Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults.

PubMed

Ali, Arham; Herndon, David N; Mamachen, Ashish; Hasan, Samir; Andersen, Clark R; Grogans, Ro-Jon; Brewer, Jordan L; Lee, Jong O; Heffernan, Jamie; Suman, Oscar E; Finnerty, Celeste C

2015-05-04

Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge. Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P < 0.05). The average number of days between skin grafting procedures was also lower in propranolol patients (10 ± 5 days) than in control patients (17 ± 12 days; P = 0.02), indicative of a faster donor site healing time in the propranolol group. Packed red blood cell infusion was similar between groups (control 5.3 ± 5.4 units vs. propranolol 4.4 ± 3.1 units, P = 0.89). Propranolol was associated with a 5 to 7% improvement in perioperative hematocrit during grafting procedures of 4,000 to 16,000 cm(2) compared to control (P = 0.002). Administration of propranolol during the acute

Wound healing in mammals and amphibians: toward limb regeneration in mammals.

PubMed

Kawasumi, Aiko; Sagawa, Natsume; Hayashi, Shinichi; Yokoyama, Hitoshi; Tamura, Koji

2013-01-01

Mammalian fetal skin regenerates perfectly, but adult skin repairs by the formation of scar tissue. The cause of this imperfect repair by adult skin is not understood. In contrast, wounded adult amphibian (urodeles and anurans) skin is like mammalian fetal skin in that it repairs by regeneration, not scarring. Scar-free wound repair in adult Xenopus is associated with expression of the paired homeobox transcription factor Prx1 by mesenchymal cells of the wound, a feature shared by mesenchymal cells of the regeneration blastema of the axolotl limb. Furthermore, mesenchymal cells of Xenopus skin wounds that harbor the mouse Prx1-limb-enhancer as a transgene exhibit activation of the enhancer despite the fact that they are Xenopus cells, suggesting that the mouse Prx1 enhancer possesses all elements required for its activation in skin wound healing, even though activation of the same enhancer in the mouse is not seen in the wounded skin of an adult mouse. Elucidation of the role of the Prx1 gene in amphibian skin wound healing will help to clarify the molecular mechanisms of scarless wound healing. Shifting the molecular mechanism of wound repair in mammals to that of amphibians, including reactivation of the Prx1-limb-enhancer, will be an important clue to stimulate scarless wound repair in mammalian adult skin. Finding or creating Prx1-positive stem cells in adult mammal skin by activating the Prx1-limb-enhancer may be a fast and reliable way to provide for scarless skin wound repair, and even directly lead to limb regeneration in mammals.

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

Sanativo Wound Healing Product Does Not Accelerate Reepithelialization in a Mouse Cutaneous Wound Healing Model.

PubMed

Marshall, Clement D; Hu, Michael S; Leavitt, Tripp; Barnes, Leandra A; Cheung, Alexander T M; Malhotra, Samir; Lorenz, H Peter; Delp, Scott L; Quake, Stephen R; Longaker, Michael T

2017-02-01

Sanativo is an over-the-counter Brazilian product derived from Amazon rainforest plant extract that is purported to improve the healing of skin wounds. Two experimental studies have shown accelerated closure of nonsplinted excisional wounds in rat models. However, these models allow for significant contraction of the wound and do not approximate healing in the tight skin of humans. Full-thickness excisional wounds were created on the dorsal skin of mice and were splinted with silicone rings, a model that forces the wound to heal by granulation and reepithelialization. Sanativo or a control solution was applied either daily or every other day to the wounds. Photographs were taken every other day, and the degree of reepithelialization of the wounds was determined. With both daily and every-other-day applications, Sanativo delayed reepithelialization of the wounds. Average time to complete healing was faster with control solution versus Sanativo in the daily application group (9.4 versus 15.2 days; p < 0.0001) and the every-other-day application group (11 versus 13 days; p = 0.017). The size of visible scar at the last time point of the study was not significantly different between the groups, and no differences were found on histologic examination. Sanativo wound healing compound delayed wound reepithelialization in a mouse splinted excisional wound model that approximates human wound healing. The size of visible scar after complete healing was not improved with the application of Sanativo. These results should cast doubt on claims that this product can improve wound healing in humans.

Injury-activated glial cells promote wound healing of the adult skin in mice.

PubMed

Parfejevs, Vadims; Debbache, Julien; Shakhova, Olga; Schaefer, Simon M; Glausch, Mareen; Wegner, Michael; Suter, Ueli; Riekstina, Una; Werner, Sabine; Sommer, Lukas

2018-01-16

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.

Estrogen Effects on Wound Healing

PubMed Central

Horng, Huann-Cheng; Chang, Wen-Hsun; Yeh, Chang-Ching; Huang, Ben-Shian; Chang, Chia-Pei; Chen, Yi-Jen; Tsui, Kuan-Hao

2017-01-01

Wound healing is a physiological process, involving three successive and overlapping phases—hemostasis/inflammation, proliferation, and remodeling—to maintain the integrity of skin after trauma, either by accident or by procedure. Any disruption or unbalanced distribution of these processes might result in abnormal wound healing. Many molecular and clinical data support the effects of estrogen on normal skin homeostasis and wound healing. Estrogen deficiency, for example in postmenopausal women, is detrimental to wound healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment may reverse these effects. Understanding the role of estrogen on skin might provide further opportunities to develop estrogen-related therapy for assistance in wound healing. PMID:29099810

Mesenchymal stem cell therapy for attenuation of scar formation during wound healing.

PubMed

Jackson, Wesley M; Nesti, Leon J; Tuan, Rocky S

2012-05-31

Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts, and although it is inferior to the uninjured skin, it is able to restore integrity to the boundary between the body and its environment. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury. Adult tissue-derived mesenchymal stem cells, which participate in normal wound healing, are trophic mediators of tissue repair. These cells participate in attenuating inflammation in the wound and reprogramming the resident immune and wound healing cells to favor tissue regeneration and inhibit fibrotic tissue formation. As a result, these cells have been considered and tested as a likely candidate for a cellular therapy to promote scar-less wound healing. This review identifies specific mechanisms by which mesenchymal stem cells can limit tissue fibrosis and summarizes recent in vivo studies where these cells have been used successfully to limit scar formation.

Bulge Hair Follicle Stem Cells Accelerate Cutaneous Wound Healing in Rats.

PubMed

Heidari, Fatemeh; Yari, Abazar; Rasoolijazi, Homa; Soleimani, Mansoureh; Dehpoor, Ahmadreza; Sajedi, Nayereh; Joulai Veijouye, Sanaz; Nobakht, Maliheh

2016-04-01

Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing. Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses. Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group. Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.

Prx-1 expression in Xenopus laevis scarless skin-wound healing and its resemblance to epimorphic regeneration.

PubMed

Yokoyama, Hitoshi; Maruoka, Tamae; Aruga, Akio; Amano, Takanori; Ohgo, Shiro; Shiroishi, Toshihiko; Tamura, Koji

2011-12-01

Despite a strong clinical need for inducing scarless wound healing, the molecular factors required to accomplish it are unknown. Although skin-wound healing in adult mammals often results in scarring, some amphibians can regenerate injured body parts, even an amputated limb, without it. To understand the mechanisms of perfect skin-wound healing in regenerative tetrapods, we studied the healing process in young adult Xenopus "froglets" after experimental skin excision. We found that the excision wound healed completely in Xenopus froglets, without scarring. Mononuclear cells expressing a homeobox gene, prx1, accumulated under the new epidermis of skin wounds on the limb and trunk and at the regenerating limb. In transgenic Xenopus froglets expressing a reporter for the mouse prx1 limb-specific enhancer, activity was seen in the healing skin and in the regenerating limb. Comparable activity did not accompany skin-wound healing in adult mice. Our results suggest that scarless skin-wound healing may require activation of the prx1 limb enhancer, and competence to activate the enhancer is probably a prerequisite for epimorphic regeneration, such as limb regeneration. Finally, the induction of this prx1 enhancer activity may be useful as a reliable marker for therapeutically induced scarless wound healing in mammals.

Blood-derived small Dot cells reduce scar in wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Wuyi; Li Shaowei; Longaker, Michael T.

2008-04-15

Wounds in fetal skin heal without scar, however the mechanism is unknown. We identified a novel group of E-cadherin positive cells in the blood of fetal and adult mice and named them 'Dot cells'. The percentage of Dot cells in E16.5 fetal mice blood is more than twenty times higher compared to adult blood. Dot cells also express integrin {beta}1, CD184, CD34, CD13{sup low} and Sca1{sup low}, but not CD45, CD44, and CD117. Dot cells have a tiny dot shape between 1 and 7 {mu}m diameters with fast proliferation in vitro. Most of the Dot cells remain positive for E-cadherinmore » and integrin {beta}1 after one month in culture. Transplantation of Dot cells to adult mice heals skin wounds with less scar due to reduced smooth muscle actin and collagen expression in the repair tissue. Tracking GFP-positive Dot cells demonstrates that Dot cells migrate to wounds and differentiate into dermal cells, which also express strongly to FGF-2, and later lose their GFP expression. Our results indicate that Dot cells are a group of previously unidentified cells that have strong wound healing effect. The mechanism of scarless wound healing in fetal skin is due to the presence of a large number of Dot cells.« less

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

Mast cells contribute to scar formation during fetal wound healing.

PubMed

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

2012-02-01

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; however, they 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 Kit(W/W-v) mice compared with 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.

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. © 2015 by the Wound Healing Society.

Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration

PubMed Central

Kanji, Suman

2017-01-01

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process. PMID:29213192

Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration.

PubMed

Kanji, Suman; Das, Hiranmoy

2017-01-01

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-01-01

Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p < 0.05) were determined and subsequently tested on a holdout sample of data. A different model predicted healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics. © 2013 by the Wound Healing Society.

Burn Wound Healing and Tissue Engineering.

PubMed

Singer, Adam J; Boyce, Steven T

In 2016 the American Burn Association held a State of the Science conference to help identify burn research priorities for the next decade. The current paper summarizes the work of the sub-committee on Burn Wound Healing and Tissue Engineering. We first present the priorities in wound healing research over the next 10 years. We then summarize the current state of the science related to burn wound healing and tissue engineering including determination of burn depth, limiting burn injury progression, eschar removal, management of microbial contamination and wound infection, measuring wound closure, accelerating wound healing and durable wound closure, and skin substitutes and tissue engineering. Finally, a summary of the round table discussion is presented.

Pollution dilemma in Asian population: CNG and wound healing.

PubMed

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

2009-11-01

Automobile exhaust constituents contribute significantly to air pollution in urban areas and compressed natural gas (CNG) is considered one of the most promising fuel alternatives for the future. CNG-powered four-stroke engine auto-rickshaws are ubiquitous in South Asian cities as taxi and for commercial transportation. Automotive exhaust contains several toxins, which are overwhelmingly toxic to the processes of wound healing. By utilizing the in vivo mouse model of wound healing, this report analyzes the effects of CNG-powered four-stroke auto-rickshaws smoke solution (4SARSS) on different events of wound healing; dermal matrix regeneration, re-epithelialization and neovascularization. A total of 72 adult mice, divided in eight groups were exposed to 4SARSS for 12 days. A highly significant reduction (P<0.001) in wound closure was observed among all 4SARSS treated groups, at each time point of the experiment. An immature development in both the neoepidermis and the neodermis was observed among all 4SARSS treated wounds with defective re-epithelialization, dermal matrix regeneration and maturation of collagen bundles. Abbott curve, angular spectrum, 3D surface topographies, and histological investigations of wounds explicated highly significant activation (P<0.001) of delayed-neovascularization among 4SARSS treated wounds. All these annotations advocate excessive toxicity of emission from CNG-powered auto-rickshaws to the process of wound healing and people occupationally exposed to this toxic emissions may suffer varying degree of delayed wound healing. Crown Copyright © 2009. Published by Elsevier B.V. All rights reserved.

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

Oxygen in acute and chronic wound healing.

PubMed

Schreml, S; Szeimies, R M; Prantl, L; Karrer, S; Landthaler, M; Babilas, P

2010-08-01

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.

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

Principles of Wound Management and Wound Healing in the Exotic Pets

PubMed Central

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

2015-01-01

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

Potential benefits of allogeneic bone marrow mesenchymal stem cells for wound healing

PubMed Central

Badiavas, Alexander R.; Badiavas, Evangelos V.

2011-01-01

Introduction It is becoming increasingly evident that select adult stem cells have the capacity to participate in repair and regeneration of damaged and/or diseased tissues. Mesenchymal stem cells have been among the most studied adult stem cells for the treatment of a variety of conditions including wound healing. Areas covered Mesenchymal stem cell features potentially beneficial to cutaneous wound healing applications are reviewed. Expert opinion Given their potential for in vitro expansion and immune modulatory effects, both autologous and allogeneic mesenchymal stem cells appear to be well suited as wound healing therapies. Allogeneic mesenchymal stem cells derived from young healthy donors could have particular advantage over autologous sources where age and systemic disease can be significant factors. PMID:21854302

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-10-23

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

Healing the wounded, neglected inner child of the past.

PubMed

Kneisl, C R

1991-09-01

Childhood experiences of the past can have a destructive effect on the present. The inner child in each person is the core of the personality that has been molded by the directions on how to act to be loved that the person receives in childhood. Painful experiences and lack of nurturing in dysfunctional families wound the inner child and contaminate adult experiences. Many persons with eating disorders have a wounded or neglected inner child that affects their adult lives. Characteristically, they demonstrate problems with trust, intimacy, addictive and compulsive behaviors, and codependence among others. Healing the inner child by grieving neglected childhood developmental needs is a long process, but one that improves the quality of one's life. Nurses, depending on their educational background and clinical skills, can help clients move toward understanding and healing the wounded, neglected inner child of the past.

Effects of glutamine on wound healing.

PubMed

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

2015-06-01

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

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.

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

Progress in corneal wound healing.

PubMed

Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

2015-11-01

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

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

Intracellular Adenosine Triphosphate Delivery Enhanced Skin Wound Healing in Rabbits

PubMed Central

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

2016-01-01

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

Hypothyroidism and Wound Healing After Salvage Laryngectomy.

PubMed

Rosko, Andrew J; Birkeland, Andrew C; Bellile, Emily; Kovatch, Kevin J; Miller, Ashley L; Jaffe, Craig C; Shuman, Andrew G; Chinn, Steven B; Stucken, Chaz L; Malloy, Kelly M; Moyer, Jeffrey S; Casper, Keith A; Prince, Mark E P; Bradford, Carol R; Wolf, Gregory T; Chepeha, Douglas B; Spector, Matthew E

2018-05-01

Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established. A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n = 182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5 mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed. The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8-7.1; p = 0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6-49.9; p = 0.001). The risk for fistula (p = 0.003) and reoperation (p = 0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH. Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.

The growth receptors and their role in wound healing.

PubMed

Rolfe, Kerstin J; Grobbelaar, Adriaan O

2010-11-01

Abnormal wound healing is a major problem in healthcare today, with both scarring and chronic wounds affecting large numbers of individuals worldwide. Wound healing is a complex process involving several variables, including growth factors and their receptors. Chronic wounds fail to complete the wound healing process, while scarring is considered to be an overzealous wound healing process. Growth factor receptors and their ligands are being investigated to assess their potential in the development of therapeutic strategies to improve wound healing. This review discusses potential therapeutics for manipulating growth factors and their corresponding receptors for the treatment of abnormal wound healing.

Conducted healing to treat large skin wounds.

PubMed

Salgado, M I; Petroianu, A; Alberti, L R; Burgarelli, G L; Barbosa, A J A

2013-01-01

Improvement of the healing process to provide better aesthetical and functional results continues to be a surgical challenge. This study compared the treatment of skin wounds by means of conducted healing (an original method of treatment by secondary healing) and by the use of autogenous skin grafts. Two skin segments, one on each side of the dorsum,were removed from 17 rabbits. The side that served as a graft donor site was left open as to undergo conducted healing (A)and was submitted only to debridement and local care with dressings. The skin removed from the side mentioned above was implanted as a graft (B) to cover the wound on the other side. Thus, each animal received the two types of treatment on its dorsum (A and B). The rabbits were divided into two groups according to the size of the wounds: Group 1 - A and B (4 cm2)and Group 2 - A and B (25 cm2). The healing time was 19 days for Group 1 and 35 days for Group 2. The final macro- and microscopic aspects of the healing process were analysed comparatively among all subgroups. The presence of inflammatory cells, epidermal cysts and of giant cells was evaluated. No macro- or microscopic differences were observed while comparing the wounds that underwent conducted healing and those in which grafting was employed, although the wounds submitted to conducted healing healed more rapidly. Conducted wound healing was effective for the treatment of skin wounds. Celsius.

Modeling of anisotropic wound healing

NASA Astrophysics Data System (ADS)

Valero, C.; Javierre, E.; García-Aznar, J. M.; Gómez-Benito, M. J.; Menzel, A.

2015-06-01

Biological soft tissues exhibit non-linear complex properties, the quantification of which presents a challenge. Nevertheless, these properties, such as skin anisotropy, highly influence different processes that occur in soft tissues, for instance wound healing, and thus its correct identification and quantification is crucial to understand them. Experimental and computational works are required in order to find the most precise model to replicate the tissues' properties. In this work, we present a wound healing model focused on the proliferative stage that includes angiogenesis and wound contraction in three dimensions and which relies on the accurate representation of the mechanical behavior of the skin. Thus, an anisotropic hyperelastic model has been considered to analyze the effect of collagen fibers on the healing evolution of an ellipsoidal wound. The implemented model accounts for the contribution of the ground matrix and two mechanically equivalent families of fibers. Simulation results show the evolution of the cellular and chemical species in the wound and the wound volume evolution. Moreover, the local strain directions depend on the relative wound orientation with respect to the fibers.

Lumican as a multivalent effector in wound healing.

PubMed

Karamanou, Konstantina; Perrot, Gwenn; Maquart, Francois-Xavier; Brézillon, Stéphane

2018-03-01

Wound healing, a complex physiological process, is responsible for tissue repair after exposure to destructive stimuli, without resulting in complete functional regeneration. Injuries can be stromal or epithelial, and most cases of wound repair have been studied in the skin and cornea. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrices of several tissues, such as the cornea, cartilage, and skin. This molecule has been shown to regulate collagen fibrillogenesis, keratinocyte phenotypes, and corneal transparency modulation. Lumican is also involved in the extravasation of inflammatory cells and angiogenesis, which are both critical in stromal wound healing. Lumican is the only member of the small leucine-rich proteoglycan family expressed by the epithelia during wound healing. This review summarizes the importance of lumican in wound healing and potential methods of lumican drug delivery to target wound repair are discussed. The involvement of lumican in corneal wound healing is described based on in vitro and in vivo models, with critical emphasis on its underlying mechanisms of action. Similarly, the expression and role of lumican in the healing of other tissues are presented, with emphasis on skin wound healing. Overall, lumican promotes normal wound repair and broadens new therapeutic perspectives for impaired wound healing. Copyright © 2018. Published by Elsevier B.V.

Emerging drugs for the treatment of wound healing.

PubMed

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

2015-06-01

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

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

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.

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. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effect of Oral Medication on Wound Healing.

PubMed

Levine, Jeffrey M

2017-03-01

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

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Insulin and wound healing.

PubMed

Hrynyk, Michael; Neufeld, Ronald J

2014-12-01

Skin is a dynamic and complex organ that relies on the interaction of different cell types, biomacromolecules and signaling molecules. Injury triggers a cascade of events designed to quickly restore skin integrity. Depending on the size and severity of the wound, extensive physiological and metabolic changes can occur, resulting in impaired wound healing and increased morbidity resulting in higher rates of death. While wound dressings provide a temporary barrier, they are inherently incapable of significantly restoring metabolic upsets, post-burn insulin resistance, and impaired wound healing in patients with extensive burns. Exogenous insulin application has therefore been investigated as a potential therapeutic intervention for nearly a century to improve wound recovery. This review will highlight the important achievements that demonstrate insulin's ability to stimulate cellular migration and burn wound recovery, as well as providing a perspective on future therapeutic applications and research directions. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

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

PubMed

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

2015-01-01

Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds. © 2015 by the Wound Healing Society.

Elements affecting wound healing time: An evidence based analysis.

PubMed

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

2015-01-01

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

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

PubMed

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

2015-09-01

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

Circadian rhythms accelerate wound healing in female Siberian hamsters

PubMed Central

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

2017-01-01

Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are absent 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 3 h after light onset (ZT03) or 2 h 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. PMID:27998755

Hyperbaric Oxygen, Vasculogenic Stem Cells, and Wound Healing

PubMed Central

Fosen, Katina M.

