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Showing papers on "Chronic wound published in 2009"


Journal ArticleDOI
TL;DR: The immense economic and social impact of wounds in the authors' society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.
Abstract: In the United States, chronic wounds affect 6.5 million patients. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds and the burden is rapidly growing due to increasing health care costs, an aging population and a sharp rise in the incidence of diabetes and obesity worldwide. The annual wound care products market is projected to reach $15.3 billion by 2010. Chronic wounds are rarely seen in individuals who are otherwise healthy. In fact, chronic wound patients frequently suffer from "highly branded" diseases such as diabetes and obesity. This seems to have overshadowed the significance of wounds per se as a major health problem. For example, NIH's Research Portfolio Online Reporting Tool (RePORT; http://report.nih.gov/), directed at providing access to estimates of funding for various disease conditions does list several rare diseases but does not list wounds. Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.

2,353 citations


Journal ArticleDOI
TL;DR: Wound classification, the physiology of the wound healing process and the methods used in wound management are discussed.
Abstract: Wound healing remains a challenging clinical problem and correct, efficient wound management is essential. Much effort has been focused on wound care with an emphasis on new therapeutic approaches and the development of technologies for acute and chronic wound management. Wound healing involves multiple cell populations, the extracellular matrix and the action of soluble mediators such as growth factors and cytokines. Although the process of healing is continuous, it may be arbitrarily divided into four phases: (i) coagulation and haemostasis; (ii) inflammation; (iii) proliferation; and (iv) wound remodelling with scar tissue formation. The correct approach to wound management may effectively influence the clinical outcome. This review discusses wound classification, the physiology of the wound healing process and the methods used in wound management.

1,679 citations


Journal ArticleDOI
TL;DR: Experimental data supports the hypothesis that VEGF stimulates epithelialization and collagen deposition in a wound, but likely promotes collagen deposition and epithelization as well, and stimulates wound healing through angiogenesis.

865 citations


Journal ArticleDOI
TL;DR: Clinical relevant information is provided on currently available topical antimicrobial agents used to treat infected wounds and how to treat poorly healing wounds with "secondary" signs suggesting infection.
Abstract: Various agents have been applied topically to treat infected wounds for millennia, but their proper role remains unclear. Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful. Clinically infected wounds usually require systemic antibiotic therapy, whereas clinically uninfected wounds that are healing as expected do not require antimicrobials. There is controversy over how to treat poorly healing wounds with "secondary" signs suggesting infection; these may benefit from topical antimicrobial agents. Some evidence supports using topical agents for malodorous or burn wounds. Meta-analyses and systematic reviews suggest there are few proven indications for topical antimicrobials. Use of a newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings) is preferable to use of topical antibiotics, especially agents that are available for systemic use. We provide clinically relevant information on currently available topical antimicrobial agents.

455 citations


Journal ArticleDOI
TL;DR: It is demonstrated that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model and provides new insight into the understanding of chronic wound persistence.
Abstract: Epidermal T cells have been shown to play unique roles in tissue homeostasis and repair in mice through local secretion of distinct growth factors in the skin. Human epidermis contains both αβ+ and γδ+ T cells whose functional capabilities are not understood. We demonstrate that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model. Moreover, an analysis of the functional capabilities of T cells isolated from acute versus chronic wounds revealed a striking difference. Both αβ+ and Vδ1+ T cells isolated from acute wounds actively produced IGF-1, demonstrating that they are activated during tissue damage to participate in wound repair. In contrast, IGF-1 production could not be detected in T cells isolated from chronic wounds. In fact, skin T cells isolated from chronic wounds were refractory to further stimulation, suggesting an unresponsive state. Collectively, these results define a novel role for human epidermis–resident T cells in wound healing and provide new insight into our understanding of chronic wound persistence.

