibrous dressing is a promising topical drug delivery system. Furthermore, AS-functionalized SF/GT nanofibrous dressing is an excellent topical therapeutic that could be applied to promote healing and elicit anti-scar effects on partial-thickness burn wound.

  2. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma.

    PubMed

    La, Wan-Geun; Yang, Hee Seok

    2015-04-01

    Platelet-rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long-term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) can provide long-term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long-term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet-derived growth factor-BB (PDGF-BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG-PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full-thickness skin wound treatment in mice with FG-HCPN-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG-HCPN or FG-PRP. The enhanced wound healing using FG-HCPN-PRP may be due to the prolonged release not only of PDGF-BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site.

  3. Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair.

    PubMed

    Hunter, Miranda V; Lee, Donghoon M; Harris, Tony J C; Fernandez-Gonzalez, Rodrigo

    2015-08-31

    Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes wound closure. Actomyosin cable formation is accompanied by junctional rearrangements at the wound margin. We used in vivo time-lapse quantitative microscopy to show that clathrin, dynamin, and the ADP-ribosylation factor 6, three components of the endocytic machinery, accumulate around wounds in Drosophila melanogaster embryos in a process that requires calcium signaling and actomyosin contractility. Blocking endocytosis with pharmacological or genetic approaches disrupted wound repair. The defect in wound closure was accompanied by impaired removal of E-cadherin from the wound edge and defective actomyosin cable assembly. E-cadherin overexpression also resulted in reduced actin accumulation around wounds and slower wound closure. Reducing E-cadherin levels in embryos in which endocytosis was blocked rescued actin localization to the wound margin. Our results demonstrate a central role for endocytosis in wound healing and indicate that polarized E-cadherin endocytosis is necessary for actomyosin remodeling during embryonic wound repair.

  4. Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair

    PubMed Central

    Hunter, Miranda V.; Lee, Donghoon M.; Harris, Tony J.C.

    2015-01-01

    Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes wound closure. Actomyosin cable formation is accompanied by junctional rearrangements at the wound margin. We used in vivo time-lapse quantitative microscopy to show that clathrin, dynamin, and the ADP-ribosylation factor 6, three components of the endocytic machinery, accumulate around wounds in Drosophila melanogaster embryos in a process that requires calcium signaling and actomyosin contractility. Blocking endocytosis with pharmacological or genetic approaches disrupted wound repair. The defect in wound closure was accompanied by impaired removal of E-cadherin from the wound edge and defective actomyosin cable assembly. E-cadherin overexpression also resulted in reduced actin accumulation around wounds and slower wound closure. Reducing E-cadherin levels in embryos in which endocytosis was blocked rescued actin localization to the wound margin. Our results demonstrate a central role for endocytosis in wound healing and indicate that polarized E-cadherin endocytosis is necessary for actomyosin remodeling during embryonic wound repair. PMID:26304727

  5. Combat Wound Initiative Program

    DTIC Science & Technology

    2010-07-01

    Stasis Ulcer 4 16.0 15 60.0 4.0 5 20.0 Decubitus Ulcer 8 66.7 2 16.7 8.3 8.3 Plaster Cast Pressure Sore 6 85.7 0 0 I 14.3 0 0 Arterial Insufficiency...causes were emolled including: failed primary surgical closure, traumatic wounds, arterial and venous insufficiency ulcers , pressure sores, and... Ulcer 2 40.0 3 60.0 0 0 0 0 Bum 6 85.7 0 0 14.3 0 0 ESWT Treatments 0.001 Mean 2.3 :t 0.2 3.6 :t 0.3 3.4 :t 0.3 5.6 :t 0.7 Healing 0.001

  6. Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey

    PubMed Central

    Ertugrul, Bulent M.; Buke, Cagri; Ersoy, Ozlem Saylak; Ay, Bengisu; Demirez, Dilek Senen; Savk, Oner

    2015-01-01

    Background Intralesional recombinant epidermal growth factor (EGF) was produced in the Centre for Genetic Engineering and Biotechnology (CIGB), Cuba, in 1988 and licensed in 2006. Because it may accelerate wound healing, it is a potential new treatment option in patients with a diabetic foot wound (whether infected or not) as an adjunct to standard treatment (i.e. debridement, antibiotics). We conducted the initial evaluation of EGF for diabetic foot wounds in Turkey. Methods We enrolled 17 patients who were hospitalized in various medical centers for a foot ulcer and/or infection and for whom below the knee amputation was suggested to all except one. All patients received 75 μg intralesional EGF three times per week on alternate days. Results The appearance of new granulation tissue on the wound site (≥75%) was observed in 13 patients (76%), and complete wound closure was observed in 3 patients (18%), yielding a ‘complete recovery’ rate of 94%. The most common side effects were tremor (n=10, 59%) and nausea (n=6, 35%). In only one case,a serious side effect requiring cessation of EGF treatment was noted. That patient experienced severe hypotension at the 16th application session, and treatment was discontinued. At baseline, a total of 21 causative bacteria were isolated from 15 patients, whereascultures were sterile in two patients. The most frequently isolated species was Pseudomonas aeruginosa. Conclusion Thus, this preliminary study suggests that EGF seems to be a potential adjunctive treatment option in patients with limb-threatening diabetic foot wounds. PMID:26268583