2014-01-01

Abstract Significance: Oxidative stress is recognized as playing a role in stem cell mobilization from peripheral sites and also cell function. Recent Advances: This review focuses on the impact of hyperoxia on vasculogenic stem cells and elements of wound healing. Critical Issues: Components of the wound-healing process in which oxidative stress has a positive impact on the various cells involved in wound healing are highlighted. A slightly different view of wound-healing physiology is adopted by departing from the often used notion of sequential stages: hemostatic, inflammatory, proliferative, and remodeling and instead organizes the cascade of wound healing as overlapping events or waves pertaining to reactive oxygen species, lactate, and nitric oxide. This was done because hyperoxia has effects of a number of cell signaling events that converge to influence cell recruitment/chemotaxis and gene regulation/protein synthesis responses which mediate wound healing. Future Directions: Our alternative perspective of the stages of wound healing eases recognition of the multiple sites where oxidative stress has an impact on wound healing. This aids the focus on mechanistic events and the interplay among various cell types and biochemical processes. It also highlights the areas where additional research is needed. Antioxid. Redox Signal. 21, 1634–1647. PMID:24730726

Wound Blush Obtainment Is the Most Important Angiographic Endpoint for Wound Healing.

PubMed

Utsunomiya, Makoto; Takahara, Mitsuyoshi; Iida, Osamu; Yamauchi, Yasutaka; Kawasaki, Daizo; Yokoi, Yoshiaki; Soga, Yoshimistu; Ohura, Norihiko; Nakamura, Masato

2017-01-23

This study aimed to assess the optimal angiographic endpoint of endovascular therapy (EVT) for wound healing. Several reports have demonstrated acceptable patency and limb salvage rates following infrapopliteal interventions for the treatment of critical limb ischemia (CLI). However, the optimal angiographic endpoint of EVT remains unclear. We conducted a subanalysis of the prospective multicenter OLIVE (Endovascular Treatment for Infrainguinal Vessels in Patients with Critical Limb Ischemia) registry investigation assessing patients who received infrainguinal EVT for CLI. We analyzed data from 185 limbs with ischemic ulcerations classified as Rutherford class 5 or 6, managed with EVT alone (i.e., not undergoing bypass surgery). The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between final angiographic data and wound healing was assessed employing a Cox proportional hazards model. The overall wound healing rate was 73.5%. The probabilities of wound healing in patients with wound blush obtainment was significantly higher than that of those without wound blush (79.6% vs. 46.5%; p = 0.01). In the multivariate analysis, wound blush obtainment was an independent predictor of wound healing. The presence of wound blush after EVT is significantly associated with wound healing. Wound blush as an angiographic endpoint for EVT may serve as a novel predictor of wound healing in patients with CLI. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

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.

Inflammation and Neuropeptides: The Connection in Diabetic Wound Healing

PubMed Central

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

2013-01-01

This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization are essential phases of wound healing. The link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. The bidirectional connection between the nervous and the immune systems and the role it plays in wound healing has emerged as one of the focal features of the wound healing dogma. The mediators of this connection include neuropeptides and the cytokines released from different cells including immune and cutaneous cells. Therefore, to develop successful wound healing therapies, it is vital to understand in depth the signaling pathways in the neuro-immune axis and their implication in diabetic wound healing. PMID:19138453

Wound Healing and Care

MedlinePlus

... wound because the area is cleaned with an antibacterial solution before surgery — and it's in a place ... may be frustrating having to hold back on activities like sports while a wound heals. But if ...

Impaired Laparotomy Wound Healing in Obese Rats

PubMed Central

Xing, Liyu; Culbertson, Eric J.; Wen, Yuan; Robson, Martin C.

2015-01-01

Background Obesity increases the risk of laparotomy dehiscence and incisional hernia. The aim of this study was to measure the biological effect of obesity on laparotomy wound healing and the formation of incisional hernias. Methods Normal-weight Sprague–Dawley (SD) and obese Zucker rats were used in an established laparotomy wound healing and incisional ventral hernia model. Mechanical testing was performed on abdominal wall strips collected from laparotomy wounds. Hernia size was measured by digital imaging. Picrosirius staining for collagen isoforms was observed with polarized microscopy. Abdominal wall fibroblasts were cultured to measure collagen matrix remodeling and proliferation. Results Laparotomy wound healing was significantly impaired in obese rats. Mechanical strength was lower than in normal-weight rats. Yield load was reduced in the obese group at all time points. Picrosirius red staining showed increased immature type III collagen content and disorganized type I collagen fibers within laparotomy wounds of obese rats. Wound size was significantly larger in the obese group. Collagen matrix remodeling was impaired with fibroblasts from obese rats, but there was no difference in fibroblast proliferation between the obese and normal-weight groups. Conclusions We observed for the first time that laparotomy wound healing is impaired in obese rats. The recovery of laparotomy wound strength is delayed due to abnormal collagen maturation and remodeling, possibly due to a defect in fibroblast function. Strategies to improve outcomes for laparotomy wound healing in obese patients should include correcting the wound healing defect, possibly with growth factor or cell therapy. PMID:21347822

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2014-07-29

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-08-23

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2012-06-13

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 27 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1); Ovid MEDLINE (2010 to January Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 26, 2012); Ovid EMBASE (2010 to 2012 Week 03); and EBSCO CINAHL (2010 to January 6 2012). All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-05-03

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Wound Healing Effects of Curcumin: A Short Review.

PubMed

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

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.

The contribution of interleukin-2 to effective wound healing.

PubMed

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

2017-02-01

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

The contribution of interleukin-2 to effective wound healing

PubMed Central

DelloStritto, Daniel J; Newell-Rogers, M Karen

2016-01-01

Ineffective skin wound healing is a significant source of morbidity and mortality. Roughly 6.5 million Americans experience chronically open wounds and the cost of treating these wounds numbers in the billions of dollars annually. In contrast, robust wound healing can lead to the development of either hypertrophic scarring or keloidosis, both of which can cause discomfort and can be cosmetically undesirable. Appropriate wound healing requires the interplay of a variety of factors, including the skin, the local microenvironment, the immune system, and the external environment. When these interactions are perturbed, wounds can be a nidus for infection, which can cause them to remain open an extended period of time, or can scar excessively. Interleukin-2, a cytokine that directs T-cell expansion and phenotypic development, appears to play an important role in wound healing. The best-studied role for Interleukin-2 is in influencing T-cell development. However, other cell types, including fibroblasts, the skin cells responsible for closing wounds, express the Interleukin-2 receptor, and therefore may respond to Interleukin-2. Studies have shown that treatment with Interleukin-2 can improve the strength of healed skin, which implicates Interleukin-2 in the wound healing process. Furthermore, diseases that involve impaired wound healing, such as diabetes and systemic lupus erythematosus, have been linked to deficiencies in Interleukin-2 or defects Interleukin-2-receptor signaling. The focus of this review is to summarize the current understanding of the role of Interleukin-2 in wound healing, to highlight diseases in which Interleukin-2 and its receptor may contribute to impaired wound healing, and to assess Interleukin-2-modulating approaches as potential therapies to improve wound healing. PMID:27798123

Recent advances in electrospun nanofibers for wound healing.

PubMed

Chen, Shixuan; Liu, Bing; Carlson, Mark A; Gombart, Adrian F; Reilly, Debra A; Xie, Jingwei

2017-06-01

Electrospun nanofibers represent a novel class of materials that show great potential in many biomedical applications including biosensing, regenerative medicine, tissue engineering, drug delivery and wound healing. In this work, we review recent advances in electrospun nanofibers for wound healing. This article begins with a brief introduction on the wound, and then discusses the unique features of electrospun nanofibers critical for wound healing. It further highlights recent studies that have used electrospun nanofibers for wound healing applications and devices, including sutures, multifunctional dressings, dermal substitutes, engineered epidermis and full-thickness skin regeneration. Finally, we finish with conclusions and future perspective in this field.

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

PubMed

Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

2017-01-13

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

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

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.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

PubMed

Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

Some factors affecting skin and wound healing.

PubMed

Winter, G D

2006-05-01

The domestic pig is the preferred animal for studying the effects of environmental factors on skin and wound because its integument is more like that of man than any other. The three factors that most drastically affect the pattern, speed and quality of healing are dehydration of exposed tissues, the status of the blood supply bringing oxygen and nutrients to the area and sepsis. Wounds exposed to the air lose water vapour, the upper dermis dries and healing takes place beneath a dry scab. Covering a wound with an occlusive dressing prevents scab formation and radically alters the pattern of epidermal wound healing. Blowing on wounds creates a scab within three hours instead of the normal 24 hours but more tissue is sacrificed in the process. This may only be justified if it can be shown that rapid artificial scab formation significantly cuts down the incidence of severe infections, i.e. in large burns. Less serious wounds heal faster when covered with a suitable occlusive dressing. Indolent wounds are characterised by a rim of infected, necrotic tissue in which leucocytes and macrophages are unable to function effectively through lack of oxygen. A suitable dressing changed frequently can bring about mild debridement and re-establish the conditions for healing.

Wound healing in pre-tibial injuries--an observation study.

PubMed

McClelland, Heather M; Stephenson, John; Ousey, Karen J; Gillibrand, Warren P; Underwood, Paul

2012-06-01

Pre-tibial lacerations are complex wounds affecting a primarily aged population, with poor healing and a potentially significant impact on social well-being. Management of these wounds has changed little in 20 years, despite significant advances in wound care. A retrospective observational study was undertaken to observe current wound care practice and to assess the effect of various medical factors on wound healing time on 24 elderly patients throughout their wound journey. Wound length was found to be substantively and significantly associated with wound healing time, with a reduction in instantaneous healing rate of about 30% for every increase of 1 cm in wound length. Hence, longer wounds are associated with longer wound healing times. Prescription of several categories of drugs, including those for ischaemic heart disease (IHD), hypertension, respiratory disease or asthma; and the age of the patient were not significantly associated with wound healing times, although substantive significance could be inferred in the case of prescription for IHD and asthma. Despite the small sample size, this study identified a clear association between healing and length of wound. Neither the comorbidities nor prescriptions explored showed any significant association although some seem to be more prevalent in this patient group. The study also highlighted other issues that require further exploration including the social and economic impact of these wounds. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Effects of genistein on early-stage cutaneous wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

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 bymore » 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

Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with hydrosheets composed of chitin/chitosan, fucoidan, and alginate as wound dressings.

PubMed

Murakami, Kaoru; Ishihara, Masayuki; Aoki, Hiroshi; Nakamura, Shingo; Nakamura, Shin-Ichiro; Yanagibayashi, Satoshi; Takikawa, Megumi; Kishimoto, Satoko; Yokoe, Hidetaka; Kiyosawa, Tomoharu; Sato, Yasunori

2010-01-01

To create a moist environment for rapid wound healing, a hydrosheet composed of alginate, chitin/chitosan, and fucoidan (ACF-HS) has been developed as a functional wound dressing. The aim of this study was to evaluate the accelerating effect of ACF-HS on wound healing for rat mitomycin C-treated healing-impaired wounds. Full-thickness skin defects were made on the back of rats and mitomycin C was applied onto the wound for 10 minutes to prepare a healing-impaired wound. After thoroughly washing out the mitomycin C, ACF-HS was applied to the healing-impaired wounds. The rats were later euthanized and histological sections of the wounds were prepared. The histological examinations showed significantly advanced granulation tissue and capillary formations in the healing-impaired wounds treated with ACF-HS on days 7 and 14, in comparison with that in alginate fiber (Kaltostat), hydrogel wound dressing (DuoACTIVE), and nontreatment (negative control). Furthermore, in cell culture studies, ACF-HS-absorbed serum and fibroblast growth factor-2 was found to be proliferative for fibroblasts and endothelial cells, respectively, and ACF-HS-absorbed serum was found to be chemoattractive for fibroblasts. However, our results may not be strictly comparable with general healing-impaired wound models in humans because of the cell damage by mitomycin C. In addition, more biocompatibility studies of fucoidan are essential due to the possibility of renal toxicity. © 2010 by the Wound Healing Society.

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

The wound healing, chronic fibrosis, and cancer progression triad

PubMed Central

Rybinski, Brad; Franco-Barraza, Janusz

2014-01-01

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

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.

Leptin promotes wound healing in the oral mucosa.

PubMed

Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

2014-01-01

Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

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

Silver oxysalts promote cutaneous wound healing independent of infection.

PubMed

Thomason, Helen A; Lovett, Jodie M; Spina, Carla J; Stephenson, Christian; McBain, Andrew J; Hardman, Matthew J

2018-03-12

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag 2+ /Ag 3+ ). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared with control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting reepithelialization, and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyze the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide. © 2018 by the Wound Healing Society.

Muscle wound healing in rainbow trout (Oncorhynchus mykiss).

PubMed

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

2016-01-01

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

Apitherapeutics and phage-loaded nanofibers as wound dressings with enhanced wound healing and antibacterial activity.

PubMed

Sarhan, Wessam A; Azzazy, Hassan Me

2017-09-01

Develop green wound dressings which exhibit enhanced wound-healing ability and potent antibacterial effects. Honey, polyvinyl alcohol, chitosan nanofibers were electrospun and loaded with bee venom, propolis and/or bacteriophage against the multidrug-resistant Pseudomonas aeruginosa and examined for their antibacterial, wound-healing ability and cytotoxicity. Among different formulations of nanofibers, honey, polyvinyl alcohol, chitosan-bee venom/bacteriophage exhibited the most potent antibacterial activity against all tested bacterial strains (Gram-positive and -negative strains) and achieved nearly complete killing of multidrug-resistant P. aeruginosa. In vivo testing revealed enhanced wound-healing results and cytotoxicity testing proved improved biocompatibility. The developed biocompatible nanofibers represent competitive wound-healing dressings with potent antibacterial and wound-healing activity.

The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

PubMed Central

Reid, Brian; Zhao, Min

2014-01-01

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

Differential Apoptosis in Mucosal and Dermal Wound Healing

PubMed Central

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

2014-01-01

Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; p<0.05), Casp7 (at D5; p<0.05), Trp53 (at 24 h and D5; p<0.05), Tnfrsf1b (at 24 h; p<0.05), FasR (at 24 h, D5, and D7; p<0.05), and Casp8 (at 24 h; p<0.05) and significantly lower gene expression of Tradd (at 24 h; p<0.05). Innovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

Mast Cells Regulate Wound Healing in Diabetes.

PubMed

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; Veves, Aristidis

2016-07-01

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. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Clinical approach to wounds: débridement and wound bed preparation including the use of dressings and wound-healing adjuvants.

PubMed

Attinger, Christopher E; Janis, Jeffrey E; Steinberg, John; Schwartz, Jaime; Al-Attar, Ali; Couch, Kara

2006-06-01

This is a clinical review of current techniques in wound bed preparation found to be effective in assisting the wound-healing process. The process begins with the identification of a correct diagnosis of the wound's etiology and continues with optimizing the patient's medical condition, including blood flow to the wound site. Débridement as the basis of most wound-healing strategies is then emphasized. Various débridement techniques, including surgery, topical agents, and biosurgery, are thoroughly discussed and illustrated. Wound dressings, including the use of negative pressure wound therapy, are then reviewed. To properly determine the timing of advance therapeutic intervention, the wound-healing progress needs to be monitored carefully with weekly measurements. A reduction in wound area of 10 to 15 percent per week represents normal healing and does not mandate a change in the current wound-healing strategy. However, if this level of wound area reduction is not met consistently on a weekly basis, then alternative healing interventions should be considered. There is a growing body of evidence that can provide guidance on the appropriate use of such adjuvants in the problem wound. Several adjuvants are discussed, including growth factor, bioengineered tissues, and hyperbaric medicine.

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

Disrupting the biofilm matrix improves wound healing outcomes.

PubMed

Wolcott, R

2015-08-01

The most unyielding molecular component of biofilm communities is the matrix structure that it can create around the individual microbes that constitute the biofilm. The type of polymeric substances (polymeric sugars, bacterial proteins, bacterial DNA and even co-opted host substances) are dependent on the microbial species present within the biofilm. The extracellular polymeric substances that make up the matrix give the wound biofilm incredible colony defences against host immunity, host healing and wound care treatments. This polymeric slime layer, which is secreted by bacteria, encases the population of microbes, creating a physical barrier that limits the ingress of treatment agents to the bacteria. The aim of this study was to determine if degrading the wound biofilm matrix would improve wound healing outcomes and if so, if there was a synergy between treating agents that disrupted biofilm defenses with Next Science Wound Gel (wound gel) and cidal agents (topical antibiotics). A three-armed randomised controlled trial was designed to determine if standard of care (SOC) was superior to SOC plus wound gel (SOC + gel) and wound gel alone. The wound gel used in this study contains components that directly attack the biofilm extracellular polymeric substance. The gel was applied directly to the wound bed on a Monday-Wednesday-Friday interval, either alone or with SOC topical antibiotics. Using a surrogate endpoint of 50% reduction in wound volume, the results showed that SOC healed at 53%, wound gel healed at 80%, while SOC plus wound gel showed 93% of wounds being successfully treated. By directly targeting the wound biofilm matrix, wound healing outcomes are improved.

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice.

PubMed

Dong, Muchen; Di, Guohu; Zhang, Xiaoping; Zhou, Qingjun; Shi, Weiyun

2017-03-01

To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-β3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

Biology and Biomarkers for Wound Healing

PubMed Central

Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-01-01

Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

Wound Healing in Patients With Impaired Kidney Function

PubMed Central

Maroz, Natallia; Simman, Richard

2014-01-01

Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium–phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients. PMID:26199882

Evaluation of Cynodon dactylon for wound healing activity.

PubMed

Biswas, Tuhin Kanti; Pandit, Srikanta; Chakrabarti, Shrabana; Banerjee, Saheli; Poyra, Nandini; Seal, Tapan

2017-02-02

Research in the field of wound healing is very recent. The concept of wound healing is changing from day to day. Ayurveda is the richest source of plant drugs for management of wounds and Cynodon dactylon L. is one such. The plant is used as hemostatic and wound healing agent from ethnopharmacological point of view. Aim of the present study is scientific validation of the plant for wound healing activity in detail. Aqueous extract of the plant was prepared and phytochemical constituents were detected by HPLC analysis. Acute and dermatological toxicity study of the extract was performed. Pharmacological testing of 15% ointment (w/w) of the extract with respect to placebo control and standard comparator framycetin were done on full thickness punch wound in Wister rats and effects were evaluated based on parameters like wound contraction size (mm 2 ), tensile strength (g); tissue DNA, RNA, protein, hydroxyproline and histological examination. The ointment was applied on selected clinical cases of chronic and complicated wounds and efficacy was evaluated on basis of scoring on granulation, epithelialization, vascularity as well as routine hematological investigations. Significant results (p<0.05) were observed both in pharmacological and clinical studies. The present research with aqueous extract of Cynodon dactylon explores its potential wound healing activity in animal model and subsequent feasibility in human subjects. Phenolic acids and flavonoids present in c. dactylon supports its wound healing property for its anti-oxidative activity that are responsible for collagenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcription factor scleraxis vitally contributes to progenitor lineage direction in wound healing of adult tendon in mice.

PubMed

Sakabe, Tomoya; Sakai, Keiko; Maeda, Toru; Sunaga, Ataru; Furuta, Nao; Schweitzer, Ronen; Sasaki, Takako; Sakai, Takao

2018-04-20

Tendon is a dense connective tissue that transmits high mechanical forces from skeletal muscle to bone. The transcription factor scleraxis (Scx) is a highly specific marker of both precursor and mature tendon cells (tenocytes). Mice lacking scx exhibit a specific and virtually complete loss of tendons during development. However, the functional contribution of Scx to wound healing in adult tendon has not yet been fully characterized. Here, using ScxGFP -tracking and loss-of-function systems, we show in an adult mouse model of Achilles tendon injury that paratenon cells, representing a stem cell antigen-1 (Sca-1)-positive and Scx-negative progenitor subpopulation, display Scx induction, migrate to the wound site, and produce extracellular matrix (ECM) to bridge the defect, whereas resident tenocytes exhibit a delayed response. Scx induction in the progenitors is initiated by transforming growth factor β (TGF-β) signaling. scx -deficient mice had migration of Sca-1-positive progenitor cell to the lesion site but impaired ECM assembly to bridge the defect. Mechanistically, scx -null progenitors displayed higher chondrogenic potential with up-regulation of SRY-box 9 (Sox9) coactivator PPAR-γ coactivator-1α (PGC-1α) in vitro , and knock-in analysis revealed that forced expression of full-length scx significantly inhibited Sox9 expression. Accordingly, scx -null wounds formed cartilage-like tissues that developed ectopic ossification. Our findings indicate a critical role of Scx in a progenitor-cell lineage in wound healing of adult mouse tendon. These progenitor cells could represent targets in strategies to facilitate tendon repair. We propose that this lineage-regulatory mechanism in tissue progenitors could apply to a broader set of tissues or biological systems in the body. © 2018 Sakabe et al.

