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Sample records for corneal wound healing

  1. Progress in corneal wound healing.

    Science.gov (United States)

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

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

  2. Progress in corneal wound healing

    Science.gov (United States)

    Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

    2015-01-01

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

  3. Genomics of corneal wound healing: a review of the literature.

    Science.gov (United States)

    Maycock, Nick J R; Marshall, John

    2014-05-01

    Corneal wound healing is a complex process: its mechanisms and the underlying genetic control are not fully understood. It involves the integrated actions of multiple growth factors, cytokines and proteases produced by epithelial cells, stromal keratocytes, inflammatory cells and lacrimal gland cells. Following an epithelial insult, multiple cytokines are released triggering a cascade of events that leads to repair the epithelial defect and remodelling of the stroma to minimize the loss of transparency and function. In this review, we examine the literature surrounding the genomics of corneal wound healing with respect to the following topics: epithelial and stromal wound healing (including inhibition); corneal neovascularisation; the role of corneal nerves in wound healing; the endothelium; the role of aquaporins and aptamers. We also examine the effect of ectasia on corneal wound healing with regard to keratoconus and following corneal surgery. A better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design treatments that selectively modulate key phases of the healing process resulting in scars that more closely resemble normal corneal architecture.

  4. Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats.

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    Nagai, Noriaki; Ogata, Fumihiko; Kawasaki, Naohito; Ito, Yoshimasa; Funakami, Yoshinori; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    Hypercalcemia is often observed in postmenopausal women as well as in patients with primary hyperparathyroidism or malignant tumors. In this study, we investigated the relationship between calcium ion (Ca(2+)) levels in lacrimal fluid and the rate of corneal wound healing in hypercalcemia using ovariectomized (OVX) rat debrided corneal epithelium. We also determined the effects of Ca(2+) levels on cell adhesion, proliferation and viability in a human cornea epithelial cell line (HCE-T). The calcium content in bones of OVX rats decreased after ovariectomy. Moreover, the Ca(2+) content in the blood of OVX rats was increased 1 month after ovariectomy, and decreased. The Ca(2+) content in the lacrimal fluid of OVX rats was also increased after ovariectomy, and then decreased similarly as in blood. Corneal wound healing in OVX rats was delayed in comparison with Sham rats (control rats), and a close relationship was observed between the Ca(2+) levels in lacrimal fluid and the rate of corneal wound healing in Sham and OVX rats (y=-0.7863x+8.785, R=0.78, n=25). In addition, an enhancement in Ca(2+) levels caused a decrease in the viability in HCE-T cells. It is possible that enhanced Ca(2+) levels in lacrimal fluid may cause a decrease in the viability of corneal epithelial cells, resulting in a delay in corneal wound healing. These findings provide significant information that can be used to design further studies aimed at reducing corneal damage of patients with hypercalcemia.

  5. Acacia honey accelerates in vitro corneal ulcer wound healing model.

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    Abd Ghafar, Norzana; Ker-Woon, Choy; Hui, Chua Kien; Mohd Yusof, Yasmin Anum; Wan Ngah, Wan Zurinah

    2016-07-29

    The study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts. Stromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0.025 % AH. Wound areas were recorded at day 0, 3 and 6 post wound creation. Genes and proteins associated with wound healing and differentiation such as aldehyde dehydrogenase (ALDH), vimentin, alpha-smooth muscle actin (α-SMA), collagen type I, lumican and matrix metalloproteinase 12 (MMP12) were evaluated using qRT-PCR and immunocytochemistry respectively. Cells cultured with AH-enriched FDS media achieved complete wound closure at day 6 post wound creation. The cells cultured in AH-enriched FDS media increased the expression of vimentin, collagen type I and lumican genes and decreased the ALDH, α-SMA and MMP12 gene expressions. Protein expression of ALDH, vimentin and α-SMA were in accordance with the gene expression analyses. These results demonstrated AH accelerate corneal fibroblasts migration and differentiation of the in vitro corneal ulcer model while increasing the genes and proteins associated with stromal wound healing.

  6. Heat-shock protein expression in canine corneal wound healing.

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    Peterson, Cornelia W M; Carter, Renee T; Bentley, Ellison; Murphy, Christopher J; Chandler, Heather L

    2016-05-01

    Heat-shock proteins, particularly the 70-kDa member (Hsp70), have been implicated in facilitating wound healing in multiple tissues. Expression and localization of three HSPs were assessed in normal and wounded canine corneas to elucidate a role in epithelial healing. Paraffin-embedded normal corneas, acute and repeatedly abraded corneas, and keratectomies of spontaneous chronic corneal epithelial defects (SCCEDs) were subjected to routine immunohistochemistry for Hsp27, 47, and 70 expression. Ex vivo corneal defects were created and treated with anti-HSPs or IgG controls, and wound healing was monitored. Primary cultures of canine corneal stromal fibroblasts and corneal epithelial cells were treated with exogenous Hsp70, and an artificial wound was created in vitro to monitor restoration of the monolayer. Normal canine corneas exhibited constitutive expression of all HSPs evaluated. Inducible expression was demonstrated in acutely wounded tissues, and expression in the chronically abraded corneas was relocalized. All HSP expression was below the limits of detection in the epithelium of SCCED samples. Inhibition of HSPs in culture resulted in delayed wound healing when compared to controls. Hsp70-treated fibroblasts demonstrated significantly (P healing response, and suppressed expression may contribute to the pathophysiology of nonhealing defects. © 2015 American College of Veterinary Ophthalmologists.

  7. In vivo fluorescent labeling of corneal wound healing fibroblasts.

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    Gatlin, Joel; Melkus, Michael W; Padgett, Angela; Petroll, W Matthew; Cavanagh, H Dwight; Garcia, J Victor; Jester, James V

    2003-03-01

    Numerous studies have shown that fibroblasts play an important role in corneal wound healing, however, the dynamic cellular events underlying wound tissue organization and contraction remain unclear. The purpose of this study was to develop a system to enable live cell imaging of corneal wound healing fibroblasts in situ. To this end, concentrated preparations of an RD114 pseudotyped MLV-based vector expressing the enhanced green fluorescent protein (EGFP) were evaluated in vitro for gene transfer efficiency using cultured rabbit corneal keratocytes. Primary rabbit keratocytes were efficiently labeled in vitro (up to 50% EGFP(+)) at a low multiplicity of infection (MOI=10). To evaluate this gene transfer vector in vivo, rabbit corneal fibroblasts were transduced by direct application of vector supernatant to injured corneas following lamellar keratectomy. Fluorescent fibroblasts were then visualized in situ using epifluorescence microscopy and multiphoton confocal microscopy of excised fresh tissue at multiple time points from 14 days to four months following gene transfer. Fourteen days post-transduction, labeled fibroblasts expressing EGFP were readily detectable by fluorescence microscopy. Detectable fluorescence was noted up to eight weeks post-transduction. Labeled fibroblasts were detected in clusters located predominantly along the margin circumscribing the wound and to a lesser extent within the wound area. Cell growth in clusters was suggestive of the expansion of individual transduced clones. High-resolution imaging showed fluorescent fibroblasts to have a broad, flattened, dendritic morphology, distinct from the spindle shape of cultured fibroblasts. Utilizing multiphoton confocal microscopy, three-dimensional imaging of viable, labeled cells showed wound healing fibroblasts to be extensively interconnected and multi-layered within the corneal wound. These results demonstrate that rabbit corneal fibroblasts can be efficiently transduced in vitro and in

  8. Corneal wound healing is compromised by immunoproteasome deficiency.

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    Deborah A Ferrington

    Full Text Available Recent studies have revealed roles for immunoproteasome in regulating cell processes essential for maintaining homeostasis and in responding to stress and injury. The current study investigates how the absence of immunoproteasome affects the corneal epithelium under normal and stressed conditions by comparing corneas from wildtype (WT mice and those deficient in two immunoproteasome catalytic subunits (lmp7(-/-/mecl-1(-/-, L7M1. Immunoproteasome expression was confirmed in WT epithelial cells and in cells of the immune system that were present in the cornea. More apoptotic cells were found in both corneal explant cultures and uninjured corneas of L7M1 compared to WT mice. Following mechanical debridement, L7M1 corneas displayed delayed wound healing, including delayed re-epithelialization and re-establishment of the epithelial barrier, as well as altered inflammatory cytokine production compared to WT mice. These results suggest that immunoproteasome plays an important role in corneal homeostasis and wound healing.

  9. Corneal cellular proliferation and wound healing

    OpenAIRE

    Gan, Lisha

    2000-01-01

    Background. Cellular proliferation plays an important role in both physiological and pathological processes. Epithelial hyperplasia in the epithelium, excessive scar formation in retrocorneal membrane formation and neovascularization are examples of excessive proliferation of cornea cells. Lack of proliferative ability causes corneal degeneration. The degree of proliferative and metabolic activity will directly influence corneal transparency and very evidently refractive res...

  10. Hevin plays a pivotal role in corneal wound healing.

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    Shyam S Chaurasia

    Full Text Available BACKGROUND: Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK in hevin-null (hevin(-/- mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin to rescue the stromal cellular components damaged by the excimer laser. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and hevin (-/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM, transmission electron microscopy (TEM, immunohistochemistry (IHC and western blotting (WB. IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin (-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts, inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. CONCLUSIONS/SIGNIFICANCE: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin (-/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued

  11. [Macroscopic observations on corneal epithelial wound healing in the rabbit].

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    Hayashi, K

    1991-02-01

    A newly-developed macroscope was applied to observe the healing process of corneal epithelial wound in vivo. After removing epithelium of the central cornea, the changes of the corneal surface were observed with the macroscope and the findings were compared with histological examinations. At 12 hours after abrasion, areas unstained with Richardson's staining (R staining) appeared. In the histological section, a single layer of regenerating epithelial cells covered the same area. At 24 and 36 hours after abrasion, the epithelial defects became smaller but surrounding epithelium was rough and showed dot-like staining with R solution. By 2 days, the epithelial defects disappeared. On macroscopic observation, the central corneal surface showed a pavement-like appearance. Histology revealed that the regenerating epithelium still consisted of one or two layers. At 3 days, dot-like stainings were present only in the center and the corneal surface appeared considerably smooth. Histology also showed that regenerating epithelium became columnar and multilayered, thereby suggesting stratification. By 7 days, the abraded corneal surface had recovered its smooth appearance. Histologic sections also demonstrated that the epithelium had regained its normal structure. Thus, using this macroscope, findings suggesting the process of epithelial migration and proliferation could be observed.

  12. Corneal Wound Healing Requires IKB kinase β Signaling in Keratocytes.

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    Chen, Liang; Mongan, Maureen; Meng, Qinghang; Wang, Qin; Kao, Winston; Xia, Ying

    2016-01-01

    IkB kinase β (IKKβ) is a key signaling kinase for inflammatory responses, but it also plays diverse cell type-specific roles that are not yet fully understood. Here we investigated the role of IKKβ in the cornea using Ikkβ(ΔCS) mice in which the Ikkβ gene was specifically deleted in the corneal stromal keratocytes. The Ikkβ(ΔCS) corneas had normal morphology, transparency and thickness; however, they did not heal well from mild alkali burn injury. In contrast to the Ikkβ(F/F) corneas that restored transparency in 2 weeks after injury, over 50% of the Ikkβ(ΔCS) corneas failed to fully recover. They instead developed recurrent haze with increased stromal thickness, severe inflammation and apoptosis. This pathogenesis correlated with sustained myofibroblast transformation with increased α smooth muscle actin (α-SMA) expression, higher levels of senescence β-Gal activity and scar tissue formation at the late stage of wound healing. In addition, the Ikkβ(ΔCS) corneas displayed elevated expression of hemo-oxygenase-1 (HO-1), a marker of oxidative stress, and activation of stress signaling pathways with increased JNK, c-Jun and SMAD2/3 phosphorylation. These data suggest that IKKβ in keratocytes is required to repress oxidative stress and attenuate fibrogenesis and senescence in corneal wound healing.

  13. Corneal Wound Healing Requires IKB kinase β Signaling in Keratocytes.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available IkB kinase β (IKKβ is a key signaling kinase for inflammatory responses, but it also plays diverse cell type-specific roles that are not yet fully understood. Here we investigated the role of IKKβ in the cornea using Ikkβ(ΔCS mice in which the Ikkβ gene was specifically deleted in the corneal stromal keratocytes. The Ikkβ(ΔCS corneas had normal morphology, transparency and thickness; however, they did not heal well from mild alkali burn injury. In contrast to the Ikkβ(F/F corneas that restored transparency in 2 weeks after injury, over 50% of the Ikkβ(ΔCS corneas failed to fully recover. They instead developed recurrent haze with increased stromal thickness, severe inflammation and apoptosis. This pathogenesis correlated with sustained myofibroblast transformation with increased α smooth muscle actin (α-SMA expression, higher levels of senescence β-Gal activity and scar tissue formation at the late stage of wound healing. In addition, the Ikkβ(ΔCS corneas displayed elevated expression of hemo-oxygenase-1 (HO-1, a marker of oxidative stress, and activation of stress signaling pathways with increased JNK, c-Jun and SMAD2/3 phosphorylation. These data suggest that IKKβ in keratocytes is required to repress oxidative stress and attenuate fibrogenesis and senescence in corneal wound healing.

  14. Histology of corneal wound healing after deep lamellar endothelial keratoplasty

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    Chaoran Zhang

    2008-03-01

    Full Text Available Chaoran Zhang1, Jianjiang Xu1, Rongjia Chen21Ophthalmology Department, 2Pathology Department, Eye and Ear Nose Throat Hospital, Fudan University, Shanghai, ChinaAbstract: Deep lamellar endothelial keratoplasty (DLEK has become an alternative procedure for bullous keratopathy. Herein, the histopathological characteristics of corneal wound healing after DLEK were reported. A 71-year-old man suffering from left psuedophakia bullous keratopathy received small incision DLEK. Twenty months later, another penetrating keratoplasty (PK was performed because of the graft failure. The histopathology of the corneal button removed during PK demonstrated the regularity of stromal fiber alignment at the graft interface. Fibrotic repair was limited to the peripheral margins.Keywords: Deep lamellar endothelial keratoplasty, DLEK, bullous keratopathy, penetrating keratoplasty

  15. Effects of different sutures on fibrosis and wound healing in a rabbit model of corneal wounds.

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    Li, Ying; Chen, Hui J; Zhang, Hua; Wu, Jian G; Hu, Yun T; Ma, Zhi Z

    2016-11-01

    The aim of the study was to investigate wound healing and scar formation in rabbit corneal lamellar wounds repaired with simple interrupted sutures (SIS) or horizontal mattress sutures (HMS). Two parallel 'I'-shaped lamellar cornea wounds were created in one eye of 40 white New Zealand rabbits, while 5 uninjured rabbits were sacrificed to serve as normal controls. One side of the wounds, in the test rabbits, was closed with SIS, while the other side was treated with HMS. Ten days later, the stitches were removed under anesthesia. The animals were sacrificed on days 14 and 21, and months 3 and 6 after the suturing surgery, and corneal samples were subjected to histological and immunofluorescent studies: α-smooth muscle actin (α-SMA) and vimentin were used to detect myofibroblasts and fibroblasts, respectively, and collagen type I and III was used to detect extracellular matrix (ECM) deposition. Relevant mRNA levels were assessed by quantitative polymerase chain reaction (qPCR) to elucidate the differences in wound healing and formation of fibrosis. Macroscopic and hematoxylin and eosin staining observations showed that the two sides of the wounds developed the most prominent fibrotic tissue on day 21. The immunofluorescence and qPCR results showed that HMS wounds produced increased α-SMA, vimentin and collagen type III compared to the SIS wounds on day 14 or 21. The collagen type I expression showed no distinctive difference in SIS and HMS wounds. In conclusion, corneal lamellar wounds treated with SIS developed less fibrotic-related proteins and related mRNA in the early stages of wound healing than wounds treated with HMS. Although differences were not distinct after 3 months, the results of the present study suggest a benefit in choosing SIS over HMS, as at least the initial fibrotic process seems more benign with SIS. Corneal wounds should be carefully sutured, ensuring the tissue is well aligned.

  16. Downregulation of PTEN at Corneal Wound Sites Accelerates Wound Healing through Increased Cell Migration

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    Cao, Lin; Graue-Hernandez, Enrique O.; Tran, Vu; Reid, Brian; Pu, Jin; Mannis, Mark J.

    2011-01-01

    Purpose. The PI3K/Akt pathway is required for cell polarization and migration, whereas the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has inhibitory effects on the PI3K/Akt pathway. The authors therefore hypothesized that wounding would downregulate PTEN and that this downregulation would enhance wound healing. Methods. In human corneal epithelial (HCE) cell monolayer and rat cornea scratch wound models, the authors investigated PTEN and Akt expression using Western blot and immunofluorescence analyses. The effects of PTEN and PI3K inhibitors dipotassium bisperoxo (picolinato) oxovanadate (bpv(pic)) and LY294002 on cell migration and wound closure were investigated using time-lapse imaging. Finally, the authors investigated the effect of PTEN inhibition on wound healing in whole rat eyes. Results. In HCE cell monolayer and rat cornea, PTEN was downregulated at the wound edges within 30 minutes of wounding. The downregulation of PTEN was causal in a simultaneous increase in Akt activation, which was responsible for a significant increase in individual cell migration rate from 8.8 μm/h to 17.3 μm/h. An increased migration rate was maintained for 20 hours. PTEN inhibition significantly enhanced the wound healing rate in the HCE cell monolayer from 10 minutes onward after treatment and reduced the healing time in eye organ culture from 30 to 20 hours. Conclusions. Injury to the corneal epithelium downregulates the expression of PTEN at wound edges, allowing increased PI3K/Akt signaling, thereby contributing to a significant enhancement of cell migration and wound healing. These results suggest that PTEN inhibition may be an effective treatment for corneal injury. PMID:21212174

  17. Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

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    Tsai, Ching-Yao; Woung, Lin-Chung; Yen, Jiin-Cherng; Tseng, Po-Chen; Chiou, Shih-Hwa; Sung, Yen-Jen; Liu, Kuan-Ting; Cheng, Yung-Hsin

    2016-01-01

    Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.

  18. ICAM-1 is necessary for epithelial recruitment of gammadelta T cells and efficient corneal wound healing.

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    Wound healing and inflammation are both significantly reduced in mice that lack gammadelta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gammadelta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epi...

  19. [Corneal wound healing after experimental penetrating keratoplasty after excimer laser trephination in free form].

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    Schmitz, K; Lang, G K; Behrens-Baumann, W

    2006-12-01

    The postoperative clinical course after penetrating keratoplasty and trephination in free form using a guided excimer laser beam has been published before. Here the findings of light-microscopy comparing corneal wound healing after experimental penetrating keratoplasty after laser trephination and after conventional mechanical trephination are presented. Homologous penetrating keratoplasty was performed on 12 NZW rabbits (6 animals with mechanical trephination, 6 animals with excimer laser trephination). The cutting edges achieved by both trephination techniques were examined by light microscopy in the remaining donor rings. During the postoperative follow-up animals were sacrificed at 3 and 6 weeks and at 3 months. Corneal specimens were retrieved and corneal healing processes were evaluated by light microscopy. The cutting edges of corneal excisions with the excimer laser demonstrated a high precision with only minimal collateral damage to adjacent tissue structures. At the different intervals both trephination groups demonstrated comparable stages of corneal wound healing regarding epithelial regeneration, stromal fibroblast migration with collagen synthesis and Descemet repair by endothelial synthesis of basement membrane. After 6 months corneal specimens of both groups demonstrated complete healing with nearly parallel orientation of newly synthesised collagen lamellae. Corneal thickness in the wound areas did not differ significantly from normal corneal tissue. Experimental follow-up studies to evaluate the feasibility of the developed technology of laser trephination in the living eye have shown no differences between conventional mechanical and excimer laser trephination with a guided beam. The present histology study also does not demonstrate any significant differences in corneal wound healing between the two trephination groups. Although excimer laser trephination along metal masks has now been established for several years, the here presented technique

  20. Impaired corneal wound healing associated with ketorolac 0.5% after uncomplicated extracapsular cataract extraction.

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    Arey, Mark L; Sullivan, Brian R; Reinert, Carol G; McCulley, James P

    2007-12-01

    To describe an apparent association between the use of ketorolac 0.5% (Acular; Allergan) for cystoid macular edema (CME) prophylaxis and impaired corneal wound healing in patients undergoing extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation. A retrospective case series reviewing 7 eyes of 7 patients who underwent uncomplicated ECCE with IOL implantation and were treated postoperatively with ketorolac 0.5% 4 times daily as a prophylactic measure against CME. Patients were treated with ketorolac 0.5% 4 times a day for an average of 30 days (range, 20-44 days) after uncomplicated ECCE with IOL implantation. Two eyes developed postoperative endophthalmitis necessitating vitreous tap with intravitreal antibiotic injection; 1 eye went on to require pars plana vitrectomy with corneal wound resuturing. One eye developed corneal wound dehiscence that required wound resuturing in the operating room. One eye developed an inadvertent filtering bleb despite the lack of postoperative suture lysis. Three others were followed up closely postoperatively with slit-lamp evidence of impaired wound healing, manifested by wound avascularity and/or wound gape, and did not require surgical intervention. The use of nonsteroidal anti-inflammatory agents for prophylaxis of CME after cataract surgery is an evolving trend. This retrospective case series showed a possible link between the use of ketorolac 0.5% and impaired corneal wound healing, and caution is urged in the liberal use of this agent postoperatively after ECCE.

  1. Effect of topical administration of tramadol on corneal wound healing in rats.

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    Cuvas Apan, Ozgun; Ozer, Murat Atabey; Takir, Selcuk; Apan, Alparslan; Sengul, Demet

    2016-10-01

    In this study, we aimed to investigate the effects of topical tramadol administration on corneal wound healing, and examine ophthalmic structures and intraocular pressure 7 days after tramadol administration. The experiments were conducted on eight male Wistar rats (250-300 g). After ophthalmic examination, epithelial cell layers in the central cornea were wounded. Rats received 30 μL of tramadol hydrochloride in one eye (Group Tramadol) and the same volume of vehicle in the other (Group Control) every 12 h for 7 days. Both eyes were stained with fluorescein dye, photographed, and wound area was calculated every 8 h until complete healing was observed. Eye blink frequency and corneal reflex tests were measured before and after drug administrations. After 7 days, slit lamp biomicroscopy, fundoscopy, Goldmann applanation tonometry, and histological evaluation were performed. There was no difference in the corneal wound healing rates between the tramadol and control groups. Reduction in wound area over time was also similar; group-time interaction was insignificant (F = 738.911; p = 0.225). Tramadol application resulted in blinking and blepharospasm for 30 s, but vehicle did not. Corneal reflex was intact and eye blink frequency test results were similar in all measurement times in both groups. Slit lamp biomicroscopy, fundoscopy, and intraocular pressures were within normal range. Corneal cells appeared unaffected by the repeated doses of tramadol for 7 days. Topical tramadol application on the cornea did not cause any side effect, except for initial temporary blinking and blepharospasm. Corneal wound healing was not affected, either.

  2. NK cells modulate the inflammatory response to corneal epithelial abrasion and thereby support wound healing

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    Natural killer cells are lymphocytes of the innate immune system that have crucial cytotoxic and regulatory roles in adaptive immunity and inflammation. Herein, we consider a role for these cells in corneal wound healing. After a 2-mm central epithelial abrasion of the mouse cornea, a subset of clas...

  3. Effect of platelet-derived growth factor on rabbit corneal wound healing.

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    Stern, M E; Waltz, K M; Beurerman, R W; Ghosn, C R; Mantras, C E; Nicolson, M; Assouline, M; Stern, K L; Wheeler, L A

    1995-01-01

    Human recombinant platelet-derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet-derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 microg/ml when compared with control; however, the platelet-derived growth factor-BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet-derived growth factor-BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet-derived growth factor-BB-treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet-derived growth factor exhibited a dose-dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet-derived growth factor is active in the corneal wound healing process.

  4. Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells

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    Jing Zhong

    2016-01-01

    Full Text Available Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.

  5. Hyaluronate Acid-Dependent Protection and Enhanced Corneal Wound Healing against Oxidative Damage in Corneal Epithelial Cells.

    Science.gov (United States)

    Zhong, Jing; Deng, Yuqing; Tian, Bishan; Wang, Bowen; Sun, Yifang; Huang, Haixiang; Chen, Ling; Ling, Shiqi; Yuan, Jin

    2016-01-01

    Purpose. To evaluate the effects and mechanism of exogenous hyaluronate (HA) in promoting corneal wound healing. Methods. Human corneal epithelial cells (HCECs) were incubated with different concentrations of HA to evaluate their efficiency in promoting cell migration and their modulation of repair factors. After inducing hyperosmolar conditions, the cell morphologies, cell apoptosis, and expression levels of TNF-α and MMP-9 were detected to assess the protective role of HA. Corneal epithelium-injured rat models were established to test the therapeutic effects of 0.3% HA. Then, the wound healing rates, the RNA expression levels of inflammatory cytokines, and repair factors were examined. Results. HCECs in the 0.03% and 0.3% HA groups showed fewer morphological alterations and lower rates of cell apoptosis following preincubation with HA under hyperosmolar conditions, as well as the expression levels of MMP-9 and TNF-α. In the rat model, the areas of fluorescein staining in the corneas of 0.3% HA group were significantly smaller than the control group. The expression levels of IL-1β and MMP-9 were decreased, while CD44 and FN were increased in the 0.3% HA group. Conclusion. HA enhanced corneal epithelial cell wound healing by promoting cell migration, upregulating repair responses, and suppressing inflammatory responses.

  6. Pirfenidone nanoparticles improve corneal wound healing and prevent scarring following alkali burn.

    Directory of Open Access Journals (Sweden)

    Sushovan Chowdhury

    Full Text Available PURPOSE: To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn. METHODS: Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide (PLGA nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry. RESULTS: Pirfenidone prevented (P<0.05 increase in TGF β induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05 reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn. CONCLUSION: Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases.

  7. Corneal Fibroblast Migration Patterns During Intrastromal Wound Healing Correlate With ECM Structure and Alignment.

    Science.gov (United States)

    Petroll, W Matthew; Kivanany, Pouriska B; Hagenasr, Daniela; Graham, Eric K

    2015-11-01

    To assess keratocyte backscattering, alignment, morphology, and connectivity in vivo following a full-thickness corneal injury using the Heidelberg Retina Tomograph Rostock Cornea Module (HRT-RCM), and to correlate these findings with en bloc three-dimensional (3-D) confocal fluorescence and second harmonic generation (SHG) imaging. Rabbit corneas were scanned in vivo both before and 3, 7, 14, and 28 days after transcorneal freeze injury (FI), which damages all corneal cell layers. Corneal tissue was also fixed and labeled for f-actin and nuclei en bloc, and imaged using 3-D confocal fluorescence microscopy and SHG imaging. Using the modified HRT-RCM, full-thickness scans of all cell layers were consistently obtained. Following FI, stromal cells repopulating the damaged tissue assumed an elongated fibroblastic morphology, and a significant increase in cellular light scattering was measured. This stromal haze gradually decreased as wound healing progressed. Parallel, interconnected streams of aligned corneal fibroblasts were observed both in vivo (from HRT-RCM reflection images) and ex vivo (from f-actin and nuclear labeling) during wound healing, particularly in the posterior cornea. Second harmonic generation imaging demonstrated that these cells were aligned parallel to the collagen lamellae. The modified HRT-RCM allows in vivo measurements of sublayer thickness, assessment of cell morphology, alignment and connectivity, and estimation of stromal backscatter during wound healing. In this study, these in vivo observations led to the novel finding that the pattern of corneal fibroblast alignment is highly correlated with lamellar organization, suggesting contact guidance of intrastromal migration that may facilitate more rapid wound repopulation.

  8. IκB kinase β regulates epithelium migration during corneal wound healing.

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    Liang Chen

    Full Text Available The IKKβ is known to regulate transcription factor NF-κB activation leading to inflammatory responses. Recent gene knockout studies have shown that IKKβ can orchestrate local inflammatory responses and regulate homeostasis of epithelial tissues. To investigate whether IKKβ has an intrinsic role in epithelial cells, we established an in vivo system in the immune privileged corneal epithelium. We generated triple transgenic Krt12(rtTA/rtTAt/tet-O-Cre/Ikkβ(F/F (Ikkβ(ΔCE/ΔCE mice by crossing the Krt12-rtTA knock-in mice, which express the reverse tetracycline transcription activator in corneal epithelial cells, with the tet-O-Cre and Ikkβ(F/F mice. Doxycycline-induced IKKβ ablation occurred in corneal epithelial cells of triple transgenic Ikkβ(ΔCE/ΔCE mice, but loss of IKKβ did not cause ocular abnormalities in fetal development and postnatal maintenance. Instead, loss of IKKβ significantly delayed healing of corneal epithelial debridement without affecting cell proliferation, apoptosis or macrophage infiltration. In vitro studies with human corneal epithelial cells (HCEpi also showed that IKKβ was required for cytokine-induced cell migration and wound closure but was dispensable for cell proliferation. In both in vivo and in vitro settings, IKKβ was required for optimal activation of NF-κB and p38 signaling in corneal epithelial cells, and p38 activation is likely mediated through formation of an IKKβ-p38 protein complex. Thus, our studies in corneal epithelium reveal a previously un-recognized role for IKKβ in the control of epithelial cell motility and wound healing.

  9. The effect of subconjunctival platelet-rich plasma on corneal epithelial wound healing.

    Science.gov (United States)

    Tanidir, Suzan Tayfun; Yuksel, Nursen; Altintas, Ozgul; Yildiz, Demir Kursat; Sener, Ender; Caglar, Yusuf

    2010-06-01

    Single-dose subconjunctival platelet-rich plasma (sPRP) injections with or without antibiotic treatment were investigated for their effect on corneal epithelial wound healing in a rabbit model. A total of 24 rabbits were used in this study. After collecting intracardiac blood samples from 16 rabbits, platelet-rich plasma was obtained by centrifugation. Animals were divided into 3 groups. A mechanical corneal epithelial defect of 7-mm diameter was created on the central cornea of the right eye of each animal. Group 1 (n = 8) received only sPRP, whereas group 2 (n = 8) received sPRP with topical antibiotic throughout the study. The third group (n = 8) served as the control group. Each animal was examined daily under biomicroscope for 10 days. Epithelial defect was measured in horizontal and vertical diameter with a 1/100 sensitive micrometer, and area of the defect was calculated. One animal was sacrificed in each group on the third and seventh day, and all remaining animals were sacrificed on the 10th day. Corneal histopathology was investigated for epithelial regeneration, presence of inflammation, and structural integrity of fibroblasts. All data were statistically analyzed for difference between the study groups. Group 1 had a significantly smaller size in horizontal and vertical defect diameters on each day as compared with the control group. Healing of the epithelial defect in group 1 was found to be significantly different than that in the control group (P fibroblast migration, quicker epithelial regeneration, and less inflammation in group 1 as compared with the other 2 groups. sPRP seems to improve corneal epithelial wound healing. However, antibiotic and sPRP combination may have a retarded healing effect as compared with platelet-rich plasma alone.

  10. Epidermal growth factor (EGF)-induced corneal epithelial wound healing through nuclear factor κB subtype-regulated CCCTC binding factor (CTCF) activation.

    Science.gov (United States)

    Wang, Ling; Wu, Xiaolin; Shi, Ting; Lu, Luo

    2013-08-23

    Epidermal growth factor (EGF) plays an important role in corneal epithelial migration and proliferation to improve the wound healing process. This study aimed to understand the role of NFκB in EGF-induced corneal epithelial wound healing through regulation of CTCF activity, which plays important roles in cell motility and migration to promote wound healing. The effect of NFκB p50 on corneal epithelial wound healing was investigated by comparing the eyes of wild-type and p50 knockout mice. We found that there was a significant retardation in corneal epithelial wound healing in the corneas of p50 knockout mice. Wound closure rates were measured in human corneal epithelial cells transfected with an NFκB activation-sensitive CTCF expression construct to demonstrate the effect of human CTCF expression under the control of EGF-induced NFκB activation on wound healing. EGF stimulation activated NFκB, which directly triggered the expression of the exogenous human CTCF in transfected cells and, subsequently, promoted human corneal epithelial cell motility, migration, and wound healing. Overexpression of CTCF in corneal epithelial cells and mouse corneas significantly enhanced the wound healing process. Furthermore, the effect of overexpressing NFκB p50 in corneal epithelial cells on the promotion of wound healing was abolished by knockdown of CTCF with CTCF-specific shRNA. Thus, a direct regulatory relationship between EGF-induced NFκB p50 and CTCF activation affecting corneal epithelial wound healing has been established, indicating that CTCF is, indeed, a NFκB p50-targeted and effective gene product in the core transcriptional network downstream from the growth factor-induced NFκB signaling pathway.

  11. Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

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    Keping Xu

    2011-02-01

    Full Text Available Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK was removed and carboxymethylcellulose (CMC was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%, bromfenac 0.09%, and nepafenac 0.1%.Methods: Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM, corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control, or MEM (negative control, followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels. Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results: The mean (±SD original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments, 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM. In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%, 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P < 0.01 vs MEM and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs

  12. Corneal wound healing after ultraviolet-A/riboflavin collagen cross-linking: a rabbit study.

    Science.gov (United States)

    Salomão, Marcella Q; Chaurasia, Shyam S; Sinha-Roy, Abhijit; Ambrósio, Renato; Esposito, Andrew; Sepulveda, Ricardo; Agrawal, Vandana; Wilson, Steven E

    2011-06-01

    To investigate corneal wound healing following ultraviolet-A (UVA)/riboflavin corneal collagen cross-linking (CXL) in rabbit corneas. Thirty-six rabbits were enrolled in the study. Animals were divided into three treatment groups and corneas were analyzed at 24 hours and 4 weeks postoperatively. Thus, each group had 6 rabbits at each time point. Treatment groups were: 1) standard UVA+riboflavin CXL, 2) UVA alone, and 3) riboflavin alone. One eye of each rabbit served as an untreated control eye. TUNEL assay was performed to detect stromal cell apoptosis. Immunocytochemistry was performed to detect the inflammatory marker CD11b expressed in monocytes and the alpha-smooth muscle actin (SMA) marker expressed in myofibroblasts. At 24 hours, corneas from the UVA+riboflavin CXL group had significantly more apoptosis than the UVA alone and riboflavin alone groups. Eyes from all three groups had significantly more inflammatory cell influx into the cornea than unwounded controls. Four weeks after the procedure, many corneas in the UVA+riboflavin CXL group had mild haze, but very few SMA-positive myofibroblasts could be detected in the central cornea. Riboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts. Copyright 2011, SLACK Incorporated.

  13. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Science.gov (United States)

    Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

    2015-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  14. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Directory of Open Access Journals (Sweden)

    Chang Rae Rho

    Full Text Available Granulocyte-macrophage colony-stimulating factor (GM-CSF is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs. We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF. An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml. MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  15. Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Jong; Soo; Lee; Seung; Uk; Lee; Cheng-Ye; Che; Ji-Eun; Lee

    2015-01-01

    AIM: To investigate the cytotoxic effect on human corneal epithelial cells(HCECs) and the ability to faciliate corneal epithelial wound healing of carboxymethylcellulose(CMC) and hyaluronic acid(HA).METHODS: HCECs were exposed to 0.5% CMC(Refresh plus, Allergan, Irvine, California, USA) and 0.1% and 0.3%HA(Kynex , Alcon, Seoul, Korea, and Hyalein mini,Santen, Osaka, Japan) for the period of 30 min, and 4, 12,and 24 h. Methyl thiazolyl tetrazoiun(MTT)-based calorimetric assay was performed to assess the metabolic activity of cellular proliferation and lactate dehydrogenase(LDH) leakage assay to assess the cytotoxicity. apoptotic response was evaluated with flow cytometric analysis and fluorescence staining with Annexin V and propiodium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. The wound widths were measured 24 h after confluent HCECs were scratch wounded.RESULTS: The inhibitory effect of human corneal epithelial proliferation and cytotoxicity showed the time-dependent response but no significant effect. Apoptosis developed in flow cytometry and apoptotic cells weredemonstrated in fluorescent micrograph. The damaged HCECs were detached from the bottom of the dish and showed the well-developed vacuole formations. Both CMC and HA stimulated reepithehlialization of HCECs scratched, which were more observed in CMC.CONCLUSION: CMC and HA, used in artificial tear formulation, could be utilized without any significant toxic effect on HCECs. Both significantly stimulated HCEC reepithelialization of corneal wounds.