279 citations


Journal ArticleDOI
TL;DR: This work presents a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm, the first direct evidence for the effect of bacterial biofilms on cutaneous wounds healing.
Abstract: Bacterial biofilms have gained increasing visibility in recent years as a ubiquitous form of survival for microorganisms in myriad environments. A number of in vivo models exist for the study of biofilms in the setting of medically relevant implanted foreign bodies. Growing evidence has demonstrated the presence of bacterial biofilms in the setting of a number of chronic wound states including pressure sores, diabetic foot ulcers, and venous stasis ulcers. Here we present a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm. We established biofilms using either Staphylococcus aureus or Staphylococcus epidermidis in splinted cutaneous punch wounds created on the backs of normal C57Bl6/J mice. Wound reepithelialization was significantly delayed by bacterial biofilms. This effect was specifically dependent on the ability of the bacteria to form biofilms as demonstrated by exogenous administration of biofilm inhibiting peptides and the use of mutant Staphylococcus spp. deficient in biofilm formation. This represents the first direct evidence for the effect of bacterial biofilms on cutaneous wound healing.

272 citations


Journal Article
03 Feb 2009-ePlasty
TL;DR: It is found that nutrition is a critical component in all the wound healing processes and the use of anabolic agents can significantly increase overall lean mass synthesis and directly or indirectly improves healing by increasing protein synthesis.
Abstract: Optimum nutrition is well recognized to be a key factor in maintaining all phases of wound healing There are 2 processes that can complicate healing One is activation of the stress response to injury, and the second is the development of any protein-energy malnutrition (PEM) Any significant wound leads to a hypermetabolic and catabolic state, and nutritional needs are significantly increased The healing wound depends on adequate nutrient flow (Fig ​(Fig1)1) Of particular concern is the presence of any PEM, PEM being defined as a deficiency of energy and protein intake to meet bodily demands PEM in the presence of a wound leads to the loss of lean body mass (LBM) or protein stores, which will in and of itself impede the healing process Early aggressive nutrient and micronutritional feeding is essential to control and prevent this process from developing PEM is commonly seen in the chronic wound population, especially the elderly, disabled, or chronically ill populations where chronic wounds tend to develop1–5 Figure 1 Balance between adequacy of macronutrients and net anabolism and catabolism and its impact on wound healing Hunter, in 1954, followed by Culbertson and Moore, identified the fact that a wound being a threat to human existence takes preference for the available nutrients to heal, especially amino acids, at the expense of the host LBM6–8 This process leads to an autocannibalism of available LBM to obtain the necessary amino acids for the required protein synthesis in the wound If inadequate intake is present to keep up with needs, then PEM can develop If inadequate glucose is available for the healing wound, proteins will break down into amino acids and through the alanine shunt lead to glucose synthesis by the liver However, with severe losses of LBM, the host takes preference over the wound9–13 This entire process is the result of the activation of the “stress response” to injury or wounding with its hormonal imbalance favoring body protein catabolism for substrate, needed for protein synthesis There is also increased metabolic or calorie demand9–13 There is a fundamental difference between the adequate intake seen in the unstressed patient and one where trauma or infection has activated the host stress response14,15 Starvation alone produces a self-protective hormonal environment, which spares LBM with more than 90% of calories obtained from fat14–16 To optimize healing, a substrate that is more dependent on intake than on the bodily breakdown of protein needs to be available Chronic wounds are more complicated because the biology of the healing process is significantly altered However, a stress response is activated with any wound and any existing PEM will accentuate the already poor healing process17–19 For the above reasons, one cannot dissociate the normal process of healing from the nutritional status