Synthesis of Novel Derivatives of Quinazoline Schiff base Compound Promotes Epithelial Wound Healing.

PubMed

Bagheri, Elham; Saremi, Kamelia; Hajiaghaalipour, Fatemeh; Faraj, Fadhil Lafta; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Khaing, Si Lay; Salehen, Nur'Ain

2018-01-30

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of synthetic quinazoline compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and eosin (H&E), Masson's trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drosophila as a model of wound healing and tissue regeneration in vertebrates.

PubMed

Belacortu, Yaiza; Paricio, Nuria

2011-11-01

Understanding the molecular basis of wound healing and regeneration in vertebrates is one of the main challenges in biology and medicine. This understanding will lead to medical advances allowing accelerated tissue repair after wounding, rebuilding new tissues/organs and restoring homeostasis. Drosophila has emerged as a valuable model for studying these processes because the genetic networks and cytoskeletal machinery involved in epithelial movements occurring during embryonic dorsal closure, larval imaginal disc fusion/regeneration, and epithelial repair are similar to those acting during wound healing and regeneration in vertebrates. Recent studies have also focused on the use of Drosophila adult stem cells to maintain tissue homeostasis. Here, we review how Drosophila has contributed to our understanding of these processes, primarily through live-imaging and genetic tools that are impractical in mammals. Furthermore, we highlight future research areas where this insect may provide novel insights and potential therapeutic strategies for wound healing and regeneration. Copyright © 2011 Wiley Periodicals, Inc.

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

Cold Atmospheric Plasma (CAP) Changes Gene Expression of Key Molecules of the Wound Healing Machinery and Improves Wound Healing In Vitro and In Vivo

PubMed Central

Arndt, Stephanie; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Heinlin, Julia; Li, Yang-Fang; Thomas, Hubertus M.; Morfill, Gregor E.; Zimmermann, Julia L.

2013-01-01

Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated. PMID:24265766

Review: African medicinal plants with wound healing properties.

PubMed

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

2016-01-11

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

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.

Tortuous Microvessels Contribute to Wound Healing via Sprouting Angiogenesis.

PubMed

Chong, Diana C; Yu, Zhixian; Brighton, Hailey E; Bear, James E; Bautch, Victoria L

2017-10-01

Wound healing is accompanied by neoangiogenesis, and new vessels are thought to originate primarily from the microcirculation; however, how these vessels form and resolve during wound healing is poorly understood. Here, we investigated properties of the smallest capillaries during wound healing to determine their spatial organization and the kinetics of formation and resolution. We used intravital imaging and high-resolution microscopy to identify a new type of vessel in wounds, called tortuous microvessels. Longitudinal studies showed that tortuous microvessels increased in frequency after injury, normalized as the wound healed, and were closely associated with the wound site. Tortuous microvessels had aberrant cell shapes, increased permeability, and distinct interactions with circulating microspheres, suggesting altered flow dynamics. Moreover, tortuous microvessels disproportionately contributed to wound angiogenesis by sprouting exuberantly and significantly more frequently than nearby normal capillaries. A new type of transient wound vessel, tortuous microvessels, sprout dynamically and disproportionately contribute to wound-healing neoangiogenesis, likely as a result of altered properties downstream of flow disturbances. These new findings suggest entry points for therapeutic intervention. © 2017 The Authors.

Inflammation and wound healing: The role of the macrophage

PubMed Central

Koh, Timothy J.; DiPietro, Luisa Ann

2013-01-01

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

Syndecan-4 enhances PDGF-BB activity in diabetic wound healing.

PubMed

Das, Subhamoy; Majid, Marjan; Baker, Aaron B

2016-09-15

Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is

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.

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. © 2015 Anatomical Society.

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

PubMed Central

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

2015-01-01

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

Cold temperature delays wound healing in postharvest sugarbeet roots

USDA-ARS?s Scientific Manuscript database

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

Antibiotics and antiseptics for surgical wounds healing by secondary intention.

PubMed

Norman, Gill; Dumville, Jo C; Mohapatra, Devi Prasad; Owens, Gemma L; Crosbie, Emma J

2016-03-29

Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesives (glue) or clips. This process helps the cut edges heal together and is called 'healing by primary intention'. However, a minority of surgical wounds are not closed in this way. Where the risk of infection is high or there has been significant loss of tissue, wounds may be left open to heal by the growth of new tissue rather than by primary closure; this is known as 'healing by secondary intention'. There is a risk of infection in open wounds, which may impact on wound healing, and antiseptic or antibiotic treatments may be used with the aim of preventing or treating such infections. This review is one of a suite of Cochrane reviews investigating the evidence on antiseptics and antibiotics in different types of wounds. It aims to present current evidence related to the use of antiseptics and antibiotics for surgical wounds healing by secondary intention (SWHSI). To assess the effects of systemic and topical antibiotics, and topical antiseptics for the treatment of surgical wounds healing by secondary intention. In November 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions with respect to language, date of publication or study setting. Randomised controlled trials which enrolled adults with a surgical wound healing by secondary intention and assessed treatment with an antiseptic or antibiotic treatment. Studies enrolling people with skin graft donor sites were not included, neither were studies of wounds with a non-surgical origin which had subsequently undergone sharp or surgical debridement or other surgical

Wound healing potential of adipose tissue stem cell extract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Na, You Kyung; Ban, Jae-Jun; Lee, Mijung

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 wasmore » 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. - Highlights: • Topical application of ATSC-Ex results in faster wound closure than normal wound in vivo. • ATSC-Ex enhances dermal fibroblast proliferation, migration and extracellular matrix production. • This study suggests that ATSC-Ex is an effective source to augment wound healing.« less

Computational Modeling of Inflammation and Wound Healing

PubMed Central

Ziraldo, Cordelia; Mi, Qi; An, Gary; Vodovotz, Yoram

2013-01-01

Objective Inflammation is both central to proper wound healing and a key driver of chronic tissue injury via a positive-feedback loop incited by incidental cell damage. We seek to derive actionable insights into the role of inflammation in wound healing in order to improve outcomes for individual patients. Approach To date, dynamic computational models have been used to study the time evolution of inflammation in wound healing. Emerging clinical data on histo-pathological and macroscopic images of evolving wounds, as well as noninvasive measures of blood flow, suggested the need for tissue-realistic, agent-based, and hybrid mechanistic computational simulations of inflammation and wound healing. Innovation We developed a computational modeling system, Simple Platform for Agent-based Representation of Knowledge, to facilitate the construction of tissue-realistic models. Results A hybrid equation–agent-based model (ABM) of pressure ulcer formation in both spinal cord-injured and -uninjured patients was used to identify control points that reduce stress caused by tissue ischemia/reperfusion. An ABM of arterial restenosis revealed new dynamics of cell migration during neointimal hyperplasia that match histological features, but contradict the currently prevailing mechanistic hypothesis. ABMs of vocal fold inflammation were used to predict inflammatory trajectories in individuals, possibly allowing for personalized treatment. Conclusions The intertwined inflammatory and wound healing responses can be modeled computationally to make predictions in individuals, simulate therapies, and gain mechanistic insights. PMID:24527362

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

Models of wound healing: an emphasis on clinical studies.

PubMed

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

2017-02-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel

2012-11-15

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

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

PubMed

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

2013-12-01

Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Houreld, Nicolette N.

2014-02-01

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

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.

Red Maca (Lepidium meyenii), a Plant from the Peruvian Highlands, Promotes Skin Wound Healing at Sea Level and at High Altitude in Adult Male Mice.

PubMed

Nuñez, Denisse; Olavegoya, Paola; Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia

2017-12-01

Nuñez, Denisse, Paola Olavegoya, Gustavo F. Gonzales, and Cynthia Gonzales-Castañeda. Red maca (Lepidium meyenii), a plant from the Peruvian highlands, promotes skin wound healing at sea level and at high altitude in adult male mice. High Alt Med Biol 18:373-383, 2017.-Wound healing consists of three simultaneous phases: inflammation, proliferation, and remodeling. Previous studies suggest that there is a delay in the healing process in high altitude, mainly due to alterations in the inflammatory phase. Maca (Lepidium meyenii) is a Peruvian plant with diverse biological properties, such as the ability to protect the skin from inflammatory lesions caused by ultraviolet radiation, as well as its antioxidant and immunomodulatory properties. The aim of this study was to determine the effect of high altitude on tissue repair and the effect of the topical administration of the spray-dried extract of red maca (RM) in tissue repair. Studies were conducted in male Balb/c mice at sea level and high altitude. Lesions were inflicted through a 10 mm-diameter excisional wound in the skin dorsal surface. Treatments consisted of either (1) spray-dried RM extract or (2) vehicle (VH). Animals wounded at high altitude had a delayed healing rate and an increased wound width compared with those at sea level. Moreover, wounding at high altitude was associated with an increase in inflammatory cells. Treatment with RM accelerated wound closure, decreased the level of epidermal hyperplasia, and decreased the number of inflammatory cells at the wound site. In conclusion, RM at high altitude generate a positive effect on wound healing, decreasing the number of neutrophils and increasing the number of macrophages in the wound healing at day 7 postwounding. This phenomenon is not observed at sea level.

Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects

PubMed Central

Dai, Tianhong; Tanaka, Masamitsu; Huang, Ying-Ying; Hamblin, Michael R

2011-01-01

Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns. PMID:21810057

Nutritional Aspects of Gastrointestinal Wound Healing

PubMed Central

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

2016-01-01

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

Effects of topical oxygen therapy on ischemic wound healing.

PubMed

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

2016-01-01

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

Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management

PubMed Central

Chicharro-Alcántara, Deborah; Damiá-Giménez, Elena; Carrillo-Poveda, José M.; Peláez-Gorrea, Pau

2018-01-01

The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process. PMID:29346333

NeutroPhase® in chronic non-healing wounds

PubMed Central

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

2012-01-01

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

A new, easy-to-make pectin-honey hydrogel enhances wound healing in rats.

PubMed

Giusto, Gessica; Vercelli, Cristina; Comino, Francesco; Caramello, Vittorio; Tursi, Massimiliano; Gandini, Marco

2017-05-16

Honey, alone or in combination, has been used for wound healing since ancient times and has reemerged as a topic of interest in the last decade. Pectin has recently been investigated for its use in various biomedical applications such as drug delivery, skin protection, and scaffolding for cells. The aim of the present study was to develop and evaluate a pectin-honey hydrogel (PHH) as a wound healing membrane and to compare this dressing to liquid honey. Thirty-six adult male Sprague-Dawley rats were anesthetized and a 2 × 2 cm excisional wound was created on the dorsum. Animals were randomly assigned to four groups (PHH, LH, Pec, and C): in the PHH group, the pectin-honey hydrogel was applied under a bandage on the wound; in the LH group, liquid Manuka honey was applied; in the Pec group, pectin hydrogel was applied (Pec); and in the C group, only bandage was applied to the wound. Images of the wound were taken at defined time points, and the wound area reduction rate was calculated and compared between groups. The wound area reduction rate was faster in the PHH, LH, and Pec groups compared to the control group and was significantly faster in the PHH group. Surprisingly, the Pec group exhibited faster wound healing than the LH group, but this effect was not statistically significant. This is the first study using pectin in combination with honey to produce biomedical hydrogels for wound treatment. The results indicate that the use of PHH is effective for promoting and accelerating wound healing.

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

PubMed Central

Gbedema, Stephen Y.; Emelia, Kisseih; Francis, Adu; Kofi, Annan; Eric, Woode

2010-01-01

As part of our general objective of investigating indigenous plants used in wound healing in Ghana, we hereby report our findings from some in vitro and in vivo studies related to wound healing activities of Clerodendron splendens G. Don (Verbanaceae). Methanolic extract of the aerial parts of the plant was tested for antimicrobial activity against Gram positive bacteria (Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Micrococcus flavus, as well as resistant strains of Staph. aureus SA1199B, RN4220 and XU212), Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteous mirabilis, Klebsiella pneumoniae) and Candida albicans using the micro-well dilution method. Survivor–time studies of the microorganisms, radical scavenging activity using 2,2’-diphenylpicrylhydrazyl (DPPH) and various in vivo wound healing activity studies were also conducted on the extract. The extract exhibited biostatic action against all the test microorganisms with a Minimum Inhibition Concentration (MIC) ranging between 64 and 512 μg/ml and a free radical scavenging property with an IC50 value of 103.2 μg/ml. The results of the in vivo wound healing tests showed that upon application of C. splendens ointment, there was a reduction in the epithelization period from 26.7 days (control) to 13.6 days along with a marked decrease in the scar area from 54.2 mm2 (control) to 25.2 mm2. Significant increase in the tensile strength and hydroxyproline content were also observed as compared to the control and was comparable to nitrofurazone. The above results appear to justify the traditional use of C. splendens in wound healing and treatment of skin infections in Ghana. PMID:21808542

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.

Wound healing properties of Artocarpus heterophyllus Lam.

PubMed

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

2009-04-01

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

Effect of systemic insulin treatment on diabetic wound healing.

PubMed

Vatankhah, Nasibeh; Jahangiri, Younes; Landry, Gregory J; Moneta, Gregory L; Azarbal, Amir F

2017-04-01

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates. © 2017 by the Wound Healing Society.

Role of adipose-derived stem cells in wound healing.

PubMed

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

2014-01-01

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

Pharmacological modulation of wound healing in experimental burns.

PubMed

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

2007-11-01

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

Effect of methotrexate on bone and wound healing.

PubMed

Pountos, Ippokratis; Giannoudis, Peter V

2017-05-01

Methotrexate (MTX) is one of the most commonly used disease modifying drugs administered for wide spectrum of conditions. Through the expansion of the indications of MTX use, an increasing number of patients nowadays attend orthopaedic departments receiving this pharmacological agent. The aim of this manuscript is to present our current understanding on the effect of MTX on bone and wound healing. Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of MTX on bone and wound healing. The authors also analyse the available literature and describe the incidence of complications after elective orthopaedic surgery in patients receiving MTX. Expert opinion: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions on the effect of MTX on bone healing. Regarding wound healing, in vitro and experimental animal studies suggest that MTX can adversely affect wound healing, whilst the clinical studies show that lose-dose MTX is safe and does not affect the incidence of postoperative wound complications.

Wounding the Cornea to Learn How it Heals

PubMed Central

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

2014-01-01

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

Wound Healing from Dermal Grafts Containing CD34+ Cells Is Comparable to Wound Healing with Split-Thickness Skin Micrografts.

PubMed

Nuutila, Kristo; Singh, Mansher; Kruse, Carla; Eriksson, Elof

2017-08-01

Epidermal stem cells present in the skin appendages of the dermis might be crucial in wound healing. In this study, the authors located these cells in the dermis and evaluated their contribution to full-thickness wound healing in a porcine model. Four sequentially deeper 0.35-mm-thick skin grafts were harvested from the same donor site going down to 1.4 mm in depth (layers 1 through 4). The layers were minced to 0.8 × 0.8 × 0.35-mm micrografts and transplanted (1:2) onto full-thickness porcine wounds. Healing was monitored up to 28 days and biopsy specimens were collected on days 6 and 10. Multiple wound healing parameters were used to assess the quality of healing. The authors' results showed that wounds transplanted with layer 2 (0.35 to 0.7 mm) and layer 3 (0.7 to 1.05 mm) micrografts demonstrated reepithelialization rates comparable to that of split-thickness skin graft (layer 1, 0.00 to 0.35 mm; split-thickness skin graft) at day 10. At day 28, dermal micrografts (layers 2 and 3) showed quality of healing comparable to that of split-thickness skin grafts (layer 1) in terms of wound contraction and scar elevation index. The amounts of epidermal stem cells [cluster of differentiation (CD) 34] and basal keratinocytes (KRT14) at each layer were quantified by immunohistochemistry. The analysis showed that layers 2 and 3 contained the most CD34 cells and layer 1 was the richest in KRT14 cells. The immunohistochemistry also indicated that, by day 6, CD34 cells had differentiated into KRT14 cells, which migrated from the grafts and contributed to the reepithelialization of the wound.

New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications

PubMed Central

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

2013-01-01

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

New guar biopolymer silver nanocomposites for wound healing applications.

PubMed

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

2013-01-01

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

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

PubMed

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

2016-02-01

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

Wound healing properties of Artocarpus heterophyllus Lam

PubMed Central

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

2009-01-01

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

Distinct Fibroblasts in the Papillary and Reticular Dermis: Implications for Wound Healing.

PubMed

Woodley, David T

2017-01-01

Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct lineages of cells that have distinct cell markers and, more importantly, distinct functional abilities. Human skin wound healing largely involves the dermal fibroblast lineage from the reticular dermis and not the papillary dermis. If scientists could find a way to stimulate the dermal fibroblast lineages from the papillary dermis in early wound healing, perhaps human skin wounds could heal without scarring and with skin appendages. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of caffeine on wound healing.

PubMed

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

2016-10-01

The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Effects of Silk Sericin on Incision Wound Healing in a Dorsal Skin Flap Wound Healing Rat Model.

PubMed

Ersel, Murat; Uyanikgil, Yigit; Karbek Akarca, Funda; Ozcete, Enver; Altunci, Yusuf Ali; Karabey, Fatih; Cavusoglu, Turker; Meral, Ayfer; Yigitturk, Gurkan; Oyku Cetin, Emel

2016-04-01

The wound healing process is complex and still poorly understood. Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective of this study was to evaluate in vivo wound healing effects of a sericin-containing gel formulation in an incision wound model in rats. Twenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention or treatment was applied to the Intact control group. For other groups, a dorsal skin flap (9×3 cm) was drawn and pulled up with sharp dissection. The Sham operated group received no treatment. The Placebo group received placebo gel without sericin applied to the incision area once a day from day 0 to day 9. The Sericin Group 3 received 1% sericin gel applied to the incision area once a day from day 0 to day 9. Hematoxylin and eosin stain was applied for histological analysis and Mallory-Azan staining was applied for histoimmunochemical analysis of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied to paraffin sections of skin wound specimens. Parameters of oxidative stress were measured in the wound area. Epidermal thickness and vascularization were increased, and hair root degeneration, edema, cellular infiltration, collagen discoloration, and necrosis were decreased in Sericin group in comparison to the Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were increased in the sericin group. We found that sericin had significant positive effects on wound healing and antioxidant activity. Sericin-based formulations can improve healing of incision wounds.

Effects of Silk Sericin on Incision Wound Healing in a Dorsal Skin Flap Wound Healing Rat Model

PubMed Central

Ersel, Murat; Uyanikgil, Yigit; Akarca, Funda Karbek; Ozcete, Enver; Altunci, Yusuf Ali; Karabey, Fatih; Cavusoglu, Turker; Meral, Ayfer; Yigitturk, Gurkan; Cetin, Emel Oyku

2016-01-01

Background The wound healing process is complex and still poorly understood. Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective of this study was to evaluate in vivo wound healing effects of a sericin-containing gel formulation in an incision wound model in rats. Material/Methods Twenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention or treatment was applied to the Intact control group. For other groups, a dorsal skin flap (9×3 cm) was drawn and pulled up with sharp dissection. The Sham operated group received no treatment. The Placebo group received placebo gel without sericin applied to the incision area once a day from day 0 to day 9. The Sericin Group 3 received 1% sericin gel applied to the incision area once a day from day 0 to day 9. Hematoxylin and eosin stain was applied for histological analysis and Mallory-Azan staining was applied for histoimmunochemical analysis of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied to paraffin sections of skin wound specimens. Parameters of oxidative stress were measured in the wound area. Results Epidermal thickness and vascularization were increased, and hair root degeneration, edema, cellular infiltration, collagen discoloration, and necrosis were decreased in Sericin group in comparison to the Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were increased in the sericin group. Conclusions We found that sericin had significant positive effects on wound healing and antioxidant activity. Sericin-based formulations can improve healing of incision wounds. PMID:27032876

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.

Multimodal noninvasive monitoring of soft tissue wound healing.

