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Sample records for cutaneous wound healing

  1. Chemokines in cutaneous wound healing.

    PubMed

    Gillitzer, R; Goebeler, M

    2001-04-01

    Healing of wounds is one of the most complex biological events after birth as a result of the interplay of different tissue structures and a large number of resident and infiltrating cell types. The latter are mainly constituted by leukocyte subsets (neutrophils, macrophages, mast cells, and lymphocytes), which sequentially infiltrate the wound site and serve as immunological effector cells but also as sources of inflammatory and growth-promoting cytokines. Recent data demonstrate that recruitment of leukocyte subtypes is tightly regulated by chemokines. Moreover, the presence of chemokine receptors on resident cells (e.g., keratinocytes, endothelial cells) indicates that chemokines also contribute to the regulation of epithelialization, tissue remodeling, and angiogenesis. Thus, chemokines are in an exclusive position to integrate inflammatory events and reparative processes and are important modulators of human-skin wound healing. This review will focus preferentially on the role of chemokines during skin wound healing and intends to provide an update on the multiple functions of individual chemokines during the phases of wound repair.

  2. Stem Cells for Cutaneous Wound Healing

    PubMed Central

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

    2015-01-01

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

  3. Acceleration of cutaneous wound healing by brassinosteroids

    PubMed Central

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

    2013-01-01

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

  4. Effect of astaxanthin on cutaneous wound healing.

    PubMed

    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.

  5. Effect of astaxanthin on cutaneous wound healing

    PubMed Central

    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. PMID:28761364

  6. Acceleration of cutaneous wound healing by brassinosteroids.

    PubMed

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

    2013-01-01

    Brassinosteroids are plant growth hormones involved in cell growth, division, and differentiation. Their effects in animals are largely unknown, although recent studies showed that the anabolic properties of brassinosteroids are possibly mediated through the phosphoinositide 3-kinase/protein kinase B signaling pathway. Here, we examined biological activity of homobrassinolide (HB) and its synthetic analogues in in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full-thickness dermal wound, and the rate of wound closure was assessed daily for 10 days, with adenosine receptor agonist CGS-21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of transforming growth factor beta and intercellular adhesion molecule 1 were significantly lower, while tumor necrosis factor alpha was nearly suppressed in the wounds from treated mice. Our data suggest that topical application of brassinosteroids accelerates wound healing by positively modulating inflammatory and reepithelialization phases of the wound repair process, in part by enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in the wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing. © 2013 by the Wound Healing Society.

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

    PubMed

    Ashrafi, Mohammed; Baguneid, Mohamed; Bayat, Ardeshir

    2016-06-15

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

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

    PubMed

    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.

  9. Wound Healing of Cutaneous Sulfur Mustard Injuries

    PubMed Central

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

    2005-01-01

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

  10. Exploring the role of stem cells in cutaneous wound healing.

    PubMed

    Lau, Katherine; Paus, Ralf; Tiede, Stephan; Day, Philip; Bayat, Ardeshir

    2009-11-01

    The skin offers a perfect model system for studying the wound healing cascade, which involves a finely tuned interplay between several cell types, pathways and processes. The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars such as hypertrophic and keloid scars. As the contribution of stem cells towards tissue regeneration and wound healing is increasingly appreciated, a rising number of stem cell therapies for cutaneous wounds are currently under development, encouraged by emerging preliminary findings in both animal models and human studies. However, we still lack an in-depth understanding of the underlying mechanisms through which stem cells contribute to cutaneous wound healing. The aim of this review is, therefore, to present a critical synthesis of our current understanding of the role of stem cells in normal cutaneous wound healing. In addition to summarizing wound healing principles and related key molecular and cellular players, we discuss the potential participation of different cutaneous stem cell populations in wound healing, and list corresponding stem cells markers. In summary, this review delineates current strategies, future applications, and limitations of stem cell-based or stem cell-targeted therapy in the management of acute and chronic skin wounds.

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

    PubMed Central

    Klein, Kenneth C; Guha, Somes Chandra

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed Central

    Chadwick, Sarah; Heath, Rebecca; Shah, Mamta

    2012-01-01

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

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

    SciTech Connect

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

    2011-07-08

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

  16. Dietary L-arginine and cutaneous wound healing.

    PubMed

    Naderpour, Masoud; Rad, Jafar Soleimani; Ayat, Esmail; Mesgari, Mehran; Farahani, Ramin M; Roshangar, Leila; Tubbs, R Shane; Shoja, Mohammadali M

    2008-01-01

    Skin wound healing has been the subject of extensive studies and various drugs have been used in an attempt to improve wound healing. There are conflicting data regarding the effects of L-arginine, the substrate of nitric oxide, on wound healing. We examined the 1-week rate of cutaneous wound healing and collagen deposition in three groups of rats who received a (1) L-arginine (2% in drinking water)-supplemented diet from three days before until the seventh day following injury (Group 1), (2) L-arginine-supplemented diet for three days before injury (Group 2), and (3) a standard diet without L-arginine supplementation (Group 3). The wound length and width were measured each day and then the open wound area and cumulative percentage of open wound area reduction were calculated. Wound biopsy samples were examined with Trichrome-Masson stain in a subgroup of animals. Results showed that Group 1 rats had a significantly lower cumulative percentage of open wound area reduction on day 7 compared to other two groups (Mann-Whitney U test, P < 0.05). Relatively higher degrees of wound collagen deposit (day 7) were noted in groups 2 and 3. It may be concluded that L-arginine (2% in water) administered three days before until the seventh day following skin wound induction may diminish the rate of skin wound healing and collagen deposition.

  17. Antibodies to wounded tissue enhance cutaneous wound healing.

    PubMed

    Nishio, Naomi; Ito, Sachiko; Suzuki, Haruhiko; Isobe, Ken-ichi

    2009-11-01

    The wound repair process is a highly ordered sequence of events that encompasses haemostasis, inflammatory cell infiltration, tissue regrowth and remodelling. Wound healing follows tissue destruction so we hypothesized that antibodies might bind to wounded tissues, which would facilitate the engulfment of damaged tissues by macrophages. Here, we show that B cells, which produce antibodies to damaged tissues, are engaged in the process of wound healing. Splenectomy delayed wound healing, and transfer of spleen cells into splenectomized mice recovered the delay in wound healing. Furthermore, wound healing in splenectomized nude mice was also delayed. Transfer of enriched B220(+) cells by magnetic beads accelerated wound healing in splenectomized mice. We detected immunoglobulin G1 (IgG1) binding to wounded tissues by using fluorescein isothiocyanate-labelled anti-IgG1 6-24 hr after wounding. Splenectomy reduced the amount of IgG1 binding to wounded tissues. Immunoblotting studies revealed several bands, which were reduced by splenectomy. Using immunoprecipitation with anti-IgG bound to protein G we found that the intensity of several bands was lower in the serum from splenectomized mice than in that from sham-operated mice. These bands were matched to myosin IIA, carbamoyl-phosphate synthase, argininosuccinate synthase, actin and alpha-actinin-4 by liquid chromatography tandem mass spectrometry analysis.

  18. Embelin accelerates cutaneous wound healing in diabetic rats.

    PubMed

    Deshmukh, Pradeep T; Gupta, Vipin B

    2013-01-01

    This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat.

  19. Sympathetic denervation impairs epidermal healing in cutaneous wounds.

    PubMed

    Kim, L R; Whelpdale, K; Zurowski, M; Pomeranz, B

    1998-01-01

    The involvement of peripheral nerves in dermal wound healing, particularly in the inflammatory response has not been extensively studied. Therefore, this study was performed to examine the role of peripheral nerves in the healing of rat skin linear incisions. We report that chemical sympathectomy with 6-hydroxydopamine significantly impaired wound healing as measured on days 7, 11, and 14 postsurgery (by day 14, 48% of the sympathectomized rats were healed in contrast with 84% of the controls; p = 0.0104). In contrast, neonatal capsaicin treatment, which predominantly destroys sensory afferents, had no effect on wound healing (p > 0.05 on all days). These results support the hypothesis that sympathetic efferents are important for wound healing. Unlike previous research, which showed that peripheral nerves influence ischemic skin flaps, we are the first to demonstrate a role for peripheral nerves in the healing of skin incisions. Because inflammation is an important step in cutaneous wound healing, we propose that a reduction of neurogenic inflammation caused by sympathectomy may explain the impaired wound healing that we observed in our study.

  20. Combined gene and stem cell therapy for cutaneous wound healing.

    PubMed

    Gauglitz, Gerd G; Jeschke, Marc G

    2011-10-03

    In current medical practice, wound therapy remains a clinical challenge and much effort has been focused on the development of novel therapeutic approaches for wound treatment. Gene therapy, initially developed for treatment of congenital defects, represents a promising option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have shown the most potential. The majority of gene delivery systems are based on viral transfection, naked DNA application, high pressure injection, and liposomal vectors. Besides advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, there has been a significant increase in the understanding of stem cell biology in the field of cutaneous wound healing. A variety of sources, such as bone marrow, umbilical cord blood, adipose tissue and skin/hair follicles, have been utilized to isolate stem cells and to modulate the healing response of acute and chronic wounds. Recent data have demonstrated the feasibility of autologous adult stem cell therapy in cutaneous repair and regeneration. Very recently, stem cell based skin engineering in conjunction with gene recombination, in which the stem cells act as both the seed cells and the vehicle for gene delivery to the wound site, represents the most attractive field for generating a regenerative strategy for wound therapy. The aim of this article is to discuss the use and the potential of these novel technologies in order to improve wound healing capacities.

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

    PubMed Central

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

    2016-01-01

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

  2. MicroRNA in cutaneous wound healing: a new paradigm.

    PubMed

    Shilo, Shani; Roy, Sashwati; Khanna, Savita; Sen, Chandan K

    2007-04-01

    Repair of a defect in the human skin is a highly orchestrated physiological process involving numerous factors that act in a temporally resolved synergistic manner to re-establish barrier function by regenerating new skin. The inducible expression and repression of genes represents a key component of this regenerative process. MicroRNAs (miRNAs) are approximately 22-nucleotide-long endogenously expressed non-coding RNAs that regulate the expression of gene products by inhibition of translation and/or transcription in animals. miRNAs play a key role in skin morphogenesis and in regulating angiogenesis. The vascular endothelial growth factor signaling path seems to be under repressor control by miRNAs. Mature miRNA-dependent mechanisms impair angiogenesis in vivo. It is critically important to recognize that the understanding of cutaneous wound healing is incomplete without appreciating the functional significance of wound-induced miRNA. Ongoing work in our laboratory has led to the observation that the cutaneous wound healing process involves changes in the expression of specific miRNA at specific phases of wound healing. We hypothesize that dysregulation of specific miRNA is critical in derailing the healing sequence in chronic problem wounds. If tested positive, this hypothesis is likely to lead to completely novel diagnostic and therapeutic strategies for the treatment of problem wounds.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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.

  5. MFG-E8 Regulates Angiogenesis in Cutaneous Wound Healing

    PubMed Central

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

    2015-01-01

    Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF–PDGFRβ signaling mediated by integrin–growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31+ blood vessels, and MFG-E8 colocalized with PDGFRβ+, αSMA+, and NG2+ pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. PMID:24838098

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

    PubMed

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

    2014-07-01

    Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF-PDGFRβ signaling mediated by integrin-growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31(+) blood vessels, and MFG-E8 colocalized with PDGFRβ(+), αSMA(+), and NG2(+) pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-11-01

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

  8. Variation of intensity on the healing of cutaneous wounds

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed Central

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

    2015-01-01

    Treatment of wounds is very important and was subject of different investigations. In this regard, natural substance plays crucial role as complementary medicine. Various studies reported that aloe vera has useful effects on wounds especially cutaneous wounds healing. Therefore in the current review, we examined the effect of aloe vera on cutaneous wound healing and concluded that although aloe vera improves the wound healing as well as other procedures both clinically and experimentally, more studies are still needed to approve the outcomes. PMID:26090436

  11. Human skin transcriptome during superficial cutaneous wound healing.

    PubMed

    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. Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil

    PubMed Central

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

    2012-01-01

    Leishmania braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. In the mouse, Fli1 was identified as a gene influencing enhanced wound healing and resistance to CL caused by L. major. Polymorphism at FLI1 is associated with CL caused by L. braziliensis in humans, with an inverse association observed for ML disease. Here we extend the analysis to look at other wound healing genes, including CTGF, TGFB1, TGFBR1/2, SMADS 2/3/4/7 and FLII, all functionally linked along with FLI1 in the TGF beta pathway. Haplotype tagging single nucleotide polymorphisms (tag-SNPs) were genotyped using Taqman technology in 325 nuclear families (652 CL cases; 126 ML cases) from Brazil. Robust case-pseudocontrol (CPC) conditional logistic regression analysis showed associations between CL and SNPs at CTGF (SNP rs6918698; CC genotype; OR 1.67; 95%CI 1.10–2.54; P=0.016), TGFBR2 (rs1962859; OR 1.50; 95%CI 1.12–1.99; P=0.005), SMAD2 (rs1792658; OR 1.57; 95%CI 1.04–2.38; P=0.03), SMAD7 (rs4464148; AA genotype; OR 2.80; 95%CI 1.00–7.87; P=0.05) and FLII (rs2071242; OR 1.60; 95%CI 1.14–2.24; P=0.005), and between ML and SNPs at SMAD3 (rs1465841; OR 2.15; 95%CI 1.13–4.07; P=0.018) and SMAD7 (rs2337107; TT genotype; OR 3.70; 95%CI 1.27–10.7; P=0.016). Stepwise logistic regression analysis showed that all SNPs associated with CL at FLI1, CTGF, TGFBR2, and FLII showed independent effects from each other, but SNPs at SMAD2 and SMAD7 did not add independent effects to SNPs from other genes. These results suggest that TGFβ signalling via SMAD2 is important in directing events that contribute to CL, whereas signalling via SMAD3 is important in ML. Both are modulated by the inhibitory SMAD7 that acts upstream of SMAD2 and SMAD3 in this signalling pathway. Along with the published FLI1 association, these data further contribute to the hypothesis that wound healing processes are important determinants of pathology associated with cutaneous forms of leishmaniasis. PMID:22554650

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

    PubMed

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

    2016-05-02

    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.

  14. Healing of chronic cutaneous wounds by topical treatment with basic fibroblast growth factor.

    PubMed

    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.

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

    PubMed

    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. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Cutaneous wound healing in Ehlers-Danlos syndrome.

    PubMed

    Freeman, L J; Hegreberg, G A; Robinette, J D

    1989-01-01

    Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  19. Gonadal hormones differently modulate cutaneous wound healing of chronically stressed mice.

    PubMed

    Romana-Souza, Bruna; Assis de Brito, Thatiana L; Pereira, Gabriela R; Monte-Alto-Costa, Andréa

    2014-02-01

    Gonadal hormones influence physiological responses to stress and cutaneous wound healing. The aim of this study was to investigate the role of gonadal hormones on cutaneous wound healing in chronically stressed mice. Male and female mice were gonadectomized, and after 25 days, they were spun daily at 115 rpm for 15 min every hour until euthanasia. Twenty-eight days after the gonadectomy, an excisional lesion was created. The animals were killed 7 or 14 days after wounding, and the lesions were collected. Myofibroblast density, macrophage number, catecholamine level, collagen deposition, and blood vessel number were evaluated. In the intact and gonadectomized groups, stress increased the plasma catecholamine levels in both genders. In intact groups, stress impaired wound contraction and re-epithelialization and increased the macrophage number in males but not in females. In addition, stress compromised myofibroblastic differentiation and blood vessel formation and decreased collagen deposition in males but not in females. In contrast to intact mice, wound healing in ovariectomized female mice was affected by stress, while wound healing in castrated male mice was not. In conclusion, gender differences contribute to the cutaneous wound healing of chronically stressed mice. In addition, androgens contribute to the stress-induced impairment of the healing of cutaneous wounds but estrogens inhibit it. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-12-01

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

  1. AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

    PubMed Central

    Guo, Yuanyuan; Lin, Cai; Xu, Peng; Wu, Shan; Fu, Xiujun; Xia, Weidong; Yao, Min

    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, inhibition of autophagy by 3-MA restores delayed healing in C57BL/6 or db/db mice, demonstrating that autophagy is involved in regulating wound healing. Furthermore, we identify that macrophage is a major cell type underwent autophagy in wounds and increased autophagy induces macrophages polarization into M1 with elevated CD11c population and gene expressions of proinflammatory cytokines. To explore the mechanism underlying autophagy-impaired wound healing, we tested the role of IRF8, a regulator of autophagy, in autophagy-modulated macrophages polarization. IRF8 activation is up-regulating autophagy and M1 polarization of macrophages after AGEs (advanced glycation endproducts) treatment, blocking the IRF8 with shIRF8 inhibits autophagic activity and M1 polarization. In summary, this study elucidates that AGEs induces autophagy and modulates macrophage polarization to M1 via IRF8 activation in impairment of cutaneous wound healing. PMID:27805071

  2. Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing.

    PubMed

    Guo, Yuanyuan; Yang, Zhiyin; Wu, Shan; Xu, Peng; Peng, Yinbo; Yao, Min

    2017-02-01

    The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage-related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.

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

    PubMed Central

    Ud-Din, Sara; Bayat, Ardeshir

    2014-01-01

    Electrical stimulation (ES) has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC), alternating current (AC), high-voltage pulsed current (HVPC), low-intensity direct current (LIDC) and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE) for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used. PMID:27429287

  4. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    PubMed

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

    2016-10-14

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

  5. Ala42S100A8 Ameliorates Psychological-Stress Impaired Cutaneous Wound Healing

    PubMed Central

    Sroussi, Herve Y.; Williams, Richard L.; Zhang, Qing. L.; Villines, Dana.; Marucha, Phillip. T.

    2009-01-01

    Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation sensitive repellent of human neutrophils in-vitro. Ala42S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild type and ala42S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala42S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing. PMID:19336252

  6. Bulbine natalensis and Bulbine frutescens promote cutaneous wound healing.

    PubMed

    Pather, Nalini; Kramer, Beverley

    2012-12-18

    The gel from the leaves of Bulbine natalensis (BN) and Bulbine frutescens (BF) is commonly used as a traditional medicine in South Africa for the treatment of skin wounds and burns. Treatment with both leaf gel extracts has previously been demonstrated to increase tensile strength and protein and DNA content in pig dermal wounds. This study examined the effect of the leaf gel extracts in vivo on histology of wound healing in pigs to elucidate the mechanism of increased tensile strength. Mirror imaged wounds on the dorsum of 12 post weaning female pigs were treated with either BN or BF, biopsied at days 2, 4, 7, 10 and 16 post-wounding and fixed. Sections of wound tissue were then stained with haematoxylin and eosin and Mallory's stain to analyse the general morphology and collagen arrangement; and smooth muscle actin, vascular endothelial growth factor (VEGF) and transforming growth factor β (TGFβ) receptors were immunolocalised. Histological analysis of the wound tissue in the study indicated earlier wound contraction and collagen deposition in both treatment groups with re-organisation of the collagen (indicating collagen maturation) evident as early as at day 10. The results of this study suggests that the leaf extracts increase tensile strength by increasing fibroplasia, differentiation of fibroblasts into myofibroblasts, and increased collagen deposition and maturation. This study further validates the use of the Bulbine leaf gels for the treatment of skin wounds. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2014-01-01

    In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS) generated in the skin by ultraviolet (UVA) 320–400 nm portion of the UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation. PMID:25071575

  8. Photobiomodulation improves cutaneous wound healing in an animal model of type II diabetes.

    PubMed

    Byrnes, Kimberly R; Barna, Lauren; Chenault, V Michelle; Waynant, Ronald W; Ilev, Ilko K; Longo, Leonardo; Miracco, Clelia; Johnson, Bryan; Anders, Juanita J

    2004-08-01

    We investigated the effects of photobiomodulation (PBM) on cutaneous wound healing in an animal model of type II diabetes, Psammomys obesus (Sand Rats). 632-nm light has been established as the most effective wavelength for treatment of cutaneous wounds; however, the inconsistent efficacy of PBM may be due to inadequate treatment parameter selection. Using 632-nm light, an initial series of experiments were done to establish optimal treatment parameters for this model. Following creation of bilateral full-thickness skin wounds, non-diabetic Sand Rats were treated with PBM of differing dosages. Wound healing was assessed according to wound closure and histological characteristics of healing. Optimal treatment parameters were then used to treat type II diabetic Sand Rats while a diabetic control group received no irradiation. In order to elucidate the mechanism behind an improvement in wound healing, expression of basic fibroblast growth factor (bFGF) was assessed. Significant improvement in wound healing histology and wound closure were found following treatment with 4 J/cm(2) (16 mW, 250-sec treatments for 4 consecutive days; p < 0.05). The 4 J/cm(2) dosage significantly improved histology and closure of wounds in the diabetic group in comparison to the non-irradiated diabetic group. Quantitative analysis of bFGF expression at 36 h post-injury revealed a threefold increase in the diabetic and non-diabetic Sand Rats after PBM. The results demonstrate that PBM at an energy density of 4 J/cm(2) is effective in improving the healing of cutaneous wounds in an animal model of type II diabetes, suggesting that PBM (632 nm, 4 J/cm(2)) would be effective in treating chronic cutaneous wounds in diabetic patients.

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

    PubMed Central

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

    2013-01-01

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

  10. Impaired aquaporin 3 expression in reepithelialization of cutaneous wound healing in the diabetic rat.

    PubMed

    Sugimoto, Takashi; Huang, Lijuan; Minematsu, Takeo; Yamamoto, Yuko; Asada, Mayumi; Nakagami, Gojiro; Akase, Tomoko; Nagase, Takashi; Oe, Makoto; Mori, Taketoshi; Sanada, Hiromi

    2013-07-01

    Impaired cutaneous wound healing is a serious complication of diabetes mellitus (DM). Currently, little is known about reepithelialization in DM. However, recent studies identified aquaporin 3 (AQP3), a transmembrane protein that functions as a pore-like passive transporter, to be a key molecule in cutaneous epidermal wound healing. AQP3 expression is downregulated in response to tumor necrosis factor-alpha (TNF- α). Given that systemic TNF-α levels are functionally connected to impaired healing in diabetic mice and that both diabetic and Aqp3-deficient animals exhibit impaired reepithelialization, the authors hypothesized that impaired AQP3 expression might contribute to diabetes-impaired wound healing. In the present study, the authors examined AQP3 expression in the regenerating epidermis during cutaneous full thickness wound healing and in intact skin of a streptozotocin-induced diabetic rat model. Aqp3 messenger RNA expression levels were decreased in wounds of DM rats compared to controls. Immunohistochemical analysis showed an absence of AQP3 in the stratum spinosum of the regenerating epidermis in the DM group, whereas the stratum basale was positive for AQP3 in both groups. In summary, these findings suggest that there may be a relationship between impaired AQP3 expression and diabetes-delayed reepithelialization. Thus, future nursing studies should focus on this mechanism in diabetic wound healing.

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

    PubMed

    Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang; Choi, Kang-Yell

    2015-06-29

    Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5(-/-) mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)-Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. © 2015 Lee et al.

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

    PubMed Central

    Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang

    2015-01-01

    Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing. PMID:26056233

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

    PubMed

    Jetten, Nadine; Roumans, Nadia; Gijbels, Marion J; Romano, Andrea; Post, Mark J; de Winther, Menno P J; van der Hulst, Rene R W J; Xanthoulea, Sofia

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.

  14. Instructional PowerPoint presentations for cutaneous wound healing and tissue response to sutures.

    PubMed

    Stroncek, John D; Bell, Nicole; Reichert, W Monty

    2009-09-15

    Wound healing is an intricate process involving the interaction of cells and molecules, resulting in a complex series of events that change the morphology and characteristics of the wounded area. Interactive animations are useful for illustrating challenging concepts, helping students learn and retain new material. Instructional PowerPoint presentations describing the basic elements of cutaneous wound healing and the response of cutaneous tissue to sutures were developed by seven biomedical engineering students at Duke University. "Cutaneous Wound Healing.ppt" is an interactive presentation reviewing the four phases of wound healing (hemostasis, inflammation, repair, and remodeling) as well as the major molecular and cellular mechanisms that comprise these processes for cutaneous tissue. "Tissue Response to Sutures.ppt" is an interactive presentation that uses sutures to illustrate the foreign body response to biomaterials in cutaneous tissue. The tissue response program reviews the basics of suturing, common suture materials, and the tissue, cellular, and molecular responses to absorbable and nonabsorbable sutures. This manuscript provides a brief overview of the programs that are freely available on the Duke Center for Biomolecular and Tissue Engineering web site at http://bte.egr.duke.edu. Copyright 2008 Wiley Periodicals, Inc.

  15. Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

    PubMed Central

    Lee, Soung-Hoon; Zahoor, Muhammad; Hwang, Jae-Kwan; Min, Do Sik; Choi, Kang-Yell

    2012-01-01

    Background Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. Methods and Findings We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA), collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathways. Conclusions VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes. PMID:23144972

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

    PubMed

    Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C; Kim, Brian S; Wang, Kelvin; Bayat, Ardeshir; Artis, David; Volk, Susan W

    2016-02-01

    Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after exposure to allergens, pathogens, or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. In addition, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity after injury.

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

    PubMed Central

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

    2015-01-01

    Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung and gut and promote pro-inflammatory or epithelial repair functions following exposure to allergens, pathogens or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. Additionally, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity following injury. PMID:26802241

  18. Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies

    PubMed Central

    Pence, Brandt D.; Woods, Jeffrey A.

    2014-01-01

    Significance: Impaired cutaneous wound healing is a major health concern. Obesity has been shown in a number of studies to impair wound healing, and chronic nonhealing wounds in obesity and diabetes are a major cause of limb amputations in the United States. Recent Advances: Recent evidence indicates that aberrant wound site inflammation may be an underlying cause for delayed healing. Obesity, diabetes, and other conditions such as stress and aging can result in a chronic low-level inflammatory state, thereby potentially affecting wound healing negatively. Critical Issues: Interventions which can speed the healing rate in individuals with slowly healing or nonhealing wounds are of critical importance. Recently, physical exercise training has been shown to speed healing in both aged and obese mice and in older adults. Exercise is a relatively low-cost intervention strategy which may be able to be used clinically to prevent or treat impairments in the wound-healing process. Future Directions: Little is known about the mechanisms by which exercise speeds healing. Future translational studies should address potential mechanisms for these exercise effects. Additionally, clinical studies in obese humans are necessary to determine if findings in obese rodent models translate to the human population. PMID:24761347

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

    PubMed

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

    2013-09-01

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

  20. Role of Nerve Growth Factor in Cutaneous Wound Healing: Accelerating Effects in Normal and Healing-impaired Diabetic Mice

    PubMed Central

    Matsuda, Hiroshi; Koyama, Hiromi; Sato, Hiroaki; Sawada, Junko; Itakura, Atsuko; Tanaka, Akane; Matsumoto, Masahiro; Konno, Katsuhiko; Ushio, Hiroko; Matsuda, Kuniko

    1998-01-01

    Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal mice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing. PMID:9449710

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

    PubMed

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

    2009-06-02

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

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

    NASA Astrophysics Data System (ADS)

    Lange-Asschenfeldt, Susanne; Bob, Adrienne; Terhorst, Dorothea; Ulrich, Martina; Fluhr, Joachim; Mendez, Gil; Roewert-Huber, Hans-Joachim; Stockfleth, Eggert; Lange-Asschenfeldt, Bernhard

    2012-07-01

    There is a high demand for noninvasive imaging techniques for wound assessment. In vivo reflectance confocal laser scanning microscopy (CLSM) represents an innovative optical technique for noninvasive evaluation of normal and diseased skin in vivo at near cellular resolution. This study was designed to test the feasibility of CLSM for noninvasive analysis of cutaneous wound healing in 15 patients (7 male/8 female), including acute and chronic, superficial and deep dermal skin wounds. A commercially available CLSM system was used for the assessment of wound bed and wound margins in order to obtain descriptive cellular and morphological parameters of cutaneous wound repair noninvasively and over time. CLSM was able to visualize features of cutaneous wound repair in epidermal and superficial dermal wounds, including aspects of inflammation, neovascularisation, and tissue remodelling in vivo. Limitations include the lack of mechanic fixation of the optical system on moist surfaces restricting the analysis of chronic skin wounds to the wound margins, as well as a limited optical resolution in areas of significant slough formation. By describing CLSM features of cutaneous inflammation, vascularisation, and epithelialisation, the findings of this study support the role of CLSM in modern wound research and management.

