Science.gov

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. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain.

    PubMed

    Waters, C M; Savla, U

    1999-12-01

    The airway epithelium may be damaged by inhalation of noxious agents, in response to pathogens, or during endotracheal intubation and mechanical ventilation. Maintenance of an intact epithelium is important for lung fluid balance, and the loss of epithelium may stimulate inflammatory responses. Epithelial repair in the airways following injury must occur on a substrate that undergoes cyclic elongation and compression during respiration. We have previously shown that cyclic mechanical strain inhibits wound closure in the airway epithelium (Savla and Waters, 1998b). In this study, we investigated the stimulation of epithelial wound closure by keratinocyte growth factor (KGF) in vitro and the mechanisms by which KGF overcomes the inhibition due to mechanical strain. Primary cultures of normal human bronchial epithelial cells (NHBE) and a cell line of human airway epithelial cells, Calu 3, were grown on Silastic membranes, and a wound was scraped across the well. The wells were then exposed to cyclic strain using the Flexercell Strain Unit, and wound closure was measured. While cyclic elongation (20% maximum) and cyclic compression (approximately 2%) both inhibited wound closure in untreated wells, treatment with KGF (50 ng/ml) significantly accelerated wound closure and overcame the inhibition due to cyclic strain. Since wound closure involves cell spreading, migration, and proliferation, we investigated the effect of cyclic strain on cell area, cell-cell distance, and cell velocity at the wound edge. While the cell area increased in unstretched monolayers, the cell area of monolayers in compressed regions decreased significantly. Treatment with KGF increased the cell area in both cyclically elongated and compressed cells. Also, when cells were treated with KGF, cell velocity was significantly increased in both static and cyclically strained monolayers, and cyclic strain did not inhibit cell migration. These results suggest that KGF is an important factor in

  3. 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. PMID:23788174

  4. Topical application of aminopeptidase N-neutralizing antibody accelerates wound closure.

    PubMed

    Lai, Amy; Hosseini-Tabatabaei, Azadeh; Hartwell, Ryan; Rahmani-Neishaboor, Elham; Kilani, Ruhangiz Taghi; Ghahary, Aziz

    2013-01-01

    Upon release from keratinocytes, 14-3-3 sigma (also known as stratifin) acts on the dermal fibroblast and modulates its production of extracellular matrix proteins. Subsequent to the recent identification as a receptor responsible for stratifin-mediated matrix turnover in dermal fibroblasts, aminopeptidase N has been implicated in the regulation of epidermal-dermal communication and expression of key matrix proteases and adhesion molecules. In light of the growing importance of aminopeptidase N in modulation of the fibroblast phenotype, the present study evaluates the potential of targeting the ectoenzyme in cutaneous repair, and demonstrates that neutralization of aminopeptidase N led to acceleration of wound closure. This was attributed to at least in part an increase of collagen deposition and fibroblast contractility in the granulation tissue. These findings confirmed the important role of aminopeptidase N in post-injury tissue remodeling and wound contraction. PMID:23054189

  5. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling

    PubMed Central

    Correll, Kelly; Schiel, John A.; Finigan, Jay H.; Prekeris, Rytis; Mason, Robert J.

    2014-01-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. PMID:24748602

  6. Mechanosensitive ATP release from hemichannels and Ca²⁺ influx through TRPC6 accelerate wound closure in keratinocytes.

    PubMed

    Takada, Hiroya; Furuya, Kishio; Sokabe, Masahiro

    2014-10-01

    Cutaneous wound healing is accelerated by exogenous mechanical forces and is impaired in TRPC6-knockout mice. Therefore, we designed experiments to determine how mechanical force and TRPC6 channels contribute to wound healing using HaCaT keratinocytes. HaCaT cells were pretreated with hyperforin, a major component of a traditional herbal medicine for wound healing and also a TRPC6 activator, and cultured in an elastic chamber. At 3 h after scratching the confluent cell layer, the ATP release and intracellular Ca(2+) increases in response to stretching (20%) were live-imaged. ATP release was observed only in cells at the frontier facing the scar. The diffusion of released ATP caused intercellular Ca(2+) waves that propagated towards the rear cells in a P2Y-receptor-dependent manner. The Ca(2+) response and wound healing were inhibited by ATP diphosphohydrolase apyrase, the P2Y antagonist suramin, the hemichannel blocker CBX and the TRPC6 inhibitor diC8-PIP2. Finally, the hemichannel-permeable dye calcein was taken up only by ATP-releasing cells. These results suggest that stretch-accelerated wound closure is due to the ATP release through mechanosensitive hemichannels from the foremost cells and the subsequent Ca(2+) waves mediated by P2Y and TRPC6 activation. PMID:25097230

  7. Assisted closure of fasciotomy wounds

    PubMed Central

    Fowler, J. R.; Kleiner, M. T.; Das, R.; Gaughan, J. P.; Rehman, S.

    2012-01-01

    Introduction Negative pressure wound therapy (NPWT) and vessel loop assisted closure are two common methods used to assist with the closure of fasciotomy wounds. This retrospective review compares these two methods using a primary outcome measurement of skin graft requirement. Methods A retrospective search was performed to identify patients who underwent fasciotomy at our institution. Patient demographics, location of the fasciotomy, type of assisted closure, injury characteristics, need for skin graft, length of stay and evidence of infection within 90 days were recorded. Results A total of 56 patients met the inclusion criteria. Of these, 49 underwent vessel loop closure and seven underwent NPWT assisted closure. Patients who underwent NPWT assisted closure were at higher risk for requiring skin grafting than patients who underwent vessel loop closure, with an odds ratio of 5.9 (95% confidence interval 1.11 to 31.24). There was no difference in the rate of infection or length of stay between the two groups. Demographic factors such as age, gender, fracture mechanism, location of fasciotomy and presence of open fracture were not predictive of the need for skin grafting. Conclusion This retrospective descriptive case series demonstrates an increased risk of skin grafting in patients who underwent fasciotomy and were treated with NPWT assisted wound closure. In our series, vessel loop closure was protective against the need for skin grafting. Due to the small sample size in the NPWT group, caution should be taken when generalising these results. Further research is needed to determine if NPWT assisted closure of fasciotomy wounds truly leads to an increased requirement for skin grafting, or if the vascular injury is the main risk factor. PMID:23610668

  8. Acceleration of cutaneous wound healing by brassinosteroids

    PubMed Central

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

    2013-01-01

    Brassinosteroids are plant growth hormones involved in cell growth, division and differentiation. Their effects in animals are largely unknown, although recent studies showed the anabolic properties of brassinosteroids possibly mediated through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Here we examined biological activity of homobrassinolide (HB) and its synthetic analogues on in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration, and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full thickness dermal wound, and the rate of wound closure was assessed daily for 10 d alongside adenosine receptor agonist CGS-21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of TGF-β and ICAM-1 were significantly lower, while TNF-α was nearly suppressed in the wounds from treated mice. Our data suggest that topical brassinosteroids accelerate wound healing by positively modulating inflammatory and re-epithelialization phases of the wound-repair process, in partby enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in a wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing. PMID:23937635

  9. Accelerated Wound Closure In Vitro by Fibroblasts from a Subgroup of Cleft Lip/Palate Patients: Role of Transforming Growth Factor-α

    PubMed Central

    Beyeler, Joël; Schnyder, Isabelle; Katsaros, Christos; Chiquet, Matthias

    2014-01-01

    In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely “fast”, “intermediate”, and “slow”. Most cleft lip/palate fibroblasts were distributed between the “fast” (5 strains) and the “intermediate” group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the “fast” group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the “intermediate” migratory group to the level of the “fast”, but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of “fast” cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling. PMID:25360592

  10. Accelerated wound closure in vitro by fibroblasts from a subgroup of cleft lip/palate patients: role of transforming growth factor-α.

    PubMed

    Beyeler, Joël; Schnyder, Isabelle; Katsaros, Christos; Chiquet, Matthias

    2014-01-01

    In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely "fast", "intermediate", and "slow". Most cleft lip/palate fibroblasts were distributed between the "fast" (5 strains) and the "intermediate" group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the "fast" group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the "intermediate" migratory group to the level of the "fast", but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of "fast" cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling. PMID:25360592

  11. 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

  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. 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

  14. Lifting and wound closure with barbed sutures.

    PubMed

    Mulholland, R Stephen; Paul, Malcolm D

    2011-07-01

    The advent of barbed sutures has been a novel and useful adjunct for the aesthetic plastic surgeon in properly selected patients. The deployment of a barbed suture minimizes the risks of cheese wiring and stress relaxation, facilitating the minimally invasive repositioning of soft tissue in the head and neck, as well as optimizing and enhancing traditionally long and potentially tedious procedures in body contouring. This article highlights the advances, advantages, and efficacy associated with the use of barbed sutures in lifting and wound closure. PMID:21824547

  15. 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.

  16. Keratinocyte-Secreted Heat Shock Protein-90alpha: Leading Wound Reepithelialization and Closure

    PubMed Central

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Woodley, David T.; Li, Wei

    2016-01-01

    Significance: Delayed and nonhealing wounds pose a health, economic, and social problem worldwide. For decades, the conventional wisdom pointed to growth factors as the driving force of wound healing and granted them a center stage for therapeutic development. To date, few have obtained US FDA approvals or shown clinical effectiveness and safety. Critical Issue: Wound closure is the initial and most critical step during wound healing. Closing chronic wounds to shut down continued infection is the primary and likely the only achievable goal at the clinic in the foreseeable future. The critical question here is to identify the factor(s) in wounded tissues that drives the initial wound closure. Recent Advances: We made an unexpected discovery of the secreted form of heat shock protein-90alpha (Hsp90α) for promoting skin cell motility, reepithelialization, and wound closure. Secreted Hsp90α possesses unique properties to remain functional under the hostile wound environment that compromises conventional growth factors' effectiveness. Through the common lipoprotein receptor-related protein-1 cell surface receptor and activation of the Akt signaling pathway, topical application of human recombinant Hsp90α protein greatly accelerates excision, burn, and diabetic skin wound closure in rodent and porcine models. Future Directions: In almost all cells, the 2–3% of their total proteins (∼7,000 per cell) are Hsp90 (α and β), a long unraveled puzzle. Our new finding of Hsp90 secretion in wounded tissues suggests that the stockpile of Hsp90α by all cells is to rapidly supply the need for extracellular Hsp90α to repair damaged tissues. We propose that keratinocytes at the wound edge secrete Hsp90α that leads the reepithelialization process to close the wound. PMID:27076995

  17. 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.

  18. Modeling closure of circular wounds through coordinated collective motion.

    PubMed

    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. PMID:26871883

  19. 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.

  20. 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.

  1. 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.

  2. A morphoelastic model for dermal wound closure.

    PubMed

    Bowden, L G; Byrne, H M; Maini, P K; Moulton, D E

    2016-06-01

    We develop a model of wound healing in the framework of finite elasticity, focussing our attention on the processes of growth and contraction in the dermal layer of the skin. The dermal tissue is treated as a hyperelastic cylinder that surrounds the wound and is subject to symmetric deformations. By considering the initial recoil that is observed upon the application of a circular wound, we estimate the degree of residual tension in the skin and build an evolution law for mechanosensitive growth of the dermal tissue. Contraction of the wound is governed by a phenomenological law in which radial pressure is prescribed at the wound edge. The model reproduces three main phases of the healing process. Initially, the wound recoils due to residual stress in the surrounding tissue; the wound then heals as a result of contraction and growth; and finally, healing slows as contraction and growth decrease. Over a longer time period, the surrounding tissue remodels, returning to the residually stressed state. We identify the steady state growth profile associated with this remodelled state. The model is then used to predict the outcome of rewounding experiments designed to quantify the amount of stress in the tissue, and also to simulate the application of pressure treatments. PMID:26264498

  3. 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

  4. 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. PMID:27487012

  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. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  8. 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

  9. Loxoscelism and negative pressure wound therapy (vacuum-assisted closure): an experimental study.

    PubMed

    Wong, S Lindsey; Schneider, Andrew M; Argenta, Louis C; Morykwas, Michael J

    2010-12-01

    Brown recluse spider (Loxosceles) bites cause lesions ranging from chronic necrotic ulcers to acute life-threatening sepsis. Based on our experience in treating acute and chronic wounds with negative pressure, we postulated that vacuum-assisted closure (VAC) would be valuable in this application. Chester pigs were procured and injected with purified brown recluse spider venom, 1 µl of venom in two anterior sites and 0·1 µl of venom in two posterior sites on their dorsum. For each concentration of venom, treatment consisted of either VAC or dry, non adherent dressings (control group). Each day, the wounds were inspected and measured. For wounds receiving 1·0 µl of venom, the control wounds decreased in surface area to 50% of initial size after 7 days and none had healed, whereas VAC-treated wounds were less than 50% after 48 hours and completely healed and reepithelialised after 8 days. Wounds with 0·1 µl of venom had 50% reduction after 5 days with no complete healing for control wounds, and the VAC wounds were 50% after 48 hours and all had closed and reepithelialised after 5 days. Our experimental study showed an accelerated healing time in the animals treated with the VAC as compared with controls. PMID:20666855

  10. Oxygenation state as a driver of myofibroblast differentiation and wound contraction: hypoxia impairs wound closure.

    PubMed

    Sen, Chandan K; Roy, Sashwati

    2010-12-01

    Myofibroblasts are ubiquitous in the human body and may form from the differentiation of fibroblasts, epithelial cells, endothelial cells, and mononuclear cells, among others. Their clinical significance could be substantial, depending on biomedical context. Myofibroblasts help contract open skin wounds, but they could also be key drivers of fibrosis across numerous tissue systems and support tumor invasiveness. Understanding the molecular events underlying myofibroblast formation is significant for many human diseases. In this issue, Modarressi et al. address the significance of wound tissue hypoxia in impairing wound contraction by compromising myofibroblast formation. They present compelling evidence indicating tissue hypoxia conflicts with wound closure. We are reminded that correcting wound tissue hypoxia is critical for the tissue's response to other therapeutic interventions. PMID:21068734

  11. Osmotic surveillance mediates rapid wound closure through nucleotide release

    PubMed Central

    Gault, William J.; Enyedi, Balázs

    2014-01-01

    Osmotic cues from the environment mediate rapid detection of epithelial breaches by leukocytes in larval zebrafish tail fins. Using intravital luminescence and fluorescence microscopy, we now show that osmolarity differences between the interstitial fluid and the external environment trigger ATP release at tail fin wounds to initiate rapid wound closure through long-range activation of basal epithelial cell motility. Extracellular nucleotide breakdown, at least in part mediated by ecto-nucleoside triphosphate diphosphohydrolase 3 (Entpd3), restricts the range and duration of osmotically induced cell migration after injury. Thus, in zebrafish larvae, wound repair is driven by an autoregulatory circuit that generates pro-migratory tissue signals as a function of environmental exposure of the inside of the tissue. PMID:25533845

  12. LXA4 actions direct fibroblast function and wound closure.

    PubMed

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

    2015-09-01

    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 A4 (LXA4), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA4 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 LXA4 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 LXA4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA4 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. LXA4 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 LXA4 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. PMID:26188508

  13. 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. PMID:26718553

  14. 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

  15. 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.

  16. Stochastic particle acceleration and statistical closures

    SciTech Connect

    Dimits, A.M.; Krommes, J.A.

    1985-10-01

    In a recent paper, Maasjost and Elsasser (ME) concluded, from the results of numerical experiments and heuristic arguments, that the Bourret and the direct-interaction approximation (DIA) are ''of no use in connection with the stochastic acceleration problem'' because (1) their predictions were equivalent to that of the simpler Fokker-Planck (FP) theory, and (2) either all or none of the closures were in good agreement with the data. Here some analytically tractable cases are studied and used to test the accuracy of these closures. The cause of the discrepancy (2) is found to be the highly non-Gaussian nature of the force used by ME, a point not stressed by them. For the case where the force is a position-independent Ornstein-Uhlenbeck (i.e., Gaussian) process, an effective Kubo number K can be defined. For K << 1 an FP description is adequate, and conclusion (1) of ME follows; however, for K greater than or equal to 1 the DIA behaves much better qualitatively than the other two closures. For the non-Gaussian stochastic force used by ME, all common approximations fail, in agreement with (2).

  17. Report on immediate irradiation of a rapidly growing sarcoma of the scalp prior to wound closure.

    PubMed

    Müller, Cornelia Sigrid Lissi; Jungmann, Janina; Pföhler, Claudia; Mohammad, Farid; Rübe, Christian; Vogt, Thomas

    2016-05-01

    Cutaneous sarcomas are primarily treated with extensive surgery, and occasionally require adjuvant radiation therapy following complete wound healing. Thus, sarcoma surgery leads to large and deep wounds, and the initiation of adjuvant radiation therapy depends on the time required for defect closure. We present the case of a male patient with pleomorphic sarcoma of the temporal skin, which was treated with multiple wide and deep excisions, instant application of an Integra(®) bilayer, and immediate radiation therapy prior to wound closure. The objective was to investigate the usefulness of a dermal substitute (Integra(®) ) in accelerating the effect of adjuvant radiation therapy on scalp defects after tumor surgery. A ring-shaped skin area - at risk for recurrence - around the Integra(®) bilayer was irradiated with a total of 59.4 Gy. No necrosis, infection, or major radiotoxicity was observed, and a subsequent split skin graft following radiation therapy remained fully vital until complete healing. In conclusion, a combined procedure consisting of sequential tumor surgery and subsequent application of a dermal substitute in conjunction with immediate initiation of adjuvant radiation therapy is, in principle, possible, and may permit innovative therapeutic options in dermatooncology and dermatosurgery. PMID:27119488

  18. Potential Activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein Accelerating Wound Healing in Rats

    PubMed Central

    Dhiyaaldeen, Summaya M.; Alshawsh, Mohammed A.; Salama, Suzy M.; Alwajeeh, Nahla S. I.

    2014-01-01

    Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson's trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP (P < 0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-β and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing. PMID:24587992

  19. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

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

    PubMed Central

    Lundvig, Ditte M S; Scharstuhl, Alwin; Cremers, Niels A J; Pennings, Sebastiaan W C; te Paske, Jeroen; van Rheden, René; van Run-van Breda, Coby; Regan, Raymond F; Russel, Frans G M; Carels, Carine E; Maltha, Jaap C; Wagener, Frank A D T G

    2014-01-01

    Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal wound healing in HO-2 deficient mice is impaired with exorbitant inflammation and absence of HO-1 expression. This study addresses the role of HO-2 in cutaneous excisional wound healing using HO-2 knockout (KO) mice. Here, we show that HO-2 deficiency also delays cutaneous wound closure compared to WT controls. In addition, we detected reduced collagen deposition and vessel density in the wounds of HO-2 KO mice compared to WT controls. Surprisingly, wound closure in HO-2 KO mice was accompanied by an inflammatory response comparable to WT mice. HO-1 induction in HO-2 deficient skin was also similar to WT controls and may explain this protection against exaggerated cutaneous inflammation but not the delayed wound closure. Proliferation and myofibroblast differentiation were similar in both two genotypes. Next, we screened for candidate genes to explain the observed delayed wound closure, and detected delayed gene and protein expression profiles of the chemokine (C-X-C) ligand-11 (CXCL-11) in wounds of HO-2 KO mice. Abnormal regulation of CXCL-11 has been linked to delayed wound healing and disturbed angiogenesis. However, whether aberrant CXCL-11 expression in HO-2 KO mice is caused by or is causing delayed wound healing needs to be further investigated. PMID:25224969

  1. 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

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  2. 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

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  3. 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

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  4. 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

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  5. Delayed primary closure of deep sternal wound infections.

    PubMed Central

    Zacharias, A; Habib, R H

    1996-01-01

    Deep infections of the sternum and mediastinum, with prevalence of osteomyelitis and tissue necrosis, were documented in 38 of 8,056 patients (0.47%) who underwent open-heart surgery (1975 through 1994) in our service. The incidences of insulin-dependent diabetes, obesity, and emergency surgery in these patients were relatively high at 39%, 47%, and 18%, respectively. Treatment with antibiotics, débridement, open packing, and delayed closure was administered to 33 patients (87%), with 100% healing. There were no deaths in this group. Flap reconstruction was indicated in 5 gravely ill patients (13%) in whom excessively large wound defects did not allow reapproximation. There were 2 deaths in this group, and 4 reoperations were necessary in the surviving patients because of sequelae arising from flap reconstruction. The overall mortality was 5.3% and the median period of hospitalization was 29 days. The length of stay decreased substantially over the period of this study (median = 21 days, year > or = 1987). Accordingly, we believe that treatment of deep sternal infections with delayed primary closure is safe and effective. Also, given the increased potential for complications and long-term sequelae, we believe that flap reconstruction should be used selectively and should be limited to patients with large defects, uncontrolled mediastinal bleeding, or both. PMID:8885104

  6. Seed oil of Joannesia princeps improves cutaneous wound closure in experimental mice.

    PubMed

    Donato-Trancoso, Aline; Gonçalves, Lenicio; Monte-Alto-Costa, Andréa; da Silva, Francisco de Assis; Romana-Souza, Bruna

    2014-09-01

    Joannesia princeps (Cotieira) is a well known medicinal plant in Brazil, however, the therapeutic effects of oil obtained from its seeds have still not been demonstrated. The beneficial effects of J. princeps seed oil on cutaneous wound healing on the back of experimental mice were investigated. An excisional lesion in male Swiss mice (n=20 per group) was topically treated with mineral oil or J. princeps seed oil once a day beginning on the day of lesion until the third day after wounding. Animals were killed and lesions collected after 14 days. Murine skin fibroblast cultures were treated with J. princeps seed oil and fibroblast activity was evaluated. In the in vivo assay, J. princeps seed oil increased wound contraction and migratory tongue length, but reduced neutrophil and macrophage number when compared with the control group. Blood vessel number, collagen deposition, and VEGF levels were increased in treated lesions when compared with control lesions. However, J. princeps seed oil reduced myofibroblast density and carbonyl protein levels when compared with the control group. In the in vitro assay, treatment with J. princeps seed oil increased fibroblast migration and proliferation, but reduced myofibroblastic differentiation in vitro. In conclusion, J. princeps seed oil accelerates wound closure increasing angiogenesis, keratinocyte migration, and fibroblast activity while reducing inflammatory response and oxidative damage. PMID:25053454

  7. Delay of cutaneous wound closure by morphine via local blockade of peripheral tachykinin release

    PubMed Central

    Rook, Jerri M.; McCarson, Kenneth E.

    2007-01-01

    Topically applied morphine is routinely used to alleviate pain in cutaneous wounds such as burns and pressure sores. Evidence suggests the topical administration of exogenous opioid drugs may impair wound closure. This study examined the effects of topical morphine on a standardized model of cutaneous wound healing in the rat. Full-thickness 4mm diameter circular skin flaps were excised from the intrascapular region of male Sprague-Dawley rats. IntraSite™® Gel infused with either morphine-sulfate, neurokinin-1 (NK-1) or neurokinin-2 (NK-2) receptor antagonists, substance P (SP), neurokinin A (NKA), SP + morphine-sulfate, or NKA + morphine-sulfate was applied to the wound twice daily. Results demonstrated a significant overall delay in the time course of wound contraction in morphine-treated animals when compared with gel-only treated controls. The delay in wound contraction seen in morphine-treated animals increased in a concentration-dependent manner. Topical application of NK-1 or NK-2 receptor antagonists mimicked the effects of morphine in delaying wound closure, suggesting topical opioids impair wound closure via the inhibition of SP and NKA release peripherally into the healing wound. Additionally, no significant delays in closure were seen in rats receiving morphine combined with SP or NKA, demonstrating the ability of each neuropeptide to attenuate the effects of morphine in delaying wound closure and restore normal wound closure rates. The combination of SP or NKA and morphine-sulfate for wound therapy may provide local analgesia while maintaining normal closure rates. PMID:17632084

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

    PubMed

    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. 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

  10. Computer simulation of wound closure in epithelial tissues: Cell-basal-lamina adhesion

    NASA Astrophysics Data System (ADS)

    Nagai, Tatsuzo; Honda, Hisao

    2009-12-01

    The mechanism of wound closure in epithelial tissues, i.e., cell monolayer sheets, is investigated through computer simulations. A wound means an area in which some cells have been removed from the normal tissue. The vertex dynamics cell model [T. Nagai and H. Honda, Philos. Mag. B 81, 699 (2001)], which describes morphogenesis of epithelial tissues using the concepts of statistical physics, is modified and applied to the closure of small wounds without mitosis. It is shown that cell-basal-lamina adhesion governs the wound closure competing with cell-cell adhesion and cell elasticity. The simulation results reproduce the actual wound closure process qualitatively and partly quantitatively. The closing proceeds with the translation of the edges of wound polygons toward the wound center and the intermittent reduction in the number of polygon edges. Over time, the process leads to an exponential decrease in the wound area. A shape factor is introduced to describe the wound shape quantitatively and is used to examine the time variation thereof. A method for determining model parameters by comparison with the experiments is given.

  11. 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.

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

    PubMed

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

    2016-06-15

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

  14. 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. PMID:25794496

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

    PubMed

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

    2015-01-01

    Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP-1 (96/320 μg kg BW) was topically applied to the wound daily and wound size measured. At days 3, 7, and 14, skin samples were collected from the wound sites. AM/AMBP-1 treated group had significantly smaller wound surface area than the vehicle group over the 14-day time course. At day 3, AM/AMBP-1 promoted neutrophil infiltration (MPO), increased cytokine levels (IL-6 and TNF-α), angiogenesis (CD31, VEGF and TGFβ-1) and cell proliferation (Ki67). By day 7 and 14, AM/AMBP-1 treatment decreased MPO, followed by a rapid resolution of inflammation characterized by a decrease in cytokines. At the matured stage, AM/AMBP-1 treatment increased the alpha smooth muscle actin expression (mature blood vessels) and Masson-Trichrome staining (collagen deposition) along the granulation area, and increased MMP-9 and decreased MMP-2 mRNA expressions. TGFβ-1 mRNA levels in AM/AMBP-1 group were 5.3 times lower than those in the vehicle group. AM/AMBP-1 accelerated wound healing by promoting angiogenesis, collagen deposition and remodeling. Treatment also shortened the days to reach plateau for wound closure. Thus, AM/AMBP-1 may be further developed as a therapeutic for cutaneous wound healing. PMID:25781901

  16. A comparison of three methods of wound closure following arthroplasty: a prospective, randomised, controlled trial.

    PubMed

    Khan, R J K; Fick, D; Yao, F; Tang, K; Hurworth, M; Nivbrant, B; Wood, D

    2006-02-01

    We carried out a blinded prospective randomised controlled trial comparing 2-octylcyanoacrylate (OCA), subcuticular suture (monocryl) and skin staples for skin closure following total hip and total knee arthroplasty. We included 102 hip replacements and 85 of the knee.OCA was associated with less wound discharge in the first 24 hours for both the hip and the knee. However, with total knee replacement there was a trend for a more prolonged wound discharge with OCA. With total hip replacement there was no significant difference between the groups for either early or late complications. Closure of the wound with skin staples was significantly faster than with OCA or suture. There was no significant difference in the length of stay in hospital, Hollander wound evaluation score (cosmesis) or patient satisfaction between the groups at six weeks for either hips or knees. We consider that skin staples are the skin closure of choice for both hip and knee replacements. PMID:16434531

  17. Granzyme B degrades extracellular matrix and contributes to delayed wound closure in apolipoprotein E knockout mice

    PubMed Central

    Hiebert, P R; Wu, D; Granville, D J

    2013-01-01

    Chronic inflammation and excessive protease activity have a major role in the persistence of non-healing wounds. Granzyme B (GzmB) is a serine protease expressed during chronic inflammation that, in conjunction with perforin, has a well-established role in initiating apoptotic cell death. GzmB is also capable of acting extracellularly, independent of perforin and can degrade several extracellular matrix (ECM) proteins that are critical during wound healing. We used apolipoprotein E (ApoE) knockout (AKO) mice as a novel model of chronic inflammation and impaired wound healing to investigate the role of GzmB in chronic wounds. Wild-type and AKO mice were grown to 7 weeks (young) or 37 weeks (old) of age on a regular chow or high-fat diet (HFD), given a 1-cm diameter full thickness wound on their mid dorsum and allowed to heal for 16 days. Old AKO mice fed a HFD exhibited reduced wound closure, delayed contraction, chronic inflammation and altered ECM remodeling. Conversely, GzmB/ApoE double knockout mice displayed improved wound closure and contraction rates. In addition, murine GzmB was found to degrade both fibronectin and vitronectin derived from healthy mouse granulation tissue. In addition, GzmB-mediated degradation of fibronectin generated a fragment similar in size to that observed in non-healing mouse wounds. These results provide the first direct evidence that GzmB contributes to chronic wound healing in part through degradation of ECM. PMID:23912712

  18. Evaluation of negative pressure vacuum-assisted system in acute and chronic wounds closure: our experience.

    PubMed

    Chiummariello, S; Guarro, G; Pica, A; Alfano, C

    2012-10-01

    Negative-pressure therapy or vacuum-assisted closure (VAC) has been used in clinical applications since the 1940's and has increased in popularity over the past decade. This dressing technique consists of an open cell foam dressing put into the wound cavity, a vacuum pump produces a negative pressure and an adhesive drape. A controlled sub atmospheric pressure from 75 to 150 mmHg is applied. The vacuum-assisted closure has been applied by many clinicians to chronic wounds in humans; however it cannot be used as a replacement for surgical debridement. The initial treatment for every contaminated wound should be the necrosectomy. The VAC therapy has a complementary function and the range of its indications includes pressure sores, stasis ulcers, chronic wounds such as diabetic foot ulcers, post traumatic and post operative wounds, infected wounds such as necrotizing fasciitis or sternal wounds, soft-tissue injuries, bone exposed injuries, abdominal open wounds and for securing a skin graft. We describe our experience with the VAC dressing used to manage acute and chronic wounds in a series of 135 patients, with excellent results together with satisfaction of the patients. PMID:23095568

  19. Engineered human vascularized constructs accelerate diabetic wound healing.

    PubMed

    Shen, Yu-I; Cho, Hongkwan; Papa, Arianne E; Burke, Jacqueline A; Chan, Xin Yi; Duh, Elia J; Gerecht, Sharon

    2016-09-01

    Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy. PMID:27328431

  20. 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. PMID:26177141

  1. Calcium-Based Nanoparticles Accelerate Skin Wound Healing

    PubMed Central

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

    2011-01-01

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

  2. 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

    2015-05-01

    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

  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. A randomized, prospective study of total hip wound closure with resorbable subcuticular staples.

    PubMed

    Fisher, David A; Bengero, Lowell L; Clapp, Brenda C; Burgess, Mary

    2010-09-01

    Resorbable subcuticular staples are a new way to close surgical wounds and have not been reported in the orthopedic literature. This randomized, controlled study compared a resorbable subcuticular staple system with stainless steel wound stapling in patients undergoing unilateral primary total hip arthroplasty (THA). Institutional Review Board approval and patient consent was obtained for all patients. Sixty patients (30 each group) were randomized to receive either resorbable subcuticular staples or stainless steel staples after primary THA. Incision length, number of staples used, and any staple insertion problems were recorded. Subjective reports of pain levels or incision complaints were solicited, and wound photographs were obtained on days 1 and 14 and 6 weeks postoperatively. The presence of wound drainage, erythema, wound separation, or echymosis was recorded at each visit, as well as all postoperative complications. The average incision length in the resorbable group was 13.2 cm and required 16 staples for closure, compared to 15 cm and 20 staples for the metal staple group. No infections occurred in either group, although the incidence of erythema and wound drainage at 2 weeks was higher for patients in the stainless steel group. One patient with metal staples had a postoperative hematoma requiring secondary irrigation and debridement. Patient satisfaction was higher with the resorbable staples. A resorbable subcuticular staple system can provide comparable wound closure to stainless steel staples following THA and may do so with less local discomfort, wound drainage, or erythematous reaction. PMID:20839703

  5. Feasibility and Safety of Absorbable Knotless Wound Closure Device in Laparoscopic Myomectomy

    PubMed Central

    Chan, Chying-Chyuan; Lee, Ching-Yu

    2016-01-01

    Purpose. Myomectomy has been performed through laparoscopy. Suturing is known as rate-limiting step in laparoscopic myomectomy. The present study was aimed at comparing the clinical outcomes of absorbable knotless wound closure device with the results of conventional suturing. Methods. This prospective study included 62 women who underwent laparoscopic myomectomy at Taipei City Hospital, Zhongxiao Branch, from January 2010 through to August 2012. The patients were randomized into two groups according to suturing materials, the knotless group and the 2-0 Vicryl suture group. Patient demographics, overall operative time, and intraoperative blood loss were compared between two groups. Results. Demographic characteristics and laboratory variables before surgery were comparable. Operative time was significantly shorter in knotless group compared with that in 2-0 Vicryl suture group (112 ± 47 versus 147 ± 63 minutes; p < 0.05). The results revealed a significant difference in intraoperative blood loss between two groups (knotless versus 2-0 Vicryl: 112.8 ± 54.2 versus 143.6 ± 64.9). Use of absorbable knotless wound closure device was associated with greater hemostasis compared with that of 2-0 Vicryl. During a 2-year follow-up period, 12 patients (46.2%) from the group with absorbable knotless wound closure device and 14 patients (38.9%) from 2-0 Vicryl suture group became pregnant. Conclusion. Closure of myometrium using absorbable knotless wound closure device after laparoscopic myomectomy resulted in a shorter operative time and less blood loss. PMID:27429977

  6. Loxoscelism and negative pressure wound therapy (vacuum-assisted closure): a clinical case series.

    PubMed

    Wong, S Lindsey; Defranzo, Andrew J; Morykwas, Michael J; Argenta, Louis C

    2009-11-01

    Brown recluse spider (Loxosceles sp) bites continue to be a significant challenge to manage clinically. Sequelae from these lesions range from chronic necrotic ulcers that persist for months to an acute life-threatening course of sepsis. Negative pressure wound therapy using vacuum-assisted closure (VAC) has been described for use in both acute and chronic wounds. We present a novel application for the use of this therapy in a retrospective review of eight clinical cases treated with the VAC. PMID:19927520

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

    PubMed

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

    1997-03-01

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

  8. 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.