  7. Facial gunshot wound debridement: debridement of facial soft tissue gunshot wounds.

    PubMed

    Shvyrkov, Michael B

    2013-01-01

    Over the period 1981-1985 the author treated 1486 patients with facial gunshot wounds sustained in combat in Afghanistan. In the last quarter of 20th century, more powerful and destructive weapons such as M-16 rifles, AK-47 and Kalashnikov submachine guns, became available and a new approach to gunshot wound debridement is required. Modern surgeons have little experience in treatment of such wounds because of rare contact with similar pathology. This article is intended to explore modern wound debridement. The management of 502 isolated soft tissue injuries is presented. Existing principles recommend the sparing of damaged tissues. The author's experience was that tissue sparing lead to a high rate of complications (47.6%). Radical primary surgical debridement (RPSD) of wounds was then adopted with radical excision of necrotic non-viable wound margins containing infection to the point of active capillary bleeding and immediate primary wound closure. After radical debridement wound infection and breakdown decreased by a factor of 10. Plastic operations with local and remote soft tissue were made on 14, 7% of the wounded. Only 0.7% patients required discharge from the army due to facial muscle paralysis and/or facial skin impregnation with particles of gunpowder from mine explosions. Gunshot face wound; modern debridement.

  8. Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds.

    PubMed

    Rayner, T E; Cowin, A J; Robertson, J G; Cooter, R D; Harries, R C; Regester, G O; Smithers, G W; Goddard, C; Belford, D A

    2000-06-01

    The ability of single growth factors to promote healing of normal and compromised wounds has been well described, but wound healing is a process requiring the coordinated action of multiple growth factors. Only the synergistic effect on wound healing of combinations containing at most two individual growth factors has been reported. We sought to assess the ability of a novel milk-derived growth factor-enriched preparation ¿mitogenic bovine whey extract (MBWE), which contains six known growth factors, to promote repair processes in organotypic in vitro models and incisional wounds in vivo. MBWE stimulated the contraction of fibroblast-populated collagen lattices in a dose-dependent fashion and promoted the closure of excisional wounds in embryonic day 17 fetal rat skin. Application of MBWE increased incisional wound strength in normal animals on days 3, 5, 7, and 10 and reversed the decrease in wound strength observed following steroid treatment. Wound histology showed increased fibroblast numbers in wounds from normal and steroid-compromised animals. These data suggest the mixture of factors present in bovine milk exerts a direct action on the cells of cutaneous wound repair to enhance both normal and compromised healing.

  9. Barbed suture for gastrointestinal closure: a randomized control trial.

    PubMed

    Demyttenaere, Sebastian V; Nau, Peter; Henn, Matthew; Beck, Catherine; Zaruby, Jeffrey; Primavera, Michael; Kirsch, David; Miller, Jeffrey; Liu, James J; Bellizzi, Andrew; Melvin, W Scott

    2009-09-01

    In an effort to make laparoscopic suturing more efficient, the V-Loc advanced wound closure device (Covidien, Mansfield, MA) has been produced. This device is a self-anchoring barbed suture that obviates the need for knot tying. The goal of this initial feasibility study was to investigate the use of the barbed suture in gastrointestinal enterotomy closure. A randomized study of 12 pigs comparing enterotomy closure with barbed versus a nonbarbed suture of similar tensile strength was performed. To this end, 25 mm enterotomies were made in the stomach (1 control, 1 treatment), jejunum (2 controls, 2 treatments), and descending colon (1 control, 1 treatment). Animals were killed at 3, 7, and 14 days postoperatively (4 each group) and their gastrointestinal tracts harvested; 6 of the 8 enterotomies from each pig underwent burst strength testing. The remaining 2 were fixed in formalin and sent for histological examination. All 12 pigs survived until they were killed without any major complications. Enterotomy closure with barbed suture revealed adhesion scores, burst strength pressures, and histology scores that were similar to those for the control. Jejunal closures resulted in 6 failures at 7 days (3 control, 3 barbed) and 4 failures at 14 days (2 control, 2 barbed). The barbed suture significantly reduced suturing time in the stomach, jejunum, and colon. The V-Loc wound closure device appears to offer comparable gastrointestinal closure to 3-0 Maxon while being significantly faster. Further studies with V-Loc are required to assess its use in laparoscopic surgery.