236 citations


Journal ArticleDOI
31 Jul 2009-PLOS ONE
TL;DR: The 16S rRNA gene-based analyses revealed complex bacterial communities including anaerobic bacteria that may play causative roles in the non-healing state of some chronic wounds and suggest that antimicrobial therapy alters community structure—reducing some bacteria while selecting for others.
Abstract: Background: Bacterial colonization is hypothesized to play a pathogenic role in the non-healing state of chronic wounds. We characterized wound bacteria from a cohort of chronic wound patients using a 16S rRNA gene-based pyrosequencing approach and assessed the impact of diabetes and antibiotics on chronic wound microbiota. Methodology/Principal Findings: We prospectively enrolled 24 patients at a referral wound center in Baltimore, MD; sampled patients' wounds by curette; cultured samples under aerobic and anaerobic conditions; and pyrosequenced the 16S rRNA V3 hypervariable region. The 16S rRNA gene-based analyses revealed an average of 10 different bacterial families in wounds-approximately 4 times more than estimated by culture-based analyses. Fastidious anaerobic bacteria belonging to the Clostridiales family XI were among the most prevalent bacteria identified exclusively by 16S rRNA gene-based analyses. Community-scale analyses showed that wound microbiota from antibiotic treated patients were significantly different from untreated patients (p = 0.007) and were characterized by increased Pseudomonadaceae abundance. These analyses also revealed that antibiotic use was associated with decreased Streptococcaceae among diabetics and that Streptococcaceae was more abundant among diabetics as compared to non-diabetics. Conclusions/Significance: The 16S rRNA gene-based analyses revealed complex bacterial communities including anaerobic bacteria that may play causative roles in the non-healing state of some chronic wounds. Our data suggest that antimicrobial therapy alters community structure-reducing some bacteria while selecting for others.

218 citations


Journal ArticleDOI
TL;DR: A comprehensive in vitro approach is suggested to enable the assessment of wound dressings to support optimal conditions for wound healing and alginate showed antibacterial activity and high biocompatibility.
Abstract: Chronic wounds contain elevated levels of proteases, proinflammatory cytokines, and free radicals. The presence of bacteria further exaggerates the tissue-damaging processes. For successful treatment, the wound dressing needs to manage wound exudates, create a moist environment, inhibit infection, bind pathophysiological factors that are detrimental to wound healing, and provide thermal isolation. Furthermore, it has to relieve pain, be easy to use, show no allergic potency, and not release toxic residues. The present study suggests a comprehensive in vitro approach to enable the assessment of wound dressings to support optimal conditions for wound healing. Three alginate-based wound dressings: alginate alone, alginate containing ionic silver, and alginate with nanocrystalline silver, were tested for biocompatibility, antimicrobial activity, and influence on chronic wound parameters such as elastase, matrix metalloproteases-2, tumor necrosis factor-alpha, interleukin-8, and free radical formation. Alginate was found to bind considerable amounts of elastase, reduce the concentration of proinflammatory cytokines and inhibit the formation of free radicals. Furthermore, alginate showed antibacterial activity and high biocompatibility. Incorporation of silver into alginate fibers increased antimicrobial activity and improved the binding affinity for elastase, matrix metalloproteases-2, and the proinflammatory cytokines tested. Addition of silver also enhanced the antioxidant capacity. However, a distinct negative effect of silver-containing alginates on human HaCaT keratinocytes was noted in vitro.

149 citations


Journal ArticleDOI
TL;DR: Treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo‐angiogenesis and tissue regeneration, and topical anti‐inflammatory response.
Abstract: Extracorporeal shock-wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio-mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 x 5 cm) in a streptozotocin-induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW-1) on day 3 (800 impulses at 0.09 mJ/mm(2)) postwounding; group IV included rats that underwent two sessions of ESWT (ESW-2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW-3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT-treated rats, especially in the ESW-2 and ESW-3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro-inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW-2 and ESW-3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo-angiogenesis and tissue regeneration, and topical anti-inflammatory response.

149 citations


Journal ArticleDOI
TL;DR: A major advance in resolving or addressing the chronic wound has been the concept of WBP, which allows us to address the problems of wound healing individually the presence of necrotic tissue, hypoxia, high bacterial burden, corrupt matrix, and senescent cells within the wound bed.