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

    PubMed

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

    2010-09-01

    The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflammation accelerates wound closure with subsequent increased fibroblast function and collagen synthesis. On the contrary, prolonged chronic inflammation results in very limited wound healing. Using histological and immunohistochemical techniques, we investigated the effects of a new wound dressing called Vulnamin that contains four essential amino acids for collagen and elastin synthesis plus sodium ialuronate (Na-Ial), compared with Na-Ial alone, in closure of experimental cutaneous wounds of aged rats. Our results showed that the application of Vulnamin dressings modulated the inflammatory response with a reduction in the number of inflammatory cells and inducible nitric oxide synthase (iNOS) immunolocalisation, while increasing endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta1 (TGF-beta1) immunolocalisation. Furthermore, the dressing increased the distribution density of fibroblasts and aided the synthesis of thin collagen fibers resulting in a reduction in healing time. The nutritive approach using this new wound dressing can provide an efficacious and safe strategy to accelerate wound healing in elderly subjects, simplifying therapeutic procedures and leading to an improved quality of life. 2009 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    2017-03-06

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

  5. Induction of Specific MicroRNAs Inhibits Cutaneous Wound Healing*

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Buff-Lindner, Amanda Haley

    Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increases in wound closure, antibacterial activities and innate immune responses. Treatment with nanofibers results in increased defensin, small antimicrobial peptides, expression both in vitro and in vivo. Induction of defensin expression results in bacterial clearance in a cutaneous wound model. Our data show that Akt1 plays a central role in the regulation of these activities. Interestingly, pGlcNAc treatment of cutaneous wounds in mice results in decreased scar sizes. Additionally, treatment of cutaneous wounds with pGlcNAc results in increased elasticity and a rescue of tensile strength. Masson Trichrome staining suggests that pGlcNAc treated wounds exhibit decreased collagen content as well as increased collagen alignment with collagen fibers oriented similarly to unwounded tissue. Utilizing a fibrin gel assay to analyze the effect of pGlcNAc nanofiber treatment on fibroblast alignment in vitro, pGlcNAc stimulation of embedded fibroblasts results in fibroblasts alignment as compared to untreated controls, by a process that is Akt1 dependent. Our data show that in Akt1 null animals pGlcNAc treatment does not increase tensile strength or elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in wound closure, the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

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

    PubMed

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

    2016-05-01

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

  9. Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice.

    PubMed

    Chen, Bin; Kao, Huang-Kai; Dong, Ziqing; Jiang, Zhaohua; Guo, Lifei

    2017-01-01

    Negative-pressure wound therapy and pulsed radiofrequency energy are two clinical modalities used to treat soft-tissue wounds. They are purported to affect healing differently. The aim of this experimental study was to contrast the two modalities at a mechanistic level and to investigate whether their combined therapy could achieve additive and complementary effects on wound healing. Full-thickness dorsal cutaneous wounds of diabetic, db/db, mice were treated with either negative-pressure wound therapy, pulsed radiofrequency energy, or combined therapies. Macroscopic healing kinetics were examined. Epidermal regeneration (proliferation rate and length of reepithelialization) and neovascularization (blood vessel density) were investigated. Messenger RNA levels indicative of angiogenic (basic fibroblast growth factor), profibrotic (transforming growth factor-β), epidermal proliferative (keratinocyte growth factor), and extracellular matrix remodeling (collagen 1) processes were measured in wound tissues. All three treatment groups displayed faster wound healing. The negative-pressure wound therapy/pulsed radiofrequency energy combined therapy led to significantly faster healing than either the negative-pressure wound therapy or pulsed radiofrequency energy therapy alone. Epidermal regeneration and neovascularization were enhanced in all three groups. The two negative-pressure wound therapy groups (alone and combined with pulsed radiofrequency energy) demonstrated more significant increases in expression of all assayed growth factors than the pulsed radiofrequency energy group. Furthermore, the combined therapy exhibited a more profound elevation in collagen 1 expression than either of the two therapies alone. Combining the negative-pressure wound therapy and pulsed radiofrequency energy modalities can achieve additive benefits in cutaneous healing, and the two therapies can be easily used together to complement each other in clinical wound treatments.

  10. Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing.

    PubMed

    Than, Uyen Thi Trang; Guanzon, Dominic; Leavesley, David; Parker, Tony

    2017-05-01

    Extracellular vesicles (EVs) are membrane-enclosed vesicles that are released into the extracellular environment by various cell types, which can be classified as apoptotic bodies, microvesicles and exosomes. EVs have been shown to carry DNA, small RNAs, proteins and membrane lipids which are derived from the parental cells. Recently, several studies have demonstrated that EVs can regulate many biological processes, such as cancer progression, the immune response, cell proliferation, cell migration and blood vessel tube formation. This regulation is achieved through the release and transport of EVs and the transfer of their parental cell-derived molecular cargo to recipient cells. This thereby influences various physiological and sometimes pathological functions within the target cells. While intensive investigation of EVs has focused on pathological processes, the involvement of EVs in normal wound healing is less clear; however, recent preliminarily investigations have produced some initial insights. This review will provide an overview of EVs and discuss the current literature regarding the role of EVs in wound healing, especially, their influence on coagulation, cell proliferation, migration, angiogenesis, collagen production and extracellular matrix remodelling.

  11. Modulation of cutaneous wound healing by ozone: differences between young and aged mice.

    PubMed

    Lim, Yunsook; Phung, Anh D; Corbacho, Ana M; Aung, Hnin Hnin; Maioli, Emanuela; Reznick, Abraham Z; Cross, Carroll E; Davis, Paul A; Valacchi, Giuseppe

    2006-01-05

    Cutaneous tissues are frequently exposed to prooxidative environments, including UV radiation and air pollutants. Among the latter, ozone (O(3)) is of particular concern because of its high and dominating presence in photochemical smog. It is well known that O(3) depletes small molecular weight antioxidants, oxidizes proteins, induces lipid peroxidation and activates cellular responses in various tissues. Using an in vivo model (SKH-1 hairless mice), the interaction between O(3) exposure (0.5ppmx6h/day) and age was examined in relation to cutaneous wound healing. Compared to younger (8 weeks) mice, older (18 months) mice exposed to O(3) (day 0 to day 9 after wounding) exhibited delayed wound closure, increased lipid peroxidation (measured as 4-HNE protein adducts) and protein oxidation (measured as carbonyls concentration) and decreased levels of P-IkappaBalpha and TGFbeta protein. These findings support the hypothesis that oxidant pollutant exposure and age interact so as to disrupt normal wound healing processes.

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

    PubMed

    Sabino, Fabio; Hermes, Olivia; Egli, Fabian E; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N; Smola, Hans; auf dem Keller, Ulrich

    2015-02-01

    Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease

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

    PubMed Central

    Sabino, Fabio; Hermes, Olivia; Egli, Fabian E.; Kockmann, Tobias; Schlage, Pascal; Croizat, Pierre; Kizhakkedathu, Jayachandran N.; Smola, Hans; auf dem Keller, Ulrich

    2015-01-01

    Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ∼450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease

  14. 17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

    PubMed

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

    2016-10-01

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

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

    PubMed Central

    2011-01-01

    Background Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. Methods The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. Results After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ. Conclusion The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts. PMID:21982053

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

    PubMed Central

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

    1999-01-01

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

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

    PubMed

    Li, Kun; Diao, Yunpeng; Zhang, Houli; Wang, Shouyu; Zhang, Zhen; Yu, Bo; Huang, Shanshan; Yang, Hong

    2011-10-07

    Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ. The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.

  18. Effect of aqueous extract of Elaeagnus angustifolia fruit on experimental cutaneous wound healing in rats.

    PubMed

    Mehrabani Natanzi, Mahboobeh; Pasalar, Parvin; Kamalinejad, Mohammad; Dehpour, Ahmad Reza; Tavangar, Seyed Mohammad; Sharifi, Roya; Ghanadian, Naghmeh; Rahimi-Balaei, Maryam; Gerayesh-Nejad, Siavash

    2012-01-01

    The present study was conducted to investigate the histological changes and wound healing effect of aqueous extract of Elaeagnus angustifolia. After creating full-thickness skin wounds on the back of 45 male Sprague-Dawley rats they were randomly divided into three groups. Treated group received the extract, positive control group were treated with mupirocin ointment 2% and control group did not receive any treatment. Wound healing rates were calculated on days 3, 5, 8, 10, 12 and 15 post-wounding and the wound tissues were harvested at 5, 10, and 15 days for histological analysis and hydroxyproline content measurement. The results indicated a significant increase in the percentage of wound contraction and hydroxyproline content in the treated group comparing to the control and positive control groups. A significant increase in the assigned histological scores was observed at 10 and 15 days in the treated and positive control groups compared to the control group. The results demonstrate that aqueous extract of Elaeagnus angustifolia accelerates cutaneous wound healing, and its effect may be due to the increased re-epithelialization and collagen deposition in wound and so it can be considered as a therapeutic agent for wound healing.

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

    PubMed

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

    2015-12-28

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2010-03-01

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

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

    PubMed

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

    2011-02-01

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

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

    PubMed

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

    2015-11-10

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

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

    PubMed

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

    2016-03-01

    This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs.

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

    PubMed Central

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

    2016-01-01

    This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs. PMID:27051343

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

    PubMed Central

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

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Santos, Nicole R. S.; Cangussú, Maria C. T.; N. dos Santos, Jean; Pinheiro, Antonio L. B.

    2011-03-01

    We aimed assess the effects of different energy densities of the association of red/IR laser light on the healing of cutaneous wounds infected Staphylococcus aureus. Background: Wound infection is the most common complication on healing wounds and cause both vascular and cellular responses on the tissue. Several therapeutics is used for improving wound healing including the use of different light sources, such as the Laser. Some energy densities present positive photobiological effects on the healing process. Material and Methods: 24 young adult male Wistar rats, under general anesthesia, had their dorsum shaven, cleaned and a 1 x 1cm cutaneous wound created with a scalpel and left without no suturing or dressings. The wounds were infected with Staphylococcus aureus and were randomly divided in 8 subgroups of 3 animals in each: Control, Group 10J/cm2, Group 20J/cm2, and Group 30J/cm2, 7 and 14 days each group. Laser phototherapy was carried out with a diode (λ680nm/790nm, P= 30mW/40mW, CW, Laser, Ø = 3mm, PD=424mW/cm2 and 566mW/cm2, t=11.8/ 8.8 sec, E=0.35J) and started immediately after surgery and repeated at every other day during 7 days. Laser light was applied on 4 points around wounded area. The animals were killed at either 8th or 15th day after contamination. Specimens were taken, routinely cut and processed to wax, stained and underwent histological analysis. The results were statistically analyzed. Results: Both 20 and 30J/cm2 caused intense collagen deposition at the end of the experimental time. But, when 20 J/cm2 was used the fibers were also well organized. Conclusion: Our results indicate that irradiated subjects showed improved wound healing being the 20 J/cm2 the energy the caused better histological response.

  8. Wound Healing Effect of Slightly Acidic Electrolyzed Water on Cutaneous Wounds in Hairless Mice via Immune-Redox Modulation.

    PubMed

    You, Hae Sun; Fadriquela, Ailyn; Sajo, Ma Easter Joy; Bajgai, Johny; Ara, Jesmin; Kim, Cheol Su; Kim, Soo-Ki; Oh, Jin Rok; Shim, Kwang Yong; Lim, Hyun Kyo; Lee, Kyu-Jae

    2017-01-01

    Acidic electrolyzed water is an innovative sanitizer having a wide-spectrum of applications in food industry, and healthcare industry but little is known on its effect and mechanism in wound healing. The study was conducted to identify the effect and mechanism of slightly acidic electrolyzed water (SAEW) on cutaneous wounds in hairless mice. SAEW (pH: 5-6.5, oxidation reduction potential: 800 mV, chlorine concentration: 25 ppm) was prepared through electrolysis of water and was applied to the wounds of hairless mice three times a day for seven days. Wound size, immune response and oxidative stress were explored and compared to conventional agents such as Betadine and alcohol. We found that SAEW-treated group showed the highest wound reduction percentage (p<0.01). Antioxidant activities such as glutathione peroxidase, catalase and myeloperoxidase activities of SAEW group surpassed the total reactive oxygen species in skin. Nuclear factor erythroid-2-related-factor-2 and aryl hydrocarbon receptor were upregulated in SAEW group. Further, SAEW recruited the production of intracellular calcium and promoted its utilization for faster healing. In line, SAEW treatment decreased pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, keratinocyte chemoattractant, and tumor necrosis factor-α] in serum. Other hallmarks of wound healing, matrixmetalloproteinases (MMP)1 and MMP9 were also upregulated. Collectively, our study indicates that SAEW is effective in wound healing of hairless mice via immune-redox modulation, and heals better/faster than conventional agents.

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

    PubMed

    de Almeida, Taís Fontoura; de Castro Pires, Taiza; Monte-Alto-Costa, Andréa

    2016-02-01

    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic-pituitary-adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway. © 2016 by the Society for Experimental Biology and Medicine.

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

    PubMed Central

    de Almeida, Taís Fontoura; de Castro Pires, Taiza

    2016-01-01

    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic–pituitary–adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway. PMID:26515142

  11. Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing.

    PubMed

    Zhao, Xin; Wu, Hao; Guo, Baolin; Dong, Ruonan; Qiu, Yusheng; Ma, Peter X

    2017-04-01

    Injectable self-healing hydrogel dressing with multifunctional properties including anti-infection, anti-oxidative and conductivity promoting wound healing process will be highly desired in wound healing application and its design is still a challenge. We developed a series of injectable conductive self-healed hydrogels based on quaternized chitosan-g-polyaniline (QCSP) and benzaldehyde group functionalized poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS-FA) as antibacterial, anti-oxidant and electroactive dressing for cutaneous wound healing. These hydrogels presented good self-healing, electroactivity, free radical scavenging capacity, antibacterial activity, adhesiveness, conductivity, swelling ratio, and biocompatibility. Interestingly, the hydrogel with an optimal crosslinker concentration of 1.5 wt% PEGS-FA showed excellent in vivo blood clotting capacity, and it significantly enhanced in vivo wound healing process in a full-thickness skin defect model than quaternized chitosan/PEGS-FA hydrogel and commercial dressing (Tegaderm™ film) by upregulating the gene expression of growth factors including VEGF, EGF and TGF-β and then promoting granulation tissue thickness and collagen deposition. Taken together, the antibacterial electroactive injectable hydrogel dressing prolonged the lifespan of dressing relying on self-healing ability and significantly promoted the in vivo wound healing process attributed to its multifunctional properties, meaning that they are excellent candidates for full-thickness skin wound healing.

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

    PubMed

    Godwin, Andrew; Sharma, Archna; Yang, Weng-Lang; Wang, Zhimin; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2015-01-01

    Wound healing consists of a complex, dynamic and overlapping process involving inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular level is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3) controls programmed necrosis in response to TNF-α during inflammation and has been shown to be highly induced during cutaneous wound repair. However, its role in wound healing remains to be demonstrated. To study this, we created dorsal cutaneous wounds on male wild-type (WT) and RIPK3-deficient (Ripk3-/-) mice. Wound area was measured daily until day 14 post-wound and skin tissues were collected from wound sites at various days for analysis. The wound healing rate in Ripk3-/- mice was slower than the WT mice over the 14-day course; especially, at day 7, the wound size in Ripk3-/- mice was 53% larger than that of WT mice. H&E and Masson-Trichrome staining analysis showed impaired quality of wound closure in Ripk3-/- wounds with delayed re-epithelialization and angiogenesis and defected granulation tissue formation and collagen deposition compared to WT. The neutrophil infiltration pattern was altered in Ripk3-/- wounds with less neutrophils at day 1 and more neutrophils at day 3. This altered pattern was also reflected in the differential expression of IL-6, KC, IL-1β and TNF-α between WT and Ripk3-/- wounds. MMP-9 protein expression was decreased with increased Timp-1 mRNA in the Ripk3-/- wounds compared to WT. The microvascular density along with the intensity and timing of induction of proangiogenic growth factors VEGF and TGF-β1 were also decreased or delayed in the Ripk3-/- wounds. Furthermore, mouse embryonic fibroblasts (MEFs) from Ripk3-/- mice migrated less towards chemoattractants TGF-β1 and PDGF than MEFs from WT mice. These results clearly demonstrate that RIPK3 is an essential molecule to maintain the temporal manner of the normal progression

  13. Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing.

    PubMed

    Kuck, Monika; Strese, Helene; Alawi, Seyed Arash; Meinke, Martina C; Fluhr, Joachim W; Burbach, Guido J; Krah, Martin; Sterry, Wolfram; Lademann, Jürgen

    2014-02-01

    The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2009-06-01

    This study was undertaken to evaluate the therapeutic effects of topical ozonated olive oil on acute cutaneous wound healing in a guinea pig model and also to elucidate its therapeutic mechanism. After creating full-thickness skin wounds on the backs of guinea pigs by using a 6 mm punch biopsy, we examined the wound healing effect of topically applied ozonated olive oil (ozone group), as compared to the pure olive oil (oil group) and non-treatment (control group). The ozone group of guinea pig had a significantly smaller wound size and a residual wound area than the oil group, on days 5 (P<0.05) and 7 (P<0.01 and P<0.05) after wound surgery, respectively. Both hematoxylin-eosin staining and Masson-trichrome staining revealed an increased intensity of collagen fibers and a greater number of fibroblasts in the ozone group than that in the oil group on day 7. Immunohistochemical staining demonstrated upregulation of platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7, as compared with the oil group. In conclusion, these results demonstrate that topical application of ozonated olive oil can accelerate acute cutaneous wound repair in a guinea pig in association with the increased expression of PDGF, TGF-beta, and VEGF.

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

    PubMed Central

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

    2009-01-01

    This study was undertaken to evaluate the therapeutic effects of topical ozonated olive oil on acute cutaneous wound healing in a guinea pig model and also to elucidate its therapeutic mechanism. After creating full-thickness skin wounds on the backs of guinea pigs by using a 6 mm punch biopsy, we examined the wound healing effect of topically applied ozonated olive oil (ozone group), as compared to the pure olive oil (oil group) and non-treatment (control group). The ozone group of guinea pig had a significantly smaller wound size and a residual wound area than the oil group, on days 5 (P<0.05) and 7 (P<0.01 and P<0.05) after wound surgery, respectively. Both hematoxylin-eosin staining and Masson-trichrome staining revealed an increased intensity of collagen fibers and a greater number of fibroblasts in the ozone group than that in the oil group on day 7. Immunohistochemical staining demonstrated upregulation of platelet derived growth factor (PDGF), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7, as compared with the oil group. In conclusion, these results demonstrate that topical application of ozonated olive oil can accelerate acute cutaneous wound repair in a guinea pig in association with the increased expression of PDGF, TGF-β, and VEGF. PMID:19543419

  16. The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.

    PubMed

    Nishikori, Yoriko; Shiota, Naotaka; Okunishi, Hideki

    2014-11-01

    Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.

  17. Oxidant and antioxidant events during epidermal growth factor therapy to cutaneous wound healing in rats.

    PubMed

    Kalay, Zeynep; Cevher, Sule Coskun

    2012-08-01

    Cutaneous wound healing is a highly complex process, which includes inflammation, cell proliferation, matrix deposition and remodelling phases. Various growth factors, like epidermal growth factor (EGF), play an important role during wound healing. However, little is known about relationship between EGF and oxidant-antioxidant events in cutaneous wound healing models. Thus we planned to evaluate the connection between EGF therapy and oxidative stress in dermal tissue followed by wounding. Fifty-four adult male Wistar-albino rats were randomly divided into three groups: control, untreated and topical EGF administrated group. A linear full-thickness excision of 40 mm in length on both sides of spinal cord was made on the back of each rat and sutured under anaesthesia and sterile conditions. Excision was closed with 4/0 atraumatic silk suture. EGF solution was freshly prepared at 10 ng/ml dose in thilotears gel under aseptic conditions. Following the surgery, 1 ml of EGF solution was administered to wound strips one time in everyday. The animals were euthanised and wound tissues were collected on days 1, 5, 7 and 14. Thiobarbituric acid reactive substans (TBARS), glutathione (GSH), reactive nitrogen oxide species (NOx), ascorbic acid levels and superoxide dismutase activity were measured spectrophotometrically. TBARS levels decreased and NOx levels increased on day 5 after operation, and GSH levels were increased on day 14 in EGF administered group compared with untreated group. Our data showed that EGF may act like an antioxidant by scavenging toxic oxidation products in wound tissue. In addition, it may contribute healing of the wound tissue in earlier stages and suggest a potential effective role for antioxidant therapies, especially until day 5. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  18. Wound healing.

    PubMed

    Harvey, Carol

    2005-01-01

    Wound healing in orthopaedic care is affected by the causes of the wound, as well as concomitant therapies used to repair musculoskeletal structures. Promoting the health of the host and creating an environment to foster natural healing processes is essential for helping to restore skin integrity. Normal wound healing physiologic processes, factors affecting wound healing, wound classification systems, unique characteristics of orthopaedic wounds, wound contamination and drainage characteristics, and potential complications are important to understand in anticipation of patient needs. Accurate wound assessment and knowledge of nursing implications with specific wound care measures (cleansing, debridement, and dressings) is important for quality care. New technologies are enhancing traditional wound care measures with goals of effective comfortable wound care to promote restoration of skin integrity.

  19. Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing.

    PubMed

    Gupta, Asheesh; Raghubir, Ram

    2005-02-01

    The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects.

  20. Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing.

    PubMed

    Huang, Xin; Zhang, Yaqing; Zhang, Xiangmei; Xu, Ling; Chen, Xin; Wei, Shicheng

    2013-12-01

    A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague-Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing.

  1. Stellera chamaejasme and its constituents induce cutaneous wound healing and anti-inflammatory activities

    PubMed Central

    Kim, Myungsuk; Lee, Hee Ju; Randy, Ahmad; Yun, Ji Ho; Oh, Sang-Rok; Nho, Chu Won

    2017-01-01

    Stellera chamaejasme L. (Thymelaeaceae) is a perennial herb that is widely used in traditional Chinese medicine to treat tumours, tuberculosis and psoriasis. S. chamaejasme extract (SCE) possesses anti-inflammatory, analgesic and wound healing activities; however, the effect of S. chamaejasme and its active compounds on cutaneous wound healing has not been investigated. We assessed full-thickness wounds of Sprague-Dawley (SD) rats and topically applied SCE for 2 weeks. In vitro studies were performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW 264.7 macrophages to determine cell viability (MTT assay), cell migration, collagen expression, nitric oxide (NO) production, prostaglandin E2 (PGE2) production, inflammatory cytokine expression and β-catenin activation. In vivo, wound size was reduced and epithelisation was improved in SCE-treated SD rats. In vitro, SCE and its active compounds induced keratinocyte migration by regulating the β-catenin, extracellular signal-regulated kinase and Akt signalling pathways. Furthermore, SCE and its active compounds increased mRNA expression of type I and III collagen in Hs68 fibroblasts. SCE and chamechromone inhibited NO and PGE2 release and mRNA expression of inflammatory mediators in RAW 264.7 macrophages. SCE enhances the motility of HaCaT keratinocytes and improves cutaneous wound healing in SD rats. PMID:28220834

  2. Stellera chamaejasme and its constituents induce cutaneous wound healing and anti-inflammatory activities.

    PubMed

    Kim, Myungsuk; Lee, Hee Ju; Randy, Ahmad; Yun, Ji Ho; Oh, Sang-Rok; Nho, Chu Won

    2017-02-21

    Stellera chamaejasme L. (Thymelaeaceae) is a perennial herb that is widely used in traditional Chinese medicine to treat tumours, tuberculosis and psoriasis. S. chamaejasme extract (SCE) possesses anti-inflammatory, analgesic and wound healing activities; however, the effect of S. chamaejasme and its active compounds on cutaneous wound healing has not been investigated. We assessed full-thickness wounds of Sprague-Dawley (SD) rats and topically applied SCE for 2 weeks. In vitro studies were performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW 264.7 macrophages to determine cell viability (MTT assay), cell migration, collagen expression, nitric oxide (NO) production, prostaglandin E2 (PGE2) production, inflammatory cytokine expression and β-catenin activation. In vivo, wound size was reduced and epithelisation was improved in SCE-treated SD rats. In vitro, SCE and its active compounds induced keratinocyte migration by regulating the β-catenin, extracellular signal-regulated kinase and Akt signalling pathways. Furthermore, SCE and its active compounds increased mRNA expression of type I and III collagen in Hs68 fibroblasts. SCE and chamechromone inhibited NO and PGE2 release and mRNA expression of inflammatory mediators in RAW 264.7 macrophages. SCE enhances the motility of HaCaT keratinocytes and improves cutaneous wound healing in SD rats.

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

    PubMed

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

    2014-01-01

    Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.

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

    PubMed Central

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

    2014-01-01

    Abstract. Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies. PMID:25036212

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

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients.

  7. Effects of supplementation with different edible oils on cutaneous wound healing.

    PubMed

    Otranto, Marcela; Do Nascimento, Adriana Paulino; Monte-Alto-Costa, Andréa

    2010-01-01

    Fatty acids are bioactive molecules, but their effects on cutaneous wound healing are not well understood. Our aim was to investigate the effects of supplementation with edible oils on cutaneous healing. Thirty days before wounding, rats were started on daily supplements of sunflower oil, linseed oil, fish oil, or water. Supplementation lasted until euthanasia. On day 0, an excisional wound was made on the back of each animal. Fourteen days later, the animals were euthanized, and the wound and adjacent skin were collected. Wound closure was higher in the control group compared with the other groups at days 7 and 14. Inflammatory cells were abundant in the control, linseed, and fish groups, but scarce in the sunflower group. Large numbers of myofibroblasts were observed in the control and sunflower groups. The linseed and fish groups presented a high density of dilated blood vessels. The control and sunflower groups showed a moderate density of collagen fibers; a high density of fibers was observed in the linseed and fish groups. Hydroxyproline levels were lowest in the control and sunflower groups. Supplementation with different types of edible oils delayed wound closure and affected the inflammatory infiltrate and collagen deposition.

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

    PubMed

    Valacchi, Giuseppe; Lim, Yunsook; Belmonte, Giuseppe; Miracco, Clelia; Zanardi, Iacopo; Bocci, Velio; Travagli, Valter

    2011-01-01

    Ozone is well recognized as a bactericidal agent and its beneficial effect on wound healing could be a consequence of this property. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects should be the results of oxidative reaction. For this reason, ozonated oils could be a way to deliver ozone messengers to the skin. This paper evaluated the therapeutic effects of three different grades of ozonated sesame oil in acute cutaneous wounds made in the skin of SKH1 mice. Specifically, wound closure rate, histological parameters, and the level of key proteins such as vascular endothelial growth factors and cyclin D1 have been analyzed in relation to the peroxide level present in the ozonated oil. Treatment with moderately ozonated sesame oil--expressed as peroxide value about 1,500)--has a faster wound closure rate in the first 7 days than treatment with oil containing either lower or higher peroxide value, and even with controls. Moreover, under the same treatment, an earlier and higher response of cells involved in wound repair, a higher angiogenesis, as well as an enhanced vascular endothelial growth factors and cyclin D1 expression were observed. The present study shows the validity of ozonated sesame oil in cutaneous wound healing and emphasizes the importance of the ozonation grade.

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

    PubMed Central

    2012-01-01

    Background Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. Methods Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β) antibodies. Results Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group. Conclusions This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing. PMID:23234369

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

    PubMed

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

    2012-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Gene transfer by pulsed electric field is highly promising in cutaneous wound healing.

    PubMed

    Gibot, Laure; Rols, Marie-Pierre

    2016-01-01

    Tremendous progress has been achieved during the last decades in electroporation-based technologies for medicine. Understanding the basic underlying mechanisms of gene delivery opens the way for clinical gene therapy and DNA vaccination. This review focuses on the use of gene electrotherapy in cutaneous tissue repair and how it affects healing. Gene electrotherapy is safe, efficient and promising as shown by the increasing number of publications reporting evidence for its potential in wound healing. Going deeper into the mechanisms of DNA delivery and expression as well as into skin regeneration at the molecular, cellular and tissues levels will help make it an attractive approach for the treatment of skin pathologies in general.

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

    PubMed

    Oryan, Ahmad; Mohammadalipour, Adel; Moshiri, Ali; Tabandeh, Mohammad R

    2015-12-01

    We investigated the effects of avocado/soybean unsaponifiables (ASU) on the healing response of cutaneous wound defect in rats. Sixty male rats were randomly divided into three groups including control, vehicle and treatment (n = 20 in each group). A 2 × 2 cm(2) wound defect was made on the dorsum. The control, vehicle and treatment groups were treated daily with topical application of saline, cream and cream/ASU for 10 days, respectively. The wounds were monitored daily. The animals were euthanised at 10, 20 and 30 days post injury (D). The dry matter, hydroxyproline, collagen, n-acetyl glucosamine (NAGLA) and n-acetyl galactosamine (NAGAA) contents of the skin samples were measured and the histopathological and biomechanical characteristics of the samples were investigated. Statistics of P < 0·05 was considered significant. Treatment significantly increased tissue glycosaminoglycans and collagen contents at various stages of wound healing compared to controls. Treatment modulated inflammation, improved fibroplasia and produced high amounts of scar tissue at short term. At long term, treatment reduced the scar tissue size and increased the quality and rate of wound contraction and reepithelisation compared to controls. The treated lesions were more cosmetically pleasing and had significantly higher biomechanical characteristics than controls. ASU was effective in rat wound healing.