  9. 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

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

    PubMed

    Heymanns, Verena; Oseni, Abidemi W; Alyeldien, Ameer; Maslehaty, Homajoun; Parvin, Richard; Scholz, Martin; Petridis, Athanasios K

    2016-04-26

    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

  11. Inertial-particle accelerations in turbulence: a Lagrangian closure

    NASA Astrophysics Data System (ADS)

    Vajedi, S.; Gustavsson, K.; Mehlig, B.; Biferale, L.

    2016-07-01

    The distribution of particle accelerations in turbulence is intermittent, with non-Gaussian tails that are quite different for light and heavy particles. In this article we analyse a closure scheme for the acceleration fluctuations of light and heavy inertial particles in turbulence, formulated in terms of Lagrangian correlation functions of fluid tracers. We compute the variance and the flatness of inertial particle accelerations and we discuss their dependency on the Stokes number. The closure incorporates effects induced by the Lagrangian correlations along the trajectories of fluid tracers, and its predictions agree well with results of direct numerical simulations of inertial particles in turbulence, provided that the effects induced by the inertial preferential sampling of heavy/light particles outside/inside vortices are negligible. In particular, the scheme predicts the correct functional behaviour of the acceleration variance, as a function of Stokes, as well as the presence of a minimum/maximum for the flatness of the acceleration of heavy/light particles, in good qualitative agreement with numerical data. We also show that the closure works well when applied to the Lagrangian evolution of particles using a stochastic surrogate for the underlying Eulerian velocity field. Our results support the conclusion that there exist important contributions to the statistics of the acceleration of inertial particles independent of the preferential sampling. For heavy particles we observe deviations between the predictions of the closure scheme and direct numerical simulations, at Stokes numbers of order unity. For light particles the deviation occurs for larger Stokes numbers.

  12. Wound closure in the lamellipodia of single cells: mediation by actin polymerization in the absence of an actomyosin purse string.

    PubMed

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

    2002-03-01

    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

  13. Vacuum-assisted closure increases ICAM-1, MIF, VEGF and collagen I expression in wound therapy

    PubMed Central

    WANG, WEIYANG; PAN, ZHENYU; HU, XIANG; LI, ZONGHUAN; ZHAO, YONG; YU, AI-XI

    2014-01-01

    Severe traumatic wounds are challenging to manage during surgery. The introduction of vacuum-assisted closure (VAC) is a breakthrough in wound management. The aim of the present study was to investigate the effect of VAC on cytokines in wounds during the management of severe traumatic wounds following initial debridement. VAC and conventional wound care (CWC) were independently applied to severe traumatic wounds on pigs. The expression levels of intercellular adhesion molecule-1 (ICAM-1), migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor, collagen I and human fibroblast collagenase 1 were detected by quantitative polymerase chain reaction and western blotting. VAC significantly increased the expression of ICAM-1, MIF, VEGF and collagen I compared with that induced by CWC at the protein and mRNA levels. Therefore, the results of the present study indicate that VAC therapy is an effective method for treating severe traumatic wounds, as it increases the expression of cytokines in wounds. VAC significantly increases the expression of ICAM-1, MIF, VEGF and collagen I to manage severe traumatic wounds. PMID:24940415

  14. Enhancement of lysine acetylation accelerates wound repair

    PubMed Central

    Spallotta, Francesco; Cencioni, Chiara; Straino, Stefania; Sbardella, Gianluca; Castellano, Sabrina; Capogrossi, Maurizio C; Martelli, Fabio; Gaetano, Carlo

    2013-01-01

    In physiopathological conditions, such as diabetes, wound healing is significantly compromised and chronic complications, including ulcers, may occur. In a mouse model of skin repair, we recently reported that wound treatment with Sirtuin activators and class I HDAC inhibitors induced keratinocyte proliferation and enhanced healing via a nitric oxide (NO) dependent mechanism. We observed an increase in total protein acetylation in the wound area, as determined by acetylation of α-tubulin and histone H3 Lysine 9. We reasoned that this process activated cell function as well as regulated gene expression to foster tissue repair. We report here that the direct activation of P300/CBP-associated factor (PCAF) by the histone acetylase activator pentadecylidenemalonate 1b (SPV-106) induced Lysine acetylation in the wound area. This intervention was sufficient to enhance repair process by a NO-independent mechanism. Hence, an impairment of PCAF and/or other GCN5 family acetylases may delay skin repair in physiopathological conditions. PMID:24265859

  15. A blinded, prospective, randomized controlled trial of topical negative pressure wound closure in India.

    PubMed

    Mody, Gita N; Nirmal, Ida Anita; Duraisamy, Sulochana; Perakath, Benjamin

    2008-12-01

    Wound closure using topical negative pressure (TNP) has been reported to be effective, but equipment costs can be prohibitive in resource-challenged countries. Because nonhealing wounds are exceedingly common in developing countries such as India, the ability to optimize wound care with limited resources is very important. To investigate the feasibility and efficacy of providing TNP in an Indian medical referral center, a randomized controlled trial comparing a locally constructed TNP device (treatment) to wet-to-dry gauze dressings (control) was conducted. Eligible study participants (N = 48) were recruited from the inpatient wards. Wound etiologies included diabetic foot ulcers (15), pressure ulcers (11), cellulitis/fasciitis (11), and "other" (11). Following enrollment, wound size was assessed using computer-aided measurements of digital photographs and block-randomized to the study arms using a concealed allocation table. Wounds in both treatment groups were débrided before dressing application and patients were followed until wound closure or being lost to follow-up for an average of 26.3 days (+/- 18.5) in the control and 33.1 days (+/- 37.3) in the treatment group. No statistically significant differences in time to closure between the two treatment groups were observed except in a subset analysis of pressure ulcers (mean 10 +/- 7.11 days for treatment and 27 +/- 10.6 days in control group, P = 0.05). Direct costs to close a pressure ulcer also were lower in the TNP than in the control group. A review of the literature suggests the outcomes obtained using a locally constructed TNP device are similar to those obtained using commercially available devices. As a result of this study, a dedicated tissue viability team has been established to identify wounds suitable for TNP, oversee treatment, monitor the need for surgical débridement, and employ wound healing principles and technology appropriately. These results suggest that inexpensive materials can be

  16. Recombinant basic fibroblast growth factor accelerates wound healing.

    PubMed

    McGee, G S; Davidson, J M; Buckley, A; Sommer, A; Woodward, S C; Aquino, A M; Barbour, R; Demetriou, A A

    1988-07-01

    Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds. PMID:3392988

  17. 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. PMID:26749197

  18. Immobilized thrombin receptor agonist peptide accelerates wound healing in mice.

    PubMed

    Strukova, S M; Dugina, T N; Chistov, I V; Lange, M; Markvicheva, E A; Kuptsova, S; Zubov, V P; Glusa, E

    2001-10-01

    To accelerate the healing processes in wound repair, attempts have been repeatedly made to use growth factors including thrombin and its peptide fragments. Unfortunately, the employment of thrombin is limited because of its high liability and pro-inflammatory actions at high concentrations. Some cellular effects of thrombin in wound healing are mediated by the activation of protease activated receptor-1 (PAR-1). The thrombin receptor agonist peptide (TRAP:SFLLRN) activates this receptor and mimics the effects of thrombin, but TRAP is a relatively weak agonist. We speculated that the encapsulated peptide may be more effective for PAR-1 activation than nonimmobilized peptide and developed a novel method for TRAP encapsulation in hydrogel films based on natural and synthetic polymers. The effects of an encapsulated TRAP in composite poly(N-vinyl caprolactam)-calcium alginate (PVCL) hydrogel films were investigated in a mouse model of wound healing. On day 7 the wound sizes decreased by about 60% under TRAP-chitosan-containing PVCL films, as compared with control films without TRAP. In the case of TRAP-polylysine-containing films no significant decrease in wound sizes was found. The fibroblast/macrophage ratio increased under TRAP-containing films on day 3 and on day 7. The number of proliferating fibroblasts increased to 150% under TRAP-chitosan films on day 7 as compared with control films. The number of [3H]-thymidine labeled endothelial and epithelial cells in granulation tissues was also enhanced. Thus, the immobilized TRAP to PVCL-chitosan hydrogel films were found to promote wound healing following the stimulation of fibroblast and epithelial cell proliferation and neovascularization. Furthermore, TRAP was shown to inhibit the secretion of the inflammatory mediator PAF from stimulated rat peritoneal mast cells due to augmentation of NO release from the mast cells. The encapsulated TRAP is suggested to accelerate wound healing due to the anti-inflammatory effects

  19. Negative pressure wound therapy accelerates rats diabetic wound by promoting agenesis

    PubMed Central

    Li, Xiaoqiang; Liu, Jiaqi; Liu, Yang; Hu, Xiaolong; Dong, Maolong; Wang, Hongtao; Hu, Dahai

    2015-01-01

    Negative Pressure Wound Therapy (NPWT) has become widely adopted to several wound treatment over the last 15 years, including diabetic foot ulcer (DFU). Much of the existing evidence supports that NPWT increase in blood flow, reduce in edema, decrease bacterial proliferation and accelerate granulation-tissue formation. However, the accurate mechanism is not clear till now. The aim of the present study was to further elucidate the effects of NPWT on angiogenesis of diabetic wound model. As result, our data showed: 1) NPWT promoted the wound healing and blood perfusion on both diabetic and normal wound compared with control, 2) The NPWT increased wound vessel density, and the wound treated with NPWT showed well developed and more functional vessels at day 7 post operation compared with control 3) NPWT up regulated the expression of VEGF at day 3 and Ang1 at day 7 on RNA and protein level. 4) Ang2 was up regulated in diabetic rats but NPWT attenuated this affection. Our data indicated that NPWT increased vessel density and promoted the maturation of neovascular over the potential mechanism of up regulated VEGF and Ang1 and down regulated of Ang2. PMID:26064242

  20. Morphine-induced early delays in wound closure: involvement of sensory neuropeptides and modification of neurokinin receptor expression

    PubMed Central

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

    2014-01-01

    Dose-limiting side effects of centrally-acting opioid drugs have led to the use of topical opioids to reduce the pain associated with chronic cutaneous wounds. However, previous studies indicate that topical morphine application impairs wound healing. This study was designed to elucidate the mechanisms by which morphine delays wound closure. Rats were depleted of sensory neuropeptides by treatment with capsaicin, and full-thickness 4 mm diameter wounds were excised from the intrascapular region. Wounds were treated topically twice daily with 5 mM morphine sulfate, 1 mM substance P, 1 mM neurokinin A, or 5 mM morphine combined with 1 m M substance P or neurokinin A and wound areas assessed. During closure, wound tissue was taken 1, 3, 5, and 8 days post-wounding from control and morphine-treated rats and immunostained for neurokinin receptors and markers for macrophages, myofibroblasts, and vasculature. Results obtained from capsaicin-treated animals demonstrated a significant delay in the early stages of wound contraction that was reversed by neuropeptide application. Treatment of capsaicin-treated rats with topical morphine did not further delay wound closure, suggesting that topical opioids impair wound closure via the inhibition of peripheral neuropeptide release into the healing wound. Morphine application altered neurokinin-1 and neurokinin-2 receptor expression in inflammatory and parenchymal cells essential for wound healing in a cell-specific manner, demonstrating a direct effect of morphine on neurokinin receptor regulation within an array of cells involved in wound healing. These data provide evidence indicating a potentially detrimental effect of topical morphine application on the dynamic wound healing process. PMID:19428329

  1. 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

  2. Effect of Adhesive Strips and Dermal Sutures vs Dermal Sutures Only on Wound Closure

    PubMed Central

    Custis, Trenton; Armstrong, April W.; King, Thomas H.; Sharon, Victoria R.; Eisen, Daniel B.

    2016-01-01

    IMPORTANCE Although applying adhesive strips to a wound closure has been shown to have outcomes equivalent to those with cuticular suturing, it is unknown whether adhesive strips provide additional benefit compared with dermal suturing alone. OBJECTIVE To determine whether the addition of adhesive strips to a wound closed with buried interrupted subcuticular sutures improves outcomes following wound closure. DESIGN, SETTING, AND PARTICIPANTS A prospective, randomized split-wound intervention was conducted between November 14, 2013, and May 16, 2014, in patients who underwent cutaneous surgical procedures at the University of California, Davis, outpatient dermatology clinic. Fifty-seven patients 18 years or older with postoperative defects of at least 3 cm, resulting from either Mohs micrographic surgical procedures or surgical excision, were screened for participation. Nine patients were excluded and 48 were enrolled. INTERVENTIONS Half of each wound was randomized to receive buried interrupted subcuticular sutures and overlying adhesive strips and the other half received buried interrupted subcuticular sutures only. MAIN OUTCOMES AND MEASURES At 3 months’ follow-up, each patient and 2 blinded observers evaluated the wound using the Patient Observer Scar Assessment Scale. RESULTS The total mean (SD) Patient Observer Scar Assessment Scale score for observers for the side that received a combination of adhesive strips and buried interrupted subcuticular suturing (12.3 [4.8]) and the side that received sutures only (12.9 [6.3]) did not differ significantly at 3 months (P = .32). There was no significant difference in the total patient assessment scale score between the combination closure (14.0 [7.6]) and sutures only (14.7 [7.6]) sides at 3 months (P = .39). There was also no significant difference between the 2 closure methods in terms of mean (SD) scar width (both methods: 1.1 [0.8] mm, P = .89) at follow-up. CONCLUSIONS AND RELEVANCE Combination closure with

  3. Sutureless closure of scleral wounds in animal models by the use of laser welded biocompatible patches

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Matteini, Paolo; Menabuoni, Luca; Lenzetti, Ivo; Pini, Roberto

    2011-03-01

    The common procedures used to seal the scleral or conjunctival injuries are based on the traditional suturing techniques, that may induce foreign body reaction during the follow up, with subsequent inflammation and distress for the patient. In this work we present an experimental study on the laser welding of biocompatible patches onto ocular tissues, for the closure of surgical or trauma wounds. The study was performed ex vivo in animal models (porcine eyes). A penetrating perforation of the ocular tissue was performed with a surgical knife. The wound walls were approximated, and a biocompatible patch was put onto the outer surface of the tissue, in order to completely cover the wound as a plaster. The patches were prepared with a biocompatible and biodegradable polymer, showing high mechanical strength, good elasticity, high permeability for vapour and gases and rather low biodegradation. During preparation, Indocyanine Green (ICG) was included in the biopolymeric matrix, so that the films presented high absorption at 810 nm. Effective adhesion of the membranes to the ocular tissues was obtained by using diode laser light emitted from an 810 nm diode laser and delivered by means of a 300 μm core diameter optical fiber, to produce spots of local film/tissue adhesion, due to the photothermal effect at the interface. The result is an immediate closure of the wound, thus reducing post-operative complications due to inflammation.

  4. Mathematical modeling of airway epithelial wound closure during cyclic mechanical strain.

    PubMed

    Savla, Ushma; Olson, Lars E; Waters, Christopher M

    2004-02-01

    The repair of airway epithelium after injury is crucial in restoring epithelial barrier integrity. Because the airways are stretched and compressed due to changes in both circumferential and longitudinal dimensions during respiration and may be overdistended during mechanical ventilation, we investigated the effect of cyclic strain on the repair of epithelial wounds. Both cyclic elongation and compression significantly slowed repair, with compression having the greatest effect. We developed a mathematical model of the mechanisms involved in airway epithelial cell wound closure. The model focuses on the differences in spreading, migration, and proliferation with cyclic strain by using separate parameters for each process and incorporating a time delay for the mitotic component. Numerical solutions of model equations determine the shape of the diffusive wave solutions of cell density that correspond to the influx of cells into the wound during the initial phase of reepithelialization. Model simulations were compared with experimental measurements of cell density and the rate of wound closure, and parameters were determined based on measurements from airway epithelial cells from several different sources. The contributions of spreading, migration, and mitosis were investigated both numerically and experimentally by using cytochalasin D to inhibit cell motility and mitomycin C to inhibit proliferation. PMID:14715680

  5. Extensive Mine-Shrapnel and Gunshot Wound Closure Using Keystone Island Perforator Flaps

    PubMed Central

    Sliesarenko, Sergii V.; Sliesarenko, Kirill S.

    2016-01-01

    Background: During military operations, one aspect of a plastic surgeon’s work is to restore extensive and deep wound defects in a short period of time and provide a high degree of functional recovery to the damaged area. Because many injuries caused by military operations cannot be closed using a primary suture, the specialist has to select another surgical approach to close the wound defect. Surgeons must select methods that not only cover the extensive wound defect in 1 step but also allow skin coverage that is anatomically, functionally, and visually similar to the surrounding tissues to reduce the length of the hospital stay and ensure optimal functional recovery of the damaged organ. Methods: From 2014 to 2015, 25 patients underwent 36 reconstructions at our center after receiving mine-shrapnel and gunshot wounds. All reconstructions occurred during the acute period and used keystone island perforator flaps. The authors’ wound management technique was characterized by an aggressive surgical and antibiotic therapy protocol. Results: In all cases, after surgical debridement, the mine-shrapnel and gunshot wound defects were completely closed in 1 stage during the acute period. The working time in the operating room to perform the transposition of the flap ranged from 45 to 90 minutes, with an average of 68 minutes. All displaced flaps were similar in structure and color to the surrounding tissues and did not change the contours of the body. The adequate restoration of skin allowed patients to begin early recovery of functional activity. Conclusions: Local keystone island perforator flaps can be considered one of the primary methods of plastic closure of extensive defects caused by mine-shrapnel and gunshot wounds at different anatomical locations, providing that the tissue surrounding the defect is intact and usable as a donor resource. PMID:27579247

  6. Environmental Assessment for the Accelerated Tank Closure Demonstration Project

    SciTech Connect

    N /A

    2003-06-16

    The U.S. Department of Energy's (DOE) Office of River Protection (ORP) needs to collect engineering and technical information on (1) the physical response and behavior of a Phase I grout fill in an actual tank, (2) field deployment of grout production equipment and (3) the conduct of component closure activities for single-shell tank (SST) 241-C-106 (C-106). Activities associated with this Accelerated Tank Closure Demonstration (ATCD) project include placement of grout in C-106 following retrieval, and associated component closure activities. The activities will provide information that will be used in determining future closure actions for the remaining SSTs and tank farms at the Hanford Site. This information may also support preparation of the Environmental Impact Statement (EIS) for Retrieval, Treatment, and Disposal of Tank Waste and Closure of Single-Shell Tanks at the Hanford Site, Richland, Washington (Tank Closure EIS). Information will be obtained from the various activities associated with the component closure activities for C-106 located in the 241-C tank farm (C tank farm) under the ''Resource Conservation and Recovery Act of 1976'' (RCRA) and the Hanford Federal Facility Agreement and Consent Order (HFFACO) (Ecology et al. 1989). The impacts of retrieving waste from C-106 are bounded by the analysis in the Tank Waste Remediation System (TWRS) EIS (DOE/EIS-0189), hereinafter referred to as the TWRS EIS. DOE has conducted and continues to conduct retrieval activities at C-106 in preparation for the ATCD Project. For major federal actions significantly affecting the quality of the human environment, the ''National Environmental Policy Act of 1969'' (NEPA) requires that federal agencies evaluate the environmental effects of their proposed and alternative actions before making decisions to take action. The President's Council on Environmental Quality (CEQ) has developed regulations for implementing NEPA. These regulations are found in Title 40 of the Code

  7. Annexin 2 Regulates Intestinal Epithelial Cell Spreading and Wound Closure through Rho-Related Signaling

    PubMed Central

    Babbin, Brian A.; Parkos, Charles A.; Mandell, Kenneth J.; Winfree, L. Matthew; Laur, Oskar; Ivanov, Andrei I.; Nusrat, Asma

    2007-01-01

    Epithelial cell migration is a critical event in gastrointestinal mucosal wound healing and is dependent on actin cytoskeletal reorganization. We observed increased expression of an actin regulatory protein, annexin 2, in migrating intestinal epithelial cells. Small interfering RNA (siRNA)-mediated knockdown of annexin 2 expression in Caco-2 epithelial cells resulted in significant reductions in cell spreading and wound closure associated with decreased formation of filamentous actin bundles along the base of migrating cells. Because annexin 2 has been shown to influences actin cytoskeletal remodeling through targeting signaling molecules to membrane domains, we examined the membrane association and activation status of Rho GTPases after annexin 2 knockdown. We observed Rho dissociation from membranes and decreased Rho activity following annexin 2 siRNA transfection. Inhibition of cell spreading and wound closure in annexin 2 siRNA-transfected cells was prevented by expression of constitutively active RhoA. Rho colocalized with annexin 2 in lamellipodia and along the cytoplasmic face of the plasma membrane. In addition, annexin 2 was observed to co-immunoprecipitate with endogenous Rho and constitutively active RhoA. These findings suggest that annexin 2 plays a role in targeting Rho to cellular membranes, thereby modulating Rho-related signaling events regulating cytoskeletal reorganization during epithelial cell migration. PMID:17322380

  8. 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

  9. Offset layered closure reduces deep wound infection in early-onset scoliosis surgery.

    PubMed

    Grzywna, Alexandra M; Miller, Patricia E; Glotzbecker, Michael P; Emans, John B

    2016-07-01

    Deep wound infection is a common complication in early-onset scoliosis (EOS) surgery. Soft tissue technique has received less attention as a means to reduce infection. A retrospective review of 1170 EOS surgeries (single surgeon, institution) investigated the impact of offset layered closure (OLC) and soft tissue awareness. The introduction of OLC reduced deep infection from 3.0% in 99 surgeries to 0.37% in 1071. Logistic regression confirmed that OLC led to significantly lower odds of infection (P=0.007). This deep infection rate (0.37%) is more typical of elective surgery, providing a more optimistic view of infection in EOS surgery than generally reported. PMID:27196268

  10. Barbed versus traditional sutures for wound closure in knee arthroplasty: a systematic review and meta-analysis

    PubMed Central

    Zhang, Wei; Xue, Deting; Yin, Houfa; Xie, Hui; Ma, Honghai; Chen, Erman; Hu, Dongcai; Pan, Zhijun

    2016-01-01

    Sutures are an increasing focus of research in knee arthroplasty (KA). Whether knotless barbed sutures (KBS) are safe and efficient in KA remains controversial. The objective of our study is to compare the clinical outcomes of KA according to wound closure method: KBS versus knotted traditional sutures (KTS). To clarify this, we conducted a systematic review and meta-analysis. Nine articles involving 10 studies were included in this study. The dataset consisted of 1729 patients with 1754 KA. Among these, 814 patients’ wounds were closed with KBS and 915 with KTS. Our analysis indicates that KBS is preferable for KA wound closure given its shorter wound closure time and lower total cost; postoperative Knee Society scores and complication rates were similar to those of surgeries using KTS. The subgroup analysis revealed that closure of arthrotomy with KBS appears to be associated with a lower risk of complications. This meta-analysis indicates that use of KBS in KA reduces operative time and cost. KBS is the preferred option for wound closures, including arthrotomy and reattachment of subcutaneous and subcuticular tissues. Given the possible biases, adequately powered and better-designed studies with longer follow-up are required to reach a firmer conclusion. PMID:26805714

  11. Topical 5-azacytidine accelerates skin wound healing in rats.

    PubMed

    Gomes, Fabiana S; de-Souza, Gabriela F; Nascimento, Lucas F; Arantes, Eva L; Pedro, Rafael M; Vitorino, Daniele C; Nunez, Carla E; Melo Lima, Maria H; Velloso, Lício A; Araújo, Eliana P

    2014-01-01

    The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5-azacytidine on wound healing in rats. 5-Azacytidine decreases the expression of follistatin-1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight-week-old male Wistar rats were submitted to 8.0-mm punch-wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5-azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5-azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5-Azacytidine treatment also resulted in increased gene expression of transforming growth factor-beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor-alpha and interleukin-10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5-azacytidine, most of the beneficial effects of the drug were lost. Thus, 5-azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents. PMID:25039304

  12. 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

  13. Liposome-encapsulated hemoglobin accelerates skin wound healing in mice.

    PubMed

    Fukui, Tsuyoshi; Kawaguchi, Akira T; Takekoshi, Susumu; Miyasaka, Muneo; Tanaka, Rica

    2012-02-01

    Effects of liposome-encapsulated hemoglobin with high O₂ affinity (m-LEH, P₅₀O₂ = 17 mm Hg) on skin wound healing in mice were examined. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in Balb/c mice. Two days later (day 2), the animals randomly received intravenous m-LEH (2 mL/kg, n = 12), homologous blood transfusion (red blood cell [RBC], n = 11), or saline (n = 12). The same treatment was repeated 4 days after wounding (day 4), and the sizes of the skin defects and ulcers were monitored on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies. While the size of the skin defect in relation to the stent ring remained the same in all groups, the size of the ulcer compared with the skin defect (or silicone stent) became significantly reduced on days 4 and 7 in mice treated with m-LEH (46 ± 10% of pretreatment size, P < 0.01) compared with mice treated with RBC transfusion (73 ± 6%) or saline (76 ± 7%). m-LEH treatment significantly accelerated granulation, increased epithelial thickness, suppressed early granulocyte infiltration, and increased Ki67 expression in accordance with the ulcer size reduction, while there was no difference in surface blood flow or CD31 expression among the groups. The results suggest that m-LEH (2 mL/kg) may accelerate skin wound healing in Balb/c mice via mechanism(s) involving reduced inflammation and increased metabolism, but not by improved hemodynamics or endothelial regeneration. PMID:22339725

  14. 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. PMID:24626875

  15. 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

  16. The effect of regional block over pain levels during vacuum-assisted wound closure.

    PubMed

    Findikcioglu, Kemal; Sezgin, Billur; Kaya, Basar; Ozkose, Zerrin; Ayhan, Suhan

    2014-02-01

    Despite being a wound treatment method with a broad spectrum of indications, vacuum-assisted wound closure (VAWC) can be a painful treatment modality which may even result with patient unwillingness for the continuation of treatment. A prospective study was undertaken to determine the effect of regional pain blocks (RPB) for patients who wanted to abandon treatment due to pain after the first application. Patients were asked to score their pain using a visual analogue scale for two different time frames (i) during dressing changes and (ii) while daytime treatment. This evaluation was carried out for conventional wound dressings, VAWC before RPB and finally for VAWC after RPB. The pain experienced with blocks was significantly lesser than conventional and VAWC dressing changes that were applied without pain blocks. Also, the pain was significantly lesser under pain blocks for daytime treatment. For patients with refractory pain where VAWC would prove to be of most benefit, RPB can be discussed with the patient and used. This study has shown that effective pain control can be obtained through regional blocks for patients with excruciating pain undergoing VAWC treatment. PMID:22883639

  17. Staged approach for abdominal wound closure following combined liver and intestinal transplantation from living donors in pediatric patients.

    PubMed

    Grevious, Mark A; Iqbal, Ronak; Raofi, Vandad; Beatty, Elizabeth; Oberholzer, José; Cohen, Mimis; Abcarian, Herand; Testa, Giuliano; Benedetti, Enrico

    2009-03-01

    Primary closure of the abdominal wall after combined liver and intestine transplantation from a living donor into a pediatric patient is usually not possible, because of the size of the donor organ, graft edema, and preexisting scars or stomas of the abdominal wall. Closure under tension may lead to abdominal compartment syndrome with vascular compromise and necrosis of the transplanted organ. We describe our experience of abdominal wound closure after liver and intestinal transplant in the pediatric patient using a staged approach. From February 2003 to June 2006, we managed five pediatric liver and intestinal living donor transplant recipients. Because of the large post-transplantation abdominal wall defect, a staged technique of abdominal wound closure was utilized. Initially, an absorbable Polygalactin mesh was sutured around the layer of the defect. As soon as adequate granulation tissue was formed over the mesh a STSG was applied. From the wound stand point all five patients were managed successfully with staged wound closure after transplantation. Granulation tissue filled and covered the mesh within 7.6 wk. A STSG was then used to cover the defect. All infants recovered well and none had a significant wound complication in the immediate post-operative period following STSG. At a mean follow-up of 24 months only one patient developed an entero-cutaneous fistula five months post-transplant. Staged abdominal wall coverage with the use of Polygalactin mesh followed by STSG is a simple and effective technique. A closed wound is achieved in a timely fashion with protection of the viscera. Residual ventral hernia will need to be managed in the future with one of several reconstructive techniques. PMID:18537902

  18. Successful management of abdominal wound dehiscence using a vacuum assisted closure system combined with mesh-mediated medial traction

    PubMed Central

    Hompes, R; Venkatasubramaniam, A; Arnold, S

    2015-01-01

    Management of the open abdomen has advanced significantly in recent years with the increasing use of vacuum assisted closure (VAC) techniques leading to increased rates of fascial closure. We present the case of a patient who suffered two complete abdominal wall dehiscences after an elective laparotomy, meaning primary closure was no longer possible. She was treated successfully with a VAC system combined with continuous medial traction using a Prolene® mesh. This technique has not been described before in the management of patients following wound dehiscence. PMID:25519257

  19. Successful management of abdominal wound dehiscence using a vacuum assisted closure system combined with mesh-mediated medial traction.

    PubMed

    Lord, A C; Hompes, R; Venkatasubramaniam, A; Arnold, S

    2015-01-01

    Management of the open abdomen has advanced significantly in recent years with the increasing use of vacuum assisted closure (VAC) techniques leading to increased rates of fascial closure. We present the case of a patient who suffered two complete abdominal wall dehiscences after an elective laparotomy, meaning primary closure was no longer possible. She was treated successfully with a VAC system combined with continuous medial traction using a Prolene(®) mesh. This technique has not been described before in the management of patients following wound dehiscence. PMID:25519257

  20. 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

  1. 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

  2. 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. PMID:26454169

  3. 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

  4. 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. PMID:23723146

  5. Wound conditioning by vacuum assisted closure (V.A.C.) in postoperative infections after dorsal spine surgery

    PubMed Central

    Keel, Marius; Trentz, Otmar; Heinzelmann, Michael

    2006-01-01

    The use of vacuum assisted closure (V.A.C.) therapy in postoperative infections after dorsal spinal surgery was studied retrospectively. Successful treatment was defined as a stable healed wound that showed no signs of acute or chronic infection. The treatment of the infected back wounds consisted of repeated debridement, irrigation and open wound treatment with temporary closure by V.A.C. The instrumentation was exchanged or removed if necessary. Fifteen patients with deep subfascial infections after posterior spinal surgery were treated. The implants were exchanged in seven cases, removed completely in five cases and left without changing in one case. In two cases spinal surgery consisted of laminectomy without instrumentation. In two cases only the wound defects were closed by muscle flap, the remaining ones were closed by delayed suturing. Antibiotic treatment was necessary in all cases. Follow up was possible in 14 patients. One patient showed a new infection after treatment. The study illustrates the usefulness of V.A.C. therapy as a new alternative management for wound conditioning of complex back wounds after deep subfascial infection. PMID:16835734

  6. 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

  7. 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

  8. 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

  9. Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix

    PubMed Central

    Mohammadi, Hamid; Pinto, Vanessa I.; Wang, Yongqiang; Hinz, Boris; Janmey, Paul A.; McCulloch, Christopher A.

    2016-01-01

    Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~ 4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix. PMID:26134946

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

    PubMed

    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

  11. Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition.

    PubMed

    Han, George; Nguyen, Long N; Macherla, Chitralekha; Chi, Yuling; Friedman, Joel M; Nosanchuk, Joshua D; Martinez, Luis R

    2012-04-01

    Wound healing is a complex process that involves coordinated interactions between diverse immunological and biological systems. Long-term wounds remain a challenging clinical problem, affecting approximately 6 million patients per year, with a high economic impact. To exacerbate the problem, these wounds render the individual susceptible to life-threatening microbial infections. Because current therapeutic strategies have proved suboptimal, it is imperative to focus on new therapeutic approaches and the development of technologies for both short- and long-term wound management. In recent years, nitric oxide (NO) has emerged as a critical molecule in wound healing, with NO levels increasing rapidly after skin damage and gradually decreasing as the healing process progresses. In this study, we examined the effects of a novel NO-releasing nanoparticle technology on wound healing in mice. The results show that the NO nanoparticles (NO-np) significantly accelerated wound healing. NO-np modified leukocyte migration and increased tumor growth factor-β production in the wound area, which subsequently promoted angiogenesis to enhance the healing process. By using human dermal fibroblasts, we demonstrate that NO-np increased fibroblast migration and collagen deposition in wounded tissue. Together, these data show that NO-releasing nanoparticles have the ability to modulate and accelerate wound healing in a pleiotropic manner. PMID:22306734

  12. Radially Aligned, Electrospun Nanofibers as Dural Substitutes for Wound Closure and Tissue Regeneration Applications

    PubMed Central

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

    2010-01-01

    This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector comprised 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. PMID:20695478

  13. Inhibition of pathogenic bacterial growth on excision wound by green synthesized copper oxide nanoparticles leads to accelerated wound healing activity in Wistar Albino rats.