Journal ArticleDOI
TL;DR: It is suggested that combining molecular and culturing methods provides a more complete characterization of the microbial diversity of chronic wounds, and can thereby expand the understanding of how microbiology impacts chronic wound pathology and healing.
Abstract: Chronic wounds expose the dermal matrix and underlying tissue to a diversity of microbes from the body and surrounding environment. We determined the microbial diversity of 19 chronic wounds using both molecular methods (sequence analysis of rRNA genes) and routine clinical culturing methods using swab samples. We identified 93 phylotypes in 2,653 rRNA clone sequences and found that compared with other environments, the microbial diversityof chronic wounds is relatively well characterized, i.e., 95% of sequences have! 97% identity with known human commensals. In total, 75% of sequences belonged to four well-known wound-associated phylotypes: Staphylococcus (25%), Corynebacterium (20%), Clostridiales (18%), and Pseudomonas (12%). Approximately 0.5% of sequences (seven phylotypes) belonged to potentially new species. Individual wound samples contained four to 22 phylotypes, but in all wounds only a few (one to three) phylotypes were dominant. In more than half the wound specimens, polymerase chain reaction and culturing methods gave different diversity and dominance information about the microbes present. This exploratory study suggests that combining molecular and culturing methods provides a more complete characterization of the microbial diversity of chronic wounds, and can thereby expand our understanding of how microbiology impacts chronic wound pathology and healing.

Journal ArticleDOI
TL;DR: It was clearly showed that aging affects chronic wound healing negatively, and the effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60.
Abstract: With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5-year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (>or=70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.

Journal ArticleDOI
TL;DR: This short review examines how changes in the expression of molecular factors are related to altered morphology in diabetic foot ulceration and very briefly considers treatment strategies at molecular level.
Abstract: The continuously increasing worldwide prevalence of diabetes will be accompanied by a greater incidence of diabetic foot ulcer, a complication in which many of the morphological processes involved in normal wound healing are disrupted. The highly complex and integrated process of wound healing is regulated by a large array of molecular factors. These often have overlapping functions, ensuring a certain degree of tolerance through redundancy. In diabetes, changes to the expression of a large number of molecular factors have been observed, overwhelming this inbuilt redundancy. This results in delayed healing or incomplete healing as in ulceration. Understanding the relationship between altered levels of molecular factors and the inhibited healing process in such ulcers will permit the development of targeted treatments aimed to greatly improve the quality of life of patients, at the same time helping to reduce the huge costs associated with treating this diabetic condition and its long-term consequences. This short review examines how changes in the expression of molecular factors are related to altered morphology in diabetic foot ulceration and very briefly considers treatment strategies at molecular level.

Journal ArticleDOI
TL;DR: The objective was to establish a potential role for matrix metalloproteinase-9 (MMP-9) in chronic wound healing and measure its measurement in diabetic foot ulcers.
Abstract: We thank the authors for their comment (1) on our study (2) and we agree that the pathophysiology of diabetic foot ulcers is complex and not well understood. We recognize that we are not the first to establish a potential role for matrix metalloproteinase-9 (MMP-9) in chronic wound healing. However, we report that its measurement …

Journal ArticleDOI
TL;DR: Treating ulcers involves recognizing the four stages of healing: coagulation, inflammation, proliferation, and maturation, and moving past the inflammation stage requires considering the bacterial burden, necrotic tissue, and moisture balance of the wound being treated.
Abstract: With our aging population, chronic diseases that compromise skin integrity such as diabetes, peripheral vascular disease (venous hypertension, arterial insufficiency) are becoming increasingly common. Skin breakdown with ulcer and chronic wound formation is a frequent consequence of these diseases. Types of ulcers include pressure ulcers, vascular ulcers (arterial and venous hypertension), and neuropathic ulcers. Treatment of these ulcers involves recognizing the four stages of healing: coagulation, inflammation, proliferation, and maturation. Chronic wounds are frequently stalled in the inflammatory stage. Moving past the inflammation stage requires considering the bacterial burden, necrotic tissue, and moisture balance of the wound being treated. Bacterial overgrowth or infection needs to be treated with topical or systemic agents. In most cases, necrotic tissue needs to be debrided and moisture balance needs to be addressed by wetting dry tissue and drying wet tissue. Special dressings have been developed to accomplish these tasks. They include films, hydrocolloids, hydrogel dressings, foams, hydrofibers, composite and alginate dressings.