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

    PubMed

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

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

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

    PubMed Central

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

    2016-01-01

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

  16. The Effect of 17β-Estradiol on Cutaneous Wound Healing in Protein-Malnourished Ovariectomized Female Mouse Model

    PubMed Central

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

    2014-01-01

    Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration. PMID:25518000

  17. Effects of acute diabetes on rat cutaneous wound healing.

    PubMed

    Komesu, Marilena Chinali; Tanga, Marcelo Benetti; Buttros, Kemli Raquel; Nakao, Cristiano

    2004-10-01

    INTRODUCTION:: Diabetes mellitus is a chronic hyperglycaemic disorder. Complicated metabolic mechanisms and increased incidence of infections are clinical hallmarks, mostly associated with its chronicity. There is little information about the early pathological processes in diabetes. The objective of our study was to evaluate the healing process during early phases of experimental diabetes on rat skin. METHODS:: Alloxan induced diabetic rats were used. Non-injected animals were used as control. Punch byopsies on dorsal skin had histopathological evaluation of the healing areas made on days 1, 3 and 7 post-surgery. RESULTS:: The results showed that: (1) in diabetics, the inflammation, the initial healing phase, has a slow beginning and tends to last longer; and (2) diabetic animals showed lower density of neutrophils in healing areas up to 3 days after surgery, and in addition, after day 3, when the neutrophils should leave the healing area, and be replaced by macrophages, compared to controls, diabetic animals showed higher numbers of neutrophils. PRINCIPAL CONCLUSION:: Although diabetes is a chronic progressive disease, acute diabetes can be associated to subclinical alterations, and responsible for deficiencies in defense cells and in repair tissue failures.

  18. Struthanthus vulgaris ointment prevents an over expression of inflammatory response and accelerates the cutaneous wound healing.

    PubMed

    Dos Santos Gramma, Luciane Souza; Marques, Franciane Martins; Vittorazzi, Cátia; de Andrade, Thiago Antônio Moretti; Frade, Marco Andrey Cipriani; de Andrade, Tadeu Uggere; Endringer, Denise Coutinho; Scherer, Rodrigo; Fronza, Marcio

    2016-08-22

    Struthanthus vulgaris (Vell.) Mart. (Loranthaceae) has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various skin disorders, including wounds. To investigated the influence of 5% Struthanthus vulgaris ointment during cutaneous wound healing in rats. Twenty Wistar rats were used in each group according the daily treatment, S. vulgaris 5% ointment (SV 5%) and vehicle control groups. Four full thicknesses wounds were punched in back side skin of each animal, and five animals were sacrificed after 2, 7, 14 and 21 days after surgery for histological, immunological and biochemical analysis. A significant wound closured area in the S. vulgaris 5% group of about 38% and 35% as compared to 19% and 21% in the control group was observed after 2 and 5 days, respectively. Histological and biochemical analysis of the skin biopsies showed that S. vulgaris treated wounds exhibited increased granulation tissue and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines like IL-1α, TNF-α and IL-10, nitric oxide and, growth factors like TGF-β. Moreover, S. vulgaris showed a marked and robust increase in the deposition and organization of collagen fibers in the wounds, and improve the quality of the scar tissue. Altogether these data revealed that S. vulgaris seems to prevent an over expression of inflammation and accelerates wound epithelialization and might be beneficial for treating healing disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Treatment with corticosterone delays cutaneous wound healing in male and female salamanders.

    PubMed

    Thomas, Jessica R; Woodley, Sarah K

    2015-05-15

    In vertebrates, exposure to stressors and stress hormones has a number of physiological effects including modulation of immune function. These effects on immune function have been well studied in mammals, but less is known in other groups, in particular amphibians. To analyze the effects of exposure to stressors and the stress hormone corticosterone, we monitored cutaneous wound healing as a measure of integrated immunity in male and female semi-terrestrial salamanders (Desmognathus ochrophaeus) that were chased to induce endogenous release of corticosterone or were treated with physiologically relevant doses of corticosterone. As predicted, subjects treated daily with corticosterone healed more slowly than did controls. In contrast, subjects that had been chased daily healed at the same rate as controls. Surprisingly, repeated chasing did not elevate plasma corticosterone despite causing drops in body mass and survival. Additionally, females healed more slowly than males, possibly due to energetic constraints.

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

    PubMed Central

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

    2016-01-01

    Wound healing is a complex process that involves several biological events, and a delay in this process may cause economic and social problems for the patient. The search continues for new alternative treatments to aid healing, including the use of herbal medicines. Members of the genus Caesalpinia are used in traditional medicine to treat wounds. The related species Poincianella pluviosa (DC.) L.P. Queiroz increases the cell viability of keratinocytes and fibroblasts and stimulates the proliferation of keratinocytes in vitro. The crude extract (CE) from bark of P. pluviosa was evaluated in the wound-healing process in vivo, to validate the traditional use and the in vitro activity. Standardized CE was incorporated into a gel and applied on cutaneous wounds (TCEG) and compared with the formulation without CE (Control) for 4, 7, 10, or 14 days of treatment. The effects of the CE on wound re-epithelialization; cell proliferation; permeation, using photoacoustic spectroscopy (PAS); and proteins, including vascular endothelial growth factor (VEGF), superoxide dismutase 2 (SOD-2) and cyclooxygenase 2 (COX-2) were evaluated. The TCEG stimulated the migration of keratinocytes at day 4 and proliferation on the following days, with a high concentration of cells in metaphase at 7 days. Type I collagen formed more rapidly in the TCEG. PAS showed that the CE had permeated through the skin. TCEG stimulated VEGF at day 4 and SOD-2 and COX-2 at day 7. The results suggest that the CE promoted the regulation of proteins and helped to accelerate the processes involved in healing, promoting early angiogenesis. This led to an increase in the re-epithelialized surface, with significant mitotic activity. Maturation of collagen fibers was also enhanced, which may affect the resistance of the extracellular matrix. PAS indicated a correlation between the rate of diffusion and biological events during the healing process. The CE from P. pluviosa appears promising as an aid in healing. PMID

  1. Improved cutaneous wound healing after intraperitoneal injection of alpha-melanocyte-stimulating hormone.

    PubMed

    de Souza, Kênia Soares; Cantaruti, Thiago Anselmo; Azevedo, Geraldo Magela; Galdino, Daniel Antero de Almeida; Rodrigues, Claudiney Melquíades; Costa, Raquel Alves; Vaz, Nelson Monteiro; Carvalho, Cláudia Rocha

    2015-03-01

    Skin wound healing is a complex process involving many types of cells and molecules and often results in scar tissue formation in adult mammals. However, scarless healing occurs in foetal skin and minimal scars may occur after cutaneous healing in the adult with reduced inflammation. Alpha-melanocyte-stimulating hormone (α-MSH) is widely distributed within the central nervous system and in other body regions, such as the skin, and has strong anti-inflammatory activity. The aim in the present experiments was to learn whether intraperitoneal (i.p) injection of α-MSH just before skin wounds antagonize inflammation and improves skin wound healing in adult mice. C57BL/6 young adult mice received an i.p. injection of 1 mg/kg of α-MSH and, 30 min later, two circular through-and-through holes (6.5 mm diameter) were made in their dorsal skin under anaesthesia. Control mice were wounded after vehicle injection. The wound healing process was analysed macroscopically and microscopically at 3, 7, 40 and 60 days. Skin samples were fixed in formalin, embedded in paraffin, sectioned at 5 μm, stained with H&E or toluidine blue for cell analysis or Gomori's trichrome for extracellular matrix (ECM) analysis. Other samples were fixed in DMSO+methanol, embedded in paraplast and incubated with anti-CD45, antismooth muscle actin, anticollagen-I and anticollagen-III for immunofluorescence analysis. Alpha-MSH significantly reduced the number of leucocytes, mast cells and fibroblasts at 3 and 7 days after injury. On days 40 and 60, α-MSH reduced scar area and improved the organization of the collagen fibres indicating that it may direct the healing into a more-regenerative/less-scarring pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2017-05-15

    Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocin-induced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats. Open cutaneous excision wound was created on the back of each of the 60 diabetic rats. Wound-inflicted rats were equally divided into three groups namely, control, gel treated, and SP + curcumin treated. Normal saline, pluronic gel, and SP (0.5 × 10(-6)M) + curcumin (0.15%) were topically applied once daily for 19 d to these control, gel-treated, and SP + curcumin groups, respectively. SP + curcumin combination significantly accelerated wound closure and decreased messenger RNA expressions of tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell-derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase, and activities of superoxide dismutase, catalase, and glutathione peroxidase in granulation-healing tissue, compared with control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth-associated protein 43-positive nerve fibers, and thick regenerated epithelial layer. The combination of SP and curcumin accelerated wound healing in diabetic rats and both the drugs were compatible at the doses used in this study. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Adult zebrafish as a model system for cutaneous wound-healing research.

    PubMed

    Richardson, Rebecca; Slanchev, Krasimir; Kraus, Christopher; Knyphausen, Philipp; Eming, Sabine; Hammerschmidt, Matthias

    2013-06-01

    Upon injury, the skin must quickly regenerate to regain its barrier function. In mammals, wound healing is rapid and scar free during embryogenesis, whereas in adults it involves multiple steps including blood clotting, inflammation, re-epithelialization, vascularization, and granulation tissue formation and maturation, resulting in a scar. We have established a rapid and robust method to introduce full-thickness wounds onto the flank of adult zebrafish, and show that apart from external fibrin clot formation, all steps of adult mammalian wound repair also exist in zebrafish. Wound re-epithelialization is extremely rapid and initiates with no apparent lag phase, subsequently followed by the immigration of inflammatory cells and the formation of granulation tissue, consisting of macrophages, fibroblasts, blood vessels, and collagen. The granulation tissue later regresses, resulting in minimal scar formation. Studies after chemical treatment or with transgenic fish further suggest that wound re-epithelialization occurs independently of inflammation and fibroblast growth factor signaling, whereas both are essential for fibroblast recruitment and granulation tissue formation. Together, these results demonstrate that major steps and principles of cutaneous wound healing are conserved among adult mammals and adult zebrafish, making zebrafish a valuable model for studying vertebrate skin repair.

  4. Wound healing potential of topical bacteriophage therapy on diabetic cutaneous wounds.

    PubMed

    Mendes, João J; Leandro, Clara; Corte-Real, Sofia; Barbosa, Raquel; Cavaco-Silva, Patrícia; Melo-Cristino, José; Górski, Andrzej; Garcia, Miguel

    2013-01-01

    Chronic wounds that fail to heal are a common complication of diabetes mellitus and the most common precipitating reason for nontraumatic lower limb amputation. Unfortunately, the bacterial species that cause these infections are becoming more resistant to antibiotics, making them increasingly difficult to treat. We assessed the feasibility of combating chronic bacterial infections with a topically delivered bacteriophage cocktail in two animal models of diabetes mellitus. Microbiological, planimetric, and histological parameters were compared in debrided infected wounds with or without topical bacteriophage treatment. We determined that bacteriophage treatment effectively decreased bacterial colony counts and improved wound healing, as indicated by smaller epithelial and dermal gaps, in Staphylococcus aureus and Pseudomonas aeruginosa infections but was not as effective against Acinetobacter baumannii. Although the improvements were more significant in the rodent model than in the porcine model, our results suggest that topically administered bacteriophage treatment may be effective in resolving chronic infections, especially when applied in conjunction with wound debridement. These findings have important implications for the feasibility of using topical antimicrobial therapies to safely treat chronic infections in diabetes mellitus patients. © 2013 by the Wound Healing Society.

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

    PubMed

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

    2013-01-01

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

  6. Evaluation of Therapeutic Intervention with a Natural Product in Cutaneous Wound Healing: The Use of Capybara Oil

    PubMed Central

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

    2013-01-01

    Capybara oil is commonly used for cutaneous wound healing in traditional South American medicine, although its beneficial effect has never been experimentally proven. The aim of this study was to investigate the effects of the topical application of capybara oil on skin wounds in Swiss mice. The following characteristics of the wounds were observed and evaluated: wound contraction and reepithelialization, the number of polymorphonuclear leukocytes and mast cells, the thickness of the neoepidermis, and the distribution of collagen and elastic fibers. Our study showed that oil extracted from subcutaneous capybara fat was beneficial for wound healing, indicating that capybara oil plays an important role in promoting tissue repair. PMID:23840249

  7. Crocodile oil enhances cutaneous burn wound healing and reduces scar formation in rats.

    PubMed

    Li, Hua-Liang; Chen, Li-Ping; Hu, Yong-Hua; Qin, Yan; Liang, Ge; Xiong, You-Xiong; Chen, Qing-Xi

    2012-03-01

    This study was performed to evaluate the burn wound-healing efficacy of crocodile oil from Crocodylus siamensis by employing deep second-degree burns in a Wistar rat model. Twenty-four rats were assigned equally into four groups using a random-number table, and two burns were created on the dorsum of each animal except for the sham group. The three treatment groups received with saline solution (12 burns, served as negative control), silver sulfadiazine (12 burns, served as positive control), or crocodile oil (12 burns). Silver sulfadiazine cream was used as standard care, and the treatments were repeated twice daily for 28 days. After day 28 the animals were euthanized and the wounds were removed for quantitative real-time polymerase chain reaction, histologic, and immunohistochemical study. Crocodile oil accelerated the wound-healing process as indicated by a significant decrease in wound closure time in comparison to the burn control and silver sulfadiazine treatment groups. Histologic results showed well-organized and distributed skin structure and collagen deposition in the animals treated with crocodile oil. Transforming growth factor-β1 (TGF-β1), a key cytokine promoting scarring, was also observed to play a role in the burn wound healing. Immunohistochemical staining results showed the negative expression of TGF-β1 and Smad3 in the 28-days-postburn skin of crocodile oil group versus positive in the epidermis of burn controls. Compared to the burn control group, expressions of TGF-β1 and Smad3 mRNA decreased significantly (p < 0.01) in the 28-days-postburn skin of the crocodile oil group. Our results showed that crocodile oil could enhance cutaneous burn wound healing and reduce scar formation in rats, which might be related to TGF-β1/Smad3 signaling. © 2012 by the Society for Academic Emergency Medicine.

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    PubMed

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

    2009-01-01

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

  10. Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats.

    PubMed

    Almeida, J S; Benvegnú, D M; Boufleur, N; Reckziegel, P; Barcelos, R C S; Coradini, K; de Carvalho, L M; Bürger, M E; Beck, R C R

    2012-07-01

    Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats. Hydrogels were prepared using Carbopol Ultrez® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress. Hydrogels showed adequate pH values (5.50-6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels. This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  12. Identification of novel AP-1 target genes in fibroblasts regulated during cutaneous wound healing.

    PubMed

    Florin, Lore; Hummerich, Lars; Dittrich, Bernd Thilo; Kokocinski, Felix; Wrobel, Gunnar; Gack, Sabine; Schorpp-Kistner, Marina; Werner, Sabine; Hahn, Meinhard; Lichter, Peter; Szabowski, Axel; Angel, Peter

    2004-09-16

    Mesenchymal-epithelial interactions are increasingly considered to be of vital importance for epithelial homeostasis and regeneration. In skin, the transcription factor AP-1 was shown to be critically involved in the communication between keratinocytes and dermal fibroblasts. After skin injury, the release of IL-1 from keratinocytes induces the activity of the AP-1 subunits c-Jun and JunB in fibroblasts leading to a global change in gene expression. To identify AP-1 target genes in fibroblasts, which are involved in the process of cutaneous repair, we performed gene expression profiling of wild-type, c-jun- and junB-deficient fibroblasts in response to IL-1, mimicking the initial phase of wound healing. Using a 15K cDNA collection, over 1000 genes were found to be Jun-dependent and additional 300 clones showed IL-1 responsiveness. Combinatorial evaluation allowed for the dissection of the specific contribution of either AP-1 subunit to gene regulation. Besides previously identified genes that are involved in cutaneous repair, we have identified novel genes regulated during wound healing in vivo and showed their expression by fibroblasts on wound sections. The identification of novel Jun target genes should provide a basis for understanding the molecular mechanisms underlying mesenchymal-epithelial interactions and the critical contribution of AP-1 to tissue homeostasis and repair.

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

    PubMed Central

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

    2015-01-01

    Background The influence of skin substitutes upon angiogenesis during wound healing is unclear. Objectives To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention. Methods On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2 was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft). Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis. Results Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and vessel number derived from CD31-based immunohistochemistry (p = 0.046) were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004). Conclusion Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses. PMID:25602294

  14. Factors Affecting Wound Healing

    PubMed Central

    Guo, S.; DiPietro, L.A.

    2010-01-01

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

  15. Heterogeneity of macrophage populations and expression of galectin-3 in cutaneous wound healing in rats.

    PubMed

    Juniantito, V; Izawa, T; Yamamoto, E; Murai, F; Kuwamura, M; Yamate, J

    2011-11-01

    The aim of this study was to investigate the properties of macrophages that infiltrated the sites of cutaneous wound healing in rats between 1 and 26 days post wounding (dpw). During the inflammation phase (1-3 dpw), ED1(+) (CD68(+)) macrophages with enhanced lysosomal activity dominated. From 5 to 7 dpw there was formation of granulation tissue as indicated by the presence of myofibroblasts expressing α-smooth muscle actin. At this stage, ED2(+) (CD163(+)) macrophages, capable of producing inflammatory factors, were dominant. The majority of ED1(+) macrophages expressed galectin-3, a regulator of fibrosis. Corresponding to the increased numbers of ED1(+) and ED2(+) macrophages at 3-9 dpw, there was increased expression of genes encoding transforming growth factor-β1 (a major fibrogenic factor), monocyte chemoattractant protein-1 and colony stimulating factor-1. These macrophage-related factors might contribute to inflammation and formation of granulation tissue. OX6(+) macrophages expressing class II molecules of the major histocompatibility complex became predominant in the healing stages (15-26 dpw), indicating important roles for antigen-presenting cells in tissue remodelling. The OX6(+) macrophages were most likely derived from ED1(+) macrophages. The results of this study show that infiltration of phenotypically- and functionally-distinct macrophage populations characterizes different stages of the wound healing process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

    PubMed

    Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

    2017-10-01

    Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

    PubMed

    Ud-Din, Sara; Bayat, Ardeshir

    2016-08-01

    Objective evaluation of cutaneous wounds through the use of non-invasive devices is important for diagnosis, monitoring treatment response and can lead to the development of improved theranostic strategies. The need for objective monitoring of wound healing and scar formation is evident as this enables accurate diagnosis, evaluation and prognosis for clinicians and allows for the standardisation and validation of methodology for researchers. Therefore, this review provides an overview of the current application of non-invasive objective technologies for the assessment of wound healing through the different phases of repair. We propose that cutaneous healing parameters can be split into three core domains: anatomical, mechanical and physiological. These categories can be further subdivided with respect to specific phases of healing. There is no single instrument, which can measure all the parameters of healing simultaneously; thus, it is important to choose the correct device for the particular healing characteristics being monitored. However, multiprobe systems, which include a number of devices connected to one main unit, are useful as they enable multiple measurements of different parameters. Many of the devices have not been validated against histological examination. Additionally, some of the instruments have not been evaluated in all wound or scar types and may not be useful throughout all phases of cutaneous wound healing. In conclusion, non-invasive objective devices are useful in the assessment of cutaneous wound healing, as these tools can link the treatment and diagnosis by evaluating response to treatment and thus could aid as a marker for healing and scar maturation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: Role of COL1A1

    PubMed Central

    Almeida, Lucas; Oliveira, Joyce; Guimarães, Luiz Henrique; Carvalho, Edgar M; Blackwell, Jenefer M

    2015-01-01

    Previous studies have demonstrated a role for wound healing genes in resolution of cutaneous lesions caused by Leishmania spp. in both mice and humans, including the gene FLI1 encoding Friend leukaemia virus integration 1. Reduction of Fli1 expression in mice has been shown to result in up-regulation of collagen type I alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression is involved in activation of the profibrotic gene program. Here we examined single nucleotide polymorphisms (SNPs) in these genes as risk factors for cutaneous (CL) and mucosal leishmaniasis (ML), and leishmaniasis per se, caused by L. braziliensis in humans. SNPs were genotyped in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Family-based association tests (FBAT) showed the strongest association between SNPs rs1061237 (combined P=0.002) and rs2586488 (combined P=0.027) at COL1A1 and CL disease. This contributes to our further understanding of the role of wound healing in the resolution of CL disease, providing potential for therapies modulating COL1A1 via drugs acting on FLI1. PMID:25562121

  19. Paracrine action of mesenchymal stromal cells delivered by microspheres contributes to cutaneous wound healing and prevents scar formation in mice.

    PubMed

    Huang, Sha; Wu, Yan; Gao, Dongyun; Fu, Xiaobing

    2015-07-01

    Accumulating evidence suggests that mesenchymal stromal cells (MSCs) participate in wound healing to favor tissue regeneration and inhibit fibrotic tissue formation. However, the evidence of MSCs to suppress cutaneous scar is extremely rare, and the mechanism remains unidentified. This study aimed to demonstrate whether MSCs-as the result of their paracrine actions on damaged tissues-would accelerate wound healing and prevent cutaneous fibrosis. For efficient delivery of MSCs to skin wounds, microspheres were used to maintain MSC potency. Whether MSCs can accelerate wound healing and alleviate cutaneous fibrosis through paracrine action was investigated with the use of a Transwell co-culture system in vitro and a murine model in vivo. MSCs cultured on gelatin microspheres fully retained their cell surface marker expression profile, proliferation, differentiation and paracrine potential. Co-cultures of MSCs and fibroblasts indicated that the benefits of MSCs on suppressing fibroblast proliferation and its fibrotic behavior induced by inflammatory cytokines probably were caused by paracrine actions. Importantly, microspheres successfully delivered MSCs into wound margins and significantly accelerated wound healing and concomitantly reduced the fibrotic activities of cells within the wounds and excessive accumulation of extracellular matrix as well as the transforming growth factor-β1/transforming growth factor-β3 ratio. This study provides insight into what we believe to be a previously undescribed, multifaceted role of MSC-released protein in reducing cutaneous fibrotic formation. Paracrine action of MSCs delivered by microspheres may thus qualify as a promising strategy to enhance tissue repair and to prevent excessive fibrosis during cutaneous wound healing. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. Energy metabolism during cutaneous wound healing in immunocompromised and aged rats.

    PubMed

    Gupta, Asheesh; Manhas, Namratta; Raghubir, Ram

    2004-04-01

    Cutaneous cells primarily depend upon carbohydrate metabolism for their energy requirement during healing process. But, it may be greatly hampered during various pathological and altered physiological conditions. The present study was therefore undertaken to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the granulation tissues of immunocompromised and aged rats following excision-type of cutaneous injury. The activities of key regulatory enzymes hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the wound tissues of immunocompromised and aged rats at different time intervals (2, 7, 14 and 21 days) of postwounding. The activities of HK and CS were found significantly decreased both in immunocompromised and aged rats as compared to control subjects. However G6PD exhibited an elevated activity at early stage followed by a decreased activity at later phase of healing both in immunocompromised and aged rats. The PFK and LDH demonstrated an upward trend in immunocompromised rats but a decreasing trend in aged rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the granulation tissues in both immunocompromised as well as in aged rats may overall affect the energy availability for cellular activity needed for repair process. Hence, this may perhaps be one of the factor responsible for impaired healing in these subjects.

  1. Impaired cutaneous wound healing in transforming growth factor-β inducible early gene1 knockout mice.

    PubMed

    Hori, Keijiro; Ding, Jie; Marcoux, Yvonne; Iwashina, Takashi; Sakurai, Hiroyuki; Tredget, Edward E

    2012-01-01

    Transforming growth factor-β inducible early gene (TIEG) is induced by transforming growth factor-β (TGF-β) and acts as the primary response gene in the TGF-β/Smad pathway. TGF-β is a multifunctional growth factor that affects dermal wound healing; however, the mechanism of how TGF-β affects wound healing is still not well understood because of the complexity of its function and signaling pathways. We hypothesize that TIEG may play a role in dermal wound healing, with involvement in wound closure, contraction, and reepithelialization. In this study, we have shown that TIEG1 knockout (TIEG1-/-) mice have a delay in wound closure related to an impairment in wound contraction, granulation tissue formation, collagen synthesis, and reepithelialization. We also found that Smad7 was increased in the wounds and appeared to play a role in this wound healing model in TIEG1-/- mice. © 2012 by the Wound Healing Society.

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

    PubMed

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

    2016-09-12

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  6. Expression of Kruppel-Like Factor KLF4 in Mouse Hair Follicle Stem Cells Contributes to Cutaneous Wound Healing

    PubMed Central

    Wang, Junfeng; Yu, Fang; Morris, Rebecca J.; Wang, Timothy C.; Huang, Shiang; Ai, Walden

    2012-01-01

    Background Kruppel-like factor KLF4 is a transcription factor critical for the establishment of the barrier function of the skin. Its function in stem cell biology has been recently recognized. Previous studies have revealed that hair follicle stem cells contribute to cutaneous wound healing. However, expression of KLF4 in hair follicle stem cells and the importance of such expression in cutaneous wound healing have not been investigated. Methodology/Principal Findings Quantitative real time polymerase chain reaction (RT-PCR) analysis showed higher KLF4 expression in hair follicle stem cell-enriched mouse skin keratinocytes than that in control keratinocytes. We generated KLF4 promoter-driven enhanced green fluorescence protein (KLF4/EGFP) transgenic mice and tamoxifen-inducible KLF4 knockout mice by crossing KLF4 promoter-driven Cre recombinase fused with tamoxifen-inducible estrogen receptor (KLF4/CreER™) transgenic mice with KLF4(flox) mice. KLF4/EGFP cells purified from dorsal skin keratinocytes of KLF4/EGFP transgenic mice were co-localized with 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells by flow cytometric analysis and immunohistochemistry. Lineage tracing was performed in the context of cutaneous wound healing, using KLF4/CreER™ and Rosa26RLacZ double transgenic mice, to examine the involvement of KLF4 in wound healing. We found that KLF4 expressing cells were likely derived from bulge stem cells. In addition, KLF4 expressing multipotent cells migrated to the wound and contributed to the wound healing. After knocking out KLF4 by tamoxifen induction of KLF4/CreER™ and KLF4(flox) double transgenic mice, we found that the population of bulge stem cell-enriched population was decreased, which was accompanied by significantly delayed cutaneous wound healing. Consistently, KLF4 knockdown by KLF4-specific small hairpin RNA in human A431 epidermoid carcinoma cells decreased the stem cell population and was accompanied by compromised cell migration

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

    PubMed

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

    2013-01-01

    In adults, repair of deeply injured skin wounds results in the formation of scar tissue, whereas in embryos wounds heal almost scar-free. Macrophages are important mediators of wound healing and secrete cytokines and tissue remodeling enzymes. In contrast to host defense mediated by inflammatory M1 macrophages, wound healing and tissue repair involve regulatory M2/M2-like macrophages. Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound healing. In the present study, we asked whether atopical application of ex vivo generated, embryonic stem cell-derived macrophages (ESDM) improve wound healing in mice. ESDM were tested side by side with bone marrow-derived macrophages (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like macrophage subtype as indicated by their reduced responsiveness to lipopolysaccharide, reduced expression of Toll-like receptors, and reduced bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture, ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds had more scar formation compared to wounds receiving BMDM or cell-free treatment. Our data indicate that atopical application of ex vivo generated macrophages is not a suitable cell therapy of dermal wounds. © 2012 by the Wound Healing Society.

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

    PubMed

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

    2015-02-25

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

  9. How wounds heal

    MedlinePlus

    ... care to prevent infection. Continue Reading Stages of Wound Healing Wounds heal in stages. The smaller the wound, ... How lacerations heal References Leong M, Phillips LG. Wound healing. In: Townsend CM, Beauchamp RD, Evers BM, Mattox ...

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

    NASA Astrophysics Data System (ADS)

    Ramalho, Luciana Maria Pedreira; Weyll, Barbara Mayoral Pedroso; da Costa Lino, Maíra Dória M.; Ramalho, Maria Jose Pedreira; Barbosa Pinheiro, Antonio Luis

    2010-02-01

    The aim of this study was to assess the influence of low-level laser therapy (LLLT) or polarized light (PL) in cutaneous wound healing of hypothyroid rats at dosages of 20 or 40J/cm2. Bioestimulatory effects of Laser radiation and Polarized light are recognized alternative therapies to improve healing on systemic disease patients, but their usefulness in the improvement of hypothyroidism healing impairment is uncertain till date. Forty Wistar rats were used in this study. Hypothyroidism was propylthiouracil- induced. Standard excisional cutaneous wounds were created without suturing and LLLT (λ660nm, 30mW, φ 3mm) or PL (λ 400-2000nm, 40mW, φ 10mm) was applied every 48 hours up to seven days on experimental groups. The rats were killed on the eighth day when wound contraction was assessed. The healing features were evaluated by light microscopy (H/E and Sirius Red). The cutaneous wounds of hypothyroid rats showed delayed healing process characterized by reduced thickness of epithelial layers, incipient formation of disorganized collagen fibers and wound contraction to a lesser extent (FISHER, p=0.0276), when compared to the euthyroid group. The use of both the Laser and Polarized Light on hypothyroid rats increased the amount of fibroblasts and the thickness of collagen fibers, especially on the L 20J/cm2 group. Euthyroid rats have still demonstrated more regular collagen fibers pattern than hypothyroid rats. It was therefore concluded that hypothyroidism delays wound healing and both Laser photobiomodulation and Polarized Light at 20j/cm2 dosages had improved the healing process in hypothyroid rats.