    PubMed

    Sankar, Renu; Baskaran, Athmanathan; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2015-07-01

    An impaired wound healing is one of the major health related problem in diabetic and non-diabetic patients around the globe. The pathogenic bacteria play a predominant role in delayed wound healing, owing to interaction in the wound area. In our previous work we developed green chemistry mediated copper oxide nanoparticles using Ficus religiosa leaf extract. In the present study we make an attempt to evaluate the anti-bacterial, and wound healing activity of green synthesized copper oxide nanoparticles in male Wistar Albino rats. The agar well diffusion assay revealed copper oxide nanoparticles have substantial inhibition activity against human pathogenic strains such as Klebsiella pneumoniae, Shigella dysenteriae, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli, which were responsible for delayed wound healing process. Furthermore, the analyses results of wound closure, histopathology and protein profiling confirmed that the F. religiosa leaf extract tailored copper oxide nanoparticles have enhanced wound healing activity in Wistar Albino rats. PMID:26194977

  14. The accelerating effect of negative pressure wound therapy with Prevena™ on the healing of a closed wound with persistent serous secretion.

    PubMed

    Altintas, Burak; Biber, Roland; Brem, Matthias H

    2015-12-01

    Negative pressure wound therapy has been lately used on closed incisions in the immediate postoperative period to accelerate wound healing. However, there are no data in the literature regarding the use of this type of therapy for wounds with persistent secretion in the early postoperative care. We present the first report of persistent postoperative serous wound secretion in a patient after femoral nailing treated successfully with Prevena™ (KCI), a closed incision negative pressure management system (CINPWT). PMID:24393137

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

    PubMed

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

    2016-09-01

    Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients. PMID:27187186

  16. Acellular Dermal Matrix Combined with Autologous Skin Grafts for Closure of Chronic Wounds after Reconstruction of Skull Defects with Titanium Mesh.

    PubMed

    Luo, Xu; Lin, Cai; Wang, Xinling; Lin, Xiangwei; He, Sunyue; Liu, Yunfeng; Zhang, Yong; Yang, Ruijin; Zhu, Xinguo

    2016-07-01

    Objective The closure of chronic wounds after skull defect reconstruction with titanium mesh is one of the most challenging problems for plastic and reconstructive surgeons. Current approaches are disappointing. Methods In 10 patients, we explored the role of acellular dermal matrix (ADM) in combination with autologous skin grafts (ASGs) for closure of chronic wounds after skull reconstruction with titanium. Results ADM and ASG survived in all patients. Grade A healing (healing well without defect) was achieved. The average operating time was 30 to 45 minutes, and the average blood loss 30 to 50 mL. After 3 months, the wound was still closed in all patients. Conclusion The combination of ADM plus ASG obtained a high wound closure rate. ADM plus ASG allows avoiding other procedures such as rotational flaps and free flaps that require more operating time, special equipment, and adequate training. PMID:27088591

  17. 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. PMID:23798557

  18. 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

  19. Topical Oxygen Therapy Induces VEGF Expression and Improves Closure of Clinically Presented Chronic Wounds

    PubMed Central

    Gordillo, Gayle M; Roy, Sashwati; Khanna, Savita; Schlanger, Richard; Khandelwal, Sorabh; Phillips, Gary; Sen, Chandan K.

    2008-01-01

    Chronic wounds, especially in diabetics, represent a serious threat to human health.Correcting a compromised state of tissue oxygenation by the administration of supplemental O2 is known to benefit wound healing. Beyond its role as a nutrient and antibiotic, O2 supports wound healing by driving redox-signaling.HBO (hyperbaric oxygen) therapy is widely used and approved by CMS to treat specific ulcerations. The current literature supports that approaches to topically oxygenate wounds may be productive.Here, we present the results of two simultaneous studies testing the effects of HBO and portable topical oxygen (TO) therapies. These two therapeutic approaches have several contrasting features.A total of 1854 patients were screened in outpatient wound clinics for non-randomized enrollments into the HBO (n=32, 31% diabetic) and TO (n=25, 52% diabetic) studies.Under the conditions of the current study, HBO treatment seemed to benefit some wounds while not benefiting the others. Overall, HBO did not result in statistically significant improvements in wound size in the given population over the time monitored in this study.TO significantly improved wound size. Among the three (VEGF, TGFβ1 and COL1A1) O2-sensitive genes studied in wound-edge tissue biopsies, TO treatment was associated with higher VEGF165 expression in healing wounds. Expression of the other genes mentioned was not affected by TO. All of the genes studied did not significantly change in expression in patients of the HBO study. This work establishes a link between VEGF gene expression and healing outcome for TO therapy.Taken together, this report presents evidence demonstrating that TO treatment benefits wound healing in patients suffering from chronic wounds. TO treatment is associated with induction in VEGF expression in the wound edge tissue and improvement in wound size. PMID:18430064

  20. Dinitrosyl iron complexes with glutathione incorporated into a collagen matrix as a base for the design of drugs accelerating skin wound healing.

    PubMed

    Shekhter, Anatoly B; Rudenko, Tatyana G; Istranov, Leonid P; Guller, Anna E; Borodulin, Rostislav R; Vanin, Anatoly F

    2015-10-12

    Composites of a collagen matrix and dinitrosyl iron complexes with glutathione (DNIC-GS) (in a dose of 4.0 μmoles per item) in the form of spongy sheets (DNIC-Col) were prepared and then topically applied in rat excisional full-thickness skin wound model. The effects of DNIC-Col were studied in comparison with spontaneously healing wounds (SpWH) and wounds treated with collagen sponges (Col) without DNIC-GS. The composites induced statistically and clinically significant acceleration of complete wound closure (21±1 day versus 23±1 day and 26±1 day for DNIC-Col, Col and SpWH, respectively). Histological examination of wound tissues on days 4, 14, 18 and 21 after surgery demonstrated that this improvement was supported by enhanced growth, maturation and fibrous transformation of granulation tissue and earlier epithelization of the injured area in rats treated with DNIC-Col composites benchmarked against Col and SpWH. It is suggested that the positive effect of the new pharmaceutical material on wound healing is based on the release of NO from decomposing DNIC. This effect is believed to be potentiated by the synergy of DNIC and collagen. PMID:26066410

  1. 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

  2. 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. PMID:24348715

  3. 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. PMID:22946413

  4. [Primary closure and healing of the perineal wound in abdomino-perineal resection of the rectum for carcinoma (author's transl)].

    PubMed

    Delpero, J R; Le Treut, Y P; Boutboul, R; Bricot, R

    1982-05-01

    The results of primary perineal closure after rectal resection for cancer are reported, about a series of 105 patients male and female; to whom this technique was systematically applied. The healing of the wound was primarily obtained in 77.2% of the cases (82.3% in males, 72.2% in females). 86% of the patients left the hospital completely healed within 30 post operative days. The authors stress the influence of the environment on the result and also discuss the practical conditions of the primary suture: hemostasis, fecal contamination, peritonisation, enlarging followed with ablation of the genital tract in women. PMID:7050136

  5. A Comparison of 2-Octyl Cyanoacrylate Adhesives versus Conventional Suture Materials for Eyelid Wound Closure in Rabbits

    PubMed Central

    Shin, Dong-Min; Roh, Mee-Sook; Jeung, Woo-Jin; Park, Woo-Chan; Rho, Sae-Heun

    2011-01-01

    Purpose To evaluate the clinical efficacy and histopathological tolerance of 2-octyl cyanoacrylate versus conventional suture materials for eyelid wound closure in rabbits. Methods We performed an experimental study on 16 eyes of eight New Zealand albino rabbits. Eyelid incisions of 15 mm were done 4mm from the upper eyelid margin in both eyes. The eyes of the rabbits were divided into two groups: eyelid incisions of the right eye were closed by a 2-octyl cyanoacrylate adhesive (group A) and eyelid incisions of the left eye were closed by 7-0 nylon sutures (group B). At 1, 2, 4, and 8 weeks after surgery, the rabbits were macroscopically examined and then sacrificed. The specimens of their eyelid tissues were stained by a hematoxylin and eosin stain and Masson-trichrome stain, and were observed under microscope. Results Both eyelid surgical closure methods were found to be equally efficacious in fixing the eyelids of groups A and B, and their clinical efficacy was similar. Histopathological findings of the hematoxylin and eosin stain of group A showed less inflammatory infiltration than group B at 2 weeks. There were no significant histopathological differences between the two groups at 1, 4, and 8 weeks. The degree of fibrosis of the Masson-trichrome stain was similar between the two groups at 8 weeks. Conclusions The 2-octyl cyanoacrylate adhesive proved to be an effective eyelid closure method and was very well tolerated by the skin surface. 2-Octyl cyanoacrylate could be used as an alternative tissue adhesive for eyelid wound closure along with conventional suture materials. PMID:21461225

  6. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway

    PubMed Central

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-01-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro. Importantly, Jag1 overexpression improves diabetic wound healing in vivo. These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  7. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.

    PubMed

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-08-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  8. 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

  9. 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. PMID:16785777

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

    PubMed

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

    2016-06-15

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

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

    PubMed

    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; Brindley, Paul J; Loukas, Alex

    2015-10-01

    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

  12. 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

  13. Biofunctionalized electrospun silk mats as a topical bioactive dressing for accelerated wound healing

    PubMed Central

    Schneider, A.; Wang, X.Y.; Kaplan, D.L.; Garlick, J.A.; Egles, C.

    2010-01-01

    Materials able to deliver topically bioactive molecules represent a new generation of biomaterials. In this article, we describe the use of silk mats, made of electrospun nanoscale silk fibers containing epidermal growth factor (EGF), for the promotion of wound healing processes. In our experiments, we demonstrated that EGF is incorporated into the silk mats and slowly released in a time-dependent manner (25% EGF release in 170 h). We tested these materials using a new model of wounded human skin-equivalents displaying the same structure as human skin and able to heal using the same molecular and cellular mechanisms found in vivo. This human three-dimensional model allows us to demonstrate that the biofunctionalized silk mats, when placed on the wounds as a dressing, aid the healing by increasing the time of wound closure by the epidermal tongue by 90%. The preservation of the structure of the mats during the healing period as demonstrated by electronic microscopy, the biological action of the dressing, as well as the biocompatibility of the silk demonstrate that this biomaterial is a new and very promising material for medical applications, especially for patients suffering from chronic wounds. PMID:19162575

  14. The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice

    PubMed Central

    Livant, Donna L.; Brabec, R. Kaye; Kurachi, Kotoku; Allen, David L.; Wu, Yanling; Haaseth, Ronald; Andrews, Philip; Ethier, Stephen P.; Markwart, Sonja

    2000-01-01

    The PHSRN sequence of the plasma fibronectin (pFn) cell-binding domain induces human keratinocytes and fibroblasts to invade the naturally serum-free extracellular matricies of sea urchin embryos. The potency of acetylated, amidated PHSRN (Ac-PHSRN-NH2) is significantly increased, making it more active on a molar basis than the 120-kDa cell-binding domain of pFn. Arginine is important to this activity because PHSAN and PHSEN are inactive, as is a randomized sequence peptide, Ac-HSPNR-NH2. One treatment with Ac-PHSRN-NH2 stimulates reepithelialization and contraction of dermal wounds in healing-impaired, obese diabetic C57BL6/KsJ db/db mice. Wound closure is equally rapid in treated db/db and db/+ mice and may be more rapid than in untreated nondiabetic db/+ littermates. In contrast, treatment with either Ac-HSPNR-NH2 or normal saline (NS) has no effect. Analysis of sectioned db/db wounds shows that, in contrast to treatment with Ac-HSPNR-NH2 or NS, a single Ac-PHSRN-NH2 treatment stimulates keratinocyte and fibroblast migration into wounds, enhances fibroplasia and vascularization in the provisional matrix, and stimulates the formation of prominent fibers that may be associated with wound contraction. PMID:10841512

  15. 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. PMID:17992147

  16. Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

    PubMed Central

    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

    2015-01-01

    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. PMID:25010393

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

    PubMed

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

    2008-02-01

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

  18. 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.

  19. 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

  20. [Wound closure after irrigation with Octenisept® without possibility for drainage].

    PubMed

    Högele, A M; Neu, J

    2011-01-01

    A 39-year-old patient suffered a stab wound of the right thenar prominence after an accident with a screwdriver. In the first hospital the deep wound was irrigated with octenidine dihydrochloride/2-phenoxyethanol and closed by suture. During the further course pressure pain and numbness of the right thenar and swelling of the right hand occurred. Three weeks after the accident an operative revision of the wound in a second hospital was performed. The intraoperative findings showed inflammation and necrosis of the right m. abductor pollicis brevis, but no infection with pus.The patient accused the first hospital of irrigating the tissue of his right hand with Octenisept®. The expert option of the Arbitration Board identified improper care in the first hospital with insufficient excision of the wound and incorrect use of the Octenisept® solution. Against the explicit advice of the manufacturing company the wound had been sutured without the possibility of drainage for the Octenisept® solution. PMID:21229225

  1. Evaluation of vacuum-assisted closure in patients with wound complications following tumour surgery.

    PubMed

    Mermerkaya, Ugur; Bekmez, Senol; Alkan, Erkan; Ayvaz, Mehmet; Tokgozoglu, Mazhar

    2016-06-01

    Covering the reconstructed area with a healthy soft-tissue envelope is a major challenge after limb-sparing surgery in patients with malignant bone and soft-tissue tumours. Negative pressure wound therapy (NPWT) of open wounds hastens healing and minimises the requirement for complex reconstructive soft-tissue surgery. The aim of this study was to investigate the effectiveness and safety of NPWT in bone and soft-tissue malignant tumour patients with postoperative wound complications. Between January 2006 and November 2009, at a single institution, 13 patients with malignant bone and soft-tissue tumours who had undergone wide resection were retrospectively analysed. NPWT was performed in all patients to temporarily close the soft-tissue defects. After obtaining the culture negativity and normal infection markers, definitive soft-tissue reconstruction was performed to close the wound with primary suturisation in two patients, split thickness grafts in four patients, full thickness grafts in two patients, rotational flaps in three patients and free flaps in two patients. Mean duration of hospitalisation was 20 (range 8-48) days and mean follow-up period was 57·3 (range 50-74) months. There was no tumour recurrence or skip metastasis in the follow-up period. In addition, there was no periprosthetic infection or complication associated with NPWT. In conclusion, NPWT therapy seems to be a safe and effective option in the management of local wound problems and secondary surgical site infections after musculoskeletal tumour surgery. PMID:24976480

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

    PubMed Central

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

    2015-01-01

    Abstract. 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. PMID:25562608

  3. 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.

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

    PubMed

    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. PMID:25562608

  5. Topical Application of Insulin Accelerates Vessel Maturation of Wounds by Regulating Angiopoietin-1 in Diabetic Mice.

    PubMed

    Li, Chaofei; Yu, Tianyi; Liu, Yan; Chen, Xuelian; Zhang, Xiong

    2015-12-01

    Reestablishment of the structural and functional microvasculature would be beneficial to promote healing of diabetic wounds. We explored the role of insulin application on microvascular maturation of diabetic wounds to determine whether it is associated with insulin-induced wound healing. We adopted the multiple injections of streptozotocin (STZ) to establish a diabetic animal model. The effect of insulin on microvessel formation, especially the effect of insulin on microvascular maturation was observed by transmission electron microscopy and laser scanning confocal microscopy. The pivotal protein regulated by insulin during healing processes was explored by tropical application neutralizing antibodies to these proteins; the specific protein was further confirmed using immunoblotting. On days 7 and 11, the blood vessel in insulin-treated wounds was surrounded by more α-smooth muscle actin (α-SMA) expressing cells. The blockage of angiopoietin-1 (Ang-1), but not angiopoietin-2 (Ang-2) or platelet-derived growth factor-B (PDGF-B), resulted in reduced maturation of newly formed blood vessels despite the presence of insulin in vivo. Further analysis showed that insulin induced an increased expression of Ang-1. The blood vessels in insulin-treated wounds showing advanced coverage of pericytes and reconstruction of new vascular basement membrane suggest that insulin is a potent accelerator of microvascular maturation, which may be involved in the mechanisms of insulin-induced wound healing. PMID:26349856

  6. Use of Vacuum-assisted closure in management of open abdominal wound with multiple enterocutaneous fistulae during chemotherapy: A case report

    PubMed Central

    Fujino, Shiki; Miyoshi, Norikatsu; Ohue, Masayuki; Noura, Shingo; Fukata, Tadafumi; Yagi, Toshiya; Fujiwara, Yoshiyuki; Yano, Masahiko

    2015-01-01

    Introduction Vacuum-assisted closure (VAC) is useful for treating complex wounds because it promotes granulation. In the present report, a successful case of VAC used for an open abdominal wound with enterocutaneous fistulae after multiple intestinal perforations during chemotherapy is described. Presentation of case A 73-year-old man was admitted to our hospital with severe abdominal pain. He underwent surgical resection for ascending colon cancer 4 years ago and was administered chemotherapy with bevacizumab for recurrence. Physical examination and computed tomography revealed perforation of the intestine, and an emergency operation was performed. Following this procedure, other intestinal perforations occurred, resulting in an open abdominal wound at postoperative day (POD) 10. To isolate enteric contents and promote granulation, VAC was applied to the abdominal wound with enterocutaneous fistulae. Oral intake started at POD 21 and the wound size became smaller. Further, an ostomy bag was directly attached to the most oral perforation site. The patient recovered from life-threatening events without severe infection and was transferred to another hospital close to his home at POD 180. Discussion Gastrointestinal perforation is known to be one of the fatal adverse events of bevacizumab. In this case four gastrointestinal perforations were observed. Isolation of enteric contents is important to heal the wound and VAC is an effective therapy for the management of open abdominal wounds even with enterocutaneous fistulae. Conclusion Innovative VAC use for the management of open abdominal wounds can improve the nutritional status and overall wound healing of the patient. PMID:26599504

  7. Lifting incise drapes off the skin during wound closure can cause contamination.

    PubMed

    Makki, D; Probert, N; Gedela, V; Kustos, I; Thonse, R; Banim, R

    2015-05-01

    Incise drapes adhere well to skin and reduce bacterial migration into the wound. We took skin swabs before and after the application of incise drapes during 49 hip and knee arthroplasty procedures. Contamination was detected under incise drapes in four cases (8.1%) and consisted mainly of skin flora. We conclude that it is important to clean the skin again with antiseptics if the incise drape is removed by the surgeon. PMID:26292465

  8. 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. PMID:24373522

  9. Layer-by-layer assembly of epidermal growth factors on polyurethane films for wound closure.

    PubMed

    Kulkarni, Abhilash; Diehl-Jones, William; Ghanbar, Sadegh; Liu, Song

    2014-02-13

    To facilitate the healing of chronic wounds, growth factors such as epidermal growth factor need to be safely encapsulated for their sustained and effective delivery to the wound bed. Using a layer-by-layer assembly technique, epidermal growth factor is successfully encapsulated on the surface of poly(acrylic acid)-modified polyurethane film. The amount of encapsulated epidermal growth factor is controlled by adjusting the number of chitosan/epidermal growth factor bilayers. A controlled release of epidermal growth factor from the surface of polyurethane film for a period of five days is achieved with well-retained bioactivity (over 90%) as evidenced by a cell proliferation assay. In an in vitro cellular wounding assay, the cell gap covered with the epidermal growth factor-loaded polyurethane film closes at a rate more than twice as fast as that covered with a control polyurethane film. Fluorescent staining of F-actin reveals that the released epidermal growth factor induces differences in cytoskeletal organization, suggesting that stimulated cell migration also contributes to the close of the cell gap. PMID:24525716

  10. 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.

  11. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways

    PubMed Central

    Jun, Eun Kyoung; Zhang, Qiankun; Yoon, Byung Sun; Moon, Jai-Hee; Lee, Gilju; Park, Gyuman; Kang, Phil Jun; Lee, Jung Han; Kim, Areee; You, Seungkwon

    2014-01-01

    In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-β1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-β/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways. PMID:24398984

  12. A beveled, conventional cutting edge surgical needle: a new innovation in wound closure.

    PubMed

    Kaulbach, H C; Towler, M A; McClelland, W A; Povinelli, K M; Becker, D G; Cantrell, R W; Edlich, R F

    1990-01-01

    A new beveled, conventional cutting edge needle has been developed with superior performance characteristics over those of other conventional cutting edge needles. It is composed of a unique stainless steel, ASTM 45500, that has been heat-treated after the curving process to enhance its resistance to bending. The angle of presentation of its cutting edges has been decreased to enhance needle sharpness. On the basis of the results of experimental and clinical investigations, this new needle is recommended for closure of lacerations. PMID:2197321

  13. 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

  14. Comparison of laser-activated tissue solders and thrombin-activated cryoprecipitate for wound closure

    NASA Astrophysics Data System (ADS)

    Kayton, Mark L.; Libutti, Steven K.; Bessler, Marc; Allendorf, John D. F.; Eiref, Simon D.; Marx, Gerard; Mou, Xiaode; Morales, Alfredo M.; Treat, Michael R.; Nowygrod, Roman

    1994-09-01

    To determine the relative strengths of various biologic adhesives at several timepoints, we compared thrombin-activated SD (solvent-detergent treated) cryoprecipitate with laser- activated SD cryoprecipitate and a laser-activated, albumin-based glue. Male Sprague-Dawley rats (n equals 79) received four, 3-cm, dorsal skin incisions which were closed with either laser- activated cryoprecipitate, laser-activated albumin solder, thrombin-activated cryoprecipitate, or standard skin staples. The cryoprecipitate was derived from pooled human plasma and was treated with a solvent-detergent process, rendering it free of envelope-coated viruses (i.e., HBV, HIV). An 808-nm diode laser was used to activate each solder with an average duration of exposure of 75 seconds per incision. Animals were sacrificed for evaluation of wound tensile strength and histology at 0 hours, 2 hours, 4 hours, and 4 days. At all timepoints tested, laser-activated solders were significantly stronger than thrombin-activated cryoprecipitate (p < 0.03) and control wounds (p < 0.003). There was no significant difference in tensile strength between the two types of laser-activated solder at any timepoint.

  15. 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.

  16. 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.

  17. Application of Coenzyme Q10 for Accelerating Soft Tissue Wound Healing after Tooth Extraction in Rats

    PubMed Central

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

    2014-01-01

    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. PMID:25514392

  18. 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. PMID:27037778

  19. 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. PMID:19842521

  20. 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. PMID:25907598

  1. Saliva and wound healing.

    PubMed

    Brand, Henk S; Veerman, Enno C I

    2013-01-01

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

  2. 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

  3. Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure.

    PubMed

    Fernández-Montequín, José I; Betancourt, Blas Y; Leyva-Gonzalez, Gisselle; Mola, Ernesto L; Galán-Naranjo, Katia; Ramírez-Navas, Mayte; Bermúdez-Rojas, Sergio; Rosales, Felix; García-Iglesias, Elizeth; Berlanga-Acosta, Jorge; Silva-Rodriguez, Ricardo; Garcia-Siverio, Marianela; Martinez, Luis H

    2009-02-01

    Previous studies have shown that an epidermal growth factor-based formulation (Heberprot-P) can enhance granulation of high-grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16.3 +/- 21.3 cm(2). Intralesional injections of 75 microg of Heberprot-P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23.6 +/- 3.8 days. Complete wound closure was obtained in 17 (85%) cases in 44.3 +/- 8.9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and odour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot-P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU. PMID:19291119

  4. Acceleration of Wound Healing by α-gal Nanoparticles Interacting with the Natural Anti-Gal Antibody

    PubMed Central

    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. PMID:25922849

  5. 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. PMID:25922849

  6. 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

  7. 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

  8. Drug loaded composite oxidized pectin and gelatin networks for accelerated wound healing.

    PubMed

    Tummalapalli, Mythili; Berthet, Morgane; Verrier, Bernard; Deopura, B L; Alam, M S; Gupta, Bhuvanesh

    2016-05-30

    Biocomposite interactive wound dressings have been designed and fabricated using oxidized pectin (OP), gelatin and nonwoven cotton fabric. Due to their inherent virtues of antimicrobial activity and cytocompatibility, these composite structures are capable of redirecting the healing cascade and influencing cell attachment and proliferation. A novel in situ reduction process has been followed to synthesize oxidized pectin-gelatin-nanosilver (OP-Gel-NS) flower like nanohydrocolloids. This encapsulation technology controls the diffusion and permeation of nanosilver into the surrounding biological tissues. Ciprofloxacin hydrochloride has also been incorporated into the OP-Gel matrix to produce OP-Gel-Cipro dressings. While OP-Gel-NS dressings exhibited 100% antimicrobial activity at extremely low loadings of 3.75μg/cm(2), OP-Gel-Cipro dressings were highly antimicrobial at 1% drug loading. While NIH3T3 mouse fibroblasts proliferated remarkably well when cultured with OP-Gel and OP-Gel-Cipro dressings, OP-Gel-NS hindered cell growth and Bactigras(®) induced complete lysis. Full thickness excisional wounds were created on C57BL/6J mice and the wound healing potential of the OP-Gel-NS dressings led to accelerated healing within 12days, while OP-Gel-Cipro dressings healed wounds at a rate similar to that of Bactigras(®). Histological examination revealed that OP-Gel-NS and OP-Gel-Cipro treatment led to organized collagen deposition, neovascularization and nuclei migration, unlike Bactigras(®). Therefore, the OP-Gel-NS and OP-Gel-Cipro biocomposite dressings exhibiting good hydrophilicity, sustained antimicrobial nature, promote cell growth and proliferation, and lead to rapid healing, can be considered viable candidates for effective management. PMID:27063849

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

    PubMed

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

    2016-01-01

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

  10. 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

  11. 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

  12. Wound Healing Activity of Elaeis guineensis Leaf Extract Ointment

    PubMed Central

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

    2012-01-01

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

  13. 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. PMID:25891093

  14. 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. PMID:26704185

  15. 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 ...

  16. He-Ne laser irradiation acceleration of healing process of open gingival wounds in cats

    NASA Astrophysics Data System (ADS)

    Abramovici, Armand; Roisman, P.; Hirsch, A.; Segal, S.; Fischer, J.

    1994-09-01

    A histopathological study on the effect of He-Ne laser treatment on the evolution of cat gingiva open wounds is presented. The irradiation initiates first a massive inflammatory cell exudate together with an antiedematic effect after the second postoperative day. A substantial acceleration of the healing process is noted on the sixth day among irradiated tissues as compared to the operated gingiva which still shows, at this period of time, inflammatory exudate and isolated fibroblasts. The persistence of inflammatory exudate and edema among the untreated gingiva seemed to have a delaying effect upon the healing process. The biostimulatory effect of soft laser seems to act photodynamically both at the intracellular level and extracellular millieu, thus promoting the proliferative capacity of fibroblasts and capillary buds formation necessary for a rapid differentiation of connective tissue. The controlled application of He-Ne laser treatment is suggested in dental healing procedures.

  17. 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

  18. Green light emitting diodes accelerate wound healing: characterization of the effect and its molecular basis in vitro and in vivo.

    PubMed

    Fushimi, Tomohiro; Inui, Shigeki; Nakajima, Takeshi; Ogasawara, Masahiro; Hosokawa, Ko; Itami, Satoshi

    2012-01-01

    Because light-emitting diodes (LEDs) are low-coherent, quasimonochromatic, and nonthermal, they are an alternative for low level laser therapy, and have photobiostimulative effects on tissue repair. However, the molecular mechanism(s) are unclear, and potential effects of blue and/or green LEDs on wound healing are still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm), and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the skin of ob/ob mice were significantly decreased on day 7 following exposure to green LEDs, and complete reepithelialization was accelerated by red and green LEDs compared with the control mice. To better understand the molecular mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts in vitro by measuring mRNA and protein levels of cytokines secreted by fibroblasts during the process of wound healing and on the migration of HaCat keratinocytes. The results suggest that some cytokines are significantly increased by exposure to LEDs, especially leptin, IL-8, and VEGF, but only by green LEDs. The migration of HaCat keratinocytes was significantly promoted by red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound healing by inducing migratory and proliferative mediators, which suggests that not only red LEDs but also green LEDs can be a new powerful therapeutic strategy for wound healing. PMID:22380691

  19. 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)

  20. Negative pressure wound therapy.

    PubMed

    Thompson, James T; Marks, Malcolm W

    2007-10-01

    Negative pressure wound therapy has become an increasingly important part of wound management. Over the last decade, numerous uses for this method of wound management have been reported, ranging from acute and chronic wounds, to closure of open sternal and abdominal wounds, to assistance with skin grafts. The biophysics behind the success of this treatment largely have focused on increased wound blood flow, increased granulation tissue formation, decreased bacterial counts, and stimulation of wound healing pathways through shear stress mechanisms. The overall success of negative pressure wound therapy has led to a multitude of clinical applications, which are discussed in this article. PMID:17967622

  1. Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

    PubMed Central

    Tsai, Min-Ling; Huang, Hui-Pei; Hsu, Jeng-Dong; Lai, Yung-Rung; Hsiao, Yu-Ping; Lu, Fung-Jou; Chang, Horng-Rong

    2014-01-01

    N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing. PMID:24798751

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

    PubMed

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

    2016-01-01

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

  3. 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

  4. The Use of Growth Factors and Other Humoral Agents to Accelerate and Enhance Burn Wound Healing

    PubMed Central

    Ching, Yiu-Hei; Sutton, Thomas L.; Pierpont, Yvonne N.; Robson, Martin C.; Payne, Wyatt G.

    2011-01-01

    Objective: Certain cytokines, especially those known as growth factors, have been demonstrated to mediate or modulate burn wound healing. Experimental and clinical evidence suggests that there are therapeutic advantages to the wound healing process when these agents are utilized. Positive effects have been reported for 4 types of wounds seen in the burn patient: partial-thickness wounds, full-thickness wounds, interstices of meshed skin grafts, and skin graft donor sites. Methods: A comprehensive literature search was performed using the MEDLINE, Ovid, and Web of Science databases to identify pertinent articles regarding growth factors and other cytokines in burns and wound healing. Results: The current knowledge about cytokine growth factors and their potential therapeutic applications in burn wound healing are discussed and reviewed. Conclusions: Platelet-derived growth factor, fibroblast growth factors, epidermal growth factors, transforming growth factor alpha, vascular endothelial growth factor, insulin-like growth factor I, nerve growth factor, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, and amnion-derived cellular cytokine solution have all been suggested to enhance the rate and quality of healing in 1 or more of these wounds encountered in burn care. PMID:22084646

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

    PubMed

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

    2014-10-01

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

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

    PubMed

    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

  7. 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

  8. Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

    PubMed Central

    Chong, Han Chung; Chan, Jeremy Soon Kiat; Goh, Chi Qin; Gounko, Natalia V; Luo, Baiwen; Wang, Xiaoling; Foo, Selin; Wong, Marcus Thien Chong; Choong, Cleo; Kersten, Sander; Tan, Nguan Soon

    2014-01-01

    Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing. PMID:24903577

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

    PubMed

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

    2014-05-15

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

  10. 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

  11. 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

  12. The anti-inflammatory agent Propolis improves wound healing in a rodent model of experimental diabetes.

    PubMed

    McLennan, Susan V; Bonner, James; Milne, Sgtephen; Lo, Lisa; Charlton, Ana; Kurup, Savita; Jia, Junhong; Yue, Dennis K; Twigg, Stephen M

    2008-01-01

    Foot ulcers and poor wound healing are problematic for patients with diabetes. The beehive protectant Propolis can improve wound healing but whether it can improve healing in diabetic wounds has not been investigated. In this study, the effect of a single application of Propolis on epithelial closure, wound morphology, cellular infiltrate, and blood vessel density were investigated. Diabetes was induced in rats using streptozocin. After 6 weeks, diabetic and control animals were wounded and the wounds were treated with Propolis or saline as control. At days 6 and 12 animals were sacrificed and wounds were excised. Compared with controls, diabetes decreased epithelial closure and reepithelialization but had no effect on wound contraction. These delays were prevented by Propolis. At day 12, the impaired macrophage infiltration (C:1.49+/-0.09 vs. D:0.25+/-0.14), persistent neutrophil infiltration (C:0.22+/-0.19 vs. D:1.33+/-0.81), and increased myeloperoxidase activity (fourfold) in diabetic wounds were prevented by Propolis. Diabetes had no effect on wound volume, vessel number, or branch points. These novel data indicate that Propolis can accelerate wound healing in diabetes. As neutrophil infiltration is normalized, its mechanism of action may be through anti-inflammatory pathways. This result and the established safety profile of Propolis provide a rationale for studying topical application of this agent in a clinical setting. PMID:19128266

  13. 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

  14. A Multicenter Randomized Controlled Trial Comparing Treatment of Venous Leg Ulcers Using Mechanically Versus Electrically Powered Negative Pressure Wound Therapy

    PubMed Central

    Marston, William A.; Armstrong, David G.; Reyzelman, Alexander M.; Kirsner, Robert S.