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

    Science.gov (United States)

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

    2017-03-09

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

  17. Determination of Novel Strategies for Hastening Corneal Wound Healing and Reducing Tissue Inflammation

    Science.gov (United States)

    2011-10-01

    concentrations ranging from 1 to 10 f.!M, in the 375 mOsm medium, hastened complete TEER restoration to its isotonic control level. It occmTed as... CONTRACTING ORGANIZATION: REPORT DATE: October 2011 TYPE OF REPORT: Final PREPARED FOR...Wound W81XWH-09-2-0162 5a. CONTRACT NUMBER Healing and Reducing Tissue Inflammation 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  18. Comparative study of the effects of recombinant human epidermal growth factor and basic fibroblast growth factor on corneal epithelial wound healing and neovascularization in vivo and in vitro.

    Science.gov (United States)

    Yan, Limeng; Wu, Wei; Wang, Zhichong; Li, Chaoyang; Lu, Xiaohe; Duan, Hucheng; Zhou, Jin; Wang, Xiaoran; Wan, Pengxia; Song, Yiyue; Tang, Jing; Han, Yu

    2013-01-01

    This study was undertaken to investigate the effects of recombinant human epidermal growth factor (rhEGF) and basic fibroblast growth factor (bFGF) on corneal wound healing and neovascularization (CNV). The positive effects of 10 ng/ml rhEGF and bFGF on the proliferation of corneal epithelial cells (SD-HCEC1s), rabbit keratocyte cells (RKCs) and human umbilical vein endothelial cells (HUVECs) as well as the effects on the migration capacity on HUVECs were observed. An animal central corneal wound and CNV model was established in rabbits. One eye of each group was chosen randomly for topical administration of rhEGF, bFGF or normal saline, and variability in the area of corneal epithelial wound healing and CNV was observed. The optimal concentration of rhEGF and bFGF for the proliferation of corneal epithelial cells was 10 ng/ml. The promotive effect of 10 ng/ml rhEGF on the proliferation of RKCs and HUVECs was less than that of 10 ng/ml bFGF. In the animal experiment, the healing rate of the corneal epithelium in the rhEGF group was better than in the other groups on day 1. On day 3, the healing rates of the 3 groups were nearly equal. The CNV area in the rhEGF group was less than that of the bFGF group. rhEGF and bFGF both had promotive effects on corneal epithelial wound healing, but rhEGF had a weaker promotive effect on CNV than bFGF. With long-term application of growth factor drugs, rhEGF is suggested for lessening the growth of CNV. Copyright © 2012 S. Karger AG, Basel.

  19. [The role of connective tissue growth factor, transforming growth factor and Smad signaling pathway during corneal wound healing].

    Science.gov (United States)

    Yang, Yong-mei; Wu, Xin-yi; Du, Li-qun

    2006-10-01

    To study the expression and location of connective tissue growth factor (CTGF) and transforming growth factor-beta(1) (TGF-beta(1)) protein and mRNA in rabbit cornea during the wound healing process. To assess the interaction between CTGF and TGF-beta(1), as well as the Smad signaling pathway involved. Twenty-six Albino white rabbits were used as experimental animals and randomly divided into 4 groups: (1) CONTROL GROUP: two rabbits. (2) Simple corneal injury group: a 3 mm diameter and 0.05 mm depth corneal tissue was excised by a trephine at the anterior central cornea as a corneal wound model in 12 rabbits. Two rabbits were randomly sacrificed at 2 h, 6 h, 1 d, 3 d, 7 d and 21 d after the trauma. (3) TGF-beta(1) antibodies treated group: 6 rabbits were injected with TGF-beta(1) antibodies (15.5 microg) subconjunctivally after corneal trephine. Two rabbits were randomly sacrificed at 3 d, 7 d and 21 d after the injection. (4) Smad4 antibodies treated group: 6 rabbits were injected with Smad4 antibodies (20 microg) subconjunctivally after corneal trephine. Two rabbits were randomly sacrificed at 3 d, 7 d and 21 d after the injection. Protein of CTGF, TGF-beta(1), and FN was assessed with immunohistochemistry. CTGF and type one collagen mRNA were measured in by in situ hybridization. (1) CTGF protein or mRNA did not exist in normal rabbit corneas, but TGF-beta(1) protein was expressed in normal rabbit cornea epithelium. (2) Cornea fibroblasts activated 6 h after the operation. Expression of CTGF, TGF-beta(1), FN protein and mRNA of CTGF and type one collagen were upregulated after cornea injury, and reached the highest level in 3 days. The expression was reduced to the basal level 21 days later. (3) Injection of TGF-beta(1) antibodies reduced the expression of CTGF, TGF-beta(1) and FN in the cornea stroma and down-regulated the expression of CTGF in corneal epithelial cells. (4) Injection of Smad4 antibodies inhibited the expression of TGF in the stroma but did not

  20. Corneal stromal wound healing in rabbits after 193-nm excimer laser surface ablation.

    Science.gov (United States)

    Hanna, K D; Pouliquen, Y; Waring, G O; Savoldelli, M; Cotter, J; Morton, K; Menasche, M

    1989-06-01

    An argon fluoride excimer laser (193 nm) with a moving slit delivery system was used to perform anterior myopic keratomileusis in both eyes of 24 New Zealand white rabbits. Rabbits were killed immediately after ablation and at intervals up to 100 days. By slit-lamp microscopy, four rabbits at day 100 exhibited four clear corneas and four corneas had central, spotty, subepithelial haze. Light and electron microscopy documented corneal healing. In the early stages a transient acellular zone in the anterior stroma appeared over a period of three weeks, followed by an increased number of fibrocytes. In the corneas with opacification, focal areas of 20-microns-thick subepithelial scarring were present. An unexpected finding was transient damage to posterior stromal keratocytes and endothelial cells. The endothelium produced a layer of granular material that migrated anteriorly across Descemet's membrane. Immunochemistry at day 6 showed a marked staining for collagen IV, proteoglycans, fibronectin, and laminin.

  1. Y-27632, a ROCK Inhibitor, Promoted Limbal Epithelial Cell Proliferation and Corneal Wound Healing.

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    Chi-Chin Sun

    Full Text Available Transplantation of ex vivo cultured limbal epithelial cells is proven effective in restoring limbal stem cell deficiency. The present study aimed to investigate the promoting effect of Y-27632 on limbal epithelial cell proliferation. Limbal explants isolated from human donor eyes were expanded three weeks on culture dishes and outgrowth of epithelial cells was subsequently subcultured for in vitro experiments. In the presence of Y-27632, the ex vivo limbal outgrowth was accelerated, particularly the cells with epithelial cell-like morphology. Y-27632 dose-dependently promoted the proliferation of in vitro cultured human limbal epithelial cells as examined by phase contrast microscopy and luminescent cell-viability assay 30 hours after the treatment. The colony forming efficacy determined 7 days after the treatment was enhanced by Y-27632 also in a dose-dependent manner. The number of p63- or Ki67-positive cells was dose-dependently increased in Y-27632-treated cultures as detected by immunofluorescent staining and western blotanalysis. Cell cycle analysis by flow cytometric method revealed an increase in S-phase proliferating cells. The epithelial woundclosure rate was shown to be faster in experimental group received topical treatment withY-27632 than the sham control using a rat corneal wounding model. These resultsdemonstrate that Y-27632 can promote both the ex vivo and in vitro proliferation oflimbal epithelial cell proliferation. The in vivo enhanced epithelial wound healingfurther implies that the Y-27632 may act as a new strategy for treating limbal stem cell deficiency.

  2. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Ligtenberg, A.J.M.; Veerman, E.C.I.; Ligtenberg, A.J.M.; Veerman, E.C.I.

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In

  3. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Ligtenberg, A.J.M.; Veerman, E.C.I.; Ligtenberg, A.J.M.; Veerman, E.C.I.

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In

  4. Wound Healing and Care

    Science.gov (United States)

    ... Right Sport for You Healthy School Lunch Planner Wound Healing and Care KidsHealth > For Teens > Wound Healing and Care Print A A A What's in ... mouth, or sunken eyes. There's good news about wound healing when you're a teen: Age is on ...

  5. Pirfenidone Nanoparticles Improve Corneal Wound Healing and Prevent Scarring Following Alkali Burn

    OpenAIRE

    Sushovan Chowdhury; Rajdeep Guha; Ruchit Trivedi; Kompella, Uday B.; Aditya Konar; Sarbani Hazra

    2013-01-01

    PURPOSE: To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn. METHODS: Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA) synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared, characterized and their cellular entry was examined in primary cor...

  6. The response of healing corneal epithelium to grooved polymer surfaces.

    NARCIS (Netherlands)

    Evans, M.D.; McFarland, G.A.; Taylor, S.; Walboomers, X.F.

    2005-01-01

    Corneal epithelial wounds heal rapidly by the inwards growth of tissue with a contracting wound front. A synthetic polymer lens to correct refractive error (an implantable contact lens) could be incorporated into the cornea using this wound healing process. Topographical cues on the polymer surface

  7. Neutrophil interactions with keratocytes during corneal epithelial wound healing: a role for CD18 integrins.

    Science.gov (United States)

    The purpose of this study was to determine the role of keratocytes and leukocyte beta(2) (CD18) integrins in neutrophil (PMN) migration through the corneal stroma after epithelial scrape injury. Using C57BL/6 wild-type and CD18(-/-) mice, corneas were excised at 6 hours (wild-type) or 24 hours (CD18...

  8. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Veerman, E.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

  9. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Veerman, E.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

  10. [Wound healing and wound dressing].

    Science.gov (United States)

    Eitel, F; Sklarek, J

    1988-01-01

    This review article intends to discuss the clinical management of wounds in respect to a pathophysiological background. Recent results of research in the field of wound healing are demonstrated. Wound healing can be seen as aseptic inflammatory response to a traumatic stimulus. The activation of the clotting cascade by the trauma induces a sequence of humoral and cellular reactions. Platelets, granulocytes and macrophages are activated stepwisely. In the first phase of wound healing the wounded tissue area will be prepared for phagocytosis by enzymatic degradation of ground substance and depolymerisation of protein macromolecules (wound edema). Following the phagocytic microdebridement mesenchymal cells proliferate and produce matrix substance. Microcirculation within the traumatized area will be restored by angiogenesis, macroscopically observed as new formed granulation tissue. This leads to the wound healing phase of scar tissue formation. In this complexity of reactions naturally many possibilities of impairment are given. The most common complication during wound healing is the infection. It can be seen as self reinforcing process. The therapy of the impairment of wound healing consists in the disruption of the specific vicious circle, in the case of an osseus infection that would be a macrodebridement (that is necrectomy) and biomechanical stabilization. The surgical management of wounds principally consists in ensuring an undisturbed sequence of the healing process. This can be done by the wound excision that supports the phagocytic microdebridement. A further possibility is to avoid overwhelming formation of edema by eliminating the traumatic stimulus, by immobilization of the injured region and by ensuring a physiological microenvironment with a primary suture if possible. There are up to the present no drugs available to enhance cell proliferation and to regulate wound healing but it seems that experimental research is successful in characterizing

  11. PATOPHYSIOLOGY OF WOUND HEALING

    OpenAIRE

    NOVINŠČAK, TOMISLAV; FILIPOVIĆ, MARINKO

    2015-01-01

    Wound healing is a basic, highly complex, logical and well orchestrated physiologic process of interaction of various speciic molecules and cells in normal tissue function and structure restoration. In essence, genetically deined and by reined physical and chemical forces driven process, in most living beings wound healing leads to imperfect but suficient tissue repair. Some rare exceptions in wound healing, like salamander or human fetus, that can achieve complete and perfect regeneration pr...

  12. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L A

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  13. 角膜基质创伤愈合的研究进展%Research progress of corneal stromal wound healing

    Institute of Scientific and Technical Information of China (English)

    樊廷俊; 白苏冉

    2016-01-01

    Corneal stroma wound healing is a complex process involving cell apoptosis,migration,proliferation,differ-entiation,and extracellular matrix remodeling.Transforming growth factor β(TGF-β)system plays central roles in regulating the transformation of stromal cells and the fibrosis of stroma,and its dysregulation might be the main cause of stromal haze,scar formation and vision damage.Recently,great progress has been made in the study of corneal stromal wound healing,and various new therapies to attenuate stromal scar have also been developed.The process of corneal stromal wound healing,cellular phenotype transformation and its regulating factors,and strategies of excessive healing control are reviewed.%角膜基质创伤愈合是一个涉及细胞调亡、迁移、增殖、分化和细胞外基质重建的复杂过程。转化生长因子β(TGF-β)系统在调控角膜基质细胞转化和基质纤维化方面具有关键作用,其失调是造成愈合后形成基质瘢痕、出现雾状混浊和视力受损的主要原因。近年来,在角膜基质创伤愈合的研究方面取得了重要进展,并开发出了一些消除基质瘢痕的新的治疗方法。本文拟围绕角膜基质的创伤愈合过程,细胞表型转化及其调控因子,以及愈合过度的控制策略进行综述。

  14. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

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

  15. Saliva and wound healing.

    Science.gov (United States)

    Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

  16. Diabetes and wound healing

    OpenAIRE

    Svendsen, Rikke; Irakunda, Gloire; Knudsen List, Karoline Cecilie; Sønderstup-Jensen, Marie; Hölmich Rosca, Mette Maria

    2014-01-01

    Diabetes is a disease where the glucose level in the blood is high, due to either insulin resistance, impaired insulin sensitivity or no insulin production. The high glucose level causes several complications, one of them being an impaired wound healing process, which might lead to chronic wounds, ulcers. Several factors play a role in the development of ulcers, and recent research indicates that microRNA might play a significant role in skin development and wound healing. The purpose of this...

  17. Wound healing in urology.

    Science.gov (United States)

    Ninan, Neethu; Thomas, Sabu; Grohens, Yves

    2015-03-01

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

  18. Microdeformation in wound healing.

    Science.gov (United States)

    Wiegand, Cornelia; White, Richard

    2013-01-01

    Mechanical forces greatly influence cellular organization and behavior. Cells respond to applied stress by changes in form and composition until a suitable state is reestablished. However, without any mechanical stimuli cells stop proliferating, discontinue migration, go into cell-cycle arrest, and eventually die. Hence, one can assume that pathologies closely depending on cell migration like cancer or atherosclerosis might be governed by biophysical parameters. Moreover, mechanical cues will have fundamental effects in wound healing. Especially negative pressure wound therapy has the potential to endorse wound healing by induction of both macrodeformation (wound contraction) and microdeformation (tissue reactions at microscopic level). So far, the capacity for researchers to study the link between mechanical stimulation and biological response has been limited by the lack of instrumentation capable of stimulating the tissue in an appropriate manner. However, first reports on application of micromechanical forces to wounds elucidate the roles of cell stretch, substrate stiffness, and tissue deformation during cell proliferation and differentiation. This review deals with their findings and tries to establish a link between the current knowledge and the questions that are essential to clinicians in the field: What is the significance of mirodeformations for wound healing? Does "dead space" impede propagation of mechanical cues? How can microdeformations induce cell proliferation? What role do fibroblasts, myofibroblasts, and mesenchymal stem cells play in chronic wounds with regard to micromechanical forces? © 2013 by the Wound Healing Society.

  19. Innovation and wound healing.

    Science.gov (United States)

    Harding, Keith

    2015-04-01

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

  20. Fibronectin and wound healing.

    Science.gov (United States)

    Grinnell, F

    1984-01-01

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

  1. Healing Invisible Wounds

    Science.gov (United States)

    Adams, Erica J.

    2010-01-01

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

  2. Phytochemicals in Wound Healing

    OpenAIRE

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

    2016-01-01

    Significance: Traditional therapies, including the use of dietary components for wound healing and skin regeneration, are very common in Asian countries such as China and India. The increasing evidence of health-protective benefits of phytochemicals, components derived from plants is generating a lot of interest, warranting further scientific evaluation and mechanistic studies.

  3. Healing Invisible Wounds

    Science.gov (United States)

    Adams, Erica J.

    2010-01-01

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

  4. Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

    Science.gov (United States)

    Lee, Jong Heon; Lee, Jong Soo; Kim, Sujin

    2017-01-01

    This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion. PMID:28280412

  5. Social facilitation of wound healing.

    Science.gov (United States)

    Detillion, Courtney E; Craft, Tara K S; Glasper, Erica R; Prendergast, Brian J; DeVries, A Courtney

    2004-09-01

    It is well documented that psychological stress impairs wound healing in humans and rodents. However, most research effort into influences on wound healing has focused on factors that compromise, rather than promote, healing. In the present study, we determined if positive social interaction, which influences hypothalamic-pituitary-adrenal (HPA) axis activity in social rodents, promotes wound healing. Siberian hamsters received a cutaneous wound and then were exposed to immobilization stress. Stress increased cortisol concentrations and impaired wound healing in isolated, but not socially housed, hamsters. Removal of endogenous cortisol via adrenalectomy eliminated the effects of stress on wound healing in isolated hamsters. Treatment of isolated hamsters with oxytocin (OT), a hormone released during social contact and associated with social bonding, also blocked stress-induced increases in cortisol concentrations and facilitated wound healing. In contrast, treating socially housed hamsters with an OT antagonist delayed wound healing. Taken together, these data suggest that social interactions buffer against stress and promote wound healing through a mechanism that involves OT-induced suppression of the HPA axis. The data imply that social isolation impairs wound healing, whereas OT treatment may ameliorate some effects of social isolation on health.

  6. Cell therapy for wound healing.

    Science.gov (United States)

    You, Hi-Jin; Han, Seung-Kyu

    2014-03-01

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

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

    Science.gov (United States)

    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

  8. MicroRNA signature in wound healing following excimer laser ablation: role of miR-133b on TGFβ1, CTGF, SMA, and COL1A1 expression levels in rabbit corneal fibroblasts.

    Science.gov (United States)

    Robinson, Paulette M; Chuang, Tsai-Der; Sriram, Sriniwas; Pi, Liya; Luo, Xiao Ping; Petersen, Bryon E; Schultz, Gregory S

    2013-10-23

    The role of microRNA (miRNA) regulation in corneal wound healing and scar formation has yet to be elucidated. This study analyzed the miRNA expression pattern involved in corneal wound healing and focused on the effect of miR-133b on expression of several profibrotic genes. Laser-ablated mouse corneas were collected at 0 and 30 minutes and 2 days. Ribonucleic acid was collected from corneas and analyzed using cell differentiation and development miRNA PCR arrays. Luciferase assay was used to determine whether miR-133b targeted the 3' untranslated region (UTR) of transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF) in rabbit corneal fibroblasts (RbCF). Quantitative real-time PCR (qRT-PCR) and Western blots were used to determine the effect of miR-133b on CTGF, smooth muscle actin (SMA), and collagen (COL1A1) in RbCF. Migration assay was used to determine the effect of miR-133b on RbCF migration. At day 2, 37 of 86 miRNAs had substantial expression fold changes. miR-133b had the greatest fold decrease at -14.33. Pre-miR-133b targeted the 3' UTR of CTGF and caused a significant decrease of 38% (P wound healing, suggesting novel miRNA targets to reduce scar formation.

  9. Molecular pathology of wound healing.

    Science.gov (United States)

    Kondo, Toshikazu; Ishida, Yuko

    2010-12-15

    Skin-wound healing is an orchestrated biological phenomena consisting of three sequential phases, inflammation, proliferation, and maturation. Many biological substances are involved in the process of wound repair, and this short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. With the development of genetically engineered animals, essential molecules for skin-wound healing have been identified. Especially, cytokines, and growth factors are useful candidates and markers for the determination of wound vitality or age. Moreover, bone marrow-derived progenitor cells would give significant information to wound age determination. In this review article, some interesting observations are presented, possibly contributing to the future practice of forensic pathologists. Copyright © 2010. Published by Elsevier Ireland Ltd.

  10. Murine models of human wound healing.

    Science.gov (United States)

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

    2013-01-01

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

  11. Wound Healing Devices Brief Vignettes

    OpenAIRE

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

    2016-01-01

    Significance: The demand for wound care therapies is increasing. New wound care products and devices are marketed at a dizzying rate. Practitioners must make informed decisions about the use of medical devices for wound healing therapy. This paper provides updated evidence and recommendations based on a review of recent publications.

  12. Wound healing: a new approach to the topical wound care.

    Science.gov (United States)

    Öztürk, Ferdi; Ermertcan, Aylin Türel

    2011-06-01

    Cutaneous wound healing is a complex and well-coordinated interaction between inflammatory cells and mediators, establishing significant overlap between the phases of wound healing. Wound healing is divided into three major phases: inflammatory phase, proliferative phase, and remodeling phase. Unlike the acute wound, the nonhealing wound is arrested in one of the phases of healing, typically the inflammatory phase. A systematic approach to the management of the chronic nonhealing wound emphasizes three important elements of wound bed preparation in chronic wounds: debridement, moisture, and countering bacterial colonization and infection. In this article, wound-healing process and new approaches to the topical wound care have been reviewed.

  13. Wound healing: part II. Clinical applications.

    Science.gov (United States)

    Janis, Jeffrey; Harrison, Bridget

    2014-03-01

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

  14. Trefoil peptides promote restitution of wounded corneal epithelial cells.

    Science.gov (United States)

    Göke, M N; Cook, J R; Kunert, K S; Fini, M E; Gipson, I K; Podolsky, D K

    2001-04-01

    The ocular surface shares many characteristics with mucosal surfaces. In both, healing is regulated by peptide growth factors, cytokines, and extracellular matrix proteins. However, these factors are not sufficient to ensure most rapid healing. Trefoil peptides are abundantly expressed epithelial cell products which exert protective effects and are key regulators of gastrointestinal epithelial restitution, the critical early phase of cell migration after mucosal injury. To assess the role of trefoil peptides in corneal epithelial wound healing, the effects of intestinal trefoil factor (ITF/TFF3) and spasmolytic polypeptide (SP/TFF2) on migration and proliferation of corneal epithelial cells were analyzed. Both ITF and SP enhanced restitution of primary rabbit corneal epithelial cells in vitro. While the restitution-enhancing effects of TGF-alpha and TGF-beta were both inhibited by neutralizing anti-TGF-beta-antibodies, trefoil peptide stimulation of restitution was not. Neither trefoil peptide significantly affected proliferation of primary corneal epithelial cells. ITF but not SP or pS2 mRNA was present in rabbit corneal and conjunctival tissues. In summary, the data indicate an unanticipated role of trefoil peptides in healing of ocular surface and demand rating their functional actions beyond the gastrointestinal tract.

  15. What is New in Wound Healing?

    OpenAIRE

    Kumar, Senthil; WONG, Peng Foo; LEAPER, David John

    2004-01-01

    Wound biology is complex. Wounds which were until recently seen only as defects in tissues are now increasingly interpreted in cellular and molecular terms. Growth factors, cytokines, proteases and adhesion molecules which participate in wound healing are discussed in this article. From a clinical perspective, conceptual shifts of importance, including moist wound healing, wound bed preparation and wound assessment, are presented. The frontiers of therapeutics employed in wound healing contin...

  16. [Specificities in children wound healing].

    Science.gov (United States)

    Sanchez, J; Antonicelli, F; Tuton, D; Mazouz Dorval, S; François, C

    2016-10-01

    Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon.

  17. Vasculogenic Cytokines in Wound Healing

    Directory of Open Access Journals (Sweden)

    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  18. WOUND HEALING IN DIABETIC ULCER

    Directory of Open Access Journals (Sweden)

    Ida Bagus Putra Pramana

    2013-03-01

    Full Text Available The mechanism of wound healing is a complex mechanism and involves a variety of cells. Injury is defined as a disruption of normal structure and function. Various types of growth factors and cytokines such as platelet derived growth factor and transforming growth factor beta involved in the mechanism of wound healing. There are four phases of wound healing mechanisms : hemostasis, inflammatory, proliferative, and remodeling. Diabetic ulcers is one major complication, occurring in 15% of patients with diabetes mellitus (DM and as much as 84% of patients with diabetic ulcers require amputation action. In DM patients there is a failure in normal wound healing mechanisms. Various histopathological studies showed elongation phase of inflammation in patients with diabetes mellitus, thus inhibiting the formation of granulation tissue. Increased blood sugar levels will lower the expressin of perlecan, increased advanced glycation endproducts, decreased the formation of nitric oxide (by ± 67%, changes in the structure and function of fibroblasts and increased activity of matrix metalolproteinases, it will cause distruption of the normal wound healing mechanisms. (MEDICINA 2012;43:49-53.

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

    Science.gov (United States)

    Davidson, Jacqueline R

    2015-05-01

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

  20. Photobiomodulation in promoting wound healing: a review.

    Science.gov (United States)

    Kuffler, Damien P

    2016-01-01

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

  1. Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

    Institute of Scientific and Technical Information of China (English)

    Fei; Li; Shao-Zhen; Zhao

    2014-01-01

    Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

  2. How wounds heal

    Science.gov (United States)

    ... chronic wounds. Poor blood flow due to clogged arteries ( arteriosclerosis ) or conditions such as varicose veins. Obesity increases the risk of infection after surgery. Being overweight can also put tension on stitches, which can make them break open. ...

  3. Chemokine Regulation of Angiogenesis During Wound Healing

    OpenAIRE

    Bodnar, Richard J.

    2015-01-01

    Significance: Angiogenesis plays a critical role in wound healing. A defect in the formation of a neovasculature induces ulcer formation. One of the challenges faced by the clinician when devising strategies to promote healing of chronic wounds is the initiation of angiogenesis and the formation of a stable vasculature to support tissue regeneration. Understanding the molecular factors regulating angiogenesis during wound healing will lead to better therapies for healing chronic wounds.

  4. The role of thrombospondin-1 in corneal wound healing%血小板反应蛋白-1对角膜创伤修复的影响

    Institute of Scientific and Technical Information of China (English)

    倪双

    2015-01-01

    Thrombospondin-1 (THBS-1),a kind of extracellular matrix proteins,whose biological action played an important role in corneal wound healing has became a research highlight.The currently research findings showed that THBS-1 could promote the healing of epithelium,stroma and endothelium through activating the transforming growth factor-β1 (TGF-β1) which can accelerate cell proliferation,promote stroma forming and inducing cell migration.It is worthful in clinical treatment of all kinds of corneal wound healing.Now we summarized the research developments which have been acquired in the field recently in this article.%血小板反应蛋白-1 (THBS-1)是一种细胞外基质蛋白,其在角膜创伤修复中发挥的作用是近年来国内外研究的热点.研究发现THBS-1可通过激活转化生长因子-β1(TGF-β1)来促进细胞增生、细胞外基质形成、诱导细胞移行,从而在上皮基底膜、基质层和内皮修复中起重要作用,这将为临床上治疗各种原因引起的角膜创伤开辟新的途径.本文就THBS-1的来源及结构、生物学功能及其在角膜创伤修复过程中所起的作用进行综述.

  5. Plasma Proteins and Wound Healing

    Science.gov (United States)

    1981-11-01

    an iron donor for proline hydroxylase synthesis. Hapto- globin also may prevent retardation of wound healing caused by infection by reducing the...dans le syndrome degression et la croissance tissulaire. Expos. Annu. Biochim. Med., 1970, 30: 149. JEEEAY, H. The metabolism of scrum proteins—III

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

    Science.gov (United States)

    Mutschler, W

    2012-09-01

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

  7. Wound Healing and Care

    Science.gov (United States)

    ... wounds can be so different, your doctor will give you instructions on how to take care of yourself after you go home from the hospital. In most cases, doctors will ask patients to do the following ... A doctor or nurse will give you instructions on how to change your dressing ...

  8. Hyperbaric oxygen and wound healing

    Directory of Open Access Journals (Sweden)

    Sourabh Bhutani

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

    The care of wounds in exotic animal species can be a challenging endeavor. Special considerations must be made in regard to the animal's temperament and behavior, unique anatomy and small size, and tendency toward secondary stress-related health problems. It is important to assess the entire patient with adequate systemic evaluation and consideration of proper nutrition and husbandry, which could ultimately affect wound healing. This article summarizes the general phases of wound healing, factors that affect healing, and principles of wound management. Emphasis is placed on novel methods of treating wounds and species differences in wound management and healing. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Influence of oxygen on wound healing.

    Science.gov (United States)

    Yip, Wai Lam

    2015-12-01

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

  11. Current management of wound healing

    DEFF Research Database (Denmark)

    Gottrup, F; Karlsmark, T

    2009-01-01

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

  12. Phases of the wound healing process.

    Science.gov (United States)

    Brown, Annemarie

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

  13. Engineered Biopolymeric Scaffolds for Chronic Wound Healing

    OpenAIRE

    Dickinson, Laura E.; Sharon Gerecht

    2016-01-01

    Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, whic...

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

    Science.gov (United States)

    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. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Wound healing in Mac-1 deficient mice.

    Science.gov (United States)

    Chen, Lin; Nagaraja, Sridevi; Zhou, Jian; Zhao, Yan; Fine, David; Mitrophanov, Alexander Y; Reifman, Jaques; DiPietro, Luisa A

    2017-05-01

    Mac-1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac-1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac-1(-/-) mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. This study examined whether Mac-1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac-1 deficient (Mac-1(-/-) ) and wild type (WT) mice, and wound healing outcomes were examined. Mac-1 deficient mice exhibited a normal rate of wound closure, generally normal levels of total collagen, and nearly normal synthesis and distribution of collagens I and III. In incisional wounds, wound breaking strength was similar for Mac-1(-/-) and WT mice. Wounds of Mac-1 deficient mice displayed normal total macrophage content, although macrophage phenotype markers were skewed as compared to WT. Interestingly, amounts of TGF-β1 and its downstream signaling molecules, SMAD2 and SMAD3, were significantly decreased in the wounds of Mac-1 deficient mice compared to WT. The results suggest that Mac-1 deficiency has little impact on the healing of small excisional and incisional wounds. Moreover, the findings demonstrate that the effect of single genetic deficiencies on wound healing may markedly differ among wound models. These conclusions have implications for the interpretation of the many prior studies that utilize a single model system to examine wound healing outcomes in genetically deficient mice. © 2017 by the Wound Healing Society.

  16. Current management of wound healing

    DEFF Research Database (Denmark)

    Gottrup, F; Karlsmark, T

    2009-01-01

    in the next decade. It is the hope that increasing parts of the new knowledge from basic wound healing research will be implemented in daily clinical practice. The development of new treatment products will also continue, and especially new technologies with combined types of dressing materials or dressing...... containing active substances will be accentuated. Further developments in the management structure and education will also continue and consensus of treatment guidelines, recommendations and organization models will hopefully be achieved....

  17. BURN WOUND HEALING ACTIVITY OF Euphorbia hirta

    OpenAIRE

    Jaiprakash, B.; Chandramohan,; Reddy, D. Narishma

    2006-01-01

    The Ethanolic extract of whole plant of Euphorbia hirta was screened for burn wound healing activity in rats as 2% W/W cream. The study was carried out based on the assessment of percentage reduction in original wound. It showed significant burn wound healing activity.

  18. Wound healing and the role of fibroblasts.

    Science.gov (United States)

    Bainbridge, P

    2013-08-01

    Fibroblasts are critical in supporting normal wound healing, involved in key processes such as breaking down the fibrin clot, creating new extra cellular matrix (ECM) and collagen structures to support the other cells associated with effective wound healing, as well as contracting the wound. This article explores and summarises the research evidence on the role of fibroblasts, their origins and activation, and how they navigate the wound bed, as well as how their activity leads to wound contraction. This article also explores the local conditions at the wound site, which activate, regulate and ultimately reduce the fibroblast activity as the skin's integrity returns on healing.

  19. The role of electrical signals in murine corneal wound re-epithelialization.

    Science.gov (United States)

    Kucerova, Romana; Walczysko, Petr; Reid, Brian; Ou, Jingxing; Leiper, Lucy J; Rajnicek, Ann M; McCaig, Colin D; Zhao, Min; Collinson, J Martin

    2011-06-01

    Ion flow from intact tissue into epithelial wound sites results in lateral electric currents that may represent a major driver of wound healing cell migration. Use of applied electric fields (EF) to promote wound healing is the basis of Medicare-approved electric stimulation therapy. This study investigated the roles for EFs in wound re-epithelialization, using the Pax6(+/-) mouse model of the human ocular surface abnormality aniridic keratopathy (in which wound healing and corneal epithelial cell migration are disrupted). Both wild-type (WT) and Pax6(+/-) corneal epithelial cells showed increased migration speeds in response to applied EFs in vitro. However, only Pax6(+/+) cells demonstrated consistent directional galvanotaxis towards the cathode, with activation of pSrc signaling, polarized to the leading edges of cells. In vivo, the epithelial wound site normally represents a cathode, but 43% of Pax6(+/-) corneas exhibited reversed endogenous wound-induced currents (the wound was an anode). These corneas healed at the same rate as WT. Surprisingly, epithelial migration did not correlate with direction or magnitude of endogenous currents for WT or mutant corneas. Furthermore, during healing in vivo, no polarization of pSrc was observed. We found little evidence that Src-dependent mechanisms of cell migration, observed in response to applied EFs in vitro, normally exist in vivo. It is concluded that endogenous EFs do not drive long-term directionality of sustained healing migration in this mouse corneal epithelial model. Ion flow from wounds may nevertheless represent an important component of wound signaling initiation.

  20. Basics in nutrition and wound healing.

    Science.gov (United States)

    Wild, Thomas; Rahbarnia, Arastoo; Kellner, Martina; Sobotka, Lubos; Eberlein, Thomas

    2010-09-01

    Wound healing is a process that can be divided into three different phases (inflammatory, proliferative, and maturation). Each is characterized by certain events that require specific components. However, wound healing is not always a linear process; it can progress forward and backward through the phases depending on various intrinsic and extrinsic factors. If the wound-healing process is affected negatively, this can result in chronic wounds. Chronic wounds demand many resources in the clinical daily routine. Therefore, local wound management and good documentation of the wound is essential for non-delayed wound healing and prevention of the development of chronic wounds. During the wound-healing process much energy is needed. The energy for the building of new cells is usually released from body energy stores and protein reserves. This can be very challenging for undernourished and malnourished patients. Malnutrition is very common in geriatric patients and patients in catabolic phases of stress such as after injury or surgery. For that reason a close survey of the nutritional status of patients is necessary to start supplementation quickly, if applicable. Wound healing is indeed a very complex process that deserves special notice. There are some approaches to develop guidelines but thus far no golden standard has evolved. Because wounds, especially chronic wounds, cause also an increasing economic burden, the development of guidelines should be advanced.

  1. Human ex vivo wound healing model.

    Science.gov (United States)

    Stojadinovic, Olivera; Tomic-Canic, Marjana

    2013-01-01

    Wound healing is a spatially and temporally regulated process that progresses through sequential, yet overlapping phases and aims to restore barrier breach. To study this complex process scientists use various in vivo and in vitro models. Here we provide step-by-step instructions on how to perform and employ an ex vivo wound healing model to assess epithelization during wound healing in human skin.

  2. [Signal transduction mechanism in burn wound healing].

    Science.gov (United States)

    Luo, Xiang-dong

    2008-10-01

    After 50 years of development in science of burns care in China, we have basically solved coverage of deep wounds of burn trauma, as well as role of multiple growth factors and stem cell in wound healing, making great contribution to improving the treatment of patients with large area of deep burns. Surgeons are paying close attention to problems of wound healing, especially in the fields of scarless healing and rehabilitation. To solve these problems, we need to do further investigation on multiple growth factors as well as proliferation/differentiation of stem cells in regulation of cell growth and differentiation in wound healing. Therefore, we are facing a even more serious challenge.

  3. Engineered biopolymeric scaffolds for chronic wound healing

    Directory of Open Access Journals (Sweden)

    Laura E Dickinson

    2016-08-01

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

  4. Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

    Science.gov (United States)

    Dickinson, Laura E; Gerecht, Sharon

    2016-01-01

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

  5. Nutritional Aspects of Gastrointestinal Wound Healing

    OpenAIRE

    Mukherjee, Kaushik; Sandra L Kavalukas; Barbul, Adrian

    2016-01-01

    Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneo...