PubMed

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

2013-12-01

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

Silver nanoparticles enhance wound healing in zebrafish (Danio rerio).

PubMed

Seo, Seung Beom; Dananjaya, S H S; Nikapitiya, Chamilani; Park, Bae Keun; Gooneratne, Ravi; Kim, Tae-Yoon; Lee, Jehee; Kim, Cheol-Hee; De Zoysa, Mahanama

2017-09-01

Silver nanoparticles (AgNPs) were successfully synthesized by a chemical reduction method, physico-chemically characterized and their effect on wound-healing activity in zebrafish was investigated. The prepared AgNPs were circular-shaped, water soluble with average diameter and zeta potential of 72.66 nm and -0.45 mv, respectively. Following the creation of a laser skin wound on zebrafish, the effect of AgNPs on wound-healing activity was tested by two methods, direct skin application (2 μg/wound) and immersion in a solution of AgNPs and water (50 μg/L). The zebrafish were followed for 20 days post-wounding (dpw) by visual observation of wound size, calculating wound healing percentage (WHP), and histological examination. Visually, both direct skin application and immersion AgNPs treatments displayed clear and faster wound closure at 5, 10 and 20 dpw compared to the controls, which was confirmed by 5 dpw histology data. At 5 dpw, WHP was highest in the AgNPs immersion group (36.6%) > AgNPs direct application group (23.7%) > controls (18.2%), showing that WHP was most effective in fish immersed in AgNPs solution. In general, exposure to AgNPs induced gene expression of selected wound-healing-related genes, namely, transforming growth factor (TGF-β), matrix metalloproteinase (MMP) -9 and -13, pro-inflammatory cytokines (IL-1β and TNF-α) and antioxidant enzymes (superoxide dismutase and catalase), which observed differentiation at 12 and 24 h against the control; but the results were not consistently significant, and many either reached basal levels or were down regulated at 5 dpw in the wounded muscle. These results suggest that AgNPs are effective in acceleration of wound healing and altered the expression of some wound-healing-related genes. However, the detailed mechanism of enhanced wound healing remains to be investigated in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effect of Camellia sinensis on Wound Healing Potential in an Animal Model

PubMed Central

Kanthimathi, M. S.; Sanusi, Junedah

2013-01-01

Camellia sinensis (tea) is reported to have health benefits, including the building of healthy skin. This study evaluated the effects of topical application of Camellia sinensis extract on the rate of wound closure and the histology of wound area. A uniform area of 2.00 cm in diameter was excised from the neck of adult male Sprague Dawley rats. The animals were topically treated with 0.2 mL of vehicle (CMC), Intrasite gel (positive control), or 200 and 400 mg/mL of extract. Wounds dressed with the extract and Intrasite gel healed significantly earlier than those with vehicle. Histological analysis of the wound area after 10 days showed that wounds dressed with the extract had less scar width when compared to the control. The tissue contained less inflammatory cells and more collagen and angiogenesis, compared to wounds dressed with vehicle. In this study, Camellia sinensis showed high potential in wound healing activity. PMID:23864889

Platelet-Rich Fibrin Accelerates Skin Wound Healing in Diabetic Mice.

PubMed

Ding, Yinjia; Cui, Lei; Zhao, Qiming; Zhang, Weiqiang; Sun, Huafeng; Zheng, Lijun

2017-09-01

Diabetic foot ulcers (DFUs) are associated with an increased risk of secondary infection and amputation. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing several cytokines and growth factors, is known to promote wound healing. However, the effect of PRF on diabetic wound healing has not been adequately investigated. The aim of the study was to investigate the effect of PRF on skin wound healing in a diabetic mouse model. Platelet-rich fibrin was prepared from whole blood of 8 healthy volunteers. Two symmetrical skin wounds per mouse were created on the back of 16 diabetic nude mice. One of the 2 wounds in each mouse was treated with routine dressings (control), whereas the other wound was treated with PRF in addition to routine dressings (test), each for a period of 14 days. Skin wound healing rate was calculated.Use of PRF was associated with significantly improved skin wound healing in diabetic mice. On hematoxylin and eosin and CD31 staining, a significant increase in the number of capillaries and CD31-positive cells was observed, suggesting that PRF may have promoted blood vessel formation in the skin wound. In this study, PRF seemed to accelerate skin wound healing in diabetic mouse models, probably via increased blood vessel formation.

Improvement of wound healing by regulated oxygen-enriched negative pressure-assisted wound therapy in a rabbit model.

PubMed

Li, Y Z; Hu, X D; Lai, X M; Li, Y F; Lei, Y

2018-01-01

Development of drug therapies and other techniques for wound care have resulted in significant improvement of the cure rate and shortening of the healing time for wounds. A modified technique of regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) has been reported. To evaluate the efficacy and impact of RO-NPT on wound recovery and inflammation. Infected wounds were established on 40 adult female white rabbits, which were then randomized to one of four groups: O 2 group, regulated negative pressure-assisted wound therapy (RNPT) group, regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) group and healthy control (HC) group. Each day, the O 2 group was treated with a constant oxygen supply (1 L/min) to the wound, while the RNPT group was treated with continuous regulated negative pressure (70 ± 5 mmHg) and the RNPT + O 2 group was treated with both. The HC group was treated with gauze dressing alone, which was changed every day. Leucocyte count, colony count and wound-healing rate were calculated. Levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 were evaluated by ELISA. RO-RNPT significantly decreased bacterial count and TNF-α level, and increased the wound-healing rate. IL-1β, IL-8 and leucocyte count had a tendency to increase in the early phase of inflammation and a tendency to decrease in the later phase of inflammation in the RO-RNPT group. RO-NPT therapy assisted wound recovery and inflammation control compared with the RNPT and oxygen-enriched therapies. RO-NPT therapy also increased levels of IL-1β and IL-8 and attenuated expression of TNF-α in the early phase of inflammation. © 2017 British Association of Dermatologists.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Macrophage Differentiation in Normal and Accelerated Wound Healing.

PubMed

Kotwal, Girish J; Chien, Sufan

2017-01-01

Chronic wounds pose considerable public health challenges and burden. Wound healing is known to require the participation of macrophages, but mechanisms remain unclear. The M1 phenotype macrophages have a known scavenger function, but they also play multiple roles in tissue repair and regeneration when they transition to an M2 phenotype. Macrophage precursors (mononuclear cells/monocytes) follow the influx of PMN neutrophils into a wound during the natural wound-healing process, to become the major cells in the wound. Natural wound-healing process is a four-phase progression consisting of hemostasis, inflammation, proliferation, and remodeling. A lag phase of 3-6 days precedes the remodeling phase, which is characterized by fibroblast activation and finally collagen production. This normal wound-healing process can be accelerated by the intracellular delivery of ATP to wound tissue. This novel ATP-mediated acceleration arises due to an alternative activation of the M1 to M2 transition (macrophage polarization), a central and critical feature of the wound-healing process. This response is also characterized by an early increased release of pro-inflammatory cytokines (TNF, IL-1 beta, IL-6), a chemokine (MCP-1), an activation of purinergic receptors (a family of plasma membrane receptors found in almost all mammalian cells), and an increased production of platelets and platelet microparticles. These factors trigger a massive influx of macrophages, as well as in situ proliferation of the resident macrophages and increased synthesis of VEGFs. These responses are followed, in turn, by rapid neovascularization and collagen production by the macrophages, resulting in wound covering with granulation tissue within 24 h.

Burn wound healing properties of asiaticoside and madecassoside

PubMed Central

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

2016-01-01

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

Epithelialization in Wound Healing: A Comprehensive Review

PubMed Central

Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana

2014-01-01

Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064

The Effect of Magnetic Fields on Wound Healing

PubMed Central

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

2008-01-01

Objective: Magnets are purported to aid wound healing despite a paucity of scientific evidence. The purpose of this study was to evaluate the effect of static magnetic fields on cutaneous wound healing in an animal model. The literature was reviewed to explore the historical and scientific basis of magnet therapy and to define its current role in the evidence-based practice of plastic surgery. Methods: Standardized wounds were created on the backs of 33 Sprague-Dawley rats, which were divided into 3 groups with either a 23 gauss magnet (group 1), a sham magnet (group 2), or nothing (group 3) positioned over the wound. The rate of wound closure by secondary intention was compared between the groups. Literature review was conducted through searches of PubMed and Ovid databases for articles pertinent to magnets and wound healing. Results: Wounds in the magnet group healed in an average of 15.3 days, significantly faster than those in either the sham group (20.9 days, P = .006) or control group (20.3 days, P < .0001). There was no statistically significant difference between the sham and control groups (P = .45). Conclusions: An externally applied, low-power, static magnetic field increases the rate of secondary healing. Review of the literature reveals conflicting evidence regarding the use of magnetic energy to aid the healing of bone, tendon, and skin. Level I studies are lacking and difficult to execute but are needed to define conclusively the role of magnets in clinical practice. PMID:18725953

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

PubMed

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

2016-09-01

The purpose of this study is to report the Chinese experience of establishing hospital-based wound care centers over 15 years. A total of 69 wound-healing centers (WHCs) and wound care units (WCUs) were involved. Questionnaires were diverged to the principal directors of these sites; data extracted for this study included origin, year of establishment, medical staff, degree of hospitals, wound etiology, wound-healing rate, hospital stay, and outcomes data. The period of data extraction was defined as before and after 1 year of the establishment of WHCs and WCUs. The earliest WHC was established in 1999, and from 2010 the speeds of establishing WHCs and WCUs rapidly increased. The majority of WHCs were divisions of burn departments, and all WHCs came from departments of outpatient dressing rooms. Full-time multidisciplinary employees of WHCs differed greatly to WCUs. Types of wound and outcomes vary with those of centers reported from Western countries and the United States. Improvement in wound healing caused by the establishment of WHCs and WCUs in China occurred without doubt. Some advices include the following: rearrange and reorganize the distribution of WHCs and WCUs; enact and generalize Chinese guidelines for chronic wounds; utilize medical resources reasonably; improve multidisciplinary medical staff team; draw up and change some medical and public policies and regulations. © The Author(s) 2015.

Wound-healing outcomes using standardized assessment and care in clinical practice.

PubMed

Bolton, Laura; McNees, Patrick; van Rijswijk, Lia; de Leon, Jean; Lyder, Courtney; Kobza, Laura; Edman, Kelly; Scheurich, Anne; Shannon, Ron; Toth, Michelle

2004-01-01

Wound-healing outcomes applying standardized protocols have typically been measured within controlled clinical trials, not natural settings. Standardized protocols of wound care have been validated for clinical use, creating an opportunity to measure the resulting outcomes. Wound-healing outcomes were explored during clinical use of standardized validated protocols of care based on patient and wound assessments. This was a prospective multicenter study of wound-healing outcomes management in real-world clinical practice. Healing outcomes from March 26 to October 31, 2001, were recorded on patients in 3 long-term care facilities, 1 long-term acute care hospital, and 12 home care agencies for wounds selected by staff to receive care based on computer-generated validated wound care algorithms. After diagnosis, wound dimensions and status were assessed using a tool adapted from the Pressure Sore Status Toolfor use on all wounds. Wound, ostomy, and continence nursing professionals accessed consistent protocols of care, via telemedicine in home care or paper forms in long-term care. A physician entered assessments into a desktop computer in the wound clinic. Based on evidence that healing proceeds faster with fewer infections in environments without gauze, the protocols generally avoided gauze dressings. Most of the 767 wounds selected to receive the standardized-protocols of care were stage III-IV pressure ulcers (n = 373; mean healing time 62 days) or full-thickness venous ulcers (n = 124; mean healing time 57 days). Partial-thickness wounds healed faster than same-etiology full-thickness wounds. These results provide benchmarks for natural-setting healing outcomes and help to define and address wound care challenges. Outcomes primarily using nongauze protocols of care matched or surpassed best previously published results on similar wounds using gauze-based protocols of care, including protocols applying gauze impregnated with growth factors or other agents.

Wounding the cornea to learn how it heals.

PubMed

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

2014-04-01

Corneal wound healing studies have a long history and rich literature that describes the data obtained over the past 70 years using many different species of animals and methods of injury. These studies have lead to reduced suffering and provided clues to treatments that are now helping patients live more productive lives. In spite of the progress made, further research is required since blindness and reduced quality of life due to corneal scarring still happens. The purpose of this review is to summarize what is known about different types of wound and animal models used to study corneal wound healing. The subject of corneal wound healing is broad and includes chemical and mechanical wound models. This review focuses on mechanical injury models involving debridement and keratectomy wounds to reflect the authors' expertise. Copyright © 2014 Elsevier Ltd. All rights reserved.

Promising role of ANGPTL4 gene in diabetic wound healing.

PubMed

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

2014-03-01

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

Potential of oncostatin M to accelerate diabetic wound healing.

PubMed

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

2014-08-01

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

The Presence of Oxygen in Wound Healing.

PubMed

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

2016-08-01

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

Wound healing property of milk in full thickness wound model of rabbit.

PubMed

Hemmati, Ali Asghar; Larki-Harchegani, Amir; Shabib, Somayeh; Jalali, Amir; Rezaei, Anahita; Housmand, Gholamreza

2018-04-22

Wound healing consists of several continuous phases in which various cells and chemical intermediates are involved. Milk as a rich source of nutritional elements has proved to have potential benefits for treatment of various diseases. The present study was designed to investigate the healing effect of low-fat cow's milk on an open skin wound model in the rabbit. The 2%, 5%, and 10% (w/w) ointments of lyophilized powder of low-fat milk were prepared in the eucerin base and were applied twice daily in the treatment groups. Phenytoin 1% ointment was used as a standard control. The healing effect of the milk ointment (MO) was evaluated through the measurement of wound surface area, the extent of tissue tension, and the content of hydroxyproline. Histological evaluation of skin tissue specimens was also performed using hematoxylin and eosin staining. The results showed that the healing rate in the treatment group was significantly higher than that of untreated group and eucerin group (p < 0.01). The best healing effect was seen in 5% milk ointment with the shortest healing time (15 days) and the highest tissue tension in comparison to other groups. Although the tissue hydroxyproline content in this group was slightly lower than that of the phenytoin group, this difference was not significant. Histologic, findings indicated increased collagen fibers, increased fibroblasts and an evident decrease in inflammatory cells in that group. It can, therefore, be concluded that low-fat cow's milk has significant beneficial effects on skin wound healing. Therefore, it may be used as a healing agent in different types of the wound in humans after certain clinical trials. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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.

Publicly Reported Wound Healing Rates: The Fantasy and the Reality

PubMed Central

Fife, Caroline E.; Eckert, Kristen A.; Carter, Marissa J.

2018-01-01

Significance: We compare real-world data from the U.S. Wound Registry (USWR) with randomized controlled trials and publicly reported wound outcomes and develop criteria for honest reporting of wound outcomes, a requirement of the new Quality Payment Program (QPP). Recent Advances: Because no method has existed by which wounds could be stratified according to their likelihood of healing among real-world patients, practitioners have reported fantastically high healing rates. The USWR has developed several risk-stratified wound healing quality measures for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) as part of its Qualified Clinical Data Registry (QCDR). This allows practitioners to report DFU and VLU healing rates in comparison to the likelihood of whether the wound would have healed. Critical Issues: Under the new QPP, practitioners must report at least one practice-relevant outcome measure, and it must be risk adjusted so that clinicians caring for the sickest patients do not appear to have worse outcomes than their peers. The Wound Healing Index is a validated risk-stratification method that can predict whether a DFU or VLU will heal, leveling the playing field for outcome reporting and removing the need to artificially inflate healing rates. Wound care practitioners can report the USWR DFU and VLU risk-stratified outcome measure to satisfy the quality reporting requirements of the QPP. Future Directions: Per the requirements of the QPP, the USWR will begin publicly reporting of risk-stratified healing rates once quality measure data have met the reporting standards of the Centers for Medicare and Medicaid Services. Some basic rules for data censoring are proposed for public reporting of healing rates, and others are needed, which should be decided by consensus among the wound care community. PMID:29644145

Swatting flies: modelling wound healing and inflammation in Drosophila

PubMed Central

Razzell, William; Wood, Will; Martin, Paul

2011-01-01

Aberrant wound healing can lead to a variety of human pathologies, from non-healing chronic wounds that can become dangerously infected, to exuberant fibrotic healing in which repair is accompanied by excessive inflammation. To guide therapeutic intervention, we need a better understanding of the fundamental mechanisms driving tissue repair; this will require complementary wound-healing studies in several model organisms. Drosophila has been used to model genetic aspects of numerous human pathologies, and is being used increasingly to gain insight into the molecular and genetic aspects of tissue repair and inflammation, which have classically been modelled in mice or cultured cells. This review discusses the advantages and disadvantages of Drosophila as a wound-healing model, as well as some exciting new research opportunities that will be enabled by its use. PMID:21810906

Pharmacologic Impact (aka "Breaking Bad") of Medications on Wound Healing and Wound Development: A Literature-based Overview.

PubMed

Beitz, Janice M

2017-03-01

Patients with wounds often are provided pharmacologic interventions for their wounds as well as for their acute or chronic illnesses. Drugs can promote wound healing or substantively hinder it; some medications cause wound or skin reactions. A comprehensive review of extant literature was conducted to examine the impact of drug therapy on wound healing and skin health. MEDLINE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for English-language articles published between 2000 and 2016 using the terms drugs, medications, drug skin eruptions, adverse skin reactions, wound healing, delayed wound healing, nonhealing wound, herbals, and herbal supplements. The search yielded 140 articles (CINAHL) and 240 articles (MEDLINE) for medications and wound healing. For medications and adverse skin effects, the search identified 256 articles (CINAHL) and 259 articles (MEDLINE). The articles included mostly narrative reviews, some clinical trials, and animal studies. Notable findings were synthesized in a table per pharmacological class and/or agent focusing on wound healing impact and drug-induced adverse skin reactions. The medications most likely to impair wound healing and damage skin integrity include antibiotics, anticonvulsants, angiogenesis inhibitors, steroids, and nonsteroidal anti-inflammatory drugs. Conversely, drugs such as ferrous sulfate, insulin, thyroid hormones, and vitamins may facilitate wound healing. Selected clinical practices, including obtaining a detailed medication history that encompasses herbal supplements use; assessing nutrition status especially protein blood levels affecting drug protein binding; and scrutinizing patient history and physical characteristics for risk factors (eg, atopy history) can help diminish and/or eliminate adverse integumentary outcomes. "Deprescribing" (discontinuing unnecessary medications) should be utilized when possible. Contemporary wound care clinicians must be cognizant of these

HoxD3 accelerates wound healing in diabetic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri

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

Frequent Application of the New Gelatin-Collagen Nonwoven Accelerates Wound Healing.

PubMed

Schiefer, Jennifer L; Rath, Rebekka; Held, Manuel; Petersen, Wiebke; Werner, Jan-Ole; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin

2016-02-01

Mortality after chronic wounds is high. Thus, proper and effective therapy is of critical importance. Adult mammalian skin cannot regenerate spontaneously. It heals under scar formation in a process of repair. In general, wound closure is achieved through a combination of contraction, scar formation, and regeneration. To enhance wound healing, research groups are continuously inventing and evaluating novel skin replacement products. A single application of a new gelatin-collagen nonwoven accelerates wound closure of full-thickness skin defects. Therefore, the authors' objective was to evaluate the effect of a higher application frequency of the nonwoven on wound closure in a minipig model. Four full-thickness skin defects were created surgically on the dorsum of 12 Göttingen minipigs. Next, 3 wounds were treated randomly with a novel gelatin-collagen nonwoven in different thicknesses, while the fourth wound was left untreated and served as the control wound. Moreover, 6 minipigs achieved multiple applications of the wound dressing. During the experimental period of 21 days, a close-up photographic documentation was performed. Finally, the areas of the initial wounds were excised and examined histologically. More frequent application of the nonwoven achieved accelerated wound healing and better epidermis quality compared with a single application. Mean time until wound closure of all wounds treated with a multiple application of the nonwoven was 11.0 (± 1.2) days, compared with a single application of the nonwoven with 12.4 (± 1.26) days and control wounds with 13.5 (± 1.19) days. Furthermore, the epidermal thickness of all wounds treated with multiple applications of the nonwoven was increased by 10.67 μm (31.89 ± 8.86 μm, P = .0007) compared with a single application of the nonwoven and by 6.53 μm (27.75 ± 7.24 μm, P = .0435) compared with the control group. Multiple applications of the gelatin-collagen nonwoven may be an appropriate treatment for

The Use of Stem Cells in Burn Wound Healing: A Review

PubMed Central

Ghieh, Fadi; Jurjus, Rosalyn; Ibrahim, Amir; Geagea, Alice Gerges; El Baba, Bassel; Chams, Sana; Matar, Michel; Zein, Wadih

2015-01-01

Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stem cells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they have decreased the inflammation levels with less scar progression and fibrosis. This review aims to highlight the beneficial therapeutic effect of stem cells in burn wound healing and to discuss the involved pathways and signaling molecules. The review covers various types of burn wound healing like skin and corneal burns, along with the alternative recent therapies being studied in the field of burn wound healing. The current reflection of the attitudes of people regarding the use of stem cells in burn wound healing is also stated. PMID:26236731

Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing

PubMed Central

Feng, Yi; Sanders, Andrew J.; Ruge, Fiona; Morris, Ceri-Ann; Harding, Keith G.; Jiang, Wen G.