    2015-01-01

    Objective: This study compares two different negative pressure wound therapy (NPWT) modalities in the treatment of venous leg ulcers (VLUs), the ultraportable mechanically powered (MP) Smart Negative Pressure (SNaP®) Wound Care System to the electrically powered (EP) Vacuum-Assisted Closure (V.A.C.®) System. Approach: Patients with VLUs from 13 centers participated in this prospective randomized controlled trial. Each subject was randomly assigned to treatment with either MP NPWT or EP NPWT and evaluated for 16 weeks or complete wound closure. Results: Forty patients (n=19 MP NPWT and n=21 EP NPWT) completed the study. Primary endpoint analysis of wound size reduction found wounds in the MP NPWT group had significantly greater wound size reduction than those in the EP NPWT group at 4, 8, 12, and 16 weeks (p-value=0.0039, 0.0086, 0.0002, and 0.0005, respectively). Kaplan–Meier analyses showed greater acceleration in complete wound closure in the MP NPWT group. At 30 days, 50% wound closure was achieved in 52.6% (10/19) of patients treated with MP NPWT and 23.8% (5/21) of patients treated with EP NPWT. At 90 days, complete wound closure was achieved in 57.9% (11/19) of patients treated with MP NPWT and 38.15% (8/21) of patients treated with EP NPWT. Innovation: These data support the use of MP-NPWT for the treatment of VLUs. Conclusions: In this group of venous ulcers, wounds treated with MP NPWT demonstrated greater improvement and a higher likelihood of complete wound closure than those treated with EP NPWT. PMID:25713749

  15. A physiologically active polysaccharide hydrogel promotes wound healing.

    PubMed

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

    2010-07-01

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

  16. Kcnh2 and Kcnj8 interactively regulate skin wound healing and regeneration.

    PubMed

    Zhang, Wengeng; Bei, Marianna

    2015-01-01

    Previous studies indicate that ion channels are mediators of bioelectricity promoting wound closure/regeneration in nonmammalian, lower vertebrate systems. The role of ion channels however in regeneration of wounds in mammalian systems that do not regenerate as adults is not yet defined. Using a mammalian model system that allows us to determine differentially expressed genes when skin regenerates and when skin does not regenerate after wound induction, we identified two potassium channels, kcnh2 and kcnj8, to be (1) differentially expressed between the two states and (2) highly expressed after wound induction at the nonregenerative state. We also found that kcnh2 small molecule inhibitor enhanced wound healing while kcnj8 small molecule inhibitor did not. In contrast, kcnj8 activator accelerated wound healing and even augmented the effect of kcnh2 inhibition. These results provide evidence for the first time that potassium channels may mediate skin wound healing and regeneration interactively. PMID:26220146

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-07-01

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

  19. Celosia argentea Linn. leaf extract improves wound healing in a rat burn wound model.

    PubMed

    Priya, Kulasekaran S; Arumugam, Gnanamani; Rathinam, Bhuvaneswari; Wells, Alan; Babu, Mary

    2004-01-01

    Celosia argentea (CA) is used in traditional medicine for sores, ulcers, and skin eruptions. The present study was aimed at investigating the healing efficacy of CA extract in an ointment formulated (10 % w/w) as an alcohol extract of CA using a rat burn wound model. Wound closure occurred earlier in the treated rats (15 days vs. 30 in the untreated group; p < 0.05). Granulation tissue collected on every fifth day of healing showed an increase in collagen and hexosamine content at a faster rate in the treated wounds. This correlated with the accelerated wound closure observed in the treated groups. To probe the cellular basis of this effect, we investigated the effect of this extract on two major cellular responses; cell proliferation and cell motility, in two key cell lineages, fibroblasts and keratinocytes. CA was not toxic at concentrations of < 3 microg/ml in fibroblasts and < 30 microg/ml in keratinocytes. The alcohol extract promoted cell motility and proliferation of primary dermal fibroblasts at 0.1-1.0 microg/ml but did not alter these responses in primary keratinocytes. In an initial examination of molecular mechanisms, we found that the CA extract did not alter fibroblast and keratinocyte responses to the wound repair-associated epidermal growth factor receptor ligands. In short, we demonstrate a salutary action of the CA extract on wound healing, and suggest that this may be due to mitogenic and motogenic promotion of dermal fibroblasts. PMID:15555053

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

    PubMed Central

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

    2014-01-01

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

  1. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    PubMed

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825453

  2. 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. PMID:23922871

  3. 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

  4. 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. PMID:23553951

  5. Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality

    PubMed Central

    Faghih, Mahya; Hosseini, Sayed M.; Smith, Barbara; Ansari, Amir Mehdi.; Lay, Frank; Ahmed, Ali Karim; Inagami, Tedashi; Marti, Guy P.; Harmon, John W.; Walston, Jeremy D.; Abadir, Peter M.

    2015-01-01

    Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT1R), has been associated with impaired wound healing, suggesting a critical role for AT1R in this repair process. Biological functions of angiotensin type 2 receptors (AT2R) are less studied. We investigated effects of genetically disrupting AT2R on rate and quality of wound healing. Our results suggest that AT2R effects on rate of wound closure depends on the phase of wound healing. We observed delayed healing during early phase of wound healing (inflammation). An accelerated healing rate was seen during later stages (proliferation and remodeling). By day 12, fifty percent of AT2R−/− mice had complete wound closure as compared to none in either C57/BL6 or AT1R−/− mice. There was a significant increase in AT1R, TGFβ1 and TGFβ2 expression during the proliferative and remodeling phases in AT2R−/− mice. Despite the accelerated closure rate, AT2R−/− mice had more fragile healed skin. Our results suggest that in the absence of AT2R, wound healing rate is accelerated, but yielded worse skin quality. Elucidating the contribution of both of the angiotensin receptors may help fine tune future intervention aimed at wound repair in older individuals. PMID:26727887

  6. Amniotic epithelial cells promote wound healing in mice through high epithelialization and engraftment.

    PubMed

    Jin, Enze; Kim, Tae-Hee; Han, Seongho; Kim, Sung-Whan

    2016-07-01

    Although human amniotic epithelial cells (AMEs) are an attractive source of stem cells, their therapeutic potential in wound healing has not been fully investigated. We evaluated the therapeutic potential of AMEs for wound healing. Real-time PCR showed that the epithelialization growth factors epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-B and chemotactic factors interleukin-8 (IL-8 or CXCL8) and neutrophil-activating protein-2 (NAP-2 or CXCL7) were upregulated in AMEs compared with adipose-derived mesenchymal stem cells (ADMs). In vitro scratch wound assays revealed that AME-derived conditioned medium substantially accelerated wound closure. Wounds in NOD/SCID mice were created by skin excision, followed by AME transplantation. AMEs implantation significantly accelerated wound healing and increased cellularity and re-epithelialization. Transplanted AMEs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, suggesting direct benefits for cutaneous closure. Taken together, these data indicate that AMEs possess therapeutic capability for wound healing through the secretion of epithelialization growth factors and enhanced engraftment properties. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26174407

  7. Improved repair of dermal wounds in mice lacking microRNA-155.

    PubMed

    van Solingen, Coen; Araldi, Elisa; Chamorro-Jorganes, Aranzazu; Fernández-Hernando, Carlos; Suárez, Yajaira

    2014-06-01

    Wound healing is a well-regulated but complex process that involves haemostasis, inflammation, proliferation and maturation. Recent reports suggest that microRNAs (miRs) play important roles in dermal wound healing. In fact, miR deregulation has been linked with impaired wound repair. miR-155 has been shown to be induced by inflammatory mediators and plays a central regulatory role in immune responses. We have investigated the potential role of miR-155 in wound healing. By creating punch wounds in the skin of mice, we found an increased expression of miR-155 in wound tissue when compared with healthy skin. Interestingly, analysis of wounds of mice lacking the expression of miR-155 (miR-155(-/-) ) revealed an increased wound closure when compared with wild-type animals. Also, the accelerated wound closing correlated with elevated numbers of macrophages in wounded tissue. Gene expression analysis of wounds tissue and macrophages isolated from miR-155(-/-) mice that were treated with interleukin-4 demonstrated an increased expression of miR-155 targets (BCL6, RhoA and SHIP1) as well as, the finding in inflammatory zone-1 (FIZZ1) gene, when compared with WT mice. Moreover, the up-regulated levels of FIZZ1 in the wound tissue of miR-155(-/-) mice correlated with an increased deposition of type-1 collagens, a phenomenon known to be beneficial in wound closure. Our data indicate that the absence of miR-155 has beneficial effects in the wound healing process. PMID:24636235

  8. Improved repair of dermal wounds in mice lacking microRNA-155

    PubMed Central

    van Solingen, Coen; Araldi, Elisa; Chamorro-Jorganes, Aranzazu; Fernández-Hernando, Carlos; Suárez, Yajaira

    2014-01-01

    Wound healing is a well-regulated but complex process that involves haemostasis, inflammation, proliferation and maturation. Recent reports suggest that microRNAs (miRs) play important roles in dermal wound healing. In fact, miR deregulation has been linked with impaired wound repair. miR-155 has been shown to be induced by inflammatory mediators and plays a central regulatory role in immune responses. We have investigated the potential role of miR-155 in wound healing. By creating punch wounds in the skin of mice, we found an increased expression of miR-155 in wound tissue when compared with healthy skin. Interestingly, analysis of wounds of mice lacking the expression of miR-155 (miR-155−/−) revealed an increased wound closure when compared with wild-type animals. Also, the accelerated wound closing correlated with elevated numbers of macrophages in wounded tissue. Gene expression analysis of wounds tissue and macrophages isolated from miR-155−/− mice that were treated with interleukin-4 demonstrated an increased expression of miR-155 targets (BCL6, RhoA and SHIP1) as well as, the finding in inflammatory zone-1 (FIZZ1) gene, when compared with WT mice. Moreover, the up-regulated levels of FIZZ1 in the wound tissue of miR-155−/− mice correlated with an increased deposition of type-1 collagens, a phenomenon known to be beneficial in wound closure. Our data indicate that the absence of miR-155 has beneficial effects in the wound healing process. PMID:24636235

  9. 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

  10. The use of collagen-based matrices in the treatment of full-thickness wounds.

    PubMed

    Petersen, Wiebke; Rahmanian-Schwarz, Afshin; Werner, Jan-Ole; Schiefer, Jennifer; Rothenberger, Jens; Hübner, Gunnar; Schaller, Hans-Eberhard; Held, Manuel

    2016-09-01

    Chronic and complex full-thickness wounds have become increasingly prevalent. Besides autologous skin transplantation, innovative wound dressing products have gained interest, as the functional and esthetic outcome is still limited. In this respect, the effect of a novel modifiable collagen-gelatin fleece on the healing of deep dermal wounds was examined and compared with untreated controls and Matriderm(®). A total of 48 full-thickness skin defects were generated on six minipigs and treated with the novel collagen-gelatin fleece of different thicknesses in single or multiple application (n=36) or treated with Matriderm(®) in a single application (n=6), or the wounds were left untreated (n=6). Wound healing was analyzed planimetrically by wound closure per time and histologically with regard to epidermal thickness and cell density. Compared to untreated wounds, wound closure per time and histological skin quality with regard to the mean epidermal thickness and epidermal cell amount were enhanced in both treatment groups. Overall, the best results for the novel collagen-gelatin fleece were achieved for multiple applications with a thickness of 150g/m(2). The novel biomaterial shows accelerated and improved dermal wound repair in a minipig model. As the manufacturing process of the scaffold allows the integration of bioactive substances such as antibiotics and growth factors, we intend to design a composite biomaterial using this scaffold as a carrier matrix. PMID:27297940

  11. 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. PMID:25499914

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

    PubMed Central

    Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

    2006-01-01

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

  13. 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

  14. Quantitative stain-free and continuous multimodal monitoring of wound healing in vitro with digital holographic microscopy.

    PubMed

    Bettenworth, Dominik; Lenz, Philipp; 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

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

    PubMed

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

    2007-10-01

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

  16. Evaluation of Antimicrobial and Healing Activities of Frog Skin on Guinea Pigs Wounds

    PubMed Central

    Rezazade Bazaz, Mahere; Mashreghi, Mohammad; Mahdavi Shahri, Nasser; Mashreghi, Mansour; Asoodeh, Ahmad; Behnam Rassouli, Morteza

    2015-01-01

    Background: Frog skin secretions have potentials against a wide spectrum of bacteria. Also, frog skin compositions have healing properties. Objectives: The aim of this study was to investigate the antibacterial potentials along with healing properties of frog skin Rana ridibunda, a species which thoroughly lives in Iran marshes, as a biological dressing on wounds. Materials and Methods: In this study, excisional wounds, dressed with frog skin, were compared between experimental and control groups of guinea pigs. In the experimental groups, wounds were dressed with the dermal (FS) and epidermal (RFS) sides of fresh frog R. ridibunda skin, while only usual cotton gauze covered the wounds of the control group. Furthermore, microbial samples were taken on different days (0, 3, 5, and 7 days post injury) to count the number of the colony-forming units. Additionally, the microbial penetration test was performed on frog skin and then the progression of wound closure was evaluated. Results: In the microbial studies, the bacterial load considerably declined in the wounds treated with FS and RFS compared with the control wounds. On day 7 post injury, the numbers of the colony-forming units for the FS, RFS, and control groups were 6.75, 105, and 375, respectively. In the penetration test, fresh frog skin showed to be a bacterial resistant dressing. The results revealed that the rate of wound closure in the experimental groups significantly was accelerated in comparison with that in the control group. Conclusions: Our results demonstrated the antimicrobial properties of frog skin as a wound dressing, which has antimicrobial effects per se. This biological dressing shows promise as an effective biological wound dressing insofar as not only is it capable of resisting microbes and accelerating wound healing but also it is cost-effective and easy to use. PMID:26468364

  17. 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

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

    PubMed Central

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

    2015-01-01

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

  19. Chitosan Dermal Substitute and Chitosan Skin Substitute Contribute to Accelerated Full-Thickness Wound Healing in Irradiated Rats

    PubMed Central

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari; Jaafar, Hasnan; Asiah, Abu Bakar; Hassan, Asma

    2013-01-01

    Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation. PMID:24324974

  20. Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats.

    PubMed

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari; Jaafar, Hasnan; Asiah, Abu Bakar; Hassan, Asma

    2013-01-01

    Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation. PMID:24324974

  1. Evaluation of Vacuum Assisted Closure Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma

    PubMed Central

    Gill, S.P.S.; Sheopaltan, Sunil Kumar; Singh, Pulkesh; Dinesh; Sigh, Jasveer; Rastogi, Prateek; Mishra, L.N.

    2016-01-01

    Introduction The application of controlled levels of negative or sub atmospheric pressure for a prolonged period of time on a wound had shown to accelerate removal of excess fluid and promote hyperaemia, which eventually promote wound healing. Aim The study was conducted with the aim to evaluate the effectiveness of Vacuum Assisted Closure (VAC) therapy for soft tissue injury in open musculoskeletal trauma. Materials and Methods Twenty cases of complex musculoskeletal wound involving different parts of body were included in this progressive randomized study. In patients, aggressive debridement was done before the application of VAC therapy. Controlled negative pressure was uniformly applied to the wound. Dressings were changed after every 4 to 5 days. The evaluation of results included healing rate of the wound, eradication of infection, complication rate, and number of secondary procedures. Results VAC therapy over the wound was administered for an average of 20.4 days ±6.72 days (range 14 to 42 days). There was decrease in wound size attained by VAC therapy ranged from 2.6 to 24.4cm2, with an average reduction of 10.55 cm2. Three wounds were infected at the start of VAC therapy. However, all patients were cleared of bacterial infection by the end of VAC therapy. Conclusion VAC therapy using negative pressure promote Wound healing by increasing local capillary perfusion and increased rate of granulation tissue formation, decreases the duration of wound healing and requires fewer painful dressing change. PMID:27190906

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

    PubMed

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

    2012-01-01

    Despite advances in wound care, many wounds never heal and become chronic problems that result in significant morbidity and mortality to the patient. Cellular therapy for cutaneous wounds has recently come under investigation as a potential treatment modality for impaired wound healing. Bone marrow-derived mesenchymal stem cells (MSCs) are a promising source of adult progenitor cells for cytotherapy as they are easy to isolate and expand and have been shown to differentiate into various cell lineages. Early studies have demonstrated that MSCs may enhance epithelialization, granulation tissue formation, and neovascularization resulting in accelerated wound closure. It is currently unclear if these effects are mediated through cellular differentiation or by secretion of cytokines and growth factors. This review discusses the proposed biological contributions of MSCs to cutaneous repair and their clinical potential in cell-based therapies. PMID:22787462

  3. 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. PMID:23621008

  4. Bathysa cuspidata extract modulates the morphological reorganization of the scar tissue and accelerates skin wound healing in rats: a time-dependent study.

    PubMed

    Gonçalves, Reggiani V; Novaes, Rômulo D; Cupertino, Marli C; Araújo, Bruna M; Vilela, Emerson F; Machado, Aline T; Leite, João P V; Matta, Sérgio L P

    2014-01-01

    The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and potential applicability of an ointment-based Bathysa cuspidata extract (BCE) for the management of skin wounds in rats. Three skin wounds of 12 mm in diameter were made on the backs of the animals, which were randomized into 4 groups according to the application received, i.e. the SAL group: 0.9% saline solution, the LAN group: lanolin, the BCE 2.5% group: 2.5% BCE emulsified in lanolin and the BCE 5% group: 5% BCE emulsified in lanolin. The applications were made daily over 21 days, and every 7 days tissue from different wounds was removed. On days 7, 14 and 21, the BCE 2.5% and BCE 5% groups showed the best results in relation to wound closure, and a higher proportion (in length, density and volume) of blood vessels and fibroblasts compared to the other groups. On days 7 and 14, there was a significant increase in the number of mast cells in these 2 groups when compared to the SAL and LAN groups. On day 21, they also had a higher proportion of collagen I than collagen III. B. cuspidata in an ointment base was effective in stimulating tissue cellularity, mast cell recruitment, neoangiogenesis, synthesis and maturation of collagen, epidermal thickness and surface area in scar tissue. These events were potentially related to the best quality and speed for skin regeneration in the rats treated with the BCE ointment. PMID:25300223

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  7. An Immunomodulatory Protein (Ling Zhi-8) from a Ganoderma lucidum Induced Acceleration of Wound Healing in Rat Liver Tissues after Monopolar Electrosurgery

    PubMed Central

    Lin, Hao-Jan; Chang, Yushan-Sophie; Lin, Li-Hsiang; Haung, Chiung-Fang; Wu, Chia-Yu; Ou, Keng-Liang

    2014-01-01

    The purpose of this study was to investigate the effect of an immunomodulatory protein (Ling Zhi-8, LZ-8) on wound healing in rat liver tissues after monopolar electrosurgery. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days postoperatively. It was found that the wound with the LZ-8 treatment significantly increases wound healing. Western blot analysis clearly indicated that the expression of NF-κB was decreased at 3, 7, and 28 days when liver tissues were treated with LZ-8. Moreover, caspase-3 activity of the liver tissue also significantly decreases at 7 and 28 days, respectively. DAPI staining and TUNEL assays revealed that only a minimal dispersion of NF-κB was found on the liver tissue treated with LZ-8 at day 7 as compared with day 3 and tissues without LZ-8 treatment. Similarly, apoptosis was decreased on liver tissues treated with LZ-8 at 7 days when compared to the control (monopolar electrosurgery) tissues. Therefore, the analytical results demonstrated that LZ-8 induced acceleration of wound healing in rat liver tissues after monopolar electrosurgery. PMID:24883073

  8. 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

  9. 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. PMID:26310074

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

    PubMed

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

    2015-11-28

    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. PMID:26503372

  11. 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

  12. 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. PMID:25632675

  13. 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. PMID:26710090

  14. Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

    PubMed

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Ritsu, Masae; Kanno, Emi; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2015-12-01

    In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase. PMID:26468976

  15. Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity.

    PubMed

    Fumakia, Miral; Ho, Emmanuel A

    2016-07-01

    Wound care is a serious healthcare concern, often complicated by prolonged inflammation and bacterial infection, which contributes significantly to mortality and morbidity. Agents commonly used to treat chronic wound infections are limited due to toxicity of the therapy, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide possessing antimicrobial activity and is involved in the modulation of wound healing. Serpin A1 (A1) is an elastase inhibitor and has been shown to demonstrate wound-healing properties. Hence, our goal was to develop a topical combination nanomedicine for the controlled sustained delivery of LL37 and A1 at precise synergistic ratio combinations that will significantly promote wound closure, reduce bacterial contamination, and enhance anti-inflammatory activity. We have successfully developed the first solid lipid nanoparticle (SLN) formulation that can simultaneously deliver LL37 and A1 at specific ratios resulting in accelerated wound healing by promoting wound closure in BJ fibroblast cells and keratinocytes as well as synergistically enhancing antibacterial activity against S. aureus and E. coli in comparison to LL37 or A1 alone. PMID:27182713

  16. 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. PMID:26022525

  17. Wound management in perforated appendicitis.

    PubMed

    Lemieur, T P; Rodriguez, J L; Jacobs, D M; Bennett, M E; West, M A

    1999-05-01

    Open wound management after perforated appendicitis was common practice but, recently, primary closure has been advocated to reduce costs and morbidity. Hospital records from 319 adults who underwent appendectomy from 1993 to 1996 were reviewed to identify surgical wound infections (SWIs) and examine risk factors. Information about age, length of stay (LOS), operative time, white blood cell count, and antibiotic administration were obtained. Perforation was either noted at operation or identified microscopically by the pathologist. If primary wound closure was performed, patients with acute appendicitis and perforation had a 4-fold higher readmission rate, a 5-fold increase in SWI, and twice the LOS compared with patients with acute appendicitis without perforation. Patients with grossly perforated acute appendicitis had no difference in LOS if the wound was treated open or closed primarily. No patient with microscopic perforation and primary wound closure developed SWI. Primary wound closure after acute appendicitis was safe in the absence of clinical perforation. In the presence of clinical appendiceal perforation the wound should be left open. PMID:10231213

  18. Proliferation of Keratinocytes Induced by Adipose-Derived Stem Cells on a Chitosan Scaffold and Its Role in Wound Healing, a Review

    PubMed Central

    Gomathysankar, Sankaralakshmi; Yaacob, Nik Soriani

    2014-01-01

    In the field of tissue engineering and reconstruction, the development of efficient biomaterial is in high demand to achieve uncomplicated wound healing. Chronic wounds and excessive scarring are the major complications of tissue repair and, as this inadequate healing continues to increase, novel therapies and treatments for dysfunctional skin repair and reconstruction are important. This paper reviews the various aspects of the complications related to wound healing and focuses on chitosan because of its unique function in accelerating wound healing. The proliferation of keratinocytes is essential for wound closure, and adipose-derived stem cells play a significant role in wound healing. Thus, chitosan in combination with keratinocytes and adipose-derived stem cells may act as a vehicle for delivering cells, which would increase the proliferation of keratinocytes and help complete recovery from injuries. PMID:25276634

  19. Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.

    PubMed

    Mendez, Julio J; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum O; Steinbacher, Derek M; Leffell, David J; Niklason, Laura E

    2015-02-01

    Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608

  20. Cryptotanshinone downregulates the profibrotic activities of hypertrophic scar fibroblasts and accelerates wound healing: A potential therapy for the reduction of skin scarring.

    PubMed

    Li, Yan; Shi, Shan; Gao, Jianxin; Han, Shichao; Wu, Xue; Jia, Yanhui; Su, Linlin; Shi, Jihong; Hu, Dahai

    2016-05-01

    Hypertrophic scar (HS) is a skin fibrotic disease that causes major clinically problematic symptoms. Cryptotanshinone (CT) is an important ingredient of Danshen (Salvia miltiorrhiza Bunge extract) that has been used to treat cardio-cerebral vascular diseases. Its clinical efficacy in HS remains unclear. To investigate whether CT can inhibit HS fibrosis, HS-derived fibroblastic cells (HSFs) were established and treated with or without CT. Type-collagen-I (Col1), type-collagen-III (Col3) and α-smooth muscle actin (α-SMA) expression were measured by western blot and real-time quantitative polymerase chain reaction. HSFs migration and contraction were assessed with the scratch assay and the fibroblast-populated collagen lattice (FPCL) contraction assay, respectively. Wound healing in CT-treated Balb/c mice was assessed by immunohistochemical analysis of collagen expression and Masson's trichrome staining analysis of collagen deposition. CT treatment of HSFs down-regulated Col1, Col3 and α-SMA mRNA and protein expression, HSFs migration, and HSFs contraction, and improved FPCL architecture. In mice, CT treatment accelerated wound healing: the scar margins were narrow and there was less collagen deposition in the regenerated tissue. Thus, CT promotes wound healing and decreases excessive deposition of extracellular matrix components. CT may help to prevent and reduce scarring. PMID:27133042

  1. Endogenous N-acyl taurines regulate skin wound healing.

    PubMed

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

    2016-07-26

    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

  2. Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment.

    PubMed

    Wang, Xiaoling; Sng, Ming Keat; Foo, Selin; Chong, Han Chung; Lee, Wei Li; Tang, Mark Boon Yang; Ng, Kee Woei; Luo, Baiwen; Choong, Cleo; Wong, Marcus Thien Chong; Tong, Benny Meng Kiat; Chiba, Shunsuke; Loo, Say Chye Joachim; Zhu, Pengcheng; Tan, Nguan Soon

    2015-01-10

    Diabetic wounds are imbued with an early excessive and protracted reactive oxygen species production. Despite the studies supporting PPARβ/δ as a valuable pharmacologic wound-healing target, the therapeutic potential of PPARβ/δ agonist GW501516 (GW) as a wound healing drug was never investigated. Using topical application of polymer-encapsulated GW, we revealed that different drug release profiles can significantly influence the therapeutic efficacy of GW and consequently diabetic wound closure. We showed that double-layer encapsulated GW microparticles (PLLA:PLGA:GW) provided an earlier and sustained dose of GW to the wound and reduced the oxidative wound microenvironment to accelerate healing, in contrast to single-layered PLLA:GW microparticles. The underlying mechanism involved an early GW-mediated activation of PPARβ/δ that stimulated GPx1 and catalase expression in fibroblasts. GPx1 and catalase scavenged excessive H2O2 accumulation in diabetic wound beds, prevented H2O2-induced ECM modification and facilitated keratinocyte migration. The microparticles with early and sustained rate of GW release had better therapeutic wound healing activity. The present study underscores the importance of drug release kinetics on the therapeutic efficacy of the drug and warrants investigations to better appreciate the full potential of controlled drug release. PMID:25449811

  3. Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

    PubMed

    Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

    2015-05-01

    Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. PMID:25546438

  4. [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. PMID:23430199

  5. Wound healing for the clinician.

    PubMed

    Zitelli, J

    1987-01-01

    . (5) identification of complications; early identification of certain complications can prevent the delays in healing. These include infection, remembering infrequently cultured organisms such as yeast, malnourishment with protein and mineral deficiency, and the knowledge that adhesive-backed wound dressings can cause rewounding of otherwise normally healing wounds. (6) predicting the cosmetic result; wounds healed by secondary intention may provide a cosmetic result superior to surgical repair. Wounds in concave areas usually heal with a better result than wounds managed by flaps or grafts although wounds on convex surfaces usually look best if a skillful primary closure can be performed without distortion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3079257

  6. 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

  7. 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. PMID:27004048

  8. 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

  9. Regenerative materials that facilitate wound healing.

    PubMed

    Mulder, Gerit; Wallin, Kelly; Tenenhaus, Mayer

    2012-07-01

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

  10. 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

    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.

  11. Resolution mediator chemerin15 reprograms the wound microenvironment to promote repair and reduce scarring.

    PubMed

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

    2014-06-16

    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. 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. 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

  12. 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

  13. Acceleration of diabetic wound healing by a cryopreserved living dermal substitute created by micronized amnion seeded with fibroblasts

    PubMed Central

    Zheng, Yongjun; Ji, Shizhao; Wu, Haibin; Tian, Song; Wang, Xingtong; Luo, Pengfei; Fang, He; Wang, Zhihong; Wang, Junjie; Wang, Zhongshan; Xiao, Shichu; Xia, Zhaofan

    2015-01-01

    Bioengineered dermal substitutes have been used for the treatment of diabetic ulcers in clinics and achieved satisfactory results. However, constructing traditional tissue engineered dermal substitutes with two-step method is high-cost, time-consuming and greatly decreases fibroblast proliferative activity because of repeated trypsinization. Inthisstudy, we created a 3D micronized amniotic membrane (mAM) and used it as a natural microcarrier for ex vivo culture and amplification of human dermal fibroblasts (HDF) combined with the rotary cell culture system (RCCS). This one-step mAM-RCCS method couldamplify HDF quickly and construct a dermal substitute HDF-mAM simultaneously. To facilitate the clinical application of mAM-RCCS, anoptimized storage method was used.Post-thawing HDF-mAM retained high cell viability, intact cell morphology and active peptide secretion. When transplanted to the wounds of db/db mice, cryopreserved HDF-mAM promoted vascularization and diabetic wound healing significantly. These results demonstrate the potential application of cryopreserved HDF-mAM as a living dermal substitutefor treating diabetic ulcers and other chronic wounds in clinics. PMID:26885266

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

    PubMed

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

    2009-12-01

    Cutaneous wounds heal more slowly in elderly males than in elderly females, suggesting a role for sex hormones in the healing process. Indeed, androgen/androgen receptor (AR) signaling has been shown to inhibit cutaneous wound healing. AR is expressed in several cell types in healing skin, including keratinocytes, dermal fibroblasts, and infiltrating macrophages, but the exact role of androgen/AR signaling in these different cell types remains unclear. To address this question, we generated and studied cutaneous wound healing in cell-specific AR knockout (ARKO) mice. General and myeloid-specific ARKO mice exhibited accelerated wound healing compared with WT mice, whereas keratinocyte- and fibroblast-specific ARKO mice did not. Importantly, the rate of wound healing in the general ARKO mice was dependent on AR and not serum androgen levels. Interestingly, although dispensable for wound closure, keratinocyte AR promoted re-epithelialization, while fibroblast AR suppressed it. Further analysis indicated that AR suppressed wound healing by enhancing the inflammatory response through a localized increase in TNF-alpha expression. Furthermore, AR enhanced local TNF-alpha expression via multiple mechanisms, including increasing the inflammatory monocyte population, enhancing monocyte chemotaxis by upregulating CCR2 expression, and enhancing TNF-alpha expression in macrophages. Finally, targeting AR by topical application of a compound (ASC-J9) that degrades AR protein resulted in accelerated healing, suggesting a potential new therapeutic approach that may lead to better treatment of wound healing. PMID:19907077

  15. Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections.

    PubMed

    Warkentien, Tyler E; Shaikh, Faraz; Weintrob, Amy C; Rodriguez, Carlos J; Murray, Clinton K; Lloyd, Bradley A; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M Leigh; Tribble, David R

    2015-07-01

    Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. PMID:25972413

  16. 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. PMID:22692367

  17. Office management of minor wounds.

    PubMed Central

    Gouin, S.; Patel, H.

    2001-01-01

    OBJECTIVE: To review office interventions for minor wounds not requiring sutures, such as abrasions, bites, and lacerations. QUALITY OF EVIDENCE: Most information on minor wound management comes from descriptive studies. Few comparative studies examine the effectiveness of topical antisepsis for minor wounds. Several clinical trials have demonstrated that tissue adhesives produce short- and long-term cosmetic results equivalent to those achieved with suture materials. MAIN MESSAGE: Sterile saline is the least toxic solution for wound irrigation. Chlorhexidine (2%) and povidone iodine (10%) have been the most investigated antiseptic solutions. Systemic antibiotics are unnecessary for wounds unlikely to be infected. All bite wounds require special attention. Primary closure of bite wounds is indicated in certain circumstances: less than 12-hour-old nonpuncture wounds, uninfected wounds, and low-risk lesions (such as on the face). In spite of their many advantages, skin tapes should be used for low-tension wounds only. The popularity of tissue adhesives has greatly increased. Since the advent of newer products (with increased bonding strength and flexibility), adhesives are used to manage most lacerations except those in areas of high tension (e.g., joints) and on mucosal surfaces. CONCLUSION: Minor wounds not requiring sutures can be managed easily in the office. PMID:11340758

  18. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

    PubMed Central

    Valente, Sabrina; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andrea

    2016-01-01

    Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers. PMID:26788066

  19. Wound bed preparation: TIME for an update.

    PubMed

    Harries, Rhiannon L; Bosanquet, David C; Harding, Keith G

    2016-09-01

    While the overwhelming majority of wounds heal rapidly, a significant proportion fail to progress through the wound-healing process. These resultant chronic wounds cause considerable morbidity and are costly to treat. Wound bed preparation, summarised by the TIME (Tissue, Inflammation/infection, Moisture imbalance, Epithelial edge advancement) concept, is a systematic approach for assessing chronic wounds. Each of these components needs to be addressed and optimised to improve the chances of successful wound closure. We present an up-to-date literature review of the most important recent aspects of wound bed preparation. While there are many novel therapies that are available to the treating clinician, often, there are limited data on which to assess their clinical value, and a lack of appreciation for adequate wound bed preparation needed before expensive therapy is used to heal a wound. PMID:27547958

  20. Closure in Knee Replacement Surgery

    PubMed Central

    Kharat, Kiran

    2012-01-01

    Total Knee replacement (TKR) is one of the commonest arthroplasty surgeries performed. Various techniques of closures in TKR are described. This technical note describes an useful technique of achieving water tight closure in TKR. An optimal tension watertight closure also reduces the chances of dead space hematomas and infection. The author has described his technique where the soft tissues are never unduly compromised. In his experience the patient can be mobilized freely in bed and even allowed to sleep prone after first wound check.