  6. Overview of Wound Healing and Management.

    Science.gov (United States)

    Childs, Dylan R; Murthy, Ananth S

    2017-02-01

    Wound healing is a highly complex chain of events, and although it may never be possible to eliminate the risk of experiencing a wound, clinicians' armamentarium continues to expand with methods to manage it. The phases of wound healing are the inflammatory phase, the proliferative phase, and the maturation phase. The pathway of healing is determined by characteristics of the wound on initial presentation, and it is vital to select the appropriate method to treat the wound based on its ability to avoid hypoxia, infection, excessive edema, and foreign bodies.

  7. The external microenvironment of healing skin wounds.

    Science.gov (United States)

    Kruse, Carla R; Nuutila, Kristo; Lee, Cameron C Y; Kiwanuka, Elizabeth; Singh, Mansher; Caterson, Edward J; Eriksson, Elof; Sørensen, Jens A

    2015-01-01

    The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment methods that directly alter the features of the external wound microenvironment indirectly affect the internal wound microenvironment due to the exchange between the two compartments. In this review, we focus on the effects of temperature, pressure (positive and negative), hydration, gases (oxygen and carbon dioxide), pH, and anti-microbial treatment on the wound. These factors are well described in the literature and can be modified with treatment methods available in the clinic. Understanding the roles of these factors in wound pathophysiology is of central importance in wound treatment. © 2015 by the Wound Healing Society.

  8. Wound healing in the 21st century.

    Science.gov (United States)

    Schreml, Stephan; Szeimies, Rolf-Markus; Prantl, Lukas; Landthaler, Michael; Babilas, Philipp

    2010-11-01

    Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.

  9. Traumatic wound dehiscence after corneal keratoplasty

    Directory of Open Access Journals (Sweden)

    Patrick Frensel Tzelikis

    2015-10-01

    Full Text Available ABSTRACTPurpose:To assess patient characteristics, risk factors, outcomes, and the treatment of wound dehiscence (WD in patients after corneal keratoplasty.Methods:Retrospective chart review of 11 eyes of 11 patients with corneal grafts who underwent repair of WD from January 1, 2004 to December 31, 2012 at Hospital Oftalmologico de Brasilia.Results:Eight (72.7% patients were men and three were women. Six (54.5% patients had deep anterior lamellar keratoplasty (DALK and 5 had penetrating keratoplasty. The mean age at trauma was 31.1 years. The mean time from corneal keratoplasty to WD was 12.82 months (range, 3-33 months. The mean best-corrected visual acuity of patients before trauma was 20/60 (0.48 logMAR and after final treatment was 20/160 (0.90 logMAR (P=0.15. In one case, visual acuity decreased to no light perception because of retinal detachment and phthisis bulbi. Accidental blunt trauma and fall were the most common causes of WD.Conclusion:Patients who undergo corneal keratoplasty have a life-long risk of WD. The full-thickness rupture at the graft-host junction in our study suggests that the junction remains vulnerable, even following DALK, and can rupture with trauma. In our series, depending upon the severity of the trauma, postkeratoplastic WD can be associated with a good visual prognosis.

  10. STRESS PROLONGS WOUND HEALING POST CESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Decision for cesarean section may lead to the stress for women in delivery. Stress response requires longer recovery time in post cesarean section patients. Most of patients who experience stress before and after surgical is associated with wound healing delay. When this condition continues, the wound will have a higher risk of infection. The objective of this study was to analyze correlation between stress and wound healing phase in post cesarean section patients. Method: A cross sectional design was used in this study. The population were women with cesarean section, both elective or emergency, in Delivery Room I RSU Dr. Soetomo Surabaya. Samples were recruited by using purposive sampling, with 28 samples who met to the inclusion criterias. The observed variables were stress and wound healing phase in post cesarean section patient. Stress data were collected by interview and wound healing measurement done by observation on the 3rd day post cesarean section. Result: The result showed that women with stress experience wound healing delay. The characteristic of wound healing delay was prolonged on inflammation phase, nevertheless there was presence of granulation tissue. Spearman’s rho correlation showed that correlation value r=0.675 with p=0.000. Discussion: It can be concluded that there was strong significant correlation between stress and wound healing phase in post cesarean section patients. It is important to give this information to the patients with cesarean section in order to prevent stress and delay in wound healing phase.

  11. Current wound healing procedures and potential care.

    Science.gov (United States)

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

    2015-03-01

    In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting microRNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage microenvironment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection - all in the hopes of early detection of complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Effect of astaxanthin on cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Meephansan J

    2017-07-01

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

  13. Expression of basic fibroblast growth factor in rabbit corneal alkali wounds in the presence and absence of granulocytes.

    Science.gov (United States)

    Gan, Lisha; Fagerholm, Per; Palmblad, Jan

    2005-06-01

    To study the expression of basic fibroblast growth factor (bFGF) in the early phases of corneal wound healing in the presence or absence of granulocytes. A central penetrating corneal alkali wound was inflicted to one eye in each of 14 rabbits under general anaesthesia. Subsequently, seven of the rabbits were given fucoidin i.v. for 36 hours in order to block the selectins on the vascular endothelium, thus preventing blood granulocytes from entering the tissues. Then, corneas were prepared, stained for bFGF and evaluated by light microscopy. Whereas normal corneal epithelium expressed bFGF weakly, conjunctival epithelium did so strongly, particularly the goblet cells. The corneal endothelium showed medium staining, while keratocytes and vascular endothelial cells did not consistently express bFGF. After 36 hours of wound healing, a marked up-regulation of bFGF expression was observed in the corneal epithelial and endothelial cells, as well as in the keratocytes, that were migrating into the wound. No other changes were noted. None of these features were modulated when granulocyte emigration was prevented by fucoidin administration. The difference in bFGF expression between the corneal and conjunctival epithelium suggests a role for this growth factor in the barrier function at the limbus. Moreover, the specific presence of bFGF in cells migrating into the wound indicates the participation of bFGF in corneal wound healing. Expression of bFGF was independent of granulocytes.

  14. Polysaccharide hydrogel combined with mesenchymal stem cells promotes the healing of corneal alkali burn in rats.

    Directory of Open Access Journals (Sweden)

    Yifeng Ke

    Full Text Available Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β, antiangiogenic cytokine (TSP-1 and decrease those promoting inflammation (TNF-α, chemotaxis (MIP-1α and MCP-1 and angiogenesis (VEGF and MMP-2. This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.

  15. Rapid identification of slow healing wounds.

    Science.gov (United States)

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

    2016-01-01

    Chronic nonhealing wounds have a prevalence of 2% in the United States, and cost an estimated $50 billion annually. Accurate stratification of wounds for risk of slow healing may help guide treatment and referral decisions. We have applied modern machine learning methods and feature engineering to develop a predictive model for delayed wound healing that uses information collected during routine care in outpatient wound care centers. Patient and wound data was collected at 68 outpatient wound care centers operated by Healogics Inc. in 26 states between 2009 and 2013. The dataset included basic demographic information on 59,953 patients, as well as both quantitative and categorical information on 180,696 wounds. Wounds were split into training and test sets by randomly assigning patients to training and test sets. Wounds were considered delayed with respect to healing time if they took more than 15 weeks to heal after presentation at a wound care center. Eleven percent of wounds in this dataset met this criterion. Prognostic models were developed on training data available in the first week of care to predict delayed healing wounds. A held out subset of the training set was used for model selection, and the final model was evaluated on the test set to evaluate discriminative power and calibration. The model achieved an area under the curve of 0.842 (95% confidence interval 0.834-0.847) for the delayed healing outcome and a Brier reliability score of 0.00018. Early, accurate prediction of delayed healing wounds can improve patient care by allowing clinicians to increase the aggressiveness of intervention in patients most at risk. © 2015 by the Wound Healing Society.

  16. Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Zhong Zheng, PhD

    2014-12-01

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

  17. Wound healing and infection in surgery

    DEFF Research Database (Denmark)

    Sørensen, Lars Tue

    2012-01-01

    : The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved.......: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved....

  18. Assessment and nutritional aspects of wound healing.

    Science.gov (United States)

    Campos, Antonio C L; Groth, Anne K; Branco, Alessandra B

    2008-05-01

    The aim of this study is to review the physiopathology and the nutritional aspects of wound healing. Wound healing consists of a perfect and coordinated cascade of events that result in tissue reconstitution. The healing process is common to all wounds, independent of the agent that has caused it. It is divided didactically into three phases: inflammation, proliferation, and remodeling or maturation. Collagen is the most abundant protein in the human body and is also the main component of the wound matrix. It is organized in a thick and dynamic net, resulting from constant collagen deposition and reabsorption. Wound scar is the result of the interaction between collagen synthesis, degradation, and remodeling. There are several ways to evaluate wound healing: tensiometry, collagen morphometry, immunohistochemistry, and, more recently, the dosage of growth factors. Malnutrition adversely affects wound healing. On the contrary, the healing process can be stimulated by preoperative feeding and by certain nutrients such as glutamine, arginine, butyrate, and antioxidants. Wound healing is a complex process that started to be fully understood only in recent years. Recent research has been directed to act in the nutrition modulation of the healing process.

  19. Aloe vera: an in vitro study of effects on corneal wound closure and collagenase activity.

    Science.gov (United States)

    Curto, Elizabeth M; Labelle, Amber; Chandler, Heather L

    2014-11-01

    To evaluate the in vitro effects of an aloe vera solution on (i) the viability and wound healing response of corneal cells and (ii) the ability to alter collagenase and gelatinase activities. Primary cultures of corneal epithelial cells and fibroblasts were prepared from grossly normal enucleated canine globes and treated with an aloe solution (doses ranging from 0.0-2 mg/mL). Cellular viability was evaluated using a colorimetric assay. A corneal wound healing model was used to quantify cellular ingrowth across a defect made on the confluent surface. Anticollagenase and antigelatinase activities were evaluated by incubating a bacterial collagenase/gelatinase with aloe solution (doses ranging from 0.0-500 μg/mL) and comparing outcome measures to a general metalloproteinase inhibitor, 1, 10-phenanthroline, and canine serum (doses ranging from 0.0-100%). None of the concentrations of aloe solution tested significantly affected the viability of corneal epithelial cells or fibroblasts. Concentrations ≤175 μg/mL slightly accelerated corneal epithelial cell wound closure; this change was not significant. Concentrations ≥175 μg/mL significantly (P ≤ 0.001) slowed the rate of corneal fibroblast wound closure, while aloe concentrations Aloe solution did not alter the ability for collagenase to degrade gelatin or collagen Type I but increased the ability for collagenase to degrade Type IV collagen. Although additional experiments are required, lower concentrations of aloe solution may be beneficial in healing of superficial corneal wounds to help decrease fibrosis and speed epithelialization. An increase in collagenase activity with aloe vera warrants further testing before considering in vivo studies. © 2014 American College of Veterinary Ophthalmologists.

  20. Physics of Wound Healing I: Energy Considerations

    CERN Document Server

    Apell, S Peter; Papazoglou, Elisabeth S; Pizziconi, Vincent

    2012-01-01

    Wound healing is a complex process with many components and interrelated processes on a microscopic level. This paper addresses a macroscopic view on wound healing based on an energy conservation argument coupled with a general scaling of the metabolic rate with body mass M as M^{\\gamma} where 0 <{\\gamma}<1. Our three main findings are 1) the wound healing rate peaks at a value determined by {\\gamma} alone, suggesting a concept of wound acceleration to monitor the status of a wound. 2) We find that the time-scale for wound healing is a factor 1/(1 -{\\gamma}) longer than the average internal timescale for producing new material filling the wound cavity in corresondence with that it usually takes weeks rather than days to heal a wound. 3) The model gives a prediction for the maximum wound mass which can be generated in terms of measurable quantities related to wound status. We compare our model predictions to experimental results for a range of different wound conditions (healthy, lean, diabetic and obses...

  1. The external microenvironment of healing skin wounds

    DEFF Research Database (Denmark)

    Kruse, Carla R; Nuutila, Kristo; Lee, Cameron Cy

    2015-01-01

    The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment...... methods that directly alter the features of the external wound microenvironment indirectly affect the internal wound microenvironment due to the exchange between the two compartments. In this review, we focus on the effects of temperature, pressure (positive and negative), hydration, gases (oxygen...

  2. Acceleration of cutaneous wound healing by brassinosteroids.

    Science.gov (United States)

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

    2013-01-01

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

  3. Biomarkers for wound healing and their evaluation.

    Science.gov (United States)

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

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

  4. Wound Healing Effect of Curcumin: A Review.

    Science.gov (United States)

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

    2016-07-21

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

  5. Effect of astaxanthin on cutaneous wound healing.

    Science.gov (United States)

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

    2017-01-01

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

  6. News in wound healing and management

    DEFF Research Database (Denmark)

    Gottrup, Finn; Jørgensen, Bo; Karlsmark, Tonny

    2009-01-01

    -TNFalpha) and Lactobacillus plantarum cultures have also been successfully used in hard to heal, atypical wounds. Knowledge on influencing factors as smoking and biofilm on the healing process has also been improved. Smoking results in delayed healing and increased risk of postoperative infection, whereas the role of biofilm...

  7. Diabetic cornea wounds produce significantly weaker electric signals that may contribute to impaired healing.

    Science.gov (United States)

    Shen, Yunyun; Pfluger, Trisha; Ferreira, Fernando; Liang, Jiebing; Navedo, Manuel F; Zeng, Qunli; Reid, Brian; Zhao, Min

    2016-06-10

    Wounds naturally produce electric signals which serve as powerful cues that stimulate and guide cell migration during wound healing. In diabetic patients, impaired wound healing is one of the most challenging complications in diabetes management. A fundamental gap in knowledge is whether diabetic wounds have abnormal electric signaling. Here we used a vibrating probe to demonstrate that diabetic corneas produced significantly weaker wound electric signals than the normal cornea. This was confirmed in three independent animal models of diabetes: db/db, streptozotocin-induced and mice fed a high-fat diet. Spatial measurements illustrated that diabetic cornea wound currents at the wound edge but not wound center were significantly weaker than normal. Time lapse measurements revealed that the electric currents at diabetic corneas lost the normal rising and plateau phases. The abnormal electric signals correlated significantly with impaired wound healing. Immunostaining suggested lower expression of chloride channel 2 and cystic fibrosis transmembrane regulator in diabetic corneal epithelium. Acute high glucose exposure significantly (albeit moderately) reduced electrotaxis of human corneal epithelial cells in vitro, but did not affect the electric currents at cornea wounds. These data suggest that weaker wound electric signals and impaired electrotaxis may contribute to the impaired wound healing in diabetes.

  8. Skin wound healing modulation by macrophages.

    Science.gov (United States)

    Rodero, Mathieu P; Khosrotehrani, Kiarash

    2010-07-25

    Skin wound healing is a multi stage phenomenon that requires the activation, recruitment or activity of numerous cell types as keratinocytes, endothelial cells, fibroblast and inflammatory cells. Among the latter, macrophages appear to be central to this process. They colonize the wound at its very early stage and in addition to their protective immune role seem to organize the activity of other cell types at the following stages of the healing. Their benefit to this process is however controversial, as macrophages are described to promote the speed of healing but may also favour the fibrosis resulting from it in scars. Moreover wound healing defects are associated with abnormalities in the inflammatory phase. In this review, we summarise our knowledge on what are the Wound Associated Macrophages, and how they interact with the other cell types to control the reepithelisation, angiogenesis and the extracellular matrix remodelling. We believe this knowledge may open new avenues for therapeutic intervention on skin wounds.

  9. The receptor for advanced glycation end products RAGE is involved in corneal healing.

    Science.gov (United States)

    Nass, Norbert; Trau, Stefanie; Paulsen, Friedrich; Kaiser, Delia; Kalinski, Thomas; Sel, Saadettin

    2017-05-01

    Impaired corneal healing is still a major cause of blindness. As RAGE (receptor for advanced glycation endproducts) is involved in inflammation and wound healing in other tissues, we here investigated its relevance for corneal wound healing. Corneal re-epithelialization after alkaline injury was analysed in an ex-vivo approach with cultured, enucleated eyes from mice either of the C57Bl/6 NChR genotype (RAGE+/+) and mice of the same strain lacking the RAGE gene (RAGE-/-). The wound area was determined time dependently by fluorescence imaging using fluorescein staining. The eyes of RAGE-/- mice showed a significantly slower re-epithelialization than eyes of the RAGE+/- and the RAGE+/+ genotype. In immunohistochemistry, RAGE expression was increased in wounded corneas whereas the abundance of the RAGE ligand HMGB1 was unaffected, but an increase in S100b-like proteins was revealed upon injury. However, neither the addition of the RAGE agonist HMGB1 or an HMGB1 antagonising antibody nor bovine S100b protein to the culture medium of the wounded eyes had an effect on corneal wound closure in ex-vivo. Further gene expression analysis by RT-PCR demonstrated an increase in RAGE expression on the mRNA level, no significant regulation of HMGB1 and a differential regulation of the S100 gene family after alkaline burn of the cornea. In conclusion, RAGE is clearly involved in corneal re-epithelialization most probably mediated by signalling via S100 proteins. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. General concept of wound healing, revisited

    Directory of Open Access Journals (Sweden)

    Theddeus O.H. Prasetyono

    2009-09-01

    Full Text Available Wound healing is a transition of processes which is also recognized as one of the most complex processes in human physiology. Complex series of reactions and interactions among cells and mediators take place in the healing process of wound involving cellular and molecular events. The inflammatory phase is naturally intended to remove devitalized tissue and prevent invasive infection. The proliferative phase is characterized by the formation of granulation tissue within the wound bed, composed of new capillary network, fibroblast, and macrophages in a loose arrangement of supporting structure. This second phase lasts from day 8 to 21 after the injury is also the phase for epithelialisation. The natural period of proliferative phase is a reflection for us in treating wound to reach the goal which ultimately defines as closed wound. The final maturation phase is also characterized by the balancing between deposition of collagen and its degradation. There are at least three prerequisites which are ideal local conditions for the nature of wound to go on a normal process of healing i.e. 1 all tissue involved in the wound and surrounding should be vital, 2 no foreign bodies in the wound, and 3 free from excessive contamination/infection. The author formulated a step ladder of thinking in regards of healing intentions covering all acute and chronic wounds. Regarding the “hierarchy” of healing intention, the fi rst and ideal choice to heal wounds is by primary intention followed by tertiary intention and lastly the secondary intention. (Med J Indones 2009;18:206-14Key words: inflammatory mediator, epithelialisation, growth factor, wound healing

  11. Involvement of notch signaling in wound healing.

    Directory of Open Access Journals (Sweden)

    Srinivasulu Chigurupati

    Full Text Available The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions.

  12. Wound healing of intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Masahiro Iizuka; Shiho Konno

    2011-01-01

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

  13. Cellular events and biomarkers of wound healing

    Directory of Open Access Journals (Sweden)

    Shah Jumaat Mohd. Yussof

    2012-01-01

    Full Text Available 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.

  14. DIABETIC WOUND HEALING MANAGEMENT- A PEER REVIEW

    Directory of Open Access Journals (Sweden)

    Harshavardhan Pathapati

    2014-10-01

    Full Text Available Objectives: Diabetes is a metabolic disorder mainly impairs the body glucose utilization capacity due to this perforcely repressing the immuno-dysfunction (decreases chemotaxis, phagocytosis and intracellular killing actions and collagen synthesis which are essential in wound debridement management of diabetic patients. Delayed wound healing is considered as one of the most repulsive disabling and costly complication of diabetes. People with diabetes have extenuated circulation, poor resistance to infection and mitigate local nutrition, thus their wounds are meticulously susceptible to infection. Moreover diabetes agonizes the equilibrium exists between accumulation of extra-cellular matrix components and their re-modeling by matrix metallo-proteinases (meltrin, due to this extenuated proliferation action of fibroblasts and finally freezes the progress of wound healing frequency in hyper glycemics. However in diabetic persons the nervous system becomes numb and all feasible actions of neurons are skipped, that condition is called as diabetic neuropathy. In that situation patient body features elevated a glucose level which stiffens the arteries and lack of pain sensation in foot resulting in commencement of new wounds. Conclusion: Consider all problems associated with wound healing in diabetic persons, a proper wound healing management which includes controlling measures like optimized systemic and local factors as well as implement suitable wound dressing for necessary wound in diabeties patients.

  15. Honey: an immunomodulator in wound healing.

    Science.gov (United States)

    Majtan, Juraj

    2014-01-01

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

  16. Regeneration: the ultimate example of wound healing.

    Science.gov (United States)

    Murawala, Prayag; Tanaka, Elly M; Currie, Joshua D

    2012-12-01

    The outcome of wound repair in mammals is often characterized by fibrotic scaring. Vertebrates such as zebrafish, frogs, and salamanders not only heal scarlessly, but also can regenerate lost appendages. Decades of study on the process of animal regeneration has produced key insights into the mechanisms of how complex tissue is restored. By examining our current knowledge of regeneration, we can draw parallels with mammalian wound healing to identify the molecular determinants that produce such differing outcomes.

  17. Trehalose lyophilized platelets for wound healing.

    Science.gov (United States)

    Pietramaggiori, Giorgio; Kaipainen, Arja; Ho, David; Orser, Cindy; Pebley, Walter; Rudolph, Alan; Orgill, Dennis P

    2007-01-01

    Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds.

  18. Using behavior modification to promote wound healing.

    Science.gov (United States)

    Rivera, E; Walsh, A; Bradley, M

    2000-10-01

    Successfully caring for patients with wounds under PPS demands that current practice approaches must change. Instead of focusing on dressings and techniques alone, this article describes how first addressing patients' psychological readiness for change can move them quickly to self-care and enhance wound healing, which results in cost savings and better outcomes.

  19. Use of Oxygen Therapies in Wound Healing

    DEFF Research Database (Denmark)

    Gottrup, Finn; Dissemond, Joachim; Baines, Carol

    2017-01-01

    Among other things wound healing requires restoration of macro-And microcirculation as essential conditions for healing.1,2 One of the most 'immediate' requirements is oxygen, which is critically important for reconstruction of new vessels and connective tissue and to enable competent resistance...

  20. Mechanoregulation of Wound Healing and Skin Homeostasis

    Directory of Open Access Journals (Sweden)

    Joanna Rosińczuk

    2016-01-01

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

  1. Scarless wound healing: chasing the holy grail.

    Science.gov (United States)

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

    2015-03-01

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

  2. YAP and TAZ regulate skin wound healing.

    Science.gov (United States)

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

    2014-02-01

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

  3. Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing.

    Science.gov (United States)

    Bellner, Lars; Marrazzo, Giuseppina; van Rooijen, Nico; Dunn, Michael W; Abraham, Nader G; Schwartzman, Michal L

    2015-01-01

    Heme oxygenase (HO)-2 deficiency impairs wound healing and exacerbates inflammation following injury. We examine the impact of HO-2 deficiency on macrophage function and the contribution of macrophage HO-2 to inflammatory and repair responses to injury. Corneal epithelial debridement was performed in control and macrophage-depleted HO-2(-/-) and wild-type (WT) mice and in bone marrow chimeras. Peritoneal macrophages were collected for determination of phagocytic activity and classically activated macrophage (M1)-alternatively activated macrophage (M2) polarization. Depletion of macrophages delayed corneal healing (13.2%) and increased neutrophil infiltration (54.1%) by day 4 in WT mice, whereas in HO-2(-/-) mice, it did not worsen the already impaired wound healing and exacerbated inflammation. HO-2(-/-) macrophages displayed an altered M1 phenotype with no significant expression of M2 or M2-like activated cells and a 31.3% reduction in phagocytic capacity that was restored by inducing HO-1 activity or supplementing biliverdin. Macrophage depletion had no effect, whereas adoptive transfer of WT bone marrow improved wound healing (34% on day 4) but did not resolve the exaggerated inflammatory response in HO-2(-/-) mice. These findings indicate that HO-2-deficient macrophages are dysfunctional and that macrophage HO-2 is required for proper macrophage function but is insufficient to correct the impaired healing of the HO-2(-/-) cornea, suggesting that corneal epithelial expression of HO-2 is a key to resolution and repair in wound healing.

  4. Traumatic Wound Dehiscence following Corneal Transplantation

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Jafarinasab

    2012-01-01

    Full Text Available Purpose: To investigate the incidence, mechanisms, characteristics, and visual outcomes of traumatic wound dehiscence following keratoplasty. Methods: Medical records of 32 consecutive patients with traumatic globe rupture following keratoplasty who had been treated at our center from 2001 to 2009 were retrospectively reviewed. Results: The study population consisted of 32 eyes of 32 patients including 25 men and 7 women with history of corneal transplantation who had sustained eye trauma leading to globe rupture. Mean patient age was 38.1 (range, 8 to 87 years and median interval between keratoplasty and the traumatic event was 9 months (range, 30 days to 20 years. Associated anterior segment findings included iris prolapse in 71.9%, lens extrusion in 34.4%, and hyphema in 40.6% of eyes. Posterior segment complications included vitreous prolapse (56%, vitreous hemorrhage (28% and retinal detachment (18%. Eyes which had undergone deep anterior lamellar keratoplasty (DALK; 5 cases, 15.6% tended to have less severe presentation and better final visual acuity. There was no correlation between the time interval from keratoplasty to the traumatic event, and final visual outcomes. Conclusion: The host-graft interface demonstrates decreased stability long after surgery and the visual prognosis of traumatic wound dehiscence is poor in many cases. An intact Descemet′s membrane in DALK may mitigate the severity of ocular injuries, but even in these cases, the visual outcome of globe rupture is not good and prevention of ocular trauma should be emphasized to all patients undergoing any kind of keratoplasty.

  5. Nutritional Aspects of Gastrointestinal Wound Healing

    Science.gov (United States)

    Mukherjee, Kaushik; Kavalukas, Sandra L.; Barbul, Adrian

    2016-01-01

    Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures. PMID:27867755

  6. A wound healing model with sonographic monitoring.

    Science.gov (United States)

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

    1993-05-01

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

  7. Trends in Surgical Wound Healing

    DEFF Research Database (Denmark)

    Gottrup, F.

    2008-01-01

    The understanding of acute and chronic wound pathophysiology has progressed considerably over the past decades. Unfortunately, improvement in clinical practice has not followed suit, although new trends and developments have improved the outcome of wound treatment in many ways. This review focuses...

  8. The effects of caffeine on wound healing.

    Science.gov (United States)

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

    2016-10-01

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

  9. Forces driving epithelial wound healing

    Science.gov (United States)

    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.

  10. Microgravity and the implications for wound healing.

    Science.gov (United States)

    Farahani, Ramin Mostofizadeh; DiPietro, Luisa A

    2008-10-01

    Wound healing is a sophisticated response ubiquitous to various traumatic stimuli leading to an anatomical/functional disruption. The aim of present article was to review the current evidence regarding the effects of microgravity on wound healing dynamics. Modulation of haemostatic phase because of alteration of platelet quantity and function seems probable. Furthermore, production of growth factors that are released from activated platelets and infiltration/function of inflammatory cells seem to be impaired by microgravity. Proliferation of damaged structures is dependent on orchestrated function of various growth factors, for example transforming growth factors, platelet-derived growth factor and epidermal growth factor, all of which are affected by microgravitational status. Moreover, gravity-induced alterations of gap junction, neural inputs, and cell populations have been reported. It may be concluded that different cellular and extracellular element involved in the healing response are modified through effect of microgravity which may lead to impairment in healing dynamics.

  11. Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

    Directory of Open Access Journals (Sweden)

    Vincent A Funari

    Full Text Available MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6 and diabetic (n=6 central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR and by in situ hybridization (ISH in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR or their inhibitors (antagomirs using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

  12. Mammalian cell models to advance our understanding of wound healing: a review.

    Science.gov (United States)

    Vidmar, Jerneja; Chingwaru, Constance; Chingwaru, Walter

    2017-04-01

    Rapid and efficient healing of damaged tissue is critical for the restoration of tissue function and avoidance of tissue defects. Many in vitro cell models have been described for wound healing studies; however, the mechanisms that underlie the process, especially in chronic or complicated wounds, are not fully understood. The identification of cell culture systems that closely simulate the physiology of damaged tissue in vivo is necessary. We describe the cell culture models that have enhanced our understanding, this far, of the wound healing process or have been used in drug discovery. Cell cultures derived from the epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem cells), and the endothelium (human umbilical vein endothelial cells, primary mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and corneal endothelial cells) have played a pivotal role toward our understanding of the mechanisms of wound healing. More studies are necessary to develop co-culture cell models which closely simulate the environment of a wound in vivo. Cell culture models are invaluable tools to promote our understanding of the mechanisms that regulate the wound healing process and provide a platform for drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Epithelialization in Wound Healing: A Comprehensive Review

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Klein, Kenneth C; Guha, Somes Chandra

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kenneth C Klein

    2014-01-01

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

  16. The Presence of Oxygen in Wound Healing.

    Science.gov (United States)

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

    2016-08-01

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

  17. Kinin receptors in skin wound healing.

    Science.gov (United States)

    Soley, Bruna da Silva; Morais, Rafael Leite Tavares de; Pesquero, João Bosco; Bader, Michael; Otuki, Michel Fleith; Cabrini, Daniela Almeida

    2016-05-01

    Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B1 and B2. We aimed to evaluate the involvement of kinin receptors in the skin healing process. Knockout mice for kinin receptors (KOB1, KOB2 and KOB1B2) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing. In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB1, KOB2 and KOB1B2 from day two to the end of the healing process. Moreover, wound tissue from KOB2 and KOB1B2, but not KOB1, presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (α-SMA immunostaining). These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Cold temperature delays wound healing in postharvest sugarbeet roots

    Science.gov (United States)

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

  19. Skin wound healing and phytomedicine: a review.

    Science.gov (United States)

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

    2014-01-01

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

  20. Wound healing: an overview of acute, fibrotic and delayed healing.

    Science.gov (United States)

    Diegelmann, Robert F; Evans, Melissa C

    2004-01-01

    Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by

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

    Science.gov (United States)

    Ashrafi, Mohammed; Baguneid, Mohamed; Bayat, Ardeshir

    2016-06-15

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

  2. Emerging drugs for the treatment of wound healing.

    Science.gov (United States)

    Zielins, Elizabeth R; Brett, Elizabeth A; Luan, Anna; Hu, Michael S; Walmsley, Graham G; Paik, Kevin; Senarath-Yapa, Kshemendra; Atashroo, David A; Wearda, Taylor; Lorenz, H Peter; Wan, Derrick C; Longaker, Michael T

    2015-06-01

    Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

  3. Grand challenge in Biomaterials-wound healing

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

    Bohling, Mark W; Henderson, Ralph A

    2006-07-01

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

  6. Effects of glutamine on wound healing.

    Science.gov (United States)

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

    2015-06-01

    Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Wound healing Agents from Medicinal Plants:A Review

    Institute of Scientific and Technical Information of China (English)

    ShivaniRawat; Ramandeep Singh; Preeti Thakur; SatinderKaur; AlokSemwal

    2012-01-01

    This paper presents a review of plants identified from various ethno botanical surveys and folklore medicinal survey with Wound healing activity. Wound is defined as the disruption of the cellular and anatomic continuity of a tissue. Wound may be produced by physical, chemical, thermal, microbial or immunological insult to the tissues. The process of wound healing consists of integrated cellular and biochemical events leading to re-establishment of structural and functional integrity with regain of strength in injured tissues.This review discuss about Wound healing potential of plants, its botanicalname, Common name, family, part used and references, which are helpful for researcher to development new Wound healing formulations for human use.

  8. Cellular and Molecular Characteristics of Scarless versus Fibrotic Wound Healing

    Directory of Open Access Journals (Sweden)

    Latha Satish

    2010-01-01

    Full Text Available The purpose of this paper is to compare and contrast the discrete biology differentiating fetal wound repair from its adult counterpart. Integumentary wound healing in mammalian fetuses is essentially different from wound healing in adult skin. Adult (postnatal skin wound healing is a complex and well-orchestrated process spurred by attendant inflammation that leads to wound closure with scar formation. In contrast, fetal wound repair occurs with minimal inflammation, faster re-epithelialization, and without the accumulation of scar. Although research into scarless healing began decades ago, the critical molecular mechanisms driving the process of regenerative fetal healing remain uncertain. Understanding the molecular and cellular events during regenerative healing may provide clues that one day enable us to modulate adult wound healing and consequently reduce scarring.

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

    Science.gov (United States)

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

    2015-01-01

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

  10. The Effect of Oral Medication on Wound Healing.

    Science.gov (United States)

    Levine, Jeffrey M

    2017-03-01

    The purpose of this learning activity is to provide information about the effects of oral medications on wound healing. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Identify oral medications that aid in wound healing.2. Recognize oral medications that interfere with wound healing. Given the accelerated medical discoveries of recent decades, there is a surprising lack of oral medications that directly improve wound healing. Of the oral medications available, most target ancillary aspects of wound care such as pain management, infection mitigation, and nutrition. This article describes oral pharmacologic agents intended to build new tissue and aid in wound healing, as well as an introduction to oral medications that interfere with wound healing. This review will not discuss the pharmacology of pain management or treatment of infection, nor will it address nutritional supplements.

  11. Eicosanoids: Emerging contributors in stem cell-mediated wound healing.

    Science.gov (United States)

    Berry, Elizabeth; Liu, Yanzhou; Chen, Li; Guo, Austin M

    2016-11-05

    Eicosanoids are bioactive lipid products primarily derived from the oxidation of arachidonic acid (AA). The individual contributions of eicosanoids and stem cells to wound healing have been of great interest. This review focuses on how stem cells work in concert with eicosanoids to create a beneficial environment in the wound bed and in the promotion of wound healing. Stem cells contribute to wound healing through modulating inflammation, differentiating into skin cells or endothelial cells, and exerting paracrine effects by releasing various potent growth factors. Eicosanoids have been shown to stimulate proliferation, migration, homing, and differentiation of stem cells, all of which contribute to the process of wound healing. Increasing evidence has shown that eicosanoids improve wound healing through increasing stem cell densities, stimulating differentiation, and enhancing the angiogenic properties of stem cells. Chronic wounds have become a major problem in health care. Therefore, research regarding the effects of stem cells and eicosanoids in the promotion wound healing is of great importance.

  12. Identification of a transcriptional signature for the wound healing continuum.

    Science.gov (United States)

    Peake, Matthew A; Caley, Mathew; Giles, Peter J; Wall, Ivan; Enoch, Stuart; Davies, Lindsay C; Kipling, David; Thomas, David W; Stephens, Phil

    2014-01-01

    There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post-serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group). Sixty-six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified. Overrepresentation analysis revealed pathways directly and indirectly associated with wound healing and aging and additional categories associated with differentiation, development, and morphogenesis. Knowledge of this wound healing continuum gene signature may in turn assist in the therapeutic assessment/treatment of a patient's wounds. © 2014 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of Wound Healing Society.

  13. Chitosan-alginate membranes accelerate wound healing.

    Science.gov (United States)

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

    2015-07-01

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

  14. Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

    Directory of Open Access Journals (Sweden)

    Subhamoy Das

    2016-10-01

    Full Text Available Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice.

  15. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...chronic wounds with significant improvement in healing and scarring. Application of mesenchymal stem cell (MSC) therapy to severe burn wounds

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

    Science.gov (United States)

    Morton, Laurel M; Phillips, Tania J

    2016-04-01

    Wounds are an excellent example of how the field of dermatology represents a cross-section of many medical disciplines. For instance, wounds may be caused by trauma, vascular insufficiency, and underlying medical conditions, such as diabetes, hypertension, and rheumatologic and inflammatory disease. This continuing medical education article provides an overview of wound healing and the pathophysiology of chronic wounds and reviews the broad differential diagnosis of chronic wounds. It also describes the initial steps necessary in evaluating a chronic wound and determining its underlying etiology. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Label-free structural characterization of mitomycin C-modulated wound healing after photorefractive keratectomy by the use of multiphoton microscopy

    Science.gov (United States)

    Lo, Wen; Wang, Tsung-Jen; Chen, Wei-Liang; Hsueh, Chiu-Mei; Chen, Shean-Jen; Chen, Yang-Fang; Chou, Hsiu-Chu; Lin, Pi-Jung; Hu, Fung-Rong; Dong, Chen-Yuan

    2010-05-01

    We applied multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) microscopy to monitor corneal wound healing after photorefractive keratectomy (PRK). Our results show that keratocyte activation can be observed by an increase in its MAF, while SHG imaging of corneal stroma can show the depletion of Bowman's layer after PRK and the reticular collagen deposition in the wound healing stage. Furthermore, quantification of the keratocyte activation and collagen deposition in conjunction with immunohistochemistry and histological images demonstrate the effectiveness of mitomycin C (MMC) in suppressing myofibroblast proliferation and collagen regeneration in the post-PRK wound healing process.