Journal ArticleDOI
TL;DR: Families of genes involved in cell adhesion and extracellular matrix, cell cycle, cellular signaling, development and immune response show significant differences in regulation between banked fetal and those from banked old skin cells: with approximately 47.0% of genes over-expressed in fetal fibroblasts contributing to efficient tissue repair seen in the clinic with fetal cell therapy.

Journal ArticleDOI
TL;DR: Although a pronounced effect on the physical properties of the collagen was found, there was no significant loss in the binding affinity for polymorphonuclear elastase, matrix metalloproteinase-2, and interleukin-1beta, or in the antioxidant capacity.
Abstract: In the treatment of chronic wounds, it is necessary to establish a physiological wound milieu to improve healing. Application of collagen as wound dressing has been described as beneficial as it possesses the ability to reduce elevated levels of proteases, cytokines, and free radicals. Consequently, a wide range of wound dressings based on collagen have been developed. Native collagen is susceptible to alterations because of influences during the production process; to minimize effects on the molecule itself collagen wound dressings are usually aseptically produced. Common sterilization methods (autoclaving, irradiation, and ethylene oxide (EtO) treatment) can induce changes in the protein chemistry and physical properties, potentially affecting the absorption rate, mechanical strength, or performance. In this study, we have evaluated the influence of gamma- and beta-irradiation as well as EtO sterilization on the binding capacity of collagen type I for selected proteases and cytokines associated with nonhealing wounds. Although a pronounced effect on the physical properties of the collagen was found, there was no significant loss in the binding affinity for polymorphonuclear elastase, matrix metalloproteinase-2, and interleukin-1beta, or in the antioxidant capacity.

Journal ArticleDOI
TL;DR: In this paper, the authors developed a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds, and they predicted that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds.
Abstract: Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

Journal ArticleDOI
TL;DR: It is shown that a specific biopolymer accelerates ulcer closure and improves re-epithelialization and dermal-matrix-component remodeling and appropriate polymer-based matrix therapy is a valid and simple alternative to regenerative medicine.
Abstract: Nonhealing wounds remain a major health problem whose treatment is challenging and costly. Treatments based on cells or growth factors are still not very effective. We developed an entirely novel strategy consisting in treatment of the wound-tissue matrix with biopolymers engineered to mimic heparan sulfates called OTR4120. This compound was dextran polymer with sulfated and carboxymethyl groupments. After binding to matrix proteins, the heparan-sulfate-mimicking polymer protects the microenvironment, maintaining the normal production of signals and growth factors needed for healing to occur. Here, we show that a specific biopolymer accelerates ulcer closure and improves re-epithelialization and dermal-matrix-component remodeling. OTR4120 treatment was associated with faster maturation of epidermal structures, most notably regarding the number of epithelial-cell layers, and with an appearance that more closely resembled normal skin. Treatment had also a main effect on collagen I and III expression. Necrotic skin ulcers induced in mice with doxorubicin recovered normal collagen levels and organization, with no evidence of fibrosis. Thus, appropriate polymer-based matrix therapy is a valid and simple alternative to regenerative medicine.

