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Showing papers on "Chronic wound published in 2010"


Journal ArticleDOI
TL;DR: 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 roles of wound tissue oximetry are provided.
Abstract: 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.

541 citations


Journal ArticleDOI
TL;DR: In many instances, it is appropriate to treat these wounds empirically with a combination of topical antiseptics and systemic antibiotics, especially in the presence of invasive infections.

369 citations


Journal ArticleDOI
TL;DR: In this paper, a reproducible chronic wound model was created in diabetic mice by the application of bacterial biofilm. But, the model was not suitable for the treatment of chronic wound conditions.
Abstract: Chronic wounds are a major clinical problem that lead to considerable morbidity and mortality. We hypothesized that an important factor in the failure of chronic wounds to heal was the presence of microbial biofilm resistant to antibiotics and protected from host defenses. A major difficulty in studying chronic wounds is the absence of suitable animal models. The goal of this study was to create a reproducible chronic wound model in diabetic mice by the application of bacterial biofilm. Six-millimeter punch biopsy wounds were created on the dorsal surface of diabetic (db/db) mice, subsequently challenged with Pseudomonas aeruginosa (PAO1) biofilms 2 days postwounding, and covered with semiocclusive dressings for 2 weeks. Most of the control wounds were epithelialized by 28 days postwounding. In contrast, none of biofilm-challenged wounds were closed. Histological analysis showed extensive inflammatory cell infiltration, tissue necrosis, and epidermal hyperplasia adjacent to challenged wounds-all indicators of an inflammatory nonhealing wound. Quantitative cultures and transmission electron microscopy demonstrated that the majority of bacteria were in the scab above the wound bed rather than in the wound tissue. The model was reproducible, allowed localized cutaneous wound infections without high mortality, and demonstrated delayed wound healing following a biofilm challenge. This model may provide an approach to study the role of microbial biofilms in chronic wounds as well as the effect of specific biofilm therapy on wound healing.

195 citations


Journal ArticleDOI
TL;DR: A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy.
Abstract: The process of cutaneous wound healing comprises three overlapping major phases: inflammation, proliferation and tissue remodelling. However, while mechanisms are studied scientifically on the cellular and subcellular level, there is still a lack of knowledge concerning basic clinical parameters like wound pH or pO2. It could be proven that wound healing is affected by wound pH changes as they can lead to an inhibition of endogenous and therapeutically applied enzymes. Besides, the conformational structure of proteins and their functionality in wound healing is altered. Furthermore, the likelihood of bacterial colonization, which is a common problem in chronic wound pathogenesis, is affected by wound pH alterations. However, wound pH is rarely taken into account in current wound therapy strategies. A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy.

188 citations


Journal ArticleDOI
TL;DR: An in vitro model of chronic wound biofilms was developed to assess the efficacy of antimicrobial treatments for use in the wound environment and emphasizes the potential role of the biofilm phenotype in the observed resistance to antibiotic therapies that may occur in chronic wounds in vivo.
Abstract: The targeted disruption of biofilms in chronic wounds is an important treatment strategy and the subject of intense research. In the present study, an in vitro model of chronic wound biofilms was developed to assess the efficacy of antimicrobial treatments for use in the wound environment. Using chronic wound isolates, assays of bacterial coaggregation established that aerobic and anaerobic wound bacteria were able to coaggregate and form biofilms. A constant depth film fermenter (CDFF) was used to develop wound biofilms in vitro, which were analysed using light microscopy and scanning electron microscopy. The susceptibility of bacteria within these biofilms was examined in response to the most frequently prescribed 'chronic wound' antibiotics and a series of iodine- and silver-containing commercial antimicrobial products and lactoferrin. Defined biofilms were rapidly established within 1-2 days. Antibiotic treatment demonstrated that mixed Pseudomonas and Staphylococcus biofilms were not affected by ciprofloxacin (5 mg/L) or flucloxacillin (15 mg/L), even at concentrations equivalent to twice the observed peak serum levels. The results contrasted with the ability of povidone-iodine (1%) to disrupt the wound biofilm; an effect that was particularly pronounced in the dressing testing where iodine-based dressings completely disrupted established 7 day biofilms. In contrast, only two of six silver-containing dressings exhibited any effect on 3 day biofilms, with no effect on 7 day biofilms. This wound model emphasizes the potential role of the biofilm phenotype in the observed resistance to antibiotic therapies that may occur in chronic wounds in vivo.

151 citations


Journal ArticleDOI
01 Feb 2010-Surgery
TL;DR: It is proposed that MMP-9 interferes with the basement membrane protein structure, which in turn impedes keratinocyte migration, attachment, and the reestablishment of the epidermis.