  1. Comparison of negative pressure wound therapy (NPWT) &conventional wound dressings in the open fracture wounds

    PubMed Central

    Arti, Hamidreza; Khorami, Mohsen; Ebrahimi-Nejad, Vahid

    2016-01-01

    Objective: Successful closure is a primary step of treatment in open fracture wounds. Delayed healing or complications can lead to increased treatment duration, costs and disability rates. The aim of this study was to compare Negative Pressure Wound Therapy (NPWT) and conventional wound dressings in patients with open fracture wounds. Methods: In a prospective randomized clinical trial study, 90 patients with open fractures that were referred for treatment were enrolled between February 2013 to March 2015. Patients were divided into two groups. Group I underwent NPWT and group II underwent conventional wound dressing. Then patients were followed up for one month. Within the one month, the number of dressing change varied based on the extent of the wound. Duration of wound healing, presence of infection and the number of hospitalization days in these patients were recorded and compared at the end of the study between the two groups. Questionnaires and check lists were used to collect data. Analysis was done with SPSS 20, paired sample T-test, and chi-square tests. P<0.05 was considered significant. Results: There was a significant difference between the rate of wound healing in the group one or NPWT group and group II (conventional wound dressings) P<0.05. There was no significant difference between two groups in incidence of infection (P=0.6). Conclusion: Using NPWT expedites the healing process of extremity wounds. It is more economical and can be considered as a substitute for the treatment of extremity wounds. PMID:27022347

  2. 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.

  3. Dermal wound healing properties of redox-active grape seed proanthocyanidins.

    PubMed

    Khanna, Savita; Venojarvi, Mika; Roy, Sashwati; Sharma, Nidhi; Trikha, Prashant; Bagchi, Debasis; Bagchi, Manashi; Sen, Chandan K

    2002-10-15

    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. The wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. We proposed that oxidants in the wound microenvironment support the repair process. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Previously we have reported that a grape seed proanthycyanidin extract containing 5000 ppm resveratrol (GSPE) potently upregulates oxidant and tumor necrosis factor-alpha inducible VEGF expression in human keratinocytes (Free Radic. Biol. Med. 31:38-42, 2001). Our current objective was to follow up on that finding and test whether GSPE influences dermal wound healing in vivo. First, using a VEGF promoter-driven luciferase reporter construct we observed that the potentiating effect of GSPE on inducible VEGF expression is at the transcriptional level. The reporter assay showed that GSPE alone is able to drive VEGF transcription. Next, two dermal excisional wounds were inflicted on the back of mice and the wounds were left to heal by secondary intention. Topical application of GSPE accelerated wound contraction and closure. GSPE treatment was associated with a more well-defined hyperproliferative epithelial region, higher cell density, enhanced deposition of connective tissue, and improved histological architecture. GSPE treatment also increased VEGF and tenascin expression in the wound edge tissue. Tissue glutathione oxidation and 4-hydroxynonenal immunostaining results supported that GSPE application enhanced the oxidizing environment at the wound site. Oxidants are known to promote both VEGF as well as tenascin expression. In summary, our current study provides firm evidence to support that

  4. 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. PMID:26776318

  5. Epidermal growth factor loaded heparin-based hydrogel sheet for skin wound healing.

    PubMed

    Goh, MeeiChyn; Hwang, Youngmin; Tae, Giyoong

    2016-08-20

    A heparin-based hydrogel sheet composed of thiolated heparin and diacrylated poly (ethylene glycol) was prepared via photo polymerization and human epidermal growth factor (hEGF) were loaded into it for the purpose of wound healing. It showed a sustained release profile of hEGF in vitro. In order to evaluate its function on wound healing in vivo, full thickness wounds were created on the dorsal surface of mice. Application of hEGF loaded heparin-based hydrogel sheet accelerated the wound closure compared to the non-treated control group, hEGF solution, and hEGF loaded PEG hydrogel sheet. Histological and immunohistological examinations also demonstrated an advanced granulation tissue formation, capillary formation, and epithelialization in wounds treated by hEGF loaded heparin-based hydrogel compared to other groups, and no biocompatibility issue was observed. In conclusion, the delivery of hEGF using the heparin-based hydrogel could accelerate the skin wound healing process. PMID:27178931

  6. 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. PMID:24872149

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

    PubMed

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

    2016-01-01

    Mesenchymal stem cells (MSCs) (also known as multipotent mesenchymal stromal cells) possess the capacity for self-renewal and multi-lineage differentiation, and their ability to enhance cutaneous wound healing has been well characterized. Acting via paracrine interactions, MSCs accelerate wound closure, increase angiogenesis, promote resolution of wound inflammation, favorably regulate extracellular matrix remodeling, and encourage regeneration of skin with normal architecture and function. A number of studies have employed novel methods to amplify the delivery and efficacy of MSCs. Non-traditional sources of MSCs, including Wharton's jelly and medical waste material, have shown efficacy comparable to that of traditional sources, such as bone marrow and adipose tissue. The potential of alternative methods to both introduce MSCs into wounds and increase migration of MSCs into wound areas has also been demonstrated. Taking advantage of the associations between MSCs with M2 macrophages and microRNA, methods to enhance the immunomodulatory capacity of MSCs have shown success. New measures to enhance angiogenic capabilities have also exhibited effectiveness, often demonstrated by increased levels of proangiogenic vascular endothelial growth factor. Finally, hypoxia has been shown to have strong wound-healing potential in terms of increasing MSC efficacy. We have critically reviewed the results of the novel studies that show promise for the continued development of MSC-based wound-healing therapies and provide direction for continued research in this field. PMID:26960535

  8. 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

  9. E2F1 Hinders Skin Wound Healing by Repressing Vascular Endothelial Growth Factor (VEGF) Expression, Neovascularization, and Macrophage Recruitment

    PubMed Central

    Zeng, Ning; Wang, Haiping; Deng, Pei; Xu, Yi; Feng, Youping; Zeng, Hong; Yang, Hongxia; Hou, Kai; Wang, Andrew; Parthasarathy, Keshav; Goyal, Samaksh; Qin, Gangjian; Wu, Min

    2016-01-01

    Background Refractory surface of wound and dermal chronic ulcer are largely attributed to poor neovascularization. We have previously shown that E2F1 suppresses VEGF expression in the ischemic heart, and that genetic deletion of E2F1 leads to better cardiac recovery. However, whether E2F1 has a role in dermal wound healing is currently not known. Methods and Results Skin wounds were surgically induced in E2F1-null (E2F1–/–) mice and WT littermates. E2F1–/– displayed an accelerated wound healing including wound closure, dermal thickening and collagen deposition, which was associated with an increased endothelial cell proliferation and greater vessel density in the border zone of the wound. Furthermore, more macrophages were recruited to the skin lesions and the level of VEGF expression was markedly higher in E2F1–/– than in WT mice. Conclusions E2F1 hinders skin wound healing by suppressing VEGF expression, neovascularization, and macrophage recruitment. Strategies that target E2F1 may enhance wound healing. PMID:27490344

  10. 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

  11. 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.

  12. 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

  13. 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. PMID:26088354

  14. 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

  15. Emblica officinalis exerts wound healing action through up-regulation of collagen and extracellular signal-regulated kinases (ERK1/2).

    PubMed

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

    2009-01-01

    During wound healing, the wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. Ascorbic acid and tannins of low molecular weight, namely emblicanin A (2,3-di-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-2-keto-glucono-delta-lactone) and emblicanin B (2,3,4,6-bis-(S)-hexahydroxydiphenoyl-2-keto-glucono-delta-lactone) present in Emblica officinalis (emblica), have been shown to exhibit a very strong antioxidant action. We proposed that addition of these antioxidants to the wound microenvironment would support the repair process. The present investigation was undertaken to determine the efficacy of emblica on dermal wound healing in vivo. Full-thickness excision wounds were made on the back of the rat and topical application of emblica accelerated wound contraction and closure. Emblica increased cellular proliferation and cross-linking of collagen at the wound site, as evidenced by an increase in the activity of extracellular signal-regulated kinase 1/2, along with an increase in DNA, type III collagen, acid-soluble collagen, aldehyde content, shrinkage temperature and tensile strength. Higher levels of tissue ascorbic acid, alpha-tocopherol, reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase support the fact that emblica application promotes antioxidant activity at the wound site. In summary, this study provides firm evidence to support that topical application of emblica represents a feasible and productive approach to support dermal wound healing. PMID:19152656

  16. Transcriptional signature of epidermal keratinocytes subjected to in vitro scratch wounding reveals selective roles for ERK1/2, p38, and phosphatidylinositol 3-kinase signaling pathways.

    PubMed

    Fitsialos, Giorgos; Chassot, Anne-Amandine; Turchi, Laurent; Dayem, Manal A; LeBrigand, Kevin; Moreilhon, Chimène; Meneguzzi, Guerrino; Buscà, Roser; Mari, Bernard; Barbry, Pascal; Ponzio, Gilles

    2007-05-18

    Covering denuded dermal surfaces after injury requires migration, proliferation, and differentiation of skin keratinocytes. To clarify the major traits controlling these intermingled biological events, we surveyed the genomic modifications occurring during the course of a scratch wound closure of cultured human keratinocytes. Using a DNA microarray approach, we report the identification of 161 new markers of epidermal repair. Expression data, combined with functional analysis performed with specific inhibitors of ERK, p38(MAPK) and phosphatidylinositol 3-kinase (PI3K), demonstrate that kinase pathways exert very selective functions by precisely controlling the expression of specific genes. Inhibition of the ERK pathway totally blocks the wound closure and inactivates many early transcription factors and EGF-type growth factors. p38(MAPK) inhibition only delays "healing," probably in line with the control of genes involved in the propagation of injury-initiated signaling. In contrast, PI3K inhibition accelerates the scratch closure and potentiates the scratch-dependent stimulation of three genes related to epithelial cell transformation, namely HAS3, HBEGF, and ETS1. Our results define in vitro human keratinocyte wound closure as a repair process resulting from a fine balance between positive signals controlled by ERK and p38(MAPK) and negative ones triggered by PI3K. The perturbation of any of these pathways might lead to dysfunction in the healing process, similar to those observed in pathological wounding phenotypes, such as hypertrophic scars or keloids. PMID:17363378

  17. [Wound management].

    PubMed

    Gresser, J; Bitz, K; Hegglin, J

    1992-07-01

    The following article is a check-list for wound care giving some practical hints. Special interest has been given to the themes of local anesthesia and prevention of infections. The indications and limits of the ambulant wound care are also discussed. Finally, a short explanation is given for the treatment of wounds situated at delicate regions of the body. PMID:1440441

  18. 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. PMID:26763450

  19. The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study

    PubMed Central

    El Sadik, Abir O.; El Ghamrawy, Tarek A.; Abd El-Galil, Tarek I.

    2015-01-01

    follicles and sebaceous glands in the dermis of the healed areas more than in other groups. Conclusion MSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment. PMID:26402454

  20. 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

  1. 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

  2. Interaction and effectiveness of antimicrobials along with healing-promoting agents in a novel biocellulose wound dressing.

    PubMed

    Napavichayanun, Supamas; Amornsudthiwat, Phakdee; Pienpinijtham, Prompong; Aramwit, Pornanong

    2015-10-01

    An ideal wound dressing should keep the wound moist, allow oxygen permeation, adsorb wound exudate, accelerate re-epithelialization for wound closure, reduce pain and healing time, and prevent infection. Our novel biocellulose-based wound dressing was composed of three components: 1) biocellulose (BC), intended to create a moist and oxygen-permeated environment with exudate adsorption; 2) silk sericin (SS) known for its enhancement of collagen type I production, which is critical for re-epithelialization; and 3) the antiseptic polyhexamethylene biguanide (PHMB). To deliver an effective BC wound dressing, the interactions between the components (PHMB vs. SS) needed to be thoroughly analyzed. In this study, we investigated important parameters such as the loading sequence, loading concentration, and loading amount of the active compounds to ensure that the BC wound dressing could provide both antimicrobial activity and promote collagen production during healing. The loading sequence of SS and PHMB into BC was critical to maintain PHMB antimicrobial activity; silk sericin needed to be loaded before PHMB to avoid any negative impacts. The minimum PHMB concentration was 0.3% w/v for effective elimination of all tested bacteria (Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa). The amounts of SS and PHMB in BC were optimized to ensure that the dressings released the optimal amounts of both SS to enhance fibroblast collagen production and PHMB for effective antimicrobial activity. PMID:26117743

  3. Wound dressings.

    PubMed

    Lionelli, Gerald T; Lawrence, W Thomas

    2003-06-01

    There are currently hundreds of dressings on the market to aid in wound management. Before selecting a dressing for a particular wound, a practitioner must assess carefully the needs of the wound to understand which dressing would provide maximal benefit. Frequently, there is not one clear best choice, and it is crucial that the pros and cons of each dressing modality be understood. This article has provided a framework to assist in dressing assessment. PMID:12822729

  4. 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. PMID:26952426

  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. PMID:23193824

  6. G-CSF enhances resolution of Staphylococcus aureus wound infection in an age-dependent manner.

    PubMed

    Brubaker, Aleah L; Kovacs, Elizabeth J

    2013-10-01

    This study tested the hypothesis that heightened bacterial colonization and delayed wound closure in aged mice could be attenuated by granulocyte colony-stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had elevated bacterial levels, protracted wound closure, and reduced wound neutrophil accumulation after Staphylococcus aureus wound infection relative to young mice. In aseptic wound models, G-CSF treatment improved wound closure in aged mice to rates observed in young mice. Given these data, our objective was to determine if G-CSF could restore age-associated differences in wound bacterial burden and closure by increasing wound neutrophil recruitment. Young (3- to 4-month) and aged (18- to 20-month) BALB/c mice received three dorsal subcutaneous injections of G-CSF (250 ng/50 μL per injection) or saline control (50 μL per injection) 30 min after wound infection. Mice were killed at days 3 and 7 after wound infection, and bacterial colonization, wound size, wound leukocyte accumulation, and peripheral blood were evaluated. At days 3 and 7 after wound infection, bacterial colonization was significantly reduced in G-CSF-treated aged mice to levels observed in saline-treated young animals. Wound size was reduced in G-CSF-treated aged animals, with no effect on wound size in G-CSF-treated young mice. Local G-CSF treatment significantly enhanced neutrophil wound accumulation in aged mice, whereas there was no G-CSF-induced change in young mice. These data demonstrate that G-CSF enhances bacterial clearance and wound closure in an age-dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting of postoperative wound infection or chronic nonhealing wounds in elderly patients. PMID:23856924

  7. Impaired wound healing in bleomycin-induced murine scleroderma: a new model of wound retardation.

    PubMed

    Maeda, Tatsuo; Yamamoto, Toshiyuki; Imamura, Toru; Tsuboi, Ryoji

    2016-03-01

    Bleomycin-induced scleroderma in mice is an established model for human scleroderma. Making use of this, we have established a new model for wound retardation. After inducing dermal sclerosis by local bleomycin treatment in nude mice, a full-thickness wound was made by punch excision on the bleomycin application site. Mice pretreated with bleomycin showed a significant delay in wound closure, as compared with mice pretreated with phosphate-buffered saline. Proliferation of keratinocytes was significantly inhibited and the number of Ki-67-positive keratinocytes was significantly lower in the bleomycin-pretreated skin. Also, the number of CD31-positive blood vessels was markedly reduced in the bleomycin-treated skin. The topical daily application of basic fibroblast growth factor (bFGF) significantly promoted wound closure, while increasing blood vessel formation and reducing transforming growth factor-β and alpha-smooth muscle actin mRNA levels. Furthermore, only two applications of PG-FGF1, a fusion protein of FGF1 with heparan sulfate proteoglycan, overcame the delay in wound closure. Wound delay in this model mainly occurred as a result of decreased vessel formation and keratinocyte migration following bleomycin treatment. It is expected that this model will provide novel insights into the pathogenesis of wound healing and the exploration of possible candidate drugs for refractory or chronic wounds in the clinical setting. PMID:26660455

  8. 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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

    Reid, Brian; Zhao, Min

    2014-01-01

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

  12. 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

  13. 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

  14. On the significance of negative-pressure wound therapy with instillation in dermatology.

    PubMed

    Müller, Cornelia Sigrid Lissi; Burgard, Barbara; Zimmerman, Monika; Vogt, Thomas; Pföhler, Claudia

    2016-08-01

    Methods used in the treatment of acute and chronic wounds undergo constant evolution, reevaluation, and innovation. While negative-pressure wound therapy (NPWT) is an established treatment modality, the combination of NPWT and instillation of normal saline as well as solutions with active antiseptic components for topical treatment of the wound bed represents a novel approach. The well-known effects of NPWT may thus be combined with those of local antisepsis. They include a decrease in wound area, induction of granulation tissue, and reduction in bacterial colonization. To date, studies have focused on NPWT with instillation for orthopedic/surgical indications, whereas clinical data in dermatosurgery is limited to case reports or small case series. There are as yet no randomized prospective studies investigating NPWT with instillation in the treatment of skin disorders. The goal of this review is to present the method of NPWT with instillation, to highlight its mode of action as well as possible complications and contraindications, and to review the recent literature. In summary, there is increasing evidence that both simple and complicated wounds may be effectively treated with NPWT with instillation, resulting in markedly accelerated tissue granulation and thus earlier defect closure. PMID:27509412

  15. Acellular hydrogel for regenerative burn wound healing: translation from a porcine model

    PubMed Central

    Papa, Arianne; Burke, Jacqueline; Volk, Susan W; Gerecht, Sharon

    2015-01-01

    Currently available skin grafts and skin substitute for healing following third-degree burn injuries is fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative fashion would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate vulnerary efficacy and accelerated healing mechanism of dextran-based hydrogel in third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved reepithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared to the dressing treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients. PMID:26358387

  16. Evaluation of polypropylene mesh coated with biological hydrogels for temporary closure of open abdomen.

    PubMed

    Deng, Youming; Ren, Jianan; Chen, Guopu; Li, Guanwei; Guo, Kun; Hu, Qiongyuan; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Li, Jieshou

    2016-08-01

    Polypropylene mesh, as a temporary abdominal closure device, may cause mechanical intestine injury and inflammatory response. Chitosan/gelatin hydrogel has excellent biocompatibility, soft and elastic properties. This work is to assess the effects of the chitosan/gelatin hydrogel coated polypropylene mesh on open abdomen wounds. Histological analysis and detection of healing-related factors were conducted to evaluate the inflammation and wound healing process. After 1-day implantation in a murine model of open abdomen, the coated polypropylene mesh, compared with simple polypropylene mesh, demonstrated well protection of the intestine serosa. After 14-day implantation, it reduced the inflammation response by down-regulating the cytokines interleukin-6 and tumor necrosis factor-α, and up-regulating the anti-inflammatory factor interleukin-10. Meanwhile, the composite stimulated granulation tissue growth, and promoted matrix deposition and angiogenesis after 7 and 14 days. In conclusion, the modified temporary abdominal closure composite could significantly protect the intestines from mechanical damage and accelerate wound healing. PMID:27114442

  17. [Wound healing and wound irrigation in cesarean section of cattle].

    PubMed

    de Kruif, A; van den Brand, L P; van Kuyk, M M; Raymakers, R J; Sietsma, C; Westerbeek, A J

    1987-09-01

    Calves were delivered by Caesarean section in 128 cases during the early months of 1984. All animals were allocated alternately to a trial group and a group of controls. When the peritoneum and transverse muscle had been sutured, the wounds of the animals in the trial group were irrigated and washed with 300 ml. of Betadine (10 per cent of PVP-iodine in water). This was followed by closure of the wound. The animals of the group of controls were not treated. The procedure was performed in ninety-four primiparae (73 per cent) and thirty-four multiparae (27 per cent). The indication for Caesarean section consisted in fetal oversize in 119 cases (93 per cent). Eight calves (6 per cent) were stillborn or died immediately post partum. The proportion of animals in which the placentae were retained, was 9 per cent. Two animals died from peritonitis and intra-abdominal haemorrhage respectively. Irrigation of the wound did not have any effect on the number of wound infections (Table 3). Wound infection occurred in nineteen animals (15 per cent). The operations were performed by six veterinary surgeons (Table 4). The trial group and group of controls treated by each veterinarian did not differ essentially as regards wound healing. PMID:3672464

  18. 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

  19. 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

  20. 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

  1. Wound care in venous ulcers.

    PubMed

    Mosti, G

    2013-03-01

    Wound dressings: ulcer dressings should create and maintain a moist environment on the ulcer surface. It has been shown that in an ulcer with a hard crust and desiccated bed, the healing process is significantly slowed and sometimes completely blocked so favouring infection, inflammation and pain. In contrast a moist environment promotes autolytic debridement, angiogenesis and the more rapid formation of granulation tissue, favours keratinocytes migration and accelerates healing of wounds. Apart from these common characteristics, wound dressings are completely different in other aspects and must be used according to the ulcer stage. In necrotic ulcers, autolytic debridement by means of hydrogel and hydrocolloids or with enzymatic paste is preferred. In case of largely exuding wounds alginate or hydrofibre are indicated. When bleeding occurs alginate is indicated due to its haemostatic power. Where ulcers are covered by granulation tissue, polyurethane foams are preferred. When infection coexists antiseptics are necessary: dressing containing silver or iodine with large antibacterial spectrum have proved to be very effective. In the epithelization stage polyurethane films or membranes, thin hydrocolloids or collagen based dressings are very useful to favour advancement of the healing wound edge. Despite these considerations, a Cochrane review failed to find advantages for any dressing type compared with low-adherent dressings applied beneath compression. Surgical debridement and grafting of wounds, negative wound pressure treatment: surgical and hydrosurgical debridement are indicated in large, necrotic and infected wounds as these treatments are able to get rid of necrotic, infected tissue very quickly in a single surgical session, thereby significantly accelerating wound bed preparation and healing time. Negative wound pressure treatment creating a negative pressure on ulcer bed is able to favour granulation tissue and shorten healing time. In case of hard

  2. 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

  3. Does wound eversion improve cosmetic outcome?

    PubMed Central

    Kappel, Stefani; Kleinerman, Rebecca; King, Thomas H.; Sivamani, Raja; Taylor, Sandra; Nguyen, UyenThao; Eisen, Daniel B.

    2016-01-01

    Background Wound edge eversion has been hypothesized to improve aesthetic outcomes after cutaneous wound closure. Data supporting this assertion are sparse. Objective We sought to determine if wound eversion, achieved with interrupted subcuticular sutures, improves aesthetic outcome compared with planar closures. Methods We undertook a prospective, randomized, split-scar intervention in patients who underwent cutaneous surgery. Half of the wound was randomized to an everted or planar repair; the other side received the opposite one. At 3- and 6-month follow-up, both the patient and 2 blinded observers evaluated the wound using the Patient Observer Self-Assessment Scale (POSAS). Results The total observer POSAS score for the everted (13.59, 12.26) and planar (12.91, 12.98) sides did not differ significantly at 3 or 6 months, respectively. Similarly, there was not a significant difference in patient assessment between the everted (16.23, 12.84) and planar (15.07, 12.79) sides at 3 or 6 months, respectively. Finally, there was no significant difference between the 2 closure methods in terms of scar height or width at follow-up. Limitations This was a single-center trial, which used a validated but still subjective scar assessment instrument. Conclusion Wound eversion was not significantly associated with improved overall scar assessments by blinded observers or patient assessment. PMID:25619206

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2014-04-01

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

  6. Visual Closure.

    ERIC Educational Resources Information Center

    Groffman, Sidney

    An experimental test of visual closure based on an information-theory concept of perception was devised to test the ability to discriminate visual stimuli with reduced cues. The test is to be administered in a timed individual situation in which the subject is presented with sets of incomplete drawings of simple objects that he is required to name…

  7. Nutrition in Wound Care Management: A Comprehensive Overview.

    PubMed

    Quain, Angela M; Khardori, Nancy M

    2015-12-01

    Wound care is a multidisciplinary specialty requiring many physiologic and immunologic processes as well as physical, social, and societal factors to achieve successful wound closure. Most wounds are treated with combinations of antimicrobials, protective barriers, and topical growth agents, including skin and biologic grafts.The role of nutrition in wound healing may be overlooked in the wound care patient. Like the specialty, it is often multifaceted, with many nutritional components playing a variety of roles in the wound healing process. Suboptimal nutrition can alter immune function, collagen synthesis, and wound tensile strength, all of which are essential in the wound healing process. It is also important to remember that not all wounds are equal: a burn is different from a diabetic foot ulcer, which is different from a pressure ulcer. Nonetheless, nutrition is a common denominator for all wound patients, and what is studied in 1 wound population is often relevant in another. Due to the complexities of monitoring and measuring both wound healing and dietary intake, randomized, controlled trials of wound care patients are difficult to conduct, and much of the data concerning nutrition in wound care relies on combined supplements. In summary, it appears that some nutrients are necessary only if deficient, whereas others may become conditionally essential and serve a therapeutic role. All of the nutrients discussed should be viewed as a component of a broader, complete diet. This article is a summary of wound healing and the roles of a variety of macronutrients and micronutrients in the process. PMID:27447105

  8. Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds

    PubMed Central

    Xu, Kedi; Cantu, David Antonio; Fu, Yao; Kim, Jaehyup; Zheng, Xiaoxiang; Hematti, Peiman; Kao, W. John

    2013-01-01

    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 of 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 of 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 gelatin/poly(ethylene glycol) biomatrix localized the presentation of MSCs adjacent to the wound microenvironment and thus, mediated early resolution of inflammatory events and facilitated proliferative phases in wound healing. PMID:23811217

  9. Nitrosoglutathione generating nitric oxide nanoparticles as an improved strategy for combating Pseudomonas aeruginosa-infected wounds.

    PubMed

    Chouake, Jason; Schairer, David; Kutner, Allison; Sanchez, David A; Makdisi, Joy; Blecher-Paz, Karin; Nacharaju, Parimala; Tuckman-Vernon, Chaim; Gialanella, Phil; Friedman, Joel M; Nosanchuk, Joshua D; Friedman, Adam J

    2012-12-01

    Pseudomonas aeruginosa is a community-acquired, nosocomial pathogen that is an important cause of human morbidity and mortality; it is intrinsically resistant to several antibiotics and is capable of developing resistance to newly developed drugs via a variety of mechanisms. P aeruginosa's ubiquity and multidrug resistance (MDR) warrants the development of innovative methods that overcome its ability to develop resistance. We have previously described a nitric oxide-releasing nanoparticle (NO-np) platform that effectively kills gram-positive and gram-negative organisms in vitro and accelerates clinical recovery in vivo in murine wound and abscess infection models. We have also demonstrated that when glutathione (GSH) is added to NO-np, the nitroso intermediate S-nitrosoglutathione (GSNO) is formed, which has greater activity against P aeruginosa and other gram-negative organisms compared with NO-np alone. In the current study, we evaluate the potential of NO-np to generate GSNO both in vitro and in vivo in a murine excisional wound model infected with an MDR clinical isolate of P aeruginosa. Whereas NO-np alone inhibited P aeruginosa growth in vitro for up to 8 hours, NO-np+GSH completely inhibited P aeruginosa growth for 24 hours. Percent survival in the NO-np+GSH-treated isolates was significantly lower than in the NO-np (36.1% vs 8.3%; P=.004). In addition, NO-np+GSH accelerated wound closure in P aeruginosa-infected wounds, and NO-np+GSH-treated wounds had significantly lower bacterial burden when compared to NO-np-treated wounds (P<.001). We conclude that GSNO is easily generated from our NO-np platform and has the potential to be used as an antimicrobial agent against MDR organisms such as P aeruginosa. PMID:23377518

  10. Capillary Force Seeding of Hydrogels for Adipose-Derived Stem Cell Delivery in Wounds

    PubMed Central

    Garg, Ravi K.; Rennert, Robert C.; Duscher, Dominik; Sorkin, Michael; Kosaraju, Revanth; Auerbach, Lauren J.; Lennon, James; Chung, Michael T.; Paik, Kevin; Nimpf, Johannes; Rajadas, Jayakumar; Longaker, Michael T.

    2014-01-01

    Effective skin regeneration therapies require a successful interface between progenitor cells and biocompatible delivery systems. We previously demonstrated the efficiency of a biomimetic pullulan-collagen hydrogel scaffold for improving bone marrow-derived mesenchymal stem cell survival within ischemic skin wounds by creating a “stem cell niche” that enhances regenerative cytokine secretion. Adipose-derived mesenchymal stem cells (ASCs) represent an even more appealing source of stem cells because of their abundance and accessibility, and in this study we explored the utility of ASCs for hydrogel-based therapies. To optimize hydrogel cell seeding, a rapid, capillary force-based approach was developed and compared with previously established cell seeding methods. ASC viability and functionality following capillary hydrogel seeding were then analyzed in vitro and in vivo. In these experiments, ASCs were seeded more efficiently by capillary force than by traditional methods and remained viable and functional in this niche for up to 14 days. Additionally, hydrogel seeding of ASCs resulted in the enhanced expression of multiple stemness and angiogenesis-related genes, including Oct4, Vegf, Mcp-1, and Sdf-1. Moving in vivo, hydrogel delivery improved ASC survival, and application of both murine and human ASC-seeded hydrogels to splinted murine wounds resulted in accelerated wound closure and increased vascularity when compared with control wounds treated with unseeded hydrogels. In conclusion, capillary seeding of ASCs within a pullulan-collagen hydrogel bioscaffold provides a convenient and simple way to deliver therapeutic cells to wound environments. Moreover, ASC-seeded constructs display a significant potential to accelerate wound healing that can be easily translated to a clinical setting. PMID:25038246

  11. Recent advances in topical wound care

    PubMed Central

    Sarabahi, Sujata

    2012-01-01

    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. PMID:23162238

  12. 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

  13. 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.

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

    PubMed

    Wu, Jiang; Ye, Jingjing; Zhu, Jingjing; Xiao, Zecong; He, Chaochao; Shi, Hongxue; Wang, Yadong; Lin, Cai; Zhang, Hongyu; Zhao, Yingzheng; Fu, Xiaobing; Chen, Hong; Li, Xiaokun; Li, Lin; Zheng, Jie; Xiao, Jian

    2016-06-13

    Effective wound healing requires complicated, coordinated interactions and responses at protein, cellular, and tissue levels involving growth factor expression, cell proliferation, wound closure, granulation tissue formation, and vascularization. In this study, we develop a heparin-based coacervate consisting of poly(ethylene argininylaspartate digylceride) (PEAD) as a storage matrix, heparin as a bridge, and fibroblast growth factor-2 (FGF2) as a cargo (namely heparin-FGF2@PEAD) for wound healing. First, in vitro characterization demonstrates the loading efficiency and control release of FGF2 from the heparin-FGF2@PEAD coacervate. The following in vivo studies examine the wound healing efficiency of the heparin-FGF2@PEAD coacervate upon delivering FGF2 to full-thickness excisional skin wounds in vivo, in comparison with the other three control groups with saline, heparin@PEAD as vehicle, and free FGF2. Collective in vivo data show that controlled release of FGF2 to the wounds by the coacervate significantly accelerates the wound healing by promoting cell proliferation, stimulating the secretion of vascular endothelial growth factor (VEGF) for re-epithelization, collagen deposition, and granulation tissue formation, and enhancing the expression of platelet endothelial cell adhesion molecule (CD31) and alpha-smooth muscle actin (α-SMA) for blood vessel maturation. In parallel, no obvious wound healing effect is found for the control, vehicle, and free FGF2 groups, indicating the important role of the coavervate in the wound healing process. This work designs a suitable delivery system that can protect and release FGF2 in a sustained and controlled manner, which provides a promising therapeutic potential for topical treatment of wounds. PMID:27196997

  15. Polyurethane foam containing rhEGF as a dressing material for healing diabetic wounds: Synthesis, characterization, in vitro and in vivo studies.

    PubMed

    Pyun, Do Gi; Choi, Hyun Jun; Yoon, Hyoung Soon; Thambi, Thavasyappan; Lee, Doo Sung

    2015-11-01

    Diabetic wounds are a major health issue associated with diabetes mellitus. To surmount this issue, we developed polyurethane foams (PUFs) incorporating varying amounts of recombinant human epidermal growth factor (rhEGF) (rhEGF-PUFs) as a wound dressing for diabetic wounds. From electron microscopy images, it was found that the pore size of the rhEGF-PUFs surface (the wound contact layer) was less than 100μm, regardless of rhEGF content. The release of rhEGF from the PUFs was evaluated using an enzyme-linked immunosorbent assay. The result showed that the release of rhEGF was time and concentration dependent, i.e., the amount of released rhEGF significantly increased as the immersion time and the rhEGF content of the PUFs increased. In vitro cytotoxicity testing showed that rhEGF-PUFs increased the viability of HaCaT human keratinocytes and CCD986-sk human fibroblasts, which indicated that the incorporated rhEGF maintained its biological activity. In an in vitro scratch wound healing assay, the wound closure rate was faster in CCD986-sk human fibroblasts than in HaCaT human keratinocytes. Finally, the rhEGF-PUFs were evaluated as an in vivo treatment in a full-thickness wound model in diabetized Sprague-Dawley rats. The result indicated that compared with PUFs, rhEGF-PUFs accelerated wound healing by promoting wound contraction, re-epithelialization, collagen deposition and the formation of a skin appendage. These findings demonstrate that rhEGF-PUFs are a promising dressing for diabetic wounds. PMID:26340359

  16. TOPICAL APPLICATION OF LAMININ-322 TO DIABETIC MOUSE WOUNDS

    PubMed Central

    Sullivan, Stephen R.; Underwood, Robert A.; Sigle, Randall O.; Fukano, Yuko; Muffley, Lara A.; Usui, Marcia L.; Gibran, Nicole S.; Antezana, Marcos A.; Carter, William G.; Olerud, John E.