2016-01-01

Cytokines play important roles in the wound healing process through various signalling pathways. The JAK-STAT pathway is utilised by most cytokines for signal transduction and is regulated by a variety of molecules, including suppressor of cytokine signalling (SOCS) proteins. SOCS are associated with inflammatory diseases and have an impact on cytokines, growth factors and key cell types involved in the wound-healing process. SOCS, a negative regulator of cytokine signalling, may hold the potential to regulate cytokine-induced signalling in the chronic wound-healing process. Wound edge tissues were collected from chronic venous leg ulcer patients and classified as non-healing and healing wounds. The expression pattern of seven SOCSs members, at the transcript and protein level, were examined in these tissues using qPCR and immunohistochemistry. Significantly higher levels of SOCS3 (P=0.0284) and SOCS4 (P=0.0376) in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level. Relocalisation of SOCS3 protein in the non-healing wound environment was evident in the investigated chronic biopsies. Thus, the results show that the expression of SOCS transcript indicated that SOCS members may act as a prognostic biomarker of chronic wounds. PMID:27635428

Prediction of venous wound healing with laser speckle imaging.

PubMed

van Vuuren, Timme Maj; Van Zandvoort, Carina; Doganci, Suat; Zwiers, Ineke; tenCate-Hoek, Arina J; Kurstjens, Ralph Lm; Wittens, Cees Ha

2017-12-01

Introduction Laser speckle imaging is used for noninvasive assessment of blood flow of cutaneous wounds. The aim of this study was to assess if laser speckle imaging can be used as a predictor of venous ulcer healing. Methods After generating the flux speckle images, three regions of interest (ROI) were identified to measure the flow. Sensitivity, specificity, negative predictive value, and positive predictive value for ulcer healing were calculated. Results In total, 17 limbs were included. A sensitivity of 92.3%, specificity of 75.0%, PPV of 80.0%, and NPV 75.0% were found in predicting wound healing based on laser speckle images. Mean flux values were lowest in the center (ROI I) and showed an increase at the wound edge (ROI II, p = 0.03). Conclusion Laser speckle imaging shows acceptable sensitivity and specificity rates in predicting venous ulcer healing. The wound edge proved to be the best probability for the prediction of wound healing.

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

PubMed

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

2014-02-01

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

The effect of Mindfulness-Based Stress Reduction on wound healing: a preliminary study.

PubMed

Meesters, Astrid; den Bosch-Meevissen, Yvo M C In; Weijzen, Chantal A H; Buurman, Wim A; Losen, Mario; Schepers, Jan; Thissen, Monique R T M; Alberts, Hugo J E M; Schalkwijk, Casper G; Peters, Madelon L

2018-06-01

Psychological factors have been shown to influence the process of wound healing. This study examined the effect of Mindfulness-Based Stress Reduction (MBSR) on the speed of wound healing. The local production of pro-inflammatory cytokines and growth factors was studied as potential underlying mechanism. Forty-nine adults were randomly allocated to a waiting-list control group (n = 26) or an 8-week MBSR group (n = 23). Pre- and post-intervention/waiting period assessment for both groups consisted of questionnaires. Standardized skin wounds were induced on the forearm using a suction blister method. Primary outcomes were skin permeability and reduction in wound size monitored once a day at day 3, 4, 5, 6, 7, and 10 after injury. Secondary outcomes were cytokines and growth factors and were measured in wound exudates obtained at 3, 6, and 22 h after wounding. Although there was no overall condition effect on skin permeability or wound size, post hoc analyses indicated that larger increases in mindfulness were related to greater reductions in skin permeability 3 and 4 days after wound induction. In addition, MBSR was associated with lower levels of interleukin (IL)-8 and placental growth factor in the wound fluid 22 h after wound induction. These outcomes suggest that increasing mindfulness by MBSR might have beneficial effects on early stages of wound healing. Trial Registration NTR3652, http://www.trialregister.nl.

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

PubMed Central

Xue, Meilang; Jackson, Christopher J.

2015-01-01

Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. PMID:25785236

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

PubMed

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

2017-02-01

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

Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds.

PubMed

Wu, Si-Yu; Hu, Wei; Zhang, Bo; Liu, Shuai; Wang, Jian-Min; Wang, Ai-Min

2012-08-01

In a previous study, we proposed a new therapy using topical bromelain as a supplement to simple wound-track incision for the debridement of firearm wounds. This enzymatic debridement greatly simplified the management of high-velocity gunshot wounds in a pig model, and bromelain was confirmed to improve wound healing. The purpose of the present study was to investigate the effect of bromelain on the microenvironment of firearm wounds. Sixteen Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into four groups: wound incision (group I), incision + bromelain (group IB), wound excision (group E), and control. Blood perfusion, oxygen partial pressure (pO(2)), and the content of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in wound-track tissue were measured. Wound healing was also noted. The recovery of blood perfusion in tissue and pO(2) in wound tracks was significantly more rapid in group IB and group E than in group I and control. The tissue level of TNF-α was significantly lower in group IB than in group I and control 48 h and 72 h post-wounding, and was lower than in group E 48 h post-wounding. The tissue level of TGF-β in group IB was sustained at a significantly higher level than in the other three groups. Wound healing time was also shorter in group IB. Enzymatic debridement using topical bromelain in incised wound tracks accelerates the recovery of blood perfusion, pO(2) in wound tissue, controls the expression of TNF-α and raises the expression of TGF-β. Copyright © 2012 Elsevier Inc. All rights reserved.

[Water-filtered infrared-A (wIRA) promotes wound healing].

PubMed

Winkel, R; Hoffmann, G; Hoffmann, R

2014-11-01

Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and low thermal load to the skin surface which promotes the healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic effects. Water-filtered infrared-A increases tissue temperature (+ 2.7 °C at a tissue depth of 2 cm), tissue oxygen partial pressure (+ 32 % at a tissue depth of 2 cm) and tissue perfusion. These three factors are decisive for a sufficient supply of tissue with energy and oxygen and consequently also for wound healing and infection defense. Water-filtered infrared-A promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain. These effects have been proven in a total of seven prospective studies (of these six randomized controlled studies) with most of the effects having an evidence level of Ia or Ib. The additional cases of complicated courses of wound healing presented in this article illustrate the proven effects of wIRA. Not only in the 6 presented cases wIRA turned the complicated courses of wound healing for the better and facilitated the healing of the wounds after varying total times of irradiation (in the 6 cases 51-550 h) and after variable times of wound care and mostly after transplantation of split skin grafts. In complicated courses of wound healing wIRA does not replace consultation and, when indicated, treatment by an experienced plastic surgeon and by a surgeon specialized in septic surgery. With these limitations wIRA can be recommended as a valuable complement for the treatment of acute as well as of chronic wounds.

Effect of virgin fatty oil of Pistacia lentiscus on experimental burn wound's healing in rabbits.

PubMed

Djerrou, Zouhir; Maameri, Z; Hamdi-Pacha, Y; Serakta, M; Riachi, F; Djaalab, H; Boukeloua, A

2010-04-03

This study aimed to assess the efficiency of the virgin fatty oil of Pistacia lentiscus (PLVFO) for burn wounds healing. It was carried out on 6 adult male New Zealand rabbits. Four burn wounds of deep third degree were made on the back of each animal. The first was not treated and served as control (CRL group); the others were covered immediately after burning procedure by 0.5g of one of the following products: Vaseline gel (VAS group), Madecassol(®) cream 1% (MAD group) or 1ml of PLVFO (PLVFO group). The treatments were repeated once daily until complete healing. For four days post burns, the percentage of wound contraction was assessed. Also, the different healing times were noted. The results showed that both PLVFO and Madecassol(®) significantly accelerated wound healing activity compared to wounds dressed with Vaseline and the untreated wounds. However, the level of wound contraction was significantly higher and the healing time was faster in PLVFO group than those of the MAD group, VAS group and CRL group. The different epithelization periods obtained in days were respectively: 30±3.94 (PLVFO group), 33.5±3.78 (MAD group), 34.66±3.88 (VAS group) and 37.16±3.54 (CRL group). We conclude that Pistacia lentiscus virgin fatty oil promotes significantly (p< 0.05) wound contraction and reduces epithelization period in rabbit model.

Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an experimental pilot study in rats.

PubMed

Fayazzadeh, Ehsan; Rahimpour, Sina; Ahmadi, Seyed Mohsen; Farzampour, Shahrokh; Sotoudeh Anvari, Maryam; Boroumand, Mohammad Ali; Ahmadi, Seyed Hossein

2014-01-01

Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test samples) were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7th day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples (87%±2% vs. 70%±4%, P<0.001). The majority of wounds in the test group were completely closed by the 10th day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups (0.624±0.097 vs. 0.255±0.063, P<0.05). The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects.

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

PubMed

Morton, Laurel M; Phillips, Tania J

2016-04-01

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

Differential regulation of a fibroblast growth factor-binding protein during skin carcinogenesis and wound healing.

PubMed

Kurtz, Andreas; Aigner, Achim; Cabal-Manzano, Rafael H; Butler, Robert E; Hood, Dozier R; Sessions, Roy B; Czubayko, Frank; Wellstein, Anton

2004-01-01

The initiation of premalignant lesions is associated with subtle cellular and gene expression changes. Here we describe a severe combined immunodeficiency mouse xenograft model with human adult skin and compare chemical carcinogenesis and wound healing. We focus on a secreted binding protein for fibroblast growth factors (FGF-BP) that enhances the activity of locally stored FGFs and is expressed at high levels in human epithelial cancers. Carcinogen treatment of murine skin induced papilloma within 6 weeks, whereas the human skin grafts displayed no obvious macroscopic alterations. Microscopic studies of the human skin, however, showed p53-positive keratinocytes in the epidermis, increased angiogenesis in the dermis of the treated skin, enhanced proliferation of keratinocytes in the basal layer, and an increase of FGF-BP protein and mRNA expression. In contrast, after surgical wounding of human skin grafts or of mouse skin, FGF-BP expression was upregulated within a few hours and returned to control levels after 2 days with wound closure. Enhanced motility of cultured keratinocytes and dermal fibroblasts by FGF-BP supports a role in wound healing. We conclude that adult human skin xenografts can be used to identify early molecular events during malignant transformation as well as transient changes during wound healing.

Wound Healing Potential of Formulated Extract from Hibiscus Sabdariffa Calyx

PubMed Central

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

2013-01-01

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

Healing of corneal epithelial wounds in marine and freshwater fish.

PubMed

Ubels, J L; Edelhauser, H F

The corneal epithelium of a fish is in direct contact with the aquatic environment and is a barrier to movement of ions and water into and through the cornea. This tissue layer is thus important in maintenance of corneal transparency. When the epithelium is wounded, its protective function is lost and corneal transparency remains compromised until the epithelial barrier is re-established. This study was undertaken to investigate the healing response of the fish cornea to epithelial abrasion. Wounds were stained with fluorescein and photographed during healing. Wound areas were measured by planimetry. The cornea of the sculpin, a marine teleost, becomes edematous after wounding and heals at 2.54 to 3.42 mm2/hr. Nonswelling corneas of the elasmobranchs--dogfish shark and skate--heal at 1.29 mm2/hr, respectively. The wounded eye of the rainbow trout, a freshwater teleost, is stressed by the low osmolality of the environment. Severe corneal edema and cataracts develop following epithelial wounding, and the cornea heals at 0.64 mm2/hr. Although the healing rates in teleosts differ from those in mammals, histology shows that the corneal healing mechanism is essentially the same in fish and mammals.

Adipose Tissue-Derived Stromal Cells for Wound Healing.

PubMed

Goodarzi, Parisa; Alavi-Moghadam, Sepideh; Sarvari, Masoumeh; Tayanloo Beik, Akram; Falahzadeh, Khadijeh; Aghayan, Hamidreza; Payab, Moloud; Larijani, Bagher; Gilany, Kambiz; Rahim, Fakher; Adibi, Hossein; Arjmand, Babak

2018-06-02

Skin as the outer layer covers the body. Wounds can affect this vital organ negatively and disrupt its functions. Wound healing as a biological process is initiated immediately after an injury. This process consists of three stages: inflammation, proliferation, remodeling. Generally, these three stages occur continuously and timely. However, some factors such as infection, obesity and diabetes mellitus can interfere with these stages and impede the normal healing process which results in chronic wounds. Financial burden on both patients and health care systems, negative biologic effect on the patient's general health status and reduction in quality of life are a number of issues which make chronic wounds as a considerable challenge. During recent years, along with advances in the biomedical sciences, various surgical and non-surgical therapeutic methods have been suggested. All of these suggested treatments have their own advantages and disadvantages. Recently, cell-based therapies and regenerative medicine represent promising approaches to wound healing. Accordingly, several types of mesenchymal stem cells have been used in both preclinical and clinical settings for the treatment of wounds. Adipose-derived stromal cells are a cost-effective source of mesenchymal stem cells in wound management which can be easily harvest from adipose tissues through the less invasive processes with high yield rates. In addition, their ability to secrete multiple cytokines and growth factors, and differentiation into skin cells make them an ideal cell type to use in wound treatment. This is a concise overview on the application of adipose-derived stromal cells in wound healing and their role in the treatment of chronic wounds.

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.

Effect of Zoledronate on Oral Wound Healing in Rats

PubMed Central

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

2010-01-01

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

Modeling the effect of topical oxygen therapy on wound healing

NASA Astrophysics Data System (ADS)

Agyingi, Ephraim; Ross, David; Maggelakis, Sophia

2011-11-01

Oxygen supply is a critical element for the healing of wounds. Clinical investigations have shown that topical oxygen therapy (TOT) increases the healing rate of wounds. The reason behind TOT increasing the healing rate of a wound remains unclear and hence current protocols are empirical. In this paper we present a mathematical model of wound healing that we use to simulate the application of TOT in the treatment of cutaneous wounds. At the core of our model is an account of the initiation of angiogenesis by macrophage-derived growth factors. The model is expressed as a system of reaction-diffusion equations. We present results of simulations for a version of the model with one spatial dimension.

Removal of the basement membrane enhances corneal wound healing.

PubMed

Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Stepp, Mary Ann

2011-12-01

Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, β4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

A Comparative Study of the Wound Healing Properties of Moist Exposed Burn Ointment (MEBO) and Silver Sulphadiazine

PubMed Central

Jewo, P.I.; Fadeyibi, I.O.; Babalola, O.S.; Saalu, L.C.; Benebo, A.S.; Izegbu, M.C.; Ashiru, O.A.

2009-01-01

Summary Burns expose the deeper tissues of the skin or body to invasive microbes. Topical preparations for treating burn wounds, to be useful, should ideally have antibiotic power and promote healing. Silver compounds have been the mainstay of topical burn treatment for decades. However, most chemical substances retard wound healing. Several natural agents such as honey and moist exposed burn ointment (MEBO) are believed to protect wounds from infection and promote healing without causing any of the adverse effects of purified chemicals. In this study, we compared the wound healing properties of MEBO, a herbal preparation of Chinese origin, with silver sulphadiazine (SSD), a long-standing conventional burn dressing. Ten adult Sprague Dawley rats were divided into two groups. They were housed in separate cages and received partial-thickness burn wounds on their dorsal skin. They were then treated with MEBO and SSD. The wounds were inspected daily until day 8, when all the animals were sacrificed, perfused with normal saline, and had their wounds excised and prepared for histology. It was found that animals in both groups were well preserved. No clinical infections occurred. Wound healing was at an advanced stage by day 8 in all the animals. Clinical and histological examination showed that the two agents gave the animals comparable protection and healing possibilities. It is concluded that MEBO is a suitable and efficacious alternative to conventional silver-based topical therapies for treating partial-thickness burn wounds. PMID:21991159

A Comparative Study of the Wound Healing Properties of Moist Exposed Burn Ointment (MEBO) and Silver Sulphadiazine.

PubMed

Jewo, P I; Fadeyibi, I O; Babalola, O S; Saalu, L C; Benebo, A S; Izegbu, M C; Ashiru, O A

2009-06-30

Burns expose the deeper tissues of the skin or body to invasive microbes. Topical preparations for treating burn wounds, to be useful, should ideally have antibiotic power and promote healing. Silver compounds have been the mainstay of topical burn treatment for decades. However, most chemical substances retard wound healing. Several natural agents such as honey and moist exposed burn ointment (MEBO) are believed to protect wounds from infection and promote healing without causing any of the adverse effects of purified chemicals. In this study, we compared the wound healing properties of MEBO, a herbal preparation of Chinese origin, with silver sulphadiazine (SSD), a long-standing conventional burn dressing. Ten adult Sprague Dawley rats were divided into two groups. They were housed in separate cages and received partial-thickness burn wounds on their dorsal skin. They were then treated with MEBO and SSD. The wounds were inspected daily until day 8, when all the animals were sacrificed, perfused with normal saline, and had their wounds excised and prepared for histology. It was found that animals in both groups were well preserved. No clinical infections occurred. Wound healing was at an advanced stage by day 8 in all the animals. Clinical and histological examination showed that the two agents gave the animals comparable protection and healing possibilities. It is concluded that MEBO is a suitable and efficacious alternative to conventional silver-based topical therapies for treating partial-thickness burn wounds.

Circadian actin dynamics drive rhythmic fibroblast mobilisation during wound healing

PubMed Central

Hoyle, Nathaniel P.; Seinkmane, Estere; Putker, Marrit; Feeney, Kevin A.; Krogager, Toke P.; Chesham, Johanna E.; Bray, Liam K.; Thomas, Justyn M.; Dunn, Ken; Blaikley, John; O’Neill, John S.

2017-01-01

Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping which imparts a ~24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately impact the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse’s active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than night-time wounds. We suggest that circadian regulation of the cytoskeleton influences wound healing efficacy from the cellular to the organismal scale. PMID:29118260

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

PubMed

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

2004-09-01

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

Healing of partial thickness porcine skin wounds in a liquid environment.

PubMed

Breuing, K; Eriksson, E; Liu, P; Miller, D R

1992-01-01

This study employs a liquid-tight vinyl chamber for the topical fluid-phase treatment of experimental wounds in pigs. Continuous treatment with normal saline significantly reduced the early progression of tissue destruction in partial thickness burns. Uncovered burns formed a deep layer of necrosis (0.49 +/- 0.004 mm, mean +/- SD) although burn wounds covered with empty chambers demonstrated less necrosis (0.14 +/- 0.01 mm), fluid-treated wounds formed no eschar, and little tissue necrosis could be detected (less than 0.005 mm). Topical treatment with hypertonic dextran increased water flux across burn wounds by 0.24 ml/cm2/24 hr (mean, n = 95) over saline-treated wounds during the first 5 days after wounding. When partial thickness burn and excisional wounds were immersed in isotonic saline until healed, the daily efflux of water, protein, electrolytes, and glucose across the wound surface declined during healing to baseline values found in controls (saline-covered unwounded skin). The declining protein permeability was used as a reproducible, noninvasive, endogenous marker for the return of epithelial barrier function. Saline-treated excisional wounds healed within 8.6 +/- 0.6 days (mean +/- SD, n = 27) and burn wounds within 12.1 +/- 1.4 days (mean +/- SD, n = 15). Healing of fluid-treated wounds occurred without tissue maceration and showed less inflammation and less scar formation than healing of air exposed wounds (no attempt was made to compare rates of healing between air- and fluid-exposed wounds). We consider the fluid-filled chamber a potentially very useful diagnostic, monitoring, and delivery system for wound-healing research and for human wound therapy.

Essential oil-loaded lipid nanoparticles for wound healing.