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    1988-01-01

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

  13. Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome: Implications for Wound Healing and Infection

    PubMed Central

    Holmes, Casey J.; Plichta, Jennifer K.; Gamelli, Richard L.; Radek, Katherine A.

    2015-01-01

    Significance: Humans are under constant bombardment by various stressors, including psychological anxiety and physiologic injury. Understanding how these stress responses influence the innate immune system and the skin microbiome remains elusive due to the complexity of the neuroimmune and stress response pathways. Both animal and human studies have provided critical information upon which to further elucidate the mechanisms by which mammalian stressors impair normal wound healing and/or promote chronic wound progression. Recent Advances: Development of high-throughput genomic and bioinformatic approaches has led to the discovery of both an epidermal and dermal microbiome with distinct characteristics. This technology is now being used to identify statistical correlations between specific microbiota profiles and clinical outcomes related to cutaneous wound healing and the response to pathogenic infection. Studies have also identified more prominent roles for typical skin commensal organisms in maintaining homeostasis and modulating inflammatory responses. Critical Issues: It is well-established that stress-induced factors, including catecholamines, acetylcholine, and glucocorticoids, increase the risk of impaired wound healing and susceptibility to infection. Despite the characterization of the cutaneous microbiome, little is known regarding the impact of these stress-induced molecules on the development and evolution of the cutaneous microbiome during wound healing. Future Directions: Further characterization of the mechanisms by which stress-induced molecules influence microbial proliferation and metabolism in wounds is necessary to identify altered microbial phenotypes that differentially influence host innate immune responses required for optimal healing. These mechanisms may yield beneficial as targets for manipulation of the microbiome to further benefit the host after cutaneous injury. PMID:25566412

  14. Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats

    PubMed Central

    2011-01-01

    Background Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS) production. Whey protein (WP) is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN), a wounded diabetic group (WD) and a wounded diabetic group orally supplemented with whey protein (WDWP) at a dose of 100 mg/kg body weight. Results Whey protein was found to significantly decrease the levels of malondialdehyde (MDA), nitric oxide (NO) and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1β, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. Conclusion In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines. PMID:22168406

  15. Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats.

    PubMed

    Ebaid, Hossam; Salem, Amir; Sayed, Abdalla; Metwalli, Ali

    2011-12-14

    Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS) production. Whey protein (WP) is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN), a wounded diabetic group (WD) and a wounded diabetic group orally supplemented with whey protein (WDWP) at a dose of 100 mg/kg body weight. Whey protein was found to significantly decrease the levels of malondialdehyde (MDA), nitric oxide (NO) and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1β, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines.

  16. Abietic acid isolated from pine resin (Resina Pini) enhances angiogenesis in HUVECs and accelerates cutaneous wound healing in mice.

    PubMed

    Park, Jun Yeon; Lee, Yun Kyung; Lee, Dong-Soo; Yoo, Jeong-Eun; Shin, Myoung-Sook; Yamabe, Noriko; Kim, Su-Nam; Lee, Seulah; Kim, Ki Hyun; Lee, Hae-Jeung; Roh, Seok Sun; Kang, Ki Sung

    2017-05-05

    Resin known as Resina Pini is listed in the Korean and Japanese pharmacopoeias and has been used for treating skin wounds and inflammation. Resin is composed of more than 50% abietic acid and 10% neutral substances. In the present study, the wound-healing effects of abietic acid and the possible underlying mechanism of action were investigated in various in vitro and in vivo models. The effects of abietic acid on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVECs). Protein expression of mitogen-activated protein kinase (MAPK) activation was evaluated via Western blotting analysis. The wound-healing effects of abietic acid were assessed using a mouse model of cutaneous wounds. The results showed that abietic acid enhanced cell migration and tube formation in HUVECs. Abietic acid induced significant angiogenic potential, which is associated with upregulation of extracellular signal-regulated kinase (ERK) and p38 expression. Additionally, 0.8μM abietic acid-treated groups showed accelerated wound closure compared to the controls in a mouse model of cutaneous wounds. The current data indicate that abietic acid treatment elevated cell migration and tube formation in HUVECs by the activation of ERK and p38 MAPKs. We suggest that abietic acid can be developed as a wound-healing agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing.

    PubMed

    Xanthoulea, Sofia; Deliaert, An; Romano, Andrea; Rensen, Sander S; Buurman, Wim A; van der Hulst, Rene' R W J

    2013-12-01

    The aim of the current study was to investigate the effect of nicotine in an experimental mouse model of cutaneous injury and healing responses, during the inflammatory phase of repair. Nicotine injection in full-thickness excisional skin wounds minimally affected inflammatory mediators like TNF, IL-6 and IL-12 while it induced a down-regulation in the expression of growth factors like VEGF, PDGF, TGF-β1 and TGF-β2, and the anti-inflammatory cytokine IL-10. Analysis of wound closure rate indicated no significant differences between nicotine and saline injected controls. In-vitro studies using bone marrow derived macrophages, resident peritoneal macrophages and RAW 264.7 macrophages, indicated that nicotine down-regulates TNF production. Moreover, nicotine was shown to down-regulate VEGF, PDGF and TGF-β1 in both bone marrow derived macrophages and RAW 264.7 cells. Using an NF-κB luciferase reporter RAW 264.7 cell line, we show that nicotine effects are minimally dependent on NF-κB inhibition. Moreover, nicotinic acetylcholine receptor (nAChR) subunit expression analyses indicated that while β2 nAChR subunit is expressed in mouse macrophages, α7 nAChR is not. In conclusion, while skin inflammatory parameters were not significantly affected by nicotine, a down-regulation of growth factor expression in both mouse skin and macrophages was observed. Reduced growth factor expression by nicotine might contribute, at least in part, to the overall detrimental effects of tobacco use in wound healing and skin diseases. © 2013.

  18. Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing.

    PubMed

    Volksdorf, Thomas; Heilmann, Janina; Eming, Sabine A; Schawjinski, Kathrin; Zorn-Kruppa, Michaela; Ueck, Christopher; Vidal-Y-Sy, Sabine; Windhorst, Sabine; Jücker, Manfred; Moll, Ingrid; Brandner, Johanna M

    2017-06-01

    Tight junction (TJ) proteins are known to be involved in proliferation and differentiation. These processes are essential for normal skin wound healing. Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin wound healing models and tissue samples of acute and chronic human wounds and observed major differences in localization/expression of these proteins, with chronic wounds often showing a loss of the proteins at the wound margins and/or in the regenerating epidermis. Knockdown experiments in primary human keratinocytes showed that decreased claudin-1 expression resulted in significantly impaired scratch wound healing, with delayed migration and reduced proliferation. Activation of AKT pathway was significantly attenuated after claudin-1 knockdown, and protein levels of extracellular signal-related kinase 1/2 were reduced. For occludin, down-regulation had no impact on wound healing in normal scratch assays, but after subjecting the cells to mechanical stress, which is normally present in wounds, wound healing was impaired. For both proteins we show that most of these actions are independent from the formation of barrier-forming TJ structures, thus demonstrating nonbarrier-related functions of TJ proteins in the skin. However, for claudin-1 effects on scratch wound healing were more pronounced when TJs could form. Together, our findings provide evidence for a role of claudin-1 and occludin in epidermal regeneration with potential clinical importance. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation

    PubMed Central

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice. PMID:26057238

  20. Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing

    PubMed Central

    Ojha, Navdeep; Roy, Sashwati; He, Guanglong; Biswas, Sabyasachi; Velayutham, Murugesan; Khanna, Savita; Kuppusamy, Periannan; Zweier, Jay L.; Sen, Chandan K.

    2009-01-01

    We have previously reported that H2O2 is actively generated by cells at the wound-site and that H2O2-driven redox signaling support wound angiogenesis and healing. In this study, we have standardized a novel and effective electron paramagnetic resonance (EPR) spectroscopy based approach to assess the redox environment of dermal wound site in vivo. Rac2 regulates reduced NADPH oxidase activation and other functional responses in neutrophils. Using Rac2-deficient mice we sought to investigate the significance of Rac2 in wound site redox environment and healing responses. Non-invasive measurements of metabolism of topically applied nitroxide 15N-perdeuterated tempone in murine excisional dermal wounds demonstrated that the wound site is rich in oxidants, the level of which peaks two day post-wounding in the inflammatory phase. Rac2-deficient mice had 3-fold lower production of superoxide compared to controls in similar wounds. In these mice, lower wound-site superoxide level was associated with compromised wound closure. Immunostaining of wound edges harvested during the inflammatory phase showed that the number of phagocytic cells recruited at the wound site in Rac2 deficient and control mice were similar, but the amount of lipid peroxidation was significantly lower in Rac2 deficient mice indicating compromised NADPH oxidase activity. Taken together, the findings of this study support that the wound-site is rich in oxidants. Rac2 significantly contributes to oxidant production at the wound site and supports the healing process. PMID:18068132

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

    PubMed Central

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

    2011-01-01

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

  2. miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2.

    PubMed

    Yang, Longlong; Zheng, Zhao; Zhou, Qin; Bai, Xiaozhi; Fan, Lei; Yang, Chen; Su, Linlin; Hu, Dahai

    2017-04-01

    Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.

  3. A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

    PubMed Central

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

    2010-01-01

    Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. PMID:20386608

  4. beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays rat cutaneous wound healing.

    PubMed

    Romana-Souza, Bruna; Santos, Jeanine S; Monte-Alto-Costa, Andréa

    2009-01-01

    The sympathetic nervous system plays an important role in wound healing, but its mechanism of action is poorly understood. The aim of this study was to investigate the effects of beta- and alpha-adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist), or phentolamine (alpha1- and alpha2-antagonist) dissolved in drinking water. A full-thickness excisional lesion was created and the wound area was measured. Fourteen days after wounding, lesions and adjacent skin were removed, formalin-fixed, and paraffin-embedded. Sections were stained with hematoxylin-eosin and toluidine blue, and immunostained for alpha-smooth muscle actin and proliferating cell nuclear antigen. Wound contraction was delayed in propranolol- and atenolol-treated animals but not in phentolamine-treated animals. Reepithelialization was decreased only in propranolol-treated animals. beta1- and beta2-adrenoceptor blockade delayed leukocyte migration, epidermal and connective tissue cell proliferation, myofibroblastic differentiation, and mast cell migration. The volume density of blood vessels was increased in the propranolol- and atenolol-treated animals compared with controls. The levels of matrix metalloproteases (MMP-2 and MMP-9) decreased in the propranolol- and atenolol-treated animals. alpha1- and alpha2-adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro-MMP-9 levels. In conclusion, beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays cutaneous wound healing.

  5. Improved Wound Healing of Cutaneous Sulfur Mustard Injuries in a Weanling Pig Model

    PubMed Central

    Graham, John S.; Stevenson, Robert S.; Mitcheltree, Larry W.; Simon, Marcia; Hamilton, Tracey A.; Deckert, Robin R.; Lee, Robyn B.

    2006-01-01

    Objective: The objective was to examine the efficacy of several treatment regimens in improving wound healing of cutaneous sulfur mustard (HD) injuries. Methods: Wound healing studies were conducted in weanling pigs. Superficial dermal HD injuries were debrided at 48 hours postexposure using an erbium-doped yttrium aluminum garnet (Er:YAG) laser, followed by application of a treatment adjunct. A variety of noninvasive bioengineering methods were conducted during the postsurgical observation period to examine the various cosmetic and functional aspects of the skin. Histopathology was performed at the end of each study (14 or 21 days postsurgery). Results: As noted clinically, reepithelialization was nearly complete by 7 days postsurgery for many of the sites treated with petrolatum and scarlet red dressings. By 21 days, the skin elasticity of the petrolatum-dressed sites was not significantly different from that of sham-exposed skin. Upon dressing removal on postsurgery day 4, the neoepidermis of allograft- and thin film-dressed sites was partially removed, with resultant petechial hemorrhaging. Mean pathology scores for hydrocolloid-dressed sites were significantly lower than those of untreated HD-exposed sites on postsurgery day 14. Conclusions: Care must be taken during bandage changes, and a nonadherent dressing that could be left in place for a longer period of time (eg, 7 days) would be beneficial. The use of cultured epithelial allograft material may have a potential role if grown on a completely nonadherent backing and left undisturbed for at least a week. Xeroform Petrolatum and Scarlet Red Ointment dressings are effective and inexpensive treatment adjuncts for HD injuries. PMID:17111042

  6. Application of a partial-thickness human ex vivo skin culture model in cutaneous wound healing study.

    PubMed

    Xu, Wei; Jong Hong, Seok; Jia, Shengxian; Zhao, Yanan; Galiano, Robert D; Mustoe, Thomas A

    2012-04-01

    A number of in vivo and ex vivo skin models have been applied to human wound healing studies. A reliable skin model, which recapitulates the features of human wound repair, is essential for the clinical and mechanical investigation of human cutaneous wound healing. Full-skin ex vivo culture systems have been used in wound healing studies. However, important structures of the skin, such as the differentiation of keratinocytes and epidermis-dermis junction, are poorly characterized in this model. This study aims to develop an optimized partial-thickness human ex vivo skin culture (HESC) model to maintain human skin characteristics in vitro. During our culture, the basal layer, suprabasal layer, and stratum granulosum layer of epidermis were preserved until day 8. Analyses of hemidesmosome proteins, bullous pemphigoid antigen 1 (BP180) and 2 (BP230), showed that the integrity of the basement membrane of the epidermis was well preserved in the HESC model. In contrast, an organotypic culture with human keratinocytes and fibroblasts failed to show an integrated basement membrane. Maintenance of skin structure by histological analysis and proliferation of epidermal keratinocytes by Ki67 staining were observed in our model for 12 days. Complete re-epithelialization of the wounding area was observed at day 6 post wounding when a superficial incisional wound was created. The expression of Ki-67 and keratin 6, indicators of activated keratinocytes in epidermis, was significantly upregulated and new collagen synthesis was found in the dermis during the wound healing process. As control, we also used organotypic culture in studying the differentiation of the keratinocyte layers and incisional wound repair. It turned out that our model has advantage in these study fields. The results suggest that our HESC model retains important elements of in vivo skin and has significant advantages for the wound healing studies in vitro.

  7. A Comparison of the Effects of Alpha and Medical-Grade Honey Ointments on Cutaneous Wound Healing in Rats.

    PubMed

    Paydar, Shahram; Akrami, Majid; Dehghanian, Amirreza; Alavi Moghadam, Roshanak; Heidarpour, Mohsen; Bahari Khoob, Amir; Dalfardi, Behnam

    2016-01-01

    Introduction. This study compared the healing efficacy and possible adverse effects of topical Alpha and medical-grade honey ointments on cutaneous wounds in rats. Methods. To conduct the study, 22 male Sprague-Dawley rats were randomly allocated into two equal groups: (1) rats with Alpha ointment applied to the wound surface area and (2) rats with medical-grade honey ointment applied to their wounds. The ointments were applied daily during the 21-day study period. Wound contraction was examined photographically with images taken on days 0, 7, and 21 after wounding. The healing process was histopathologically assessed using skin biopsies taken from the wound sites on days 7 and 21. Results. No statistically significant difference in mean wound surface area was observed between the two study groups. According to histopathological assessment, a significant reduction in the amount of collagen deposition (P value: 0.007) and neovascularisation (P value: 0.002) was seen in the Alpha-treated rats on day 21. No tissue necrosis occurred following the application of Alpha ointment. Conclusion. Daily topical usage of Alpha ointment on a skin wound can negatively affect the healing process by inhibiting neovascularization. Topical Alpha ointment can reduce the possibility of excessive scar formation by reducing collagen deposition.

  8. A Comparison of the Effects of Alpha and Medical-Grade Honey Ointments on Cutaneous Wound Healing in Rats

    PubMed Central

    Paydar, Shahram; Akrami, Majid; Dehghanian, Amirreza; Alavi Moghadam, Roshanak; Heidarpour, Mohsen; Bahari Khoob, Amir

    2016-01-01

    Introduction. This study compared the healing efficacy and possible adverse effects of topical Alpha and medical-grade honey ointments on cutaneous wounds in rats. Methods. To conduct the study, 22 male Sprague-Dawley rats were randomly allocated into two equal groups: (1) rats with Alpha ointment applied to the wound surface area and (2) rats with medical-grade honey ointment applied to their wounds. The ointments were applied daily during the 21-day study period. Wound contraction was examined photographically with images taken on days 0, 7, and 21 after wounding. The healing process was histopathologically assessed using skin biopsies taken from the wound sites on days 7 and 21. Results. No statistically significant difference in mean wound surface area was observed between the two study groups. According to histopathological assessment, a significant reduction in the amount of collagen deposition (P value: 0.007) and neovascularisation (P value: 0.002) was seen in the Alpha-treated rats on day 21. No tissue necrosis occurred following the application of Alpha ointment. Conclusion. Daily topical usage of Alpha ointment on a skin wound can negatively affect the healing process by inhibiting neovascularization. Topical Alpha ointment can reduce the possibility of excessive scar formation by reducing collagen deposition. PMID:27885353

  9. Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo.

    PubMed Central

    Juhasz, I.; Murphy, G. F.; Yan, H. C.; Herlyn, M.; Albelda, S. M.

    1993-01-01

    Although changes in extracellular matrix proteins during wound healing have been well documented, little is known about the regulation of corresponding extracellular matrix adhesion receptors (integrins). To study this process in a human in vivo model, full thickness human skin grafts were transplanted onto severe combined immunodeficient mice and deep excisional wounds involving both the epidermal and dermal layers were then made. The changes in the expression of cell matrix proteins and epithelial integrins over time were analyzed with specific antibodies using immunohistochemistry. Wounding was associated with alterations in extracellular matrix proteins, namely, loss of laminin and type IV collagen in the region of the wound and expression of tenascin and fibronectin. Changes were also noted in the integrins on the migrating keratinocytes. There was marked up-regulation of the alpha v subunit and de novo expression of the fibronectin receptor (alpha 5 beta 1) during the stage of active migration (days 1 to 3 after wounding). In the later stages of wound healing, after epithelial integrity had been established, redistribution of the alpha 2, alpha 3, alpha 6, and beta 4 collagen/laminin-binding integrin subunits to suprabasal epidermal layers was noted. Thus, during cutaneous wound healing, keratinocytes up-regulate fibronectin/fibrinogen-binding integrins and redistribute collagen/laminin-binding integrins. This study demonstrates that the human skin/severe combined immunodeficient chimera provides a useful model to study events during human wound repair. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7694470

  10. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair.

    PubMed

    Huang, Sha; Lu, Gang; Wu, Yan; Jirigala, Enhe; Xu, Yongan; Ma, Kui; Fu, Xiaobing

    2012-04-01

    Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute to wound healing after skin injury. However, the role of BM-MSCs on repairing skin appendages in renewal tissues is incompletely explored. Moreover, most preclinical studies suggest that the therapeutic effects afforded by BM-MSCs transplantation are short-lived and relatively unstable. To assess whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery system can participate in cutaneous wound healing and sweat-gland repair in mice. For safe and effective delivery of BM-MSCs to wounds, epidermal growth factor (EGF) microspheres were firstly developed to both support cells and maintain appropriate stimuli, then cell-seeded microspheres were incorporated with biomimetic scaffolds and thus fabricated an engineered skin construct with epithelial differentiation and proliferative potential. The applied efficacy was examined by implanting them into excisional wounds on both back and paws of hind legs in mice. After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated wounds exhibited accelerated healing with increased re-epithelialization rates and less skin contraction. Furthermore, histological and immunofluorescence staining analysis revealed sweat glands-like structures became more apparent in BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM-MSCs were decreased gradually in later phases of healing progression. Our study suggests that BM-MSCs delivered by this EGF microspheres-based engineered skin model may be a promising strategy to repair sweat glands and improve cutaneous wound healing after injury and success in this study might provide a potential benefit for BM-MSCs administration clinically. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

    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.

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

    PubMed

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

    2015-01-01

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

  13. Cloning and expression of rabbit CCT subunits eta and beta in healing cutaneous wounds

    PubMed Central

    Satish, Latha; Johnson, Sandra; Abdulally, Adam; Post, J. Christopher; Ehrlich, Garth D.

    2010-01-01

    We have previously identified the CCT subunit eta as specifically reduced in healing fetal skin wounds by differential display, and observed that this reduction is not seen with any other CCT subunit. We now report the cloning and characterization of the cDNAs for rabbit CCT-eta and its closest evolutionary homolog, CCT-beta. Quantitative examination of CCT-eta and –beta message expression in healing fetal and adult wounds at 12 h post-injury confirms that CCT-eta mRNA is decreased in fetal wound tissues, but actually elevated in adult wound tissues. CCT-beta mRNA, in contrast, remains unchanged in both fetal and adult wound tissues. CCT-eta mRNA remains persistently elevated in healing adult wounds for 28 days following injury, whereas CCT-beta mRNA remains invariant throughout. CCT-eta protein is similarly increased, whereas CCT-beta protein remains unchanged. -smooth muscle actin (-SMA), a recognized substrate of CCT known to be important in integumentary wound healing, was also measured over the course of wound healing, and both mRNA and protein levels were elevated throughout the 28 days. PMID:20393890

  14. Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.

    PubMed

    Zheng, Zhong; Zhang, Xinli; Dang, Catherine; Beanes, Steven; Chang, Grace X; Chen, Yao; Li, Chen-Shuang; Lee, Kevin S; Ting, Kang; Soo, Chia

    2016-11-01

    In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-β1 nexus plays in fetal-type scarless skin repair. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

    Takzaree, Nasrin; Hadjiakhondi, Abbas; Hassanzadeh, Gholamreza; Rouini, Mohammad Reza; Manayi, Azadeh

    2016-04-01

    Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day's rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect.

  17. Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells.

    PubMed

    Hu, Melissa; Ludlow, David; Alexander, J Steven; McLarty, Jerry; Lian, Timothy

    2014-03-01

    To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues. Randomized controlled study. A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs. Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps. This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

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

    PubMed

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

    2016-06-15

    Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care. Copyright © 2016 by The American Association of Immunologists, Inc.

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

    PubMed

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

    2012-04-01

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

  20. Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

    PubMed Central

    2011-01-01

    Background Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. Methods Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet), DM (diabetic mice fed AIN 93 G purified rodent diet), VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet), and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet). After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. Results Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. Conclusions These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response. PMID:22088091

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

    PubMed

    Eo, Hyeyoon; Lim, Yunsook

    2016-02-01

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

  2. Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats.

    PubMed

    Gumel, Ahmad Mohammed; Razaif-Mazinah, Mohd Rafais Mohd; Anis, Siti Nor Syairah; Annuar, Mohamad Suffian Mohamad

    2015-07-08

    Wound management and healing in several physiological or pathological conditions, particularly when comorbidities are involved, usually proves to be difficult. This presents complications leading to socio-economic and public health burdens. The accelerative wound healing potential of biocompatible poly(3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) (PHA-PCL) composite hydrogel is reported herein. The biosynthesized PHA-PCL macromer was cross-linked with PEGMA to give a hydrogel. Twenty-four rats weighing 200-250 g each were randomly assigned to four groups of six rats. Rats in group I (negative control) were dressed with sterilized gum acacia paste in 10% normal saline while PEGMA-alone hydrogel (PH) was used to dress group II (secondary control) rats. Group III rats were dressed with PHAs-PCL cross-linked PEGMA hydrogel (PPH). For the positive control (group IV), the rats were dressed with Intrasite(®) gel. Biochemical, histomorphometric and immunohistomorphometric analyses revealed a significant difference in area closure and re-epithelialization on days 7 and 14 in PPH or Intrasite(®) gel groups compared to gum acacia or PEGMA-alone groups. Furthermore, wounds dressed with PPH or Intrasite(®) gel showed evident collagen deposition, enhanced fibrosis and extensively organized angiogenesis on day 14 compared to the negative control group. While improvement in wound healing of the PH dressed group could be observed, there was no significant difference between the negative control group and the PH dressed group in any of the tests. The findings suggested that topical application of PPH accelerated the rats' wound healing process by improving angiogenesis attributed to the increased microvessel density (MVD) and expressions of VEGF-A in tissue samples. Thus, PPH has been demonstrated to be effective in the treatment of cutaneous wounds in rats, and could be a potential novel agent in the management and acceleration of wound healing in humans and animals.

  3. Phospholipase Cε deficiency delays the early stage of cutaneous wound healing and attenuates scar formation in mice.

    PubMed

    Zhu, Xiaolong; Sun, Yue; Mu, Xin; Guo, Pan; Gao, Fei; Zhang, Jing; Zhu, Yunjuan; Zhang, Xianzhi; Chen, Lingling; Ning, Zhiwei; Bai, Yunfeng; Ren, Jiling; Man, Maoqiang; Liu, Peimei; Hu, Lizhi

    2017-02-26

    This study aimed to investigate the role of phospholipase Cε (PLCε) in the skin wound healing process. PLCε, an effect factor of Ras/Rap small G protein, plays a crucial role in skin inflammation by regulating inflammatory cytokines. Inflammatory responses are closely associated with wound healing. Full-thickness skin wounds were made in the PLCε knockout (KO) and wild-type (WT) mice, and the healing process was analyzed. The macroscopic wound closure rate declined in the PLCε KO mice on days 3, 4, and 5 after wounding, following the decreased expression of interleukin (IL)-6, chemokine (C-X-C motif) ligand (Cxcl)-1, Cxcl-2, and chemokine (C-C motif) ligand (Ccl) 20. The proliferation rate of epidermal keratinocytes was not affected by PLCε, but silencing of PLCε resulted in the delayed migration of keratinocytes. Moreover, the scars were found to be much smaller in the PLCε KO mice than in the WT mice. The mRNA expression of Ccl20, collagen (Col) 6a1, and Col17a1 decreased in the PLCε KO mice. These results were in agreement with a previous hypothesis that PLCε might delay the early stage of cutaneous wound healing by inhibiting the migration of keratinocytes, and decrease the expression of Col6a1, Col17a1, and Ccl20 by inhibiting the inflammatory response to reduce scar formation. This study shed light on a novel role of PLCε in wound healing and provided new therapeutic approaches to target PLCε for diminishing scar formation after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Emodin, an anthraquinone derivative from Rheum officinale Baill, enhances cutaneous wound healing in rats.

    PubMed

    Tang, Tian; Yin, Longwu; Yang, Jing; Shan, Guang

    2007-07-19

    Emodin (1, 3, 8-trihydroxy-6-methyl-anthraquinone) is an anthraquinone derivative from the roots of Rheum officinale Baill, a Chinese herb widely and traditionally used for wound healing. Our objective was to determine whether topically applied emodin enhanced repair of rats' excisional wounds and its possible mechanism. Wounds were treated with either topical emodin (100, 200 and 400 microg/ml), recombinant human epidermal growth factor (rhEGF, 10 microg/ml), or vehicle for 7 or 14 days consecutively. At day 5 postinjury, wounds receiving emodin (400 microg/ml) were significantly smaller than those treated with vehicle. Emodin treatments had markedly more hydroxyproline content in day 7 wounds and tensile strength in day 14 wounds than that of vehicle control. The level of transforming growth factor- beta(1) (TGF-beta(1)) in wound tissues assessed by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), showed a dose-dependent increase in emodin-treated wounds compared with vehicle. Western immunoblotting analysis of wound tissues for Smad 2, 3, 4, 7 protein expression showed increase in Smad 2, 3 in the emodin-treated wounds compared with vehicle. In contrast, a reduction of Smad 7 was observed in emodin-treated wounds compared with vehicle and no change of Smad 4. In summary, our results showed that emodin promoted repair of rats' excisional wounds via a complex mechanism involving stimulation of tissue regeneration and regulating Smads-mediated TGF-beta(1) signaling pathway.

  5. Effect of Recombinant Human Epidermal Growth Factor Against Cutaneous Scar Formation in Murine Full-thickness Wound Healing

    PubMed Central

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

    2010-01-01

    A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-β1 in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-β1, and mediating the formation of collagen. PMID:20358003

  6. Social facilitation of wound healing.

    PubMed

    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.

  7. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

    PubMed

    Liu, Lingying; Yu, Yonghui; Hou, Yusen; Chai, Jiake; Duan, Hongjie; Chu, Wanli; Zhang, Haijun; Hu, Quan; Du, Jundong

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing.

    PubMed

    Duscher, Dominik; Maan, Zeshaan N; Whittam, Alexander J; Sorkin, Michael; Hu, Michael S; Walmsley, Graham G; Baker, Hutton; Fischer, Lauren H; Januszyk, Michael; Wong, Victor W; Gurtner, Geoffrey C

    2015-11-01

    Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p < 0.05). HIF-1α knockout mice showed significantly impaired revascularization of ischemic tissue and wound closure and vascularity (p < 0.05). Loss of HIF-1α from fibroblasts results in delayed wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.