  10. Epithelialization in Wound Healing: A Comprehensive Review

    PubMed Central

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

    2014-01-01

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

  11. Epithelialization in Wound Healing: A Comprehensive Review.

    PubMed

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

    2014-07-01

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

  12. Reducing Wound Tension with Undermining or Imbrication—Do They Work?

    PubMed Central

    Krishnan, Naveen M.; Brown, Benjamin J.; Davison, Steven P.; Mauskar, Neil; Mino, Matthew; Jordan, Marion H.

    2016-01-01

    Background: For the noncolonized wound, achieving tension-free, primary wound closure is ideal. Some surgeons advocate imbrication of deeper tissues rather than undermining, posing that imbrication preserves more dermal perfusion while still reducing tension at the wound edge. We sought to determine which technique most reliably reduced wound tension while preserving dermal wound perfusion. Methods: A total of 5 standardized, symmetrical pairs of full thickness wounds were created on Duroc swine. Wound tension was measured with a Tyrolean tensiometer before and after either method of closure, whereas a speckle contrast imager was used to assess dermal edge perfusion. Skin tension and dermal perfusion were evaluated for statistical significance via paired t tests and a multivariate analysis of variance. Results: There was a significant reduction in wound tension with undermining and imbrication relative to the raw wound tension (5 and 5.9 vs 7.1 N; P < 0.05) yet no significant difference between methods of closure (P > 0.05). There was a significant reduction in dermal perfusion between unwounded skin and the imbricated wound (222 perfusion units [PU] vs 48 PU; P < 0.05) and between the unwounded skin and the undermined wound (205 vs 63 PU; P < 0.05). Conclusions: We found no significant difference in wound tension between wound undermining or imbrication and a significant decrease in dermal perfusion after imbrication and undermining although the relative decrease in perfusion was greater with imbrication. Wound undermining reduces skin tension with greater relative dermal perfusion to the skin and should be selected over wound imbrication in standard primary wound closure. PMID:27536478

  13. How wounds heal

    MedlinePlus

    ... care to prevent infection. Continue Reading Stages of Wound Healing Wounds heal in stages. The smaller the wound, ... How lacerations heal References Leong M, Phillips LG. Wound healing. In: Townsend CM, Beauchamp RD, Evers BM, Mattox ...

  14. Bacterial Wound Culture

    MedlinePlus

    ... and services. Advertising & Sponsorship: Policy | Opportunities Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  15. Chitosan application to X-ray irradiated wound in dogs.

    PubMed

    Ueno, H; Ohya, T; Ito, H; Kobayashi, Y; Yamada, K; Sato, M

    2007-01-01

    Radiation-impaired wounds are characterized by fibroblast and endothelial cell injury, resulting in delayed wound healing. Several previous studies have indicated that chitosan accelerates wound healing by up-regulating growth factor synthesis. In this study, the topical application of chitosan onto radiation-impaired wounds was investigated. An X-ray irradiated (25Gy) skin wound was treated with cotton fibre-type chitosan in dogs. Histopathologically, neovascularization was significantly accelerated in irradiated wounds in the chitosan application group (rad-chi group) when compared with irradiated wounds in the control group (rad-cont group). Vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) expression in granulation tissue was positive in the rad-chi group, but was negative in the rad-cont group. The present results confirmed advanced granulation and capillary formation in wounds treated with chitosan, even after irradiation.

  16. Management of gunshot wounds

    SciTech Connect

    Ordog, G.; Drew, R.

    1987-01-01

    Management of Gunshot Wounds provides a review of wound ballistics and a systemic review of gunshot wound management of all major body areas and systems. This volume includes information on pre-hospital care, nursing care, and care of infants, children, and the elderly patient with gunshot wounds. This volume also features information on: lead toxicity; complications of gunshot wounds; socioeconomic aspects of gunshot wounds; the forensic and pathological aspects of gunshot wounds; future directions in the care of gunshot wounds.

  17. What is important to patients in wound management.

    PubMed

    Keeton, Helen; Crouch, Robert; Lowe, Kate

    2015-02-01

    Traumatic wounds are a common reason for patients to attend emergency departments. There are many ways of managing these wounds from glue to suturing. The authors conducted a patient survey to identify the outcome measures most important to patients after closure of traumatic wounds. The results showed that having the least chance of infection was the most important outcome, followed by being looked after by caring staff and a quick recovery. These finding were consistent regardless of the anatomical location of the wound or age of the patient. This information is being used to guide the authors in the most appropriate outcome measures for further research.

  18. Episiotomy and obstetric perineal wound dehiscence: beyond soreness.

    PubMed

    Kamel, A; Khaled, M

    2014-04-01

    Postpartum episiotomy dehiscence is a rare complication of vaginal delivery. Infection rates in episiotomy wounds are surprisingly low; however, it remains the most common cause of wound dehiscence, which may lead to major physical, psychological and social problems if left untreated. Most dehisced perineal wounds are left to heal naturally by secondary intention. This approach often results in a protracted period of significant morbidity for women. There is emerging evidence that early re-suturing closure of broken-down perineal wounds may have a better outcome, but randomised controlled trials are needed to yield evidence-based guidance for this management approach.