Journal ArticleDOI
TL;DR: A comprehensive patient assessment can improve chronic leg and foot ulcer wound-related pain and healing rates and the mean pain scores are lower for patients with healed ulcers than for those who do not obtain complete wound closure.
Abstract: PURPOSE Pain is a major concern for subjects with chronic wounds, but its optimal management remains elusive. The aim of this study was to validate an organized pain management approach using the Wound Associated Pain model in subjects with chronic leg and foot ulcers. DESIGN We completed a prospective cohort study that documented pain in chronic wound subjects over a 4-week period. SUBJECTS AND SETTING A total of 111 subjects with chronic leg and foot ulcers were recruited from the community and ambulatory wound care clinics. RESULTS Using a systematic approach based on the Wound Associated Pain model, we demonstrated improved overall wound healing outcomes in 111 subjects with chronic leg and foot ulcers. Using an 11-point numerical rating scale, the average level of pain was reduced from 6.3 at week 0 to 2.8 at week 4 (P < .001). The average healing rate was 0.39 cm per week and the average relative reduction in size was 59.36% (t = 2.31; P = .023). To examine the relationship between pain and wound healing, pain levels were compared in subjects who achieved wound closure and those who did not. The mean pain score was 1.67 for the healed subjects in contrast to 3.21 for those who did not achieve complete wound closure (P < .041). CONCLUSIONS A comprehensive patient assessment can improve chronic leg and foot ulcer wound-related pain and healing rates. The mean pain scores are lower for patients with healed ulcers than for those who do not obtain complete wound closure.

Journal ArticleDOI
TL;DR: VAC therapy seems to be inducing morphological and quantitative alterations on the lymph vessel network in a wound, and an increase in the density of lymph vessels manifested histologically correlates with a better clinical outcome, in terms of healing rates and hospitalisation time.
Abstract: Summary Introduction Chronic wounds come in various forms and result from a multitude of factors that play a detrimental role in the wound-healing process. A breakthrough in wound management came with the introduction of vacuum-assisted closure (VAC). Although numerous papers have been published suggesting that VAC is based upon its unique ability to accelerate the rate of granulation tissue production, enhance angiogenesis and remove excess chronic wound fluid, no attempts have been made to investigate its effect on lymph vessels. Patients and methods From April 2005 to April 2006, 80 patients with chronic wounds were treated with VAC therapy and prospectively studied. The parameters included: the length of VAC treatment, the number of dressing changes, the number of days of hospitalisation and immunocytochemical lymphatic vessel density assessments. Results Lymph vessel proliferation was noted in all types of wounds, up to the first dressing change, but as VAC therapy continued it was apparent that patients exhibiting the same type of wounds did not exhibit the same results. Additionally, the duration of VAC therapy, dressing changes and average number of days of hospitalisation were significantly less in some cases but also prolonged in others. Conclusion VAC therapy seems to be inducing morphological and quantitative alterations on the lymph vessel network in a wound. The effect of VAC therapy varies greatly depending on the presence of underlying diseases and risk factors impairing wound healing. An increase in the density of lymph vessels manifested histologically correlates with a better clinical outcome, in terms of healing rates and hospitalisation time.

Journal ArticleDOI
TL;DR: In this article, a review of the literature to identify which matrix metalloproteinases (MMPs) are important in terms of ulcer prognosis and healing outcome is presented.
Abstract: Chronic leg ulcers are a complex medical condition with varied underlying causes and requiring diverse treatment strategies. It is generally accepted that chronic ulcers occur when the normal wound healing process is interrupted. These wounds are characterized by excessive protease activity, abundant granulation tissue, and decreased levels of growth factors, resulting in an overall poor prognosis for the patient. Many studies have focused on identifying the key proteases, specifically matrix metalloproteinases (MMPs), responsible for an ulcer's chronicity. Of note, the results of these studies are often conflicting. This report therefore focuses on a review of this literature to identify which MMPs are important in terms of ulcer prognosis and healing outcome. This has revealed that MMPs are clearly important in many biological processes in wound healing, hence are critical to consider when developing improved therapies to enhance both ulcer healing times and ulcer healing outcomes.