  18. Wound healing - A literature review*

    Science.gov (United States)

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

    2016-01-01

    Regeneration and tissue repair processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. The exsudative, proliferative, and extracellular matrix remodeling phases are sequential events that occur through the integration of dynamic processes involving soluble mediators, blood cells, and parenchymal cells. Exsudative phenomena that take place after injury contribute to the development of tissue edema. The proliferative stage seeks to reduce the area of tissue injury by contracting myofibroblasts and fibroplasia. At this stage, angiogenesis and reepithelialization processes can still be observed. Endothelial cells are able to differentiate into mesenchymal components, and this difference appears to be finely orchestrated by a set of signaling proteins that have been studied in the literature. This pathway is known as Hedgehog. The purpose of this review is to describe the various cellular and molecular aspects involved in the skin healing process. PMID:27828635

  19. Study of Topical Human Umbilical Cord Blood Serum in the Treatment of Alkaline Corneal Epithelial Wounds in Rabbit Model

    Directory of Open Access Journals (Sweden)

    B Sharifi

    2011-04-01

    Full Text Available Introduction & Objective: One of the important functions of the cornea is to maintain normal vision by refracting light onto the lens and retina. This property is dependent in part on the ability of the corneal epithelium to undergo continuous renewal. Ocular surface failure which follows a variety of endogenous and exogenous precipitating factors, the most common being: chemical trauma, infection, alkaline burn, inflammation and hereditary conditions, lid or lash abnormalities, tear deficiency or reduced sensation. The core principal underpinning management strategy for ocular surface failure is establishing or promoting new growth of healthy conjunctiva and corneal epithelium. This process is mediated by many proteins that are inducers of corneal cell migration, proliferation, and differentiation. The current study was performed to investigate the efficacy of umbilical cord serum on alkaline corneal epithelial wound healing in the rabbit model. Materials & Methods: In this study conducted at Yasuj University of Medical Sciences in 2010, thirty two rabbits were randomly assigned into two equal groups. Central corneal alkali wound was formed in one eye of the rabbits by applying a 6-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. Group one of animals received umbilical cord blood serum and group two received Sno*Tear in the eyes. The treatment was dosed 4 times a day with the eye drops, and epithelial wound closure was recorded using slit lamp. The data were analyzed to determine the rate of wound closure. Results: The mean wound radius closure rate was 0.77 mm/day (SD=0.013 for umbilical cord blood serum-treated eyes, 0.73 mm/day (SD=0.018 for artificial tear-treated eyes. Conclusion: This study shows that alkali-injured corneal epithelial wound heal faster when treated with umbilical cord blood serum than with artificial tear in rabbit model.

  20. Matrix metalloproteinases in impaired wound healing

    OpenAIRE

    auf dem Keller, Ulrich; Sabino,Fabio

    2015-01-01

    Fabio Sabino, Ulrich auf dem Keller Institute of Molecular Health Sciences, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland Abstract: Cutaneous wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to finally re-establish the skin's barrier function upon injury. Proteolytic enzymes and in particular matrix metalloproteinases (MMPs) contribute to all phas...

  1. Burn Wound Mucormycosis: A Case Study on Poor Wound Healing.

    Science.gov (United States)

    Stanistreet, Bryan; Bell, Derek

    Mucormycosis is a rare, rapidly progressive and often fatal fungal infection. The rarity of the condition lends itself to unfamiliarity, delayed treatment, and poor outcomes. Diagnosis of fungal infections early enough to enable appropriate treatment occurs in less than half of affected patients. A 56-year-old male with a history of diabetes mellitus II, hepatitis C, and intravenous drug abuse was involved in a rollover motor vehicle accident. He sustained circumferential partial and full-thickness burns to his lower extremities with 20% BSA burns. He ultimately required a below-knee amputation of his right lower extremity due to poor wound healing and nonviability of the soft tissue and foot. Debridement found muscle fibers that were necrotic and purulent. Pathology revealed Mucor species with extensive vascular invasion. This case and discussion highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are concerning signs and symptoms of serious wound complications. Caretakers of severe trauma patients should have a high level of suspicion for complications and be cognizant of the American Burn Association's guidelines for systemic inflammatory response syndrome and sepsis. Progressive necrosis outside the confines of the original burn wound should raise concern for impaired wound healing, an immunocompromised state or an underlying infection.

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

    Science.gov (United States)

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

    2015-04-01

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

  3. Wound Healing Activity of Elaeis guineensis Leaf Extract Ointment

    Directory of Open Access Journals (Sweden)

    Sreenivasan Sasidharan

    2011-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  5. Evaluation of wound healing activity of Tecomaria capensis leaves

    Institute of Scientific and Technical Information of China (English)

    Saini NK; Singhal M; Srivastava B

    2012-01-01

    The aim of the present study was to evaluate the potential wound healing activity of Tecomaria capensis leaves extract (TCLE) using different models in rats.(a) Excision wound model,(b) Incision wound model and (c) Dead space wound model.TCLE (100,300,1 000 and 2 000 mg.kg-1) was given to rats to observe acute toxicity.No toxicity was found in animals till 14 days.TCLE 5% and 10% ointment were applied topically in excision wound model and incision wound model.TCLE 200 and 400 mg·kg-1 were given orally in dead space wound model.It improved healing in excision wound model,increased breaking strength of tissue in incision wound model,and increased granuloma breaking strength and hydroxyproline content in dead space wound model.These results showed that TCLE presents significant wound healing activity.

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

    Science.gov (United States)

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

    2014-09-01

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

  7. Complement deficiency promotes cutaneous wound healing in mice.

    Science.gov (United States)

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

    2015-02-01

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

  8. In vitro electrical-stimulated wound-healing chip for studying electric field-assisted wound-healing process

    OpenAIRE

    Sun, Yung-Shin; Peng, Shih-Wei; Cheng, Ji-Yen

    2012-01-01

    The wound-healing assay is an easy and economical way to quantify cell migration under diverse stimuli. Traditional assays such as scratch assays and barrier assays are widely and commonly used, but neither of them can represent the complicated condition when a wound occurs. It has been suggested that wound-healing is related to electric fields, which were found to regulate wound re-epithelialization. As a wound occurs, the disruption of epithelial barrier short-circuits the trans-epithelial ...

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

    Science.gov (United States)

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

    2015-01-02

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

  10. Stem cells and growth factors in wound healing

    Directory of Open Access Journals (Sweden)

    Michał Pikuła

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-08

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

  12. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing.

    Science.gov (United States)

    Kimball, Andrew S; Joshi, Amrita D; Boniakowski, Anna E; Schaller, Matthew; Chung, Jooho; Allen, Ronald; Bermick, Jennifer; Carson, William F; Henke, Peter K; Maillard, Ivan; Kunkel, Steve L; Gallagher, Katherine A

    2017-01-01

    Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) on a high-fat diet), improved wound healing was seen at late time points (days 6-7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  13. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    Andrew S. Kimball

    2017-06-01

    Full Text Available Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ demonstrated delayed early healing (days 1–3 and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D, Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet, improved wound healing was seen at late time points (days 6–7. These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  14. Principles of Wound Management and Wound Healing in the Exotic Pets

    Science.gov (United States)

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

    2015-01-01

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

  15. Complements and the Wound Healing Cascade: An Updated Review

    Directory of Open Access Journals (Sweden)

    Hani Sinno

    2013-01-01

    Full Text Available Wound healing is a complex pathway of regulated reactions and cellular infiltrates. The mechanisms at play have been thoroughly studied but there is much still to learn. The health care system in the USA alone spends on average 9 billion dollars annually on treating of wounds. To help reduce patient morbidity and mortality related to abnormal or prolonged skin healing, an updated review and understanding of wound healing is essential. Recent works have helped shape the multistep process in wound healing and introduced various growth factors that can augment this process. The complement cascade has been shown to have a role in inflammation and has only recently been shown to augment wound healing. In this review, we have outlined the biology of wound healing and discussed the use of growth factors and the role of complements in this intricate pathway.

  16. Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities

    Directory of Open Access Journals (Sweden)

    Anne Bukowiecki

    2017-06-01

    Full Text Available The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

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

    Science.gov (United States)

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

    2014-10-01

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

  18. New insights into microRNAs in skin wound healing.

    Science.gov (United States)

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

    2015-12-01

    Chronic wounds are a major burden to overall healthcare cost and patient morbidity. Chronic wounds affect a large portion of the US, and billions of healthcare dollars are spent in their treatment and management. microRNAs (miRNAs) are small, noncoding double-stranded RNAs that post-transcriptionally downregulate the expression of protein-coding genes. Studies have identified miRNAs involved in all three phases of wound healing including inflammation, proliferation, and remodeling. Some miRNAs have been demonstrated in vitro with primary keratinocyte wound healing model and in vivo with mouse wound healing model through regulation of miRNA expression to affect the wound healing process. This review updates the current miRNAs involved in wound healing and discusses the future therapeutic implications and research directions. © 2015 International Union of Biochemistry and Molecular Biology.

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

    Science.gov (United States)

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

    2017-07-01

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

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

    OpenAIRE

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

    2009-01-01

    This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization ...

  1. Haematological changes and wound healing effects of sildenafil ...

    African Journals Online (AJOL)

    ADEYEYE

    2016-12-07

    Dec 7, 2016 ... Sokoto Journal of Veterinary Sciences, Volume 15 (Number 1). April ... and Biochemistry, Faculty of Veterinary Medicine, University .... citrate could potentiate wound healing process in ..... late inflammatory response to wound ...

  2. Chemokine Involvement in Fetal and Adult Wound Healing

    Science.gov (United States)

    Balaji, Swathi; Watson, Carey L.; Ranjan, Rajeev; King, Alice; Bollyky, Paul L.; Keswani, Sundeep G.

    2015-01-01

    Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing. Recent Advances: The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds. Critical Issues: Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways. Future Directions: Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets. PMID:26543680

  3. Biologic therapeutics and molecular profiling to optimize wound healing.

    Science.gov (United States)

    Menke, Marie N; Menke, Nathan B; Boardman, Cecelia H; Diegelmann, Robert F

    2008-11-01

    Non-healing wounds represent a significant cause of morbidity and mortality for a large portion of the adult population. Wounds that fail to heal are entrapped in a self-sustaining cycle of chronic inflammation leading to the destruction of the extracellular matrix. Among cancer patients, malnutrition, radiation, physical dehabilitation, chemotherapy, and the malignancy itself increase the likelihood of chronic wound formation, and these co-morbidity factors inhibit the normal wound healing process. Current wound treatments are aimed at some, but not all, of the underlying causes responsible for delayed healing of wounds. These impediments block the normal processes that allow normal progression through the specific stages of wound healing. This review summarizes the current information regarding the management and treatment of complex wounds that fail to heal normally and offers some insights into novel future therapies [Menke N, Ward KR, Diegelmann R. Non-healing wounds. Emerg Med Rep 2007; 28(4).,Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol 2007;25:19-25].

  4. Effects of isoniazid and niacin on experimental wound-healing

    DEFF Research Database (Denmark)

    Weinreich, Jürgen; Ågren, Sven Per Magnus; Bilali, Erol

    2010-01-01

    There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.......There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues....

  5. Stem cells and growth factors in wound healing

    OpenAIRE

    Michał Pikuła; Paulina Langa; Paulina Kosikowska; Piotr Trzonkowski

    2015-01-01

    Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound...

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

    Science.gov (United States)

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

    2015-09-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis. © 2015 by the Wound Healing Society.

  7. Platelet gel for healing cutaneous chronic wounds.

    Science.gov (United States)

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

    2004-04-01

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

  8. The contribution of interleukin-2 to effective wound healing.

    Science.gov (United States)

    Doersch, Karen M; DelloStritto, Daniel J; Newell-Rogers, M Karen

    2017-02-01

    Ineffective skin wound healing is a significant source of morbidity and mortality. Roughly 6.5 million Americans experience chronically open wounds and the cost of treating these wounds numbers in the billions of dollars annually. In contrast, robust wound healing can lead to the development of either hypertrophic scarring or keloidosis, both of which can cause discomfort and can be cosmetically undesirable. Appropriate wound healing requires the interplay of a variety of factors, including the skin, the local microenvironment, the immune system, and the external environment. When these interactions are perturbed, wounds can be a nidus for infection, which can cause them to remain open an extended period of time, or can scar excessively. Interleukin-2, a cytokine that directs T-cell expansion and phenotypic development, appears to play an important role in wound healing. The best-studied role for Interleukin-2 is in influencing T-cell development. However, other cell types, including fibroblasts, the skin cells responsible for closing wounds, express the Interleukin-2 receptor, and therefore may respond to Interleukin-2. Studies have shown that treatment with Interleukin-2 can improve the strength of healed skin, which implicates Interleukin-2 in the wound healing process. Furthermore, diseases that involve impaired wound healing, such as diabetes and systemic lupus erythematosus, have been linked to deficiencies in Interleukin-2 or defects Interleukin-2-receptor signaling. The focus of this review is to summarize the current understanding of the role of Interleukin-2 in wound healing, to highlight diseases in which Interleukin-2 and its receptor may contribute to impaired wound healing, and to assess Interleukin-2-modulating approaches as potential therapies to improve wound healing.

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

    DEFF Research Database (Denmark)

    Schmidt, Jacob Günther; Andersen, Elisabeth Wreford; Ersbøll, Bjarne Kjær

    2016-01-01

    We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post......-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β1 and -β3......, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least...

  10. Wound healing potential of Pterocarpus santalinus linn: a pharmacological evaluation.

    Science.gov (United States)

    Biswas, Tuhin Kanti; Maity, Lakshmi Narayan; Mukherjee, Biswapati

    2004-09-01

    The need for new therapeutics for wound healing has encouraged the drive to examine the nature and value of plant products. Ayurveda, the Indian traditional system of medicine, mentions the values of medicinal plants for wound healing. One of these is Pterocarpus santalinus. This article describes a pharmacological study to evaluate its toxicity as well as wound-healing potential in animal studies. Powder made from the wood of the P. santalinus tree was used to make up an ointment in a petroleum jelly base. No toxic effects were observed in 72 hours. Studies were done on punch and burn wound models on normal and diabetic rats using the test ointment, untreated and vehicle controls, and standard therapy. Physical and biochemical measurements were made. The test ointment-treated wounds healed significantly faster. On healing, collagenesis and biochemical measurements yielded supportive data. These studies permit the conclusion that the P. santalinus ointment is safe and effective in treating acute wounds in animal models.

  11. Human skin transcriptome during superficial cutaneous wound healing.

    Science.gov (United States)

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

    2012-01-01

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

  12. Traditional Therapies for Skin Wound Healing.

    Science.gov (United States)

    Pereira, Rúben F; Bártolo, Paulo J

    2016-05-01

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

  13. Traditional Therapies for Skin Wound Healing

    Science.gov (United States)

    Pereira, Rúben F.; Bártolo, Paulo J.

    2016-01-01

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

  14. A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties.

    Science.gov (United States)

    Kasus-Jacobi, Anne; Noor-Mohammadi, Samaneh; Griffith, Gina L; Hinsley, Heather; Mathias, Lauren; Pereira, H Anne

    2015-02-01

    CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120-146 QR, 120-146 QH, 120-146 WR, and 120-146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120-146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo.

  15. Wound healing properties and kill kinetics of Clerodendron splendens G. Don, a Ghanaian wound healing plant

    Directory of Open Access Journals (Sweden)

    Stephen Y Gbedema

    2010-01-01

    Full Text Available As part of our general objective of investigating indigenous plants used in wound healing in Ghana, we hereby report our findings from some in vitro and in vivo studies related to wound healing activities of Clerodendron splendens G. Don (Verbanaceae. Methanolic extract of the aerial parts of the plant was tested for antimicrobial activity against Gram positive bacteria (Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Micrococcus flavus, as well as resistant strains of Staph. aureus SA1199B, RN4220 and XU212, Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteous mirabilis, Klebsiella pneumoniae and Candida albicans using the micro-well dilution method. Survivor-time studies of the microorganisms, radical scavenging activity using 2,2′-diphenylpicrylhydrazyl (DPPH and various in vivo wound healing activity studies were also conducted on the extract. The extract exhibited biostatic action against all the test microorganisms with a Minimum Inhibition Concentration (MIC ranging between 64 and 512 μg/ml and a free radical scavenging property with an IC 50 value of 103.2 μg/ml. The results of the in vivo wound healing tests showed that upon application of C. splendens ointment, there was a reduction in the epithelization period from 26.7 days (control to 13.6 days along with a marked decrease in the scar area from 54.2 mm 2 (control to 25.2 mm 2 . Significant increase in the tensile strength and hydroxyproline content were also observed as compared to the control and was comparable to nitrofurazone. The above results appear to justify the traditional use of C. splendens in wound healing and treatment of skin infections in Ghana.

  16. LL-37 via EGFR transactivation to promote high glucose-attenuated epithelial wound healing in organ-cultured corneas.

    Science.gov (United States)

    Yin, Jia; Yu, Fu-Shin X

    2010-04-01

    Purpose. Patients with diabetes are at higher risk for delayed corneal reepithelialization and infection. Previous studies indicated that high glucose (HG) impairs epidermal growth factor receptor (EGFR) signaling and attenuates ex vivo corneal epithelial wound healing. The authors investigated the effects of antimicrobial peptide LL-37 on HG-attenuated corneal epithelial EGFR signaling and wound closure. Methods. Human corneal epithelial cells (HCECs) were stimulated with LL-37. Heparin-binding EGF-like growth factor (HB-EGF) shedding was assessed by measuring the release of alkaline phosphatase (AP) in a stable HCEC line expressing HB-EGF-AP. Activation of EGFR, phosphoinositide 3-kinase (PI3K), and extracellular signal-regulated kinases 1/2 (ERK1/2) was determined by Western blot analysis. Corneal epithelial wound closure was assessed in cultured HCECs and porcine corneas. LL-37 expression was determined by immune dot blot. Results. LL-37 induced HB-EGF-AP release and EGFR activation in a dose-dependent manner. LL-37 prolonged EGFR signaling in response to wounding. LL-37 enhanced the closure of a scratch wound in cultured HCECs and partially rescued HG-attenuated wound healing in an EGFR- and a PI3K-dependent manner and restored HG-impaired EGFR signaling in cultured porcine corneas. HG attenuated wounding-induced LL-37 expression in cultured HCECs. Conclusions. LL-37 is a tonic factor promoting EGFR signaling and enhancing epithelial wound healing in normal and high glucose conditions. With both antimicrobial and regenerative capabilities, LL-37 may be a potential therapeutic for diabetic keratopathy.

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

    Science.gov (United States)

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

    2016-05-02

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

  18. A small peptide with potential ability to promote wound healing.

    Science.gov (United States)

    Tang, Jing; Liu, Han; Gao, Chen; Mu, Lixian; Yang, Shilong; Rong, Mingqiang; Zhang, Zhiye; Liu, Jie; Ding, Qiang; Lai, Ren

    2014-01-01

    Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β) are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2]) containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1) the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2) the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3) tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6) in murine macrophages and activating mitogen-activated protein kinases (MAPK) signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β), tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.

  19. A small peptide with potential ability to promote wound healing.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2] containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1 the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2 the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3 tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6 in murine macrophages and activating mitogen-activated protein kinases (MAPK signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β, tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.

  20. Effects of Dermal Multipotent Cell Transplantation on Skin Wound Healing

    Institute of Scientific and Technical Information of China (English)

    ShiChunmeng; ChengTianmin; SuYongping; RanXinze; MaiYue; QuJifu; LouShufen; XuHui; LuoChengji

    2005-01-01

    There is increasing evidence that dermis contains adult multipotent stem cells. To investigate the effects of dermis-derived multipotent cells on wound healing, we transplanted a clonal population of dermis-derived multipotent cells (termed as DMCs) by topical and systemic application into the skin wound of rats with simple wounds and rats with combined wound and radiation injury. Our results suggest that both topical and systemic transplantation of DMCs accelerate the healing process in rats with a simple wound; the promoting effect by topical transplantation occurs earlier than systemic transplantation. However, systemic transplantation of DMCs promotes the healing process in irradiated rats, while topical transplantation of DMCs fails. Further studies on the mechanisms of DMCs to promote wound healing indicate that the supernatant of DMCs could promote the proliferation of fibroblasts and epidermal cells; DMCs expressed transcripts of a serics of cytokincs and cxtraccllular matrix molecules, including VEGF, PDGF, HGF, TGF-β, ICAM-1, VCAM-1, and Fibronectin, which were closely related to the wound healing by DNA microarray analysis. The implanted DMCs can engraft into recipient skin wounded tissues after transplantation by the FISH analysis with Y-chromosome-specific probe. Systemic transplantation of DMCs also promotes the recovery of peripheral white blood cells in irradiated rats. These results demonstrate the different effects of DMCs on wound healing in nonirradiated and irradiated rats and illustrate the importance of optimizing wound healing via the topical or systemic transplantation of stem cells.

  1. Connexins in wound healing; perspectives in diabetic patients.

    Science.gov (United States)

    Becker, David L; Thrasivoulou, Christopher; Phillips, Anthony R J

    2012-08-01

    Skin lesions are common events and we have evolved to rapidly heal them in order to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal without issue, but as we get older our bodies become compromised by poor blood circulation and conditions such as diabetes, leading to slower healing. This can result in stalled or hard-to-heal chronic wounds. Currently about 2% of the Western population develop a chronic wound and this figure will rise as the population ages and diabetes becomes more prevalent [1]. Patient morbidity and quality of life are profoundly altered by chronic wounds [2]. Unfortunately a significant proportion of these chronic wounds fail to respond to conventional treatment and can result in amputation of the lower limb. Life quality and expectancy following amputation is severely reduced. These hard to heal wounds also represent a growing economic burden on Western society with published estimates of costs to healthcare services in the region of $25B annually [3]. There exists a growing need for specific and effective therapeutic agents to improve healing in these wounds. In recent years the gap junction protein Cx43 has been shown to play a pivotal role early on in the acute wound healing process at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in wound edge keratinocytes was shown to underlie the poor rate of healing in diabetic rats, and targeting its expression with an antisense gel restored normal healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the poor healing of human chronic wounds and be amenable therapeutic intervention [7]. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Boateng, Joshua; Catanzano, Ovidio

    2015-11-01

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

  3. Full-thickness splinted skin wound healing models in db/db and heterozygous mice: implications for wound healing impairment.

    Science.gov (United States)

    Park, Shin Ae; Teixeira, Leandro B C; Raghunathan, Vijay Krishna; Covert, Jill; Dubielzig, Richard R; Isseroff, Roslyn Rivkah; Schurr, Michael; Abbott, Nicholas L; McAnulty, Jonathan; Murphy, Christopher J

    2014-01-01

    The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study...... to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound...... healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died...

  5. Evaluation of anti-bacterial and wound healing activity of the fruits of ...

    African Journals Online (AJOL)

    Evaluation of anti-bacterial and wound healing activity of the fruits of ... the functional roles of the fruits of Amorpha fruticosa L. during wound healing progress. ... fibroblasts proliferation and migration, leading to promotion of wound healing.

  6. Wound healing activity of Curcuma zedoaroides

    Directory of Open Access Journals (Sweden)

    Pattreeya Tungcharoen

    2016-12-01

    Full Text Available Curcuma zedoaroides rhizomes have been used in Thai folk medicine as antidote and wound care for king cobra bite wound. The inhibitory effect of C. zedoaroides extract and its fractions on inflammation were detected by reduction of nitric oxide release using RAW264.7 cells. The improvement capabilities on wound healing were determined on fibroblast L929 cells proliferation and migration assays. The results showed that crude EtOH extract, CHCl3 and hexane fractions inhibited NO release with IC50 values of 14.0, 12.4 and 14.6 μg/ml, respectively. The CHCl3 and EtOAc fractions significantly increased L929 cells proliferation, enhanced fibroblast cells migration (100% on day 3 and scavenged DPPH with IC50 of 40.9 and 7.2 μg/ml, respectively. Only the CHCl3 fraction showed marked effect against carrageenan-induced rat paw edema (IC50 = 272.4 mg/kg. From the present study, both in vitro and in vivo models support the traditional use of C. zedoaroides

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Diabetes medications: Impact on inflammation and wound healing.

    Science.gov (United States)

    Salazar, Jay J; Ennis, William J; Koh, Timothy J

    2016-01-01

    Chronic wounds are a common complication in patients with diabetes that often lead to amputation. These non-healing wounds are described as being stuck in a persistent inflammatory state characterized by accumulation of pro-inflammatory macrophages, cytokines and proteases. Some medications approved for management of type 2 diabetes have demonstrated anti-inflammatory properties independent of their marketed insulinotropic effects and thus have underappreciated potential to promote wound healing. In this review, the potential for insulin, metformin, specific sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors to promote healing is evaluated by reviewing human and animal studies on inflammation and wound healing. The available evidence indicates that diabetic medications have potential to prevent wounds from becoming arrested in the inflammatory stage of healing and to promote wound healing by downregulating pro-inflammatory cytokines, upregulating growth factors, lowering matrix metalloproteinases, stimulating angiogenesis, and increasing epithelization. However, no clinical recommendations currently exist on the potential for specific diabetic medications to impact healing of chronic wounds. Thus, we encourage further research that may guide physicians on providing personalized diabetes treatments that achieve glycemic goals while promoting healing in patients with chronic wounds.

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

    Science.gov (United States)

    Lu, Shuliang

    2014-04-01

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

  10. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pwound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

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

    Science.gov (United States)

    2015-01-01

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

  12. CEACAM1 deficiency delays important wound healing processes.

    Science.gov (United States)

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

    2011-11-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration. © 2014 by the Wound Healing Society.

  14. Models of wound healing: an emphasis on clinical studies.

    Science.gov (United States)

    Wilhelm, K-P; Wilhelm, D; Bielfeldt, S

    2017-02-01

    The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds. Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even split-thickness or full thickness wounds. Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2015-05-01

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

  16. Stem Cell Therapy in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-08-01

    a novel approach to many diseases. SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response.  KEYWORDS: wound healing, tissue regeneration, stem cells therapy

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

    Science.gov (United States)

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

    2013-01-01

    Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics. © 2013 by the Wound Healing Society.

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

    Science.gov (United States)

    Panda, Vandana; Thakur, Tejas

    2014-03-01

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

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

    Science.gov (United States)

    Volk, Susan W; Bohling, Mark W

    2013-01-01

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

  20. Antioxidant and wound healing potential of Pistia stratiotes L.

    Directory of Open Access Journals (Sweden)

    Megha Jha

    2012-10-01

    Full Text Available Objective: To investigate the effects of Pistia stratiotes on wound healing activity in Swiss albino mice by excision wound healing model and its antioxidant study was performed to understand the mechanism of wound healing potency.Methods: Mice were topically treated with extract formulated in ointment by using simple ointment vaseline as base. 5% and 10% (w/w ointment was applied once daily. A standard group was treated with Povidone iodine ointment topically. The area of wound was measured on 4, 6, 8, 10, 12, 14, 16 post-wounding days. The scar area on complete epithelization was measured. The parameters observed were wound contraction (mm2, epithelization period and tensile strength including histopathological studies. Antioxidant activity was determined by in vitro method-H2O2 radical scavenging. Results: Treatment of wound with ointment containing 5% and 10% (w/w extract of Pistia stratiotes exhibited significant (P < 0.001 wound healing activity when compared with control group. All parameters such as wound contraction (mm2, epithelization period and tensile strength and histopathological studies showed significant changes when compared to control. Extracts possess significant antioxidant activity compared to control group. Ascorbic acid was used as reference standard for antioxidant activity (P<0.001 vs Ascorbic acid. Conclusion: The results conclude that Pistia stratiotes has antioxidant properties, which may be responsible and favorable for faster wound healing and this plant extract may be useful in the management of wounds, it also supports its traditional use.

  1. The Effect of Magnetic Fields on Wound Healing

    OpenAIRE

    Henry, Steven L.; Concannon, Matthew J; Yee, Gloria J

    2008-01-01

    Objective: Magnets are purported to aid wound healing despite a paucity of scientific evidence. The purpose of this study was to evaluate the effect of static magnetic fields on cutaneous wound healing in an animal model. The literature was reviewed to explore the historical and scientific basis of magnet therapy and to define its current role in the evidence-based practice of plastic surgery. Methods: Standardized wounds were created on the backs of 33 Sprague-Dawley rats, which were divided...

  2. Curcumin: a novel therapeutic for burn pain and wound healing

    Science.gov (United States)

    2013-08-01

    for controlling pain and wound healing. Several reports clearly demonstrate that cur- cumin can directly act on nociceptive neurons and inhibit...bioavailability 5. Curcumin delivery vehicles 6. Conclusion 7. Expert opinion Review Curcumin: a novel therapeutic for burn pain and wound healing Bopaiah...Surgical Research, Battlefield Pain Management Research Task Area, Fort Sam Houston, TX, USA Introduction: Managing burn injury-associated pain and wounds

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

    Science.gov (United States)

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

    2015-10-01

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

  4. Combined effect of PLGA and curcumin on wound healing activity.

    Science.gov (United States)

    Chereddy, Kiran Kumar; Coco, Régis; Memvanga, Patrick B; Ucakar, Bernard; des Rieux, Anne; Vandermeulen, Gaëlle; Préat, Véronique

    2013-10-28

    Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. The application of exogenous lactate released from poly (lactic-co-glycolic acid) (PLGA) polymer accelerated angiogenesis and wound healing processes. Curcumin is a well-known topical wound healing agent for both normal and diabetic-impaired wounds. Hence, we hypothesized that the PLGA nanoparticles encapsulating curcumin could much potentially accelerate the wound healing. In a full thickness excisional wound healing mouse model, PLGA-curcumin nanoparticles showed a twofold higher wound healing activity compared to that of PLGA or curcumin. Histology and RT-PCR studies confirmed that PLGA-curcumin nanoparticles exhibited higher re-epithelialization, granulation tissue formation and anti-inflammatory potential. PLGA nanoparticles offered various benefits for the encapsulated curcumin like protection from light degradation, enhanced water solubility and showed a sustained release of curcumin over a period of 8 days. In conclusion, we demonstrated the additive effect of lactic acid from PLGA and encapsulated curcumin for the active healing of wounds.

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

    Science.gov (United States)

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

    2014-03-01

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

  6. Wound healing properties of Indian propolis studied on excision wound-induced rats.

    Science.gov (United States)

    Iyyam Pillai, S; Palsamy, P; Subramanian, S; Kandaswamy, M

    2010-11-01

    In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.

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

    Science.gov (United States)

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

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

  8. Wound healing and antiinflammatory potential of madhu ghrita

    Directory of Open Access Journals (Sweden)

    Charde M

    2006-01-01

    Full Text Available Madhu ghrita is a herbal formulation containing honey and ghee (clarified butterfat as its constituents. The aim of present study is to verify the wound healing and antiinflammatory claims of Madhu ghrita . Incision and excision wound models were used for evaluation of wound healing activity followed by histopathological study in which healing markers like keratinization, epithelization, fibrosis, neovascularisation and collagenation were evaluated in male Wistar rats. The results of Madhu ghrita were compared with the results of untreated control group and results of framycetine sulphate cream, considered as a positive control. The formulation was also tested for antiinflammatory activity, using carrageenan-induced paw oedema in male Wistar rats. The test formulation Madhu ghrita enhanced the tensile strength, which significantly improved over untreated wounds. The tensile strength of untreated control wound was 281±5.82, while with the Madhu ghrita and framycetine sulphate cream 1% w/w, it was 328±8.9 and 398±6.32, respectively. Treatment with Madhu ghrita alone promoted wound contraction and reduced the wound closure time, so increase in tensile strength and wound contraction shows the wound healing potential of Madhu ghrita . Histopathological study shows that proliferation of epithelial tissue promotes angiogenesis, multiplication of fibrous connective tissue due to treatment with Madhu ghrita . The test formulation Madhu ghrita also shows significant antiinflammatory activity when the results are compared with the activity of ibuprofen gel as reference standard. The present study demonstrates the wound healing and antiinflammatory potential of Madhu ghrita .

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

    Science.gov (United States)

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

    2011-07-08

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

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

    Science.gov (United States)

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

    2014-08-01

    Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P healing of diabetic wounds. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  11. Evaluation of ghee based formulation for wound healing activity.

    Science.gov (United States)

    Prasad, Vure; Dorle, Avinash Kumar

    2006-08-11

    Formulation containing neomycin and ghee was evaluated for wound-healing potential on different experimental models of wounds in rats. The rats were divided into six groups of group 1 as control, group 2 as treated with neomycin only, group 3 as treated only with ghee, group 4 treated with F-1 formulation containing ghee 40% and neomycin 0.5%, group 5 treated with F-2 formulation containing ghee 50% and neomycin 0.5% and group 6 treated with F-3 formulation containing ghee and ointment base in all two wound models, each group consisting of six rats. Wound contraction ability in excision wound model was measured at different time intervals and study was continued until wound is completely healed. Tensile strength was measured in 10-day-old incision wound and quantitative estimation of hydroxy proline content in the healed tissue was determined in 10-day-old excision wound. Histological studies were done on 10-day-old sections of regenerated tissue of incision wound. F-2 formulation containing ghee 50% and neomycin 0.5% showed statistically significant response, in terms of wound contracting ability, wound closure time, period of epithelization, tensile strength of the wound, regeneration of tissues at wound site when compared with the control group and these results were comparable to those of a reference neomycin ointment.

  12. Review: African medicinal plants with wound healing properties.

    Science.gov (United States)

    Agyare, Christian; Boakye, Yaw Duah; Bekoe, Emelia Oppong; Hensel, Andreas; Dapaah, Susana Oteng; Appiah, Theresa

    2016-01-11

    Wounds of various types including injuries, cuts, pressure, burns, diabetic, gastric and duodenal ulcers continue to have severe socio-economic impact on the cost of health care to patients, family and health care institutions in both developing and developed countries. However, most people in the developing countries, especially Africa, depend on herbal remedies for effective treatment of wounds. Various in vitro and in vivo parameters are used for the evaluation of the functional activity of medicinal plants by using extracts, fractions and isolated compounds. The aim of the review is to identify African medicinal plants with wound healing properties within the last two decades. Electronic databases such as PubMed, Scifinder(®) and Google Scholar were used to search and filter for African medicinal plants with wound healing activity. The methods employed in the evaluation of wound healing activity of these African medicinal plants comprise both in vivo and in vitro models. In vivo wound models such as excision, incision, dead space and burn wound model are commonly employed in assessing the rate of wound closure (contraction), tensile strength or breaking strength determination, antioxidant and antimicrobial activities, hydroxyproline content assay and histological investigations including epithelialisation, collagen synthesis, and granulation tissue formation. In in vitro studies, single cell systems are mostly used to study proliferation and differentiation of dermal fibroblasts and keratinocytes by monitoring typical differentiation markers like collagen and keratin. In this study, 61 plants belonging to 36 families with scientifically demonstrated or reported wound healing properties were reviewed. Various plant parts including leaves, fruits, stem bark and root extracts of the plants are used in the evaluation of plants for wound healing activities. Although, a variety of medicinal plants for wound healing can be found in literature, there is a need for the

  13. ZO-1: lamellipodial localization in a corneal fibroblast wound model.

    Science.gov (United States)

    Taliana, Lavinia; Benezra, Miriam; Greenberg, Roseanne S; Masur, Sandra K; Bernstein, Audrey M

    2005-01-01

    To explore the roles of ZO-1 in corneal fibroblasts and myofibroblasts in a model of wounding. Antibodies were used to identify ZO-1 in cultured rabbit corneal fibroblasts by immunocytochemistry, Western blot analysis, and immunoprecipitation. For colocalization studies, antibodies to beta-catenin, cadherins, connexins, integrins, alpha-actinin, and cortactin were used. G- and F-actin were identified by DNase and rhodamine phalloidin, respectively. To study ZO-1 localization during cell migration, confluent corneal fibroblasts were subjected to scrape-wounding and evaluated by immunocytochemistry. As predicted from previous studies, ZO-1 colocalized with cadherins and connexin 43 in intercellular junctions. The study revealed a new finding: ZO-1 was also detected at the leading edge of lamellipodia, especially in motile wounded fibroblasts and in freshly plated fibroblasts, before the formation of cell-cell contacts. In fibroblast lysates, ZO-1 largely partitioned to the detergent-soluble fraction compared with myofibroblast lysates, indicating that much of the fibroblast ZO-1 is not associated with insoluble structural components. Lamellipodial ZO-1 colocalized with G-actin, alpha-actinin, and cortactin, which are proteins involved with actin remodeling and cell migration. Integrins alpha5beta1 and alphavbeta3 also localized to the leading edge of migrating fibroblasts, and the association of ZO-1 with integrin was confirmed by immunoprecipitation. Finally, alkaline phosphatase treatment of fibroblast lysate decreased the molecular mass of ZO-1 in lysates of cells grown in serum, demonstrating that, in activated fibroblasts, ZO-1 is phosphorylated. ZO-1's appearance at the leading edge of migrating fibroblasts makes it a candidate for a role in the initiation and organization of integrin-dependent fibroblast adhesion complexes formed during migration and adhesion. Further, phosphorylation of ZO-1 may regulate its cellular localization.