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

    NASA Astrophysics Data System (ADS)

    De Castro, Isabele Cardoso Vieira; Paraguassú, Gardênia Matos; dod Reis Júnior, João Alves; Xavier, Flávia Caló Aquino; Rodriguez, Tânia Tavares; Ramalho, Maria José Pedreira; Pinheiro, Antônio L. B.; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Hypothyroid has been associated to a disruption of the body's metabolism, including the healing process. Laser and LED have been shown to be effective on improving healing in many situations, but their benefit in the improvement of healing on hypothyroidism remains unknown. The aim of this study was to assess, morphometrically, the influence of Laser (λ660nm, 24 J/cm2, 40mW, CW, spot output= 4mm2;) and LED (λ630nm ± 20, 24 J/cm2, 150mW, CW, spot output= 0.5 cm2) on the wound healing of rats with Hypothyroid. Under general anesthesia, a standard surgical wound (1cm2) was created on the dorsum of 72 male Wistar rats divided into 6 groups of 12 animals each: G1: Euthyroid; G2: Euthyroid + Laser; G3: Euthyroid + LED; G4: Hypothyroid; G5: Hypothyroid + Laser and G6: Hypothyroid + LED. Hypothyroidism was induced in rats with propylthiouracil (0.05g/100mL) administered orally for 4 weeks and maintained until the end of the experiment. Rats were irradiated after surgery each 48h then killed after 7 and 14 days. Statistical analysis was performed using ANOVA and Tukey's test. Hypothyroid rats with phototherapy laser or LED showed significant less wound contraction than euthyroid's rats at the 7th day (p<0.05). At the 14th day, the longitudinal measurement was significantly higher in euthyroids (control and irradiated with laser) when compared to the hypothyroid group (p <0.05). This study has shown that hypothyroidism delays wound healing and Laser and LED photobiomodulation using 24 J/cm2 per session improved cutaneous wound healing in hypothyroid rats.

  11. Noninvasive red and near-infrared wavelength-induced photobiomodulation: promoting impaired cutaneous wound healing.

    PubMed

    Yadav, Anju; Gupta, Asheesh

    2017-01-01

    The innumerable intricacies associated with chronic wounds have made the development of new painless, noninvasive, biophysical therapeutic interventions as the focus of current biomedical research. Red and near-infrared light-induced photobiomodulation therapy appears to emerge as a promising drug-free approach for promoting wound healing, reduction in inflammation, pain and restoration of function owing to penetration power in conjunction with their ability to positively modulate the biochemical and molecular responses. This review will describe the physical properties of red and near-infrared light and their interaction with skin and highlight their efficacy of wound repair and regeneration. Near-infrared (800-830 nm) was found to be the most effective and widely studied wavelength range followed by red (630-680 nm) and 904 nm superpulsed light exhibiting beneficial photobiomodulatory effects on impaired dermal wound healing.

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

    PubMed

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

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-06-16

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

  15. Autologous bone marrow-derived cells with placental extract for healing excisional cutaneous wounds in animal model.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Das, Partha; Banerjee, Dibyajyoti; Roy, Subhasis; Datta, Uttam

    2013-04-01

    Topical wound-healing potential of autologous bone marrow-derived nucleated cells along with placental extract was evaluated in comparison with buffy coat of autologous blood on full-thickness cutaneous wounds in the thoracolumbar region of 15 clinically healthy New Zealand rabbits. Three wounds of 2 × 2 cm, one on the right side of the body and two on the left side of the midline were created on the dorsal lumbar region of each rabbit under xylazine-ketamine anaesthesia. The wounds of each animal were randomly assigned to one of the three treatments: topical application of autologous bone marrow-derived cells with placental extract (group I), application of buffy coat in the autologous plasma with placental extract (group II) and autologous plasma with placental extract as control (group III). Wounds were observed for 30 days macroscopically and for granulation tissue formation, histomorphological and histochemical evaluation. Time of appearance of granulation tissues and filling of wound beds were faster in group I followed by group II and group III animals, respectively. Histomorphological findings exhibited an earlier disappearance of inflammatory reaction, better epithelialisation, significantly maximum neovascularisation, fibroplasias and collagenation in group I followed by group II and group III animals, respectively. Histochemical findings also depicted maximum number of robust, thick, interwoven type of collagen fibres, stout, highly tortuous and interwoven network of elastin fibres and numerous mesh war form of reticulin fibres within the dermal component were present in group I when compared with group II and III animals. Experiment conclude that single application of autologous bone marrow-nucleated cells with placental extract topically could be a novel option for faster healing in complicated non healing wounds both in human beings and animals. © 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines

  16. Keratinocyte-targeted overexpression of the glucocorticoid receptor delays cutaneous wound healing.

    PubMed

    Sanchis, Ana; Alba, Lorena; Latorre, Víctor; Sevilla, Lisa M; Pérez, Paloma

    2012-01-01

    Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC) analogs, which act through the ligand-dependent transcription factor GC-receptor (GR). GR function is exerted through DNA-binding-dependent and -independent mechanisms, classically referred to as transactivation (TA) and transrepression (TR). Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown. We evaluated skin wound healing in transgenic mice with keratinocyte-restricted expression of either wild type GR or a mutant GR that is TA-defective but efficient in TR (K5-GR and K5-GR-TR mice, respectively). Our data show that at days (d) 4 and 8 following wounding, healing in K5-GR mice was delayed relative to WT, with reduced recruitment of granulocytes and macrophages and diminished TNF-α and IL-1β expression. TGF-β1 and Kgf expression was repressed in K5-GR skin whereas TGF-β3 was up-regulated. The re-epithelialization rate was reduced in K5-GR relative to WT, as was formation of granulation tissue. In contrast, K5-GR-TR mice showed delays in healing at d4 but re-established the skin breach at d8 concomitant with decreased repression of pro-inflammatory cytokines and growth factors relative to K5-GR mice. Keratinocytes from both transgenic mice closed in vitro wounds slower relative to WT, consistent with the in vivo defects in cell migration. Overall, the delay in the early stages of wound healing in both transgenic models is similar to that elicited by systemic treatment with dexamethasone. Wound responses in the transgenic keratinocytes correlated with reduced ERK activity both in vivo and in vitro. We conclude that the TR function of GR is sufficient for negatively regulating early stages of wound closure, while TA by GR is required for delaying later stages of healing.

  17. Keratinocyte-Targeted Overexpression of the Glucocorticoid Receptor Delays Cutaneous Wound Healing

    PubMed Central

    Sanchis, Ana; Alba, Lorena; Latorre, Víctor; Sevilla, Lisa M.; Pérez, Paloma

    2012-01-01

    Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC) analogs, which act through the ligand-dependent transcription factor GC-receptor (GR). GR function is exerted through DNA-binding-dependent and –independent mechanisms, classically referred to as transactivation (TA) and transrepression (TR). Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown. We evaluated skin wound healing in transgenic mice with keratinocyte-restricted expression of either wild type GR or a mutant GR that is TA-defective but efficient in TR (K5-GR and K5-GR-TR mice, respectively). Our data show that at days (d) 4 and 8 following wounding, healing in K5-GR mice was delayed relative to WT, with reduced recruitment of granulocytes and macrophages and diminished TNF-α and IL-1β expression. TGF-β1 and Kgf expression was repressed in K5-GR skin whereas TGF-β3 was up-regulated. The re-epithelialization rate was reduced in K5-GR relative to WT, as was formation of granulation tissue. In contrast, K5-GR-TR mice showed delays in healing at d4 but re-established the skin breach at d8 concomitant with decreased repression of pro-inflammatory cytokines and growth factors relative to K5-GR mice. Keratinocytes from both transgenic mice closed in vitro wounds slower relative to WT, consistent with the in vivo defects in cell migration. Overall, the delay in the early stages of wound healing in both transgenic models is similar to that elicited by systemic treatment with dexamethasone. Wound responses in the transgenic keratinocytes correlated with reduced ERK activity both in vivo and in vitro. We conclude that the TR function of GR is sufficient for negatively regulating early stages of wound closure, while TA by GR is required for delaying later stages of healing. PMID:22235328

  18. Adenoviral gene transfer of an NF-kappaB super-repressor increases collagen deposition in rodent cutaneous wound healing.

    PubMed

    Schreiber, Jeffrey; Efron, Philip A; Park, Julie E; Moldawer, Lyle L; Barbul, Adrian

    2005-11-01

    The transcription factor nuclear factor-kappaB (NF-kappaB) plays an essential role in inflammation. To date, no studies have investigated the effect of inhibiting NF-kappaB-mediated inflammation on normal cutaneous wound healing. We tested this by locally administering an adenovirus recombinant that constitutively expresses a super-repressor isoform of inhibitory-kappaB (IkappaB) into rats undergoing a well-established model of dorsal wound healing. Seventy-two Sprague-Dawley rats underwent insertion of a sponge-pump construct into a dorsal subcutaneous pocket. One group of rats received pumps filled with the adenovirus expressing I-kappaB (rAd-Ikappab), a second group received pumps filled with adenovirus expressing green fluorescent protein (GFP) (rAd-gfp), and a third received pumps filled with normal saline (NS). Rats were killed in groups of 6 on days 1, 3, 5 and 7 postoperation. The wound fluid was analyzed for nitrite/nitrate (NOx) and tumor necrosis factor-alpha (TNF-alpha) concentrations. The wound fluid was assayed for hydroxyproline (OHP) content, an index of reparative collagen deposition. Administration of rAd-Ikappab for 7 days resulted in higher collagen deposition (OHP) compared with the rAd-gfp and NS groups. NOx levels were significantly higher in the rAd-gfp group on day 1 and marginally so on day 5. TNF-alpha quantitation analysis found no significant difference among the 3 groups. IkappaB expression through an adenoviral vector in the cutaneous wound may improve rodent healing, as shown by increased collagen deposition, through decreased inflammation. This mechanism appears to be TNF-alpha independent. Inhibition of NF-kappaB may reduce inflammation by reducing the local NOx concentrations.

  19. Biomodulative effects of polarized light on the healing of cutaneous wounds on nourished and undernourished Wistar rats.

    PubMed

    Pinheiro, Antonio Luiz Barbosa; Meireles, Gyselle Cynthia Silva; Carvalho, Carolina Montagn; de Barros Vieira, Alessandro Leonardo; dos Santos, Jean Nunes; Ramalho, Luciana Maria Pedreira

    2006-10-01

    This study aimed to evaluate, by light microcopy, the differences in healing process of cutaneous wounds on nourished or undernourished rats following illumination by polarized light (lambda400-2000 nm) with 20 or 40 J/cm(2). There are some reports in the literature on different effects of polarized light on wound healing. Amongst the factors that interfere with wound healing one is the nutritional status of the subject. Thirty nourished or undernourished Wistar rats had one standardized surgical wound created on the dorsum and were divided into six groups: group 1, control (standard diet); group 2, control (Northeastern Brazilian Basic Diet [DBR]); group 3, standard diet + polarized light (20 J/cm(2)); group 4, standard diet + polarized light (40 J/cm(2)); group 5, DBR + polarized light (20 J/cm(2)); group 6, DBR + polarized light (40 J/cm(2)). The first application of treatment was carried out immediately after wounding and repeated every 24 h during 7 days. The animals were sacrificed, and specimens were taken and routinely processed to wax, cut, and stain with hematoxylin and eosin (H&E) and Sirius Red. These were then analyzed under light microscopy. The analysis included re-epitheliialization, inflammatory infiltrate, and fibroblastic proliferation. Sirius Red-stained slides were used to perform descriptive analysis of collagen. The analysis of the results showed better results in these groups illuminated with 20 J/cm(2). It is concluded that nutritional status influenced the progression of the healing process as well as the quality of the healed tissue, and that the use of polarized light resulted in a positive biomodulatory effect.

  20. Mechanical Unloading Impairs Keratinocyte Migration and Angiogenesis During Cutaneous Wound Healing

    DTIC Science & Technology

    2008-02-01

    Research, Fort Sam Houston, Texas; and 4Center for Wound Healing and Tissue Regeneration, College of Dentistry , University of Illinois at Chicago...exhibited significant hypotension and bradycardia, en- hanced vasoconstriction , and vascular resistance (35, 58), in- dicating that variations in...enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism. Am J Physiol Heart Circ Physiol 288

  1. Negative regulation of GADD34 on myofibroblasts during cutaneous wound healing.

    PubMed

    Liu, Lintao; Nishio, Naomi; Ito, Sachiko; Tanaka, Yuriko; Isobe, Ken-ichi

    2014-01-01

    The growth arrest and DNA damage-inducible protein, GADD34, has been proved to be involved in TGF-β signaling pathway and correlates with cell death, which are two important mechanisms in regulating myofibroblast differentiation and apoptosis during tissue repair. But roles of GADD34 in myofibroblasts differentiation and apoptosis remain unknown. To investigate the function of GADD34 in these processes, we subjected WT and GADD34(-/-) mice to dermal wound healing. Here we show that GADD34(-/-) mice exhibited accelerated wound closure compared with WT mice. In addition, GADD34(-/-) mice showed increased number of myofibroblasts, elevated collagen production, and decreased cell apoptosis during wound healing. Moreover, we found that GADD34(-/-) mice showed increased phosphorylation of Smad3 and lower level of cleaved caspase-3. Thus these results indicate that GADD34 appears to suppress myofibroblast differentiation through inhibiting Smad3-dependent TGFβ signal pathway and promote its apoptosis by activating caspase-3 pathway.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

    Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed Central

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

    2014-01-01

    Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here we report a skin-like electronics platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of ‘epidermal’ electronics system in a realistic, clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management. PMID:24668927

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

    DOE PAGES

    Hattori, Yoshiaki; Falgout, Leo; Lee, Woosik; ...

    2014-03-26

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

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

    SciTech Connect

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

    2014-03-26

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

  7. Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation

    PubMed Central

    Nardini, Christine; Devescovi, Valentina; Liu, Yuanhua; Zhou, Xiaoyuan; Lu, Youtao; Dent, Jennifer E.

    2016-01-01

    Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Current therapies attempt to control the immune response to limit degeneration, commonly promoting immunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) and it has recently been proposed locally for its therapeutic potential on severely injured areas. As the early stages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored the potential of this early signal to spread, over time, beyond the stimulation district and become systemic, to impact on distributed or otherwise unreachable injured areas. We report in a model of arthritis in rats how stimulations delivered in the subcutaneous dorsal tissue result, over time, in the control and healing of the degeneration of the paws’ joints, concomitantly with the systemic activation of wound healing phenomena in blood and in correlation with a more eubiotic microbiome in the gut intestinal district. PMID:28008941

  8. Brazilian red propolis improves cutaneous wound healing suppressing inflammation-associated transcription factor NFκB.

    PubMed

    Corrêa, Flavia Regina Sobreira; Schanuel, Fernanda Seabra; Moura-Nunes, Nathalia; Monte-Alto-Costa, Andréa; Daleprane, Julio Beltrame

    2017-02-01

    The use of natural products in wound healing has been extensively studied in the context of complementary and alternative medicine. Propolis, a natural product, is a polyphenol-rich resin used for this purpose. This study aimed to investigate the effect of Brazilian Red Propolis Extract (BRPE) on inflammation and wound healing in mice, using a tissue repair model. The BRPE polyphenol content was analyzed by liquid chromatography coupled to mass spectrometry (LC/MS). A full-thickness excision lesion was created, and mice were treated orally with daily doses of vehicle solution (water-alcohol solution containing 2% of ethanol, control group) or 100mg/kg of BRPE (P100 group) during nine consecutive days. BRPE chemical composition analysis showed that this complex matrix contains several phenolic compounds such as phenolic acids, phenolic terpenes and flavonoids (especially catechins, flavonols, chalcones, isoflavones, isoflavans, pterocarpans and bioflavonoids). After BRPE administration, it was observed that, when compared to the control group, P100 group presented faster wound closure (p<0.001); less neutrophils per mm(2) (p<0.05) and macrophages (p<0.01) in tissue analyses, down regulation of the inflammatory transcription factor pNF-κB protein expression, and reduced production of inflammatory cytokine, such as TGF-β, TNF-α (p<0.0001), and IL-6 (p<0.001). These findings suggest a positive role of BRPE oral administration in the wound healing process via suppressing the inflammatory response during tissue repair.

  9. Delayed cutaneous wound healing in Fam129b/Minerva-deficient mice.

    PubMed

    Oishi, Hisashi; Itoh, Susumu; Matsumoto, Ken; Ishitobi, Hiroyuki; Suzuki, Rumiko; Ema, Masatsugu; Kojima, Takahiro; Uchida, Kazuhiko; Kato, Mitsuyasu; Miyata, Toshio; Takahashi, Satoru

    2012-12-01

    A recent integrative analysis using a phosphoproteomic approach identified FAM129B, also known as MINERVA, as a downstream effector of the MAP kinase pathway in human melanoma cells. FAM129B protein, which is a member of a small family of proteins, was also found to suppress TNFα/cycloheximide-induced apoptosis in HeLa cells. To investigate the physiological functions of Fam129b in vivo, we generated gene-targeted Fam129b-mutant mice in which, the amino terminal coding exon was replaced by lacZ. We found that homozygous mutant mice are viable and fertile and that Fam129b is considerably expressed in most of the epidermal keratinocytes of both embryonic and adult mice. Although no gross defect was observed in the skin of the Fam129b-deficient mice, wound healing subsequent to skin puncturing was significantly delayed. Furthermore, overexpression of Fam129b promoted HaCaT cell motility in an N-terminal pleckstrin homology domain-dependent manner, but not proliferation. Microarray analysis of the Fam129b transfectant exhibited substantial upregulation of several genes related to wound repair and cell motility. These results suggest that expression of Fam129b in epidermal keratinocytes accompanied by alteration of wound healing-related gene expression is necessary for regulation of cell motility and thereby, contributes to the appropriate wound healing process.

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

    PubMed

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

    2014-06-01

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

  11. Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns.

    PubMed Central

    Gilpin, D A; Barrow, R E; Rutan, R L; Broemeling, L; Herndon, D N

    1994-01-01

    OBJECTIVE: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. SUMMARY BACKGROUND DATA: Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children. METHODS: Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site. RESULTS: Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Activation of the δ-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration

    PubMed Central

    Bigliardi, P L; Neumann, C; Teo, Y L; Pant, A; Bigliardi-Qi, M

    2015-01-01

    BACKGROUND AND PURPOSE In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in δ-opioid receptor knockout mice (DOPr–/–). Hence, we investigated δ-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on the migratory behaviour of keratinocytes. EXPERIMENTAL APPROACH Expression levels of desmosomal cadherins in wild-type and DOPr–/– mice, and the morphology of intercellular adhesion in human keratinocytes were analysed by immunofluorescence. To investigate the δ-opioid receptor activation pathway, protein expression was studied using Western blot and its effect on cellular migration determined by in vitro live cell migration recordings from human keratinocytes. KEY RESULTS Expression of the desmosomal cadherins, desmogleins 1 and 4, was up-regulated in skin from DOPr–/– mice, and down-regulated in δ-opioid receptor-overexpressing human keratinocytes. The localization of desmoplakin expression was rearranged from linear arrays emanating from cell borders to puncta in cell periphery, resulting in less stable intercellular adhesion. Migration and wound recovery were enhanced in human keratinocyte monolayers overexpressing δ-opioid receptors in vitro. These δ-opioid receptor effects were antagonized by specific PKCα/β inhibition indicating they were mediated through the PKC signalling pathway. Finally, cells overexpressing δ-opioid receptors developed characteristically long but undirected protrusions containing filamentous actin and δ-opioid receptors, indicating an enhanced migratory phenotype. CONCLUSION AND IMPLICATIONS Opioid receptors affect intercellular adhesion and wound healing mechanisms, underlining the importance of a cutaneous neuroendocrine system in wound healing and skin homeostasis. LINKED ARTICLES This article is part of a themed section on

  16. Activation of the δ-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration.

    PubMed

    Bigliardi, P L; Neumann, C; Teo, Y L; Pant, A; Bigliardi-Qi, M

    2015-01-01

    In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in δ-opioid receptor knockout mice (DOPr(-/-) ). Hence, we investigated δ-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on the migratory behaviour of keratinocytes. Expression levels of desmosomal cadherins in wild-type and DOPr(-/-) mice, and the morphology of intercellular adhesion in human keratinocytes were analysed by immunofluorescence. To investigate the δ-opioid receptor activation pathway, protein expression was studied using Western blot and its effect on cellular migration determined by in vitro live cell migration recordings from human keratinocytes. Expression of the desmosomal cadherins, desmogleins 1 and 4, was up-regulated in skin from DOPr(-/-) mice, and down-regulated in δ-opioid receptor-overexpressing human keratinocytes. The localization of desmoplakin expression was rearranged from linear arrays emanating from cell borders to puncta in cell periphery, resulting in less stable intercellular adhesion. Migration and wound recovery were enhanced in human keratinocyte monolayers overexpressing δ-opioid receptors in vitro. These δ-opioid receptor effects were antagonized by specific PKCα/β inhibition indicating they were mediated through the PKC signalling pathway. Finally, cells overexpressing δ-opioid receptors developed characteristically long but undirected protrusions containing filamentous actin and δ-opioid receptors, indicating an enhanced migratory phenotype. Opioid receptors affect intercellular adhesion and wound healing mechanisms, underlining the importance of a cutaneous neuroendocrine system in wound healing and skin homeostasis. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

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

    PubMed

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

    2014-01-01

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

  18. Wound Healing and Care

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness 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 ...

  19. Biomodulative effects of visible and IR laser light on the healing of cutaneous wounds of nourished and undernourished Wistar rats.

    PubMed

    Pinheiro, Antonio Luiz Barbosa; Meireles, Gyselle Cynthia Silva; Carvalho, Carolina Montagn; Ramalho, Luciana Maria Pedreira; dos Santos, Jean Nunes

    2009-12-01

    We evaluated histologically the differences in the healing of cutaneous wounds on nourished or undernourished rats following laser phototherapy (LPT) (20 or 40 J/cm2). Wound healing occurs due to a competitive mechanism between the synthesis and lysis of collagen. Any factor that increases the lysis or reduces the synthesis of collagen may change the healing process. Nutritional deficiencies have a great effect on wound healing. Fifty nourished or undernourished Wistar rats had one standardized wound created on the dorsum and were divided into 10 subgroups: Control (standard diet); Control [Northeastern Brazilian basic diet (DBR)]; Standard diet+LPT (lambda635 nm; spatial average energy fluence (SAEF) 20 J/cm2); Standard diet+LPT (lambda635 nm; SAEF 40 J/cm2); Standard diet+LPT (lambda780 nm; SAEF 20 J/cm2); Standard diet+LPT (lambda780 nm; SAEF 40 J/cm2); DBR+LPT (lambda635 nm; SAEF 20 J/cm2); DBR+LPT (lambda635 nm; SAEF 40 J/cm2); DBR+LPT (lambda780 nm; SAEF 20 J/cm2); DBR+LPT (lambda780 nm; SAEF 40 J/cm2). The first application of the treatment was carried out immediately and repeated daily for seven days. The specimens were routinely processed to wax, cut, stained with H&E and Sirius Red stains, and analyzed using light microscopy. The analyses included re-epithelization, inflammatory infiltrate, and fibroblastic proliferation. Sirius Red stained slides were used to perform descriptive analyses of the collagen fibers. The results showed that LPT with lambda635 wavelength was more effective for the treatment of undernourished subjects, treated with either LPT with lambda730 nm with SAEF of 20 J/cm2 or lambda780 nm with SAEF of 40 J/cm2. Nutritional status influenced the progression of the healing process as well as the quality of the healed tissue. In addition, the use of both wavelengths resulted in a positive biomodulatory effect on both nourished and undernourished subjects.

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

    PubMed

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

    2014-01-01

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

  1. Effectiveness of Changing the Application of Japanese Honey to a Hydrocolloid Dressing in Between the Inflammatory and Proliferative Phases on Cutaneous Wound Healing in Male Mice.

    PubMed

    Mukai, Kanae; Komatsu, Emi; Yamanishi, Misa; Hutakuchi, Misako; Kanzaka, Kayo; Uno, Yuka; Yamazaki, Shizuka; Kato, Shizuka; Yamamoto, Tomomi; Hattori, Mayumi; Nakajima, Yukari; Urai, Tamae; Asano, Kimi; Murakado, Naoko; Okuwa, Mayumi; Nakatani, Toshio

    2017-01-01

    The aim of this study was to investigate the effects of changing the application of Japanese honey to a hydrocolloid dressing (HCD) in between the inflammatory and proliferative phases on cutaneous wound healing in 8-week-old, BALB/cCrSlc male mice. Mice were divided into 4 groups: acacia honey followed by a HCD, buckwheat flour honey followed by a HCD, Chinese milk vetch honey followed by a HCD, and a HCD alone (control group). All mice received 2 full-thickness wounds on both sides of the dorsum using a Disposable Biopsy Punch. The wounds of the control group were covered with a HCD, whereas wounds in the other groups were treated with 0.1 mL of the relevant type of honey until day 3 post-wound and then were covered with a HCD from days 4 to 14. In the experimental groups, the wound area ratio was significantly smaller in the inflammatory phase but significantly larger in the proliferative phase. Reepithelialization, collagen deposition, and wound contraction were significantly delayed compared with those in the control group. The re-expansion of the wounds in the proliferative phase could not be prevented, and reepithelialization, collagen deposition, and wound contraction were delayed compared with those upon the use of a HCD. The study's authors concluded that these methods do not promote cutaneous wound healing better than the use of a HCD alone.

  2. Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing.

    PubMed

    Singh, Purva; Chen, Chun; Pal-Ghosh, Sonali; Stepp, Mary Ann; Sheppard, Dean; Van De Water, Livingston

    2009-01-01

    The wound microenvironment comprises constituents, such as the extracellular matrix (ECM), that regulate with temporal and spatial precision, the migratory, proliferative, and contractility of wound cells. Prompt closure of the wound is an early and critical phase of healing and beta1 integrins are important in this process. We previously reported a marked increase in integrin alpha9beta1 expression in epidermal keratinocytes in cutaneous and corneal wounds. However, the functional role of keratinocyte alpha9beta1 during re-epithelialization is unknown and analysis has been precluded by the lethal phenotype of integrin alpha9beta1 knockout mice. We now report that in conditional integrin alpha9 knockout (K14-alpha9 null) mice, normal proliferation occurs in epidermal keratinocytes and corneal basal cells. Normal epidermal keratinocyte morphology is also retained. However, corneal basal cell morphology and epithelial thickness are altered, suggesting that loss of integrin alpha9beta1 results in abnormal corneal differentiation. In cutaneous wounds, the number of proliferating epidermal keratinocytes is significantly reduced in K14-alpha9 null mice compared with alpha9(fl/-) mice, but not in Cre (control) mice. The decreased keratinocyte proliferation observed in K14-alpha9 null mice negatively impacts healing, resulting in a thinner migrating epithelium, demonstrating that alpha9beta1 is crucial for efficient and proper re-epithelialization during cutaneous wound healing.

  3. Healing activity of proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis in a cutaneous wound excision model.

    PubMed

    Freitas, K M; Barcelos, L S; Caliari, M V; Salas, C E; Lopes, M T P

    2017-10-05

    The proteolytic enzymes from Vasconcellea cundinamarcensis have demonstrated efficacy to accelerate healing of skin lesions. We report here the efficacy of the proteolytic fraction - P1G10 during repair of excisional wounds in rodent model and analyze possible mediators involved. Using 0.05% P1G10 we observed on day 3rd increased wound contraction accompanied by an increase in activated neutrophils and VEGF relative to the control. On day 7th neutrophils returned to normal levels, and at 0.01% P1G10, an increase in NAG activity used to monitor monocyte/macrophage, was observed. On the other hand, on day 7th, we observed a decrease in TGF-β at 0.05% P1G10, accompanied by an increased transformation of the latent TGF-β to its active form. Also, on day 7th a reduction in MMP-9 activity and the number of apoptotic cells was observed along with an increase in fibroblast levels. Morphometrically, it appears that treatment with P1G10 accelerates the decline of initial inflammatory phase and reduces some unwanted effects likely caused by remaining TGF-β or MMPs, thus enhancing the quality of scar. Overall, these data suggest that the active proteolytic fraction P1G10 enhances the efficacy of repair in excisional cutaneous wounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Wound healing in the 21st century.

    PubMed

    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. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Action of AlGaInP laser and high frequency generator in cutaneous wound healing. A comparative study.

    PubMed

    Sousa, Rayssilane Cardoso de; Maia Filho, Antônio Luiz Martins; Nicolau, Renata Amadei; Mendes, Lianna Martha Soares; Barros, Talvany Luis de; Neves, Silvana Maria Véras

    2015-12-01

    To evaluate in a macroscopic, histological and histomorphometric manner the healing process of cutaneous wounds in mice. The sample consisted of 40 male mice and was divided in four groups: 1st group (control, n=10), 2nd group (High Frequency Generator - HF, the maximum amplitude range, 120s, n=10), 3rd group (AlGaInP Laser 660 nm, 30mW power, 5 J/cm2, applying scan mode, 120s, n=10) and 4thgroup (AlGaInP Laser 660 nm, 30 mW power, 8 J/cm2, applying scan mode, n=10). The surgical incision was made with an 8 mm diameter punch perpendicularly to the back of the animal. The statistical analysis was achieved by the statistical test One Way Anova post hoc Tukey Test and significance at p<0.05 in GraphPad Prism program. It was observed that in the acute phase the AlGaInP Laser at 5 J/cm2 provided a greater stimulus to healing, and both lasers were effective in the remodeling phase. The AlGaInP lasers from 5 J/cm2 to 8 J/cm2 showed better biomodulatory results in the acute and remodeling phases respectively, however, the HF was less effective than the laser, providing significant benefits only in the acute phase of tissue repair.