01 Jan 2009
TL;DR: A review of the literature has revealed that MMPs are clearly important in many biological processes in wound healing, hence are critical to consider when developing improved therapies to enhance both ulcer healing times and ulcers healing outcomes.
Abstract: Chronic leg ulcers are a complex medical condition with varied underlying causes and requiring diverse treatment strategies. It is generally accepted that chronic ulcers occur when the normal wound healing process is interrupted. These wounds are characterized by excessive protease activity, abundant granulation tissue, and decreased levels of growth factors, resulting in an overall poor prognosis for the patient. Many studies have focused on identifying the key proteases, specifically matrix metalloproteinases (MMPs), responsible for an ulcer's chronicity. Of note, the results of these studies are often conflicting. This report therefore focuses on a review of this literature to identify which MMPs are important in terms of ulcer prognosis and healing outcome. This has revealed that MMPs are clearly important in many biological processes in wound healing, hence are critical to consider when developing improved therapies to enhance both ulcer healing times and ulcer healing outcomes.

01 Sep 2009
TL;DR: An initial study of 15 patients with venous leg ulcers demonstrated the effectiveness of a new sensor to monitor moisture levels at the wound bed, and a major advance would be to monitor the moisture level at the wounds while leaving the dressing undisturbed.
Abstract: The cost of chronic wounds is estimated in the UK to be £2.6 billion per annum, with 200,000 patients at any one time having a chronic wound (Posnett and Franks, 2005). The nursing time involved in dressing changes takes up a considerable amount of this cost. A major advance would be to monitor the moisture level at the wound bed while leaving the dressing undisturbed, with changes taking place only when necessary. An initial study of 15 patients with venous leg ulcers demonstrated the effectiveness of a new sensor to monitor moisture levels at the wound bed.

Journal ArticleDOI
TL;DR: Both salt solutions and the wound rinsing solution were found to remove protein from the test wound coatings, whereas the test coatings became fixed and insoluble when immersed in antiseptic solution.
Abstract: Wound coatings can severely delay chronic wound healing by inducing ischaemia and degradation of viable tissue and increasing susceptibility to infection. It is, therefore, essential to cleanse wounds gently and thoroughly to remove the detrimental coatings. In this study, an in-vitro model that mimics wound coatings (human plasma dried onto adhesive glass slides) was used to compare the efficacy of four sterile solutions used to cleanse wounds: saline and Ringer's (both salt solutions), a betaine surfactant-containing wound rinsing solution (Prontosan B. Braun) and an antiseptic solution (Octenisept Schulke & Mayr). Both salt solutions and the wound rinsing solution were found to remove protein from the test wound coatings, whereas the test coatings became fixed and insoluble when immersed in antiseptic solution.

Journal Article
TL;DR: The history of HBOT, the rationale of the physiological treatment, clinical indication and contraindications, patient selection, treatment protocols and side effects are elaborates on.
Abstract: c hronic wounds are a significant challenge to the health care system and its professionals. It has been estimated that 1–2% of the population in the industrial world will suffer from leg wounds that might need professional treatment during their lifetime. In 2001, McGuckin et al. [1] estimated that 3 billion dollars a year are expended for the treatment of leg ulcers in the United States. Moreover, this figure does not include the loss of 2 million working days. In 1994 Lazarus and colleagues [2] defined chronic wound as a wound that fails to proceed through an orderly and timely process to produce anatomic and functional integrity, or proceed through the repair process and stages without establishing a sustained anatomic and functional result. Another way to define a chronic wound is by the healing time, i.e., a wound that does not demonstrate a tendency towards healing after 8 weeks of standard wound care. Other terminologies that are used in the literature for the treatment of difficult wounds include: "non-healing wound," "hard to heal wound," "problem wound" and "chronic cutaneous ulcer." The treatment approach to non-healing wounds is based on three principles: a) treating the main etiology, b) locating and removing the delaying factors, and c) providing the optimal environment for wound healing. Local wound treatment includes: cleansing and debridement, modern wound dressing, and innovative treatments for wound healing – such as negative pressure wound treatment, topical growth factors, cultured skin, and macrophages. Oxygen is an essential component of wound healing, and the rate of healing can be directly linked to the level of tissue oxygenation. According to Mogford and Mustoe [3], wound ischemia is, arguably, the most common cause of wound-healing failure. Hyperbaric oxygen therapy is a treatment for hypoxic wounds. It utilizes oxygen as a drug and the hyperbaric chamber as the mechanical tool for elevating its concentration at the target area. During the treatment, the patient breathes 100% of oxygen, while the surrounding atmospheric pressure is higher than at sea level. This review article elaborates on the history of HBOT, the rationale of the physiological treatment, clinical indication and contraindications, patient selection, treatment protocols and side effects.