PubMed

Saporito, Francesca; Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Boselli, Cinzia; Icaro Cornaglia, Antonia; Mannucci, Barbara; Grisoli, Pietro; Vigani, Barbara; Ferrari, Franca

2018-01-01

Chronic wounds and severe burns are diseases responsible for severe morbidity and even death. Wound repair is a crucial process and tissue regeneration enhancement and infection prevention are key factors to minimize pain, discomfort, and scar formation. The aim of this work was the development of lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with eucalyptus or rosemary essential oils and to be used, as medical devices, to enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids: cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids. Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their aggregation. The systems were prepared by high shear homogenization followed by ultrasound application. Nanoparticles were characterized for physical-chemical properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward normal human dermal fibroblasts. Antimicrobial activity of nanoparticles was evaluated against two reference microbial strains, one of Staphylococcus aureus , the other of Streptococcus pyogenes . Finally, the capability of nanoparticles to promote wound healing in vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with eucalyptus oil showed appropriate physical-chemical properties, good bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward fibroblasts, associated to antimicrobial properties. Moreover, the in vivo results evidenced the capability of these NLC to enhance the healing process. Olive oil, which is characterized by a high content of oleic acid, proved to exert a synergic effect with eucalyptus oil with respect to antimicrobial activity and wound repair promotion.

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat.

PubMed

Lansdown, A B; Sampson, B; Laupattarakasem, P; Vuttivirojana, A

1997-11-01

Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL of silver nitrate (SN) at 0.01, 0.1 or 1.0% w/v aqueous solution, or 0.5 g silver sulphadiazine (SSD) over a 10-day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0.1 or 1.0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four-fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated with changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important.

Aggressive Wound Care by a Multidisciplinary Team Improves Wound Healing after Infrainguinal Bypass in Patients with Critical Limb Ischemia.

PubMed

Mii, Shinsuke; Tanaka, Kiyoshi; Kyuragi, Ryoichi; Ishimura, Hiroshi; Yasukawa, Shinsuke; Guntani, Atsushi; Kawakubo, Eisuke

2017-05-01

A long period is generally required for ischemic ulcer to heal after revascularization. The strategy of postoperative wound care can affect wound healing. This study was conducted to investigate the degree to which aggressive wound care (AWC) by a team of multidisciplinary specialists actually shortens the time to wound healing and increases the rate of wound healing in limbs undergoing surgical bypass for ischemic tissue loss in a real clinical setting. A total of consecutive 126 patients undergoing infrainguinal bypass for tissue loss from April 2011 to March 2015 were reviewed. Prior to March 2013, standard wound care (SWC) including typical daily dressing change with disinfection and irrigation, occasional surgical debridement, and negative pressure wound therapy (when necessary) was performed by vascular surgeons. Thereafter, in addition to SWC, AWC including intense daily bedside surgical debridement under a sciatic nerve block by an anesthesiologist and active skin grafting by a dermatologist, if necessary, was performed. Wound healing and major amputation were defined as the end points. The 1-year outcomes of the 2 groups were calculated using the Kaplan-Meier method and compared, and the significant predictors of each outcome were determined by a Cox proportional hazards analysis. The wound healing of the AWC group was superior to that of the SWC group (AWC versus SWC, 1-year wound healing rate: 92% vs. 80%; mean wound healing time: 48 days vs. 82 days; P = 0.011), and no significant difference between the 2 regimens in the freedom from major amputation was observed. AWC, Rutherford 5, no wound infection, normal serum albumin, direct angiosome, and cilostazol use were significant predictors of wound healing, and female gender and no cilostazol use were significant predictors of major amputation by a multivariate analysis. Aggressive wound care by the team consisting of multidisciplinary specialists remarkably shortened the time to wound healing and

Biology and Biomarkers for Wound Healing.

PubMed

Lindley, Linsey E; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-09-01

As the population grows older, the incidence and prevalence of conditions that lead to a predisposition for poor wound healing also increase. Ultimately, this increase in nonhealing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has and will continue to be the leading pathway to the discovery of therapeutic targets, as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of nonhealing patients for whom biomarker-guided approaches may aid in healing. A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Currently, biomarkers are being identified using biomaterials sourced locally from human wounds and/or systemically using high-throughput "omics" modalities (genomic, proteomic, lipidomic, and metabolomic analysis). In this review, we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum, including those measured in tissue specimens, for example, β-catenin and c-myc, wound fluid, matrix metalloproteinases and interleukins, swabs, wound microbiota, and serum, for example, procalcitonin and matrix metalloproteinases. Identification of numerous potential biomarkers using different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity and consistent implementation of these biomarkers, as well as an emphasis on efficacious follow-up therapeutics, is necessary for transition of this technology to clinically feasible point-of-care applications.

The TallyHo polygenic mouse model of diabetes: implications in wound healing.

PubMed

Buck, Donald W; Jin, Da P; Geringer, Matthew; Hong, Seok Jong; Galiano, Robert D; Mustoe, Thomas A

2011-11-01

Impairments in wound healing represent a significant source of morbidity and mortality in patients with diabetes. To help uncover the derangements associated with diabetic wound healing, murine animal models have been extensively used. In this article, the authors present results, and the accompanying wound healing implications, from experiments across three validated wound healing models using a newer polygenic strain of diabetes. The authors investigated the wound healing impairments of the TallyHo/JnJ diabetic mouse strain, using three validated wound healing models: an incisional model, a splinted excisional model, and a cutaneous ischemia-reperfusion injury model. Appropriate control strain mice were used for comparison. Wounds were analyzed using gross, histologic, and molecular techniques. TallyHo mice displayed deficits across all three wound healing models. There was a reduced resistance/response to oxidative stress and a global decrease in the initial inflammatory response to healing. In addition, there was a global decrease in the stimulus for angiogenesis and collagen formation, ultimately leading to reduced reepithelialization, granulation tissue formation, wound contraction, and wound tensile strength. Gross and histologic findings were corroborated with molecular data, which revealed a significant down-regulation of important cytokines, including vascular endothelial growth factor, neutrophilic attractant protein-2, monocyte chemoattractant protien-1, heme oxygenase-1, interleukin-1β, and interleukin-6, when normalized to the control strain (p<0.05). The TallyHo polygenic mouse model of diabetes demonstrates predictable and clinically relevant wound healing impairments that offer important implications into the derangements of diabetic wound healing observed clinically. Therapeutics targeting these specific derangements could provide improvements in the care of diabetic wounds.

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

PubMed

Panda, Vandana; Thakur, Tejas

2014-03-01

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

[Advances in the research of molecular mechanism of negative pressure wound therapy in improving wound healing].

PubMed

Liu, Y; Hu, D H

2017-11-20

Recently, negative pressure wound therapy (NPWT) is a rising technology to improve wound healing. In clinical application, it benefits fast debridement and wound close, limits infection, and promotes wound healing. It is an effective therapy for all kinds of acute or chronic wound. Currently, researches demonstrate that NPWT promotes angiogenesis, granulation tissue growth, and extracellular matrix remodeling through regulating the signaling of anti-inflammatory cytokines, mechanicalreceptor and chemoreceptor, which is related to several growth factors and inflammatory factors. Here we focus on the recent advances in the mechanism of NPWT in promoting wound healing, looking forward to providing a review of NPWT and related researches.

Growth factor-functionalized silk membranes support wound healing in vitro.

PubMed

Bienert, M; Hoss, M; Bartneck, M; Weinandy, S; Böbel, M; Jockenhövel, S; Knüchel, R; Pottbacker, K; Wöltje, M; Jahnen-Dechent, W; Neuss, S

2017-08-16

Chronic wounds represent a serious problem in daily medical routine requiring improved wound care. Silk of the domesticated silkworm (Bombyx mori) has been used to form a variety of biomaterials for medical applications. We genetically engineered B. mori to produce silk functionalized with growth factors to promote wound healing in vitro. In this study FGF-, EGF-, KGF-, PDGF- or VEGF-functionalized silk membranes were compared to native B. mori silk membranes without growth factors for their ability to support wound healing in vitro. All silk membranes were cytocompatible and supported macrophage secretion of neutrophil recruiting factor CXCL1 and monocyte chemoattractant protein 1 (MCP-1). VEGF-functionalized silk significantly outperformed other growth factor-functionalized silk membranes, but not native silk in angiogenesis assays. In addition, EGF- and VEGF-functionalized silk membranes slightly enhanced macrophage adhesion compared to silk without growth factors. In wound healing assays in vitro (reduction of wound lesion), dermal equivalents showed a higher wound healing capacity when covered with EGF-, FGF- or VEGF-functionalized silk membranes compared to native, KGF- or PDGF-functionalized silk membranes. Keratinocyte migration and growth is overstimulated by KGF- and VEGF-functionalized silk membranes. In conclusion, growth factor-functionalized silk membranes prepared from genetically engineered silk worm glands are promising wound dressings for future wound healing therapies.

Nanoparticles in wound healing; from hope to promise, from promise to routine.

PubMed

Naderi, Naghmeh; Karponis, Dimitrios; Mosahebi, Afshin; Seifalian, Alexander M

2018-01-01

Chronic non-healing wounds represent a growing problem due to their high morbidity and cost. Despite recent advances in wound healing, several systemic and local factors can disrupt the weighed physiologic healing process. This paper critically reviews and discusses the role of nanotechnology in promoting the wound healing process. Nanotechnology-based materials have physicochemical, optical and biological properties unique from their bulk equivalent. These nanoparticles can be incorporated into scaffolds to create nanocomposite smart materials, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and pro-angiogenic properties. Owed to their high surface area, nanoparticles have also been used for drug delivery as well as gene delivery vectors. In addition, nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.

Far infrared promotes wound healing through activation of Notch1 signaling.

PubMed

Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

2017-11-01

The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing.

PubMed

Castilho, R M; Squarize, C H; Gutkind, J S

2013-09-01

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K-PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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…

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

PubMed Central

Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

2015-01-01

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

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

PKM2 released by neutrophils at wound site facilitates early wound healing by promoting angiogenesis.

PubMed

Zhang, Yinwei; Li, Liangwei; Liu, Yuan; Liu, Zhi-Ren

2016-03-01

Neutrophils infiltration/activation following wound induction marks the early inflammatory response in wound repair. However, the role of the infiltrated/activated neutrophils in tissue regeneration/proliferation during wound repair is not well understood. Here, we report that infiltrated/activated neutrophils at wound site release pyruvate kinase M2 (PKM2) by its secretive mechanisms during early stages of wound repair. The released extracellular PKM2 facilitates early wound healing by promoting angiogenesis at wound site. Our studies reveal a new and important molecular linker between the early inflammatory response and proliferation phase in tissue repair process. © 2016 by the Wound Healing Society.

Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing.

PubMed

Feng, Yi; Sanders, Andrew J; Ruge, Fiona; Morris, Ceri-Ann; Harding, Keith G; Jiang, Wen G

2016-11-01

Cytokines play important roles in the wound healing process through various signalling pathways. The JAK-STAT pathway is utilised by most cytokines for signal transduction and is regulated by a variety of molecules, including suppressor of cytokine signalling (SOCS) proteins. SOCS are associated with inflammatory diseases and have an impact on cytokines, growth factors and key cell types involved in the wound‑healing process. SOCS, a negative regulator of cytokine signalling, may hold the potential to regulate cytokine‑induced signalling in the chronic wound‑healing process. Wound edge tissues were collected from chronic venous leg ulcer patients and classified as non-healing and healing wounds. The expression pattern of seven SOCSs members, at the transcript and protein level, were examined in these tissues using qPCR and immunohistochemistry. Significantly higher levels of SOCS3 (P=0.0284) and SOCS4 (P=0.0376) in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level. Relocalisation of SOCS3 protein in the non-healing wound environment was evident in the investigated chronic biopsies. Thus, the results show that the expression of SOCS transcript indicated that SOCS members may act as a prognostic biomarker of chronic wounds.

Approaches to cutaneous wound healing: basics and future directions.

PubMed

Zeng, Ruijie; Lin, Chuangqiang; Lin, Zehuo; Chen, Hong; Lu, Weiye; Lin, Changmin; Li, Haihong

2018-04-10

The skin provides essential functions, such as thermoregulation, hydration, excretion and synthesis of vitamin D. Major disruptions of the skin cause impairment of critical functions, resulting in high morbidity and death, or leave one with life-changing cosmetic damage. Due to the complexity of the skin, diverse approaches are needed, including both traditional and advanced, to improve cutaneous wound healing. Cutaneous wounds undergo four phases of healing. Traditional management, including skin grafts and wound dressings, is still commonly used in current practice but in combination with newer technology, such as using engineered skin substitutes in skin grafts or combining traditional cotton gauze with anti-bacterial nanoparticles. Various upcoming methods, such as vacuum-assisted wound closure, engineered skin substitutes, stem cell therapy, growth factors and cytokine therapy, have emerged in recent years and are being used to assist wound healing, or even to replace traditional methods. However, many of these methods still lack assessment by large-scale studies and/or extensive application. Conceptual changes, for example, precision medicine and the rapid advancement of science and technology, such as RNA interference and 3D printing, offer tremendous potential. In this review, we focus on the basics of wound treatment and summarize recent developments involving both traditional and hi-tech therapeutic methods that lead to both rapid healing and better cosmetic results. Future studies should explore a more cost-effective, convenient and efficient approach to cutaneous wound healing. Graphical abstract Combination of various materials to create advanced wound dressings.

Use of dehydrated human amniotic membrane allografts to promote healing in patients with refractory non healing wounds.

PubMed

Sheikh, Emran S; Sheikh, Ednan S; Fetterolf, Donald E

2014-12-01

Non healing wounds present a significant social and economic burden. Chronic non healing wounds are estimated to affect as many as 1-2% of individuals during their lifetime, and account for billions of dollars of expense annually on both a national and global basis. Our purpose is to describe the use of a novel dehydrated amniotic membrane allograft (EpiFix(®) ; MiMedx Group, Inc., Kennesaw, GA) for the treatment of chronic non healing wounds. We describe the results of EpiFix treatment in four patients who had not achieved wound closure with both conservative and advanced measures, and had been referred for a definitive plastic surgery procedure. Healing was observed in a variety of wounds with one to three applications of the dehydrated amniotic membrane material. The material was well tolerated by patients. Healed wounds did not recur in long-term follow-up. Further investigation of the use of dehydrated amniotic membrane in broader application to various types of dermal wounds should be considered. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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

Low-Intensity Vibration Improves Angiogenesis and Wound Healing in Diabetic Mice

PubMed Central

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. PMID:24618702

Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

PubMed

Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

2017-09-01

Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

Topical effects of frog "Rana ridibunda" skin secretions on wound healing and reduction of wound microbial load.

PubMed

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

2013-02-13

Study of the interrelationships between human and the animals in their environment has always been a subject of interest and caused discoveries of the animal applications in medicine. From the latest century, these remedies called back in traditional medicine of Vietnam and South America and frog skin was used as a biological dressing and had good effects in healing wounds. Also, frog skin secretions have wound healing properties and reduce inflammation. In this study we applied these secretions in the form of ointment to investigate their healing activities. Skin secretions were extracted from Rana ridibunda to evaluate their effects on wound healing in mice. Secretion used as raw extract (RE) and ultrafiltrated extract, using a membrane with cutoff 10kDa as under 10kDa (U10E), was administrated as ointment every 48h on wound site. Control group was left without any treatment and also there was other group treated with ointment (O group) alone. On 2, 4 and 6 days post injury, animals were euthanized and images were taken for wound closure evaluation. Then wound locations were removed for histological assays. Also wound microbial load was examined. Observational parameters including wound closure and wound microbiology in experimental groups compared with the control and O groups have been studied. The results showed U10E group has better effects than RE, O and control groups. Histological parameters, including numbers of inflammatory and fibroblast cells and amount of collagen fibers, neovascularization, as well, represented greater degree of wound healing in U10E group compared with RE, O, and control groups. Our results showed that frog skin secretions were significantly effective in promoting wound healing process. The U10E extract from the frog R. ridibunda possesses a potent accelerating wound healing effect that promises good potential for clinical application in wound care. Further studies will be required to characterize special molecules encompassing

PLGA based drug delivery systems: Promising carriers for wound healing activity.

PubMed

Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

2016-03-01

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

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

Low energy laser irradiation treatment for second intention wound healing in horses

PubMed Central

Fretz, Peter B.; Li, Zhong

1992-01-01

Low energy helium-neon laser irradiation was administered to full thickness skin wounds (3 cm × 3 cm) on the dorsal surface of the metacarpophalangeal/metatarsophalangeal joints and cranial surface of the tarsocrural joints of eight horses. The effects on wound healing were analyzed statistically. There were no differences (p > 0.55) observed in the rate of wound healing between the low energy laser irradiated wounds and the control wounds. There was a significant difference (p < 0.006) observed in the rate of healing between the anatomical sites. Tarsal wounds healed more rapidly than fetlock wounds. PMID:17424089

Essential oil-loaded lipid nanoparticles for wound healing

PubMed Central

Saporito, Francesca; Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Boselli, Cinzia; Icaro Cornaglia, Antonia; Mannucci, Barbara; Grisoli, Pietro; Vigani, Barbara; Ferrari, Franca

2018-01-01

Chronic wounds and severe burns are diseases responsible for severe morbidity and even death. Wound repair is a crucial process and tissue regeneration enhancement and infection prevention are key factors to minimize pain, discomfort, and scar formation. The aim of this work was the development of lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with eucalyptus or rosemary essential oils and to be used, as medical devices, to enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids: cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids. Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their aggregation. The systems were prepared by high shear homogenization followed by ultrasound application. Nanoparticles were characterized for physical–chemical properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward normal human dermal fibroblasts. Antimicrobial activity of nanoparticles was evaluated against two reference microbial strains, one of Staphylococcus aureus, the other of Streptococcus pyogenes. Finally, the capability of nanoparticles to promote wound healing in vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with eucalyptus oil showed appropriate physical–chemical properties, good bioadhesion, cytocompatibility, in vitro proliferation enhancement, and wound healing properties toward fibroblasts, associated to antimicrobial properties. Moreover, the in vivo results evidenced the capability of these NLC to enhance the healing process. Olive oil, which is characterized by a high content of oleic acid, proved to exert a synergic effect with eucalyptus oil with respect to antimicrobial activity and wound repair promotion. PMID:29343956

The Efficacy of Gelam Honey Dressing towards Excisional Wound Healing

PubMed Central

Tan, Mui Koon; Hasan Adli, Durriyyah Sharifah; Tumiran, Mohd Amzari; Abdulla, Mahmood Ameen; Yusoff, Kamaruddin Mohd

2012-01-01

Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing. PMID:22536292

Antioxidant therapies for wound healing: a clinical guide to currently commercially available products.

PubMed

Fitzmaurice, S D; Sivamani, R K; Isseroff, R R

2011-01-01

Many facets of wound healing under redox control require a delicate balance between oxidative stress and antioxidants. While the normal physiology of wound healing depends on low levels of reactive oxygen species and oxidative stress, an overexposure to oxidative stress leads to impaired wound healing. Antioxidants are postulated to help control wound oxidative stress and thereby accelerate wound healing. Many antioxidants are available over the counter or by prescription, but only one, Medihoney®, has been specifically FDA approved for wound healing. Here we review the existing evidence for the use of antioxidants for wound healing, with a review of the pertinent animal and clinical studies. Natural products and naturally derived antioxidants are becoming more popular, and we specifically review the evidence for the use of naturally derived antioxidants in wound healing. Antioxidant therapy for wound healing is promising, but only few animal studies and even fewer clinical studies are available. Because only few products have undergone FDA approval, the consumer is advised to scrutinize them for purity and contaminants prior to use, and this may require direct contact with the companies that sell them. As a field of science, the use of antioxidants for wound healing is in its infancy, and future studies will better elucidate the role of antioxidants in wound healing. Copyright © 2011 S. Karger AG, Basel.

Evaluation of wound healing activity of root of Mimosa pudica.

PubMed

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

2009-07-15

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

Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.

PubMed

Yamauchi, Makoto; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Matsumoto, Yoshitaka; Yamashita, Ken; Kayama, Musashi; Sato, Noriyuki; Yotsuyanagi, Takatoshi

2016-05-13

Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and TNF-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-α production model using spleen cells revealed that TNF-α production was significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in kl/kl mouse may have a role to increase TNF-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin Wound Healing: An Update on the Current Knowledge and Concepts.

PubMed

Sorg, Heiko; Tilkorn, Daniel J; Hager, Stephan; Hauser, Jörg; Mirastschijski, Ursula

2017-01-01

The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. Although wound healing mechanisms and specific cell functions in wound

Influence of phytochemicals in piper betle linn leaf extract on wound healing.