    2007-01-01

    Background Keratinocyte migration is essential for wound healing and diabetic wound keratinocytes migrate poorly. Keratinocyte migration and anchorage appears to be mediated by laminin-332 (LM-332). Impaired diabetic wound healing may be due to defective LM-332 mediated keratinocyte migration. Objective To evaluate LM-332 expression in diabetic (db/db) and control (db/-) mice and to test LM-332 wound healing effects when applied to mouse wounds. Methods LM-332 expression in mouse wounds was evaluated using immunohistochemistry. LM-332 wound healing effects were evaluated by directly applying soluble LM-332, a LM-332 biomaterial, or a control to mouse wounds. Percent wound closure and histology score, based on healing extent, were measured. Results Precursor LM-332 expression was markedly reduced in db/db when compared to db/- mice. In vitro, soluble LM-332 and LM-332 biomaterial demonstrated significant keratinocyte adhesion. In vivo, soluble LM-332 treated wounds had the highest histology score, but significant differences were not found between wound treatments (p>0.05). No differences in percentage wound closure between treatment and control wounds were found (p>0.05). Conclusion The db/db wounds express less precursor LM-332 when compared to db/-. However, LM-332 application did not improve db/db wound healing. LM-332 purified from keratinocytes was primarily physiologically cleaved LM-332 and may not regulate keratinocyte migration. Application of precursor LM-332 rather than cleaved LM-332 may be necessary to improve wound healing, but this isoform is not currently available in quantities sufficient for testing. PMID:17719208

  17. [General principles of wound management in emergency departments].

    PubMed

    Zacher, M T; Högele, A M; Hanschen, M; von Matthey, F; Beer, A-K; Gebhardt, F; Biberthaler, P; Kanz, K-G

    2016-04-01

    Wound management is one of the major tasks in emergency departments. The surrounding intact skin but not the wound itself should be disinfected before starting definitive wound treatment. Hair should first be removed by clipping to 1-2 mm above the skin with scissors or clippers as shaving the area with a razor damages the hair follicles and increases the risk of wound infections. Administration of local anesthetics should be performed directly through the exposed edges of the wound. After wound examination, irrigation is performed with Ringer's solution, normal saline or distilled water. The next step is débridement of contaminated and devitalized tissue. There are several wound closure techniques available, including adhesive tapes, staples, tissue adhesives and numerous forms of sutures. Management of specific wounds requires particular strategies. A bleeding control problem frequently occurs with scalp lacerations. Superficial scalp lacerations can be closed by alternative wound closure methods, for example by twisting and fixing hair and the use of tissue adhesives, i.e. hair apposition technique (HAT). For strongly bleeding lacerations of the scalp, the epicranial aponeurosis should be incorporated into the hemostasis. Aftercare varies depending on both the characteristics of the wound and those of the patient and includes adequate analgesia as well as minimizing the risk of infection. Sufficient wound aftercare starts with the treating physician informing the patient about the course of events, potential complications and providing relevant instructions. PMID:27059794

  18. Effect of dehydrozingerone, a half analog of curcumin on dexamethasone-delayed wound healing in albino rats.

    PubMed

    Rao, Mallikarjuna C; Sudheendra, Arun T; Nayak, Pawan G; Paul, Piya; Kutty, Gopalan N; Shenoy, Rekha R

    2011-09-01

    Oxidative stress is triggered by the wound which results in the production of reactive oxygen species (ROS), thereby delaying normal wound repair. Therefore, it is important to reduce the level of ROS to improve healing. A known antioxidant, dehydrozingerone (DHZ) was synthesized and selected for the study. The authors aimed to investigate the wound healing action of topical (100 mg/wound) and systemic (100 mg/kg, p. o.). DHZ on different wound models in normal and dexamethasone (DEX)-suppressed healing. Topical DHZ showed a significant (P < 0.05) rise in tensile strength when compared to control in normal healing. Significant (P < 0.05) wound closure was observed from 3 to 9 days in DHZ oral and gel treated groups. There was a significant (P < 0.05) rise in hydroxyproline content with the DHZ treated groups when compared to control. Systemic DHZ exhibited a significant (P < 0.05) increase in lysyl oxidase (LO) levels of 3.73 ± 0.15 nmol of H(2)O(2) when compared to control. In DEX-suppressed healing, showed good pro-healing activity with respect to the parameters mentioned above. DHZ treatment exhibited a parabolic dose response of ROS inhibition with a plateau effect at 75 μM. There was a steady and constant increase in the % NO inhibition with increasing doses of DHZ. Oral DHZ is effective in accelerating the healing process in both normal and dexamethasone-suppressed wounds. Our study suggests that DHZ (half analog of curcumin) supplementation reduces the steroid-induced delay in wound healing. PMID:21567208

  19. Hexokinase mediates stomatal closure.

    PubMed

    Kelly, Gilor; Moshelion, Menachem; David-Schwartz, Rakefet; Halperin, Ofer; Wallach, Rony; Attia, Ziv; Belausov, Eduard; Granot, David

    2013-09-01

    Stomata, composed of two guard cells, are the gates whose controlled movement allows the plant to balance the demand for CO2 for photosynthesis with the loss of water through transpiration. Increased guard-cell osmolarity leads to the opening of the stomata and decreased osmolarity causes the stomata to close. The role of sugars in the regulation of stomata is not yet clear. In this study, we examined the role of hexokinase (HXK), a sugar-phosphorylating enzyme involved in sugar-sensing, in guard cells and its effect on stomatal aperture. We show here that increased expression of HXK in guard cells accelerates stomatal closure. We further show that this closure is induced by sugar and is mediated by abscisic acid. These findings support the existence of a feedback-inhibition mechanism that is mediated by a product of photosynthesis, namely sucrose. When the rate of sucrose production exceeds the rate at which sucrose is loaded into the phloem, the surplus sucrose is carried toward the stomata by the transpiration stream and stimulates stomatal closure via HXK, thereby preventing the loss of precious water. PMID:23738737

  20. Bacterial Wound Culture

    MedlinePlus

    ... Home Visit Global Sites Search Help? Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  1. Evaluation of in-vivo wound healing activity of Hypericum patulum (Family: hypericaceae) leaf extract on different wound model in rats.

    PubMed

    Mukherjee, P K; Verpoorte, R; Suresh, B

    2000-06-01

    The methanol extract of Hypericum patulum Thumb. leaves were investigated for the evaluation of their wound healing potential on different experimental models of wounds in rats. The methanol extract of leaves (HPM), in the form of an ointment with two different concentrations (5% and 10% w/w ointment of leaf extract in simple ointment base) was evaluated for wound healing potential in an excision wound model and an incision wound model in rats. Both concentrations of the methanol extract ointment showed significant responses in both the wound types tested when compared with the control group. The effect produced by the extract ointment, in terms of wound contracting ability, wound closure time, regeneration of tissues at wound site, tensile strength of the wound and histopathological characteristics were comparable to those of a standard drug nitrofurazone ointment. PMID:10837993

  2. 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

  3. 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. PMID:25995620

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

    PubMed Central

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

    2016-01-01

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

  5. 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

  6. 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. PMID:26304727

  7. 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

  8. 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. PMID:25284020

  9. 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. PMID:25556053

  10. Propolis induces chondroitin/dermatan sulphate and hyaluronic Acid accumulation in the skin of burned wound.

    PubMed

    Olczyk, Pawel; Komosinska-Vassev, Katarzyna; Winsz-Szczotka, Katarzyna; Stojko, Jerzy; Klimek, Katarzyna; Kozma, Ewa M

    2013-01-01

    Changes in extracellular matrix glycosaminoglycans during the wound repair allowed us to apply the burn model in which therapeutic efficacy of propolis and silver sulfadiazine was compared. Burns were inflicted on four pigs. Glycosaminoglycans isolated from healthy and burned skin were quantified using a hexuronic acid assay, electrophoretic fractionation, and densitometric analyses. Using the reverse-phase HPLC the profile of sulfated disaccharides released by chondroitinase ABC from chondroitin/dermatan sulfates was estimated. Chondroitin/dermatan sulfates and hyaluronic acid were found in all samples. Propolis stimulated significant changes in the content of particular glycosaminoglycan types during burn healing. Glycosaminoglycans alterations after silver sulfadiazine application were less expressed. Propolis maintained high contribution of 4-O-sulfated disaccharides to chondroitin/dermatan sulfates structure and low level of 6-O-sulfated ones throughout the observed period of healing. Propolis led to preservation of significant contribution of disulfated disaccharides especially 2,4-O-disulfated ones to chondroitin sulfates/dermatan sulfates structure throughout the observed period of healing. Our findings demonstrate that propolis accelerates the burned tissue repair by stimulation of the wound bed glycosaminoglycan accumulation needed for granulation, tissue growth, and wound closure. Moreover, propolis accelerates chondroitin/dermatan sulfates structure modification responsible for binding growth factors playing the crucial role in the tissue repair. PMID:23533471

  11. Propolis Induces Chondroitin/Dermatan Sulphate and Hyaluronic Acid Accumulation in the Skin of Burned Wound

    PubMed Central

    Olczyk, Pawel; Komosinska-Vassev, Katarzyna; Winsz-Szczotka, Katarzyna; Stojko, Jerzy; Klimek, Katarzyna; Kozma, Ewa M.

    2013-01-01

    Changes in extracellular matrix glycosaminoglycans during the wound repair allowed us to apply the burn model in which therapeutic efficacy of propolis and silver sulfadiazine was compared. Burns were inflicted on four pigs. Glycosaminoglycans isolated from healthy and burned skin were quantified using a hexuronic acid assay, electrophoretic fractionation, and densitometric analyses. Using the reverse-phase HPLC the profile of sulfated disaccharides released by chondroitinase ABC from chondroitin/dermatan sulfates was estimated. Chondroitin/dermatan sulfates and hyaluronic acid were found in all samples. Propolis stimulated significant changes in the content of particular glycosaminoglycan types during burn healing. Glycosaminoglycans alterations after silver sulfadiazine application were less expressed. Propolis maintained high contribution of 4-O-sulfated disaccharides to chondroitin/dermatan sulfates structure and low level of 6-O-sulfated ones throughout the observed period of healing. Propolis led to preservation of significant contribution of disulfated disaccharides especially 2,4-O-disulfated ones to chondroitin sulfates/dermatan sulfates structure throughout the observed period of healing. Our findings demonstrate that propolis accelerates the burned tissue repair by stimulation of the wound bed glycosaminoglycan accumulation needed for granulation, tissue growth, and wound closure. Moreover, propolis accelerates chondroitin/dermatan sulfates structure modification responsible for binding growth factors playing the crucial role in the tissue repair. PMID:23533471

  12. Managing surgical wound care: review of Leukomed Control dressings.

    PubMed

    Milne, Jeanette

    2016-03-01

    Optimal management of surgical wounds is an important part of postoperative recovery. The aim of postoperative wound care is to facilitate rapid wound closure, while preventing complications and promoting minimal disturbance, to achieve the best functional and aesthetic results. Health professionals should seek to optimise the process of acute wound healing, observe progress, and prevent wound complications. Dressings that permit extended wear time, and are transparent and so allow early recognition without the need for unnecessary changes, have the potential to minimise the effect on patients and the wider health economy. This article reviews recommendations for surgical wound care, and introduces the recently launched Leukomed Control dressing that is entirely transparent and allows greater flexibility, breathability, and visualisation of the wound. PMID:27019183

  13. 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

  14. Angiotensin II inhibitor facilitates epidermal wound regeneration in diabetic mice

    PubMed Central

    Kamber, Maria; Papalazarou, Vasileios; Rouni, Georgia; Papageorgopoulou, Evagelia; Papalois, Apostolos; Kostourou, Vassiliki

    2015-01-01

    Tissue regeneration and wound healing are severely impaired in diabetes and are associated with poor circulation and dysfunctional blood vessels. Angiotensin II inhibitors are anti-hypertensive drugs used in clinical practice to regulate blood pressure and could affect tissue remodeling. We hypothesize that blocking angiotensin II, using Losartan, could facilitate tissue regeneration in diabetic mice. To this end, we established an experimental model of wound healing in streptozotocin-induced diabetic mice. Our data demonstrated that Losartan accelerates wound repair and normalizes wound stromal responses, having a beneficial role in wounds of diabetic individuals. Our findings highlight a potential therapeutic use of Losartan in improving wound repair in diabetic conditions. PMID:26106332

  15. 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

  16. 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

    2016-01-01

    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 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

  18. 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. PMID:24132703

  19. 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.

  20. Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

    PubMed Central

    Bhattacharya, Sushant; Aggarwal, Rangoli; Singh, Vijay Pal; Ramachandran, Srinivasan; Datta, Malabika

    2015-01-01

    Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing. PMID:26602065

  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. The emergency care of traumatic wounds: current recommendations.

    PubMed

    Gfeller, R W; Crowe, D T

    1994-11-01

    Emergency management of wounds involves examination and protection of the wound with a wet dressing (when possible) to prevent further contamination and desiccation. Analgesia (or preferably anesthesia) is provided and the patient and the wound are prepared for surgery. Copious amounts of lavage solution are used under moderate pressure. Proper and thorough debridement under irrigation is tedious and time consuming, but is the most important factor that influences subsequent wound healing. Incomplete removal of devitalized or contaminated tissue and debris are a common cause of wound infection, breakdown, and delayed healing. Wound closure is only accomplished when the veterinarian is certain that all devitalized and contaminated tissue has been removed and there is adequate skin. Covering the wound to heal by second intention or delayed closure should be considered more often in veterinary medicine. All too often, the wound is closed prematurely, resulting in dehiscence and infection a few days later. This provides a source of complications to the pet, as well as a source of dissatisfaction for the client. If, after initial debridement and irrigation, there is any doubt about the advisability of surgical closure, the clinician should cover the wound with a proper dressing and continue daily (or more often) dressing changes with local irrigation and debridement as required. Drainage of wound fluid is critical to healing in contaminated wounds. Wound fluids interfere with healing and increase the likelihood of infection. Passive drains (Penrose) are frequently used, often incorrectly. The exposed end of passive drains should be covered with a sterile, absorbent dressing. Active drainage is more efficient than passive drainage and can be accomplished with minimal additional skill and material. Improper use of drains can cause more problems than no drainage at all. Patients suffering painful traumatic (or surgical) wounds should receive analgesic medications. The

  3. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair.

    PubMed Central

    Pierce, G. F.; Tarpley, J. E.; Yanagihara, D.; Mustoe, T. A.; Fox, G. M.; Thomason, A.

    1992-01-01

    Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF) can accelerate healing of soft tissues. However, little information is available characterizing the components of wound matrix induced by these growth factors and the molecular mechanisms underlying accelerated repair and wound maturation. In this study, the composition, quantity, and rate of extracellular matrix deposition within growth factor-treated lapine ear excisional wounds were analyzed at different stages of healing using specific histochemical and immunohistochemical stains, coupled with image analysis techniques. Single application of optimal concentrations of each growth factor accelerated normal healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly greater levels of collagen later in the repair process, compared with untreated wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and maturation, without increased GAG deposition. In contrast, rbFGF treatment induced a predominantly angiogenic response in wounds, with a marked increase in endothelia and neovessels (P less than 0.0001), and increased wound collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve into collagen-containing scars and continued to accumulate only provisional matrix well past wound closure. These results provide new evidence that growth factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic response which may lead to a marked delay in wound maturation, and the possible loss of the normal signal(s) required to stop repair. These results suggest that specific growth factors may selectively regulate

  4. Enhancement of wound healing by curcumin in animals.

    PubMed

    Sidhu, G S; Singh, A K; Thaloor, D; Banaudha, K K; Patnaik, G K; Srimal, R C; Maheshwari, R K

    1998-01-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. In this study, we evaluated the in vivo effects of curcumin (difeurloylmethane), a natural product obtained from the rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We observed faster wound closure of punch wounds in curcumin-treated animals in comparison with untreated controls. Biopsies of the wound showed reepithelialization of the epidermis and increased migration of various cells including myofibroblasts, fibroblasts, and macrophages in the wound bed. Multiple areas within the dermis showed extensive neovascularization, and Masson's Trichrome staining showed greater collagen deposition in curcumin-treated wounds. Immunohistochemical localization of transforming growth factor-beta1 showed an increase in curcumin-treated wounds as compared with untreated wounds. In situ hybridization and polymerase chain reaction analysis also showed an increase in the mRNA transcripts of transforming growth factor-beta1 and fibronectin in curcumin-treated wounds. Because transforming growth factor-beta1 is known to enhance wound healing, it may be possible that transforming growth factor-beta1 plays an important role in the enhancement of wound healing by curcumin. PMID:9776860

  5. Sutures versus staples for skin closure in orthopaedic surgery: meta-analysis

    PubMed Central

    Sexton, Debbie; Mann, Charles; Donell, Simon

    2010-01-01

    Objective To compare the clinical outcomes of staples versus sutures in wound closure after orthopaedic surgery. Design Meta-analysis. Data sources Medline, CINAHL, AMED, Embase, Scopus, and the Cochrane Library databases were searched, in addition to the grey literature, in all languages from 1950 to September 2009. Additional studies were identified from cited references. Selection criteria Two authors independently assessed papers for eligibility. Included studies were randomised and non-randomised controlled trials that compared the use of staples with suture material for wound closure after orthopaedic surgery procedures. All studies were included, and publications were not excluded because of poor methodological quality. Review methods Two authors independently reviewed studies for methodological quality and extracted data from each paper. Final data for analysis were collated through consensus. The primary outcome measure was the assessment of superficial wound infection after wound closure with staples compared with sutures. Relative risk and mean difference with 95% confidence intervals were calculated and pooled with a random effects model. Heterogeneity was assessed with I2 and χ2 statistical test. Results Six papers, which included 683 wounds, were identified; 332 patients underwent suture closure and 351 staple closure. The risk of developing a superficial wound infection after orthopaedic procedures was over three times greater after staple closure than suture closure (relative risk 3.83, 95% confidence interval 1.38 to 10.68; P=0.01). On subgroup analysis of hip surgery alone, the risk of developing a wound infection was four times greater after staple closure than suture closure (4.79, 1.24 to 18.47; P=0.02). There was no significant difference between sutures and staples in the development of inflammation, discharge, dehiscence, necrosis, and allergic reaction. The included studies had several major methodological limitations, including the

  6. [Modern wound dressings].

    PubMed

    Triller, Ciril; Huljev, Dubravko; Planinsek Rucigaj, Tanja

    2013-10-01

    Chronic wounds are, due to the slow healing, a major clinical problem. In addition to classic materials, a great number of supportive wound dressings for chronic wound treatment, developed on the basis of new knowledge about the pathophysiological events in non-healing wounds, are available on the market. Today we know that modern wound dressings provide the best local environment for optimal healing (moisture, warmth, appropriate pH). Wound dressings control the amount of exudate from the wound and bacterial load, thus protecting local skin from the wound exudate and the wound from secondary infections from the environment. Using supportive wound dressings makes sense only when the wound has been properly assessed, the etiologic factors have been clarified and the obstacles making the wound chronic identified. The choice of dressing is correlated with the characteristics of the wound, the knowledge and experience of the medical staff, and the patient's needs. We believe that the main advantage of modern wound dressing versus conventional dressing is more effective wound cleaning, simple dressing application, painless bandaging owing to reduced adhesion to the wound, and increased absorption of the wound exudate. Faster wound granulation shortens the length of patient hospitalization, and eventually facilitates the work of medical staff. The overall cost of treatment is a minor issue due to faster wound healing despite the fact that modern supportive wound dressings are more expensive than conventional bandaging. The article describes different types of modern supportive wound dressings, as well as their characteristics and indications for use. PMID:24371980

  7. 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. PMID:27215871

  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. Difficult wounds: an update.

    PubMed

    Edlich, Richard F; Winters, Kathryne L; Britt, L D; Long, William B; Gubler, K Dean; Drake, David B

    2005-01-01

    The purpose of this collective review is to describe revolutionary advances in the treatment of Gardner's syndrome (GS), pseudofolliculitis barbae, nasal septal perforation, factitious wounds, and hidradenitis suppurativa (HS). Gardner's syndrome or familial polyposis has various manifestations that appear to be controlled by a single genetic locus. Apart from the large bowel adenomas, which are always present, a common extracolonic symptom of Gardner's syndrome is the occurrence of epidermal cysts. These cysts can be seen before the intestinal polyps are evident. Because epidermal cysts in patients with Gardner's syndrome are always benign, we excise these cysts using incisions that are commonly used for rhytidectomy. Pseudofolliculitis barbae, a pseudofolliculitis caused by ingrown hairs, effects 85% of blacks who shave their beards. When this disease is allowed to progress to keloid formation, we use a surgical approach that includes excision of the keloidal scar, meticulous debridement of all residual ingrown hairs in the underlying wound, and coverage of the defect with a split-thickness skin graft. More recently, laser therapy has revolutionized the treatment of pseudofolliculitis barbae and has enabled a cure for the first time for those plagued with this disorder and for whom a beardless face is acceptable. Nasal septal perforation is a well recognized complication of septal surgery. Other iatrogenic causes of perforation include cryosurgery, electrocoagulation for epitaxis, nasotracheal intubation, or nose packing. In recent years drugs such as cocaine account for an increasing number of perforations. It has only been with the use of an external approach for the repair of the nasal septal defect that surgical closure has become easier and more reliable. The external approach allows for greater surgical closure and enables the surgeon to use both hands with the aid of binocular vision to mobilize and suture local mucosal advancement flaps and the

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

    PubMed

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

    2016-08-01

    Various types of wound dressings have been designed for different purposes and functions. Controlling bacterial burden in a wound during the early phase is important for successful wound repair. Once bacterial burden is under control, the active promotion of wound healing is another important factor for efficient wound healing. This study investigated the potential of three silver-containing dressings, namely KoCarbonAg(®) , Aquacel(®) Ag and Acticoat 7, in reducing bacterial survival and promoting wound healing. The ability of these dressings to block the entry of bacteria from external environment and retain intrinsic bacteria was studied in vitro. In addition, the study used a rat model to compare the healing efficiencies of the three dressings and investigate the quantity of collagen synthesis in vivo. In vitro results indicated that the silver-containing dressings prevented bacterial growth in wounds by blocking the entry of external bacteria and by retaining the bacteria in the dressing. In vivo study indicated that reduction in bacterial burden accelerated wound healing. Wounds treated by the silver-containing dressings showed better healing than those treated with gauze. Moreover, KoCarbonAg(®) further accelerated wound healing by promoting collagen synthesis and arrangement. PMID:26043261

  11. [Fascial healing and wound failure].

    PubMed

    Fackeldey, V; Höer, J; Klinge, U

    2004-05-01

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

  12. No Association between Glycemia and Wound Healing in an Experimental db/db Mouse Model

    PubMed Central

    2013-01-01

    Impaired wound healing is a frequent problem in diabetes. Hyperglycemia may be an operative mechanism, but a link between glycemic control and wound healing has never been established. Wounds in db/db mice have been extensively studied. This study was undertaken to see if plasma glucose was a predictor of wound healing. An excisional wound was made (149 db/db mice). Wound closure was studied versus metabolic variables. The animals were 11.8 ± 0.2 weeks (mean ± standard error of the mean), obese (38.1 ± 0.5 g), and hyperglycemic (fasting plasma glucose 21.0 ± 0.7 mmol/L). Wound closure at day 13 was 30.1 ± 1.6%. In linear mixed model analyses neither fasting plasma glucose nor its change from start to end of experiment was a significant predictor of wound closure (β = 0.15, P = 0.07, 95% CI: −0.01 to 0.31 and β = 0.06, P = 0.5, 95% CI: −0.11 to 0.23, resp.). However, increase in body weight significantly and independently predicted wound closure (for weight change, β = 0.22, P = 0.008, 95% CI: 0.06 to 0.38). This study strongly suggests that wound healing in db/db mice is independent of prevailing glycemia but dependent on anabolic changes such as weight gain over time. PMID:24251043

  13. 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

  14. [Overview of primary sternal closure techniques].

    PubMed

    Nešpor, D; Fila, P; Černý, J; Němec, P

    2015-02-01

    The aim of the overview study is to describe the currently used methods of primary median sternotomy closure in adult cardiac surgery. In the review of published literature, we draw on the data and focus on the methodology, indications, advantages, limitations, biomechanical and clinical results of the different methods in relation to the incidence of deep sternal wound complications after median sternotomy in adult cardiac surgery.Key words: sternum sternotomy adult cardiac surgery surgical procedures. PMID:25659253

  15. Boundary crossing in epithelial wound healing

    PubMed Central

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

    2010-01-01

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

  16. Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.

    PubMed

    Simkin, Jennifer; Sammarco, Mimi C; Dawson, Lindsay A; Tucker, Catherine; Taylor, Louis J; Van Meter, Keith; Muneoka, Ken

    2015-06-01

    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

  17. 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

  18. A retrospective review of leg wound complications after coronary artery bypass surgery.

    PubMed

    East, Susan A; Lorenz, Rebecca A; Armbrecht, Eric S

    2013-10-01

    Little research or attention has been paid to finding out whether wound closure with sutures or staples attains the best outcomes after saphenous vein harvest for coronary artery bypass grafting. We undertook a quality improvement project to compare the prevalence of leg wound complications (eg, infection, seroma, hematoma, dehiscence) between two types of skin closure (ie, staples, subcuticular sutures) after conventional open surgery with bridging between incisions and vein harvesting during coronary revascularization to determine the need for practice changes. We found no significant differences between patients with wound complications and those without. However, in this project, the risk for infections was greater for patients with diabetes whose wounds were closed by using subcuticular sutures. These findings have led to practice changes for reducing leg wound complications within our institution: clinicians now assess patients for increased risk of leg wound complications preoperatively and opt to close wounds with staples for patients who have diabetes. PMID:24075335

  19. Fibromodulin-deficiency alters temporospatial expression patterns of transforming growth factor-β ligands and receptors during adult mouse skin wound healing.

    PubMed

    Zheng, Zhong; Lee, Kevin S; Zhang, Xinli; Nguyen, Calvin; Hsu, Chingyun; Wang, Joyce Z; Rackohn, Todd Matthew; Enjamuri, Dwarak Reddy; Murphy, Maxwell; Ting, Kang; Soo, Chia

    2014-01-01

    Fibromodulin (FMOD) is a small leucine-rich proteoglycan required for scarless fetal cutaneous wound repair. Interestingly, increased FMOD levels have been correlated with decreased transforming growth factor (TGF)-β1 expression in multiple fetal and adult rodent models. Our previous studies demonstrated that FMOD-deficiency in adult animals results in delayed wound closure and increased scar size accompanied by loose package collagen fiber networks with increased fibril diameter. In addition, we found that FMOD modulates in vitro expression and activities of TGF-β ligands in an isoform-specific manner. In this study, temporospatial expression profiles of TGF-β ligands and receptors in FMOD-null and wild-type (WT) mice were compared by immunohistochemical staining and quantitative reverse transcriptase-polymerase chain reaction using a full-thickness, primary intention wound closure model. During the inflammatory stage, elevated inflammatory infiltration accompanied by increased type I TGF-β receptor levels in individual inflammatory cells was observed in FMOD-null wounds. This increased inflammation was correlated with accelerated epithelial migration during the proliferative stage. On the other hand, significantly more robust expression of TGF-β3 and TGF-β receptors in FMOD-null wounds during the proliferative stage was associated with delayed dermal cell migration and proliferation, which led to postponed granulation tissue formation and wound closure and increased scar size. Compared with WT controls, expression of TGF-β ligands and receptors by FMOD-null dermal cells was markedly reduced during the remodeling stage, which may have contributed to the declined collagen synthesis capability and unordinary collagen architecture. Taken together, this study demonstrates that a single missing gene, FMOD, leads to conspicuous alternations in TGF-β ligand and receptor expression at all stages of wound repair in various cell types. Therefore, FMOD critically

  20. Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and Myofibroblast Differentiation

    PubMed Central

    Lévigne, Dominik; Modarressi, Ali; Atashi, Fatemeh; Villard, Frederic; Hinz, Boris

    2015-01-01

    Background: Hyperglycemia is known to adversely affect the outcome of ischemic insults, but its interaction with ischemia has not been investigated in wound repair yet. In this study, we develop a new animal model allowing to investigate the interaction between hyperglycemia and ischemia during the wound repair process. We focus on myofibroblast differentiation, a key element of wound repair. Methods: Ischemia was inflicted in Wistar rats by resection of the femoral to popliteal arteries on the left side, whereas arteries were dissected without resection on the right side. Full-thickness skin wounds (1 cm2) were created on both feet. Hyperglycemia was induced by injection of streptozotocin. Normoglycemic animals served as control (n = 23/group). Blood flow, wound closure, and myofibroblast expression were measured. Results: Wound closure was significantly delayed in ischemic compared with nonischemic wounds in all rats. This delay was almost 5-fold exacerbated in hyperglycemic rats compared with normoglycemic rats, while hyperglycemia alone showed only a slight effect on wound repair. Delayed wound repair was associated with impaired wound contraction and myofibroblast differentiation. Conclusions: Our model allows to specifically quantify the effect of hyperglycemia and ischemia alone or in combination on wound repair. We show that hyperglycemia amplifies the inhibitory effect of ischemia on wound repair and myofibroblast expression. Our data reveal for the first time the synergic aspect of this interaction and therefore stress the importance of a strict glycemic control in the management of ischemic wounds. PMID:26301160

  1. Practices in Wound Healing Studies of Plants

    PubMed Central

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

    2011-01-01

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

  2. Molecular mechanisms of enhanced wound healing by copper oxide-impregnated dressings.

    PubMed

    Borkow, Gadi; Gabbay, Jeffrey; Dardik, Rima; Eidelman, Arthur I; Lavie, Yossi; Grunfeld, Yona; Ikher, Sergey; Huszar, Monica; Zatcoff, Richard C; Marikovsky, Moshe

    2010-01-01

    ABSTRACT Copper plays a key role in angiogenesis and in the synthesis and stabilization of extracellular matrix skin proteins, which are critical processes of skin formation. We hypothesized that introducing copper into wound dressings would enhance wound repair. Application of wound dressings containing copper oxide to wounds inflicted in genetically engineered diabetic mice (C57BL/KsOlaHsd-Lepr(db)) resulted in increased gene and in situ up-regulation of proangiogenic factors (e.g., placental growth factor, hypoxia-inducible factor-1 alpha, and vascular endothelial growth factor), increased blood vessel formation (p<0.05), and enhanced wound closure (p<0.01) as compared with control dressings (without copper) or commercial wound dressings containing silver. This study proves the capacity of copper oxide-containing wound dressings to enhance wound healing and sheds light onto the molecular mechanisms by which copper oxide-impregnated dressings stimulate wound healing. PMID:20409151

  3. Nitric Oxide Chemical Donor Affects the Early Phases of In Vitro Wound Healing Process.

    PubMed

    La Torre, Cristina; Cinque, Benedetta; Lombardi, Francesca; Miconi, Gianfranca; Palumbo, Paola; Evtoski, Zoran; Placidi, Giuseppe; Fanini, Donatella; Cimini, Anna Maria; Benedetti, Elisabetta; Giuliani, Maurizio; Cifone, Maria Grazia

    2016-10-01

    An artificial wound in a confluent monolayer of human keratinocyte HaCaT cells or mouse embryo fibroblast Swiss NIH 3T3 cells was used to analyze the effects of the nitric oxide (NO) chemical donor, S-nitroso-N-acetylpenicillamine (SNAP). SNAP exposure promoted an enhanced rate of wound closure and accelerated motility of both keratinocytes and fibroblasts compared to control cells. The wounded monolayer cultures of HaCaT and NIH 3T3 cells, treated with or without SNAP, were monitored under a phase contrast microscope. Structural and ultrastructural modifications were analyzed by scanning electron microscopy (SEM). The images were captured by a digital camera at different time points (0-28 h) and the wound area was analyzed through software included in Matlab®. As early as 15 min, SNAP induced significant cytoskeletal remodeling, as shown by immunostaining (phalloidin-labelling), which in turn was associated with increased filopodium number and length rise. NO donor treatment also induced overexpression of Ki-67 protein, a typical marker of cell proliferation, as shown by immunostaining. Both SNAP-induced migration and proliferation were antagonized by the NO-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[-4,3-a]quinoxalin-1-one (ODQ), which suggests activation of the NO/cGMP signalling cascade in the observed SNAP-induced effects in the early stages of the healing process. Moreover, we provide evidence that PPAR-β antagonist (GSK0660) may interfere with NO-mediated wound healing process. J. Cell. Physiol. 231: 2185-2195, 2016. © 2016 Wiley Periodicals, Inc. PMID:26841260

  4. Effects of epidermal growth factor-loaded mucoadhesive films on wounded oral tissue rafts.

    PubMed

    Ramineni, Sandeep K; Fowler, Craig B; Fisher, Paul D; Cunningham, Larry L; Puleo, David A

    2015-02-01

    Current treatments for traumatic oral mucosal wounds include the gold standard of autologous tissue and alternative tissue-engineered grafts. While use of autografts has disadvantages of minimal availability of oral keratinized tissue, second surgery, and donor site discomfort, tissue-engineered grafts are limited by their unavailability as off-the-shelf products owing to their fabrication time of 4-8 weeks. Hence, the current work aimed to develop a potentially cost-effective, readily available device capable of enhancing native mucosal regeneration. Considering the key role of epidermal growth factor (EGF) in promoting mucosal wound regeneration and the advantages of mucoadhesive delivery systems, mucoadhesive films composed of polyvinylpyrrolidone and carboxymethylcellulose were developed to provide sustained release of EGF for a minimum of 6 h. Bioactivity of released EGF supernatants was then confirmed by its ability to promote proliferation of BALB/3T3 fibroblasts. Efficacy of the developed system was then investigated in vitro using buccal tissues (ORL 300-FT) as a potential replacement for small animal studies. Although the mucoadhesive films achieved their desired role of delivering bioactive EGF in a sustained manner, treatment with EGF, irrespective of its release from the films or solubilized in medium, caused a hyperparakeratotic response from in vitro tissues with distinguishable histological features including thickening of the spinous layer, intra- and intercellular edema, and pyknotic nuclei. These significant morphological changes were associated with no improvements in wound closure. These observations raise questions about the potential of using in vitro tissues as a wound healing model and substitute for small animal studies. The mucoadhesive delivery system developed, however, with its potential for sustained release of bioactive growth factors and small molecules, may be loaded with other desired compounds, with or without EGF, to accelerate

  5. Effects of Epidermal Growth Factor-Loaded Mucoadhesive Films on Wounded Oral Tissue Rafts

    PubMed Central

    Ramineni, Sandeep K.; Fowler, Craig B.; Fisher, Paul D.; Cunningham, Larry L.; Puleo, David A.