Journal ArticleDOI
TL;DR: This study demonstrates for the first time that microbicidal gene therapy via microvascular free flap gene therapy is able to clear chronic infections such as occurs with osteomyelitis resulting from trauma or an infected foreign body.
Abstract: Background: The success of antimicrobial therapy has been impaired by the emergence of resistant bacterial strains. Antimicrobial peptides are ubiquitous proteins that are part of the innate immune system and are successful against such antibiotic-resistant microorganisms. The authors have previously demonstrated the feasibility of protein delivery via microvascular free flap gene therapy and here they examine this approach for recalcitrant infections. Methods: The authors investigated the production of the human cathelicidin antimicrobial peptide-LL37, delivered by ex vivo transduction of the rodent superficial inferior epigastric free flap with Ad/CMV-LL37. The vascular permeabilizing agent vascular endothelial growth factor ( VEGF) was co-administered during ex vivo transduction with adenoviral vectors in an attempt to augment transduction efficiency. A rodent model of chronic wound/foreign body infection seeded with bioluminescent Staphylococcus aureus was used to assess the biological efficacy of delivering therapeutic antimicrobial genes using this technology. Results: The authors were successful in demonstrating significant LL37 expression, which persisted for 14 days after ex vivo transduction with Ad/CMV-LL37. Transduction efficiency was significantly improved with the co-administration of 5 mu g of VEGF during transduction without significantly increasing systemic dissemination of adenovirus or systemic toxicity. They were able to demonstrate in the rodent model of chronic wound/foreign body infections a significant reduction in bacterial loads from infected catheters following transduction with Ad/CMV-LL37 and increased bacterial clearance. Conclusion: This study demonstrates for the first time that microbicidal gene therapy via microvascular free flaps is able to clear chronic infections such as occurs with osteomyelitis resulting from trauma or an infected foreign body. ( Plast. Reconstr. Surg. 123: 1157, 2009.)

Journal Article
TL;DR: Wound characteristics associated with a wound emergency are described, supporting that new or increasing wound pain, cellulitis, and/or nonpurulent drainage or presence of significant undermining may be indicative of an invasive infection and that patients presenting with these signs and symptoms require an immediate treatment plan and consideration of hospital admission.
Abstract: Chronic wounds such as diabetic foot ulcers, venous ulcers, and pressure ulcers are a major source of morbidity and mortality. To describe wound characteristics associated with a wound emergency, the Wound Electronic Medical Records (WEMR) of 200 consecutive admissions (139 patients, average number of admissions 1.4) to a dedicated inpatient wound healing unit over a period of 5 months were retrospectively reviewed. Patient mean age was 62 +/- 16 years, 59% were men, 27% had a foot ulcer and diabetes mellitus, and 29% had venous ulcers. Presenting signs and symptoms included wound pain, cellulitis, nonpurulent drainage, and undermining, but few presented with classic local clinical signs of infection. Treatment consisted of sharp debridement with deep tissue culture and pathology from the wound base and/or systemic antibiotics. Twenty-percent (20%) of patients had pathology-confirmed and 38% had pathology- or radiology-confirmed osteomyelitis on admission, supporting that new or increasing wound pain, cellulitis, and/or nonpurulent drainage or presence of significant undermining may be indicative of an invasive infection and that patients presenting with these signs and symptoms require an immediate treatment plan and consideration of hospital admission. Use of an objective documentation system such as the WEMR may help alert clinicians to subtle wound changes that require aggressive treatment; thereby, avoiding emergency room visits and hospital admissions. Future research is needed utilizing the WEMR across multiple medical centers to further define criteria for a chronic wound emergency.