143 citations


Journal ArticleDOI
TL;DR: Considerable evidence has indicated that collagen-based dressings may be capable of stimulating healing by manipulating wound biochemistry, and the possibility that these agents benefit the wound healing process at a biochemical level is suggested.
Abstract: Collagen, which is produced by fibroblasts, is the most abundant protein in the human body. A natural structural protein, collagen is involved in all 3 phases of the wound-healing cascade. It stimulates cellular migration and contributes to new tissue development. Because of their chemotactic properties on wound fibroblasts, collagen dressings encourage the deposition and organization of newly formed collagen, creating an environment that fosters healing. Collagen-based biomaterials stimulate and recruit specific cells, such as macrophages and fibroblasts, along the healing cascade to enhance and influence wound healing. These biomaterials can provide moisture or absorption, depending on the delivery system. Collagen dressings are easy to apply and remove and are conformable. Collagen dressings are usually formulated with bovine, avian, or porcine collagen. Oxidized regenerated cellulose, a plant-based material, has been combined with collagen to produce a dressing capable of binding to and protecting growth factors by binding and inactivating matrix metalloproteinases in the wound environment. The increased understanding of the biochemical processes involved in chronic wound healing allows the design of wound care products aimed at correcting imbalances in the wound microenvironment. Traditional advanced wound care products tend to address the wound’s macroenvironment, including moist wound environment control, fluid management, and controlled transpiration of wound fluids. The newer class of biomaterials and wound-healing agents, such as collagen and growth factors, targets specific defects in the chronic wound environment. In vitro laboratory data point to the possibility that these agents benefit the wound healing process at a biochemical level. Considerable evidence has indicated that collagen-based dressings may be capable of stimulating healing by manipulating wound biochemistry.

137 citations


Journal ArticleDOI
TL;DR: A focused, well‐designed study is needed to elucidate the effect of surgical debridement on the healing status of chronic wounds, as five published clinical trials met the criteria and investigated surgical debridgeement of diabetic foot ulcers to enhance healing.
Abstract: An estimated 15% of patients with diabetes mellitus will develop a foot ulcer during their lifetime. Debridement is included in multiple guidelines and algorithms for the care of patients with diabetic neuropathic foot ulcers, and it has long been considered an essential step in the protocol for treating diabetic foot ulcers. In addition to altering the environment of the chronic wound, debridement is a technique aimed at removing nonviable and necrotic tissue, thought to be detrimental to healing. This is accomplished by removing abnormal wound bed and wound edge tissue, such as hyperkeratotic epidermis (callus) and necrotic dermal tissue, foreign debris, and bacteria elements known to have an inhibitory effect on wound healing. While the rationale for surgical debridement seems logical, the evidence for its role in enhancing healing is deficient. In this paper, we systematically review five published clinical trials, which met the criteria and investigated surgical debridement of diabetic foot ulcers to enhance healing. Most existing studies are not randomized clinical trials optimized to test the relationship between debridement of diabetic foot ulcers and wound healing. Therefore, a focused, well-designed study is needed to elucidate the effect of surgical debridement on the healing status of chronic wounds.

128 citations


Journal ArticleDOI
TL;DR: It is recommended that, in addition to traditional biofilm-based wound care strategies, an antimicrobial/antibiofilm treatment program can be tailored to each patient's respective wound microflora.
Abstract: Decubitus ulcers, also known as bedsores or pressure ulcers, affect millions of hospitalized patients each year. The microflora of chronic wounds such as ulcers most commonly exist in the biofilm phenotype and have been known to significantly impair normal healing trajectories. Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP), a universal bacterial identification method, was used to identify bacterial populations in 49 decubitus ulcers. Diversity estimators were utilized and wound community compositions analyzed in relation to metadata such as Age, race, gender, and comorbidities. Decubitus ulcers are shown to be polymicrobial in nature with no single bacterium exclusively colonizing the wounds. The microbial community among such ulcers is highly variable. While there are between 3 and 10 primary populations in each wound there can be hundreds of different species present many of which are in trace amounts. There is no clearly significant differences in the microbial ecology of decubitus ulcer in relation to metadata except when considering diabetes. The microbial populations and composition in the decubitus ulcers of diabetics may be significantly different from the communities in non-diabetics. Based upon the continued elucidation of chronic wound bioburdens as polymicrobial infections, it is recommended that, in addition to traditional biofilm-based wound care strategies, an antimicrobial/antibiofilm treatment program can be tailored to each patient's respective wound microflora.