  6. NGF Accelerates Cutaneous Wound Healing by Promoting the Migration of Dermal Fibroblasts via the PI3K/Akt-Rac1-JNK and ERK Pathways

    PubMed Central

    Chen, Ji-Cai; Lin, Bei-Bei; Hu, Hou-Wen; Lin, Cai; Jin, Wen-Yang; Zhang, Fa-Biao; Zhu, Yan-An; Lu, Cai-Jiao; Wei, Xiao-Jie; Chen, Rui-Jie

    2014-01-01

    As a well-known neurotrophic factor, nerve growth factor (NGF) has also been extensively recognized for its acceleration of healing in cutaneous wounds in both animal models and randomized clinical trials. However, the underlying mechanisms accounting for the therapeutic effect of NGF on skin wounds are not fully understood. NGF treatment significantly accelerated the rate of wound healing by promoting wound reepithelialization, the formation of granulation tissue, and collagen production. To explore the possible mechanisms of this process, the expression levels of CD68, VEGF, PCNA, and TGF-β1 in wounds were detected by immunohistochemical staining. The levels of these proteins were all significantly raised in NGF-treated wounds compared to untreated controls. NGF also significantly promoted the migration, but not the proliferation, of dermal fibroblasts. NGF induced a remarkable increase in the activity of PI3K/Akt, JNK, ERK, and Rac1, and blockade with their specific inhibitors significantly impaired the NGF-induced migration. In conclusion, NGF significantly accelerated the healing of skin excisional wounds in rats and the fibroblast migration induced by NGF may contribute to this healing process. The activation of PI3K/Akt, Rac1, JNK, and ERK were all involved in the regulation of NGF-induced fibroblast migration. PMID:25006578

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

    PubMed

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

    2006-01-01

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

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

    PubMed

    Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

    2016-01-01

    Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was <12% even at 37°C and <5% at 4°C within 1 month. In vitro skin permeation, skin distribution, and burn wound healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.

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

    PubMed Central

    Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

    2016-01-01

    Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was <12% even at 37°C and <5% at 4°C within 1 month. In vitro skin permeation, skin distribution, and burn wound healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress. PMID:27486319

  10. Clinical and histological findings of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans) housed in unheated outdoor enclosures.

    PubMed

    Negrini, Joao; Ginel, Pedro J; Novales, Manuel; Guerra, Rafael; Mozos, Elena

    2016-10-01

    Cutaneous wounds are common in chelonians. The clinical and histological features of wound healing in these species are not well described and this prevents evaluation of new therapies. To describe clinical and histopathological features of cutaneous wound healing in the red-eared slider turtle (Trachemys scripta elegans). Twenty four healthy adult females housed in outdoor facilities with free access to water and exposed to daily variations in temperature. Full thickness 6 mm skin biopsy punch wounds were created in the rear limbs. The turtles were assigned to Group 1 (n = 12 for clinical evaluation) and Group 2 (n = 12 for microscopic study). Group 1 was photographed on Day 1 and weekly, until 28 days post wounding. Wound retraction was expressed as the percentage of perimeter reduction. For Group 2, three skin wounds were sampled at 2, 7, 14, 21, 28, 42, 60 and 135 days post wounding for histological study. The avidin-biotin-peroxidase (ABC) staining method was used to evaluate five commercial antibodies. Wound contraction was limited; crust persisted at least 28 days. Re-epithelialization was complete by Day 14 in many animals; active inflammation persisted until 28 days; connective tissue re-constitution and remodelling was achieved from 42 to 135 days. Antibodies AE1/AE3, Factor VIII, MAC 387, CD3 and NCL-MSA showed cross reactivity with the cell counterpart in turtle tissues. Second intention wound healing progressed slowly and with an indolent behaviour. Microscopically there was marked overlapping of the inflammatory and proliferative phases over a long time period. © 2016 ESVD and ACVD.

  11. Saliva and wound healing.

    PubMed

    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.

  12. Metalloproteinases and Wound Healing

    PubMed Central

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

    2015-01-01

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

  13. Transcription factor binding site analysis identifies FOXO transcription factors as regulators of the cutaneous wound healing process.

    PubMed

    Roupé, Karl Markus; Veerla, Srinivas; Olson, Joshua; Stone, Erica L; Sørensen, Ole E; Hedrick, Stephen M; Nizet, Victor

    2014-01-01

    The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors during wound healing in vivo in both human and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin was observed, with FOXO3 having the highest expression level in non wounded skin. Impaired re-epithelialization was found in cultures of primary human keratinocytes expressing a constitutively active variant of FOXO3. Conversely knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo mouse model with FOXO3 knockout mice we detected significantly accelerated wound healing. This article illustrates that the proposed approach is a viable method for identifying important regulators of complex biological processes using in vivo samples. FOXO3 has not previously been implicated as an important regulator of wound healing and its exact function in this process calls for further investigation.

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

    PubMed

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

    2016-03-01

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

  15. Stress and wound healing.

    PubMed

    Cohen, I

    1979-01-01

    An experiment was performed to compare the effects of stressors--cold, heat and noise--on primary wound activity (i.e., wound closure in the first 24 h after wound infliction) and on rate of healing in mice. A significant correlation was found between reduced primary wound activity and a faster rate of healing. Conversely, a correlation was found between relatively greater primary wound activity and a slower rate of healing. A possible explanation of this correlation is a compensatory mechanism inherent to the skin healing process. This mechanism is visualized as (1) stress exposure affecting the skin by (a) causing it to become thinner and tauter and (b) causing it to have less elastic recoil; therefore, (2) when a square wound is produced in stressed skin, (a) the wound does not recoil readily or gapes soon after cutting and (b) a longer wound perimeter results. Because there is evidence that rate of healing is governed by cells on the wound perimeter, the greater the perimeter, the greater the number of cells that will undergo rapid mitosis and the faster will be the rate of healing. Therefore, stressed skin will heal at a faster rate, compensating for the loss of elasticity and cellular depletion caused by stress. This study is of interest to anthropology because it deals with dynamic adaptation, trying to grasp the meaning of the elusive endocrine interface between environmental stimulation and a measurable physical entity like healing. This work may have revealed a functional complex that is common to the healing of all mammalian skin, whereby retarding effects of stress on the healing process are obviated.

  16. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

    PubMed

    Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

    2017-03-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

  17. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

    PubMed Central

    Shin, Jihyun; Yang, Soo Jin

    2016-01-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. PMID:28211759

  18. Human platelet-rich plasma- and extracellular matrix-derived peptides promote impaired cutaneous wound healing in vivo.

    PubMed

    Demidova-Rice, Tatiana N; Wolf, Lindsey; Deckenback, Jeffry; Hamblin, Michael R; Herman, Ira M

    2012-01-01

    Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.

  19. Wound healing in urology.

    PubMed

    Ninan, Neethu; Thomas, Sabu; Grohens, Yves

    2015-03-01

    Wound healing is a dynamic and complex phenomenon of replacing devitalized tissues in the body. Urethral healing takes place in four phases namely inflammation, proliferation, maturation and remodelling, similar to dermal healing. However, the duration of each phase of wound healing in urology is extended for a longer period when compared to that of dermatology. An ideal wound dressing material removes exudate, creates a moist environment, offers protection from foreign substances and promotes tissue regeneration. A single wound dressing material shall not be sufficient to treat all kinds of wounds as each wound is distinct. This review includes the recent attempts to explore the hidden potential of growth factors, stem cells, siRNA, miRNA and drugs for promoting wound healing in urology. The review also discusses the different technologies used in hospitals to treat wounds in urology, which make use of innovative biomaterials synthesised in regenerative medicines like hydrogels, hydrocolloids, foams, films etc., incorporated with growth factors, drug molecules or nanoparticles. These include surgical zippers, laser tissue welding, negative pressure wound therapy, and hyperbaric oxygen treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Blockade of interaction of alpha9 integrin with its ligands hinders the formation of granulation in cutaneous wound healing.

    PubMed

    Nakayama, Yosuke; Kon, Shigeyuki; Kurotaki, Daisuke; Morimoto, Junko; Matsui, Yutaka; Uede, Toshimitsu

    2010-06-01

    The wound healing is a complex process consisting of inflammatory reaction, proliferation of mesenchymal cells, and formation and contraction of granulation tissue. The integrin receptors have crucial roles in this process. Recently, alpha9 integrin has also been detected on keratinocytes within wound sites. However, its functional significance at various wound healing processes was not fully elucidated. To address the role of alpha9 integrin in wound healing process, we made a full-thickness skin excisional wound and treated mice with anti-alpha9 integrin antibody. It has been shown that wound healing process was divided into three distinct phases: first, the re-epithelialization phase, second, the phase of granulation tissue formation, and finally the phase of contraction of granulation tissue. We found that contraction of granulation tissue was not impaired by blocking the interaction of alpha9 integrin with its ligands, indicating that alpha9 integrin is not involved in myofibroblast differentiation. It is noteworthy that the formation of granulation tissue, as characterized by dense vimentin and CD31-positive area, was impaired. The hindrance of granulation tissue formation is because of the inhibition of adhesion and migration of alpha9 integrin-positive dermal fibroblasts. In conclusion, alpha9 integrin is involved in the formation of granulation tissue through regulating migration and adhesion of dermal fibroblasts in the full-thickness skin excisional wound model.

  1. Wound Healing of Cutaneous Sulfur Mustard Injuries: Strategies for the Development of Improved Therapies

    DTIC Science & Technology

    2005-01-05

    of much greater potency that would likely be very efficacious if used early in the lesion development stage, such as betamethasone dipropionate ...Hunt Valley, MD. pp. 1179- 1186. 108. Miller TL, Graham JS, Hayes TL, Reid FM. Stability of sulfur mustard in vehicles suitable for cutaneous

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

    PubMed Central

    2013-01-01

    Background Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. The aim of this study was to evaluate clinical and histopathological alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rat. Methods In present study 24 Wister -albino rats weighing 150–200 g were selected and divided to two treatment groups as Nitrofurazone ointment (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM) route. Furthermore, upon preparation of dorsal region of the animal for surgery, a piece of full-thickness skin removed (2 × 2 cm). In order to comparing wounds healing clinically and histologically, once every four days from the commencement, the wounds were photographed and the healed surface was measured by Scion image software. Result The clinical findings indicated that the Kombucha fungus resulted in precipitating healing than Nitrofurazone; however, it was not significant (p > 0.05). In order to pathological comparing of wound healing process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days. Additionally, the histopathological results demonstrated that there was inflammation in Nitrofurazone group through twelveth day, somehow the epithelium was formed and abundant vessels were visible. Although on 16th day and the previous days the healing condition of Kombucha fungus was considered as minimal rate, revealing it is similar to Nitrofurazone group on 20th day. Conclusions To wrap up. These observations suggest that the Kombucha fungus healing quality was rapid from 12th day to the end of the research, whereas no significant difference was observed. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196 PMID:23866960

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

    PubMed

    Barati, Fardin; Javanbakht, Javad; Adib-Hashemi, Farajollah; Hosseini, Ehsan; Safaeie, Reyhaneh; Rajabian, Mojtaba; Razmjoo, Mostafa; Sedaghat, Reza; Aghamohammad Hassan, Mehdi

    2013-07-17

    Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. The aim of this study was to evaluate clinical and histopathological alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rat. In present study 24 Wister -albino rats weighing 150-200 g were selected and divided to two treatment groups as Nitrofurazone ointment (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM) route. Furthermore, upon preparation of dorsal region of the animal for surgery, a piece of full-thickness skin removed (2 × 2 cm). In order to comparing wounds healing clinically and histologically, once every four days from the commencement, the wounds were photographed and the healed surface was measured by Scion image software. The clinical findings indicated that the Kombucha fungus resulted in precipitating healing than Nitrofurazone; however, it was not significant (p > 0.05). In order to pathological comparing of wound healing process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days. Additionally, the histopathological results demonstrated that there was inflammation in Nitrofurazone group through twelveth day, somehow the epithelium was formed and abundant vessels were visible. Although on 16th day and the previous days the healing condition of Kombucha fungus was considered as minimal rate, revealing it is similar to Nitrofurazone group on 20th day. To wrap up. These observations suggest that the Kombucha fungus healing quality was rapid from 12th day to the end of the research, whereas no significant difference was observed. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196.

  4. Microdeformation in wound healing.

    PubMed

    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.

  5. Wound Healing and Care

    MedlinePlus

    ... of collagen. So they're tougher and less flexible than the skin around them. Caring for Serious Wounds at Home Serious wounds don't heal overnight. It can take weeks for the body to build new tissue. So after you leave ...

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

    PubMed

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

    2016-02-01

    Wound healing remains a major challenge in modern medicine. Bone marrow- (BM) and adipose tissue- (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT-MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM- or AT-MSCs were administered intradermally (1 x 10(6) cells) into partial-thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC-injected wounds were associated with improved appearance and faster re-epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM- and AT-MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM- and AT-MSC for treatment of cutaneous wounds through modulation of healing and epithelialization. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis

    PubMed Central

    Bajaj, Gaurav; Guha, Gunjan; Wang, Zhixing; Jang, Hyo-Sang; Leid, Mark; Indra, Arup Kumar; Ganguli-Indra, Gitali

    2012-01-01

    Background COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2ep−/− mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2−/−) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. Methodology/Principal Findings Full thickness excisional wound healing experiments were performed on Ctip2L2/L2 and Ctip2ep−/− animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2ep−/− mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. Conclusions/Significance Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure. PMID:22383956

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

  9. Innovation and wound healing.

    PubMed

    Harding, Keith

    2015-04-01

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

  10. MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2.

    PubMed

    Wu, Yan; Zhong, Julia Li; Hou, Ning; Sun, Yaolan; Ma, Benting; Nisar, Muhammad Farrukh; Teng, Yan; Tan, Zhaoli; Chen, Keping; Wang, Youliang; Yang, Xiao

    2017-02-01

    Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Phytochemicals in Wound Healing

    PubMed Central

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

    2016-01-01

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

  12. The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing

    PubMed Central

    Fadini, Gian Paolo; Albiero, Mattia; Menegazzo, Lisa; Boscaro, Elisa; Pagnin, Elisa; Iori, Elisabetta; Cosma, Chiara; Lapolla, Annunziata; Pengo, Vittorio; Stendardo, Massimo; Agostini, Carlo; Pelicci, Pier Giuseppe; Giorgio, Marco; Avogaro, Angelo

    2010-01-01

    OBJECTIVE The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS Skin wounds were created in wild-type (WT) and p66Shc−/− control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and β-catenin. Response to hind limb ischemia was also evaluated. RESULTS Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of β-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc−/− than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and β-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc−/− dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication. PMID:20566667

  13. Image-guided plasma therapy of cutaneous wound

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  14. Electrical stimulation to accelerate wound healing.

    PubMed

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

    2013-09-16

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

  15. Electrical stimulation to accelerate wound healing

    PubMed Central

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

    2013-01-01

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

  16. Healing Invisible Wounds

    ERIC Educational Resources Information Center

    Adams, Erica J.

    2010-01-01

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

  17. Healing Invisible Wounds

    ERIC Educational Resources Information Center

    Adams, Erica J.

    2010-01-01

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

  18. Placenta Growth Factor in Diabetic Wound Healing

    PubMed Central

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

    2006-01-01

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

  19. Wound healing for the clinician.

    PubMed

    Zitelli, J

    1987-01-01

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

  20. The molecular biology in wound healing & non-healing wound.

    PubMed

    Qing, Chun

    2017-08-01

    The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  1. Honey and Wound Healing: An Update.

    PubMed

    Saikaly, Sami K; Khachemoune, Amor

    2017-04-01

    For centuries, honey has been utilized for wound healing purposes. In recent times, this specific topic has become a field of interest, possibly due to the advent of antibiotic resistance in microbial pathogens. With constant technological advancement, the information regarding honey's mechanisms of action on wound healing has accumulated at a rapid pace. Similarly, clinical studies comparing honey with traditional wound care therapies are steadily emerging. As a follow-up to a previous review published in the journal in 2011, the current review article outlines publications regarding honey and wound healing that have been published between June 2010 and August 2016. Here we describe the most recent evidence regarding multiple types of honey and their mechanisms of action as antimicrobial agents, immunologic modulators, and physiologic mediators. In addition, outcomes of clinical studies involving a multitude of cutaneous wounds are also examined.

  2. Multimodal imaging of cutaneous wound tissue

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  3. Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

    PubMed Central

    Das, Subhamoy; Baker, Aaron B.

    2016-01-01

    Wound healing is an intricate process that requires complex coordination between many cell types 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 are currently used in clinical practice. PMID:27843895

  4. Radiotherapy and wound healing.

    PubMed

    Devalia, Haresh L; Mansfield, Lucy

    2008-03-01

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

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

    PubMed

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

    2013-05-01

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

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

    PubMed

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

    2012-01-01

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

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

    SciTech Connect

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

    2005-03-10

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

  8. Cell therapy for wound healing.

    PubMed

    You, Hi-Jin; Han, Seung-Kyu

    2014-03-01

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

  9. Stabilized Hemoglobin Wound Healing Development

    DTIC Science & Technology

    2012-10-01

    tissue oxygen capacitance after hyperbaric oxygen therapy: a new physiologic concept. Plast. Reconstruc. Surg.; 99: 148-155 8 4. Mustoe, T. 2004...Wound healing essentials: let there be oxygen. Wound Repair Regen, 17: 1-18 6. Chambers A.C. and Leaper D.J. 2011. Role of oxygen in wound healing: a

  10. Wound healing after laser surgery.

    PubMed

    Hendrick, D A; Meyers, A

    1995-10-01

    Compared with scalpel wounds, CO2 laser wounds show delays in inflammation, collagen production, reepithelialization, and tensile strength in the early stages of healing. Some of these delays are similar to those seen with electrocautery and burn wounds. Later stages compensate for these early deficiencies, because scalpel and laser wounds become more similar in epithelialization and wound strength over time. Healed CO2 laser wounds tend to have less scar contraction than scalpel wounds. Débridement of initial laser wound char, tissue cooling techniques during lasering, and pulsed modes of laser delivery all seem to result in more rapid, favorable healing. Similar wound healing trends have been seen with the CO2 laser in bone, with other lasers, and with laser vascular and neural anastomosis. Biostimulation with low-level laser energy is a complex subject of ongoing investigations.

  11. Curcumin as a wound healing agent.

    PubMed

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

    2014-10-22

    Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarizes and discusses recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Isoniazid and Wound Healing

    PubMed Central

    Martyn, John W.; Campbell, H. Hoyle

    1963-01-01

    In non-tuberculous patients with lesions exhibiting a delayed healing process oral isoniazid in doses of 3 mg./kg. was found to be rapidly effective in stimulating the wounded area to produce healthy granulation tissue. The prompt healing of these defects was accomplished by the formation of scar tissue which resisted stress in a superior manner. A topical ointment of 2% isoniazid in eucerin had a similar beneficial effect in patients with indolent skin ulcers who had failed to respond to routine treatment. Epithelialization rapidly ensued once the granulating base was established. A further series of patients with delayed wound healing and failure to respond to antibiotics or isoniazid alone showed satisfactory response when both measures were used simultaneously. It is postulated that isoniazid provides a stimulus to the growth of normal granulation tissue, may promote greater tensile strength in scars, and may be of benefit in antibiotic-resistant infections because of its ability to boost the host's normal repair mechanisms. ImagesFig. 1Fig. 2Fig. 3 PMID:13933176

  13. Wound Healing Devices Brief Vignettes

    PubMed Central

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

    2016-01-01

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

  14. Wound Healing and Skin Regeneration

    PubMed Central

    Takeo, Makoto; Lee, Wendy; Ito, Mayumi

    2015-01-01

    The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages to wound healing and, conversely, skin appendage regeneration following injuries. PMID:25561722

  15. Rapid Healing of Cutaneous Leishmaniasis by High-Frequency Electrocauterization and Hydrogel Wound Care with or without DAC N-055: A Randomized Controlled Phase IIa Trial in Kabul

    PubMed Central

    Steiner, Reto; Wentker, Pia; Mahfuz, Farouq; Stahl, Hans-Christian; Amin, Faquir Mohammad; Bogdan, Christian; Stahl, Kurt-Wilhelm

    2014-01-01

    Background Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1st), after wound closure (2nd) and after 6 months (3rd). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p = 0.83). In patients with Leishmania-positive 2nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of

  16. Wound healing in plants

    PubMed Central

    Tisi, Alessandra; Angelini, Riccardo

    2008-01-01

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

  17. Wound Healing Studies.

    DTIC Science & Technology

    1986-11-15

    parallel groups of rats, that is. we found no evidence of stimulator( s ) or inhibitor( s ) in the sera of normal or shafr- hepatectomized dogs , but we...the dog was without insulin for 7 days. (continued next page) P5 P 107 , S .= P. ,, F. influenc@ of Clofbrate anc 4&feno. r o-" L ve’ G’owtO ’c 1...WM-103 400 WOUND HEALING STUDIES(U) ALBERT EINSTEIN COLL OF 1/2 MEDICINE BRONX NY S N LEVENSON 15 NOV 86I DADA±-76-C-BBBS UNCLAISSIFIED F/G 6/14 M

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

    PubMed

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

    2017-03-15

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

  19. Wound healing activity of honey: A pilot study.

    PubMed

    Vijaya, Kumari K; Nishteswar, K

    2012-07-01

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

  20. Nutritional support for wound healing.

    PubMed

    MacKay, Douglas; Miller, Alan L

    2003-11-01

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

  1. Honey: a potent agent for wound healing?

    PubMed

    Lusby, P E; Coombes, A; Wilkinson, J M

    2002-11-01

    Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized. Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (eg, osmotic effects and pH) of honey also aid in its antibacterial actions. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey). This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types.

  2. Molecular pathology of wound healing.

    PubMed

    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.

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

    PubMed

    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.

  4. Laser biostimulation of wound healing: bioimpedance measurements support histology.

    PubMed

    Solmaz, Hakan; Dervisoglu, Sergulen; Gulsoy, Murat; Ulgen, Yekta

    2016-11-01

    Laser biostimulation in medicine has become widespread supporting the idea of therapeutic effects of photobiomodulation in biological tissues. The aim of this study was to investigate the biostimulation effect of laser irradiation on healing of cutaneous skin wounds, in vivo, by means of bioimpedance measurements and histological examinations. Cutaneous skin wounds on rats were subjected to 635 nm diode laser irradiations at two energy densities of 1 and 3 J/cm(2) separately. Changes in the electrical properties of the wound sites were examined with multi-frequency electrical impedance measurements performed on the 3rd, 7th, 10th, and 14th days following the wounding. Tissue samples were both morphologically and histologically examined to determine the relationship between electrical properties and structure of tissues during healing. Laser irradiations of both energy densities stimulated the wound healing process. In particular, laser irradiation of lower energy density had more evidence especially for the first days of healing process. On the 7th day of healing, 3 J/cm(2) laser-irradiated tissues had significantly smaller wound areas compared to non-irradiated wounds (p < 0.05). The electrical impedance results supported the idea of laser biostimulation on healing of cutaneous skin wounds. Thus, bioimpedance measurements may be considered as a non-invasive supplementary method for following the healing process of laser-irradiated tissues.

  5. Antioxidant and hemolytic activities, and effects in rat cutaneous wound healing of a novel polysaccharide from fenugreek (Trigonella foenum-graecum) seeds.

    PubMed

    Ktari, Naourez; Trabelsi, Imen; Bardaa, Sana; Triki, Mehdi; Bkhairia, Intidhar; Ben Slama-Ben Salem, Rabab; Nasri, Moncef; Ben Salah, Riadh

    2017-02-01

    The aim of this work was to evaluate the antioxidant and hemolytic activities as well as the in vivo wound healing performance of a novel polysaccharide (FWEP) extracted from fenugreek (Trigonella foenum-graecum) seeds. The antioxidant activity was evaluated in vivo and in vitro using various assays. Results showed that FWEP exhibited strong antioxidant activities but no hemolytic activity was observed towards bovine erythrocytes. The application of FWEP hydrogel on the wound site in a rat model enhanced significantly wound healing activity and accelerated the wound closure after 14days of wound induction. Histological examination also demonstrated fully re-epithelialized wound with a complete epidermal regeneration. Altogether, these evidences demonstrated that FWEP had strong wound healing potential presumably achieved through its antioxidant activities. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Wound healing potential of adipose tissue stem cell extract.

    PubMed

    Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

    2017-03-25

    Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2010-04-01

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

  8. Wound healing: part II. Clinical applications.

    PubMed

    Janis, Jeffrey; Harrison, Bridget

    2014-03-01

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

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

    PubMed

    Volk, Susan W; Bohling, Mark W

    2013-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    Ebaid, Hossam

    2014-03-04

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

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

    PubMed

    Abu-al-Basal, Mariam A

    2012-04-01

    Dead Sea (DS) mud and salts are known for their therapeutic and cosmetic properties. Previous studies confirmed their efficacy in treating the more frequent skin diseases such as psoriasis and atopic dermatitis. Therefore, this study aimed to evaluate the wound healing potential of natural and compounded skin-care product (facial mask) of DS black mud in BALB/c mice. Two full-thickness excision round wounds were created on the dorsum region of mouse. Each wound of mice test group were treated topically with 50 microL of 0.1% natural or compounded DS black mud or 50 microL of 0.2% nitrofurazone once a day for 2 consecutive days and the mice control group were left untreated. Healing was assessed by measuring the granulation tissue weight and percentage of wound contraction at day 3, 7, 14 and 21 after wounding. In addition to period of epithelialization and histological evaluation of the regenerated wound area at day 7 and 14 after wounding. Results revealed that DS black mud accelerate wound healing process by enhancing granulation, wound contraction, epithelialization, angiogenesis and collagen deposition. This may be due to high content of minerals and trace elements that possibly act as anti-microbial, anti-inflammatory and antioxidant with enhancement effect on cell proliferation, migration and fibroblast cellular activity. However, the healing property of DS black mud compounded in skin-care product was greater than that of natural black mud, when compared to reference drug, nitrofurazone.

  13. Wound healing and skin regeneration.

    PubMed

    Takeo, Makoto; Lee, Wendy; Ito, Mayumi

    2015-01-05

    The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages to wound healing and, conversely, skin appendage regeneration following injuries. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Multimodal imaging of cutaneous wound tissue

    PubMed Central

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

    2015-01-01

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

  15. Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice.

    PubMed

    Abu-Al-Basal, Mariam A

    2010-09-15

    Rosmarinus officinalis (Rosemary) used in Jordanian folk medicine for wound management and treatment. Therefore, the present study was conducted to assess the healing efficacy of both aqueous extract and essential oil of the aerial parts on alloxan-induced diabetic BALB/c mice. Two full-thickness round wounds were created in the dorsal area of each mouse. Animals were divided into four groups of twenty mice each: untreated normal, untreated diabetic, aqueous extract- (intraperitoneal injection of 0.2 ml at a dose of 10% for 3 days) and essential oil-treated diabetic mice (topical application of 25 microl/excision wound, twice a day for 3 days). For 15 days, the wounds were visually observed; blood glucose level, body weight, regenerated granulation tissue weight and the percentage of wound contraction were measured. On days 6 and 15 after wounding, the animals were sacrificed and the histology of wound area was examined. Significant positive differences (p<0.01) between treated and control groups were observed at different aspects of diabetic wound healing process. Reduced inflammation and enhanced wound contraction, re-epithelialization, regeneration of granulation tissue, angiogenesis and collagen deposition were detected in the treated wounds. Results indicated that the essential oil of Rosmarinus officinalis was the most active in healing diabetic wounds and provide a scientific evidence for the traditional use of this herb in wound treatment. However, further scientific verification is required to confirm and assess the range of wound healing potential of essential oils of Rosemary chemotypes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. [Wound healing after vacuum drainage].

    PubMed

    Davydov, Iu A; Larichev, A B; Abramov, A Iu

    1992-01-01

    Vacuum therapy was applied in the management of 63 patients with postoperative ventral hernias, 101 patients with a similar pathological conditions were treated by the traditional method for wound healing. From analysis of the results of treatment and with due consideration for the results of additional methods of examination it was established that vacuum prevents accumulation of exudate and blood clots in the wound cavity and removes the risk medium for the development of pyo-inflammatory complications. Moreover, by promoting the coming together of the wound edges and liquidation of the wound cavity, vacuum therapy affects the metabolic reorganizations in the tissues and leads to stabilization of the regeneration mechanisms. The use of vacuum therapy in the postoperative period creates the possibility of regulating the reparative reactions through an active effect on the healing of the wound in the phase of inflammation, protecting in this manner the biology of the wound process and preventing infectious complications.

  17. [Specificities in children wound healing].

    PubMed

    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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Role of neuropeptides, neurotrophins, and neurohormones in skin wound healing.