PubMed

Lien, Le Thi; Tho, Nguyen Thi; Ha, Do Minh; Hang, Pham Luong; Nghia, Phan Tuan; Thang, Nguyen Dinh

2015-01-01

Wound healing has being extensively investigated over the world. Healing impairment is caused by many reasons including increasing of free-radicals-mediated damage, delaying in granulation tissue formation, reducing in angiogenesis and decreasing in collagen reorganization. These facts consequently lead to chronic wound healing. Piper betle Linn (Betle) leaves have been folklore used as an ingredient of drugs for cutaneous wound treatment. However, the effect of betle leaf on wound healing is not yet well elucidated. In this study, we aimed to investigate the healing efficacy of methanol leaf extract of Piper betle Linn on proliferation of fibroblast NIH3T3 cells as well as full-thickness burn and excision wounds in swiss mice. Scratch wound healing assays were conducted to examine the effects of betle leaf extract on healing activity of fibroblast cells. Burn and excision wounds on swiss mouse skins were created for investigating the wound healing progress caused by the betle leaf extract. Malondialdehyde (MDA) was also evaluated to examine the products of lipid hydroperoxide (LPO) under conditions of with or without betle leaf extract treatment. The results of this study showed that Piper betle Linn leaf extract in methanol increased proliferation of NIH3T3 cells and promoted wound healing in vitro and in vivo with both burn wound and excision wound models. In addition, this extract significant decreased level of malondialdehyde (MDA) in liver of treated-mice compared with that in non-treated mice. Our results suggest that Piper betle Linn can be used as an ingredient in developing natural origin drugs for treatment of cutaneous wounds.

Identifying the trends in wound-healing patents for successful investment strategies

PubMed Central

Gwak, Jae Ha

2017-01-01

Background Recently, the need for rapid wound-healing has significantly increased because of the increasing number of patients who are diagnosed with diabetes and obesity. These conditions have contributed to a surge in the number of patients with chronic wounds worldwide. Furthermore, many cost-effective wound-healing technologies have been developed in order to keep up with the increased demand. In this paper, we performed a quantitative study of the trends associated with wound-healing technologies using patent data. Methodology We analyzed the trends considering four different groups of patent applicants: firms, universities, research institutes, and individuals using a structural topic model. In addition, we analyzed the knowledge flow between patent applicants using citation analysis, and confirmed the role of applicants in the knowledge-flow network using k-means clustering. As a result, the primary wound-healing technology patents applied for by the four groups varied considerably, and we classified the roles of patent applicants were found in the knowledge-flow network. Conclusions Our results showed the organizations that are leading each area of wound-healing technology. Furthermore, from the results, we identified specific institutions that are efficient for spreading knowledge related to wound-healing technology based on the patents. This information can contribute to the planning of investment strategies and technology policies related to wound-healing. PMID:28306732

Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.

PubMed

Yoon, Dong Suk; Lee, Yunki; Ryu, Hyun Aae; Jang, Yeonsue; Lee, Kyoung-Mi; Choi, Yoorim; Choi, Woo Jin; Lee, Moses; Park, Kyung Min; Park, Ki Dong; Lee, Jin Woo

2016-07-01

In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound

Delayed Wound Healing in Heat Stable Antigen (HSA/CD24)-Deficient Mice.

PubMed

Shapira, Shiran; Ben-Amotz, Oded; Sher, Osnat; Kazanov, Dina; Mashiah, Jacob; Kraus, Sarah; Gur, Eyal; Arber, Nadir

2015-01-01

Healthy individuals rarely have problems with wound healing. Most skin lesions heal rapidly and efficiently within one to two weeks. However, many medical and surgical complications can be attributed to deficiencies in wound repair. Open wounds have lost the barrier that protects tissues from bacterial invasion and allows the escape of vital fluids. Without expeditious healing, infections become more frequent. The CD24 gene encodes a heavily-glycosylated cell surface protein anchored to the membrane by phosphatidylinositol. CD24 plays an important role in the adaptive immune response and controls an important genetic checkpoint for homeostasis and autoimmune diseases in both mice and humans. We have previously shown that overexpression of CD24 results in increased proliferation and migration rates. To examine the role of CD24 in the wound healing process. An excisional model of wound healing was used and delayed wound healing was studied in genetically modified heat stable antigen (HSA/CD24)-deficient mice (HSA-/-) compared to wild-type (WT) mice. Large full-thickness skin wounds, excised on the back of mice, exhibited a significant delay in the formation of granulation tissue, and in wound closure when compared to their WTHSA+/+ littermates. Wounds were histologically analyzed and scored, based on the degree of cellular invasion, granulation tissue formation, vascularity, and re-epithelialization. Additionally, in stitched wounds, the HSA-/- mice failed to maintain their stitches; they did not hold and fell already 24 hours, revealing erythematous wound fields. Re-expression of HSA, delivered by lentivirus, restored the normal healing phenotype, within 24 hours post-injury, and even improved the healing in WT, and in BalbC mice. Delayed wound-healing in the absence of HSA/CD24 suggests that CD24 plays an important role in this process. Increased expression of CD24, even in the normal state, may be used to enhance wound repair.

Enhance wound healing monitoring through a thermal imaging based smartphone app

NASA Astrophysics Data System (ADS)

Yi, Steven; Lu, Minta; Yee, Adam; Harmon, John; Meng, Frank; Hinduja, Saurabh

2018-03-01

In this paper, we present a thermal imaging based app to augment traditional appearance based wound growth monitoring. Accurate diagnose and track of wound healing enables physicians to effectively assess, document, and individualize the treatment plan given to each wound patient. Currently, wounds are primarily examined by physicians through visual appearance and wound area. However, visual information alone cannot present a complete picture on a wound's condition. In this paper, we use a smartphone attached thermal imager and evaluate its effectiveness on augmenting visual appearance based wound diagnosis. Instead of only monitoring wound temperature changes on a wound, our app presents physicians a comprehensive measurements including relative temperature, wound healing thermal index, and wound blood flow. Through the rat wound experiments and by monitoring the integrated thermal measurements over 3 weeks of time frame, our app is able to show the underlying healing process through the blood flow. The implied significance of our app design and experiment includes: (a) It is possible to use a low cost smartphone attached thermal imager for added value on wound assessment, tracking, and treatment; and (b) Thermal mobile app can be used for remote wound healing assessment for mobile health based solution.

Silk sericin ameliorates wound healing and its clinical efficacy in burn wounds.

PubMed

Aramwit, Pornanong; Palapinyo, Sirinoot; Srichana, Teerapol; Chottanapund, Suthat; Muangman, Pornprom

2013-09-01

The aim of this study was to evaluate the effect of silk sericin, a protein from silkworm cocoon, on scratch wound healing in vitro. For applicable result in clinical use, we also study the efficacy of sericin added to a standard antimicrobial cream, silver zinc sulfadiazine, for open wound care in the treatment of second-degree burn wounds. In vitro scratch assays show that sericin at concentration 100 μg/mL can promote the migration of fibroblast L929 cells similar to epidermal growth factor (positive control) at 100 μg/mL. After 1 day of treatment, the length of scratch in wounds treated with sericin was significantly shorter than the length of negative control wounds (culture medium without sericin). For clinical study, a total of 29 patients with 65 burn wounds which covered no less than 15 % of total body surface area were randomly assigned to either control (wounds treated with silver zinc sulfadiazine cream) or treatment (wounds treated with silver zinc sulfadiazine with added sericin cream) group in this randomized, double-blind, standard-controlled study. The results showed that the average time to reach 70 % re-epithelialization of the burned surface and complete healing in the treatment group was significantly shorter, approximately 5-7 days, than in the control group. Regarding time for complete healing, control wounds took approximately 29.28 ± 9.27 days, while wounds treated with silver zinc sulfadiazine with added sericin cream took approximately 22.42 ± 6.33 days, (p = 0.001). No infection or severe reaction was found in any wounds. This is the first clinical study to show that silk sericin is safe and beneficial for burn wound treatment when it is added to silver sulfadiazine cream.

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

PubMed Central

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

2016-01-01

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

Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition.

PubMed

Chaudhary, Amrita; Bag, Swarnendu; Barui, Ananya; Banerjee, Provas; Chatterjee, Jyotirmoy

2015-01-01

Honey is known as a popular healing agent against tropical infections and wounds. However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing under hypoxic condition is still not explored. In this study, we examined whether honey dilution have wound healing potential under hypoxic stress. The antioxidant potential and healing efficacy of honey dilution on in vitro wound of human epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2 ), and normoxia is explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the changes in cellular function was observed microscopically. Further, the cell proliferation, migration, cell-cell adhesion, and relevant gene expression were studied by flow cytometry, migration/scratch assay, immunocytochemistry, and reverse transcription-polymerase chain reaction, respectively. The expression pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F-actin, p63, and hypoxia marker Hif 1α were examined. Honey dilution in 0.1% v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%). Its wound healing potential was quantified by immunocytochemistry and real-time PCR for the associated molecular features that were responsible for cell proliferation and migration. Our data showed that honey dilution can be effective in hypoxic wound healing. Additionally, it reduced superoxide generation and supplied favorable bioambience for cell proliferation, migration, and differentiation during hypoxic wound healing. These findings may reveal the importance of honey as an alternative and cost effective therapeutic natural product for wound healing in hypoxic condition. © 2015 by the Wound Healing Society.

Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing.

PubMed

Wu, Song; Deng, Liang; Hsia, Hanson; Xu, Kai; He, Yu; Huang, Qiangru; Peng, Yi; Zhou, Zhihua; Peng, Cheng

2017-05-01

Excellent wound dressings maintain a warm and moist environment, thus accelerating wound healing. In this study, we cross-linked gelatin and hyaluronic acid with ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in different ratios (gelatin/hyaluronic acid = 8:2, gelatin/hyaluronic acid = 5:5, gelatin/hyaluronic acid = 2:8), and explored the effects and mechanisms of gelatinhyaluronic acid hydrogels on wound healing. This was done by examining dressing properties, such as fluid uptake ability, water vapor transmission rate, and the rate of water evaporation. We further verified biological function by using in vitro and in vivo wound models. The hydrogels display appropriate fluid uptake ability and good water vapor transmission rate and rate of water evaporation all of which can provide an adequate moisture environment for wound healing. Cell cytotoxicity and proliferation tests show that the hydrogels have no cytotoxicity, furthermore, gelatin/hyaluronic acid = 8:2 hydrogels have the potential to promote cell proliferation. Animal wound models demonstrate that the hydrogels can effectively promote wound healing in vivo, in particular, the gelatin/hyaluronic acid = 8:2 group which promoted the most rapid healing. Accordingly, gelatin-hyaluronic acid dressings, especially the gelatin/hyaluronic acid = 8:2 hydrogels, have a promising outlook for clinical applications in wound healing.

Collagen VII plays a dual role in wound healing

PubMed Central

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

2013-01-01

Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds. PMID:23867500

[Wound healing is still a game of " blind men and an elephant"].

PubMed

Han, C M

2016-10-20

The wound healing includes non-healing and overhealing of the wounds. The results of wound healing are well known by people such as non-healing of the diabetic ulcer or hypertrophic scar after deep burn. In this issue, three papers involve in wound healing, one about autologous adipose-derived mesenchymal stem cells injected into wound or scar of rabbit ear, one about severe hypoxia and hypoalbuminemia inducing human hypertrophic scar derived fibroblast apoptosis in vitro, and another about the dysfunction of protein kinase B/mammalian target of rapamycin signaling pathway contributing to the pathophysiological characteristics of diabetic skin and non-healing wound. The basic problem of hypertrophic scar study is lacking an ideal animal model. Although rabbit ear model or red Duroc pig model has been used widely for study on hypertrophic scar, they can not fully represent human dermal fibrosis after deep trauma on the skin. I recommend A novel nude mouse model of hypertrophic scarring using scratched full thickness human skin grafts recently published in Advances in Wound Care to the readers. The author emphasizes that the wound healing study is still in the situation like the game of " blind men and an elephant" .

Evaluation of dressings to aid healing of mulesing wounds on sheep.

PubMed

Levot, G W; Hughes, P B; Kaldor, C J

1989-11-01

Five proprietary and one experimental dressing were compared with no treatment in their ability to aid healing of mulesing wounds in over 1900 young lambs. Healing was judged as the completeness of shrinkage of the mulesing cuts and the condition of scabs on the new skin surface. When assessed at 21 d it was found that treatment with Heriots Crown Wound Powder or Coopers Mulesing Powder offered a significant advantage over leaving the wounds untreated. Neither aqueous organophosphate washes, Defiance nor Defiance containing 0.08% chlorfenvinphos offered any healing advantage over controls. However, washing the wounds with an aqueous organophosphate solution aided healing more than the Defiance-based dressings. It was considered that the powders or the washes encouraged quick scab formation either by creating a dry covering (powders) or by washing away blood and allowing fast drying of the wound. The Defiance-type dressings slowed healing by keeping the wound moist for up to 10 d, but healing was not significantly different to the untreated group by 21 d.

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

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

A Surgical Device to Study the Efficacy of Bioengineered Skin Substitutes in Mice Wound Healing Models.

PubMed

Jeschke, Marc G; Sadri, Ali-Reza; Belo, Cassandra; Amini-Nik, Saeid

2017-04-01

Due to the poor regenerative capacity of adult mammalian skin, there is a need to develop effective skin substitutes for promoting skin regeneration after a severe wound. However, the complexity of skin biology has made it difficult to enable perfect regeneration of skin. Thus, animal models are being used to test potential skin substitutes. Murine models are valuable but their healing process involves dermal contraction. We have developed a device called a dome that is able to eliminate the contraction effect of rodent skin while simultaneously housing a bioengineered skin graft. The dome comes in two models, which enables researchers to evaluate the cells that contribute in wound healing from neighboring intact tissue during skin healing/regeneration. This protocol simplifies grafting of skin substitutes, eliminates the contraction effect of surrounding skin, and summarizes a simple method for animal surgery for wound healing and skin regeneration studies.

Steroid depressed wound healing and Tridax procumbens.

PubMed

Diwan, P V; Tilloo, L D; Kulkarni, D R

1983-01-01

Dexamethasone 0.33 mg/kg (I.M.) on first day and half this dose thereafter daily, depressed wound contraction, epithelization, tensile strength and process of granulation of wounds in experimental animals. Juice from the leaves of Tridex procumbens (T.P. 1 ml, I.P., daily) resembled dexamethasone in effects on wound contraction and granulation; but it significantly (P less than 0.001) counteracted the effects of dexamethasone on tensile strength and epithelization. TP caused increase in adrenal weight and decrease in thymus weight. These observations suggest that TP exerts a direct pro-healing effect along with an indirect anti-healing influences probably mediated through release of adrenal steroids.

SCF increases in utero-labeled stem cells migration and improves wound healing.

PubMed

Zgheib, Carlos; Xu, Junwang; Mallette, Andrew C; Caskey, Robert C; Zhang, Liping; Hu, Junyi; Liechty, Kenneth W

2015-01-01

Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin. © 2015 by the Wound Healing Society.

Histopathological assessment of OASIS Ultra on critical-sized wound healing: a pilot study.

PubMed

Yeh, Daniel Dante; Nazarian, Rosalynn M; Demetri, Leah; Mesar, Tomaz; Dijkink, Suzan; Larentzakis, Andreas; Velmahos, George; Sadik, Karim Walid

2017-06-01

Dermatopathologists assess wounds secondary to trauma, infection, or oncologic resection that can be challenging to reconstruct. OASIS Ultra, an extracellular matrix, has been described for use in chronic and burn wounds. The aim of this pilot study is to assess wound healing in post-traumatic and infective wounds treated with OASIS using histological markers of repair. Adults with traumatic, infective or iatrogenic wound defects with size precluding primary closure were eligible. Half the wound was randomly assigned to receive OASIS plus standard therapy; the other half received standard of care (SOC) therapy. During dressing changes, standardized-scale photographs were taken and biopsies obtained. Histologic sections were reviewed for degree of acute inflammation and extent of tissue repair. Neutrophils, edema, hemorrhage, necrosis, fibroblasts, collagen density and neovascularization were semi-quantitatively assessed. Forty-four skin biopsies from 7 patients with 10 acute wounds met eligibility criteria. Histologically, OASIS samples demonstrated improved acute inflammation scores compared to SOC. No patients experienced OASIS-related complications. OASIS-treated wound halves trended toward more wound contraction and improved tissue repair. Our scoring system aids histopathological wound assessment. Treatment of critical-sized, post-traumatic, acute wounds with OASIS resulted in decreased inflammation, and potentially more advanced wound healing, compared to SOC. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Establishment of a cell-based wound healing assay for bio-relevant testing of wound therapeutics.

PubMed

Planz, Viktoria; Wang, Jing; Windbergs, Maike

Predictive in vitro testing of novel wound therapeutics requires adequate cell-based bio-assays. Such assays represent an integral part during preclinical development as pre-step before entering in vivo studies. Simple "scratch tests" based on defected skin cell monolayers exist, however these can solely be used for testing liquids, as cell monolayer destruction and excessive hydration limit their applicability for (semi-)solid systems like wound dressings. In this context, a cell-based wound healing assay is introduced for rapid and predictive testing of wound therapeutics independent of their physical state in a bio-relevant environment. A novel wound healing assay was established for bio-relevant and predictive testing of (semi-) solid wound therapeutics. The assay allows for physiologically relevant hydration of the tested wound therapeutics at the air-liquid interface and their removal without cell monolayer disruption. In a proof-of-concept study, the applicability and discriminative power could be demonstrated by examining unloaded and drug-loaded wound dressings with two different established wound healing actives (dexpanthenol and metyrapone) and their effect on skin cell behavior. The influence of the released drug on the cells´ healing behavior could successfully be monitored over time. Wound size assessment after 96h resulted in an eight fold smaller wound area for drug treated models compared to the ones treated with unloaded fibers and non-treated wounds. This assay provides valuable first insights towards the establishment of a valid screening and evaluation tool for preclinical wound therapeutic development from liquid to (semi-)solid systems to improve predictability in a simple, yet standardized way. Copyright © 2017 Elsevier Inc. All rights reserved.

The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation.

PubMed

Ayuk, Sandra Matabi; Abrahamse, Heidi; Houreld, Nicolette Nadene

2016-01-01

The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

Computational and Experimental Study of the Mechanics of Embryonic Wound Healing

PubMed Central

Varner, Victor D.; Taber, Larry A.

2013-01-01

Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (“purse string”) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30 seconds. Circular and elliptical wounds (~100 µm in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia. PMID:23973771

Effect of Neem oil and Haridra on non-healing wounds.

PubMed

Singh, Anjali; Singh, Anil Kumar; Narayan, G; Singh, Teja B; Shukla, Vijay Kumar

2014-01-01

In Ayurveda, Vrana (wound) has stated as tissue destruction and discoloration of viable tissue due to various etiology. In Sushruta Samhita, Sushruta described Vrana as a main subject. Most commonly Vrana can be classified into Shuddha and Dushta Vrana (chronic wound/nonhealing ulcers). Among the various drugs mentioned for Dushta Vrana, two of them, Neem (Azadirechta indica A. Juss) oil and Haridra (Curcuma longa Linn.) powder are selected for their wide spectrum action on wound. To compare the effect of Neem oil and Haridra in the treatment of chronic non-healing wounds. Total 60 patients of wounds with more than 6 weeks duration were enrolled and alternatively allocated to Group I (topical application of Neem oil), Group II (Haridra powder capsules, 1 g 3 times orally) and Group III (both drugs). Duration of treatment was considered until complete healing of the wound, whereas 4(th) and 8(th) week were considered for assessment of 50% healing. Wound size was measured and recorded at weekly intervals. Wound biopsy was repeated after 4 weeks for assessment of angiogenesis and deoxyribonucleic acid (DNA) analysis. After 8 weeks of treatment, 50% wound healing was observed in 43.80% patients of Group I, 18.20% patients of Group II, and 70.00% patients of Group III. Microscopic angiogenesis grading system scores and DNA concentration showed highly significant effect of combined use of both drugs when compared before and after results of treatment (P < 0.001). Topical use of Neem oil and oral use of Haridra powder capsule used in combination were found effective for chronic non-healing wounds.