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

    Directory of Open Access Journals (Sweden)

    Inna Maltseva

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

  15. Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection

    DEFF Research Database (Denmark)

    Steinstraesser, Lars; Hirsch, Tobias; Schulte, Matthias

    2012-01-01

    . Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR......-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL......-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However...

  16. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing

    Science.gov (United States)

    Schmidt, Barbara A.; Horsley, Valerie

    2013-01-01

    Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cells are activated and function during acute skin wound healing. We find that adipocyte precursor cells proliferate and mature adipocytes repopulate skin wounds following inflammation and in parallel with fibroblast migration. Functional analysis of mice with defects in adipogenesis demonstrates that adipocytes are necessary for fibroblast recruitment and dermal reconstruction. These data implicate adipocytes as a key component of the intercellular communication that mediates fibroblast function during skin wound healing. PMID:23482487

  17. Collective cell migration: Implications for wound healing and cancer invasion

    Directory of Open Access Journals (Sweden)

    Li Li

    2013-07-01

    Full Text Available During embryonic morphogenesis, wound repair and cancer invasion, cells often migrate collectively via tight cell-cell junctions, a process named collective migration. During such migration, cells move as coherent groups, large cell sheets, strands or tubes rather than individually. One unexpected finding regarding collective cell migration is that being a "multicellular structure" enables cells to better respond to chemical and physical cues, when compared with isolated cells. This is important because epithelial cells heal wounds via the migration of large sheets of cells with tight intercellular connections. Recent studies have gained some mechanistic insights that will benefit the clinical understanding of wound healing in general. In this review, we will briefly introduce the role of collective cell migration in wound healing, regeneration and cancer invasion and discuss its underlying mechanisms as well as implications for wound healing.

  18. EFFECT OF TASPINE ON WOUND HEALING AND FIBROBLAST PROLIFERATION

    Institute of Scientific and Technical Information of China (English)

    Dong Yalin; He Langchong; Chen Fang

    2005-01-01

    Objective To study the effect and mechanism of taspine on wound healing and fibroblast proliferation. Methods The effect of taspine on skin wound was observed in vivo. The different concentration of taspine hydrochloride was added to L929 fibroblast cultivated in vitro, and lactate dehydrogenase was detected and MTT method was applied to observe effect of taspine on fibroblast proliferation. Results The local application of taspine 3 mg/Ml and 1.5 mg/mL accelerated the healing of skin wounded. In vitro, 0.01~0.5 μg/mL of taspine hydrochloride showed no effect on the change of lactate dehydrogenase activity and fibroblast proliferation. Conclusion Taspine is a kind of active alkaloid from leontice robustum which can enhance wound healing, its mechanism on wound healing is not by means of accelerating the proliferation of fibroblast, other mechanisms are necessary for being further studied.

  19. Macrophage PPARγ and impaired wound healing in type 2 diabetes.

    Science.gov (United States)

    Mirza, Rita E; Fang, Milie M; Novak, Margaret L; Urao, Norifumi; Sui, Audrey; Ennis, William J; Koh, Timothy J

    2015-08-01

    Macrophages undergo a transition from pro-inflammatory to healing-associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up-regulation of the peroxisome proliferator-activated receptor (PPAR)γ and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up-regulation of PPARγ activity was impaired by sustained expression of IL-1β in both mouse and human wounds. In addition, experiments with myeloid-specific PPARγ knockout mice indicated that loss of PPARγ in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARγ agonists promoted a healing-associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARγ agonists improved healing in diabetic mice, suggesting an appealing strategy for down-regulating inflammation and improving the healing of chronic wounds.

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

    Science.gov (United States)

    Galili, Uri

    2017-01-01

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

  1. A potential wound healing-promoting peptide from frog skin.

    Science.gov (United States)

    Liu, Han; Mu, Lixian; Tang, Jing; Shen, Chuanbin; Gao, Chen; Rong, Mingqiang; Zhang, Zhiye; Liu, Jie; Wu, Xiaoyang; Yu, Haining; Lai, Ren

    2014-04-01

    Cutaneous wound healing is a dynamic, complex, and well-organized process that requires the orchestration of many different cell types and cellular processes. Transforming growth factor β1 is an important factor that plays a key role during wound healing. Amphibian skin has been proven to possess excellent wound healing ability, whilst no bioactive substrate related to it has ever been identified. Here, a potential wound healing-promoting peptide (AH90, ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami. It showed potential wound healing-promoting activity in a murine model with full thickness dermal wound. AH90 promoted release of transforming growth factor β1 through activation of nuclear factor-κB and c-Jun NH2-terminal kinase mitogen-activated protein kinases signaling pathways, while inhibitors of nuclear factor-κB and c-Jun NH2-terminal kinase inhibited the process. In addition, the effects of AH90 on Smads family proteins, key regulators in transforming growth factor β1 signaling pathways, could also be inhibited by transforming growth factor β1 antibody. Altogether, this indicated that AH90 promoted wound healing by inducing the release of transforming growth factor β1. This current study may facilitate the understanding of effective factors involved in the wound repair of amphibians and the underlying mechanisms as well. Considering its favorable traits as a small peptide that greatly promoting generation of endogenous wound healing agents (transforming growth factor β1) without mitogenic effects, AH90 might be an excellent template for the future development of novel wound-healing agents.

  2. WOUND HEALING ACTIVITY OF ETHANOL EXTRACT OF PSEUDARTHRIA VISCIDA LINN

    Directory of Open Access Journals (Sweden)

    M. Vijayabaskaran

    2011-04-01

    Full Text Available The wound healing activity of topically applied ethanol extract of Pseudarthria viscida was evaluated in wistar rat by excision wound model for a period of 12 days. The extract was prepared as ointment form (5 and 10% w/w and applied on Wistar rats. Neomycin ointment 0.5%w/w was used as standard drug. The healing of the wound was assessed by the rate of wound contraction, period of epithelialisation, skin breaking strength. Both the ointments (5% and 10% w/w of Pseudarthria viscida extract promoted the wound-healing activity significantly when compared to the standard drug. High rate of wound contraction, decrease the period for epithelialisation, high skin breaking strength were observed in animals treated with 10% w/w extract ointment when compared to the control group of animals. So ethanol extract of Pseudarthria viscida in the form of 10% ointment promote wound-healing activity better than the former concentration, 5%. The result obtained from this study indicates that ethanol extract of Pseudarthria viscida accelerates the wound healing process by decreasing the surface area of the wound.

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

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    Abolghasem Esmaeili

    2010-01-01

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

  4. Evaluation of wound healing activity of root of Mimosa pudica.

    Science.gov (United States)

    Kokane, Dnyaneshwar D; More, Rahul Y; Kale, Mandar B; Nehete, Minakshi N; Mehendale, Prachi C; Gadgoli, Chhaya H

    2009-07-15

    Mimosa pudica, commonly known as touch-me-not, is used in folklore medicine in arresting bleeding and in skin diseases. There was no scientific evidence justifying the use of Mimosa pudica, therefore the present study was aimed at evaluation of wound healing activity of the plant. In the present study the roots of Mimosa pudica were studied for wound healing activity by incorporating the methanolic and the total aqueous extract in simple ointment base B.P. in concentration of 0.5% (w/w), 1% (w/w) and 2% (w/w). Wound healing activity was studied in three types of model in rats viz. excision, incision and estimation of biochemical parameter. In case of the excision wound model wound contraction and period of epithelization was studied while in incision wound model was evaluated by determining tensile strength and hydroxyproline content in the scab. Treatment of wound with ointment containing 2% (w/w) the methanolic and 2% (w/w) the total aqueous extract exhibited significant (P<0.001) wound healing activity. The methanolic and total aqueous extracts were analyzed for total phenols content equivalent to Gallic acid. The content of total phenols was 11% (w/w) and 17% (w/w) in methanolic and total aqueous extract respectively. The methanolic extract exhibited good wound healing activity probably due to phenols constituents.

  5. Wound healing and wound location in critical limb ischemia following endovascular treatment.

    Science.gov (United States)

    Kobayashi, Norihiro; Hirano, Keisuke; Nakano, Masatsugu; Muramatsu, Toshiya; Tsukahara, Reiko; Ito, Yoshiaki; Ishimori, Hiroshi

    2014-01-01

    The differences in wound healing according to wound location remain unclear. Between April 2007 and October 2011, 138 patients (166 limbs) with critical limb ischemia with tissue loss were treated with endovascular treatment. On these limbs, 177 individual wounds were identified on the foot and were evaluated for wound healing rates and time to healing according to their locations. Wound locations were divided into 3 groups: group T (Toe wounds, n=112), group H (Heel wounds, n=25), and group E (Extensive wounds extending onto the fore- or mid-foot along with dorsum or plantar surfaces, n=40). The mean follow-up period was 23±19 months. At 3, 6, 9, and 12 months, wound healing rates were 51%, 64%, 75%, and 75%, respectively, in group T; 12%, 36%, 36%, and 52%, respectively, in group H; and 0%, 5%, 8%, and 13%, respectively, in group E. The median time to healing was 64 days (interquartile range 25-156 days) in group T, 168 days (interquartile range 123-316 days) in group H, and 267 days (interquartile range 177-316 days) in group E (P=0.038). Extensive wounds extending onto the fore- or mid-foot along with dorsum or plantar surfaces were the most difficult type of wound to heal.

  6. Adult stem cells in small animal wound healing models.

    Science.gov (United States)

    Nauta, Allison C; Gurtner, Geoffrey C; Longaker, Michael T

    2013-01-01

    This chapter broadly reviews the use of stem cells as a means to accelerate wound healing, focusing first on the properties of stem cells that make them attractive agents to influence repair, both alone and as vehicles for growth factor delivery. Major stem cell reservoirs are described, including adult, embryonic, and induced pluripotent cell sources, outlining the advantages and limitations of each source as wound healing agents, as well as the possible mechanisms responsible for wound healing acceleration. Finally, the chapter includes a materials and methods section that provides an in-depth description of adult tissue harvest techniques.

  7. Gene expression profiling of cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2007-02-01

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

  8. Corneal Wound Repair After Rose Bengal and Green Light Crosslinking: Clinical and Histologic Study.

    Science.gov (United States)

    Gallego-Muñoz, Patricia; Ibares-Frías, Lucía; Lorenzo, Elvira; Marcos, Susana; Peréz-Merino, Pablo; Bekesi, Nandor; Kochevar, Irene E; Martínez-García, M Carmen

    2017-07-01

    To evaluate corneal wound healing after treatment with a new collagen crosslinking protocol using rose bengal dye and green light (RGX). One cornea of 20 New Zealand rabbits was de-epithelialized (DE) in an 8-mm diameter circle and, in another group (n = 25), the DE corneas were then stained with 0.1% rose bengal for 2 minutes and exposed to green light (532 nm) for 7 minutes (RGX). The contralateral eyes without treatment acted as controls. The animals were clinically followed including fluorescein staining and pachymetry. Healing events were analyzed after euthanasia at 2, 30, and 60 days. Cell death (TUNEL assay), cell proliferation (5-bromo-2'-deoxyuridine incorporation), and cell differentiation to myofibroblasts (α-SMA labeling) were carried out. In addition, loss of keratocytes and subsequent repopulation of the corneal stroma were quantified on hematoxylin-eosin-stained sections. Wound closure was slower after RGX (4.4 days) then after DE (3.3 days). Cell death was restricted to the anterior central stroma, and the cellular decrease did not differ significantly between RGX and DE corneas. Cell proliferation in the epithelium and stroma appeared at 2 days. In both DE and RGX corneas, recovery of the epithelium was complete at day 30, although cell repopulation of the stroma was not complete at 60 days. The healing response in corneas after RGX is very similar to that observed after DE alone, suggesting that, along with its short treatment time and limited effect on keratocytes, RGX displays good potential for clinical cornea stiffening.

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

    Science.gov (United States)

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

    2002-08-01

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

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

    Science.gov (United States)

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

    2015-09-01

    The cytoskeletal protein Flightless (Flii) is a negative regulator of wound healing. Upregulation of Flii is associated with impaired migration, proliferation and adhesion of both fibroblasts and keratinocytes. Importantly, Flii translocates from the cytoplasm to the nucleus in response to wounding in fibroblasts but not keratinocytes. This cell-specific nuclear translocation of Flii suggests that Flii may directly regulate gene expression in fibroblasts, providing one potential mechanism of action for Flii in the wound healing response. To determine whether the tissue-specific upregulation of Flii in fibroblasts was important for the observed inhibitory effects of Flii on wound healing, an inducible fibroblast-specific Flii overexpressing mouse model was generated. The inducible ROSA26 system allowed the overexpression of Flii in a temporal and tissue-specific manner in response to tamoxifen treatment. Wound healing in the inducible mice was impaired, with wounds at day 7 postwounding significantly larger than those from non-inducible controls. There was also reduced collagen maturation, increased myofibroblast infiltration and elevated inflammation. The impaired healing response was similar in magnitude to that observed in mice with non-tissue-specific upregulation of Flii suggesting that fibroblast-derived Flii may have an important role in the wound healing response. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. MicroRNA as Therapeutic Targets for Chronic Wound Healing

    Directory of Open Access Journals (Sweden)

    Eoghan J. Mulholland

    2017-09-01

    Full Text Available Wound healing is a highly complex biological process composed of three overlapping phases: inflammation, proliferation, and remodeling. Impairments at any one or more of these stages can lead to compromised healing. MicroRNAs (miRs are non-coding RNAs that act as post-transcriptional regulators of multiple proteins and associated pathways. Thus, identification of the appropriate miR involved in the different phases of wound healing could reveal an effective third-generation genetic therapy in chronic wound care. Several miRs have been shown to be upregulated or downregulated during the wound healing process. This article examines the biological processes involved in wound healing, the miR involved at each stage, and how expression levels are modulated in the chronic wound environment. Key miRs are highlighted as possible therapeutic targets, either through underexpression or overexpression, and the healing benefits are interrogated. These are prime miR candidates that could be considered as a gene therapy option for patients suffering from chronic wounds. The success of miR as a gene therapy, however, is reliant on the development of an appropriate delivery system that must be designed to overcome both extracellular and intracellular barriers.

  12. MicroRNA as Therapeutic Targets for Chronic Wound Healing.

    Science.gov (United States)

    Mulholland, Eoghan J; Dunne, Nicholas; McCarthy, Helen O

    2017-09-15

    Wound healing is a highly complex biological process composed of three overlapping phases: inflammation, proliferation, and remodeling. Impairments at any one or more of these stages can lead to compromised healing. MicroRNAs (miRs) are non-coding RNAs that act as post-transcriptional regulators of multiple proteins and associated pathways. Thus, identification of the appropriate miR involved in the different phases of wound healing could reveal an effective third-generation genetic therapy in chronic wound care. Several miRs have been shown to be upregulated or downregulated during the wound healing process. This article examines the biological processes involved in wound healing, the miR involved at each stage, and how expression levels are modulated in the chronic wound environment. Key miRs are highlighted as possible therapeutic targets, either through underexpression or overexpression, and the healing benefits are interrogated. These are prime miR candidates that could be considered as a gene therapy option for patients suffering from chronic wounds. The success of miR as a gene therapy, however, is reliant on the development of an appropriate delivery system that must be designed to overcome both extracellular and intracellular barriers. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Wound healing activity of Sida cordifolia Linn. in rats.

    Science.gov (United States)

    Pawar, Rajesh S; Chaurasiya, Pradeep K; Rajak, Harish; Singour, Pradeep K; Toppo, Fedelic Ashish; Jain, Ankit

    2013-01-01

    The present study provides a scientific evaluation for the wound healing potential of ethanolic (EtOH) extract of Sida cordifolia Linn. (SCL) plant. Excision, incision and burn wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base). Group II was treated with 10% EtOH extract ointment. Group III was treated with standard silver sulfadiazine (0.01%) cream. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. It was noted that the effect produced by the ethanolic extract of SCL ointment showed significant (P < 0.01) healing in all wound models when compared with the control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant (P < 0.01) changes when compared with the control. The ethanolic extract ointment of SCL effectively stimulates wound contraction; increases tensile strength of excision, incision and burn wounds.

  14. Burn wound healing: present concepts, treatment strategies and future directions.

    Science.gov (United States)

    Oryan, A; Alemzadeh, E; Moshiri, A

    2017-01-02

    Burns are the most extensive forms of soft tissue injuries occasionally resulting in extensive and deep wounds and death. Burns can lead to severe mental and emotional distress, because of excessive scarring and skin contractures. Treatment of burns has always been a difficult medical problem and many different methods have been used to treat such injuries, locally. Biofilms are a collection of microorganisms that delay wound healing. One of the new methods of prevention and treatment of burn wound infections is application of antimicrobials, which act on biofilms and prevent the wound infection. Biofilm initiates a persistent, low-grade, inflammatory response, impairing both the epithelialisation and granulation tissue formation. Skin grafts have been shown to dramatically reduce deaths from infection. However, grafting has considerable limitations. Such injuries are long-lasting and many patients suffer from chronic pain for a long time. Tissue engineering is a new approach in reducing the limitations of conventional treatments and producing a supply of immunologically tolerant artificial tissue, leading to a permanent solution for damaged tissues; such criteria make it a cost-effective and reliable treatment modality. To overcome the present limitations of burn wound healing, knowledge about the latest findings regarding healing mechanisms is important. Here the authors discuss the most important events regarding burn wound healing and review the latest treatment strategies that have been used for burn wounds from in vitro to clinical levels. Finally, we discuss the role of tissue engineering and regenerative medicine in the future of burn wound healing, modelling and remodelling.

  15. New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications

    Directory of Open Access Journals (Sweden)

    Runa Ghosh Auddy

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Non-Coding RNAs: New Players in Skin Wound Healing.

    Science.gov (United States)

    Herter, Eva K; Xu Landén, Ning

    2017-03-01

    Significance: Wound healing is a basic physiological process that is utilized to keep the integrity of the skin. Impaired wound repair, such as chronic wounds and pathological scars, presents a major health and economic burden worldwide. To date, efficient targeted treatment for these wound disorders is still lacking, which is largely due to our limited understanding of the biological mechanisms underlying these diseases. Research driven around discovering new therapies for these complications is, therefore, an urgent need. Recent Advances: The vast majority of the human genome is transcribed to RNAs that lack protein-coding capacity. Intensive research in the recent decade has revealed that these non-coding RNAs (ncRNAs) function as important regulators of cellular physiology and pathology, which makes them promising therapeutic and diagnostic entities. Critical Issues: A class of short ncRNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important roles in the pathogenesis of wound complications. The role of long ncRNAs (lncRNA) in skin wound healing remains largely unexplored. Recent studies revealed the essential role of lncRNAs in epidermal differentiation and stress response, indicating their potential importance for skin wound healing, which warrants future research. Future Directions: An investigation of ncRNAs will add new layers of complexity to our understanding of normal skin wound healing as well as to the pathogenesis of wound disorders. Development of ncRNA-based biomarkers and treatments is an interesting and important avenue for future research on wound healing.

  18. Wound healing activity of Abroma augusta in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Shanbhag T; Dattachaudhuri A; Shenoy S; Bairy KL

    2009-01-01

    Objective:The study was undertaken to evaluate the wound healing profile of alcoholic extract of Abroma au-gusta and its effect on dexamethasone suppressed wound healing in Wistar rats.Methods:An alcoholic extract of Abroma augusta was prepared.Three models were used -incision,excision and dead space wound models. Four groups of animals were used for each model.They were administered 2% gum acacia (orally),alcoholic extract of Abroma augusta (orally),dexamethasone (intramuscularly)and combination of Abroma augusta (o-rally)with dexamethasone (intramuscularly)respectively.The parameters studied included breaking strength of incision wound,period of epithelization and wound contraction rate in the excision wound,breaking strength,dry weight and hydroxyproline content of granulation tissue in dead space wound.Results:The breaking strength of incision wound of Abroma augusta treated group was significantly increased (P <0.001) while that of dexamethasone treated animals was significantly decreased (P <0.001)as compared to control. Coadministration of dexamethasone and Abroma augusta significantly reversed the dexamethasone suppressed wound healing in incision wound model (P <0.001).Animals treated with both dexamethasone and Abroma augusta also showed significant (P <0.004)increase in the breaking strength of granulation tissue in the dead space wound and a significant (P <0.011)reduction in the period of epithelization in the excision wound as compared to rats treated with dexamethasone alone.The rate of wound contraction was not significantly altered in any of the groups.Conclusion:The alcoholic extract of Abroma augusta was found to reverse dexametha-sone suppressed wound healing.

  19. Appraisal on the wound healing activity of different extracts obtained ...

    African Journals Online (AJOL)

    2015-12-02

    Dec 2, 2015 ... All extracts obtained from AM and MP facilitated the wound healing process in all experimental models. ... [4] The fibroblast is the connective tissue ...... of ethanolic extract of leaves of Hyptis suaveolens with supportive role of.

  20. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Nevine M.F. El Deeb

    2014-06-20

    Jun 20, 2014 ... Abstract Objective: During the wound healing process, lymphatic regeneration in the injured skin has not .... posed of newly-formed blood vessels and fibroblasts .... age plays a role in connection with traumatic deaths due to.

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

    OpenAIRE

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

    2016-01-01

    Significance: Fibroblasts play a critical role in normal wound healing. Various extracellular matrix (ECM) components, including collagens, fibrin, fibronectin, proteoglycans, glycosaminoglycans, and matricellular proteins, can be considered potent protagonists of fibroblast survival, migration, and metabolism.

  2. Metalloproteinases and Their Inhibitors: Regulators of Wound Healing

    Science.gov (United States)

    Gill, Sean E.; Parks, William C.

    2008-01-01

    Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many gene products that are essential for restoration normal tissue architecture, several members of the matrix metalloproteinase (MMP) function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions. PMID:18083622

  3. Graphene-based composite materials beneficial to wound healing

    Science.gov (United States)

    Lu, Bingan; Li, Ting; Zhao, Haitao; Li, Xiaodong; Gao, Caitian; Zhang, Shengxiang; Xie, Erqing

    2012-04-01

    We use electrospinning to prepare chitosan-PVA nanofibers containing graphene. The nanofibers can be directly used in wound healing: graphene, as an antibacterial material, can be beneficial for this. A possible antibacterial mechanism for graphene is presented.

  4. Enhancement of wound healing by shikonin analogue 93/637 in normal and impaired healing.

    Science.gov (United States)

    Mani, H; Sidhu, G S; Singh, A K; Gaddipati, J; Banaudha, K K; Raj, K; Maheshwari, R K

    2004-01-01

    Wound healing is a complicated biological process, which involves interactions of multiple cell types, various growth factors, their mediators and the extracellular matrix proteins. In this study, we evaluated the effects of shikonin analogue 93/637 (SA), derived from the plant Arnebia nobilis, on normal and hydrocortisone-induced impaired healing in full thickness cutaneous punch wounds in rats. SA (0.1%) was applied topically daily as an ointment in polyethylene glycol base on wounds. SA treatment significantly accelerated healing of wounds, as measured by wound contraction compared to controls in hydrocortisone-impaired animals. SA treatment promoted formation of granulation tissue including cell migration and neovascularization, collagenization and reepithelialization. The expression of basic fibroblast growth factor (bFGF) was higher as revealed by immunohistochemistry in treated wounds compared to controls. However, the expression of transforming growth factor-beta(1) was not affected by SA treatment. Since bFGF is known to accelerate wound healing, the increased expression of bFGF by SA may be partly responsible for the enhancement of wound healing. These studies suggest that SA could be further studied for clinical use to enhance wound healing.

  5. Principles of Wound Management and Wound Healing in the Exotic Pets

    OpenAIRE

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

    2016-01-01

    The care of wounds in exotic animal species can be a challenging endeavor. Special considerations must be made in regards to the animal’s temperament and behavior, unique anatomy and small size, and tendency towards secondary stress-related health problems. It is important to assess the entire patient with adequate systemic evaluation and consideration of proper nutrition and husbandry, which could ultimately impact wound healing. This article summarizes the general phases of wound healing, f...

  6. MicroRNAs as regulators of cutaneous wound healing

    Indian Academy of Sciences (India)

    Wing-Fu Lai; Parco M Siu

    2014-06-01

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

  7. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

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

    Science.gov (United States)

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

    2011-02-01

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

  9. Chitosan as a starting material for wound healing applications

    OpenAIRE

    Patrulea,Viorica; Ostafe, V.; Borchard, Gerrit; Jordan, Olivier

    2015-01-01

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

  10. Cardiac fibroblast in development and wound healing.

    Science.gov (United States)

    Deb, Arjun; Ubil, Eric

    2014-05-01

    Cardiac fibroblasts are the most abundant cell type in the mammalian heart and comprise approximately two-thirds of the total number of cardiac cell types. During development, epicardial cells undergo epithelial-mesenchymal-transition to generate cardiac fibroblasts that subsequently migrate into the developing myocardium to become resident cardiac fibroblasts. Fibroblasts form a structural scaffold for the attachment of cardiac cell types during development, express growth factors and cytokines and regulate proliferation of embryonic cardiomyocytes. In post natal life, cardiac fibroblasts play a critical role in orchestrating an injury response. Fibroblast activation and proliferation early after cardiac injury are critical for maintaining cardiac integrity and function, while the persistence of fibroblasts long after injury leads to chronic scarring and adverse ventricular remodeling. In this review, we discuss the physiologic function of the fibroblast during cardiac development and wound healing, molecular mediators of activation that could be possible targets for drug development for fibrosis and finally the use of reprogramming technologies for reversing scar. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Studies on Zinc and Copper Ion in Relation to Wound Healing in ...

    African Journals Online (AJOL)

    olayemitoyin

    of both male and female goats could also be a factor for wound healing in the animals. Keywords: Wound ... and healing of wounds. The direct role of copper in facilitating angiogenesis .... well as activities of fibroblasts and skin immune cells.

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

    Science.gov (United States)

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

    2016-02-01

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

  13. The modern concept of wound healing in glaucoma surgery

    Directory of Open Access Journals (Sweden)

    S. Yu. Petrov

    2015-01-01

    Full Text Available Post-operative wound healing is one of the key-factors, defining success of filtrating surgery in late post-operative period. Wound healing is a physiological response directed at tissue structure reconstruction and function restoration, performed by several interacting cellular pathways. Surgical trauma leads to plasma proteins penetration to the filtration zone, as well as coagulation pathway and complement activation. The process of wound healing can be divided into three interconnected stages: inflammation, proliferation and scar remodeling. Inflammation is a protective response to tissue damage, that helps preserve its structure and cellular functions. It is characterized by neutrophil and monocyte arrival at the wound site. Neutrophils phagocytose the wound infecting bacteria and clean the wound site. Macrofages aid wound cleansing, participate in phagocytosis and produce a range of factors, necessary for new tissue formation. Proliferation stage consists of reepithelization and granulation tissue formation, which is accompanied by growth factors release. The growth factors stimulate the extracellular matrix formation and fibroblast proliferation. The last stage of the wound healing process is characterized by extracellular matrix remodeling with wound debridement achieved by a simultaneous synthesis and destruction of certain matrix components, cell differentiation, maturation and apoptosis. Apoptosis disturbance prolongs the fibroblast cell life and promotes excessive scarring. Three growth factors are thought to play a pivotal role in tissue healing and scarring transforming growth factor β, connective tissue growth factor and vascular endothelial growth factor. The article contains a review of their isoforms, role in wound healing and the possibility of their inhibition to alter the process. Matrix metalloproteinases are a protein family that can digest extracellular matrix components. Due to their influence on the tenon’s capsule

  14. Inflammation and wound healing: The role of the macrophage

    Science.gov (United States)

    Koh, Timothy J.; DiPietro, Luisa Ann

    2013-01-01

    The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602

  15. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  19. NeutroPhase® in chronic non-healing wounds

    Science.gov (United States)

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

    2012-01-01

    Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient’s morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase® as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase® is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase® with and without NPWT. NeutroPhase® was non-toxic to living tissues. PMID:23272294

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    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.

  2. Wound healing potential of Tephrosia purpurea (Linn.) Pers. in rats.

    Science.gov (United States)

    Lodhi, Santram; Pawar, Rajesh Singh; Jain, Alok Pal; Singhai, A K

    2006-11-24

    Tephrosia purpurea is a well-known herb for its hepatoprotective, anticancer, antiulcer, antibacterial and in healing bleeding piles, etc. The present study was aimed for wound healing potential of ethanolic extract of Tephrosia purpurea (aerial part) in the form of simple ointment using three types of wound models in rats as incision wound, excision wound and dead space wound. The results were comparable to standard drug Fluticasone propionate ointment, in terms of wound contraction, tensile strength, histopathological and biochemical parameters such as hydroxyproline content, protein level, etc. Histopathological study showed significant (P<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters were observed significant (P<0.05) in comparison to control group.

  3. Nitric oxide: a newly discovered function on wound healing

    Institute of Scientific and Technical Information of China (English)

    Jian-dong LUO; Alex F CHEN

    2005-01-01

    Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric oxide (NO) plays a key role in wound repair. The beneficial effects of NO on wound repair may be attributed to its functional influences on angiogenesis,inflammation, cell proliferation, matrix deposition, and remodeling. Recent findings from in vitro and in vivo studies of NO on wound repair are summarized in this review. The unveiled novel mechanisms support the use of NO-containing agents and/or NO synthase gene therapy as new therapeutic regimens for impaired wound healing.

  4. Collagen VII plays a dual role in wound healing.

    Science.gov (United States)

    Nyström, Alexander; Velati, Daniela; Mittapalli, Venugopal R; Fritsch, Anja; Kern, Johannes S; Bruckner-Tuderman, Leena

    2013-08-01

    Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.

  5. Fibroblast subpopulations in intra-oral wound healing.

    NARCIS (Netherlands)

    Beurden, H.E. van; Snoek, P.A.; Hoff, J.W. Von den; Torensma, R.; Kuijpers-Jagtman, A.M.

    2003-01-01

    The objective of this study was to characterize fibroblasts at sequential time points during intra-oral wound healing in the rat. Experimental wounds were made at several time points in the mucoperiosteum of the palate of 35-day-old Wistar rats. Fibroblasts were cultured from the biopsies under

  6. Establishment of a novel in vitro model of stratified epithelial wound healing with barrier function.

    Science.gov (United States)

    Gonzalez-Andrades, Miguel; Alonso-Pastor, Luis; Mauris, Jérôme; Cruzat, Andrea; Dohlman, Claes H; Argüeso, Pablo

    2016-01-13

    The repair of wounds through collective movement of epithelial cells is a fundamental process in multicellular organisms. In stratified epithelia such as the cornea and skin, healing occurs in three steps that include a latent, migratory, and reconstruction phases. Several simple and inexpensive assays have been developed to study the biology of cell migration in vitro. However, these assays are mostly based on monolayer systems that fail to reproduce the differentiation processes associated to multilayered systems. Here, we describe a straightforward in vitro wound assay to evaluate the healing and restoration of barrier function in stratified human corneal epithelial cells. In this assay, circular punch injuries lead to the collective migration of the epithelium as coherent sheets. The closure of the wound was associated with the restoration of the transcellular barrier and the re-establishment of apical intercellular junctions. Altogether, this new model of wound healing provides an important research tool to study the mechanisms leading to barrier function in stratified epithelia and may facilitate the development of future therapeutic applications.

  7. Influence of pH on wound-healing: a new perspective for wound-therapy?

    Science.gov (United States)

    Schneider, Lars Alexander; Korber, Andreas; Grabbe, Stephan; Dissemond, Joachim

    2007-02-01

    Wound healing is a complex regeneration process, which is characterised by intercalating degradation and re-assembly of connective tissue and epidermal layer. The pH value within the wound-milieu influences indirectly and directly all biochemical reactions taking place in this process of healing. Interestingly it is so far a neglected parameter for the overall outcome. For more than three decades the common assumption amongst physicians was that a low pH value, such as it is found on normal skin, is favourable for wound healing. However, investigations have shown that in fact some healing processes such as the take-rate of skin-grafts require an alkaline milieu. The matter is thus much more complicated than it was assumed. This review article summarises the existing literature dealing with the topic of pH value within the wound-milieu, its influence on wound healing and critically discusses the currently existing data in this field. The conclusion to be drawn at present is that the wound pH indeed proves to be a potent influential factor for the healing process and that different pH ranges are required for certain distinct phases of wound healing. Further systematic data needs to be collected for a better understanding of the pH requirements under specific circumstances. This is important as it will help to develop new pH targeted therapeutic strategies.

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

    Science.gov (United States)

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

    2010-07-01

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

  9. Wound-healing property of Momordica charantia L. fruit powder.

    Science.gov (United States)

    Prasad, Vure; Jain, Vikas; Girish, Dugapati; Dorle, Avinash Kumar

    2006-01-01

    Momordica charantia Linn. fruit powder, in the form of an ointment (10% w/w dried powder in simple ointment base), was evaluated for wound-healing potential in an excision, incision and dead space wound model in rats. The rats were divided into three groups of control, treatment and reference in all three wound models, each group consisting of six rats. Wound-contraction ability in excision wound mode was measured at different time intervals on days 4, 8, 10, 12 and 14 , and the study was continued until the wound had completely healed. Tensile strength was measured in 10-day-old incision and granuloma wound. Histological studies were performed on 10-day-old sections of regenerated tissue. Powder ointment showed a statistically significant response (P < 0.01), in terms of wound-contracting ability, wound closure time, period of epithelization, tensile strength of the wound and regeneration of tissues at wound site when compared with the control group, and these results were comparable to those of a reference drug povidone iodine ointment.

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

    Directory of Open Access Journals (Sweden)

    Sarah Chadwick

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Han, George

    2014-01-01

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

  13. Wound healing potential of formulated extract from hibiscus sabdariffa calyx.

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2000-01-01

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

  15. Scientific production on the applicability of phenytoin in wound healing

    Directory of Open Access Journals (Sweden)

    Flávia Firmino

    2014-02-01

    Full Text Available Phenytoin is an anticonvulsant that has been used in wound healing. The objectives of this study were to describe how the scientific production presents the use ofphenytoinas a healing agent and to discuss its applicability in wounds. A literature review and hierarchy analysis of evidence-based practices was performed. Eighteen articles were analyzed that tested the intervention in wounds such as leprosy ulcers, leg ulcers, diabetic foot ulcers, pressure ulcers, trophic ulcers, war wounds, burns, preparation of recipient graft area, radiodermatitis and post-extraction of melanocytic nevi. Systemic use ofphenytoinin the treatment of fistulas and the hypothesis of topical use in the treatment of vitiligo were found. In conclusion, topical use ofphenytoinis scientifically evidenced. However robust research is needed that supports a protocol for the use ofphenytoinas another option of a healing agent in clinical practice.