    2015-01-01

    Current treatments for traumatic oral mucosal wounds include the gold standard of autologous tissue and alternative tissue engineered grafts. While use of autografts has disadvantages of minimal availability of oral keratinized tissue, second surgery, and donor site discomfort, tissue engineered grafts are limited by their unavailability as off-the-shelf products owing to their fabrication time of 4–8 weeks. Hence, the current work aimed to develop a potentially cost-effective, readily available device capable of enhancing native mucosal regeneration. Considering the key role of epidermal growth factor (EGF) in promoting mucosal wound regeneration and the advantages of mucoadhesive delivery systems, mucoadhesive films composed of polyvinylpyrrolidone and carboxymethylcellulose were developed to provide sustained release of EGF for minimum of 6 hours. Bioactivity of released EGF supernatants was then confirmed by its ability to promote proliferation of BALB/3T3 fibroblasts. Efficacy of the developed system was then investigated in vitro using buccal tissues (ORL 300-FT) as a potential replacement for small animal studies. Although the mucoadhesive films achieved their desired role of delivering bioactive EGF in a sustained manner, treatment with EGF, irrespective of its release from the films or solubilized in medium, caused a hyperparakeratotic response from in vitro tissues with distinguishable histological features including thickening of the spinous layer, intra- and intercellular edema, and pyknotic nuclei. These significant morphological changes were associated with no improvements in wound closure. These observations raise questions about the potential of using in vitro tissues as a wound healing model and substitute for small animal studies. The mucoadhesive delivery system developed, however, with its potential for sustained release of bioactive growth factors and small molecules, may be loaded with other desired compounds, with or without EGF, to

  6. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats.

    PubMed

    Mehanna, Radwa A; Nabil, Iman; Attia, Noha; Bary, Amany A; Razek, Khalid A; Ahmed, Tamer A E; Elsayed, Fatma

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although--later--none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM-via fibrin vehicle--could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740

  7. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats

    PubMed Central

    Mehanna, Radwa A.; Nabil, Iman; Attia, Noha; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Elsayed, Fatma

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740

  8. Evaluation of a highly skin permeable low-molecular-weight protamine conjugated epidermal growth factor for novel burn wound healing therapy.

    PubMed

    Lee, Ji Hae; Bae, Il-Hong; Choi, Jin Kyu; Park, Jin Woo

    2013-11-01

    We evaluated the laser induced burn wound healing efficacy of a recombinant low-molecular-weight protamine conjugated epidermal growth factor (rLMWP-EGF). rLMWP-EGF was prepared by genetically combining LMWP with the N-terminal sequence of EGF; we obtained a homogeneous modified EGF without reduced biological activity. Because of the protein transduction domain of LMWP, rLMWP-EGF showed enhanced drug penetration across artificial skin constructs and excised mouse skin layers versus EGF and showed significantly improved burn wound healing efficacy, with accelerated wound closure and minimized eschar and scar formation, compared with EGF or no treatment. Histological examination also revealed that rLMWP-EGF permeated through the intact skin around the wound and facilitated residual epithelial cell proliferation in an integrated manner to reform an intact epidermis. Radiofrequency microwound formation was effective for reducing large hypertrophic scars formed after severe laser burning by collagen remodeling but rLMWP-EGF did not show a meaningful synergistic effect in burn scar reduction. However, rLMWP-EGF was helpful for forming skin with a more normal appearance and texture. Thus, rLMWP-EGF demonstrated therapeutic potential as a novel topical burn wound healing drug with no obvious toxic effect. PMID:24018779

  9. Epidermal Wound Healing in the Nematode Caenorhabditis elegans

    PubMed Central

    Chisholm, Andrew D.

    2015-01-01

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

  10. Acute and chronic wound fluids influence keratinocyte function differently.

    PubMed

    Thamm, Oliver C; Koenen, Paola; Bader, Nicola; Schneider, Alina; Wutzler, Sebastian; Neugebauer, Edmund A M; Spanholtz, Timo A

    2015-04-01

    Wound healing requires a proper functioning of keratinocytes that migrate, proliferate and lead to a competent wound closure. Impaired wound healing might be due to a disturbed keratinocyte function caused by the wound environment. Basically, chronic wound fluid (CWF) differs from acute wound fluid (AWF). The aim of this study was to analyse the effects of AWF and CWF on keratinocyte function. We therefore investigated keratinocyte migration and proliferation under the influence of AWF and CWF using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test and scratch assay. We further measured the gene expression by qRT-PCR regarding growth factors and matrixmetalloproteinases (MMPs) involved in regeneration processes. AWF had a positive impact on keratinocyte proliferation over time, whereas CWF had an anti-proliferative effect. Keratinocyte migration was significantly impaired by CWF in contrast to an undisturbed wound closure under the influence of AWF. MMP-9 expression was strongly upregulated by CWF compared with AWF. Keratinocyte function was significantly impaired by CWF. An excessive induction of MMP-9 by CWF might lead to a permanent degradation of extracellular matrix and thereby prevent wounds from healing. PMID:23517467

  11. [Chronic wounds: differential diagnosis].

    PubMed

    Situm, Mirna; Kolić, Maja

    2013-10-01

    Wound is a disruption of anatomic and physiologic continuity of the skin. According to the healing process, wounds are classified as acute and chronic wounds. A wound is considered chronic if standard medical procedures do not lead to the expected healing, or if the wound does not heal within six weeks. Chronic wounds are classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic wounds. Diabetic foot and decubitus ulcers stand out as a specific entity among typical wounds. About 80 percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder are mostly neuropathic ulcers. About 95 percent of chronic wounds manifest as one of the above-mentioned entities. Other forms of chronic wounds are atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome). Although atypical wounds are a rare cause of chronic wounds, it should always be taken in consideration during diagnostic procedure. PMID:24371971

  12. Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.

    PubMed

    Zhu, Yunxiao; Hoshi, Ryan; Chen, Siyu; Yi, Ji; Duan, Chongwen; Galiano, Robert D; Zhang, Hao F; Ameer, Guillermo A

    2016-09-28

    Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Altered cell migration due to microcirculatory deficiencies as well as excessive and prolonged reactive oxygen species production are implicated in the delayed healing of DFUs. The goal of this research was to assess whether sustained release of SDF-1, a chemokine that promotes endothelial progenitor cell homing and angiogenesis, from a citrate-based antioxidant thermoresponsive polymer would significantly improve impaired dermal wound healing in diabetes. Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesized via sequential polycondensation and free radical polymerization reactions. SDF-1 was entrapped via gelation of the PPCN+SDF-1 solution above its lower critical solution temperature (LCST) and its release and bioactivity was measured. The effect of sustained release of SDF-1 from PPCN (PPCN+SDF-1) versus a bolus application of SDF-1 in phosphate buffered saline (PBS) on wound healing was evaluated in a diabetic murine splinted excisional dermal wound model using gross observation, histology, immunohistochemistry, and optical coherence tomography microangiography. Increasing PPCN concentration decreased SDF-1 release rate. The time to 50% wound closure was 11days, 16days, 14days, and 17days for wounds treated with PPCN+SDF-1, SDF-1 only, PPCN only, and PBS, respectively. Wounds treated with PPCN+SDF-1 had the shortest time for complete healing (24days) and exhibited accelerated granulation tissue production, epithelial maturation, and the highest density of perfused blood vessels. In conclusion, sustained release of SDF-1 from PPCN is a promising and easy to use therapeutic strategy to improve the treatment of chronic non-healing DFUs. PMID:27473766

  13. Post-surgical wound management of pilonidal cysts with a haemoglobin spray: a case series.

    PubMed

    Mustafi, N; Engels, P

    2016-04-01

    Painful acute cysts in the natal cleft or lower back, known as pilonidal sinus disease, are a severe burden to many younger patients. Although surgical intervention is the preferred first line treatment, postsurgical wound healing disturbances are frequently reported due to infection or other complications. Different treatment options of pilonidal cysts have been discussed in the literature, however, no standardised guideline for the postsurgical wound treatment is available. After surgery, a common recommended treatment to patients is rinsing the wound with clean water and dressing with a sterile compress. We present a case series of seven patients with wounds healing by secondary intention after surgical intervention of a pilonidal cyst. The average age of the patients was 40 years old. Of the seven patients, three had developed a wound healing disturbance, one wound had started to develop a fibrin coating and three were in a good condition. The applied wound care regimens comprised appropriate mechanical or autolytic debridement, rinsing with an antimicrobial solution, haemoglobin application, and primary and secondary dressings. In all seven cases a complete wound closure was achieved within an average of 76 days with six out of seven wounds achieving wound closure within 23-98 days. Aesthetic appearance was deemed excellent in five out of seven cases excellent and acceptable in one. Treatment of one case with a sustained healing disturbance did result in wound closure but with a poor aesthetic outcome and an extensive cicatrisation of the new tissue. Based on these results we recommend that to avoid healing disturbances of wounds healing by secondary intention after surgical pilonidal cyst intervention, an adequate wound care regime comprising appropriate wound debridement, rinsing, topically applied haemoglobin and adequate wound dressing is recommendable as early as possible after surgery. PMID:27064368

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Tolg, Cornelia; Telmer, Patrick; Turley, Eva

    2014-01-01

    The extracellular matrix polysaccharide hyaluronan (HA) plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa) of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous. PMID:24551108

  16. Novel silk fibroin/elastin wound dressings.

    PubMed

    Vasconcelos, Andreia; Gomes, Andreia C; Cavaco-Paulo, Artur

    2012-08-01

    Silk fibroin (SF) and elastin (EL) scaffolds were successfully produced for the first time for the treatment of burn wounds. The self-assembly properties of SF, together with the excellent chemical and mechanical stability and biocompatibility, were combined with elastin protein to produce scaffolds with the ability to mimic the extracellular matrix (ECM). Porous scaffolds were obtained by lyophilization and were further crosslinked with genipin (GE). Genipin crosslinking induces the conformational transition from random coil to β-sheet of SF chains, yielding scaffolds with smaller pore size and reduced swelling ratios, degradation and release rates. All results indicated that the composition of the scaffolds had a significant effect on their physical properties, and that can easily be tuned to obtain scaffolds suitable for biological applications. Wound healing was assessed through the use of human full-thickness skin equivalents (EpidermFT). Standardized burn wounds were induced by a cautery and the best re-epithelialization and the fastest wound closure was obtained in wounds treated with 50SF scaffolds; these contain the highest amount of elastin after 6 days of healing in comparison with other dressings and controls. The cytocompatibility demonstrated with human skin fibroblasts together with the healing improvement make these SF/EL scaffolds suitable for wound dressing applications. PMID:22546517

  17. [Wound management for cuts and lacerations].

    PubMed

    Kluwe, Wolfram

    2015-02-01

    Skin cuts and lacerations are frequent injuries. A perfect result of the treatment is going without saying for the patient and its relatives. But there are some aspects to note for an adequate wound management. The main aims of wound management are clear: assist in hemostasis, to avoid infection and pain, and to ensure an esthetically pleasing scar. For these we have to treat not only the wound. Taking care for the hole patient and treating the sore pain and preventing painfull manipulations is the goal for the patients satisfaction. The basic aspects of wound healing and wound management will be described. Sutures, tissue adhesives, staples, and skin-closure tapes are options in the outpatient setting. Although suturing is the preferred method for laceration repair, tissue adhesives are similar in patient satisfaction, infection rates, and scarring risk in low skin-tension areas and may be also more cost-effective. Patient education and appropriate procedural coding are important after the repair. Please do not forget in every case to ask for the tetanus immunization and to think about an antibiotic therapy in case of human or animal bites and for wounds in risk areas and with contamination. PMID:26376539

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

    PubMed Central

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

    2015-01-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  20. Developing a toolbox for analysis of warrior wound biopsies: vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; O'Brien, Frederick P.; Forsberg, Jonathan A.; Potter, Benjamin K.; Elster, Eric A.

    2011-03-01

    The management of modern traumatic war wounds remains a significant challenge for clinicians. This is a reflection of the extensive osseous and soft-tissue damage caused by blasts and high-energy projectiles. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjectively based. Some wounds require an extended period of time to close or fail to remain closed, despite the use and application of novel wound-specific treatment modalities. Aside from impaired wound healing, additional wound complications include wound infection, biofilm formation, and heterotopic ossification (the pathological mineralization of soft tissues). An understanding of the molecular environment of acute wounds throughout the debridement process can provide valuable insight into the mechanisms associated with the eventual wound outcome. The analysis of Raman spectra of ex vivo wound biopsy tissue obtained from serial traumatic wound debridements reveals a decreased 1665 cm-1/1445 cm-1 band area ratio in impaired healing wounds, indicative of an impaired remodeling process, in addition to a decreased 1240 cm-1/1270cm-1. The examination of debrided tissue exhibits mineralization during the early development of heterotopic ossification. Finally, preliminary results suggest that Fourier transform infrared (FT-IR) images of wound effluent may be able to provide early microbiological information about the wound.

  1. Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice.

    PubMed

    Zhang, Eryun; Gao, Bo; Yang, Li; Wu, Xiaojun; Wang, Zhengtao

    2016-02-01

    Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P2Y12 and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production via PI3K/Akt/mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with phosphate-buffered saline (PBS) treatment (15.8 versus 20.9 days). Meanwhile, Ft1 increased the rate of re-epithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, transforming growth factor (TGF)-β1 and TGF-β3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation, and consequent scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor at either mRNA or protein levels and alleviated the inflammation of infiltrated monocytes indicated by reduced tumor necrosis factor-α and interleukin-6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis, and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU. PMID:26567319

  2. A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin staples

    PubMed Central

    Iamthanaporn, K.; Hongnaparak, T.; Tangtrakulwanich, B.

    2016-01-01

    Objectives Nylon sutures and skin staples are used commonly in total knee arthroplasty (TKA) surgical wound closure. However, there is no study that compares the wound healing efficacy and patient satisfaction scores of both techniques in the same knee. Methods We randomised 70 patients who underwent primary TKA into two groups. In one group of 34 patients, the skin at the upper half of the wound was closed with skin staples and the lower half of the wound was closed with simple interrupted nylon sutures. In the other group of 36 patients, the skin at the upper half of the wound was closed with nylon stitches and the lower half of the wound was closed with skin staples. We recorded the wound closure time, pain score at the time of stitch removal, wound complication rate, patient satisfaction score, and the Hollander wound evaluation score at the post-operative periods of five days, 14 days, six weeks, three months, and six months. Each half wound was analysed separately. Results The mean patient body mass index was 26.8 kg/m2 (standard deviation 6.3). A total of 70 nylon stitched wounds and 70 skin stapled wounds were analysed. There were no significant differences in wound complication rates, patient satisfaction score, and the Hollander wound evaluation score between both types of wounds (p > 0.05). The wound closure time for skin stapled wounds was significantly lower than the nylon stitched wounds (p < 0.001). However, the skin stapled wounds had a significantly higher pain score at the time of stitch removal (p < 0.001). Conclusion Skin staples and nylon stitches had comparable results with respect to wound healing and patient satisfaction in TKA wound closure in non-obese patients. The benefit of skin staples over nylon stitches was a decrease in operative time, but was more painful upon removal. Cite this article: V. Yuenyongviwat. A randomised controlled trial comparing skin closure in total knee arthroplasty in the same knee: nylon sutures versus skin

  3. 40 CFR 264.113 - Closure; time allowed for closure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Closure; time allowed for closure. 264... (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Closure and Post-Closure § 264.113 Closure; time allowed for closure. (a) Within 90 days after...

  4. 40 CFR 265.113 - Closure; time allowed for closure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Closure; time allowed for closure. 265... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Closure and Post-Closure § 265.113 Closure; time allowed for closure. (a) Within...

  5. Treatment of Sternal Wound Infection Using a Free Myocutaneous Flap.

    PubMed

    Chiang, I-han; Chen, Shyi-Gen; Wang, Chih-Hsin

    2015-11-01

    Deep sternal wound infections are potentially life-threatening complications after cardiac operations because they can spread into the mediastinum and cause postoperative morbidity and mortality. We present a 65-year-old man with a history of coronary artery bypass grafting. A large sternal defect was left after debridement. After brief vacuum-assisted closure (VAC), a free myocutaneous flap of the anterolateral thigh (ALT) was used to fill the dead space. At the 9-month follow-up, the wound had healed completely without tissue loss or complications, and the patient returned to normal life. This was a successful treatment of a deep sternal wound with free flap coverage. PMID:26522542

  6. Effective management of major lower extremity wounds using an acellular regenerative tissue matrix: a pilot study.

    PubMed

    Brigido, Stephen A; Boc, Steven F; Lopez, Ramon C

    2004-01-01

    Wound healing is a significant problem in orthopedics. Graftjacket tissue matrix (Wright Medical Technology, Inc, Arlington, Tenn), a novel acellular regenerative tissue matrix, has been designed to aid wound closure. A prospective, randomized study was initiated to determine the efficacy of this tissue product in wound repair compared with conventional treatment. Lower extremity wounds are refractile to healing in patients with diabetes mellitus. Therefore, researchers used diabetic foot ulcers to evaluate the efficacy of GraftJacket tissue matrix in wound repair. Only a single administration of the tissue matrix was required. After 1 month of treatment, preliminary results demonstrate that this novel tissue matrix promotes faster healing at a statistically significant rate over conventional treatment. Because wounds in this series of patients are deep and circulation around the wound is poor, the preliminary results suggest that this tissue matrix will be applicable to other types of orthopedic wounds. PMID:14763548

  7. Abdominal stab wounds: self-inflicted wounds versus assault wounds.

    PubMed

    Venara, Aurélien; Jousset, Nathalie; Airagnes, Guillaume; Arnaud, Jean-Pierre; Rougé-Maillart, Clotilde

    2013-05-01

    Intentional penetrating wounds, self inflicted or inflicted by others, are increasingly common. As a result, it can be difficult for the forensic examiner to determine whether the cause is self-inflicted or not. This type of trauma has been studied from a psychological perspective and from a surgical perspective but the literature concerning the forensic perspective is poorer. The objective of this study was to compare the epidemiology of abdominal stab wounds so as to distinguish specific features of each type. This could help the forensic scientist to determine the manner of infliction of the wound. We proposed a retrospective monocentric study that included all patients with an abdominal wound who were managed by the visceral surgery department at Angers University Hospital. Demographic criteria, patient history, circumstances and location of the wound were noted and compared. A comparison was drawn between group 1 (self inflicted wound) and group 2 (assault). This study showed that the only significant differences are represented by the patient's prior history and the circumstances surrounding the wound, i.e. the scene and time of day. In our study, neither the site, nor the injuries sustained reveal significant clues as to the origin of the wound. According to our findings, in order to determine the cause, the forensic examiner should thus carefully study the circumstances and any associated injuries. PMID:23622473

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

    PubMed Central

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

    2016-01-01

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

  9. An overview of factors maximizing successful split-thickness skin grafting in diabetic wounds

    PubMed Central

    Donegan, Ryan J.; Schmidt, Brian M.; Blume, Peter A.

    2014-01-01

    Open wounds, from ulcerations or slow healing, are one of the comorbidities in diabetic patients that can lead to amputation. Therefore, an optimal way to close and heal wounds quickly in diabetic patients is required. Split-thickness skin grafts (STSG) offer a quick method of wound closure for diabetic patients. This article review will look at causes of failure in STSG, and ways to optimize success.

  10. Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

    SciTech Connect

    Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel; Herrero-Fresneda, Inmaculada; Garcia del Moral, Raimundo; Dedhar, Shoukat; Ruiz-Torres, Maria P.; Rodriguez-Puyol, Diego

    2012-11-15

    Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing. -- Highlights: Black-Right-Pointing-Pointer ILK deletion results in decreased HGF expression and delayed scratch wound repair. Black-Right-Pointing-Pointer PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. Black-Right-Pointing-Pointer An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. Black-Right-Pointing-Pointer ILK-KO mice are used to confirm the requirement for ILK function in wound healing. Black-Right-Pointing-Pointer Human HGF treatment restores delayed wound closure in vitro and in vivo.

  11. Wound repair: role of immune–epithelial interactions

    PubMed Central

    Leoni, G; Neumann, P-A; Sumagin, R; Denning, TL; Nusrat, A

    2016-01-01

    The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair. PMID:26174765

  12. Postoperative radiation of open head and neck wounds

    SciTech Connect

    Isaacs, J.H. Jr.; Thompson, W.B.; Cassisi, N.J.; Million, R.R.

    1987-03-01

    Complication rates are lower using postoperative radiation therapy and cure rates at least compatible to preoperative radiation therapy. However, one of the concerns with postoperative radiation treatment is the possibility of delay in beginning the treatment because of an unhealed surgical wound. A delay of more than 6 weeks is detrimental. In order to study the effect of radiation therapy on incompletely healed wounds, a retrospective chart review of such cases during the period 1977 to 1984 was undertaken. One hundred and eighty-five patients had planned postoperative radiation therapy, and 13 of these began radiation therapy with an unhealed wound or fistula. Six of 10 wounds closed spontaneously, 4 required surgical closure, and 3 failed to heal. Seven patients in this study died with cancer, 2 died of other causes, 3 are alive without disease, and 1 patient remains alive with disease. We conclude that giving radiation therapy to an open wound with appropriate precaution can be done without serious complications.

  13. Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles.

    PubMed

    Im, A-Rang; Kim, Jee Young; Kim, Hyun-Seok; Cho, Seonho; Park, Youmie; Kim, Yeong Shik

    2013-10-01

    For topical applications in wound healing, silver nanoparticles (AgNPs) have attracted much attention as antibacterial agents. Herein, we describe a green-synthetic route for the production of biocompatible and crystalline AgNPs using two glycosaminoglycans, chondroitin sulfate (CS) and acharan sulfate (AS), as reducing agents. The synthetic approach avoids the use of toxic chemicals, and the yield of AgNPs formation is found to be 98.1% and 91.1% for the chondroitin sulfate-reduced silver nanoparticles (CS-AgNPs) and the acharan sulfate-reduced silver nanoparticles (AS-AgNPs), respectively. Nanoparticles with mostly spherical and amorphous shapes were observed, with an average diameter of 6.16 ± 2.26 nm for CS-AgNPs and 5.79 ± 3.10 nm for AS-AgNPs. Images of the CS-AgNPs obtained from atomic force microscopy revealed the self-assembled structure of CS was similar to a densely packed woven mat with AgNPs sprinkled on the CS. These nanoparticles were stable under cell culture conditions without any noticeable aggregation. An approximately 128-fold enhancement of the antibacterial activities of the AgNPs was observed against Enterobacter cloacae and Escherichia coli when compared to CS and AS alone. In addition, an in vivo animal model of wound healing activity was tested using mice that were subjected to deep incision wounds. In comparison to the controls, the ointments containing CS-AgNPs and AS-AgNPs stimulated wound closure under histological examination and accelerated the deposition of granulation tissue and collagen in the wound area. The wound healing activity of the ointments containing CS-AgNPs and AS-AgNPs are comparable to that of a commercial formulation of silver sulfadiazine even though the newly prepared ointments contain a lower silver concentration. Therefore, the newly prepared AgNPs demonstrate potential for use as an attractive biocompatible nanocomposite for topical applications in the treatment of wounds. PMID:24008263

  14. An ordinary differential equation model for full thickness wounds and the effects of diabetes.

    PubMed

    Bowden, L G; Maini, P K; Moulton, D E; Tang, J B; Wang, X T; Liu, P Y; Byrne, H M

    2014-11-21

    Wound healing is a complex process in which a sequence of interrelated phases contributes to a reduction in wound size. For diabetic patients, many of these processes are compromised, so that wound healing slows down. In this paper we present a simple ordinary differential equation model for wound healing in which attention focusses on the dominant processes that contribute to closure of a full thickness wound. Asymptotic analysis of the resulting model reveals that normal healing occurs in stages: the initial and rapid elastic recoil of the wound is followed by a longer proliferative phase during which growth in the dermis dominates healing. At longer times, fibroblasts exert contractile forces on the dermal tissue, the resulting tension stimulating further dermal tissue growth and enhancing wound closure. By fitting the model to experimental data we find that the major difference between normal and diabetic healing is a marked reduction in the rate of dermal tissue growth for diabetic patients. The model is used to estimate the breakdown of dermal healing into two processes: tissue growth and contraction, the proportions of which provide information about the quality of the healed wound. We show further that increasing dermal tissue growth in the diabetic wound produces closure times similar to those associated with normal healing and we discuss the clinical implications of this hypothesised treatment. PMID:25017724

  15. Orientation and shape dependence of embryonic wound healing

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

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

  16. Crawling Cells Can Close Wounds without Purse Strings or Signaling

    PubMed Central

    Lee, Pilhwa; Wolgemuth, Charles W.

    2011-01-01

    When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the “wound.” In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell signaling has been proposed to play a significant role in directing cells to move into the denuded area. However, wounds made in monolayers of Madin-Darby canine kidney (MDCK) cells still close even when a row of cells is deactivated at the periphery of the wound, and recent experiments show complex, highly-correlated cellular motions that extend tens of cell lengths away from the boundary. These experiments suggest a dominant role for mechanics in wound healing. Here we present a biophysical description of the collective migration of epithelial cells during wound healing based on the basic motility of single cells and cell-cell interactions. This model quantitatively captures the dynamics of wound closure and reproduces the complex cellular flows that are observed. These results suggest that wound healing is predominantly a mechanical process that is modified, but not produced, by cell-cell signaling. PMID:21423710

  17. Pollution dilemma in Asian population: CNG and wound healing.

    PubMed

    Ejaz, Sohail; Chekarova, Irina; Ahmad, Mukhtar; Nasir, Amir; Ashraf, Muhammad; Lim, Chae Woong

    2009-11-01

    Automobile exhaust constituents contribute significantly to air pollution in urban areas and compressed natural gas (CNG) is considered one of the most promising fuel alternatives for the future. CNG-powered four-stroke engine auto-rickshaws are ubiquitous in South Asian cities as taxi and for commercial transportation. Automotive exhaust contains several toxins, which are overwhelmingly toxic to the processes of wound healing. By utilizing the in vivo mouse model of wound healing, this report analyzes the effects of CNG-powered four-stroke auto-rickshaws smoke solution (4SARSS) on different events of wound healing; dermal matrix regeneration, re-epithelialization and neovascularization. A total of 72 adult mice, divided in eight groups were exposed to 4SARSS for 12 days. A highly significant reduction (P<0.001) in wound closure was observed among all 4SARSS treated groups, at each time point of the experiment. An immature development in both the neoepidermis and the neodermis was observed among all 4SARSS treated wounds with defective re-epithelialization, dermal matrix regeneration and maturation of collagen bundles. Abbott curve, angular spectrum, 3D surface topographies, and histological investigations of wounds explicated highly significant activation (P<0.001) of delayed-neovascularization among 4SARSS treated wounds. All these annotations advocate excessive toxicity of emission from CNG-powered auto-rickshaws to the process of wound healing and people occupationally exposed to this toxic emissions may suffer varying degree of delayed wound healing. PMID:21784023

  18. Mechanics of fatigue crack closure

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr. (Editor); Elber, Wolf (Editor)

    1988-01-01

    Papers are presented on plasticity induced crack closure, crack closure in fatigue crack growth, the dependence of crack closure on fatigue loading variables, and a procedure for standardizing crack closure levels. Also considered are a statistical approach to crack closure determination, the crack closure behavior of surface cracks under pure bending, closure measurements on short fatigue cracks, and crack closure under plane strain conditions. Other topics include fatigue crack closure behavior at high stress ratios, the use of acoustic waves for the characterization of closed fatigue cracks, and the influence of fatigue crack wake length and state of stress on crack closure.

  19. Microbial cellulose wound dressing in the treatment of nonhealing lower extremity ulcers.

    PubMed

    Portal, Orlando; Clark, William A; Levinson, Dennis J

    2009-01-01

    Following standard care, nonhealing lower extremity (LE) ulcers were managed with a bacterial cellulose (BC) wound dressing, Dermafill™, (AMD/Ritmed, Tonawanda, NY), derived from Acetobacter xylinum. The time to 75% reduction in wound size was compared in 11 chronic wounds before and after the application of BC. The mean period of observation before the application of BC was 315 days; (95% CI: 239-392 days). With the application of BC to these chronic wounds, the mean time to 75% epithelization was reduced to 81 days (95% CI: 50-111 days) with a median of 79 days. The rate of wound closure with BC was significantly faster than with standard care (P < 0.001). When applied to nonhealing LE ulcers, a BC wound dressing shortens the time to wound closure over standard care. PMID:25904579

  20. Preclinical Evaluation of Tegaderm™ Supported Nanofibrous Wound Matrix Dressing on Porcine Wound Healing Model

    PubMed Central

    Ong, Chee Tian; Zhang, Yanzhong; Lim, Raymond; Samsonraj, Rebekah; Masilamani, Jeyakumar; Phan, Tran Hong Ha; Ramakrishna, Seeram; Lim, Ivor; Kee, Irene; Fahamy, Mohammad; Templonuevo, Vilma; Lim, Chwee Teck; Phan, Toan Thang

    2015-01-01

    Objective: Nanofibers for tissue scaffolding and wound dressings hold great potential in realizing enhanced healing of wounds in comparison with conventional counterparts. Previously, we demonstrated good fibroblast adherence and growth on a newly developed scaffold, Tegaderm™-Nanofiber (TG-NF), made from poly ɛ-caprolactone (PCL)/gelatin nanofibers electrospun onto Tegaderm (TG). The purpose of this study is to evaluate the performance and safety of TG-NF dressings in partial-thickness wound in a pig healing model. Approach: To evaluate the rate of reepithelialization, control TG, human dermal fibroblast-seeded TG-NF(+) and -unseeded TG-NF(−) were randomly dressed onto 80 partial-thickness burns created on four female and four male pigs. Wound inspections and dressings were done after burns on day 7, 14, 21, and 28. On day 28, full-thickness biopsies were taken for histopathological evaluation by Masson-Trichrome staining for collagen and hematoxylin–eosin staining for cell counting. Results: No infection and severe inflammation were recorded. Wounds treated with TG-NF(+) reepithelialized significantly faster than TG-NF(−) and control. Wound site inflammatory responses to study groups were similar as total cell counts on granulation tissues show no significant differences. Most of the wounds completely reepithelialized by day 28, except for two wounds in control and TG-NF(−). A higher collagen coverage was also recorded in the granulation tissues treated with TG-NF(+). Innovation and Conclusion: With better reepithelialization achieved by TG-NF(+) and similar rates of wound closure by TG-NF(−) and control, and the absence of elevated inflammatory responses to TG-NF constructs, TG-NF constructs are safe and demonstrated good healing potentials that are comparable to Tegaderm. PMID:25713753

  1. Quantifying cell behaviors during embryonic wound healing

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

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

    PubMed

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

    2016-04-01

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

  3. Surgical wound care - open

    MedlinePlus

    ... around your wound: Use a normal saline solution (salt water) or mild soapy water. Soak the gauze or ... wash out, your wound: Fill a syringe with salt water or soapy water, whichever your doctor recommends. Hold ...

  4. Gunshot wounds -- aftercare

    MedlinePlus

    ... remove pieces of broken or shattered bone To clean the wound Gunshots wounds that pass through the ... mind: Keep the dressing and area around it clean and dry. Take any antibiotics or pain relievers ...