  19. [Wound dressings].

    PubMed

    Breuninger, H

    1988-01-01

    The wide variety of dermatologic surgical procedures has resulted in a corresponding choice of wound dressings. Considering the chemical and physical properties as well as the function of the dressings, standardized dressing techniques can be performed with relatively few materials. This saves both time and money.

  20. 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.

  1. Cellular events and biomarkers of wound healing

    PubMed Central

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

    2012-01-01

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

  2. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5.

    PubMed

    Wright, Catherine S; Berends, Rebecca F; Flint, David J; Martin, Patricia E M

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance.

  3. Wounded, Ill, and Injured Challenges.

    PubMed

    Jones, Stephen L

    2016-01-01

    The Washington Post articles of February 2007 led to a close examination of the care provided Wounded Warriors at Walter Reed Army Medical Center. Subsequent reports by the President's Commission, Independent Review Group, and Defense Health Board all recommended ways to improve care. Joint Task Force National Capital Region Medical was established to implement the recommended improvements in Warrior care, and the recommendations of the Base Realignment and Closure Commission to close Walter Reed and realign the staff into a new Walter Reed National Military Medical Center and Fort Belvoir Community Hospital. It accomplished these tasks, maintained existing wounded, ill, and injured care, and safely transferred patients during the height of the fighting season in Afghanistan. It successfully accomplished its mission through engaged leadership, establishing an appropriate environment for Warrior care, careful management of casualty flow, and robust communication with all parties affected by the changes. The lessons learned in Warrior care should be considered when planning future military medical operations.

  4. The Wound Healing and Antibacterial Activity of Five Ethnomedical Calophyllum inophyllum Oils: An Alternative Therapeutic Strategy to Treat Infected Wounds

    PubMed Central

    Léguillier, Teddy; Lecsö-Bornet, Marylin; Lémus, Christelle; Rousseau-Ralliard, Delphine; Lebouvier, Nicolas; Hnawia, Edouard; Nour, Mohammed; Aalbersberg, William; Ghazi, Kamelia; Raharivelomanana, Phila; Rat, Patrice

    2015-01-01

    Background Calophyllum inophyllum L. (Calophyllaceae) is an evergreen tree ethno-medically used along the seashores and islands of the Indian and Pacific Oceans, especially in Polynesia. Oil extracted from the seeds is traditionally used topically to treat a wide range of skin injuries from burn, scar and infected wounds to skin diseases such as dermatosis, urticaria and eczema. However, very few scientific studies reported and quantified the therapeutic properties of Calophyllum inophyllum oil (CIO). In this work, five CIO from Indonesia (CIO1), Tahiti (CIO2, 3), Fiji islands (CIO4) and New Caledonia (CIO5) were studied and their cytotoxic, wound healing, and antibacterial properties were presented in order to provide a scientific support to their traditional use and verify their safety. Methods The safety of the five CIO was ascertained using the Alamar blue assay on human keratinocyte cells. CIO wound healing properties were determined using the scratch test assay on human keratinocyte cells. CIO-stimulated antibacterial innate immune response was evaluated using ELISA by measuring β defensin-2 release in human derivative macrophage cells. CIO antibacterial activity was tested using oilogramme against twenty aerobic Gram- bacteria species, twenty aerobic Gram+ bacteria species, including a multi-drug resistant Staphylococcus aureus strain and two anaerobic Gram+ bacteria species e.g. Propionibacterium acnes and Propionibacterium granulosum. To detect polarity profile of the components responsible of the antibacterial activity, we performed bioautography against a Staphylococcus aureus strain. Results Based on Alamar Blue assay, we showed that CIO can be safely used on keratinocyte cells between 2.7% and 11.2% depending on CIO origin. Concerning the healing activity, all the CIO tested accelerated in vitro wound closure, the healing factor being 1.3 to 2.1 higher compared to control when keratinocytes were incubated after scratch with CIO at 0.1%. Furthermore

  5. Soft tissue sarcoma resection volume associated with wound-healing complications.

    PubMed

    Geller, David S; Hornicek, Francis J; Mankin, Henry J; Raskin, Kevin A

    2007-06-01

    Limb-salvage surgery has become the standard of care for most soft tissue sarcomas. While primary closure is often possible, it is frequently complicated by wound-healing complications in the setting of previously irradiated tissue and surgical wounds closed under tension. We sought to identify a relationship between the volume of resected soft tissue and the rate of wound-healing complications. We retrospectively reviewed 108 patients who were treated over a 17-month period for soft-tissue sarcomas using limb-sa