  16. The roles of calcium signaling and ERK1/2 phosphorylation in a Pax6+/- mouse model of epithelial wound-healing delay

    Directory of Open Access Journals (Sweden)

    McCaig Colin D

    2006-08-01

    Full Text Available Abstract Background Congenital aniridia caused by heterozygousity at the PAX6 locus is associated with ocular surface disease including keratopathy. It is not clear whether the keratopathy is a direct result of reduced PAX6 gene dosage in the cornea itself, or due to recurrent corneal trauma secondary to defects such as dry eye caused by loss of PAX6 in other tissues. We investigated the hypothesis that reducing Pax6 gene dosage leads to corneal wound-healing defects. and assayed the immediate molecular responses to wounding in wild-type and mutant corneal epithelial cells. Results Pax6+/- mouse corneal epithelia exhibited a 2-hour delay in their response to wounding, but subsequently the cells migrated normally to repair the wound. Both Pax6+/+ and Pax6+/- epithelia activated immediate wound-induced waves of intracellular calcium signaling. However, the intensity and speed of propagation of the calcium wave, mediated by release from intracellular stores, was reduced in Pax6+/- cells. Initiation and propagation of the calcium wave could be largely decoupled, and both phases of the calcium wave responses were required for wound healing. Wounded cells phosphorylated the extracellular signal-related kinases 1/2 (phospho-ERK1/2. ERK1/2 activation was shown to be required for rapid initiation of wound healing, but had only a minor effect on the rate of cell migration in a healing epithelial sheet. Addition of exogenous epidermal growth factor (EGF to wounded Pax6+/- cells restored the calcium wave, increased ERK1/2 activation and restored the immediate healing response to wild-type levels. Conclusion The study links Pax6 deficiency to a previously overlooked wound-healing delay. It demonstrates that defective calcium signaling in Pax6+/- cells underlies this delay, and shows that it can be pharmacologically corrected. ERK1/2 phosphorylation is required for the rapid initiation of wound healing. A model is presented whereby minor abrasions, which are

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

    Energy Technology Data Exchange (ETDEWEB)

    McCaw, D.L.

    1989-11-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

    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.

  20. Oxygen therapies and their effects on wound healing.

    Science.gov (United States)

    de Smet, Gijs H J; Kroese, Leonard F; Menon, Anand G; Jeekel, Johannes; van Pelt, Antoon W J; Kleinrensink, Gert-Jan; Lange, Johan F

    2017-08-07

    Oxygen is an important factor for wound healing. Although several different therapies investigated the use of oxygen to aid wound healing, the results of these studies are not unequivocal. This systematic review summarizes the clinical and experimental studies regarding different oxygen therapies for promoting wound healing, and evaluates the outcomes according the methodological details. A systematic literature search was conducted using Embase, Medline, Web of Science, Cochrane, PubMed publisher, and Google Scholar libraries. Clinical and experimental studies investigating oxygen for wound healing were selected. Included articles were categorized according to the kind of therapy, study design, and wound type. The methodological details were extracted and analyzed. Sixty-five articles were identified and divided in three different oxygen therapies: Local oxygen therapy, hyperbaric oxygen therapy, and supplemental inspired oxygen therapy. More than half of the included local oxygen and hyperbaric oxygen studies had one or more significant positive outcomes, 77 and 63%, respectively. Supplemental inspired oxygen therapy during gastrointestinal and vascular surgery was more likely to have a positive result than during other surgical interventions reducing surgical site infections. These many positive outcomes promote the use of oxygen treatment in the stimulation of wound healing. However, the lack of clinical studies and vast methodological diversity made it impossible to perform a proper comparison within and between the different therapies. Further randomized clinical studies are warranted to examine the value of these therapies, especially studies that investigate the more patient-friendly oxygen dressings and topical wound oxygen therapies. Also, to achieve more solid and consistent data, studies should use more standardized methods and subjects. © 2017 by the Wound Healing Society.

  1. Wound healing activity of the leaves of Artocarpus heterophyllus Lam. (Moraceae on ex-vivo porcine skin wound healing model

    Directory of Open Access Journals (Sweden)

    K Periyanayagam

    2013-05-01

    Full Text Available ABSTRACT Objective: To prescreen the ex- vivo wound healing activity of flavonoid rich fraction of ethyl acetate extract of the leaves of Artocarpus heterophyllus Lam. Family Moraceae using porcine skin wound healing model (PSWHM along with  phytochemical, XRF, HPTLC analysis. The aim of this present study is to provide pharmacological validation to the traditional claim for wound healing activity of Artocarpus heterophyllus leaves. Method: Total phenolic content by UV spectral methods and ursolic acid content by HPTLC, trace elements by X-ray fluorescence were determined.  The wound healing effect of the ethyl acetate extract of the leaves of A.heterophyllus (EAAH was evaluated using ex- vivo porcine skin wound healing model - a novel organ culture model system for evaluation of drugs in cell-cell junction in the wound healing process. Results: Total phenolic content by UV method, HPTLC determination of ursolic acid content of EAAH was found to be 376.5mg/g GAE, 134mg/g respectively. XRF study showed the presence of calcium (39.4%, potassium (29.6%, magnesium (2.06%, Iron (0.99%, sulphur (1.83%, zinc (0.083%, strontium (0.23%, manganese (0.13% and aluminium (0.005%.   Histopathological evaluation showed all treated wounds were sound with no signs of apoptosis, necrosis or bacterial contamination and no toxicity of the tested concentrations of EAAH of the leaves. Morphology of the wound margins, epidermis and dermis layer were found to be normal. Epidermal migration or keratinocyte migration distances from the edges of each wound were measured, normalized with the PBS control group and expressed as mean%. The result clearly showed EAAH (1.5% promoted statistically significant wound healing effect is comparable to the standard drug Mupirocin. Conclusion: This study indicates that the ethyl acetate extract of the leaves of A.heterophyllus possesses potential wound healing activity on ex-vivo porcine skin wound healing model. Wound healing

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2013-12-01

    This study examined the effect of monochromatic infrared energy (MIRE) on diabetic wound healing. Fifteen diabetic rats were given MIRE intervention on their skin wounds located on the dorsum and compared with 15 control diabetic rats. Assessments were conducted for each group at weeks 1, 2 and 4 post wounding (five rats at each time point) by calculating the percentage of wound closures (WCs) and performing histological and immunohistochemical staining on sections of wound tissue. Evaluations of WCs and histological examinations of reepithelialisation, cellular content and granulation tissue formation showed no significant difference between the MIRE and the control group at each time point. Through semi-quantitative immunohistochemical staining, the deposition of type I collagen in the MIRE group was found to have improved when compared with the control group at the end of week 2 (P = 0.05). No significant differences in the myofibroblast population were detected between the two groups. In conclusion, MIRE appeared to promote collagen deposition in the early stage of wound healing in diabetic rats, but the overall wound healing in the MIRE group was not significantly different from that of the control group. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  4. Innate defense regulator peptide 1018 in wound healing and wound infection.

    Directory of Open Access Journals (Sweden)

    Lars Steinstraesser

    Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Peilang Yang

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

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

    Science.gov (United States)

    Houreld, Nicolette N.

    2014-02-01

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

  8. Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing.

    Science.gov (United States)

    Liu, Xiangyu; Niu, Yuqing; Chen, Kevin C; Chen, Shiguo

    2017-02-01

    A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50-130μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Josephine Anne Wright

    2014-07-01

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

  10. Pharmacological modulation of wound healing in experimental burns.

    Science.gov (United States)

    Jurjus, Abdo; Atiyeh, Bishara S; Abdallah, Inaya M; Jurjus, Rosalyne A; Hayek, Shady N; Jaoude, Marlene Abou; Gerges, Alice; Tohme, Rania A

    2007-11-01

    Factors involved in wound healing and their interdependence are not yet fully understood; nevertheless, new prospects for therapy to favor speedy and optimal healing are emerging. Reports about wound healing modulation by local application of simple and natural agents abound even in the recent literature, however, most are anecdotal and lack solid scientific evidence. We describe the effect of silver sulfadiazine and moist exposed burn ointment (MEBO), a recently described burn ointment of herbal origin, on mast cells and several wound healing cytokines (bFGF, IL-1, TGF-beta, and NGF) in the rabbit experimental burn model. The results demonstrate that various inflammatory cells, growth factors and cytokines present in the wound bed may be modulated by application of local agents with drastic effects on their expression dynamics with characteristic temporal and spatial regulation and changes in the expression pattern. Such data are likely to be important for the development of novel strategies for wound healing since they shed some light on the potential formulations of temporally and combinatory optimized therapeutic regimens.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-07-08

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

  13. Thyrotropin-releasing hormone and its analogs accelerate wound healing.

    Science.gov (United States)

    Nie, Chunlei; Yang, Daping; Liu, Nan; Dong, Deli; Xu, Jin; Zhang, Jiewu

    2014-06-15

    Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Dong Joo Yang

    2016-07-01

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

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

    Science.gov (United States)

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

    1992-01-01

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

  16. Aging-dependent reduction in glyoxalase 1 delays wound healing.

    Science.gov (United States)

    Fleming, Thomas H; Theilen, Till-Martin; Masania, Jinit; Wunderle, Marius; Karimi, Jamshid; Vittas, Spiros; Bernauer, Rainer; Bierhaus, Angelika; Rabbani, Naila; Thornalley, Paul J; Kroll, Jens; Tyedmers, Jens; Nawrotzki, Ralph; Herzig, Stephan; Brownlee, Michael; Nawroth, Peter P

    2013-01-01

    Methylglyoxal (MG), the major dicarbonyl substrate of the enzyme glyoxalase 1 (GLO1), is a reactive metabolite formed via glycolytic flux. Decreased GLO1 activity in situ has been shown to result in an accumulation of MG and increased formation of advanced glycation endproducts, both of which can accumulate during physiological aging and at an accelerated rate in diabetes and other chronic degenerative diseases. To determine the physiological consequences which result from elevated MG levels and the role of MG and GLO1 in aging, wound healing in young (≤12 weeks) and old (≥52 weeks) wild-type mice was studied. Old mice were found to have a significantly slower rate of wound healing compared to young mice (74.9 ± 2.2 vs. 55.4 ± 1.5% wound closure at day 6; 26% decrease; p wounds of young mice, decreased wound healing by 24% compared to untreated mice, whereas application of BSA modified minimally by MG had no effect. Treatment of either young or old mice with aminoguanidine, a scavenger of free MG, significantly increased wound closure by 16% (66.8 ± 1.6 vs. 77.2 ± 3.1%; p wound healing in the old mice was restored to the level observed in the young mice. These findings were confirmed in vitro, as MG reduced migration and proliferation of fibroblasts derived from young and old, wild-type mice. The data demonstrate that the balance between MG and age-dependent GLO1 downregulation contributes to delayed wound healing in old mice. Copyright © 2013 S. Karger AG, Basel.

  17. Sprouty2 downregulates angiogenesis during mouse skin wound healing

    Science.gov (United States)

    Wietecha, Mateusz S.; Chen, Lin; Ranzer, Matthew J.; Anderson, Kimberly; Ying, Chunyi; Patel, Tarun B.

    2011-01-01

    Angiogenesis is regulated by signals received by receptor tyrosine kinases such as vascular endothelial growth factor receptors. Mammalian Sprouty (Spry) proteins are known to function by specifically antagonizing the activation of the mitogen-activated protein kinase signaling pathway by receptor tyrosine kinases, a pathway known to promote angiogenesis. To examine the role of Spry2 in the regulation of angiogenesis during wound repair, we used a model of murine dermal wound healing. Full-thickness excisional wounds (3 mm) were made on the dorsum of anesthetized adult female FVB mice. Samples were harvested at multiple time points postwounding and analyzed using real-time RT-PCR, Western blot analysis, and immunofluorescent histochemistry. Spry2 mRNA and protein levels in the wound bed increased significantly during the resolving phases of healing, coincident with the onset of vascular regression in this wound model. In another experiment, intracellular levels of Spry2 or its dominant-negative mutant (Y55F) were elevated by a topical application to the wounds of controlled-release gel containing cell permeable, transactivator of transcription-tagged Spry2, Spry2Y55F, or green fluorescent protein (as control). Wound samples were analyzed for vascularity using CD31 immunofluorescent histochemistry as well as for total and phospho-Erk1/2 protein content. The treatment of wounds with Spry2 resulted in a significant decrease in vascularity and a reduced abundance of phospho-Erk1/2 compared with wounds treated with the green fluorescent protein control. In contrast, the wounds treated with the dominant-negative Spry2Y55F exhibited a moderate increase in vascularity and elevated phospho-Erk1/2 content. These results indicate that endogenous Spry2 functions to downregulate angiogenesis in the healing murine skin wound, potentially by inhibiting the mitogen-activated protein kinase signaling pathway. PMID:21076020

  18. Sprouty2 downregulates angiogenesis during mouse skin wound healing.

    Science.gov (United States)

    Wietecha, Mateusz S; Chen, Lin; Ranzer, Matthew J; Anderson, Kimberly; Ying, Chunyi; Patel, Tarun B; DiPietro, Luisa A

    2011-02-01

    Angiogenesis is regulated by signals received by receptor tyrosine kinases such as vascular endothelial growth factor receptors. Mammalian Sprouty (Spry) proteins are known to function by specifically antagonizing the activation of the mitogen-activated protein kinase signaling pathway by receptor tyrosine kinases, a pathway known to promote angiogenesis. To examine the role of Spry2 in the regulation of angiogenesis during wound repair, we used a model of murine dermal wound healing. Full-thickness excisional wounds (3 mm) were made on the dorsum of anesthetized adult female FVB mice. Samples were harvested at multiple time points postwounding and analyzed using real-time RT-PCR, Western blot analysis, and immunofluorescent histochemistry. Spry2 mRNA and protein levels in the wound bed increased significantly during the resolving phases of healing, coincident with the onset of vascular regression in this wound model. In another experiment, intracellular levels of Spry2 or its dominant-negative mutant (Y55F) were elevated by a topical application to the wounds of controlled-release gel containing cell permeable, transactivator of transcription-tagged Spry2, Spry2Y55F, or green fluorescent protein (as control). Wound samples were analyzed for vascularity using CD31 immunofluorescent histochemistry as well as for total and phospho-Erk1/2 protein content. The treatment of wounds with Spry2 resulted in a significant decrease in vascularity and a reduced abundance of phospho-Erk1/2 compared with wounds treated with the green fluorescent protein control. In contrast, the wounds treated with the dominant-negative Spry2Y55F exhibited a moderate increase in vascularity and elevated phospho-Erk1/2 content. These results indicate that endogenous Spry2 functions to downregulate angiogenesis in the healing murine skin wound, potentially by inhibiting the mitogen-activated protein kinase signaling pathway.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Tian, Ruirui; Li, Na; Wei, Li

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

    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) plight at low fluence does not impair in vitro wound healing. The significant decrease in IL-6 suggests that 470nm light is anti-inflammatory.

  4. Efficacy of frog skin lipids in wound healing

    Directory of Open Access Journals (Sweden)

    Rajaram Rama

    2010-07-01

    Full Text Available Abstract Background Frog skin has been sequentially and scientifically evaluated by our group for its wound healing efficiency. Owing to the complex structure of skin, attempts were being made to analyse the role of individual constituents in different phases of healing. Our earlier papers have shown the significance of frog skin not only in wound healing but also enhancing the proliferating activity of the epidermal and dermal cells which are instrumental for normal healing process. We also have identified for the first time novel antimicrobial peptides from the skin of Rana tigerina and thereby reduce the complications involved in the sepsis. Purpose of the study and Results The current study envisages the role of frog skin lipids in the inflammatory phase of wound healing. The lipid moiety of the frog skin dominated by phospholipids exhibited a dose dependent acceleration of healing irrespective of the mode of application. The efficiency of the extract is attributed partially to the anti-inflammatory activity as observed by the histochemical and immunostimulatory together with plethysmographic studies. Conclusions Thus, frog skin for the first time has been demonstrated to possess lipid components with pharmaceutical and therapeutic potential. The identification and characterization of such natural healing molecules and evaluating their mechanism of action would therefore provide basis for understanding the cues of Nature and hence can be used for application in medicine.

  5. Wound Healing and Infection in Surgery

    DEFF Research Database (Denmark)

    Sørensen, Lars Tue

    2012-01-01

    To clarify the evidence on smoking and postoperative healing complications across surgical specialties and to determine the impact of perioperative smoking cessation intervention.......To clarify the evidence on smoking and postoperative healing complications across surgical specialties and to determine the impact of perioperative smoking cessation intervention....

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

    Science.gov (United States)

    Crane, Nicole J.; Elster, Eric A.

    2012-01-01

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

  7. Advances in research on mechanisms of the effect of negative pressure wound treatment in wound healing

    Directory of Open Access Journals (Sweden)

    Lei LI

    2014-10-01

    Full Text Available Negative pressure wound treatment (NPWT refers to apply a highly porous material between the wound and a semipermeable membrane, and it is then connected to a suction apparatus, leading to a minimal deformation of wound, resulting in promoting cell proliferation and wound repair. These devices may significantly expedite wound healing, facilitate the formation of granulation tissue, and reduce the complexity of subsequent reconstructive operations. In recent years, along with wide clinical use, the therapeutic effect of NPWT has been recognized, but the mechanism of its clinical effect still needs further research. DOI: 10.11855/j.issn.0577-7402.2014.08.15

  8. Light-emitting diodes in dermatology: stimulation of wound healing

    Directory of Open Access Journals (Sweden)

    Justyna Fryc

    2016-05-01

    Full Text Available Low-level light therapy (LLLT, which is sometimes included in phototherapy, is an effective therapeutic strategy to improve wound healing and reduce pain, inflammation and swelling. Nowadays, new sources of light, such as light-emitting diodes (LEDs with a broad range of wavelengths, are widely available. The biological effects promoted by LEDs are dependent on irradiation parameters, mainly wavelength and dose. This review article focuses on recent clinical trials using light-emitting diode low-level light therapy (LED-LLLT for enhancing wound healing. In this article, we also cover the mechanisms of action of LLLT on cells and tissues and highlight the importance of defining optimum LLLT parameters for stimulation of wound healing.

  9. Effect of St. Johns Wort (Hypericum Perforatum on Wound Healing

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    Ahmet Altan

    2015-12-01

    Full Text Available Since ancient times, plants used for various purposes have an important role in the improvement of human health. People rely on plants for their therapeutic and preventive purposes and their natural origin, and utilize herbal products for this reason. One of these plants is Hypericum perforatum, which has medical importance and is conventionally used. This plant, which is commonly used by people in order to accelerate the healing of burns and wounds, has been proven by studies to have a positive effect on wound healing. The purpose of this review is to present the current literature covering the effect of Hypericum perforatum on wound healing. [Archives Medical Review Journal 2015; 24(4.000: 578-591

  10. Effect of cow urine on wound healing property in Wister Albino Rats

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    V.P. Tikare.,Paniraj K.L and Swetha R

    Full Text Available The wound healing activity of cow urine was studied in Wistar albino rats. The efficacy of wound healing property was evaluated by excision wound model. The parameter studied was the rate of wound contraction. The studies on excision wound healing revealed that all the groups showed decreased wound area from day to day. On day 4th, the external application of urine showed significant increase in wound healing in male and female rats compared to all other groups. However, on 14th post wounding day, Group I and VIII animals showed 0 % and 0.40.4 % of healing was left, which may be due to normal immunity of the animals. Where as nitrofurazone treated animals showed 0 % and 0.50.3 % healing .The study revealed that the cow urine on external application to the wound, hastened the wound healing process. [Vet. World 2011; 4(7.000: 317-321

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

    Science.gov (United States)

    Preethi, Korengath C; Kuttan, Ramadasan

    2009-01-01

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

  12. Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots

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    Karen Klotz Fugate

    2016-04-01

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

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

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

    2012-10-01

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

  14. In vitro biomechanical strain regulation of fibroblast wound healing.

    Science.gov (United States)

    Cao, Thanh V; Hicks, Michael R; Standley, Paul R

    2013-11-01

    Strain-directed therapy such as vacuum compression and manual manipulative therapies are clinically effective, but their cellular and molecular mechanisms are not well understood. To determine the effects of modeled myofascial release (MFR) on fibroblast wound healing and to investigate the potential role of nitric oxide (NO) in mediating these responses. Using an in vitro scratch wound strain model, the authors investigated human fibroblast wound healing characteristics in response to injurious repetitive motion strain (RMS) and MFR. Secretion of NO was induced with interleukin-1β and sodium nitroprusside and inhibited with NO synthase inhibitor L-N(G)-monomethyl arginine citrate (L-NMMA) to determine the effects of NO on wound healing. Protein microarray was also performed to evaluate the expression of intracellular protein and activation of protein kinase G (PKG), extracellular signal-regulated kinase (ERK1/2), protein kinase C (PKC), and phosphoinositide 3-kinase (PI3K), the downstream effectors in the NO pathway. Fibroblasts that received RMS resulted in reduced wound closure rates (vs nonstrain, Pfibroblast wound healing. However, strained fibroblasts appeared to express increased sensitivity to NO. The authors also observed a 12.2% increase in NO secretion, an increase in PKG activation, and a downregulation of PKC and PI3K inhibitory domain in the combined strain group. If clinically translatable, these data suggest that mechanical strain such as vacuum compression therapy and manual manipulative therapy may modify PKC and PI3K to sensitize fibroblasts to NO and improve wound healing by promoting cell proliferation and migration by means of PKC and PKG signaling.

  15. Wound healing potential of Pañcavalkala formulations in a postfistulectomy wound

    OpenAIRE

    2015-01-01

    SUMMARY Sushruta mentioned sixty measures for management of wounds. Panchavalkal is the combination of five herbs having properties like Shodhana (cleaning) and Ropana (healing) of wounds. Individual drugs and in combination have Kashaya rasa (astringent) dominant and useful in the management of Vrana (wounds) as well as Shotha (inflammations). A 35 years old male patient consulted in Shalya OPD with complaints like discharge per anum, induration and intermittent pain at perianal region since...

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

    OpenAIRE

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

    2012-01-01

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

  17. Wound healing: a new perspective on glucosylated tetrahydrocurcumin

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    Bhaskar Rao A

    2015-07-01

    Full Text Available Adari Bhaskar Rao,1 Ernala Prasad,1 Seelam Siva Deepthi,1 Vennapusa Haritha,1 Sistla Ramakrishna,1 Kuncha Madhusudan,1 Mullapudi Venkata Surekha,2 Yerramilli Sri Rama Venkata Rao3 1Medicinal Chemistry and Pharmacology Division, Council of Scientific and Industrial Research – Indian Institute of Chemical Technology, 2Pathology Division, National Institute of Nutrition, 3Ashian Herbex Ltd, Hyderabad, AP, India Abstract: Wound healing represents a dynamic set of coordinated physiological processes observed in response to tissue injury. Several natural products are known to accelerate the process of wound healing. Tetrahydrocurcumin (THC, an in vivo biotransformed product/metabolite of curcumin, is known to exhibit a wide spectrum of biological activities similar to those of native curcuminoids. The poor bioavailability of these curcuminoids limits their clinical applications. The present study highlights the percutaneous absorption and wound healing activity of glucosyl-conjugated THC (glucosyl-THC in male Wistar rats. A high plasma concentration of glucosyl-THC (4.35 µg/mL was found in rats 3 hours after application. A significant enhanced wound healing activity and reduced epithelialization time were observed in rats that received glucosyl-THC. This may have been due to the improved bioavailability of the glucosyl compound. The nonstaining and lack of skin-sensitive side effects render the bioconjugated glucosyl-THC a promising therapeutic compound in the management of excision wounds and in cosmetic applications, in the near future. Keywords: glucosylation, epithelialization, granulation tissue, cosmetic, therapeutic

  18. Remodeling of skin nerve fibers during burn wound healing

    Institute of Scientific and Technical Information of China (English)

    Yongqiang Feng; Xia Li; Rui Zhang; Yu Liu; Tingting Leng; Yibing Wang

    2010-01-01

    Burn wound healing involves a complex sequence of processes.Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair.Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers.The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody,and three-dimensional morphology was observed under a laser scanning confocal microscope.Morphology and the volume fraction of collagen and nerve fibers were measured.Skin reinnervation increased during wound healing,peaked during the proliferative scar stage,and then decreased to lower levels during the maturation period.The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis.Disintegration and fragmentation were observed frequently in samples from the proliferative stage,and seldom occurred during the maturation stage.There was a remodeling process of regenerated nerve fibers during wound healing,which comprised changed innervation density and topical morphology.The mechanism of remodeling for nerve fibers requires further investigation.

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

    Science.gov (United States)

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

    2016-03-01

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

  20. Effect of Neem Leaves Extract (Azadirachta Indica on Wound Healing

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    Naveen Kumar Chundran

    2015-06-01

    Full Text Available Background: Neem leaves (Azadirachta Indica have active ingredients such as nimbidin and sodium nimbidate which possess/possesinganti-inflammatory, antibacterial, antifungal and antiviral properties that help in healing process and also contains an excellent nutrition which plays/playing a vital role information of collagen and formation of new capillaries. The aim of this experimental study is to evaluate healing activity of neem leaves. Methods: This experiment was conducted in Pharmacology Lab of Universitas Padjadjaran on October 2012. Twenty seven rats were grouped randomly into 3 groups and 1.5cm of excision wound was created. Negative control group was treated with a topical application of saline solution (sodium chloride0.9%, treatment group with a topical application of neem leaves extract and positive control group had been treated with a topical application of povidone-iodine for 15 days. Healing was assessed by the longest diameter of the raw surface of wound on days 0, 5, 10 and 15. The data were then analyzed using Mann-Whitney U test. Results: There was a significant reduction in the longest diameter of wound in group of neem leaves extract, compared with group sodium chloride 0.9%,.and there was no significant difference in the longest diameter of wound between neem leaves, extract and povidone iodine. Conclusions: Neem leaves extract has the same wound healing rate compared to povidone iodine. A further study in human should be conducted in the future

  1. Ascorbic acid for the healing of skin wounds in rats

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    CC. Lima

    Full Text Available BACKGROUND: Healing is a complex process that involves cellular and biochemical events. Several medicines have been used in order to shorten healing time and avoid aesthetic damage. OBJECTIVE: to verify the topical effect of ascorbic acid for the healing of rats' skin wounds through the number of macrophages, new vessels and fibroblast verifications in the experimental period; and analyse the thickness and the collagen fibre organization in the injured tissue. METHODS: Male Rattus norvegicus weighing 270 ± 30 g were used. After thionembutal anesthesia, 15 mm transversal incisions were made in the animals' cervical backs. They were divided into two groups: Control Group (CG, n = 12 - skin wound cleaned with water and soap daily; Treated Group (TG, n = 12 - skin wound cleaned daily and treated with ascorbic acid cream (10%. Samples of skin were collected on the 3rd, 7th and 14th days. The sections were stained with hematoxylin-eosin and picrosirius red for morphologic analysis. The images were obtained and analysed by a Digital Analyser System. RESULTS: The ascorbic acid acted on every stage of the healing process. It reduced the number of macrophages, increased the proliferation of fibroblasts and new vessels, and stimulated the synthesis of thicker and more organized collagen fibres in the wounds when compared to CG. CONCLUSION: Ascorbic acid was shown to have anti-inflammatory and healing effects, guaranteeing a suiTable environment and conditions for faster skin repair.

  2. Fibroblasts and Myofibroblasts in Wound Healing: Force Generation and Measurement

    OpenAIRE

    Li, Bin; Wang, James H-C

    2009-01-01

    Fibroblasts are one of the most abundant cell types in connective tissues. These cells are responsible for tissue homeostasis under normal physiological conditions. When tissues are injured, fibroblasts become activated and differentiate into myofibroblasts, which generate large contractions and actively produce extracellular matrix (ECM) proteins to facilitate wound closure. Both fibroblasts and myofibroblasts play a critical role in wound healing by generating traction and contractile force...

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

    Science.gov (United States)

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

    2015-08-01

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

  4. Wound healing and the effect of pineal gland and melatonin

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    Jacek Drobnik

    2012-02-01

    Full Text Available Wound healing is a complex phenomenon that is controlled by local and general regulatory mechanisms. The aim of the paper is to analyze recently-published data devoted to the regulation of wound repair by melatonin. The effect of melatonin has been reported in different wound types healed with various mechanisms. The action of the pineal indoleamine is dependent on the used dose, time of application and target organ. Moreover, melatonin influences different phases of wound repair such as inflammation, by regulating the release of inflammatory mediators, cell proliferation and migration, by influencing angiogenesis, and the proliferation of fibroblasts, as well as the synthesis phase, by regulating collagen and glycosaminoglycan accumulation in the wounded milieu. Thus, healing of the skin wound, myocardial infarction, bone fractures and gastric ulcer is influenced by melatonin. In patients with low levels of melatonin (elderly or β-blocker treated patients, its regulatory effects are expected to be impaired. Thus, the need for melatonin supplementation in those patients is postulated in the study. [J Exp Integr Med 2012; 2(1.000: 3-14

  5. Fibroblasts and myofibroblasts in wound healing: force generation and measurement.

    Science.gov (United States)

    Li, Bin; Wang, James H-C

    2011-11-01

    Fibroblasts are one of the most abundant cell types in connective tissues. These cells are responsible for tissue homeostasis under normal physiological conditions. When tissues are injured, fibroblasts become activated and differentiate into myofibroblasts, which generate large contractions and actively produce extracellular matrix (ECM) proteins to facilitate wound closure. Both fibroblasts and myofibroblasts play a critical role in wound healing by generating traction and contractile forces, respectively, to enhance wound contraction. This review focuses on the mechanisms of force generation in fibroblasts and myofibroblasts and techniques for measuring such cellular forces. Such a topic was chosen specifically because of the dual effects that fibroblasts/myofibroblasts have in wound healing process- a suitable amount of force generation and matrix deposition is beneficial for wound healing; excessive force and matrix production, however, result in tissue scarring and even malfunction of repaired tissues. Therefore, understanding how forces are generated in these cells and knowing exactly how much force they produce may guide the development of optimal protocols for more effective treatment of tissue wounds in clinical settings. Copyright © 2009 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

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

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    Aurore Schneider

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

  7. ROLE OF VACUUM ASSISTED CLOSURE (VAC - IN WOUND HEALING

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    L. Lokanadha Rao

    2016-09-01

    Full Text Available BACKGROUND Large, complicated wounds pose a significant surgical problem. Negative pressure wound therapy is one of several methods enabling to obtain better treatment results in case of open infected wounds.1,2 The use of negative pressure therapy enables to obtain a reduction in the number of bacteria which significantly reduces the number of complications.3,4,5 AIMS AND OBJECTIVES: To review the Role of VAC in wound healing in Orthopaedics. MATERIALS AND METHODS The cases presented in this study are those who were admitted in King George Hospital in the time period from January 2014 to August 2015. This is a prospective interventional study. In this study, 15 patients were assigned to the study group (Negative Pressure Wound Therapy- NPWT based on their willingness for undergoing treatment. OBSERVATIONS AND RESULTS 12 males and 3 females are involved in the study. There is decrease in the mean wound area from 64 cm2 to 38 cm2 . There is decrease in the duration of hospital stay. Finally, wound is closed by SSG or secondary suturing. DISCUSSION NPWT is known to reduce bacterial counts, although they remain colonised with organisms. Wounds covered with NPW dressing are completely isolated from the environment, thereby reduces cross infection. In our series, we had 73.3% (11 cases excellent results and 26.7% (4 cases good results and no poor results. As interpretation with results, VAC therapy is effective mode of adjuvant therapy for the management of infected wounds. CONCLUSION VAC has been proven to be a reliable method of treating a variety of infected wounds. It greatly increases the rate of granulation tissue formation and lowers bacterial counts to accelerate wound healing. It can be used as a temporary dressing to prepare wounds optimally prior to closure or as a definitive treatment for nonsurgical and surgical wounds. VAC is now being used in a multitude of clinical settings, including the treatment of surgical wounds, infected wounds

  8. Skin wound healing in different aged Xenopus laevis.

    Science.gov (United States)

    Bertolotti, Evelina; Malagoli, Davide; Franchini, Antonella

    2013-08-01

    Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation.

  9. Gender affects skin wound healing in plasminogen deficient mice.

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    Birgitte Rønø

    Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

  10. Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model.

    Science.gov (United States)

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

    2012-01-01

    Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant health care burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work showed that Pseudomonas aeruginosa (PAO1) biofilm challenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing, and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2-day-old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks. Of the biofilm-challenged wounds, 64% healed by 6 weeks, and all of the biofilm-challenged wounds healed by 8 weeks. During the wound-healing process, P. aeruginosa was gradually cleared from the wounds while the presence of Staphylococcus aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 10(7) P. aeruginosa, which was 100-fold higher than the counts isolated from wound beds (i.e., 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization, and increased inflammatory cytokines. Hypoxia inducible factor expression increased threefold in 4-week wounds. In summary, our study shows that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than nonbiofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test antibiofilm strategies for treating chronic wounds.

  11. Re-epithelialization: advancing epithelium frontier during wound healing.

    Science.gov (United States)

    Ben Amar, M; Wu, M

    2014-04-06

    The first function of the skin is to serve as a protective barrier against the environment. Its loss of integrity as a result of injury or illness may lead to a major disability and the first goal of healing is wound closure involving many biological processes for repair and tissue regeneration. In vivo wound healing has four phases, one of them being the migration of the healthy epithelium surrounding the wound in the direction of the injury in order to cover it. Here, we present a theoretical model of the re-epithelialization phase driven by chemotaxis for a circular wound. This model takes into account the diffusion of chemoattractants both in the wound and the neighbouring tissue, the uptake of these molecules by the surface receptors of epithelial cells, the migration of the neighbour epithelium, the tension and proliferation at the wound border. Using a simple Darcy's law for cell migration transforms our biological model into a free-boundary problem, which is analysed in the simplified circular geometry leading to explicit solutions for the closure and making stability analysis possible. It turns out that for realistic wound sizes of the order of centimetres and from experimental data, the re-epithelialization is always an unstable process and the perfect circle cannot be observed, a result confirmed by fully nonlinear simulations and in agreement with experimental observations.

  12. Re-epithelialization: advancing epithelium frontier during wound healing

    Science.gov (United States)

    Ben Amar, M.; Wu, M.

    2014-01-01

    The first function of the skin is to serve as a protective barrier against the environment. Its loss of integrity as a result of injury or illness may lead to a major disability and the first goal of healing is wound closure involving many biological processes for repair and tissue regeneration. In vivo wound healing has four phases, one of them being the migration of the healthy epithelium surrounding the wound in the direction of the injury in order to cover it. Here, we present a theoretical model of the re-epithelialization phase driven by chemotaxis for a circular wound. This model takes into account the diffusion of chemoattractants both in the wound and the neighbouring tissue, the uptake of these molecules by the surface receptors of epithelial cells, the migration of the neighbour epithelium, the tension and proliferation at the wound border. Using a simple Darcy's law for cell migration transforms our biological model into a free-boundary problem, which is analysed in the simplified circular geometry leading to explicit solutions for the closure and making stability analysis possible. It turns out that for realistic wound sizes of the order of centimetres and from experimental data, the re-epithelialization is always an unstable process and the perfect circle cannot be observed, a result confirmed by fully nonlinear simulations and in agreement with experimental observations. PMID:24451391

  13. Survey of Wound-Healing Centers and Wound Care Units in China.

    Science.gov (United States)

    Jiang, Yufeng; Xia, Lei; Jia, Lijing; Fu, Xiaobing

    2016-09-01

    The purpose of this study is to report the Chinese experience of establishing hospital-based wound care centers over 15 years. A total of 69 wound-healing centers (WHCs) and wound care units (WCUs) were involved. Questionnaires were diverged to the principal directors of these sites; data extracted for this study included origin, year of establishment, medical staff, degree of hospitals, wound etiology, wound-healing rate, hospital stay, and outcomes data. The period of data extraction was defined as before and after 1 year of the establishment of WHCs and WCUs. The earliest WHC was established in 1999, and from 2010 the speeds of establishing WHCs and WCUs rapidly increased. The majority of WHCs were divisions of burn departments, and all WHCs came from departments of outpatient dressing rooms. Full-time multidisciplinary employees of WHCs differed greatly to WCUs. Types of wound and outcomes vary with those of centers reported from Western countries and the United States. Improvement in wound healing caused by the establishment of WHCs and WCUs in China occurred without doubt. Some advices include the following: rearrange and reorganize the distribution of WHCs and WCUs; enact and generalize Chinese guidelines for chronic wounds; utilize medical resources reasonably; improve multidisciplinary medical staff team; draw up and change some medical and public policies and regulations.