  5. How wounds heal

    MedlinePlus

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

  6. Gunshot wounds - aftercare

    MedlinePlus

    ... 11(9):546-551. Leong M, Phillips LG. Wound Healing. In: Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery . 19th ed. ... Of Gunshot Wounds To The Limbs: A Review. The Internet Journal ...

  7. Wound care centers

    MedlinePlus

    ... multiple types of dressings as your wound heals. Hyperbaric oxygen therapy Depending on the type of wound, your doctor may recommend hyperbaric oxygen therapy . Oxygen is important for healing. During this treatment, ...

  8. Thyroid Hormone and Wound Healing

    PubMed Central

    Safer, Joshua D.

    2013-01-01

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

  9. Rash with DERMABOND PRINEO Skin Closure System Use in Bilateral Reduction Mammoplasty: A Case Series.

    PubMed

    Knackstedt, R W; Dixon, J A; O'Neill, P J; Herrera, F A

    2015-01-01

    Background. Bilateral reduction mammoplasty is a common plastic surgery procedure that can be complicated by unfavorable scar formation along incision sites. Surgical adhesives can be utilized as an alternative or as an adjunct to conventional suture closures to help achieve good wound tension and provide an adequate barrier with excellent cosmesis. The recently introduced DERMABOND PRINEO Skin Closure System Skin Closure System combines the skin adhesive 2-octyl cyanoacrylate with a self-adhering polyester-based mesh. Proposed benefits of wound closure with DERMABOND PRINEO Skin Closure System, used with or without sutures, include its watertight seal, easy removal, microbial barrier, even distribution of tension, and reduction in wound closure time. Although allergic reactions to 2-octyl cyanoacrylate have been reported, few allergic reactions to DERMABOND PRINEO Skin Closure System have been noted in the literature. This case series describes three patients who experienced an allergic reaction to DERMABOND PRINEO Skin Closure System after undergoing elective bilateral reduction mammoplasties at our institution to further explore this topic. Methods. Retrospective chart review of bilateral reduction mammoplasty patients who received DERMABOND PRINEO Skin Closure System dressing at our institution was performed. Results. Three patients were identified as having a rash in reaction to DERMABOND PRINEO Skin Closure System after bilateral reduction mammoplasty. All three patients required systemic steroid treatment to resolve the rash. One patient was identified as having a prior adhesive reaction. Conclusions. DERMABOND PRINEO Skin Closure System has demonstrated its efficacy in optimizing scar healing and appearance. However, as we demonstrate these three allergic reactions to DERMABOND PRINEO Skin Closure System, caution must be utilized in its usage, namely, in patients with a prior adhesive allergy and in sites where moisture or friction may be apparent. PMID

  10. Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats.

    PubMed

    Dhall, Sandeep; Silva, João P; Liu, Yan; Hrynyk, Michael; Garcia, Monika; Chan, Alex; Lyubovitsky, Julia; Neufeld, Ronald J; Martins-Green, Manuela

    2015-12-01

    Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischaemia, inflammation and infection costing $7.5 billion/year in the U.S.A. alone, in addition to the morbidity and mortality that occur when the burns are extensive. We previously showed that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization and stimulates angiogenesis. More recently, we developed an alginate sponge dressing (ASD) containing insulin encapsulated in PLGA [poly(D,L-lactic-co-glycolic acid)] microparticles that provides a sustained release of bioactive insulin for >20 days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring healing. Using heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04 mg insulin/cm(2) every 3 days for 9 days have faster closure, a higher rate of disintegration of dead tissue and decreased oxidative stress. In addition, in insulin-treated wounds, the pattern of neutrophil inflammatory response suggests faster clearing of the burned dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibres organized more like a basket weave (normal skin) than aligned and cross-linked (scar tissue). In summary, application of ASD-containing insulin-loaded PLGA particles on burns every 3 days stimulates faster and more regenerative healing. These results suggest insulin as a potential therapeutic agent in burn healing and, because of its long history of safe use in humans, insulin could become one of the treatments of choice when repair and regeneration are critical for proper tissue function. PMID:26310669

  11. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

    PubMed Central

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

    2015-01-01

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

  12. Surgical wound infection - treatment

    MedlinePlus

    ... there is an infection and what kind of antibiotic medicine would work best Debride the wound by removing dead or infected tissue in the wound Rinse the wound with salt water (saline solution) Drain the pocket of pus (abscess), if present ...

  13. Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia.

    PubMed

    Tong, Chuan; Hao, Haojie; Xia, Lei; Liu, Jiejie; Ti, Dongdong; Dong, Liang; Hou, Qian; Song, Haijing; Liu, Huiling; Zhao, Yali; Fu, Xiaobing; Han, Weidong

    2016-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have properties that make them promising for the treatment of chronic nonhealing wounds. The major challenge is ensuring an efficient, safe, and painless delivery of BM-MSCs. Tissue-engineered skin substitutes have considerable benefits in skin damage resulting from chronic nonhealing wounds. Here, we have constructed a three-dimensional biomimetic scaffold known as collagen-chitosan sponge scaffolds (CCSS) using the cross-linking and freeze-drying method. Scanning electron microscopy images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve biostability using swelling and degradation assays. Furthermore, BM-MSCs were seeded in CCSS using the two-step seeding method to construct tissue-engineered skin substitutes. In addition, in this three-dimensional biomimetic CCSS, BM-MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM-MSCs exhibited a significant upregulated expression of proangiogenesis factors, including HIF-1α, VEGF, and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing. PMID:26463737

  14. Gap geometry dictates epithelial closure efficiency

    PubMed Central

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J.; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  15. Gap geometry dictates epithelial closure efficiency.

    PubMed

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  16. Image-guided plasma therapy of cutaneous wound

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Tissue loads applied by a novel medical device for closing large wounds.

    PubMed

    Katzengold, Rona; Topaz, Moris; Gefen, Amit

    2016-02-01

    Closure of large soft tissue defects following surgery or trauma as well as closure of large chronic wounds constitutes substantial but common reconstructive challenges. In such cases, an attempt to use conventional suturing will result in high-tension closure, therefore alternative external skin stretching systems were developed. These types of devices were meant to reduce local mechanical loads in the skin and the underlying tissues, taking advantage of the viscoelastic properties of the skin, especially mechanical creep, for primary wound closure. Studies have shown the clinical advantages of skin stretching systems, however, quantitative bioengineering models, demonstrating closure of large wounds, are lacking. Here we present finite element (FE) modeling of the TopClosure(®) tension relief system (TRS) and its biomechanical efficacy in three (real) wound cases, compared with the alternative of a conventional surgical suturing closure technique. Our simulations showed that peak effective stresses on the skin were at least an order of magnitude greater (and sometimes nearly 2 orders-of-magnitude greater) when tension sutures were used with respect to the corresponding TRS data. For the tension suture simulations, the tensile stress was in the range of 415-648 MPa and in the TRS simulations, it was 16-30 MPa. Based on the present computational FE modeling, the TRS reduces localized tissue deformations and stress concentrations in skin and underlying tissues while closing large wounds, compared to the deformations and stresses that are inflicted during the process of suturing. This substantial reduction of loads allows surgeons to better employ the viscoelastic properties of the skin for primary wound closure. PMID:26750452

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

    PubMed

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

    2015-11-01

    Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. PMID:26360824

  20. Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; Elster, Eric A.

    2012-01-01

    Wound care and management accounted for over 1.8 million hospital discharges in 2009. The complex nature of wound physiology involves hundreds of overlapping processes that we have only begun to understand over the past three decades. The management of wounds remains a significant challenge for inexperienced clinicians. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjective. Some wounds fail to close, or dehisce, despite the use and application of novel wound-specific treatment modalities. An understanding of the molecular environment of acute and chronic wounds throughout the wound-healing process can provide valuable insight into the mechanisms associated with the patient's outcome. Pathologic alterations of wounds are accompanied by fundamental changes in the molecular environment that can be analyzed by vibrational spectroscopy. Vibrational spectroscopy, specifically Raman and Fourier transform infrared spectroscopy, offers the capability to accurately detect and identify the various molecules that compose the extracellular matrix during wound healing in their native state. The identified changes might provide the objective markers of wound healing, which can then be integrated with clinical characteristics to guide the management of wounds.

  1. Smartphone-based wound assessment system for patients with diabetes.

    PubMed

    Wang, Lei; Pedersen, Peder C; Strong, Diane M; Tulu, Bengisu; Agu, Emmanuel; Ignotz, Ronald

    2015-02-01

    Diabetic foot ulcers represent a significant health issue. Currently, clinicians and nurses mainly base their wound assessment on visual examination of wound size and healing status, while the patients themselves seldom have an opportunity to play an active role. Hence, a more quantitative and cost-effective examination method that enables the patients and their caregivers to take a more active role in daily wound care potentially can accelerate wound healing, save travel cost and reduce healthcare expenses. Considering the prevalence of smartphones with a high-resolution digital camera, assessing wounds by analyzing images of chronic foot ulcers is an attractive option. In this paper, we propose a novel wound image analysis system implemented solely on the Android smartphone. The wound image is captured by the camera on the smartphone with the assistance of an image capture box. After that, the smartphone performs wound segmentation by applying the accelerated mean-shift algorithm. Specifically, the outline of the foot is determined based on skin color, and the wound boundary is found using a simple connected region detection method. Within the wound boundary, the healing status is next assessed based on red-yellow-black color evaluation model. Moreover, the healing status is quantitatively assessed, based on trend analysis of time records for a given patient. Experimental results on wound images collected in UMASS-Memorial Health Center Wound Clinic (Worcester, MA) following an Institutional Review Board approved protocol show that our system can be efficiently used to analyze the wound healing status with promising accuracy. PMID:25248175

  2. How fast do European conifers overgrow wounds inflicted by rockfall?

    PubMed

    Schneuwly-Bollschweiler, Michelle; Schneuwly, Dominique M

    2012-08-01

    The capacity of trees to recover from mechanical disturbance is of crucial importance for tree survival but has been primarily investigated in saplings using artificially induced wounds. In this study, mature Larix decidua Mill., Picea abies (L.) Karst. and Abies alba Mill. trees growing on alpine slopes that were wounded by naturally occurring rockfall were analyzed to determine their efficiency in overgrowing wounds. In total 43 L. decidua, P. abies and A. alba trees were sampled. First, 106 samples from 27 L. decidua and P. abies trees were analyzed to reconstruct yearly and overall overgrowth rates. Cross sections were taken at the maximum extension of the injury and overgrowth rates were determined on a yearly basis. Results clearly showed that L. decidua overgrew wounds more efficiently than P. abies with an average overgrowth rate of 19° and 11.8° per year, respectively. The higher on the stem the injury was located, the faster the wound was closed. Young and small trees overgrew wounds more efficiently than older or thicker trees. In contrast, no correlation was observed between injury size or increment before/after wounding and wound closure. Second, cross sections from 16 L. decidua, P. abies and A. alba (54 injuries) were used to assess closure rates at different heights around the injury. Overgrowth was generally smallest at the height of the maximum lateral extension of the injury and increased at the upper and lower end of the injury. The efficiency with which L. decidua closes wounds inflicted by rockfall makes this species highly adapted to sites with this type of mechanical disturbance. PMID:22826380

  3. Generation of a Functional Non-Shedding Collagen XVII Mouse Model: Relevance of Collagen XVII Shedding in Wound Healing.

    PubMed

    Jacków, Joanna; Schlosser, Andreas; Sormunen, Raija; Nyström, Alexander; Sitaru, Cassian; Tasanen, Kaisa; Bruckner-Tuderman, Leena; Franzke, Claus-Werner

    2016-02-01

    Collagen XVII is a hemidesmosomal anchorage molecule of basal keratinocytes that promotes stable epidermal-dermal adhesion. One unique feature of collagen XVII is that its collagenous ectodomain is constitutively released from the cell surface by a disintegrin and metalloproteinases (ADAMs) through cleavage within its juxtamembranous linker domain. The responsivity of shedding to environmental stimuli and the high stability of the released ectodomain in several tissues suggests functions in cell detachment during epidermal morphogenesis, differentiation, and regeneration, but its physiologic relevance remained elusive. To investigate this, we generated knock-in mice, which express a functional non-sheddable collagen XVII mutant, with a 41 amino acid deletion in the linker domain spanning all ADAM cleavage sites. These mice showed no macroscopic phenotypic changes, were fertile, and had a normal lifespan. Prevention of collagen XVII shedding interfered neither with skin development nor with epidermal adhesion and differentiation. However, it led to faster wound closure due to accelerated re-epithelialization at the wound edges where shedding of wild-type collagen XVII was strongly induced. Taken together, we have successfully generated a functional non-shedding collagen XVII mouse model, which represents a powerful tool to investigate the pathophysiologic relevance of ectodomain shedding during wound regeneration and cancer invasion. PMID:26967482

  4. Evaluation of human amniotic membrane as a wound dressing for split-thickness skin-graft donor sites.

    PubMed

    Loeffelbein, Denys J; Rohleder, Nils H; Eddicks, Matthias; Baumann, Claudia M; Stoeckelhuber, Mechthild; Wolff, Klaus-D; Drecoll, Enken; Steinstraesser, Lars; Hennerbichler, Simone; Kesting, Marco R

    2014-01-01

    Human amniotic membrane (HAM) has been used as a biomaterial in various surgical procedures and exceeds some qualities of common materials. We evaluated HAM as wound dressing for split-thickness skin-graft (STSG) donor sites in a swine model (Part A) and a clinical trial (Part B). Part A: STSG donor sites in 4 piglets were treated with HAM or a clinically used conventional polyurethane (PU) foil (n = 8 each). Biopsies were taken on days 5, 7, 10, 20, 40, and 60 and investigated immunohistochemically for alpha-smooth muscle actin (αSMA: wound contraction marker), von Willebrand factor (vWF: angiogenesis), Ki-67 (cell proliferation), and laminin (basement membrane integrity). Part B: STSG donor sites in 45 adult patients (16 female/29 male) were treated with HAM covered by PU foam, solely by PU foam, or PU foil/paraffin gauze (n = 15 each). Part A revealed no difference in the rate of wound closure between groups. HAM showed improved esthetic results and inhibitory effects on cicatrization. Angioneogenesis was reduced, and basement membrane formation was accelerated in HAM group. Part B: no difference in re-epithelialization/infection rate was found. HAM caused less ichor exudation and less pruritus. HAM has no relevant advantage over conventional dressings but might be a cost-effective alternative. PMID:25003117

  5. [Surgical hygroscopic bandages for amputations, secreting wounds and diabetes foot].

    PubMed

    Topolav, J; Kirov, G; Markov, G; Girov, K; Nedkov, P; Georgieva, A

    2010-01-01

    The authors adopt in clinical practice using of sterile hygroscopic wound dressings 'pampers type'. They use these dressings in 113 patients. The appropriate patients are these with limbs amputations, diabetic foot, suppurative and plenty secreting deep wounds, atonite and decubital wounds. The dressings are sterilised using paraformaldehyde sterilization which do not injure the synthetic materials. The hygroscopic dressings are non- allergic and are well tolerated by the patients. Using these dressings facilitate the medical team work and help to reduce the contamination of the hospital linen and the patients coverlet. They help for accelerating the wound healing process. They are also economic effective by reducing the amount of used dressing material. PMID:21972719

  6. Laser thermal preconditioning enhances dermal wound repair

    NASA Astrophysics Data System (ADS)

    Wilmink, Gerald J.; Carter, Terry; Davidson, Jeffrey M.; Jansen, E. Duco

    2008-02-01

    Preconditioning tissues with an initial mild thermal stress, thereby eliciting a stress response, can serve to protect tissue from subsequent stresses. Patients at risk for impaired healing, such as diabetics, can benefit from therapeutic methods which enhance wound repair. We present a laser thermal preconditioning protocol that accelerates cutaneous wound repair in a murine model. A pulsed diode laser (λ = 1.86 μm, τ p = 2 ms, 50 Hz, H = 7.64 mJ/cm2) was used to precondition mouse skin before incisional wounds were made. The preconditioning protocol was optimized in vitro and in vivo using hsp70 expression, cell viability, and temperature measurements as benchmarks. Hsp70 expression was non-invasively monitored using a transgenic mouse strain with the hsp70 promoter driving luciferase expression. Tissue temperature recordings were acquired in real time using an infrared camera. Wound repair was assessed by measuring hsp70 expression, biomechanical properties, and wound histology for up to 24 d. Bioluminescence (BLI) was monitored with the IVIS 200 System (Xenogen) and tensile properties with a tensiometer (BTC-2000). The in vivo BLI studies indicated that the optimized laser preconditioning protocol increased hsp70 expression by 15-fold. The tensiometer data revealed that laser preconditioned wounds are ~40% stronger than control wounds at 10 days post surgery. Similar experiments in a diabetic mouse model also enhanced wound repair strength. These results indicate that 1) noninvasive imaging methods can aid in the optimization of novel laser preconditioning methods; 2) that optimized preconditioning with a 1.86 μm diode laser enhances early wound repair.

  7. New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications

    PubMed Central

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

    2013-01-01

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

  8. Use of negative-pressure wound therapy in orthopaedic trauma.

    PubMed

    Streubel, Philipp N; Stinner, Daniel J; Obremskey, William T

    2012-09-01

    Negative-pressure wound therapy (NPWT) has become an important adjunct to the management of traumatic wounds and surgical incisions related to musculoskeletal trauma. On the battlefield, this adjunct therapy allows early wound management and safe aeromedical evacuation. NPWT mechanisms of action include stabilization of the wound environment, reduction of wound edema, improvement of tissue perfusion, and stimulation of cells at the wound surface. NPWT stimulates granulation tissue and angiogenesis and may improve the likelihood of primary closure and reduce the need for free tissue transfer. In addition, NPWT reduces the bacterial bioburden of wounds contaminated with gram-negative bacilli. However, an increased risk of colonization of gram-positive cocci (eg, Staphylococcus aureus) exists. Although NPWT facilitates wound management, further research is required to determine conclusively whether this modality is superior to other management options. Ongoing research will continue to define the indications for and benefits of NPWT as well as establish the role of combination therapy, in which NPWT is used with instillation of antibiotic solutions, placement of antibiotic-laden cement beads, or silver-impregnated sponges. PMID:22941799

  9. [Toilet of chronic wound].

    PubMed

    Strok, Nevenka; Huljev, Dubravko

    2013-10-01

    Chronic wound toilet, with appropriate care of the surrounding skin, is one of the basic steps that must be performed in the treatment of patients with chronic wound. On wound cleaning and bandaging, it is of utmost importance to choose an appropriate technique of cleansing, select an appropriate solution for leaching and choose an appropriate wound dressing. In this way, the wound is protected from dirt from the environment and microorganisms, while protecting the surrounding tissue from the wound exudate, providing optimal conditions for better and faster wound healing and contributing to improved patient quality of life. The frequency of dressing change is individual and must be tailored to each patient in correlation with the psychosocial status of the patient, the type of the wound, the amount and type of wound exudate, as well as what is to be put on the wound. One of the most important elements in wound toilet is appropriate care for the surrounding skin. Basic guidelines for skin care must meet three basic criteria: adequate washing and cleansing of the skin, maintain the physiological balance of the skin and protect the skin from external damage. PMID:24371977

  10. Blue light does not impair wound healing in vitro.

    PubMed

    Masson-Meyers, Daniela Santos; Bumah, Violet Vakunseh; Enwemeka, Chukuka Samuel

    2016-07-01

    Irradiation with red or near infrared light promotes tissue repair, while treatment with blue light is known to be antimicrobial. Consequently, it is thought that infected wounds could benefit more from combined blue and red/infrared light therapy; but there is a concern that blue light may slow healing. We investigated the effect of blue 470nm light on wound healing, in terms of wound closure, total protein and collagen synthesis, growth factor and cytokines expression, in an in vitro scratch wound model. Human dermal fibroblasts were cultured for 48h until confluent. Then a linear scratch wound was created and irradiated with 3, 5, 10 or 55J/cm(2). Control plates were not irradiated. Following 24h of incubation, cells were fixed and stained for migration and fluorescence analyses and the supernatant collected for quantification of total protein, hydroxyproline, bFGF, IL-6 and IL-10. The results showed that wound closure was similar for groups treated with 3, 5 and 10J/cm(2), with a slight improvement with the 5J/cm(2) dose, and slower closure with 55J/cm(2) p<0.001). Total protein concentration increased after irradiation with 3, 5 and 10J/cm(2), reaching statistical significance at 5J/cm(2) compared to control (p<0.0001). However, hydroxyproline levels did not differ between groups. Similarly, bFGF and IL-10 concentrations did not differ between groups, but IL-6 concentration decreased progressively as fluence increased (p<0.0001). Fluorescence analysis showed viable cells regardless of irradiation fluence. We conclude that irradiation with blue light at low fluence does not impair in vitro wound healing. The significant decrease in IL-6 suggests that 470nm light is anti-inflammatory. PMID:27092999

  11. Negative Pressure Wound Therapy on Closed Surgical Wounds With Dead Space

    PubMed Central

    Suh, Hyunsuk; Lee, A-Young; Park, Eun Jung; Hong, Joon Pio

    2016-01-01

    Background Closed incisional wound surgery frequently leaves dead space under the repaired skin, which results in delayed healing. The purpose of this study was to evaluate the effect of negative pressure wound therapy (NPWT) on incisional wounds with dead space after primary closure by evaluating the fluid volume through the suction drain, blood flow of the skin, tensile strength, and histology of the wounds. Methods Bilateral 25-cm-long incisional wounds with dead space were created on the back of 6 pigs by partially removing the back muscle and then suturing the skin with nylon sutures. NPWT (experimental group) or gauze dressing (control group) was applied over the closed incision for 7 days. Analysis of the wound included monitoring the amount of closed suction drain, blood perfusion unit, tensile strength of the repaired skin, and histology of the incision site. Results The drainage amount was significantly reduced in the experimental group (49.8 mL) compared to the control group (86.2 mL) (P = 0.046). Skin perfusion was increased in the experimental group with statistical significance compared to the control group (P = 0.0175). Collagen staining was increased in the experimental group. The tensile strength of the incision site was significantly higher in the experimental group (24.6 N at 7 days, 61.67 N at 21 days) compared to the control group (18.26 N at 7 days, 50.05 N at 21 days) (P = 0.02). Conclusion This study explains some of the mechanism for using NPWT in closed incision wounds with dead space. It demonstrates that NPWT significantly reduces drainage amount, increases skin perfusion, increases tensile strength, and has the tendency to promote collagen synthesis for closed wound with dead space indicating enhanced healing. PMID:25003432

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

    PubMed Central

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

    2015-01-01

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

  13. Differential effect of wounding on actin and its associated proteins, paxillin and gelsolin, in fetal skin explants.

    PubMed

    Cowin, Allison J; Hatzirodos, Nicholas; Teusner, Jacqueline T; Belford, David A

    2003-06-01

    Skin from the embryonic day 17 rat retains the ability to epithelialize an excisional wound when isolated in serum-supplemented suspension culture. This ability is lost by embryonic day 19. We have investigated this effect of gestational age on fetal epithelial wound closure by correlating the involvement of filamentous actin (F-actin) and its associated proteins, paxillin and gelsolin, in the wound margins of embryonic day 17 and 19 rat skins, with the ability to close a full thickness excisional wound. Using fluorescent-phalloidin histochemistry and scanning confocal microscopy, actin polymerization was observed some five to six cells back from the margin of wounds in the embryonic day 17 skin as early as 3 h postwounding. As the wounds closed over the following 48-72 h, the actin further condensed around the epithelial margin before dispersing after wound closure. In contrast, no organization of actin was seen in the epithelial margin of wounds in skin from the embryonic day 19 embryos. Instead, actin filaments were observed surrounding the dermal wound margins. Chemical or mechanical disruption of the actin in wounded embryonic day 17 skins prevented epithelial closure, although wound repair was independent of cell division. In particular, incising the wound margin 24 h after wounding resulted in the "springing-open" of the embryonic day 17 wound but not the embryonic day 19 wound, reflecting the development of tension in the embryonic day 17 wound margin. Expression of paxillin mRNA was upregulated following wounding at embryonic day 17 but not at embryonic day 19. Paxillin was also observed to colocalize with actin in embryonic day 17 wounds, but not embryonic day 19 wounds, indicating a potential role for paxillin in epithelial repair of the fetal wound. In contrast, gelsolin mRNA was upregulated in embryonic day 19 fetal skin but not at embryonic day 17 and gelsolin protein was observed surrounding actin filaments at embryonic day 19 but not embryonic day

  14. The electric field near human skin wounds declines with age and provides a non-invasive indicator of wound healing

    PubMed Central

    Nuccitelli, Richard; Nuccitelli, Pamela; Li, Changyi; Narsing, Suman; Pariser, David M.; Lui, Kaying

    2011-01-01

    Due to the transepidermal potential of 15-50 mV, inside positive, an injury current is driven out of all human skin wounds. The flow of this current generates a lateral electric field within the epidermis that is more negative at the wound edge than at regions more lateral from the wound edge1. Electric fields in this region could be as large as 40 mV/mm2, and electric fields of this magnitude have been shown to stimulate human keratinocyte migration toward the wounded region3. After flowing out of the wound, the current returns through the space between the epidermis and stratum corneum, generating a lateral field above the epidermis in the opposite direction. Here we report the results from the first clinical trial designed to measure this lateral electric field adjacent to human skin wounds non-invasively. Using a new instrument, the Dermacorder®, we found that the mean lateral electric field in the space between the epidermis and stratum corneum adjacent to a lancet wound in 18-25 year olds is 107-148 mV/mm, 48% larger on average than that in 65-80 year olds. We also conducted extensive measurements of the lateral electric field adjacent to mouse wounds as they healed and compared this field with histological sections through the wound to determine the correlation between the electric field and the rate of epithelial wound closure. Immediately after wounding the average lateral electric field was 122 ± 9 mV/mm. When the wound is filled in with a thick, disorganized epidermal layer, the mean field falls to 79 ± 4 mV/mm. Once this epidermis forms a compact structure with only three cell layers, the mean field is 59 ± 5 mV/mm. Thus, the peak-to-peak spatial variation in surface potential is largest in fresh wounds and slowly declines as the wound closes. The rate of wound healing is slightly greater when wounds are kept moist as expected but we could find no correlation between the amplitude of the electric field and the rate of wound healing. PMID:22092802

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

    PubMed

    Sumitra, Miriyala; Manikandan, Panchatcharam; Suguna, Lochin

    2005-03-01

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

  16. Wound healing and cancer progression in Opisthorchis viverrini associated cholangiocarcinoma.

    PubMed

    Botelho, Monica C; Alves, Helena; Richter, Joachim

    2016-07-01

    Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). It was shown previously that O. viverrini-secreted proteins accelerate wound resolution in human cholangiocytes. Recombinant Ov-GRN-1 (O. viverrini-derived gene encoding granulin-like growth factor) induced angiogenesis and accelerated mouse wound healing. Given the striking similarities of wound healing and cancer progression, here we discuss the major implications of this finding for an infection-induced cancer of major public health significance in the developing world. PMID:27130317

  17. Equations and closure methods

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Basic differential equations governing compressible turbulent boundary layer flow are reviewed, including conservation of mass and energy, momentum equations derived from Navier-Stokes equations, and equations of state. Closure procedures were broken down into: (1) simple or zeroth-order methods, (2) first-order or mean field closure methods, and (3) second-order or mean turbulence field methods.

  18. The lateral lesser toe fillet flap for diabetic foot soft tissue closure: surgical technique and case report

    PubMed Central

    Chung, Sze-Ryn; Wong, Keng L.; Cheah, Andre E. J.

    2014-01-01

    Wound closure for the diabetic foot can be challenging and often involves amputation or reconstruction. The authors describe a surgical technique and a case report of lateral lesser toe fillet flap in the management of a diabetic foot wound. The lateral lesser toe fillet flap reconstruction is a reproducible technique that incurs comparatively minimal technical complexity and provides a favorable option in the management of diabetic foot wounds where soft tissue coverage is required. PMID:25527137

  19. Optimizing Wound Bed Preparation With Collagenase Enzymatic Debridement

    PubMed Central

    McCallon, Stanley K.; Weir, Dorothy; Lantis, John C.

    2015-01-01

    Difficult-to-heal and chronic wounds affect tens of millions of people worldwide. In the U.S. alone, the direct cost for their treatment exceeds $25 billion. Yet despite advances in wound research and treatment that have markedly improved patient care, wound healing is often delayed for weeks or months. For venous and diabetic ulcers, complete wound closure is achieved in as few as 25%–50% of chronic or hard-to-heal wounds. Wound bed preparation and the consistent application of appropriate and effective debridement techniques are recommended for the optimized treatment of chronic wounds. The TIME paradigm (Tissue, Inflammation/infection, Moisture balance and Edge of wound) provides a model to remove barriers to healing and optimize the healing process. While we often think of debridement as an episodic event that occurs in specific care giver/patient interface. There is the possibility of a maintenance debridement in which the chronic application of a medication can assist in both the macroscopic and microscopic debridement of a wound. We review the various debridement therapies available to clinicians in the United States, and explore the characteristics and capabilities of clostridial collagenase ointment (CCO), a type of enzymatic debridement, that potentially allows for epithelialization while debriding. It appears that in the case of CCO it may exert this influences by removal of the necrotic plug while promoting granulation and sustaining epithelialization. It is also easily combined with other methods of debridement, is selective to necrotic tissue, and has been safely used in various populations. We review the body of evidence has indicated that this concept of maintenance debridement, especially when combined episodic debridement may add a cost an efficacious, safe and cost-effective choice for debridement of cutaneous ulcers and burn wounds and it will likely play an expanding role in all phases of wound bed preparation. PMID:26442207

  20. Nanofibre Based Smart Pharmaceutical Scaffolds for Wound Repair and Regenerations.

    PubMed

    Dwivedi, Charu; Pandey, Himanshu; Pandey, Avinash C; Ramteke, Pramod W

    2016-01-01

    Chronic wounds and ulcers are posing a devastating manifestation on the socioeconomic status across the globe along with the patient compliance. It reinforces a need for the development of successful alternative treatments for the chronic wound care and ulcer management practices. This review explores the progressive developments being made in the fabrication of electrospun nanofibrous scaffolds towards elimination of microbial infection from chronic wounds to accelerate the wound healing process. Functional three dimensional nanofibrous scaffolds produced by electrospinning have great potential in a wide spectrum of biomedical practices, such as tissue engineering, drug/gene delivery and wound dressing. Moreover, this review also highlights the materials and post modification methods, such as the functionaliation of electrospun nanofibrous scaffolds using growth factors, so that such smart and bioactive nanofibrous scaffolds could be made suitable for wound healing applications. PMID:26666999

  1. Wound healing in porcine skin following low-output carbon dioxide laser irradiation of the incision

    SciTech Connect

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

    1987-06-01

    Wound healing of scalpel incisions to the depth of adipose tissue closed with conventional methods was compared with closure by low-output carbon dioxide laser irradiation. In 3 Pitman-Moore minipigs wound healing was evaluated at intervals from 1 to 90 days by the following methods: clinical variables of wound healing; formation of the basement membrane components bullous pemphigoid antigen, laminin, and fibronectin; and histological evaluation of the regeneration of the epidermis, neovascularization, and elastin and collagen formation. There was no significant difference in healing between wounds closed by the various conventional methods and by the low-output carbon dioxide laser.

  2. Endoscopic vacuum-assisted closure system (E-VAC): case report and review of the literature.

    PubMed

    Borejsza-Wysocki, Maciej; Szmyt, Krzysztof; Bobkiewicz, Adam; Malinger, Stanisław; Świrkowicz, Józef; Hermann, Jacek; Drews, Michał; Banasiewicz, Tomasz

    2015-07-01

    Negative pressure wound therapy (NPWT) has become a standard in the treatment of chronic and difficult healing wounds. Negative pressure wound therapy is applied to the wound via a special vacuum-sealed sponge. Nowadays, the endoscopic vacuum-assisted wound closure system (E-VAC) has been proven to be an important alternative in patients with upper and lower intestinal leakage not responding to standard endoscopic and/or surgical treatment procedures. Endoscopic vacuum-assisted wound closure system provides perfect wound drainage and closure of various kinds of defect and promotes tissue granulation. Our experience has shown that E-VAC may significantly improve the morbidity and mortality rate. Moreover, E-VAC may be useful in a multidisciplinary approach - from upper gastrointestinal to rectal surgery complications. On the other hand, major limitations of the E-VAC system are the necessity of repeated endoscopic interventions and constant presence of well-trained staff. Further, large-cohort studies need to be performed to establish the applicability and effectiveness of E-VAC before routine widespread use can be recommended. PMID:26240633

  3. Endoscopic vacuum-assisted closure system (E-VAC): case report and review of the literature

    PubMed Central

    Borejsza-Wysocki, Maciej; Bobkiewicz, Adam; Malinger, Stanisław; Świrkowicz, Józef; Hermann, Jacek; Drews, Michał; Banasiewicz, Tomasz

    2015-01-01

    Negative pressure wound therapy (NPWT) has become a standard in the treatment of chronic and difficult healing wounds. Negative pressure wound therapy is applied to the wound via a special vacuum-sealed sponge. Nowadays, the endoscopic vacuum-assisted wound closure system (E-VAC) has been proven to be an important alternative in patients with upper and lower intestinal leakage not responding to standard endoscopic and/or surgical treatment procedures. Endoscop