    PubMed

    Chéret, Jérémy; Lebonvallet, Nicolas; Carré, Jean-Luc; Misery, Laurent; Le Gall-Ianotto, Christelle

    2013-01-01

    Due to the close interactions between the skin and peripheral nervous system, there is increasing evidence that the cutaneous innervation is an important modulator of the normal wound healing process. The communication between sensory neurons and skin cells involves a variety of molecules (neuropeptides, neurohormones, and neurotrophins) and their specific receptors expressed by both neuronal and nonneuronal skin cells. It is well established that neurotransmitters and nerve growth factors released in skin have immunoregulatory roles and can exert mitogenic actions; they could also influence the functions of the different skin cell types during the wound healing process. © 2013 by the Wound Healing Society.

  19. Healing in the irradiated wound

    SciTech Connect

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

    1990-07-01

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

  20. The microenvironment of wound healing.

    PubMed

    Junker, Johan P E; Caterson, E J; Eriksson, Elof

    2013-01-01

    This review summarizes experiments performed by us and others, examining the importance of the microenvironment to wound healing. The development of a sealed polyurethane wound chamber has allowed us to perform studies evaluating the effects of growth factors, transplanted cells, and other bioactive substances on wound healing. Studies have compared wet, moist, and dry healing, with the conclusion that a wet, incubator-like microenvironment provides the fastest healing with fewest aberrations and least scar formation. The wet environment is also paramount for the survival and proliferation of transplanted cells or tissue, which has been shown in studies of porcine and human wounds. Moreover, high concentrations of antibiotics and other agents can be introduced in the wound chamber, thereby effectively fighting infection, while maintaining safe systemic concentrations. These findings have been used in clinical settings to treat wounds of different types. A titanium chamber has been developed to create an in vivo incubator, which will serve as a regenerative platform for in vivo tissue engineering.

  1. Redox Signals in Wound Healing

    PubMed Central

    Sen, Chandan K.; Roy, Sashwati

    2008-01-01

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

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

    PubMed

    Davidson, Jacqueline R

    2015-05-01

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

  3. Progress in corneal wound healing

    PubMed Central

    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

  4. Skin: histology and physiology of wound healing.

    PubMed

    Gantwerker, Eric A; Hom, David B

    2011-08-01

    It is important to understand the histology and physiology of skin for the prediction and optimization of wound healing. Optimal postoperative wound healing to minimize scarring entails minimizing local, systemic, and environmental factors that lead to poor wound healing. Keeping the wound clean and moist, minimizing trauma, and infection are the local wound tenets. Systemic tenets include minimizing medications that inhibit processes of wound healing, maintaining adequate nutrition, pain palliation, UV protection, and smoking cessation. This article presents the dynamic process of wound healing and the basic tenets to minimize scarring. 2011 Elsevier Inc. All rights reserved.

  5. Chitosan-alginate membranes accelerate wound healing.

    PubMed

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

    2015-07-01

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

  6. Topical application of Acalypha indica accelerates rat cutaneous wound healing by up-regulating the expression of Type I and III collagen.

    PubMed

    Ganeshkumar, Moorthy; Ponrasu, Thangavel; Krithika, Rajesh; Iyappan, Kuttalam; Gayathri, Vinaya Subramani; Suguna, Lonchin

    2012-06-26

    Acalypha indica Linn. (Acalypha indica) vernacularly called Kuppaimeni in Tamil, has been used as a folklore medicine since ages for the treatment of wounds by tribal people of Tamil Nadu, Southern India. The present study investigates the biochemical and molecular rationale behind the healing potential of Acalypha indica on dermal wounds in rats. Acalypha indica extract (40 mg/kg body weight) was applied topically once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of various biochemical and biophysical analyses and to observe histopathological changes with and with-out extract treatment. The serum levels of pro-inflammatory cytokine tumor necrosis factor (TNF-α) was measured at 12 h, 24 h, 48 h and 72 h post-wounding using ELISA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to study the expression pattern of transforming growth factor [TGF-β1], collagen 1 α (I) [Col 1 α (I)] and collagen 3 α (I) [Col 3 α (I)]. Likewise, linear incision wounds were created and treated with the extract and used for tensile strength measurements. Wound healing in control rats was characterized by less inflammatory cell infiltration, lack of granulation tissue formation, deficit of collagen and significant decrease in biomechanical strength of wounds. Acalypha indica treatment mitigated the oxidative stress and decreased lipid peroxidation with concomitant increase in ascorbic acid levels. It also improved cellular proliferation, increased TNF-α levels during early stages of wound healing, up-regulated TGF-β1 and elevated collagen synthesis by markedly increasing the expression of Col 1 α (I) and Col 3 α (I). Increased rates of wound contraction, epithelialization, enhanced shrinkage temperature and high tensile strength were observed in the extract treated rats. Acalypha indica extract was shown to augment the process of dermal wound healing by its ability to increase collagen

  7. [Impaired wound healing following tonsillectomy].

    PubMed

    Zengel, P; Betz, C S; Berghaus, A; Leunig, A

    2008-07-01

    Tonsillectomy is one of the most commonly performed surgical procedures in the field of otorhinolaryngology. The first tonsillectomy was done about 600 B.C. [3]. This operation is indicated for patients with recurrent tonsillitis, peritonsillar abscess, hypertrophy or asymmetry of the tonsils. Even though a routine procedure, it has a relatively high risk of complications such as post operative hemorrhage, infection or impaired wound healing. The reported case involves a 20 year old female patient who developed velopharyngeal insufficiency as a result of impaired wound healing after tonsillectomy. The patient was treated conservatively and is free of discomfort after 2 months.

  8. Heat delays skin wound healing in mice.

    PubMed

    Dos Santos-Silva, Marco Aurélio; Trajano, Eduardo Tavares Lima; Schanuel, Fernanda Seabra; Monte-Alto-Costa, Andréa

    2017-02-01

    In vivo studies have shown that the combination of infrared radiation (IR) and visible light (VIS) is responsible for the activation of metaloproteinases, causing matrix degradation and damage to healthy skin. However, the role of heat originating from the VIS spectrum on wound healing remains poorly understood. Our objective was to investigate the macroscopic, microscopic and biochemical effects of heat induced by visible light on cutaneous wound healing in mice. Male mice were anesthetized, subjected to a cutaneous excisional wound and divided into two groups ( n = 10/group) exposed to 23℃ or 43℃ in a thermal chamber for 30 min every other day, for 13 days. On day 14, the animals were sacrificed, and their lesions were processed for histochemistry, immunohistochemistry and protein expression analysis. The wound area was 42% greater 11 days ( p < 0.01) and 29% greater 14 days ( p < 0.001) after wounding in the 43℃ group than in the 23℃ group. The 43℃ group presented a lower (17%) percentage of reepithelialized wounds ( p < 0.001) 14 days after wounding. The length of the epidermal gap was greater in the 43℃ group ( p < 0.01). The volume density of myofibroblasts and the number of F4/80-positive macrophages was greater in the 43℃ group ( p < 0.05). The 43℃ group showed increased protein expression of type III collagen ( p < 0.001), decreased protein expression of type I collagen ( p < 0.05), increased MMP-1 expression ( p < 0.05), and decreased MMP-2 activity ( p < 0.001). The protein expression of fibrillin-1 ( p < 0.001), MMP-12 ( p < 0.05), TGF-β 1/2/3 ( p < 0.01) and ERK activation ( p < 0.05) was increased in the 43℃ group. Our results suggest that heat delays the stages of wound healing in mice.

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

    PubMed

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

    2011-07-01

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

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

    PubMed

    Mutschler, W

    2012-09-01

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

  11. Sirtuin-6 deficiency exacerbates diabetes induced impairment of wound healing

    PubMed Central

    Thandavarayan, Rajarajan A; Garikipati, Venkata Naga Srikanth; Joladarashi, Darukeshwara; Babu, Sahana Suresh; Jeyabal, Prince; Verma, Suresh K; Mackie, Alexander R; Khan, Mohsin; Arumugam, Somasundaram; Watanabe, Kenichi; Kishore, Raj; Krishnamurthy, Prasanna

    2015-01-01

    Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyze the role of SIRT6 in cutaneous wound healing, paired 6 mm stented wound were created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and non-sensed siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6-siRNA treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31 staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor (VEGF) expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor kB (NF-kB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α and interleukin-1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF-kB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that activation of SIRT6 signaling might be a potential therapeutic approach for promoting wound healing in diabetics. PMID:26010430

  12. Electrical Stimulation Technologies for Wound Healing

    PubMed Central

    Kloth, Luther C.

    2014-01-01

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

  13. Hyperbaric oxygen and wound healing

    PubMed Central

    Bhutani, Sourabh; Vishwanath, Guruswamy

    2012-01-01

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

  14. Peptide-modified chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting inflammation

    PubMed Central

    Chen, Xionglin; Zhang, Min; Wang, Xueer; Chen, Yinghua; Yan, Yuan; Zhang, Lu; Zhang, Lin

    2017-01-01

    Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro. This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds. PMID:28559985

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

    PubMed

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

    2016-01-01

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

  16. 635nm diode laser biostimulation on cutaneous wounds

    NASA Astrophysics Data System (ADS)

    Solmaz, Hakan; Gülsoy, Murat; Ülgen, Yekta

    2014-05-01

    Biostimulation is still a controversial subject in wound healing studies. The effect of laser depends of not only laser parameters applied but also the physiological state of the target tissue. The aim of this project is to investigate the biostimulation effects of 635nm laser irradiation on the healing processes of cutaneous wounds by means of morphological and histological examinations. 3-4 months old male Wistar Albino rats weighing 330 to 350 gr were used throughout this study. Low-level laser therapy was applied through local irradiation of red light on open skin excision wounds of 5mm in diameter prepared via punch biopsy. Each animal had three identical wounds on their right dorsal part, at which two of them were irradiated with continuous diode laser of 635nm in wavelength, 30mW of power output and two different energy densities of 1 J/cm2 and 3 J/cm2. The third wound was kept as control group and had no irradiation. In order to find out the biostimulation consequences during each step of wound healing, which are inflammation, proliferation and remodeling, wound tissues removed at days 3, 7, 10 and 14 following the laser irradiation are morphologically examined and than prepared for histological examination. Fragments of skin including the margin and neighboring healthy tissue were embedded in paraffin and 6 to 9 um thick sections cut are stained with hematoxylin and eosin. Histological examinations show that 635nm laser irradiation accelerated the healing process of cutaneous wounds while considering the changes of tissue morphology, inflammatory reaction, proliferation of newly formed fibroblasts and formation and deposition of collagen fibers. The data obtained gives rise to examine the effects of two distinct power densities of low-level laser irradiation and compare both with the non-treatment groups at different stages of healing process.

  17. Gene Therapy and Wound Healing

    PubMed Central

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

    2007-01-01

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

  18. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

    PubMed Central

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

    2015-01-01

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

  19. Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

    PubMed

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

    2015-04-14

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

  20. Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

    PubMed

    Lough, Denver M; Yang, Mei; Blum, Anthony; Reichensperger, Joel D; Cosenza, Nicole M; Wetter, Nathan; Cox, Lisa A; Harrison, Carrie E; Neumeister, Michael W

    2014-03-01

    The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated. Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls. Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls. The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell–based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.

  1. Extracellular matrix and wound healing.

    PubMed

    Maquart, F X; Monboisse, J C

    2014-04-01

    Extracellular matrix has been known for a long time as an architectural support for the tissues. Many recent data, however, have shown that extracellular matrix macromolecules (collagens, elastin, glycosaminoglycans, proteoglycans and connective tissue glycoproteins) are able to regulate many important cell functions, such as proliferation, migration, protein synthesis or degradation, apoptosis, etc., making them able to play an important role in the wound repair process. Not only the intact macromolecules but some of their specific domains, that we called "Matrikines", are also able to regulate many cell activities. In this article, we will summarize main findings showing the effects of extracellular matrix macromolecules and matrikines on connective tissue and epithelial cells, particularly in skin, and their potential implication in the wound healing process. These examples show that extracellular matrix macromolecules or some of their specific domains may play a major role in wound healing. Better knowledge of these interactions may suggest new therapeutic targets in wound healing defects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Wound Healing Problems in the Mouth

    PubMed Central

    Politis, Constantinus; Schoenaers, Joseph; Jacobs, Reinhilde; Agbaje, Jimoh O.

    2016-01-01

    Wound healing is a primary survival mechanism that is largely taken for granted. The literature includes relatively little information about disturbed wound healing, and there is no acceptable classification describing wound healing process in the oral region. Wound healing comprises a sequence of complex biological processes. All tissues follow an essentially identical pattern to complete the healing process with minimal scar formation. The oral cavity is a remarkable environment in which wound healing occurs in warm oral fluid containing millions of microorganisms. The present review provides a basic overview of the wound healing process and with a discussion of the local and general factors that play roles in achieving efficient would healing. Results of oral cavity wound healing can vary from a clinically healed wound without scar formation and with histologically normal connective tissue under epithelial cells to extreme forms of trismus caused by fibrosis. Many local and general factors affect oral wound healing, and an improved understanding of these factors will help to address issues that lead to poor oral wound healing. PMID:27853435

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

    PubMed

    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.

  4. Phases of the wound healing process.

    PubMed

    Brown, Annemarie

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

  5. Mast Cells Contribute to Scar Formation During Fetal Wound Healing

    PubMed Central

    Wulff, Brian C.; Parent, Allison E.; Meleski, Melissa A.; DiPietro, Luisa A.; Schrementi, Megan E.; Wilgus, Traci A.

    2011-01-01

    Scar formation is a potentially detrimental process of tissue restoration in adults, affecting organ form and function. During fetal development, cutaneous wounds heal without inflammation or scarring at early stages of development, but begin to heal with significant inflammation and scarring as the skin becomes more mature. One possible cell type that could regulate the change from scarless to fibrotic healing is the mast cell. We show here that dermal mast cells in scarless wounds generated at embryonic day 15 (E15) are fewer in number, less mature and do not degranulate in response to wounding as effectively as mast cells of fibrotic wounds made at embryonic day 18 (E18). Differences were also observed between cultured mast cells from E15 and E18 skin with regard to degranulation and preformed cytokine levels. Injection of mast cell lysates into E15 wounds disrupted scarless healing, suggesting that mast cells interfere with scarless repair. Finally, wounds produced at E18, which normally heal with a scar, healed with significantly smaller scars in mast cell-deficient KitW/W-v mice compared to Kit+/+ littermates. Together, these data suggest that mast cells enhance scar formation, and that these cells may mediate the transition from scarless to fibrotic healing during fetal development. PMID:21993557

  6. Fetal wound healing: implications for minimal scar formation.

    PubMed

    Leung, Alice; Crombleholme, Timothy M; Keswani, Sundeep G

    2012-06-01

    The mid-gestation fetus is capable of regenerative healing with wound healing indistinguishable from surrounding skin. This review aims to evaluate the current knowledge of how the mid-gestation fetus heals without scar and the implications of these findings in efforts to recapitulate the fetal regenerative phenotype in the postnatal environment. It has been over 30 years since the empirical observation that the fetus heals without scar; yet, the underlying mechanisms of this phenomenon have not been elucidated. Fetal wound healing is characterized by a distinct growth factor profile, an attenuated inflammatory response with an anti-inflammatory cytokine profile, an extracellular matrix rich in type III collagen and hyaluronan, attenuated biomechanical stress, and a potential role for stem cells. Current therapies to minimize scarring in postnatal wounds have attempted to recapitulate singular aspects of the fetal regenerative phenotype and have met with varying degrees of clinical success. We now have the molecular tools to more completely comprehend the fundamental mechanisms of fetal regenerative wound repair, which has the potential to provide insights into the identification of therapeutic targets to minimize the scar formation. Successful therapies that help minimize postnatal scar formation can be realized through understanding the cellular and molecular mechanisms of fetal regenerative wound healing. These insights will have implications not only for cutaneous wound healing, but also potentially for any disease process characterized by excessive fibroplasia.

  7. Fetal wound healing: implications for minimal scar formation

    PubMed Central

    Leung, Alice; Crombleholme, Timothy M.; Keswani, Sundeep G.

    2014-01-01

    Purpose of review The mid-gestation fetus is capable of regenerative healing with wound healing indistinguishable from surrounding skin. This review aims to evaluate the current knowledge of how the mid-gestation fetus heals without scar and the implications of these findings in efforts to recapitulate the fetal regenerative phenotype in the postnatal environment. Recent findings It has been over 30 years since the empirical observation that the fetus heals without scar; yet, the underlying mechanisms of this phenomenon have not been elucidated. Fetal wound healing is characterized by a distinct growth factor profile, an attenuated inflammatory response with an anti-inflammatory cytokine profile, an extracellular matrix rich in type III collagen and hyaluronan, attenuated biomechanical stress, and a potential role for stem cells. Current therapies to minimize scarring in postnatal wounds have attempted to recapitulate singular aspects of the fetal regenerative phenotype and have met with varying degrees of clinical success. We now have the molecular tools to more completely comprehend the fundamental mechanisms of fetal regenerative wound repair, which has the potential to provide insights into the identification of therapeutic targets to minimize the scar formation. Summary Successful therapies that help minimize postnatal scar formation can be realized through understanding the cellular and molecular mechanisms of fetal regenerative wound healing. These insights will have implications not only for cutaneous wound healing, but also potentially for any disease process characterized by excessive fibroplasia. PMID:22572760

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

    PubMed

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-04-01

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

  10. Wound healing in Mac-1 deficient mice.

    PubMed

    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.

  11. Amyloidogenesis in Healing Wound

    PubMed Central

    Hashimoto, Ken; Brownstein, Martin H.

    1972-01-01

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

  12. The alarmin HMGB-1 influences healing outcomes in fetal skin wounds.

    PubMed

    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.

  13. WOUND HEALING AND COLLAGEN FORMATION

    PubMed Central

    Ross, Russell; Benditt, Earl P.

    1961-01-01

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

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

    PubMed

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

    2007-06-01

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

  15. Wound healing and the role of fibroblasts.

    PubMed

    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.

  16. Lucidone Promotes the Cutaneous Wound Healing Process via Activation of the PI3K/AKT, Wnt/β-catenin and NF-κB Signaling Pathways.

    PubMed

    Yang, Hsin-Ling; Tsai, Yu-Cheng; Korivi, Mallikarjuna; Chang, Chia-Ting; Hseu, You-Cheng

    2017-01-01

    Lucidone, which comprises a naturally occurring cyclopentenedione, has been investigated for its in vitro and in vivo wound healing properties, and the underlying molecular signaling cascades in the wound healing mechanism have been elucidated. We demonstrated the cell-/dose-specific responses of lucidone (0.5-8μM) on proliferation and migration/invasion of keratinocyte HaCaT and fibroblast Hs68 cells. In keratinocytes, lucidone-induced nuclear translocation of β-catenin was accompanied by increased transcriptional target genes, including c-Myc and cyclin-D1, through GSK3β-dependent pathway. Correspondingly, lucidone promoted the cell-cycle by increasing PCNA/CDK4 and decreasing p21/p27 expressions. Lucidone induced EMT through the downregulation of epithelial (E-cadherin/occludin) and upregulation of mesenchymal (vimentin/Twist/Snail) marker proteins. Activated MMP-9/-2 and uPA/uPAR as well as suppressed TIMP-1/-2 and PAI-1 expressions by lucidone may promote the migration/invasion of keratinocytes. Notably, lucidone activated NF-κB signaling via IKK-mediated-IκB degradation, and its inhibition abolished MMP-9 activation and keratinocyte migration. Inhibition of PI3K/AKT signaling impaired the lucidone-induced proliferation/migration with corresponding suppression of β-catenin/c-Myc/cyclin-D1 and NF-κB/MMP-9 expressions. Results indicate that lucidone-induced PI3K/AKT signaling anchored the β-catenin/NF-κB-mediated healing mechanism. β-catenin knockdown substantially diminished lucidone-induced keratinocyte migration. Furthermore, lucidone increased endothelial cell proliferation/migration and triggered angiogenesis (MMP-9/uPA/ICAM-1). In macrophages, lucidone-activated NF-κB-mediated inflammation (COX-2/iNOS/NO) and VEGF, which may contribute to the growth of keratinocytes/fibroblasts and endothelial cells. Punched wounds on mice were rapidly healed with the topical application of lucidone (5mM) compared with control ointment-treated mice. Taken

  17. Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds.

    PubMed

    Rayner, T E; Cowin, A J; Robertson, J G; Cooter, R D; Harries, R C; Regester, G O; Smithers, G W; Goddard, C; Belford, D A

    2000-06-01

    The ability of single growth factors to promote healing of normal and compromised wounds has been well described, but wound healing is a process requiring the coordinated action of multiple growth factors. Only the synergistic effect on wound healing of combinations containing at most two individual growth factors has been reported. We sought to assess the ability of a novel milk-derived growth factor-enriched preparation ¿mitogenic bovine whey extract (MBWE), which contains six known growth factors, to promote repair processes in organotypic in vitro models and incisional wounds in vivo. MBWE stimulated the contraction of fibroblast-populated collagen lattices in a dose-dependent fashion and promoted the closure of excisional wounds in embryonic day 17 fetal rat skin. Application of MBWE increased incisional wound strength in normal animals on days 3, 5, 7, and 10 and reversed the decrease in wound strength observed following steroid treatment. Wound histology showed increased fibroblast numbers in wounds from normal and steroid-compromised animals. These data suggest the mixture of factors present in bovine milk exerts a direct action on the cells of cutaneous wound repair to enhance both normal and compromised healing.

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

    PubMed Central

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

    2015-01-01

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

  19. Obesity and abdominal wound healing in rats.

    PubMed

    Biondo-Simões, Maria de Lourdes Pessole; Zammar, Guilherme Roberto; Fernandes, Rodrigo dos Santos; Biondo-Simões, Rachel; Mello, Flavia Stica Ritzdorf de; Noronha, Lucia de

    2010-02-01

    Treatment for obesity essentially has to do with weight loss, which can be achieved through surgical procedures. Despite the considerable rise in the number of such procedures, the relationship between obesity and the healing process has not been totally clarified. To investigate abdominal wound healing in obese Wistar rats on the seventh and fourteenth days following a laparotomy. Thirty-six Wistar rats were randomly distributed into two groups, the control and experiment group. The control group were fed on either a standard diet for the species and the experiment group were put on a high calorie diet. After 116 days, all the animals were submitted to a laparotomy followed by laparorrhaphy. After euthanasia on the seventh or fourteenth day, fragments of the abdominal wound containing the scar were submitted to histopathological and tensiometric analysis. The average weight of the animals from the experiment group was higher than that of the control group (p<0.001). The difference in the resistance of the cutaneous scars was not significant. The aponeurotic scars were more resistant in the control group after seven days (p=0.011) and fourteen days (p=0.040). There was no difference in terms of intensity of the inflammatory reaction and the collagen density was similar in both groups. In rats, obesity lowered the resistance of the aponeurotic scars but not the skin scars. It did not interfere with the delayed inflammatory response and the collagen density.

  20. Basics in nutrition and wound healing.

    PubMed

    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.

    PubMed

    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. Electrical Activation of Wound-Healing Pathways

    PubMed Central

    Zhao, Min; Penninger, Josef; Isseroff, Roslyn Rivkah

    2011-01-01

    Background Effective wound healing has been a lasting and challenging topic in health care. Various strategies have been used to accelerate and perfect the healing process. One such strategy has involved the application of an exogenous electrical stimulus to chronic wounds with the aim of stimulating healing responses. The Problem The biology of electric stimulation to instigate healing, however, is very poorly understood. How does electric stimulation induce healing responses? Basic/Clinical Science Advances Recent research shows that the electric fields (EFs) activate multiple signaling pathways that are critical for wound healing. Importantly, the EFs provide a powerful, sometimes an overriding, directional signal for cell migration in wound healing. Unlike other stimuli, EFs have the intrinsic property of being directional. The EF-directed cell migration (electrotaxis/galvanotaxis) appears to be a consequence of EF-induced polarized signaling of epidermal growth factor receptors, integrins, and phosphoinositide 3 kinase/Pten, and may be mediated by protein kinase C, intracellular Ca2+, and cyclic adenosine monophosphate (cAMP). Because directional cell migration is a key component in wound healing, galvanotaxis may represent an important mechanism of wound healing. Clinical Care Relevance With the constantly enlarging diabetic and aging population, chronic or nonhealing wounds pose increasing health and economic problems, and currently there is no effective therapy available. Electric stimulation activates important intracellular signaling pathways that are polarized in the EF direction, resulting in enhanced and stimulated directional cell migration. Electric stimulation offers a novel approach to achieve better and accelerated wound healing. Conclusion Experimental evidence suggests a significant role of endogenous EFs in cell migration in wound healing. Most importantly, EFs are a very powerful signal to direct cell migration. Electric stimulation therefore

  3. The Role of Chemokines in Fibrotic Wound Healing

    PubMed Central

    Ding, Jie; Tredget, Edward E.

    2015-01-01

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

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

    PubMed

    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.

  5. Engineered Biopolymeric Scaffolds for Chronic Wound Healing

    PubMed Central

    Dickinson, Laura E.; Gerecht, Sharon

    2016-01-01

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

  6. Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

    PubMed

    Dickinson, Laura E; Gerecht, Sharon

    2016-01-01

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

  7. Current management of wound healing.

    PubMed

    Gottrup, F; Karlsmark, T

    2009-06-01

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

  8. Overview of Wound Healing and Management.

    PubMed

    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.

  9. The external microenvironment of healing skin wounds.

    PubMed

    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.

  10. Epidermal aquaporin-3 is increased in the cutaneous burn wound.

    PubMed

    Sebastian, R; Chau, E; Fillmore, P; Matthews, J; Price, L A; Sidhaye, V; Milner, S M

    2015-06-01

    Aquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing. However, the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We sought to assess the expression of AQP-3 in patients with burn wounds. A fresh full thickness biopsy sample was taken from the center of the burn wound, the burn wound edge, and the graft donor site in 7 patients (n=21), approximately 3-7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3 specific antibody and examined by immunofluorescence. Fresh samples were processed to quantify AQP-3 protein expression with Western blot analysis. The central portion of the burn wound revealed destruction of the epidermis and dermis with no AQP-3 present. Along the burn wound edge where the epidermal architecture was disrupted, there was robust AQP-3 staining. Western blot analysis demonstrated deeper staining along the burn wound edge compared to unburned skin (control). Quantification of the protein shows a significant amount of AQP-3 expression along the burn wound edge (3.6±0.34) compared to unburned skin (2.1±0.28, N=7, *p<0.05). There is no AQP-3 expression in the burn wound center. AQP-3 expression is increased in the burn wound following injury. While its role in wound healing has been defined, we report for the first time the effect of cutaneous burns on AQP-3 expression. Our data provides the first step in determining its functional role in burn wounds. We hypothesize that development of AQP3 targeted therapies may improve burn

  11. Tropomyosin regulates cell migration during skin wound healing.

    PubMed

    Lees, Justin G; Ching, Yu Wooi; Adams, Damian H; Bach, Cuc T T; Samuel, Michael S; Kee, Anthony J; Hardeman, Edna C; Gunning, Peter; Cowin, Allison J; O'Neill, Geraldine M

    2013-05-01

    Precise orchestration of actin polymer into filaments with distinct characteristics of stability, bundling, and branching underpins cell migration. A key regulator of actin filament specialization is the tropomyosin family of actin-associating proteins. This multi-isoform family of proteins assemble into polymers that lie in the major groove of polymerized actin filaments, which in turn determine the association of molecules that control actin filament organization. This suggests that tropomyosins may be important regulators of actin function during physiological processes dependent on cell migration, such as wound healing. We have therefore analyzed the requirement for tropomyosin isoform expression in a mouse model of cutaneous wound healing. We find that mice in which the 9D exon from the TPM3/γTm tropomyosin gene is deleted (γ9D -/-) exhibit a more rapid wound-healing response 7 days after wounding compared with wild-type mice. Accelerated wound healing was not associated with increased cell proliferation, matrix remodeling, or epidermal abnormalities, but with increased cell migration. Rac GTPase activity and paxillin phosphorylation are elevated in cells from γ9D -/- mice, suggesting the activation of paxillin/Rac signaling. Collectively, our data reveal that tropomyosin isoform expression has an important role in temporal regulation of cell migration during wound healing.

  12. The alarmin HMGB-1 influences healing outcomes in fetal skin wounds

    PubMed Central

    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 to E15 keratinocytes. After injury, HMGB-1 was released to a greater extent from keratinocytes at the margin of scar-forming E18 wounds compared to 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 to control wounds. Together, these data suggest that extracellular HMGB-1 levels influence the quality of healing in cutaneous wounds. PMID:23438257

  13. Assessment of Chicken-Egg Membrane as a Dressing for Wound Healing.

    PubMed

    Guarderas, Fernando; Leavell, Yaowaree; Sengupta, Trisha; Zhukova, Mariya; Megraw, Timothy L

    2016-03-01

    To examine the efficacy of the folk remedy of chicken-egg membrane dressing on wound healing. Full-thickness excisional wounds were created on 14 male Sprague-Dawley rats in 2 separate trials. Each animal received 2 wounds on the upper back. One wound was untreated, and the other was dressed with chicken-egg membrane to assess its impact on wound healing. Half of the rats received egg membrane treatment on the inferior wound, whereas the other half received egg membrane treatment on the superior wound. Membrane replacement, wound debridement, and imaging were done on days 5, 8, and 10 and then imaging continued on days 12, 14, 16, 18, and 20 of the experiment. Healing rate was measured based on the wound area over the 20 days of the experiment. The wounds dressed with chicken-egg membrane had a significantly (P < .01) faster rate of healing compared with the control at the early stages of healing between days 0 and 5. This group healed 21% faster during this early phase, compared with the control group. Overall, however, wound healing rates were indistinguishable from days 5 to 20. Chicken-egg membrane dressing significantly improves healing of cutaneous wounds in the early stages of wound healing.