  14. Acticoat™ stimulates inflammation, but does not delay healing, in acute full-thickness excisional wounds.

    Science.gov (United States)

    Hartmann, Carol A; Rode, Heinz; Kramer, Beverley

    2016-12-01

    Acticoat™ has antimicrobial and anti-inflammatory effects which aid wound healing. However, in vitro studies indicate that Acticoat™ is cytotoxic and clinical and in vivo studies suggest that it may delay healing in acute wounds. Therefore, this study investigated the effects of Acticoat™ on healing in acute full-thickness excisional wounds. Using a porcine model, healing was assessed on days 3, 6, 9 and 15 post-wounding. Five wounds dressed with Acticoat™ and five wounds dressed with polyurethane film (control) were assessed per day (n = 40 wounds). The rate of healing, inflammatory response, restoration of the epithelium and blood vessel and collagen formation were evaluated. No difference was found in the rate of healing between wounds treated with Acticoat™ and the control wounds. Inflammation was increased in Acticoat™-treated wounds on day 3 post-wounding compared to the control wounds. However, by day 15 post-wounding, the epithelium of the Acticoat™-treated wounds closely resembled normal epithelium. Acticoat™-treated wounds also contained a higher proportion of mature blood vessels, and differences in collagen deposition were apparent. Despite inducing an inflammatory response, Acticoat™ did not delay healing in acute wounds. Conversely, the improved quality of the epithelium and blood vessels within Acticoat™-treated wounds indicates that Acticoat™ has a beneficial effect on healing. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  15. Stimulation of wound healing by helium atmospheric pressure plasma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Nastuta, Andrei Vasile; Topala, Ionut; Pohoata, Valentin; Popa, Gheorghe [Faculty of Physics, Alexandru Ioan Cuza University, Bd. Carol No. 11, 700506, Iasi (Romania); Grigoras, Constantin, E-mail: andrei.nastuta@uaic.ro [Physiopathology Department, Grigore T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania)

    2011-03-16

    New experiments using atmospheric pressure plasma have found large application in treatment of living cells or tissues, wound healing, cancerous cell apoptosis, blood coagulation on wounds, bone tissue modification, sterilization and decontamination. In this study an atmospheric pressure plasma jet generated using a cylindrical dielectric-barrier discharge was applied for treatment of burned wounds on Wistar rats' skin. The low temperature plasma jet works in helium and is driven by high voltage pulses. Oxygen and nitrogen based impurities are identified in the jet by emission spectroscopy. This paper analyses the natural epithelization of the rats' skin wounds and two methods of assisted epithelization, a classical one using polyurethane wound dressing and a new one using daily atmospheric pressure plasma treatment of wounds. Systemic and local medical data, such as haematological, biochemical and histological parameters, were monitored during entire period of study. Increased oxidative stress was observed for plasma treated wound. This result can be related to the presence in the plasma volume of active species, such as O and OH radicals. Both methods, wound dressing and plasma-assisted epithelization, provided positive medical results related to the recovery process of burned wounds. The dynamics of the skin regeneration process was modified: the epidermis re-epitelization was accelerated, while the recovery of superficial dermis was slowed down.

  16. Stimulation of wound healing by helium atmospheric pressure plasma treatment

    Science.gov (United States)

    Vasile Nastuta, Andrei; Topala, Ionut; Grigoras, Constantin; Pohoata, Valentin; Popa, Gheorghe

    2011-03-01

    New experiments using atmospheric pressure plasma have found large application in treatment of living cells or tissues, wound healing, cancerous cell apoptosis, blood coagulation on wounds, bone tissue modification, sterilization and decontamination. In this study an atmospheric pressure plasma jet generated using a cylindrical dielectric-barrier discharge was applied for treatment of burned wounds on Wistar rats' skin. The low temperature plasma jet works in helium and is driven by high voltage pulses. Oxygen and nitrogen based impurities are identified in the jet by emission spectroscopy. This paper analyses the natural epithelization of the rats' skin wounds and two methods of assisted epithelization, a classical one using polyurethane wound dressing and a new one using daily atmospheric pressure plasma treatment of wounds. Systemic and local medical data, such as haematological, biochemical and histological parameters, were monitored during entire period of study. Increased oxidative stress was observed for plasma treated wound. This result can be related to the presence in the plasma volume of active species, such as O and OH radicals. Both methods, wound dressing and plasma-assisted epithelization, provided positive medical results related to the recovery process of burned wounds. The dynamics of the skin regeneration process was modified: the epidermis re-epitelization was accelerated, while the recovery of superficial dermis was slowed down.

  17. Wnt signaling induces epithelial differentiation during cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Hocking Anne

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Gingival wound healing: an essential response disturbed by aging?

    Science.gov (United States)

    Smith, P C; Cáceres, M; Martínez, C; Oyarzún, A; Martínez, J

    2015-03-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  1. The heme-heme oxygenase system in wound healing; implications for scar formation.

    NARCIS (Netherlands)

    Wagener, F.A.D.T.G.; Scharstuhl, A.; Tyrrell, R.M.; Hoff, J.W. von den; Jozkowicz, A.; Dulak, J.; Russel, F.G.M.; Kuijpers-Jagtman, A.M.

    2010-01-01

    Wound healing is an intricate process requiring the concerted action of keratinocytes, fibroblasts, endothelial cells, and macrophages. Here, we review the literature on normal wound healing and the pathological forms of wound healing, such as hypertrophic or excessive scar formation, with special e

  2. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

    Science.gov (United States)

    Ansurudeen, Ishrath; Sunkari, Vivekananda Gupta; Grünler, Jacob; Peters, Verena; Schmitt, Claus Peter; Catrina, Sergiu-Bogdan; Brismar, Kerstin; Forsberg, Elisabete Alcantara

    2012-07-01

    Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

  3. Targeting connexin 43 in diabetic wound healing: Future perspectives

    Directory of Open Access Journals (Sweden)

    Bajpai S

    2009-01-01

    Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

  4. Regenerative Medicine: Novel Approach in Burn Wound Healing

    Directory of Open Access Journals (Sweden)

    Zare

    2015-06-01

    Full Text Available Context Burn wounds of the skin require a long period to healing, which very often is incomplete, with functional and esthetic consequences for the patients. Stem cells in the traumatized tissue represent the promoters of the healing process and are a primary focus for regenerative medicine, which aims to find and use the triggers for the activation of stem cells of sin tissue. Evidence Acquisition At present, tissue engineering, composite epithelial autografts, multipotent stem cells and combined gene delivery with stem cell therapy are the approaches used in regenerative medicine. Alongside, the development of 3D scaffolds or matrices is a promising adjunct, as studies investigate the multiple uses of these supports for wound repair. Results Application of cells to the burn wound could be performed, either by the bedside, as a non-invasive procedure, or in the operating room, with the use of a matrix, scaffold or dermal substitute. Cell spraying, although under use in clinical setting, is not yet supported by conclusive data. Magnetic resonance imaging, optical imaging and positron emission tomography are currently used to assess the viability and location of stem cells, after transplantation. Conclusions Stem cell therapies in wound care may lessen the morbidities associated with wound healing. An ideal method for the effective administration of stem cells for burn patients has not yet been elucidated. Further comparison of the local and systemic effects in burn patients, associated with each route of stem cell delivery, needs to be performed.

  5. The effects of Ankaferd, a hemostatic agent, on wound healing

    Directory of Open Access Journals (Sweden)

    Sevgi Özbaysar Sezgin

    2015-09-01

    Full Text Available Background and Design: There have been a lot of topical and systemic agents to provide an ideal scar formation and to decrease the periods of wound healing process by affecting the factors of healing (inflammatory cells, thrombocytes, extracellular matrix etc.. In this study, we investigated the effects of Ankaferd on wound healing. Materials and Methods: Wounds were created with 8 mm punch biopsy knots on the back of 32 rats which were separated into 4 groups of 9 rats. No treatment was done in group D which was the control group while group A received topical Ankaferd treatment twice a day; group B treated with silver sulfadiazine twice a day, and group C put on base cream, which did not include any active agent, twice a day. The rats were followed for 15 days macroscopically and examined histopathologically on days 0., 3., 7., and 15. by taking biopsy specimens. Result: At the end of our study, it was detected that Ankaferd accelerated the healing process in comparison to control and base cream groups according to the macroscopic and histopathologic results. Additionally, similar to this situation, it was observed that the healing process in silver sulfadiazine group was faster than in control and base cream groups. Conclusion: More experimental and clinical studies in larger populations are needed to prove and confirm its efficacy.

  6. Serum amyloid P inhibits dermal wound healing

    Science.gov (United States)

    The repair of open wounds depends on granulation tissue formation and contraction, which is primarily mediated by myofibroblasts. A subset of myofibroblasts originates from bone-marrow-derived monocytes which differentiate into fibroblast-like cells called fibrocytes. Serum amyloid P (SAP) inhibits ...

  7. Role of Fibronectin in Wound Healing.

    Science.gov (United States)

    1986-09-12

    Detrick, Frederiek, Nmryland 21701-5012 Contract f. DAl-17-S3-C-3235 Mdloal Colle" of Georgia Augusta, GA 30912 Approved for public distribution...about 30 sec, and replaced In the abdominal cavity. The mucle layer was sutured with 4.0 silk, and the skin was closed with wound clips. Blood samples

  8. FOXO1, TGF-β regulation and wound healing.

    Science.gov (United States)

    Hameedaldeen, Alhassan; Liu, Jian; Batres, Angelika; Graves, Gabrielle S; Graves, Dana T

    2014-09-15

    Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds.

  9. Aloe Gel Enhances Angiogenesis in Healing of Diabetic Wound

    Directory of Open Access Journals (Sweden)

    Djanggan Sargowo

    2011-12-01

    Full Text Available BACKGROUND: Diabetic micro and macroangiophathy lead to the incident of diabetic foot ulcers characterized by an increased number of circulating endothelial cells (CECs and decreased function of endothelial progenitor cells (EPCs. This fact is correlated with ischemia and diabetic wound healing failure. Aloe vera gel is known to be able to stimulate vascular endothelial growth factor (VEGF expression and activity by enhancing nitric oxide (NO production as a result of nitric oxide synthase (NOS enzyme activity. Aloe vera is a potential target to enhancing angiogenesis in wound healing. OBJECTIVE: The objective of this study was to explore the major role of Aloe vera gel in wound healing of diabetic ulcers by increasing the level of EPCs, VEGF, and endothelial nitric oxide synthase (eNOS, as well as by reducing the level of CECs involved in angiogenesis process of diabetic ulcers healing. METHODS: The experimental groups was divided into five subgroups consisting of non diabetic wistar rats, diabetic rats without oral administration of aloe gel, and treatment subgroup (diabetic rats with 30, 60 and 120 mg/day of aloe gel doses for 14 days. All subgroups were wounded and daily observation was done on the wounds areas. Measurement of the number of EPCs (CD34, and CECs (CD45 and CD146 was done by flow cytometry, followed by measurement of VEGF and eNOS expression on dermal tissue by immunohistochemical method on day 0 and day 14 after treatment. The quantitative data were analyzed by One-Way ANOVA and Linear Regression, with a confidence interval 5% and significance level (p<0.05 using SPSS 16 software to compare the difference and correlation between wound diameters, number of EPCs and CECs as well as the levels of VEGF and eNOS. RESULTS: The results of this study showed that aloe gel oral treatment in diabetic wistar rats was able to accelerate the wound healing process. It was shown by significant reduction of wound diameter (0.27±0.02; the

  10. Increased collagen synthesis rate during wound healing in muscle.

    Directory of Open Access Journals (Sweden)

    Shaobo Zhou

    Full Text Available Wound healing in muscle involves the deposition of collagen, but it is not known whether this is achieved by changes in the synthesis or the degradation of collagen. We have used a reliable flooding dose method to measure collagen synthesis rate in vivo in rat abdominal muscle following a surgical incision. Collagen synthesis rate was increased by 480% and 860% on days 2 and 7 respectively after surgery in the wounded muscle compared with an undamaged area of the same muscle. Collagen content was increased by approximately 100% at both day 2 and day 7. These results demonstrate that collagen deposition during wound healing in muscle is achieved entirely by an increase in the rate of collagen synthesis.

  11. Gender affects skin wound healing in plasminogen deficient mice

    DEFF Research Database (Denmark)

    Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge;

    2013-01-01

    functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...... in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound...

  12. Wound healing: time to look for intelligent, 'natural' immunological approaches?

    Science.gov (United States)

    Garraud, Olivier; Hozzein, Wael N; Badr, Gamal

    2017-06-21

    There is now good evidence that cytokines and growth factors are key factors in tissue repair and often exert anti-infective activities. However, engineering such factors for global use, even in the most remote places, is not realistic. Instead, we propose to examine how such factors work and to evaluate the reparative tools generously provided by 'nature.' We used two approaches to address these objectives. The first approach was to reappraise the internal capacity of the factors contributing the most to healing in the body, i.e., blood platelets. The second was to revisit natural agents such as whey proteins, (honey) bee venom and propolis. The platelet approach elucidates the inflammation spectrum from physiology to pathology, whereas milk and honey derivatives accelerate diabetic wound healing. Thus, this review aims at offering a fresh view of how wound healing can be addressed by natural means.

  13. A rat uterine horn model of genital tract wound healing.

    Science.gov (United States)

    Schlaff, W D; Cooley, B C; Shen, W; Gittlesohn, A M; Rock, J A

    1987-11-01

    A rat uterine horn model of genital tract wound healing is described. Healing was reflected by acquisition of strength and elasticity, measured by burst strength (BS) and extensibility (EX), respectively. A tensiometer (Instron Corp., Canton, MA) was used to assess these characteristics in castrated and estrogen-supplemented or nonsupplemented animals. While the horn weights (HW), BS, and EX of contralateral horns were not significantly different, the intra-animal variation of HW was 7.2%, BS was 17.7% and EX was 38.2%. In a second experiment, one uterine horn was divided and anastomosed, and the animal given estrogen supplementation or a placebo pellet. Estrogen administration was found to increase BS and EX of anastomosed horns prior to 14 days, but had no beneficial effect at 21 or 42 days. The data suggest that estrogen may be required for optimal early healing of genital tract wounds.

  14. Healing the Hidden Wounds of Racial Trauma

    Science.gov (United States)

    Hardy, Kenneth V.

    2013-01-01

    This article examines racial trauma and highlights strategies for healing and transformation to support the disproportionate number of children and youth of color who fail in school and become trapped in the pipelines of treatment, social service, and justice systems. The difficulty in meeting the needs of these children and youth is failing to…

  15. Healing the Hidden Wounds of Racial Trauma

    Science.gov (United States)

    Hardy, Kenneth V.

    2013-01-01

    This article examines racial trauma and highlights strategies for healing and transformation to support the disproportionate number of children and youth of color who fail in school and become trapped in the pipelines of treatment, social service, and justice systems. The difficulty in meeting the needs of these children and youth is failing to…

  16. Effects of Silk Sericin on Incision Wound Healing in a Dorsal Skin Flap Wound Healing Rat Model

    Science.gov (United States)

    Ersel, Murat; Uyanikgil, Yigit; Akarca, Funda Karbek; Ozcete, Enver; Altunci, Yusuf Ali; Karabey, Fatih; Cavusoglu, Turker; Meral, Ayfer; Yigitturk, Gurkan; Cetin, Emel Oyku

    2016-01-01

    Background The wound healing process is complex and still poorly understood. Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective of this study was to evaluate in vivo wound healing effects of a sericin-containing gel formulation in an incision wound model in rats. Material/Methods Twenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention or treatment was applied to the Intact control group. For other groups, a dorsal skin flap (9×3 cm) was drawn and pulled up with sharp dissection. The Sham operated group received no treatment. The Placebo group received placebo gel without sericin applied to the incision area once a day from day 0 to day 9. The Sericin Group 3 received 1% sericin gel applied to the incision area once a day from day 0 to day 9. Hematoxylin and eosin stain was applied for histological analysis and Mallory-Azan staining was applied for histoimmunochemical analysis of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied to paraffin sections of skin wound specimens. Parameters of oxidative stress were measured in the wound area. Results Epidermal thickness and vascularization were increased, and hair root degeneration, edema, cellular infiltration, collagen discoloration, and necrosis were decreased in Sericin group in comparison to the Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were increased in the sericin group. Conclusions We found that sericin had significant positive effects on wound healing and antioxidant activity. Sericin-based formulations can improve healing of incision wounds. PMID:27032876

  17. Genomic Loci Modulating the Retinal Transcriptome in Wound Healing

    Directory of Open Access Journals (Sweden)

    Félix R. Vázquez-Chona

    2007-01-01

    Full Text Available Purpose: The present study predicts and tests genetic networks that modulate gene expression during the retinal wound-healing response.Methods: Upstream modulators and target genes were defined using meta-analysis and bioinfor matic approaches. Quantitative trait loci (QTLs for retinal acute phase genes (Vazquez-Chona et al. 2005 were defi ned using QTL analysis of CNS gene expression (Chesler et al. 2005. Candidate modulators were defi ned using computational analysis of gene and motif sequences. The effect of candidate genes on wound healing was tested using animal models of gene expression.Results: A network of early wound-healing genes is modulated by a locus on chromosome 12. The genetic background of the locus altered the wound-healing response of the retina. The C57BL/6 allele conferred enhanced expression of neuronal marker Thy1 and heat-shock-like crystallins, whereas the DBA/2J allele correlated with greater levels of the classic marker of retinal stress, glial fibrillary acidic protein (GFAP. Id2 and Lpin1 are candidate upstream modula tors as they strongly correlated with the segregation of DBA/2J and C57BL/6 alleles, and their dosage levels correlated with the enhanced expression of survival genes (Thy1 and crystallin genes.Conclusion: We defined a genetic network associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate modulators that control transcript levels of acute phase genes. Our results support the convergence of gene expression profiling, QTL analysis, and bioinformatics as a rational approach to discover molecular pathways controlling retinal wound healing.

  18. A bioactive molecule in a complex wound healing process: platelet-derived growth factor.

    Science.gov (United States)

    Kaltalioglu, Kaan; Coskun-Cevher, Sule

    2015-08-01

    Wound healing is considered to be particularly important after surgical procedures, and the most important wounds related to surgical procedures are incisional, excisional, and punch wounds. Research is ongoing to identify methods to heal non-closed wounds or to accelerate wound healing; however, wound healing is a complex process that includes many biological and physiological events, and it is affected by various local and systemic factors, including diabetes mellitus, infection, ischemia, and aging. Different cell types (such as platelets, macrophages, and neutrophils) release growth factors during the healing process, and platelet-derived growth factor is a particularly important mediator in most stages of wound healing. This review explores the relationship between platelet-derived growth factor and wound healing.

  19. The use of wound healing assessment methods in psychological studies: a review and recommendations.

    Science.gov (United States)

    Koschwanez, Heidi E; Broadbent, Elizabeth

    2011-02-01

    To provide a critical review of methods used to assess human wound healing in psychological research and related disciplines, in order to guide future research into psychological influences on wound healing. Acute wound models (skin blister, tape stripping, skin biopsy, oral palate biopsy, expanded polytetrafluoroethylene tubing), surgical wound healing assessment methods (wound drains, wound scoring), and chronic wound assessment techniques (surface area, volumetric measurements, wound composition, and assessment tools/scoring systems) are summarized, including merits, limitations, and recommendations. Several dermal and mucosal tissue acute wound models have been established to assess the effects of psychological stress on the inflammatory, proliferative, and repair phases of wound healing in humans, including material-based models developed to evaluate factors influencing post-surgical recovery. There is a paucity of research published on psychological factors influencing chronic wound healing. There are many assessment techniques available to study the progression of chronic wound healing but many difficulties inherent to long-term clinical studies. Researchers need to consider several design-related issues when conducting studies into the effects of psychological stress on wound healing, including the study aims, type of wound, tissue type, setting, sample characteristics and accessibility, costs, timeframe, and facilities available. Researchers should consider combining multiple wound assessment methods to increase the reliability and validity of results and to further understand mechanisms that link stress and wound healing. ©2010 The British Psychological Society.

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

    NARCIS (Netherlands)

    Boink, M.A.; van den Broek, L.J.; Roffel, S.; Nazmi, K.; Bolscher, J.G.M.; Gefen, A.; Veerman, E.C.I.; Gibbs, S.

    2016-01-01

    Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their

  1. Early wound healing and refractive response of different pocket configurations following presbyopic inlay implantation

    Science.gov (United States)

    Konstantopoulos, Aris; Liu, Yu-Chi; Teo, Ericia Pei Wen; Lwin, Nyein Chan; Yam, Gary Hin Fai; Mehta, Jodhbir S.

    2017-01-01

    Background Presbyopic inlays have mostly been implanted under a corneal flap. Implantation in a pocket has advantages including less postoperative dry eye and neurotrophic effect, and better biomechanical corneal stability. This study investigated the effect of different pocket and flocket dimensions on corneal stability and refractive power after Raindrop™ implantation, and the associated wound healing response. Methodology Ten New Zealand White rabbits had bilateral pocket Raindrop™ implantation. Eyes were allocated to 4 groups: pockets with 4mm, 6mm, and 8mm diameters, and 8mm flocket. They were examined pre-operatively, at day 1, weeks 1, 2, 3 and 4 post-surgery with anterior segment optical coherence tomography, corneal topography and in-vivo confocal microscopy. After euthanasia (week 4), CD11b, heat shock protein (HSP) 47 and fibronectin corneal immunohistochemistry was performed. Results Corneal thickness (mean±SD) increased from 360.0±16.2μm pre-operatively to 383.9±32.5, 409.4±79.3, 393.6±35.2, 396.4±50.7 and 405±20.3μm on day 1, weeks 1,2,3 and 4 respectively (pCorneal refractive power increased by 11.1±5.5, 7.5±2.5, 7.5±3.1, 7.0±3.6 and 6.3±2.9D (pCorneal astigmatism increased from 1.1±0.3D to 2.3±1.6, 1.7±0.7, 1.8±1.0, 1.6±0.9 and 1.6±0.9D respectively (p = 0.033). CT, refractive power change and astigmatism were not different between groups. The 8mm pocket and 8mm flocket groups had the least stromal keratocyte reflectivity. CD11b, fibronectin or HSP47 weren’t detected. Conclusions Anatomical and refractive stability was achieved by 1 week; the outcomes were not affected by pocket or flocket configuration. No scarring or inflammation was identified. The 8mm pocket and flocket showed the least keratocyte activation, suggesting they might be the preferred configuration. PMID:28235010

  2. Restraint stress alters neutrophil and macrophage phenotypes during wound healing.

    Science.gov (United States)

    Tymen, Stéphanie D; Rojas, Isolde G; Zhou, Xiaofeng; Fang, Zong Juan; Zhao, Yan; Marucha, Phillip T

    2013-02-01

    Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting.

  3. Influence of hydrophilic polymers on functional properties and wound healing efficacy of hydrocolloid based wound dressings.

    Science.gov (United States)

    Jin, Sung Giu; Yousaf, Abid Mehmood; Kim, Kyeong Soo; Kim, Dong Wuk; Kim, Dong Shik; Kim, Jin Ki; Yong, Chul Soon; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

    2016-03-30

    The purpose of this study was to investigate the influence of different hydrophilic polymers on the swelling, bioadhesion and mechanical strength of hydrocolloid wound dressings (HCDs) in order to provide an appropriate composition for a hydrocolloid wound dressing system. In this study, the HCDs were prepared with styrene-isoprene-styrene copolymer (SIS) and polyisobutylene (PIB) as the base using a hot melting method. Additionally, numerous SIS/PIB-based HCDs were prepared with six hydrophilic polymers, and their wound dressing properties were assessed. Finally, the wound healing efficacy of the selected formulations was compared to a commercial wound dressing. The swelling ratio, bioadhesive force and mechanical strengths of HCDs were increased in the order of sodium alginate>sodium CMC=poloxamer=HPMC>PVA=PVP, sodium alginate>sodium CMC=poloxamer>PVA>HPMC=PVP and sodium alginate≥PVA>PVP=HPMC=sodium CMC>poloxamer, respectively. Among the hydrophilic polymers tested, sodium alginate most enhanced the swelling capacity, bioadhesive force and mechanical strengths. Thus, the hydrophilic polymers played great role in the swelling, bioadhesion and mechanical strength of SIS/PIB-based HCDs. The HCD formulation composed of PIB, SIS, liquid paraffin and sodium alginate at the weight ratio of 20/25/12/43 gave better wound dressing properties and more excellent wound healing efficacy than the commercial wound dressing. Therefore, the novel HCD formulation could be a promising hydrocolloid system for wound dressings.

  4. Stem cells and chronic wound healing: state of the art

    Directory of Open Access Journals (Sweden)

    Leavitt T

    2016-03-01

    Full Text Available Tripp Leavitt, Michael S Hu, Clement D Marshall, Leandra A Barnes, Michael T Longaker, H Peter Lorenz Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA Abstract: Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells, endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition. Keywords: stem cells, chronic wounds, cell therapy, wound healing

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

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

    2009-09-01

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

  6. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    Science.gov (United States)

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

    2016-10-14

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

  7. Periostin as a multifunctional modulator of the wound healing response.

    Science.gov (United States)

    Walker, John T; McLeod, Karrington; Kim, Shawna; Conway, Simon J; Hamilton, Douglas W

    2016-09-01

    During tissue healing, the dynamic and temporal alterations required for effective repair occur in the structure and composition of the extracellular matrix (ECM). Matricellular proteins (MPs) are a group of diverse non-structural ECM components that bind cell surface receptors mediating interactions between the cell and its microenviroment, effectively regulating adhesion, migration, proliferation, signaling, and cell phenotype. Periostin (Postn), a pro-fibrogenic secreted glycoprotein, is defined as an MP based on its expression pattern and regulatory roles during development and healing and in disease processes. Postn consists of a typical signal sequence, an EMI domain responsible for binding to fibronectin, four tandem fasciclin-like domains that are responsible for integrin binding, and a C-terminal region in which multiple splice variants originate. This review focuses specifically on the role of Postn in wound healing and remodeling, an area of intense research during the last 10 years, particularly as related to skin healing and myocardium post-infarction. Postn interacts with cells through various integrin pairs and is an essential downstream effector of transforming growth factor-β superfamily signaling. Across various tissues, Postn is associated with the pro-fibrogenic process: specifically, the transition of fibroblasts to myofibroblasts, collagen fibrillogenesis, and ECM synthesis. Although the complexity of Postn as a modulator of cell behavior in tissue healing is only beginning to be elucidated, its expression is clearly a defining event in moving wound healing through the proliferative and remodeling phases.

  8. Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects

    Science.gov (United States)

    Dai, Tianhong; Tanaka, Masamitsu; Huang, Ying-Ying; Hamblin, Michael R

    2011-01-01

    Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns. PMID:21810057

  9. Superficial Burn Wound Healing with Intermittent Negative Pressure Wound Therapy Under Limited Access and Conventional Dressings

    Science.gov (United States)

    Honnegowda, Thittamaranahalli Muguregowda; Padmanabha Udupa, Echalasara Govindarama; Rao, Pragna; Kumar, Pramod; Singh, Rekha

    2016-01-01

    BACKGROUND Thermal injury is associated with several biochemical and histopathological alteration in tissue. Analysis of these objective parameters in research and clinical field are common to determine healing rate of burn wound. Negative pressure wound therapy has been achieved wide success in treating chronic wounds. This study determines superficial burn wound healing with intermittent negative pressure wound therapy under limited access and conventional dressings METHODS A total 50 patients were randomised into two equal groups: limited access and conventional dressing groups. Selective biochemical parameters such as hydroxyproline, hexosamine, total protein, and antioxidants, malondialdhyde (MDA), wound surface pH, matrix metalloproteinase-2 (MMP-2), and nitric oxide (NO) were measured in the granulation tissue. Histopathologically, necrotic tissue, amount of inflammatory infiltrate, angiogenesis and extracellular matrix deposition (ECM) were studied to determine wound healing under intermittent negative pressure. RESULTS Patients treated with limited access have shown significant increase in the mean hydroxyproline, hexosamine, total protein, reduced glutathione (GSH), glutathione peroxidase (GPx), and decrease in MDA, MMP-2, wound surface pH, and NO. Histopathologic study showed that there was a significant difference after 10 days of treatment between limited access vs conventional dressing group, Median (Q1, Q3)=3 (2, 4.25) vs 2 (1.75, 4). CONCLUSION Limited access was shown to exert its beneficial effects on wound healing by increasing ground substance, antioxidants and reducing MMP-2 activity, MDA, NO and providing optimal pH, decreasing necrotic tissue, amount of inflammatory infiltrate, increasing ECM deposition and angiogenesis. PMID:27853690

  10. Wound healing in hemophilia B mice and low tissue factor mice.

    Science.gov (United States)

    Monroe, Dougald M; Mackman, Nigel; Hoffman, Maureane

    2010-04-01

    Wound healing involves a number of physiologic mechanisms including coagulation, inflammation, formation of granulation tissue, and tissue remodeling. Coagulation with robust thrombin generation leading to fibrin formation is necessary for wound healing. It is less clear if there is a requirement for ongoing coagulation to support tissue remodeling. We have studied wound healing in mice with defects in both the initiation (low tissue factor) and propagation (hemophilia B) phases. In hemophilia B mice, dermal wound healing is delayed; this delay is associated with bleeding into the granulation tissue. Mice can be treated with replacement therapy (factor IX) or bypassing agents (factor VIIa) to restore thrombin generation. If treated just prior to wound placement, mice will have normal hemostasis in the first day of wound healing. As the therapeutic agents clear, the mice will revert to hemophilic state. If the primary role of coagulation in wound healing is to provide a stable platelet/fibrin plug that is loaded with thrombin, then treating hemophilic animals just prior to wound placement should restore normal wound healing. The results from this study did not support that hypothesis. Instead the results show that restoring thrombin generation only at the time of wound placement did not improve the delayed wound healing. In preliminary studies on low tissue factor mice, there also appears to be a delay in wound healing with evidence of bleeding into the granulation tissue. The current data suggests that ongoing coagulation function needs to be maintained to support a normal wound healing process.

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

    Science.gov (United States)

    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.

  12. Influence of surgical sutures on wound healing

    Directory of Open Access Journals (Sweden)

    Mirković Siniša

    2010-01-01

    Full Text Available Historical data on closing and suturing of surgical wounds describe a wide range of various suture materials. The choice of the surgical catgut, i.e. the type and diameter, depends on the locality, characteristics and condition of the tissue to be treated. From the standpoint of oral-surgical practice the following clinical parameters are of outstanding importance with respect to the selection of suture material: accumulation of soft deposits on the sutures, score of the adjacent soft tissues and dehiscence of the operative wound. Our prospective clinical study included 150 patients distributed into three groups of 50 subjects. The surgical procedure performed on each patient involved resection (apicotomy of the tooth root end in the intercanine sector of the upper jaw. The following suture materials were applied: Black Silc 5-0, Nylon 5-0 and Vicryl 5-0. The effects of the selected sutures were evaluated according to the wound dehiscence. The effects of the applied sutures were recorded on Days 2, 5 and 7 after the surgery. The comparison of cited parameters of the investigated materials after suturing the oral mucosa revealed that none of the used material was ideal; however, a certain advantage might be given to the synthetic monofilament suture materials.

  13. Corneal Regeneration After Photorefractive Keratectomy: A Review.

    Science.gov (United States)

    Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

    2015-01-01

    Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  14. Development of honey hydrogel dressing for enhanced wound healing

    Science.gov (United States)

    Yusof, Norimah; Ainul Hafiza, A. H.; Zohdi, Rozaini M.; Bakar, Md Zuki A.

    2007-11-01

    Radiation at 25 and 50 kGy showed no effect on the acidic pH of the local honey, Gelam, and its antimicrobial property against Staphylococcus aureus but significantly reduced the viscosity. Honey stored up to 2 years at room temperature retained all the properties studied. Radiation sterilized Gelam honey significantly stimulated the rate of burn wound healing in Sprague-Dawley rats as demonstrated by the increased rate of wound contraction and gross appearance. Gelam honey attenuates wound inflammation; and re-epithelialization was well advanced compared to the treatment using silver sulphadiazine (SSD) cream. To enhance further the use of honey in wound treatment and for easy handling, Gelam honey was incorporated into our hydrogel dressing formulation, which was then cross-linked and sterilized using electron beam at 25 kGy. Hydrogel with 6% of honey was selected based on the physical appearance.

  15. Development of honey hydrogel dressing for enhanced wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Yusof, Norimah [Malaysian Institute for Nuclear Technology Research (MINT), Bangi, 43000 Kajang, Selangor (Malaysia)], E-mail: norimah@nuclearmalaysia.gov.my; Ainul Hafiza, A.H.; Zohdi, Rozaini M. [Malaysian Institute for Nuclear Technology Research (MINT), Bangi, 43000 Kajang, Selangor (Malaysia); Bakar, Md Zuki A. [Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor (Malaysia)

    2007-11-15

    Radiation at 25 and 50 kGy showed no effect on the acidic pH of the local honey, Gelam, and its antimicrobial property against Staphylococcus aureus but significantly reduced the viscosity. Honey stored up to 2 years at room temperature retained all the properties studied. Radiation sterilized Gelam honey significantly stimulated the rate of burn wound healing in Sprague-Dawley rats as demonstrated by the increased rate of wound contraction and gross appearance. Gelam honey attenuates wound inflammation; and re-epithelialization was well advanced compared to the treatment using silver sulphadiazine (SSD) cream. To enhance further the use of honey in wound treatment and for easy handling, Gelam honey was incorporated into our hydrogel dressing formulation, which was then cross-linked and sterilized using electron beam at 25 kGy. Hydrogel with 6% of honey was selected based on the physical appearance.

  16. Wound-associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing.

    Science.gov (United States)

    Rodero, Mathieu P; Legrand, Julien M D; Bou-Gharios, George; Khosrotehrani, Kiarash

    2013-02-01

    Wound-associated fibrosis is important to provide tensile strength upon wound healing but at the same time is detrimental to proper tissue regeneration. To date, there is no clear evidence of the role of macrophages and their subpopulations in the control of the kinetics of collagen production during wound healing. To evaluate in vivo the contribution of macrophages in collagen transcription, we depleted macrophages after wounding luciferase reporter mice of the collagen 1 alpha 2 (Col 1α2) promoter activity. Our data reveal that Col 1α2 starts to be transcribed at D2 after wounding, reaching a plateau after 7 days. Sustained macrophage depletion significantly reduced collagen 1α2 transcription from D4, indicating that the control of fibrosis by macrophages occurs during the early stages of the wound healing process. In conclusion, our results demonstrate an important role of wound macrophages in the control of collagen production during wound healing.

  17. [Pathophysiological aspects of wound healing in normal and diabetic foot].

    Science.gov (United States)

    Maksimova, N V; Lyundup, A V; Lubimov, R O; Melnichenko, G A; Nikolenko, V N

    2014-01-01

    The main cause of long-term healing of ulcers in patients with diabetic foot is considered to be direct mechanical damage when walking due to reduced sensitivity to due to neuropathy, hyperglycemia, infection and peripheral artery disease. These factors determine the standard approaches to the treatment of diabeticfoot, which include: offloading, glycemic control, debridement of ulcers, antibiotic therapy and revascularization. Recently, however, disturbances in the healing process of the skin in diabetes recognized an additional factor affecting the timing of healing patients with diabetic foot. Improved understanding and correction of cellular, molecular and biochemical abnormalities in chronic wound in combination with standard of care for affords new ground for solving the problem of ulcer healing in diabetes.

  18. Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis

    Directory of Open Access Journals (Sweden)

    Shibnath Ghatak

    2015-01-01

    Full Text Available A wound is a type of injury that damages living tissues. In this review, we will be referring mainly to healing responses in the organs including skin and the lungs. Fibrosis is a process of dysregulated extracellular matrix (ECM production that leads to a dense and functionally abnormal connective tissue compartment (dermis. In tissues such as the skin, the repair of the dermis after wounding requires not only the fibroblasts that produce the ECM molecules, but also the overlying epithelial layer (keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel and white blood cells such as neutrophils and macrophages, which together orchestrate the cytokine-mediated signaling and paracrine interactions that are required to regulate the proper extent and timing of the repair process. This review will focus on the importance of extracellular molecules in the microenvironment, primarily the proteoglycans and glycosaminoglycan hyaluronan, and their roles in wound healing. First, we will briefly summarize the physiological, cellular, and biochemical elements of wound healing, including the importance of cytokine cross-talk between cell types. Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes. Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.