The Influence of Anger Expression on Wound Healing

PubMed Central

Gouin, Jean-Philippe; Kiecolt-Glaser, Janice K.; Malarkey, William B.; Glaser, Ronald

2008-01-01

Certain patterns of anger expression have been associated with maladaptive alterations in cortisol secretion, immune functioning, and surgical recovery. We hypothesized that outward and inward anger expression and lack of anger control would be associated with delayed wound healing. A sample of 98 community-dwelling participants received standardized blister wounds on their non-dominant forearm. After blistering, the wounds were monitored daily for eight days to assess speed of repair. Logistic regression was used to distinguish fast and slow healers based on their anger expression pattern. Individuals exhibiting lower levels of anger control were more likely to be categorized as slow healers. The anger control variable predicted wound repair over and above differences in hostility, negative affectivity, social support, and health behaviors. Furthermore, participants with lower levels of anger control exhibited higher cortisol reactivity during the blistering procedure. This enhanced cortisol secretion was in turn related to longer time to heal. These findings suggest that the ability to regulate the expression of one’s anger has a clinically relevant impact on wound healing. PMID:18078737

Tissue-specific contribution of macrophages to wound healing.

PubMed

Minutti, Carlos M; Knipper, Johanna A; Allen, Judith E; Zaiss, Dietmar M W

2017-01-01

Macrophages are present in all tissues, either as resident cells or monocyte-derived cells that infiltrate into tissues. The tissue site largely determines the phenotype of tissue-resident cells, which help to maintain tissue homeostasis and act as sentinels of injury. Both tissue resident and recruited macrophages make a substantial contribution to wound healing following injury. In this review, we evaluate how macrophages in two fundamentally distinct tissues, i.e. the lung and the skin, differentially contribute to the process of wound healing. We highlight the commonalities of macrophage functions during repair and contrast them with distinct, tissue-specific functions that macrophages fulfill during the different stages of wound healing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing.

PubMed

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

2016-01-13

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

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

PubMed

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

2016-06-15

Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial- or full-thickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-β- and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells - processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make re-epithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization. © 2016. Published by The Company of Biologists Ltd.

Wound healing activity of Argyreia nervosa leaves extract

PubMed Central

Singhal, AK; Gupta, H; Bhati, VS

2011-01-01

Background: Argyreia nervosa (Convolvulaceae) plant is an example of hallucinogenic plant. The antiseptic, anti-inflammatory, antispasmodic, antibacterial, antiviral, antifungal, anticonvulsant, nootropic, antifertility and aphrodisiac properties have already been reported for this plant. Aim: The aim of present work was to evaluate the wound healing property in normal and diabetic animals by oral and topical administration of ethanolic extract of leaves. Materials and Methods: Phytochemical investigations showed the presence of various biochemicals (alkaloids, flavonoids, carbohydrates, triterpenoids, proteins, saponins, steroids, tannins). A single injection of alloxan monohydrate (120 mg/kg, i.p.) prepared in citrate buffer (0.1 M, pH 4.5) was administered to produce diabetes in rats and mice, after overnight fasting. Excision wounds (sized 300 mm2 and of 2 mm depth) were used for the study of rate of contraction of wound and epithelization. The means of wound area measurement between groups at different time intervalswere compared using one-way analysis of variance (ANOVA), followed by Dunnet's test. Results: Extracts of A. nervosa showed significant wound healing effect in normal (topically treated) and diabetic (both topically and orally treated) rats. In diabetic rats, the topically treated group showed more significant effect than the orally treated groups. Conclusion: The present study demonstrates that A. nervosa leaves extract applied topically promotes healing of wounds more significantly as compared to oral application, in both normal rats and alloxan induced diabetic rats, where healing is otherwise delayed. PMID:23776770

[Effect of static magnetic field on deep wound healing of SD rats].

PubMed

Shen, Jian-Guo; Chen, Wei-Shan; Wang, Chang-Xing; Jiang, Tao; Dong, Li-Qiang

2009-05-01

To investigate the effect of static magnetic field on deep wound healing of SD rats and VEGF during the wound healing and different strength static magnetic field on deep wound healing of SD rats. Divided forty-eight SD rats into three groups: 0.16 T magnetic disk treatment (0.16 T group), 0.32 T magnetic disk treatment (0.32 T group), control group. General wounds healing situation was observated on the 3, 6, 9, 12 day. The area of every wound was calculated. The tissue of granulation was dyeing by immune tissue chemical decoration method, in which VEGF protein content with its range in tissue was measured. The healing index of 0.16 T magnetic group wounds were larger than that of control group on 6th and 9th day, there were statistical difference. The healing index of 0.32 T magnetic group wounds were larger than that of control group on 3rd, 6th, 9th and 12th day, there were statistical difference. The healing index of 0.32 T group wounds contrasted to that of 0.16 T group wounds had no statistical significance. Observation of VEGF at the course of wound healing:the expressing of VEGF in magnetic group wounds on 3rd and 6th was stronger than in control group wounds, there were statistical difference. While there were no obvious difference between them on 9th and 12th day (P>0.05). But the contrast between that in 0.32 T group and in 0.16 T group had no statistical difference. The expressing strength of VEGF in magnetic group reached the peak amplitude on the 6th day, and that in control group reached peak amplitude on 9th day. And the peak amplitude of magnetic group was stronger than that of control group. Static magnetic disc of 0.16T and 0.32 T can promote deep wound of SD rats heal. The mechanism of static magnetic field promoting wound heal may be relative to the expressing highly of VEGF during early and middle time.

Wound Healing Studies Using Punica granatum Peel: An Animal Experimental Study.

PubMed

Zekavat, Omidreza; Amanat, Aida; Karami, Mohammadyasin; Paydar, Shahram; Gramizadeh, Bita; Zareian-Jahromi, Maryam

2016-05-01

The goal of the present study was to evaluate the effects of hydroalcoholic extract-based carboxy methyl cellulose (CMC) gel of Punica granatum peel (PCMC) and CMC on healing of full-thickness skin wounds. Forty-two rats were studied. Each rat had 3 wounds that were treated topically with PCMC as the case, CMC as the positive control, and sterile saline as the negative control. All 3 wounds of each rat were photographed during the wound healing period at days 0 (onset of wound surgery), 3, 6, 9, and 12.The wound area was calculated using Adobe Photoshop CS (version 5) software (Adobe Systems Inc, San Jose, California). Electrocardiogram paper was used for reference scale. The results of this study show that macroscopic and microscopic wound healing took a significantly longer time in wounds treated with normal saline than those treated with PCMC (grossly) and CMC gel (grossly and significantly). The authors' findings show that anti-inflammatory, antihemorrhagic, and antinecrotic effects of CMC lead to early healing of skin wounds.

Evaluation of wound healing activity of ferulic acid in diabetic rats.

PubMed

Ghaisas, Mahesh M; Kshirsagar, Shashank B; Sahane, Rajkumari S

2014-10-01

In diabetic patients, there is impairment in angiogenesis, neovascularisation and failure in matrix metalloproteineases (MMPs), keratinocyte and fibroblast functions, which affects wound healing mechanism. Hence, diabetic patients are more prone to infections and ulcers, which finally result in gangrene. Ferulic acid (FA) is a natural antioxidant found in fruits and vegetables, such as tomatoes, rice bran and sweet corn. In this study, wound healing activity of FA was evaluated in streptozotocin-induced diabetic rats using excision wound model. FA-treated wounds were found to epithelise faster as compared with diabetic wound control group. The hydroxyproline and hexosamine content increased significantly when compared with diabetic wound control. FA effectively inhibited the lipid peroxidation and elevated the catalase, superoxide dismutase, glutathione and nitric oxide levels along with the increase in the serum zinc and copper levels probably aiding the wound healing process. Hence, the results indicate that FA significantly promotes wound healing in diabetic rats. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates

PubMed Central

Seifert, Ashley W.; Monaghan, James R.; Voss, S. Randal; Maden, Malcolm

2012-01-01

While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair. PMID:22485136

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

Delayed Wound Healing in Heat Stable Antigen (HSA/CD24)-Deficient Mice

PubMed Central

Shapira, Shiran; Ben-Amotz, Oded; Sher, Osnat; Kazanov, Dina; Mashiah, Jacob; Kraus, Sarah; Gur, Eyal; Arber, Nadir

2015-01-01

Background Healthy individuals rarely have problems with wound healing. Most skin lesions heal rapidly and efficiently within one to two weeks. However, many medical and surgical complications can be attributed to deficiencies in wound repair. Open wounds have lost the barrier that protects tissues from bacterial invasion and allows the escape of vital fluids. Without expeditious healing, infections become more frequent. The CD24 gene encodes a heavily-glycosylated cell surface protein anchored to the membrane by phosphatidylinositol. CD24 plays an important role in the adaptive immune response and controls an important genetic checkpoint for homeostasis and autoimmune diseases in both mice and humans. We have previously shown that overexpression of CD24 results in increased proliferation and migration rates. Aim To examine the role of CD24 in the wound healing process. Methods An excisional model of wound healing was used and delayed wound healing was studied in genetically modified heat stable antigen (HSA/CD24)-deficient mice (HSA -/-) compared to wild-type (WT) mice. Results Large full-thickness skin wounds, excised on the back of mice, exhibited a significant delay in the formation of granulation tissue, and in wound closure when compared to their WTHSA +/+ littermates. Wounds were histologically analyzed and scored, based on the degree of cellular invasion, granulation tissue formation, vascularity, and re-epithelialization. Additionally, in stitched wounds, the HSA -/- mice failed to maintain their stitches; they did not hold and fell already 24 hours, revealing erythematous wound fields. Re-expression of HSA, delivered by lentivirus, restored the normal healing phenotype, within 24 hours post-injury, and even improved the healing in WT, and in BalbC mice. Conclusions Delayed wound-healing in the absence of HSA/CD24 suggests that CD24 plays an important role in this process. Increased expression of CD24, even in the normal state, may be used to enhance wound

Evaluation of lipoic acid topical application on rats skin wound healing.

PubMed

Külkamp-Guerreiro, Irene Clemes; Souza, Marielly Nunes; Bianchin, Mariana Domingues; Isoppo, Mateus; Freitas, Joana Sachetti; Alves, João Alex; Piovezan, Anna Paula; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski

2013-10-01

To evaluate the effects of lipoic acid (thioctic acid) topical application on wound healing on rats skin, and the consequences of lipoic acid nanoencapsulation on this process. The model used was the healing activity on wounds induced by surgical incision on rats skin (n = 44). The parameters analyzed (11 days) were wound healing rate and histology (vascular proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or reepithelialization), after application of free lipoic acid or lipoic acid- loaded nanocapsules. The antioxidant activity of these formulations was evaluated by lipid peroxidation test. It was demonstrated for the first time that the topical application of lipoic acid improves wound healing. On the seventh day after surgery, the animals treated with lipoic acid showed increased healing rate (60.7 ± 8.4%) compared to the negative control group (43.0 ± 17.4%), as so improvement of histological parameters. The nanoencapsulation reverted the pro-oxidant activity presented in vitro by lipoic acid, whereas diminished wound repair. The topical application of lipoic acid produced an increase in the skin wound healing, which may be related to its pro-oxidant activity. On the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant activity, although presented minor healing activity.

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

Wakayama symposium: new therapies for modulation of epithelialization in corneal wound healing.

PubMed

Choi, Jun-Sub; Joo, Choun-Ki

2013-01-01

Many factors are involved in the corneal wound healing mechanism, including adhesion, migration, and proliferation of corneal epithelial cells. Abnormal corneal wound healing leads to corneal edema, neovascularization, scar formation, and poor vision. Three agents, 17β-estradiol, nicergoline, and β-glucan, have demonstrated positive effects on the wound healing response in laboratory experiments and may be of help in controlling wound healing in corneas that have suffered epithelial damage or have undergone refractive surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Wound Healing Effect of Arnebia euchroma gel on Excisional Wounds in Rats

PubMed Central

Mohsenikia, Maryam; Khakpour, Shahrzad; Azizian, Zahra; Ashkani-Esfahani, Soheil; Razavipour, Seyyede Tahereh; Toghiani, Pooya

2017-01-01

Background: Wound healing is a complex process leading to regeneration of damaged skin tissue. Arnebia euchroma (AE) have many effective activities such as anti-inflammatory, antimicrobial, antioxidative, and anti-tumoral effects. The extract of AE has positive effects on burn wounds. This study is designed to investigate the healing effects of AE on excisional wounds in rats. Materials and Methods: Thirty six rats with the age of 8 weeks divided into three groups. One group (E1) was treated with AE gel at a concentration of 10%. Control group (C1) received normal saline and the vehicle group (C2) was treated with carboxymethyl cellulose gel as the vehicle for 14 days. Stereological analysis was done to investigate the collagen bundle and hair follicale synthesis, vascularization, fibroblast proliferation. Pathological evaluation was also conducted. Results: In this study, pathological evaluation showed severe acute inflammation in C2 group, chronic and acute inflammation in C1 and also more wound contraction in E1 in comparison with other groups. There was a meaningful difference between E1 and C1 regarding fibroblast proliferation (P < 0.05). Conclusion: Results of this study revealed the healing effect of AE on excisional wounds and recommend its administration after further clinical investigations. PMID:28217647

Matrix- and plasma-derived peptides promote tissue-specific injury responses and wound healing in diabetic swine.

PubMed

Sheets, Anthony R; Massey, Conner J; Cronk, Stephen M; Iafrati, Mark D; Herman, Ira M

2016-07-02

Non-healing wounds are a major global health concern and account for the majority of non-traumatic limb amputations worldwide. However, compared to standard care practices, few advanced therapeutics effectively resolve these injuries stemming from cardiovascular disease, aging, and diabetes-related vasculopathies. While matrix turnover is disrupted in these injuries, debriding enzymes may promote healing by releasing matrix fragments that induce cell migration, proliferation, and morphogenesis, and plasma products may also stimulate these processes. Thus, we created matrix- and plasma-derived peptides, Comb1 and UN3, which induce cellular injury responses in vitro, and accelerate healing in rodent models of non-healing wounds. However, the effects of these peptides in non-healing wounds in diabetes are not known. Here, we interrogated whether these peptides stimulate healing in a diabetic porcine model highly reminiscent of human healing impairments in type 1 and type 2-diabetes. After 3-6 weeks of streptozotocin-induced diabetes, full-thickness wounds were surgically created on the backs of adult female Yorkshire swine under general anesthesia. Comb1 and UN3 peptides or sterile saline (negative control) were administered to wounds daily for 3-7 days. Following sacrifice, wound tissues were harvested, and quantitative histological and immunohistochemical analyses were performed for wound closure, angiogenesis and granulation tissue deposition, along with quantitative molecular analyses of factors critical for angiogenesis, epithelialization, and dermal matrix remodeling. Comb1 and UN3 significantly increase re-epithelialization and angiogenesis in diabetic porcine wounds, compared to saline-treated controls. Additionally, fluorescein-conjugated Comb1 labels keratinocytes, fibroblasts, and vascular endothelial cells in porcine wounds, and Far western blotting reveals these cell populations express multiple fluorescein-Comb1-interacting proteins in vitro. Further

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.

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

Thyrotropin-releasing hormone and its analogs accelerate wound healing.

PubMed

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

2014-06-15

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

Development of serratiopeptidase and metronidazole based alginate microspheres for wound healing.

PubMed

Rath, G; Johal, E S; Goyal, Amit K

2011-02-01

The objective of this study was to establish an effective therapy system for wound management. The present work describes preparation of metronidazole/serratiopeptidase loaded alginate microspheres by emulsification method. In vitro characterizations like particle size analysis, % yield, % encapsulation, and in vitro release were carried out. Wound healing assessment was determined by physical, histological, and biochemical methods. Wound healing performance of experimental formulations was compared with marketed product in rabbits. Result obtained for alginate microspheres showed good loading efficiency with spherical in shape. Experimentation suggests wound healing is improved by using serratiopeptidase and metronidazole in full thickness wounds in rabbits.

A conducive bioceramic/polymer composite biomaterial for diabetic wound healing.

PubMed

Lv, Fang; Wang, Jie; Xu, Peng; Han, Yiming; Ma, Hongshi; Xu, He; Chen, Shijie; Chang, Jiang; Ke, Qinfei; Liu, Mingyao; Yi, Zhengfang; Wu, Chengtie

2017-09-15

Diabetic wound is a common complication of diabetes. Biomaterials offer great promise in inducing tissue regeneration for chronic wound healing. Herein, we reported a conducive Poly (caprolactone) (PCL)/gelatin nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) for diabetic wound healing. NAGEL bioceramic particles were well distributed in the inner of PCL/gelatin nanofibers via co-electrospinning process and the Si ions maintained a sustained release from the composite scaffolds during the degradation process. The nanofibrous scaffolds significantly promoted the adhesion, proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human keratinocytes (HaCaTs) in vitro. The in vivo study demonstrated that the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization in the wound sites of diabetic mice model, as well as inhibited inflammation reaction. The mechanism for nanofibrous composite scaffolds accelerating diabetic wound healing is related to the activation of epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vivo and in vitro. Our results suggest that the released Si ions and nanofibrous structure of scaffolds have a synergetic effect on the improved efficiency of diabetic wound healing, paving the way to design functional biomaterials for tissue engineering and wound healing applications. In order to stimulate tissue regeneration for chronic wound healing, a new kind of conducive nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) were prepared via co-electrospinning process. Biological assessments revealed that the NAGEL bioceramic particles could active epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vitro and in vivo. The new composite scaffold

Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

PubMed

Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

2014-09-01

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

PubMed Central

Leal, Ermelindo C.; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E.; Kokkotou, Efi; Mooney, David J.; LoGerfo, Frank W.; Pradhan-Nabzdyk, Leena; Veves, Aristidis

2016-01-01

Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. PMID:25871534

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... generation of degradative enzymes, additional matrix proteins, and cross- linking of collagen, processes which can continue for years to months following the...tissue repair during normal physiological wound healing (5). In an uncompromised individual, the wound healing process generally proceeds with- out

Farnesyl Pyrophosphate Inhibits Epithelialization and Wound Healing through the Glucocorticoid Receptor*

PubMed Central

Vukelic, Sasa; Stojadinovic, Olivera; Pastar, Irena; Vouthounis, Constantinos; Krzyzanowska, Agata; Das, Sharmistha; Samuels, Herbert H.; Tomic-Canic, Marjana

2010-01-01

Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor. We used functional studies to evaluate the effects of FPP on wound healing. Both FPP and ZGA inhibited keratinocyte migration and epithelialization in vitro and ex vivo. These effects were independent of farnesylation and indicate that modulation of FPP levels in skin may be beneficial for wound healing. FPP inhibition of keratinocyte migration and wound healing proceeds, in part, by repression of the keratin 6 gene. Furthermore, we show that the 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitor mevastatin, which blocks FPP formation, not only promotes epithelialization in acute wounds but also reverses the effect of ZGA on activation of the GR and inhibition of epithelialization. We conclude that FPP inhibits wound healing by acting as a GR agonist. Of special interest is that FPP is naturally present in cells prior to glucocorticoid synthesis and that FPP levels can be further altered by the statins. Therefore, our findings may provide a better understanding of the pleiotropic effects of statins as well as molecular mechanisms by which they may accelerate wound healing. PMID:19903814

A preliminary study on the effect of manuka honey on second-intention healing of contaminated wounds on the distal aspect of the forelimbs of horses.

PubMed

Bischofberger, Andrea S; Dart, Christina M; Perkins, Nigel R; Dart, Andrew J

2011-10-01

To determine the effect of manuka honey on second-intention healing of contaminated, full-thickness skin wounds in horses. Experimental. Adult Standardbred horses (n = 8). One wound was created on the dorsomedial aspect of the third metacarpus in both forelimbs, contaminated with feces, and bandaged for 24 hours. Bandages were removed and wounds rinsed with isotonic saline solution. Wounds on 1 limb had manuka honey applied daily (n = 8) whereas wounds on the contralateral limb received no treatment (n = 8). Bandages were replaced and changed daily for 12 days, after which treatment stopped, bandages were removed, leaving wounds open to heal. Wound area was measured 24 hours after wound creation (day 1), then weekly for 8 weeks. Overall time for healing was recorded. Wound area and rate of healing of treated and control wounds were compared statistically. Treatment with manuka honey decreased wound retraction and treated wounds remained significantly smaller than control wounds until day 42; however, there was no difference in overall healing time between treatment and control wounds. Treatment with manuka honey reduced wound area by reducing retraction but did not affect overall healing time of full-thickness distal limb wounds using this wound-healing model. © Copyright 2011 by The American College of Veterinary Surgeons.