120 citations


Journal ArticleDOI
01 Feb 2010-Apmis
TL;DR: An in vitro model of bacterial infections in wounds and other soft tissues and its applications in wound care and wound healing are described.
Abstract: There is growing evidence that bacteria play a crucial role in the persistence of chronic wounds. These bacteria are most probably present in polymer-embedded aggregates that represent the biofilm mode of growth. Much work has been carried out to study the development of biofilms in vitro, in particular in attachment to solid surfaces. The observations from the chronic wounds indicate that the bacteria are not attached to a solid surface. Consequently, a new in vitro model is required to investigate biofilms in more wound-like settings. This study describes such a novel in vitro model, with bacteria growing as biofilm aggregates in a collagen gel matrix with serum protein mimicking the wound bed of chronic wounds. The model was verified to comprise important hallmarks of biofilms such as the bacterial embedment in a matrix and increased antibiotic tolerance. Furthermore, we have verified the relevance of the model by comparing the organization of the bacteria in the model with the organization of the bacteria in a real chronic wound. We believe that we have developed an important new model for investigating bacterial biofilms in chronic wounds. This model may be used to study biofilm development in chronic wounds and to develop novel diagnostic tools as well as treatment strategies.

103 citations


Journal ArticleDOI
TL;DR: The article presents some of the recent patents related to anti-biofilm strategy in wound care, including novel, non-invasive means of physical debridement, chemical agent strategies, and biological agent strategies.
Abstract: With an aging and obese population, chronic wounds such as diabetic ulcers, pressure ulcers, and venous leg ulcers are of an increasingly relevant medical concern in the developed world. Identification of bacterial biofilm contamination as a major contributor to non-healing wounds demands biofilm-targeted strategies to treat chronic wounds. While the current standard of care has proven marginally effective, there are components of standard care that should remain part of the wound treatment regime including systemic and topical antibiotics, antiseptics, and physical debridement of biofilm and devitalized tissue. Emerging anti-biofilm strategies include novel, non-invasive means of physical debridement, chemical agent strategies, and biological agent strategies. While aging and obesity will continue to be major burdens to wound care, the emergence of wounds associated with war require investigation and biotechnology development to address biofilm strategies that manage multi-drug resistant bacteria contaminating the chronic wound. The article presents some of the recent patents related to anti-biofilm strategy in wound care.

Journal ArticleDOI
TL;DR: In this article, the authors used molecular techniques for rapid detection and evaluation of wound biofilms, and may prove to be useful in the clinical setting, and showed that mechanical debridement appears to be essential in the eradication of a wound biofilm.

Journal ArticleDOI
TL;DR: A review of recent advances in biologically inspired devices for wound healing can be found in this paper, where the challenges facing the regulatory governance of such products are discussed. And a commentary on the challenges faced by such products can also be found.
Abstract: Successful repair of wounds and tissues remains a major healthcare and biomedical challenge in the 21st Century. In particular, chronic wounds often lead to loss of functional ability, increased pain and decreased quality of life, and can be a burden on carers and health-system resources. Advanced healing therapies employing biological dressings, skin substitutes, growth factor-based therapies and synthetic acellular matrices, all of which aim to correct irregular and dysfunctional cellular pathways present in chronic wounds, are becoming more popular. This review focuses on recent advances in biologically inspired devices for wound healing and includes a commentary on the challenges facing the regulatory governance of such products.

Journal ArticleDOI
TL;DR: A suite of real-time PCR assays for rapid identification of bacteria directly from tissue samples targets 14 common, clinically relevant, aerobic pathogens and demonstrates a high degree of sensitivity and specificity using a panel of organisms commonly associated with chronic wound infection.

Journal ArticleDOI
TL;DR: In this paper, a color-based image analysis algorithm was used to quantify a wound boundary and measure the enclosed wound area reproducibly, and the results were validated with wounds in animal models and human wounds of diverse patients.
Abstract: Progress in wound healing is primarily quantified by the rate of change of the wound's surface area. The most recent guidelines of the Wound Healing Society suggest that a reduction in wound size of <40% within 4 weeks necessitates a reevaluation of the treatment. However, accurate measurement of wound size is challenging due to the complexity of a chronic wound, the variable lighting conditions of examination rooms, and the time constraints of a busy clinical practice. In this paper, we present our methodology to quantify a wound boundary and measure the enclosed wound area reproducibly. The method derives from a combination of color-based image analysis algorithms, and our results are validated with wounds in animal models and human wounds of diverse patients. Images were taken by an inexpensive digital camera under variable lighting conditions. Approximately 100 patient images and 50 animal images were analyzed and a high overlap was achieved between the manual tracings and the calculated wound area by our method in both groups. The simplicity of our method combined with its robustness suggests that it can be a valuable tool in clinical wound evaluations. The basic challenge of our method is in deep wounds with very small surface areas where color-based detection can lead to erroneous results and which could be overcome by texture-based detection methods. The authors are willing to provide the developed MATLAB code for the work discussed in this paper.

Journal ArticleDOI
TL;DR: In this paper, the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in wound healing in diabetic mice was investigated using a diabetic mouse model.
Abstract: Summary Background Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives Using a diabetic mouse model, to investigate the role of GM-CSF in wound healing. Methods Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results There was a significant reduction (50%) in GM-CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM-CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin-6 and monocyte chemoattractant protein-1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM-CSF showed no beneficial effects in nondiabetic wound healing. Conclusions Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.