  14. Scarless fetal skin wound healing update.

    PubMed

    Lo, David D; Zimmermann, Andrew S; Nauta, Allison; Longaker, Michael T; Lorenz, H Peter

    2012-09-01

    Scar formation, a physiologic process in adult wound healing, can have devastating effects for patients; a multitude of pathologic outcomes, affecting all organ systems, stems from an amplification of this process. In contrast to adult wound repair, the early-gestation fetal skin wound heals without scar formation, a phenomenon that appears to be intrinsic to fetal skin. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to this scarless repair. Despite the great increase in knowledge gained over the past decades, the precise mechanisms regulating scarless fetal healing remain unknown. Herein, we describe the current proposed mechanisms underlying fetal scarless wound healing in an effort to recapitulate the fetal phenotype in the postnatal environment. Copyright © 2012 Wiley Periodicals, Inc.

  15. Current wound healing procedures and potential care.

    PubMed

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

    2015-03-01

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

  16. Current wound healing procedures and potential care

    PubMed Central

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

    2015-01-01

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

  17. [Perioperative hypothermia. Impact on wound healing].

    PubMed

    Pietsch, A P; Lindenblatt, N; Klar, E

    2007-09-01

    Mild perioperative hypothermia is a common complication of anesthesia and surgery associated with several adverse effects including impaired wound healing and more frequently leads to wound infections. Perioperative hypothermia affects the hemostasis and various immune functions and therefore interferes with the initial phases of the wound healing process. Furthermore, perioperative hypothermia contributes to wound complications by inhibition of deposition of collagen and prolongation of postoperative catabolism. Wound complications prolong hospitalization and substantially increase medical costs. Thus, maintaining normothermia perioperatively is essential to reduce the number of wound complications.

  18. Acceleration Of Wound Healing Ny Photodynamic Therapy

    DOEpatents

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

    2000-08-22

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

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

    PubMed

    Wilkins, Robert G; Unverdorben, Martin

    2013-04-01

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

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

    PubMed

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

    2000-01-01

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

  1. Epidermal Wound Healing in the Nematode Caenorhabditis elegans

    PubMed Central

    Chisholm, Andrew D.

    2015-01-01

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

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

    PubMed

    De Jesus, Aribet M; Aghvami, Maziar; Sander, Edward A

    2016-01-01

    Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical

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

    PubMed Central

    2016-01-01

    Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical

  4. Assessment and nutritional aspects of wound healing.

    PubMed

    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.

  5. Wound Healing in PatientsWith Cancer

    PubMed Central

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

    2008-01-01

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

  6. Wound Healing Activity of Silibinin in Mice

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. A current affair: electrotherapy in wound healing.

    PubMed

    Hunckler, Jerome; de Mel, Achala

    2017-01-01

    New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient's quality of life.

  9. A current affair: electrotherapy in wound healing

    PubMed Central

    Hunckler, Jerome; de Mel, Achala

    2017-01-01

    New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. PMID:28461755

  10. Calcium-Based Nanoparticles Accelerate Skin Wound Healing

    PubMed Central

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

    2011-01-01

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

  11. Tissue Regeneration Using Macrophage Migration Inhibitory Factor-Impregnated Gelatin Microbeads in Cutaneous Wounds

    PubMed Central

    Zhao, Yunan; Shimizu, Tadamichi; Nishihira, Jun; Koyama, Yoshikazu; Kushibiki, Toshihiro; Honda, Ayumi; Watanabe, Hirokazu; Abe, Riichiro; Tabata, Yasuhiko; Shimizu, Hiroshi

    2005-01-01

    Migration inhibitory factor (MIF) responds to tissue damage and regulates inflammatory and immunological processes. To elucidate the function of MIF in cutaneous wound healing, we analyzed MIF knockout (KO) mice. After the excision of wounds from the dorsal skin of MIF KO and wild-type (WT) mice, healing was significantly delayed in MIF KO mice compared to WT mice. Lipopolysaccharide treatment significantly increased [3H]thymidine uptake in WT mouse fibroblasts compared to MIF KO mouse fibroblasts. Furthermore, there was a significant reduction in fibroblast and keratinocyte migration observed in MIF KO mice after 1-oleoyl-2-lysophosphatidic acid treatment. We subsequently examined whether MIF-impregnated gelatin slow-release microbeads could accelerate skin wound healing. Injection of more than 1.5 μg/500 μl of MIF-impregnated gelatin microbeads around a wound edge accelerated wound healing compared to a single MIF injection without the use of microbeads. MIF-impregnated gelatin microbeads also accelerated skin wound healing in C57BL/6 mice and diabetic db/db mice. Furthermore, incorporating MIF-impregnated gelatin microbeads into an artificial dermis implanted into MIF KO mice accelerated procollagen production and capillary formation. These findings suggest that MIF is crucial in accelerating cutaneous wound healing and that MIF-impregnated gelatin microbeads represent a promising treatment to facilitate skin wound healing. PMID:16314467

  12. Ultraviolet light and hyperpigmentation in healing wounds

    SciTech Connect

    Wiemer, D.R.; Spira, M.

    1983-10-01

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

  13. The role of hyaluronan in wound healing.

    PubMed

    Frenkel, Joseph S

    2014-04-01

    The polysaccharide hyaluronan (HA) (synonyms - hyaluronic acid, hyaluronate) is a versatile, polymorphic, glycosoaminoglycan with vast biological functions. HA is found throughout the body, primarily residing in skin, thus playing an important role in wound healing. Research regarding HA's function has changed over the years, primarily focussing on a particular aspect or function. The contribution of HA in each stage of normal wound healing as well as its clinical wound dressing applications will be examined.

  14. Rapid identification of slow healing wounds

    PubMed Central

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

    2016-01-01

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

  15. Rapid identification of slow healing wounds.

    PubMed

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

    2016-01-01

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

  16. Biomarkers for wound healing and their evaluation.

    PubMed

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

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

  17. Wound Healing Effect of Curcumin: A Review.

    PubMed

    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.

  18. Ghrelin accelerates wound healing in combined radiation and wound injury in mice.

    PubMed

    Liu, Cong; Hao, Yuhui; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Li, Rong

    2017-02-01

    Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (γ-ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Monitoring diabetic wound healing by NIR spectroscopy.

    PubMed

    Papazoglou, Elisabeth S; Zubkov, Leonid; Zhu, Linda; Weingarten, Michael S; Tyagi, Som; Pourrezaei, Kambiz

    2005-01-01

    Chronic wounds represent one of the most serious complications of diabetes. Lack of quantitative assessment of healing progress makes diabetic wound management a clinical challenge. We constructed an optical device based on near infrared diffuse optical spectroscopy and monitored the change in wound optical properties during healing. A single source, four detector frequency domain instrument with multiple wavelengths was employed in a streptozotocin induced diabetic rat animal model. Optical properties including absorption and reduced scattering coefficients were measured. Our results show that there is significant difference in the absorption and reduced scattering coefficient of the wounds between diabetic and controls rats, and such difference persists throughout the healing period. Our technique would be highly useful in monitoring and quantifying the wound healing process.

  20. Low level diode laser accelerates wound healing.

    PubMed

    Dawood, Munqith S; Salman, Saif Dawood

    2013-05-01

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

  1. Can specific nutrients stimulate bowel wound healing?

    PubMed

    Ellinger, Sabine

    2016-06-24

    The purpose of review is to provide an overview on specific nutrients which play an important role in bowel wound healing, and to judge the efficacy of supplementation to derive recommendations for clinical practice. Glutamine, arginine, butyrate, ω-3 fatty acids, nucleotides, and several micronutrients are involved in bowel wound healing. However, with regard to clinical trials, the efficacy of supplementation of specific nutrients on bowel wound healing in patients with inflammatory bowel diseases has not been clarified yet. In patients undergoing colon surgery, sufficient evidence exists that the perioperative supply of an enteral immunomodulating formula enriched with arginine, nucleotides, and ω-3 fatty acids may improve intestinal wound healing, considering the lower risk of wound infections, wound dehiscence, and intra-abdominal abscess. Even if a range of nutrients are involved in bowel wound healing, only perioperative supply of an enteral immunomodulating formula to cancer patients undergoing colon surgery, can be recommended. Further randomized controlled trials are needed to elucidate the efficacy of individual nutrients on intestinal wound healing.

  2. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice.

    PubMed

    Sidhu, G S; Mani, H; Gaddipati, J P; Singh, A K; Seth, P; Banaudha, K K; Patnaik, G K; Maheshwari, R K

    1999-01-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

  3. Diabetic wound healing in a MMP9-/- mouse model.

    PubMed

    Cho, Hongkwan; Balaji, Swathi; Hone, Natalie L; Moles, Chad M; Sheikh, Abdul Q; Crombleholme, Timothy M; Keswani, Sundeep G; Narmoneva, Daria A

    2016-09-01

    Reduced mobilization of endothelial progenitor cells (EPCs) from the bone marrow (BM) and impaired EPC recruitment into the wound represent a fundamental deficiency in the chronic ulcers. However, mechanistic understanding of the role of BM-derived EPCs in cutaneous wound neovascularization and healing remains incomplete, which impedes development of EPC-based wound healing therapies. The objective of this study was to determine the role of EPCs in wound neovascularization and healing both under normal conditions and using single deficiency (EPC) or double-deficiency (EPC + diabetes) models of wound healing. MMP9 knockout (MMP9 KO) mouse model was utilized, where impaired EPC mobilization can be rescued by stem cell factor (SCF). The hypotheses were: (1) MMP9 KO mice exhibit impaired wound neovascularization and healing, which are further exacerbated with diabetes; (2) these impairments can be rescued by SCF administration. Full-thickness excisional wounds with silicone splints to minimize contraction were created on MMP9 KO mice with/without streptozotocin-induced diabetes in the presence or absence of tail-vein injected SCF. Wound morphology, vascularization, inflammation, and EPC mobilization and recruitment were quantified at day 7 postwounding. Results demonstrate no difference in wound closure and granulation tissue area between any groups. MMP9 deficiency significantly impairs wound neovascularization, increases inflammation, decreases collagen deposition, and decreases peripheral blood EPC (pb-EPC) counts when compared with wild-type (WT). Diabetes further increases inflammation, but does not cause further impairment in vascularization, as compared with MMP9 KO group. SCF improves neovascularization and increases EPCs to WT levels (both nondiabetic and diabetic MMP9 KO groups), while exacerbating inflammation in all groups. SCF rescues EPC-deficiency and impaired wound neovascularization in both diabetic and nondiabetic MMP9 KO mice. Overall, the

  4. Elevated levels of matrix metalloproteinases and chronic wound healing: an updated review of clinical evidence.

    PubMed

    Lazaro, J L; Izzo, V; Meaume, S; Davies, A H; Lobmann, R; Uccioli, L

    2016-05-01

    In the past 20 years, research and clinical trials on the healing process of chronic wounds have highlighted the key role of the family of enzymes called matrix metalloproteinases (MMPs). If a strong correlation between the course of healing of chronic wounds and the levels of a biological marker can be demonstrated, then it may be possible to: i) identify the best marker threshold to predict the clinical evolution of the pathology; and ii) if causality has been found between the marker and pathology, to improve the healing outcome, to change the marker level. The databases Medline and Embase were searched to identify clinical trials pertaining to the assessment of MMPs in chronic wounds with the following keywords 'metalloproteinase' or 'metalloprotease' and 'wound healing'. Clinical trials were considered for inclusion if they enrolled patients with cutaneous chronic wounds and were published in English. More than 50 clinical trials, consensus documents and guidelines were assessed for this review. MMPs play key roles in the wound healing process, and excessive expression and activation of some of these enzymes is seen in chronic cutaneous wounds where healing is delayed. Levels of MMPs are affected by a number of factors, including patient and wound characteristics. Levels of MMPs can be used to indicate the prognosis of chronic wounds and protease modulating treatments used to improve healing rates. The authors report no conflicts of interest in this work.

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

    PubMed

    Cheng, Chu; Singh, Vandana; Krishnan, Anand; Kan, Michelle; Martinez, Jose A; Zochodne, Douglas W

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Understanding the inflammatory process in wound healing.

    PubMed

    Gethin, Georgina

    2012-03-01

    The basic elements of wound healing can be described using three sequential and overlapping phases: inflammation, proliferation and regeneration. These phases represent a highly organized, tightly regulated and complex sequence of events that are dependent on an exquisite balance between various cell types and mediators. Inflammation is a prerequisite to healing; however, chronic wounds in particular exhibit a prolonged inflammatory response, thus providing an ideal environment for bacterial infiltration and proliferation. Considering that approximately 70% of all wounds are chronic, with the majority of wound care being delivered in the community, this paper aims to support nurses in their understanding of inflammation in order to enhance clinical practice.

  8. microRNA and Wound Healing

    PubMed Central

    Sen, Chandan K.

    2016-01-01

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

  9. [Scarless fetal wound healing and its mechanism].

    PubMed

    Li, Yaonan; Jiang, Duyin

    2014-12-01

    Scarless healing is considered as the most ideal mode of wound repair. This ability generally exists in the early period of mammalian embryos, however it gradually turns to scar healing with the development of the embryos. This phenomenon is the result of the interaction of multiple biological functions, and the mechanism is still uncertain. This article deals with a systematical review of literature concerning the mechanism of scarless healing based on the recent experimental studies, hoping to provide evidence for the treatment of wounds to realize scarless healing in adult.

  10. Systems-based approaches toward wound healing

    PubMed Central

    Buganza-Tepole, Adrian; Kuhl, Ellen

    2013-01-01

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

  11. Mast Cells Regulate Wound Healing in Diabetes

    PubMed Central

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

    2016-01-01

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

  12. Arginase inhibition promotes wound healing in mice.

    PubMed

    Kavalukas, Sandra L; Uzgare, Aarti R; Bivalacqua, Trinity J; Barbul, Adrian

    2012-02-01

    Arginase plays important regulatory roles in polyamine, ornithine, and nitric oxide syntheses. However, its role in the healing process has not been delineated. In this study, we used a highly potent and specific inhibitor of arginase, namely 2(S)-amino-6-boronohexanoic acid NH4 (ABH) to evaluate the role of arginase function in wound healing. ABH or saline was applied topically to full thickness, dorsal, excisional wounds in C57BL/6 mice every 8 hours for 14 days post surgery and the rate of wound closure was estimated planimetrically. Wound tissue was harvested from mice sacrificed on postoperative days 3 and 7 and examined histologically. The extent of epithelial, connective, and granulation tissue present within the wound area was estimated histomorphometrically. The effect of ABH on wound arginase activity, production of nitric oxide metabolites (NO(x)), and presence of smooth muscle actin positive cells (myofibroblasts) was evaluated. While arginase activity was inhibited in vivo, the rate of wound closure significantly increased 7 days post-surgery, (21 ± 4%: P < .01; Student t test) in ABH treated animals. This was accompanied by an early increase in wound granulation tissue and accumulation of NO(x) followed by enhanced re-epithelialization and localization of myofibroblasts beneath the wound epithelium. Arginase inhibition improves excisional wound healing and may be used to develop therapeutics for early wound closure. Copyright © 2012 Mosby, Inc. All rights reserved.

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

    PubMed

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

    2014-01-01

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

  14. Cellular events and biomarkers of wound healing

    PubMed Central

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

    2012-01-01

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

  15. DESOXYCORTICOSTERONE ACETATE AND WOUND HEALING

    PubMed Central

    Pirani, Conrad L.; Stepto, Robert C.; Sutherland, Kenneth

    1951-01-01

    The effect of desoxycorticosterone acetate (DCA) on the granulation tissue of healing and healed linear laparotomy wounds was studied in young adult male guinea pigs maintained on a complete diet and on a known intake of ascorbic acid. DCA induces the production of an excessive amount of granulation tissue, as evidenced by a relatively great number of fibroblasts and by a larger amount of ground substance. This effect was accompanied by a slight to moderate lag in the maturation process of both cellular and intercellular elements. These changes were observed when DCA administration was begun 5 days prior to operation, but were less obvious or absent if DCA was injected, beginning on the 5th or 10th postoperative day. The results indicate that the action of DCA on immature, proliferating connective tissue is marked, and is considerably less or absent when connective tissue elements have reached partial or almost complete maturity. The effect of DCA on connective tissue does not appear to rest on the basis of an altered nutritional status. Chemical and histochemical studies of the adrenals suggest that the action of DCA on connective tissue is probably mediated through a disturbance of adrenocortical function, namely an imbalance between hormones of the zona glomerulosa (excess of DCA) and those of the zona fasciculata (deficiency of glucocorticoids). The presence of changes in granulation tissue and the lack of them in mature resting connective tissue of DCA-treated guinea pigs confirm the view that a profound difference in the response mechanism exists between resting and actively proliferating connective tissue. PMID:14824397

  16. Shock wave therapy in wound healing.

    PubMed

    Qureshi, Ali A; Ross, Kimberly M; Ogawa, Rei; Orgill, Dennis P

    2011-12-01

    Recently, shock wave therapy has been investigated as an adjuvant therapy in the treatment of acute and chronic wounds. There are several devices with focused and unfocused shock waves that have been administered to a heterogenous group of wounds. Encouraging preclinical and clinical studies suggest that shock wave therapy may promote wound healing with little or no adverse events, prompting investigations into the mechanism of action and additional clinical trials. The peer-reviewed literature within the past 10 years was studied using an evidence-based approach. Preclinical studies demonstrate that shock wave therapy affects cellular function and leads to the expression of several genes and elaboration of growth factors known to promote wound healing. Limited clinical trials are encouraging for the use of shock wave therapy in the treatment of acute and chronic wounds. Serious complications, including wound infections, bleeding, hematomas, seromas, and petechiae, have not been reported in the largest of these studies. Shock wave therapy is an intriguing physical modality that may play an important role as an adjuvant therapy in wound healing. To date, there is no consensus on which wounds are most likely to benefit from shock wave therapy and what the optimal power, degree of focus, and frequency or number of cycles should be. Well-designed preclinical and clinical studies are necessary to better understand shock wave therapy in wound healing.

  17. Practices in Wound Healing Studies of Plants

    PubMed Central

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

    2011-01-01

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

  18. Practices in wound healing studies of plants.

    PubMed

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

    2011-01-01

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

  19. Tobacco exposure and wound healing in head and neck surgical wounds.

    PubMed

    Lassig, Amy Anne D; Bechtold, Joan E; Lindgren, Bruce R; Pisansky, Andrew; Itabiyi, Abayo; Yueh, Bevan; Joseph, Anne M

    2017-09-20

    Smoking impairs wound healing, yet the underlying pathophysiological mechanisms are unclear. We evaluated tobacco-altered healing in head and neck surgery by studying the association between biomarkers and tobacco exposure, as well as cutaneous perfusion by smoking status. Prospective cohort study, tertiary/academic care center, 2011 to present. Patients who required head and neck surgery were enrolled prospectively. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers associated with postulated mechanisms of smoking-impaired healing were assayed. These included interleukin-1, -6, and -8; tumor necrosis factor- alpha; transforming growth factor-beta; epidermal growth factor (EGF); basic fibroblastic growth factor (bFGF); C-reactive protein; vascular endothelial growth factor; soluble FMS-like tyrosine kinase-1 (sFLT-1); and placental growth factor. Tobacco exposure and clinical outcomes were recorded. Two sample two-sided t tests evaluated the differences in cytokine levels by tobacco exposure. In a second cohort, cutaneous vascular assessment via indocyanine green angiography was compared by smoking status. Twenty-eight patients were enrolled with drain fluid collection. Twenty-one subjects were current/former smokers, whereas seven were never smokers. EGF was higher in never smokers than smokers in a statistically significant manner (P = 0.030). Likewise, sFLT-1 was significantly higher in never smokers (P = 0.011). Cutaneous angiography revealed nonsmokers to have significantly higher cutaneous perfusion than smokers. In this head and neck surgical cohort, significantly higher EGF and sFLT-1 levels in wound fluid were associated with never smoking, suggesting that smoking has adverse effects on the inflammatory phase of wound healing. Cutaneous angiography supports the detrimental effect of smoking on skin perfusion. These findings suggest the need for further study as well as therapeutic targets for smokers undergoing surgery. IIb

  20. Nanotoxicity in Systemic Circulation and Wound Healing.

    PubMed

    Bakshi, Mandeep Singh

    2017-06-19

    Nanotoxicity of nanomaterials is an important issue in view of their potential applications in systemic circulation and wound healing dressing. This account specifically deals with several characteristic features of different nanomaterials which induce hemolysis and how to make them hemocompatible. The shape, size, and surface functionalities of naked metallic as well as nonmetallic nanoparticles surfaces are responsible for the hemolysis. An appropriate coating of biocompatible molecules dramatically reduces hemolysis and promotes their ability as safe drug delivery vehicles. The use of coated nanomaterials in wound healing dressing opens several new strategies for rapid wound healing processes. Properly designed nanomaterials should be selected to minimize the nanotoxicity in the wound healing process. Future directions need new synthetic methods for engineered nanomaterials for their best use in nanomedicine and nanobiotechnology.

  1. Dendritic epidermal T cells facilitate wound healing in diabetic mice

    PubMed Central

    Liu, Zhongyang; Xu, Yingbin; Chen, Lei; Xie, Julin; Tang, Jinming; Zhao, Jingling; Shu, Bin; Qi, Shaohai; Chen, Jian; Liang, Guangping; Luo, Gaoxing; Wu, Jun; He, Weifeng; Liu, Xusheng

    2016-01-01

    The impairment of skin repair in diabetic patients can lead to increased morbidity and mortality. Proper proliferation, apoptosis and migration in keratinocytes are vital for skin repair, but in diabetic patients, hyperglycemia impairs this process. Dendritic epidermal T cells (DETCs) are an important part of the resident cutaneous immunosurveillance program. We observed a reduction in the number of DETCs in a streptozotocin-induced diabetic mouse model. This reduction in DETCs resulted in decreased IGF-1 and KGF production in the epidermis, which is closely associated with diabetic delayed wound closure. DETCs ameliorated the poor wound-healing conditions in diabetic mice by increasing keratinocyte migration and proliferation and decreasing keratinocyte apoptosis in diabetes-like microenvironments. Our results elucidate a new mechanism for diabetic delayed wound closure and point to a new strategy for the treatment of wounds in diabetic patients. PMID:27347345

  2. Regeneration: the ultimate example of wound healing.

    PubMed

    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.

  3. Using behavior modification to promote wound healing.

    PubMed

    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.

  4. Wound Healing Essentials: Let There Be Oxygen

    PubMed Central

    Sen, Chandan K.

    2009-01-01

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

  5. Skin wound healing and scarring: fetal wounds and regenerative restitution.

    PubMed

    Yates, Cecelia C; Hebda, Patricia; Wells, Alan

    2012-12-01

    The adverse physiological and psychological effects of scars formation after healing of wounds are broad and a major medical problem for patients. In utero, fetal wounds heal in a regenerative manner, though the mechanisms are unknown. Differences in fetal scarless regeneration and adult repair can provide key insight into reduction of scarring therapy. Understanding the cellular and extracellular matrix alterations in excessive adult scarring in comparison to fetal scarless healing may have important implications. Herein, we propose that matrix can be controlled via cellular therapy to resemble a fetal-like matrix that will result in reduced scarring. Copyright © 2013 Wiley Periodicals, Inc.

  6. Skin Wound Healing and Scarring: Fetal Wounds and Regenerative Restitution

    PubMed Central

    Yates, Cecelia C.; Hebda, Patricia; Wells, Alan

    2014-01-01

    The adverse physiological and psychological effects of scars formation after healing of wounds are broad and a major medical problem for patients. In utero, fetal wounds heal in a regenerative manner, though the mechanisms are unknown. Differences in fetal scarless regeneration and adult repair can provide key insight into reduction of scarring therapy. Understanding the cellular and extracellular matrix alterations in excessive adult scarring in comparison to fetal scarless healing may have important implications. Herein, we propose that matrix can be controlled via cellular therapy to resemble a fetal-like matrix that will result in reduced scarring. PMID:24203921

  7. Honey: an immunomodulator in wound healing.

    PubMed

    Majtan, Juraj

    2014-01-01

    Honey is a popular natural product that is used in the treatment of burns and a broad spectrum of injuries, in particular chronic wounds. The antibacterial potential of honey has been considered the exclusive criterion for its wound healing properties. The antibacterial activity of honey has recently been fully characterized in medical-grade honeys. Recently, the multifunctional immunomodulatory properties of honey have attracted much attention. The aim of this review is to provide closer insight into the potential immunomodulatory effects of honey in wound healing. Honey and its components are able to either stimulate or inhibit the release of certain cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) from human monocytes and macrophages, depending on wound condition. Similarly, honey seems to either reduce or activate the production of reactive oxygen species from neutrophils, also depending on the wound microenvironment. The honey-induced activation of both types of immune cells could promote debridement of a wound and speed up the repair process. Similarly, human keratinocytes, fibroblasts, and endothelial cell responses (e.g., cell migration and proliferation, collagen matrix production, chemotaxis) are positively affected in the presence of honey; thus, honey may accelerate reepithelization and wound closure. The immunomodulatory activity of honey is highly complex because of the involvement of multiple quantitatively variable compounds among honeys of different origins. The identification of these individual compounds and their contributions to wound healing is crucial for a better understanding of the mechanisms behind honey-mediated healing of chronic wounds. © 2014 by the Wound Healing Society.

  8. Wound healing in acutely injured fascia.

    PubMed

    Lau, Frank H; Pomahac, Bohdan

    2014-05-01

    Fascial healing following acute injury, such as that occurring during surgical procedures, is defined functionally. For example, failure of fascial healing following celiotomy is only identified when incisional hernias are diagnosed. Such hernias incur billions of dollars per year in medical costs. Despite the importance of fascial healing, there is a paucity of data regarding the quality such healing. In clinical settings, the quantification of fascial wound healing is limited to a binary state: either there is no clinically apparent functional deficit and full fascia healing is assumed, or an incisional hernia or other functional failure is visible and the fascia did not heal. There are no clinical methods to isolate and functionally test fascia in patients. Recent studies have revealed unexpected findings regarding the recovery of tensile strength, specific surgical methods that optimize fascial healing, and the potential impact of biological pharmaceuticals in eliminating fascial healing failure. However, much remains unknown about the biology of fascial healing. © 2014 by the Wound Healing Society.

  9. Wound healing activity of latex of Euphorbia caducifolia.

    PubMed

    Goyal, Manoj; Nagori, B P; Sasmal, D

    2012-12-18

    [corrected] Euphorbia caducifolia is a Euphorbiaceae species native to Thar Desert of India, where latex of E. caducifolia (ECL) is used by the local inhabitants for treatment of bleeding wound, cutaneous eruption and other skin diseases. Looking to the medicinal importance of the plant, it was considered worthwhile to scientifically evaluate the ECL for the wound healing activity. In vitro methods, clotting of platelet free plasma and angiogenesis in chick chorioallantoic membrane (CCM) were used for studying effect of ECL on clotting and angiogenesis. Excision and incision wounds model were used to study effect of ECL on wound contraction, tensile strength and hydroxyproline and DNA content. ECL treatment stimulates the blood vessel formation in CCM, at the all dose levels. 56.77, 74.48 and 78.09% increase in area of angiogenesis was observed in ECL 2.5, 5.0 and 10mg/ml treated groups respectively. The excised skin of ECL 5.0 and 10mg/ml treated animals found to have higher content of hydroxyproline and DNA, when compared with control group. An acceleration of the wound closure was observed with an enhanced number of fibroblasts and collagen content in ECL treated mice. Result of in vitro and in vivo experiments indicate that ECL exerts significant wound healing activity, demonstrating its relevant therapeutic potential. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Minimally invasive options for cutaneous defects: secondary intention healing, partial closure, and skin grafts.

    PubMed

    Cordoro, Kelly M; Russell, Mark A

    2005-05-01

    Several wound management options are available for defects of the head and neck, and choosing the best option requires consideration of several variables. The physical characteristics of the defect, the experience and preferences of the surgeon, and the desires and medicosocial situation of the patient may influence the final reconstructive decision. As the concepts and techniques in the field of reconstructive surgery advance, conservative wound management options should not be overlooked. This article reviews the minimally invasive options for the management of cutaneous defects, including second intention healing, partial closures, and skin grafts. The authors review the basic concepts of wound healing.

  11. Mechanoregulation of Wound Healing and Skin Homeostasis

    PubMed Central

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

    2016-01-01

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