  19. Biosynthesis and wound healing activity of copper nanoparticles.

    Science.gov (United States)

    Tiwari, Mradul; Narayanan, Kasinathan; Thakar, Mitali B; Jagani, Hitesh V; Venkata Rao, Josyula

    2014-12-01

    Nanotechnologies reinvented the utilities of various substances in healthcare. Copper in its native form (copper ion) has been well studied for its antimicrobial and anti-inflammatory activities. Copper in its nano form could have better biological profile and finds many applications in healthcare. There were reports on synthesis of copper nanoparticles by physical and chemical methods and their biological activities, although these methods have limitations. Biosynthesis of nanoparticles using microbes is an ecofriendly approach helping in the synthesis of biocompatible and stable nanoparticles. With this background in mind, the present study was designed to synthesise copper nanoparticles by Pseudomonas aeruginosa and testing their efficacy in enhancing the pace of wound healing. Culture supernatant was used to synthesise copper nanoparticles. Optimum conditions were selected to maximise the biosynthesis of nanoparticles. Biosynthesised copper nanoparticles (BNCPs) were characterised by Malvern zeta sizer and scanning electron microscopy. Average particle size, polydispersivity index and zeta potential of BNCPs were found to be 110.9 nm, 0.312 and (-) 18.3 mV, respectively. BNCPs was evaluated for its wound healing activity by excision wound model in rat. The pace of wound healing was enhanced by BNCPs compared with copper in native form.

  20. Laser therapy in wound healing associated with diabetes mellitus - Review*

    Science.gov (United States)

    de Sousa, Raquel Gomes; Batista, Keila de Nazaré Madureira

    2016-01-01

    The article discusses the results of a literature review on the application of low intensity laser therapy on the healing of wounds associated diabetes mellitus in the last 10 years. Objective To determine the most effective parameter in healing wounds related to diabetes mellitus, as well as the most widely used type of laser. Methodology consisted of bibliographic searching the databases Bireme, SciELO, PubMed/Medline and Lilacs by using the keywords related to the topic. Were selected from these keywords, papers discussing the use of laser on wounds associated with diabetes, published in the period 2005-2014, in Portuguese or English. Results After analyzing the research, 12 studies consistent with the theme were selected. Conclusion Based on this review, the studies that showed more satisfactory results in healing diabetic wounds were those who applied energy densities in the range of 3-5 J/cm2, power densities equal to or below 0.2 W/cm2 and continuous emission. The He-Ne laser with a wavelength of 632.8 nm was used more often. PMID:27579745

  1. Proteomics and Metabolomics for In Situ Monitoring of Wound Healing

    Science.gov (United States)

    Kalkhof, Stefan; Förster, Yvonne; Schmidt, Johannes; Schulz, Matthias C.; Baumann, Sven; Weißflog, Anne; Gao, Wenling; Hempel, Ute; Eckelt, Uwe; Rammelt, Stefan; von Bergen, Martin

    2014-01-01

    Wound healing of soft tissue and bone defects is a complex process in which cellular differentiation and adaption are regulated by internal and external factors, among them are many different proteins. In contrast to insights into the significance of various single proteins based on model systems, the knowledge about the processes at the actual site of wound healing is still limited. This is caused by a general lack of methods that allow sampling of extracellular factors, metabolites, and proteins in situ. Sampling of wound fluids in combination with proteomics and metabolomics is one of the promising approaches to gain comprehensive and time resolved data on effector molecules. Here, we describe an approach to sample metabolites by microdialysis and to extract proteins simultaneously by adsorption. With this approach it is possible (i) to collect, enrich, and purify proteins for a comprehensive proteome analysis; (ii) to detect more than 600 proteins in different defects including more than 100 secreted proteins, of which many proteins have previously been demonstrated to have diagnostic or predictive power for the wound healing state; and (iii) to combine continuous sampling of cytokines and metabolites and discontinuous sampling of larger proteins to gain complementary information of the same defect. PMID:25162036

  2. A review of herbal medicines in wound healing.

    Science.gov (United States)

    Maver, Tina; Maver, Uroš; Stana Kleinschek, Karin; Smrke, Dragica M; Kreft, Samo

    2015-07-01

    Herbs have been integral to both traditional and non-traditional forms of medicine dating back at least 5000 years. The enduring popularity of herbal medicines may be explained by the perception that herbs cause minimal unwanted side effects. More recently, scientists increasingly rely on modern scientific methods and evidence-based medicine to prove efficacy of herbal medicines and focus on better understanding of mechanisms of their action. However, information concerning quantitative human health benefits of herbal medicines is still rare or dispersed, limiting their proper valuation. Preparations from traditional medicinal plants are often used for wound healing purposes covering a broad area of different skin-related diseases. Herbal medicines in wound management involve disinfection, debridement, and provision of a suitable environment for aiding the natural course of healing. Here we report on 22 plants used as wound healing agents in traditional medicine around the world. The aim of this review is therefore to review herbal medicines, which pose great potential for effective treatment of minor wounds.

  3. Chronic venous disease - Part I: Inflammatory biomarkers in wound healing.

    Science.gov (United States)

    Ligi, Daniela; Mosti, Giovanni; Croce, Lidia; Raffetto, Joseph D; Mannello, Ferdinando

    2016-10-01

    Venous leg ulcers (VLUs) produce wound fluid (WF), as a result of inflammatory processes within the wound. It is unclear if WF from different healing phases of VLU has a peculiar biochemical profile and how VLU microenvironment affects the wound healing mechanisms. This study was conducted to evaluate the cytokine/chemokine profiles in WF from distinct VLU phases, in WF- and LPS-stimulated monocytes and treated with glycosaminoglycan Sulodexide, a therapeutic option for VLU healing. WF and plasma were collected from patients with VLU during active inflammatory (Infl) and granulating (Gran) phases. Demographics, clinical characteristics and pain measurements were evaluated. WF, plasma, and THP-1 supernatants were analyzed for 27 inflammatory mediators by multiplex immunoassay. Our results demonstrated that: 1) pain was significantly increased in patients with Infl compared to Gran VLU; 2) cytokine profile of Infl WF was found to be statistically different from that Gran WF, as well significantly increased respect to plasma; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several cytokines compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 monocytes was able to significantly down-regulate the release of peculiar inflammatory mediators. Our study highlighted the importance to understand biomolecular processes underlying CVI when providing treatment for chronic VLU. Identification of inflammatory biomarkers in leg ulcer microenvironment, may provide useful tools for predicting healing outcome and developing targeted therapies.

  4. [Surgical wound healing in oral surgery].

    Science.gov (United States)

    Bocca, M; Coscia, D; Bottalico, L; Libro, D

    1999-12-01

    Aim of this study is to improve the in vivo knowledge about the real effects and the physiologic repair by a detached stitches silk suture in the 8th zone. The study has been carried out on 44 patients submitted to surgical extraction of the impacted 8th (19 upper and 25 lower) teeth. Clinical and histological controls have demonstrated the usefulness of this suture procedure, since it gives a good histological reaction and in easy and safe. Histological and clinical results have confirmed the usefulness of silk suture, presenting however the inconvenience of stitches removal and bacterial plaque on the surgical wound.

  5. Measurements in wound healing with observations on the effects of topical agents on full thickness dermal incised wounds.

    Science.gov (United States)

    Theunissen, D; Seymour, B; Forder, M; Cox, S G; Rode, H

    2016-05-01

    A multitude of topical wound treatments are used today. Although it is well established that the micro-environment of healing wounds can be altered to improve healing, it is difficult to measure the subtle differences in outcome where therapies are compared. We compared wound healing properties between four different topical agents in surgically incised wounds in a pig model. The four topical agents, 5% Povidone-Iodine cream, 1% Silver-Sulphadiazine, 2% Mupirocin, and 1% Silver-Sulphadiazine plus 1mg/100g recombinant-human epithelial growth factor (EGF) were randomly assigned to four test animals each. Test agents were compared to each other and to untreated controls. We investigated existing and new methodologies of measurement of wound healing: clinical and histological visual scoring systems, immuno-histochemistry, and computerized image analysis of the wounds on days 3, 7, and 28. All agents were found to have improved healing rates with better cellular architecture. Healing was faster, histological appearance resembled normal architecture sooner, clinical appearance improved, mitotic activity was stimulated and more collagen was deposited in comparison to the wounds with no agents. EGF-treated wounds showed an increased rate of epithelisation, but the rate of healing did not correlate well with evaluation of cosmetic outcome. Topical agents improve all aspects of wound healing. The addition of a human recombinant EGF to Silver-Sulphadiazine increases epithelial growth and amounts of collagen in the regenerating wounds at day 7. Copyright © 2016. Published by Elsevier Ltd.

  6. Role of polymeric biomaterials as wound healing agents.

    Science.gov (United States)

    Agrawal, Priyanka; Soni, Sandeep; Mittal, Gaurav; Bhatnagar, Aseem

    2014-09-01

    In uncontrolled hemorrhage, the main cause of death on the battlefield and in accidents, half of the deaths are caused by severe blood loss. Polymeric biomaterials have great potential in the control of severe hemorrhage from trauma, which is the second leading cause of death in the civilian community following central nervous system injuries. The intent of this article is to provide a review on currently available biopolymers used as wound dressing agents and to describe their best use as it relates to the condition and type of the wound (acute, chronic, superficial, and full thickness) and the phases of the wound healing process. These biopolymers are beneficial in tissue engineering as scaffolds, hydrogels, and films. Different types of wound dressings based on biopolymers are available in the market, with various physical, chemical, and biological properties. The use of biopolymers as a hemostatic agent depends on its biocompatibility, biodegradability, nonimmunogenicity, and optimal mechanical property. This review summarizes different biopolymers, their physiological characters, and their use as wound healing agents along with biomedical applications.

  7. Contact dermatitis presenting as non-healing wound: case report

    Directory of Open Access Journals (Sweden)

    Leelavathi M

    2011-05-01

    Full Text Available Abstract Topical antiseptics are commonly used in the management of minor wounds, burns, and infected skin. These agents are widely used by health professionals and are often self-prescribed by patients as they are easily available over-the-counter. This case illustrates a 73 year old man who presented with a non-healing wound on his right forearm for 4 weeks. The wound started from an insect bite and progressively enlarged with increasing pruritus and burning sensation. Clinically an ill-defined ulcer with surrounding erythema and erosion was noted. There was a yellow crust overlying the center of the ulcer and the periphery was scaly. Further inquiry revealed history of self treatment with a yellow solution to clean his wound for 3 weeks. Patient was provisionally diagnosed to have allergic contact dermatitis secondary to acriflavine. Topical acriflavine was stopped and the ulcer resolved after treatment with non-occlusive saline dressing. Skin patch test which is the gold standard for detection and confirmation of contact dermatitis showed a positive reaction (2+ to acriflavine. Acriflavine is widely used as a topical antiseptic agent in this part of the world. Hence, primary care physicians managing a large variety of poorly healing wounds should consider the possibility of contact allergy in recalcitrant cases, not responding to conventional treatment. Patient education is an important aspect of management as this would help curb the incidence of future contact allergies.

  8. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    Directory of Open Access Journals (Sweden)

    S. Murthy

    2013-01-01

    Full Text Available Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME was studied on wound models in rats. BME (25 mg/kg was administered orally, once daily for 10 days (incision and dead space wound models or for 21 days or more (excision wound model in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model, rate of contraction, period of epithelization, histology of skin (excision model, granulation tissue free radicals (nitric oxide and lipid peroxidation, antioxidants (catalase, superoxide dismutase, and reduced glutathione, acute inflammatory marker (myeloperoxidase, connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid, and deep connective tissue histology (dead space wound. BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

  9. Wound healing ability of Xenopus laevis embryos. I. Rapid wound closure achieved by bisectional half embryos.

    Science.gov (United States)

    Yoshii, Yasuko; Noda, Masahiro; Matsuzaki, Takashi; Ihara, Setsunosuke

    2005-10-01

    We examined wound closure in 'half embryos' produced by the transverse bisection of Xenopus laevis embryos at the primary eye vesicle stage. Both the anterior- and posterior-half embryos survived for more than 6 days, and grew into 'half tadpoles'. Histology and videomicroscopy revealed that the open wound in the half embryo was rapidly closed by an epithelial sheet movement in the wound marginal zone. The time-course of wound closure showed a downward convex curve: the wound area decreased to one-fifth of the original area within 30 min, and the wound continued to contract slowly thereafter. The rapidity of closure of the epidermis as well as the absence of inflammatory cells are typical features of an embryonic type of wound healing. There was a dorso-ventral polarity in the motility of the epidermis: the wound was predominantly closed by the ventral and lateral epidermis. The change in the contour of the wound edge with time suggested a complex mechanism involved in the wound closure that could not be explained only by the purse-string theory. The present experimental system would be a unique and useful model for analyses of cellular movements in the embryonic epithelia.

  10. Why chronic wounds will not heal: a novel hypothesis

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Kirketerp-Moller, K.; Jensen, P.O.

    2008-01-01

    The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens......, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies-the basal structures of bacterial biofilms. Several researchers have...

  11. Burn Wound Healing and Treatment: Review and Advancements

    Science.gov (United States)

    2015-06-12

    outside the scope of this review, but several key points are noteworthy. Most burns among older people occur at home , especially in the kitchen and...plasma and Rowan et al. Critical Care (2015) 19:243 Page 11 of 12 wound exudate from children with severe burns . Bull Exp Biol Med. 2009;148:771–5. 163...REVIEW Open Access Burn wound healing and treatment: review and advancements Matthew P. Rowan1*, Leopoldo C. Cancio1, Eric A. Elster2, David M

  12. Does FXIII deficiency impair wound healing after myocardial infarction?

    Directory of Open Access Journals (Sweden)

    Matthias Nahrendorf

    Full Text Available Inadequate healing of myocardial infarction may contribute to local expansion of the infarct, frequently leading to chamber dilation, heart failure, or myocardial rupture. Experimental evidence in mouse models suggests that Factor XIII might play a key role in wound healing, and low persistent values lead to increased incidence of cardiac rupture following myocardial infarction. Here we would like to share our initial clinical experiences with strikingly similar observations in patients with this grave disease, and compare these observations to experimental findings.

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

    OpenAIRE

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

    2016-01-01

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

  14. Influence of phytochemicals in piper betle linn leaf extract on wound healing

    OpenAIRE

    Lien, Le Thi; Tho, Nguyen Thi; Ha, Do Minh; Hang, Pham Luong; Nghia, Phan Tuan; Thang, Nguyen Dinh

    2015-01-01

    Background Wound healing has being extensively investigated over the world. Healing impairment is caused by many reasons including increasing of free-radicals-mediated damage, delaying in granulation tissue formation, reducing in angiogenesis and decreasing in collagen reorganization. These facts consequently lead to chronic wound healing. Piper betle Linn (Betle) leaves have been folklore used as an ingredient of drugs for cutaneous wound treatment. However, the effect of betle leaf on wound...

  15. Cold atmospheric plasma (CAP changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Stephanie Arndt

    Full Text Available Cold atmospheric plasma (CAP has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.

  16. Cold atmospheric plasma (CAP) changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo.

    Science.gov (United States)

    Arndt, Stephanie; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Heinlin, Julia; Li, Yang-Fang; Thomas, Hubertus M; Morfill, Gregor E; Zimmermann, Julia L; Bosserhoff, Anja-Katrin; Karrer, Sigrid

    2013-01-01

    Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.

  17. Antioxidant therapies for wound healing: a clinical guide to currently commercially available products.

    Science.gov (United States)

    Fitzmaurice, S D; Sivamani, R K; Isseroff, R R

    2011-01-01

    Many facets of wound healing under redox control require a delicate balance between oxidative stress and antioxidants. While the normal physiology of wound healing depends on low levels of reactive oxygen species and oxidative stress, an overexposure to oxidative stress leads to impaired wound healing. Antioxidants are postulated to help control wound oxidative stress and thereby accelerate wound healing. Many antioxidants are available over the counter or by prescription, but only one, Medihoney®, has been specifically FDA approved for wound healing. Here we review the existing evidence for the use of antioxidants for wound healing, with a review of the pertinent animal and clinical studies. Natural products and naturally derived antioxidants are becoming more popular, and we specifically review the evidence for the use of naturally derived antioxidants in wound healing. Antioxidant therapy for wound healing is promising, but only few animal studies and even fewer clinical studies are available. Because only few products have undergone FDA approval, the consumer is advised to scrutinize them for purity and contaminants prior to use, and this may require direct contact with the companies that sell them. As a field of science, the use of antioxidants for wound healing is in its infancy, and future studies will better elucidate the role of antioxidants in wound healing.

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

    Science.gov (United States)

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

    2002-03-01

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

  19. Wound healing efficacy of a 660-nm diode laser in a rat incisional wound model.

    Science.gov (United States)

    Suzuki, Ryoichi; Takakuda, Kazuo

    2016-11-01

    This study aimed to elucidate the optimum usage parameters of low reactive-level laser therapy (LLLT) in a rat incisional wound model. In Sprague-Dawley rats, surgical wounds of 15-mm length were made in the dorsal thoracic region. They were divided into groups to receive 660-nm diode laser irradiation 24 h after surgery at an energy density of 0 (control), 1, 5, or 10 J/cm(2). Tissue sections collected on postoperative day 3 were stained with hematoxylin-eosin and an antibody for ED1 to determine the number of macrophages around the wound. Samples collected on day 7 were stained with hematoxylin-eosin and observed via polarized light microscopy to measure the area occupied by collagen fibers around the wound; day 7 skin specimens were also subjected to mechanical testing to evaluate tensile strength. On postoperative day 3, the numbers of macrophages around the wound were significantly lower in the groups receiving 1 and 5 J/cm(2) irradiation, compared to the control and 10 J/cm(2) irradiation groups (p healing tissues from 1 and 5 J/cm(2) irradiation groups, compared to the control group (p wound healing in a rat incisional wound model. However, a higher radiation energy density yielded no significant enhancement.

  20. Wound healing potential of Pañcavalkala formulations in a postfistulectomy wound.

    Science.gov (United States)

    Meena, Rakesh Kumar; Dudhamal, Tukaram; Gupta, Sanjay Kumar; Mahanta, Vyasadeva

    2015-01-01

    Sushruta mentioned sixty measures for management of wounds. Panchavalkal is the combination of five herbs having properties like Shodhana (cleaning) and Ropana (healing) of wounds. Individual drugs and in combination have Kashaya rasa (astringent) dominant and useful in the management of Vrana (wounds) as well as Shotha (inflammations). A 35 years old male patient consulted in Shalya OPD with complaints like discharge per anum, induration and intermittent pain at perianal region since last five years. On inspection external opening was observed at anterior portion 1 O' clock position which was four centimeter away from anal verge. That case was diagnosed as Bhagandara (fistula-in-ano) and was treated with partial fistulectomy and application of Guggulu based Ksharasutra in the remaining tract. The big fistulectomy wound was treated with local application of Panchavalkal ointment daily and simultaneous change of Ksharasutra. The wound was assessed daily for pain, swelling, discharge, size, and shape. The wound healed completely within two and half month with normal scar having good tissue strength. This case demonstrated that post fistulectomy wound can be treated with Panchavalkal ointment.

  1. [The role of erythropoietin in improvement of wound healing].

    Science.gov (United States)

    Sorg, H; Kuhbier, J W; Menger, B; Reimers, K; Harder, Y; Vogt, P M

    2010-11-01

    Pleiotropic substances are characterized by their versatile and complex range of actions which makes them potential new active agents for the therapy of wounds. Besides its known effect to increase red blood cell production, the glycoprotein hormone erythropoietin (EPO) has been found to demonstrate a tissue protective effect in several other organs. The administration of EPO during skin wound healing is most likely essentially based on its cytopotective, proangiogenic, antiapoptotic and antiinflammatory effects. Herein EPO stimulates a coordinated interaction of different types of cells at a low or only a single dose. This review article aims to present the advantages and disadvantages of EPO administration in different experimental models to study the healing and regeneration processes of the skin and discusses possible clinical applications.

  2. Recent advances on the association of apoptosis in chronic non healing diabetic wound.

    Science.gov (United States)

    Arya, Awadhesh K; Tripathi, Richik; Kumar, Santosh; Tripathi, Kamlakar

    2014-12-15

    Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophages and myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.

  3. Recent advances on the association of apoptosis in chronic non healing diabetic wound

    Institute of Scientific and Technical Information of China (English)

    Awadhesh; K; Arya; Richik; Tripathi; Santosh; Kumar; Kamlakar; Tripathi

    2014-01-01

    Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophagesand myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.

  4. Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery.

    Science.gov (United States)

    Wang, Yiwei; Simanainen, Ulla; Cheer, Kenny; Suarez, Francia G; Gao, Yan Ru; Li, Zhe; Handelsman, David; Maitz, Peter

    2016-05-01

    The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)-mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re-epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild-type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF-PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds. © 2016 by the Wound Healing Society.

  5. Inhibition of indoleamine 2,3-dioxygenase activity accelerates skin wound healing.

    Science.gov (United States)

    Ito, Hiroyasu; Ando, Tatsuya; Ogiso, Hideyuki; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

    2015-06-01

    Skin wound healing is a complex process involving several stages that include inflammation, proliferation, and remodeling. In the inflammatory phase, pro-inflammatory cytokines and chemokines are induced at the wound site and, they contribute to the development of wound healing. These cytokines also induce indoleamine 2,3-dioxygenase (IDO1) activity; this is the rate-limiting and first enzyme in the l-tryptophan (TRP)-l-kynurenine (KYN) pathway. This study examined the effect of IDO1 on the process of skin wound healing. The expression of the Ido1 mRNA was enhanced after creating a wound in wild-type (WT) mice. TRP concentration was simultaneously reduced at the wound site. The rate of wound healing in IDO1 knockout (IDO-KO) mice was significantly higher than that in WT mice. 1-Methyl-dl-tryptophan (1-MT), a potent inhibitor of IDO1, increased the rate of wound healing in WT mice. The administration of TRP accelerated wound healing in vivo and in an in vitro experimental model, whereas the rate of wound healing was not affected by the administration of KYN. The present study identifies the role of IDO1 in skin wound healing, and indicates that the local administration of 1-MT or TRP may provide an effective strategy for accelerating wound healing.

  6. Evaluation of Wound Healing Activity of Ethanolic Extract of Pongamia pinnata Bark.

    Science.gov (United States)

    Bhandirge, S K; Tripathi, A S; Bhandirge, R K; Chinchmalatpure, T P; Desai, H G; Chandewar, A V

    2015-06-01

    Present study evaluate wound healing activity of ethanolic extract of stem bark of Pongamia pinnata (PP). Evaluation of wound healing activity, 2 wound models were used I. e., incision and excision wounds were perform in this study on Albino wistar rats (150-200 g). The rats were been treated with 10% and 5% ointment base formulation at dose 15 µl/wound topically. The parameters studied were breaking strength in case of incision wounds, epithelization period and wound area in case of excision wound. The ethanolic extract treated group showed a significant (P healing parameters of incision and excision wound models as compared to control. This study justify the traditional use of ethanolic extract of Pongamia pinnata stem bark shows wound healing property.

  7. Photobiomodulation of wound healing via visible and infrared laser irradiation.

    Science.gov (United States)

    Solmaz, Hakan; Ulgen, Yekta; Gulsoy, Murat

    2017-03-20

    Fibroblast cells are known to be one of the key elements in wound healing process, which has been under the scope of research for decades. However, the exact mechanism of photobiomodulation on wound healing is not fully understood yet. Photobiomodulation of 635 and 809 nm laser irradiation at two different energy densities were investigated with two independent experiments; first, in vitro cell proliferation and then in vivo wound healing. L929 mouse fibroblast cell suspensions were exposed with 635 and 809 nm laser irradiations of 1 and 3 J/cm(2) energy densities at 50 mW output power separately for the investigation of photobiomodulation in vitro. Viabilities of cells were examined by means of MTT assays performed at the 24th, 48th, and 72nd hours following the laser irradiations. Following the in vitro experiments, 1 cm long cutaneous incisional skin wounds on Wistar albino rats (n = 24) were exposed with the same laser sources and doses in vivo. Wound samples were examined on 3rd, 5th, and 7th days of healing by means of mechanical tensile strength tests and histological examinations. MTT assay results showed that 635 nm laser irradiation of both energy densities after 24 h were found to be proliferative. One joule per square centimeter laser irradiation results also had positive effect on cell proliferation after 72 h. However, 809 nm laser irradiation at both energy densities had neither positive nor negative affects on cell viability. In vivo experiment results showed that, 635 nm laser irradiation of both energy densities stimulated wound healing in terms of tensile strength, whereas 809 nm laser stimulation did not cause any stimulative effect. The results of mechanical tests were compatible with the histological evaluations. In this study, it is observed that 635 nm laser irradiations of low energy densities had stimulative effects in terms of cell proliferation in vitro and mechanical strength of incisions in vivo. However, 809 nm laser

  8. Efficacy of propranolol in wound healing for hospitalized burn patients.

    Science.gov (United States)

    Mohammadi, Ali Akbar; Bakhshaeekia, Alireza; Alibeigi, Peyman; Hasheminasab, Mohammad Jalal; Tolide-ei, Hamid Reza; Tavakkolian, Ahmad Reza; Mohammadi, Mohammad Kazem

    2009-01-01

    Burn patients have the highest metabolic rate among critically ill or injured patients. Because propranolol decreases energy expenditure and muscle protein catabolism, in this study, we hypothesized that propranolol would improve healing process and decrease wound-healing time. This study was a double-blind randomized clinical trial; a total of 79 burn patients who referred to this center from January 2006 to January 2007 fulfilled the inclusion criteria. Thirty-seven patients were randomly placed in propranolol group and 42 in control group. The propranolol group received propranolol orally with the dose of 1 mg/kg/d and maximum dose of 1.98 mg/kg/d given in six divided doses. This dose was adjusted to decrease the resting heart rate by 20% from each patient's baseline value. The control group received placebo. The most common cause of burn in both groups was flame followed by flash. Patients with superficial burns in the propranolol group needed less time to heal for acceptable wound healing in superficial burns (16.13+/-7.40 days vs 21.52+/-7.94 days; P=.004). We also found that patients with deep burn injury needed less time to be ready for skin graft (28.23+/-8.43 days vs 33.46+/-9.17 days; P=.007) when compared to that of the control group. The use of propranolol decreased the size of the burn wound that finally needed skin graft. Patients in the propranolol group with an average burn size of 31.42% TBSA finally needed 13.75% of TBSA skin graft compared with that of control patients with an average burn size of 33.61% TBSA who needed 18.72% of TBSA skin graft, and patients in the control group with an average burn size of 33.61% TBSA finally needed 18.72% of TBSA skin graft (P=.006). Patients in the propranolol group had a shorter hospital stay period than the control group (30.95+/-8.44 days vs 24.41+/-8.11 days; P=.05). Administration of propranolol, improved burn wound healing, and decreased healing time and hospital stay period. The use of propranolol

  9. Organization of wound healing services: the Danish experience and the importance of surgery.

    Science.gov (United States)

    Gottrup, Finn

    2003-01-01

    Thomas K. Hunt is a general surgeon. Through his basic wound healing research and clinical work with wound patients he has been a great inspiration for my work in wound healing. In order to fulfill Dr. Hunt's vision, the clinical wound healing arena must be organized in an optimal way, and this article focuses on different options. Multidisciplinary wound care teams or centers focusing on all types of problem wounds have proved to be most effective at providing treatment and care for patients with problem wounds. The ultimate model is an outpatient clinic and an inpatient ward joined within a departmental structure, which represents an integrated part of an accepted national expert program on wound healing. Different types of center models can be established with different advantages and disadvantages. Currently, the wound care arena is being organized in Denmark and the model is described in this article. Of all specialties involved in treatment of wounds, surgery is of vital importance. "Wound healing is the keystone on which surgery is founded" (Thomas K. Hunt). This has long been understood in relation to acute wounds, while the importance of surgery in the treatment of chronic wounds has been less widely recognized. Surgical procedures directly related to the wound consist of debridement of all types of problem wounds and, in more specialized procedures such as skin transplantation, different types of flap constructions, bone surgery, and tendo-Achilles lengthening. Arterial reconstruction is a type of surgery that indirectly, through improved tissue perfusion, improves healing of problem wounds. This study concludes that multidisciplinary specialized wound healing concepts integrated into the national health care system as accepted expert functions would be the ideal way to organize wound healing to best benefit patients and society. Emphasis is on the importance of surgical procedures in wound healing and care. The models described can be applied with minor

  10. CoQ10-containing eye drops prevent UVB-induced cornea cell damage and increase cornea wound healing by preserving mitochondrial function.

    Science.gov (United States)

    Mencucci, Rita; Favuzza, Eleonora; Boccalini, Carlotta; Lapucci, Andrea; Felici, Roberta; Resta, Francesco; Chiarugi, Alberto; Cavone, Leonardo

    2014-10-09

    We evaluated the potential protective effects of Coenzyme Q10 (CoQ10) on human corneal cells and rabbit eyes after ultraviolet B (UVB) exposure and a model of wound healing in rabbit eyes after corneal epithelium removal. Human corneal epithelium cells (HCE) were exposed to a source of UVB radiation (312 nM) in the presence of different CoQ10 concentrations or vehicle. The mitochondrial function and cell survival were evaluated by means of 3-(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium (MTT) reduction and lactic dehydrogenase (LDH) release. Furthermore, quantitation of oxygen consumption and mitochondrial membrane potential were conducted. In vivo rabbit models were adopted to evaluate the effect of CoQ10 on UVB-induced conjunctival vessel hyperemia and corneal recovery after ethanol induced corneal lesion. In UVB-exposed HCE cells, CoQ10 addition led to an increased survival rate and mitochondrial function. Furthermore, oxygen consumption was maintained at control levels and adenosine triphosphate (ATP) decline was completely prevented in the CoQ10-treated cells. Interestingly, in an in vivo model, CoQ10 was able dose-dependently to reduce UVB-induced vessel hyperemia. Finally, in a model of corneal epithelium removal, 12 hours from surgery, animals treated with CoQ10 showed a reduction of damaged area in respect to vehicle controls, which lasted until 48 hours. We demonstrated that CoQ10 reduces corneal damages after UVB exposure in vivo and in vitro by preserving mitochondrial function. Also, for the first time to our knowledge we showed that the administration of CoQ10 after corneal epithelium removal promotes corneal wound healing. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Chronic venous disease - Part II: Proteolytic biomarkers in wound healing.

    Science.gov (United States)

    Ligi, Daniela; Mosti, Giovanni; Croce, Lidia; Raffetto, Joseph D; Mannello, Ferdinando

    2016-10-01

    Venous leg ulcers (VLU) are characterized by sustained proteolytic microenvironment impairing the healing process. Wound fluid (WF) reflect the biomolecular activities occurring within the wound area; however, it is unclear if WF from different healing phases have different proteolytic profiles and how VLU microenvironment affects the wound healing mechanisms. We investigated the proteolytic network of WF from distinct VLU phases, and in WF- and LPS-stimulated THP-1 monocytes treated with glycosaminoglycan sulodexide, a well known therapeutic approach for VLU healing. WF were collected from patients with VLU during inflammatory (Infl) and granulating (Gran) phases. WF and THP-1 supernatants were analyzed for nine matrix metalloproteinases (MMP) and four tissue inhibitors of metalloproteinases (TIMP) by multiplex immunoassays. Our results demonstrated that: 1) WF from Infl VLU contained significantly increased concentrations of MMP-2, MMP-9, MMP-12, TIMP-1, and TIMP-2 compared to Gran WF; 2) WF from Gran VLU showed significantly increased levels of MMP-1, MMP-7, MMP-13, and TIMP-4 compared to Infl WF; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several MMP compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 significantly down-regulated the release of several MMPs. Our study provides evidence-based medicine during treatment of patients with VLU. WF from Infl and Gran VLU have different MMP and TIMP signatures, consistent with their clinical state. The modulation of proteolytic pathways in wound microenvironment by glycosaminoglycan sulodexide, provide insights for translating research into clinical practice during VLU therapy.

  13. Genomic Loci Modulating the Retinal Transcriptome in Wound Healing

    OpenAIRE

    Vázquez-Chona, Félix R; Lu Lu; Robert W Williams; Geisert, Eldon E.

    2007-01-01

    Purpose: The present study predicts and tests genetic networks that modulate gene expression during the retinal wound-healing response.Methods: Upstream modulators and target genes were defined using meta-analysis and bioinfor matic approaches. Quantitative trait loci (QTLs) for retinal acute phase genes (Vazquez-Chona et al. 2005) were defi ned using QTL analysis of CNS gene expression (Chesler et al. 2005). Candidate modulators were defi ned using computational analysis of gene and motif se...

  14. Amplification of effects of photons on wound healing

    Science.gov (United States)

    Dyson, Mary

    2009-02-01

    Following the absorption of photons by cells either resident in or in transit through the skin at and around a wound site, healing can be modulated. This is due to the primary, secondary and tertiary cellular effects of the photons. The main primary effect of phototherapy is photon absorption. This initiates secondary effects within the cells that have absorbed the photons. Secondary effects are restricted to cells that have absorbed a suprathreshold quantity of photonic energy. Photon absorption can lead to an increase in ATP synthesis and the release of reactive oxygen species that can activate specific transcription factors resulting in changes in synthesis of the enzymes needed for cellular proliferation, migration, phagocytosis and protein synthesis, all essential for wound healing. The amount of ATP production is limited in each cell by the availability of ADP and phosphate. Spatial and temporal amplification of the effects of photon absorption increases the range and duration of phototherapy. It may be caused in part by tertiary effects initiated in cells that have not absorbed photons by regulatory proteins such as cytokines secreted by cells that have absorbed photons. Amplification may also be due to changes induced by photons in immune cells, stem cells and soluble protein mediators while in transit through the dermal capillaries. The peripheral location of these capillaries makes their contents readily accessible to photons. The longer the duration of treatment, the greater will be the number of cells in transit that can be affected by photons. Depth of effect may be increased by transduction of electromagnetic energy into mechanical energy. For a treatment to be clinically effective on wound healing, its duration and power may each be important. Components of the immune system, endocrine system and nervous system may also amplify the effects of photons on wound healing.

  15. Scarless wound healing: finding the right cells and signals.

    Science.gov (United States)

    Leavitt, Tripp; Hu, Michael S; Marshall, Clement D; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

    2016-09-01

    From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal

  16. Raman spectroscopy enables noninvasive biochemical characterization and identification of the stage of healing of a wound.

    Science.gov (United States)

    Jain, Rishabh; Calderon, Diego; Kierski, Patricia R; Schurr, Michael J; Czuprynski, Charles J; Murphy, Christopher J; McAnulty, Jonathan F; Abbott, Nicholas L

    2014-04-15

    Accurate and rapid assessment of the healing status of a wound in a simple and noninvasive manner would enable clinicians to diagnose wounds in real time and promptly adjust treatments to hasten the resolution of nonhealing wounds. Histologic and biochemical characterization of biopsied wound tissue, which is currently the only reliable method for wound assessment, is invasive, complex to interpret, and slow. Here we demonstrate the use of Raman microspectroscopy coupled with multivariate spectral analysis as a simple, noninvasive method to biochemically characterize healing wounds in mice and to accurately identify different phases of healing of wounds at different time-points. Raman spectra were collected from "splinted" full thickness dermal wounds in mice at 4 time-points (0, 1, 5, and 7 days) corresponding to different phases of wound healing, as verified by histopathology. Spectra were deconvolved using multivariate factor analysis (MFA) into 3 "factor score spectra" (that act as spectral signatures for different stages of healing) that were successfully correlated with spectra of prominent pure wound bed constituents (i.e., collagen, lipids, fibrin, fibronectin, etc.) using non-negative least squares (NNLS) fitting. We show that the factor loadings (weights) of spectra that belonged to wounds at different time-points provide a quantitative measure of wound healing progress in terms of key parameters such as inflammation and granulation. Wounds at similar stages of healing were characterized by clusters of loading values and slowly healing wounds among them were successfully identified as "outliers". Overall, our results demonstrate that Raman spectroscopy can be used as a noninvasive technique to provide insight into the status of normally healing and slow-to-heal wou