Journal ArticleDOI
TL;DR: Differential expression of antimicrobial peptides in margins of chronic wounds is studied for the first time and indicates a role for Tournaisian immune response to these peptides.
Abstract: Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2010; 19: 628–632. Abstract: Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human β-defensins (hBD) and LL-37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD-2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL-37 was detected in the epidermis while expression of hBD-3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing.

Journal ArticleDOI
TL;DR: Results suggest further preclinical in vivo evaluation of dextrin-rhEGF is warranted to determine whether conjugate pharmacokinetics and rhEGF liberation into such a complex and aggressive environment can still lead to bioactivity.
Abstract: We recently developed a bioresponsive dextrin-recombinant human epidermal growth factor (rhEGF) conjugate as a polymer therapeutic with potential for use in the promotion of tissue repair. The aim of these studies was to use patient-derived wound fluid and fibroblasts to evaluate its potential for further development as a treatment for chronic wounds, such as venous leg ulceration, a growing clinical challenge in the aging population. First, the levels of EGF (ELISA assay), alpha-amylase and elastase (enzyme assays) were measured in patient-derived acute and chronic wound fluid. EGF was detected in acute, but not in chronic wound fluid. alpha-Amylase concentrations were higher in acute (188 IU/L), compared to chronic wound fluid (52 IU/L), but both were in the range of human serum levels. Although elastase was present in chronic wound fluid (2.1 +/- 1.2 RFU/min), none was detected in acute wound fluid. Dextrin-rhEGF incubation in chronic wound fluid led to endogenous a-amylase-mediated release of rhEGF (ELISA) that was maximal at 48 h. When the migration of HaCaT keratinocytes and of human fibroblasts (isolated from patient-matched, normal skin and chronic dermal wounds) was studied in vitro using the scratch wound assay, enhanced cell migration was observed in response to both free rhEGF and a-amylase-activated dextrin-rhEGF conjugate compared to controls. In addition, fibroblasts displayed increased proliferation (normal dermal fibroblasts similar to 160%; chronic wound fibroblasts similar to 140%) following incubation (72 h) with dextrin-rhEGF that had been exposed to physiological levels of alpha-amylase (93 IU/L). These results suggest further preclinical in vivo evaluation of dextrin-rhEGF is warranted to determine whether conjugate pharmacokinetics and rhEGF liberation into such a complex and aggressive environment can still lead to bioactivity.

Journal ArticleDOI
TL;DR: The treatment with the solution containing polihexanide and betaine was well tolerated by the patients and was found useful in the absorption of wound odours and pH value was significantly lower in the group treated with active cleanser.
Abstract: Wound cleansing represents a fundamental step in chronic wound management. Several investigations in recent years have led to a refinement of the wound cleansing protocol in order to obtain a better control of the bacterial burden during wound bed preparation and to avoid further cell and tissue damage. The aim of the present randomized controlled trial was to investigate the effects of a wound cleansing solution containing polihexanide and betaine in venous leg ulcers by means of clinical and instrumental assessment. A portable device was used on the wound bed to assess surface pH, which has been shown to be one of the most useful non-invasive biophysical parameters in order to correlate the level of bacterial burden in different types of chronic wounds. Baseline pH on the wound surface (median range) was initially 8.9, and after 4 weeks of cleansing treatment and moist wound dressing was reduced and stable at 7.0 in the group treated with active cleanser. The pH value was significantly lower (p < 0.05) in this group compared to the control group at the end of the study. The treatment with the solution containing polihexanide and betaine was well tolerated by the patients and was found useful in the absorption of wound odours.

01 Jan 2010
TL;DR: Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored.
Abstract: Summary Background Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives Using a diabetic mouse model, to investigate the role of GM-CSF in wound healing. Methods Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results There was a significant reduction (50%) in GM-CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM-CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin-6 and monocyte chemoattractant protein-1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM-CSF showed no beneficial effects in nondiabetic wound healing. Conclusions Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.

Journal ArticleDOI
TL;DR: A blood bank platelet concentrate offers a simple and effective treatment for diabetic foot ulcers and shows results superior to control treatment.
Abstract: Background: Many clinical trials have shown the effectiveness of platelet releasate on chronic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. Moreover, in the case of using homologous platelets, time and effort are needed to locate a suitable donor, and the donor's blood sample must be tested for a history of infectious disease. The current study was undertaken to evaluate the effect of a straightforward method using a blood bank platelet concentrate in treating diabetic foot ulcers. Methods: Fifty-two patients with diabetic foot ulcers were treated using a blood bank platelet concentrate. A control treatment (i.e., treatment with topical fibrinogen and thrombin) was performed on 48 patients. Twelve weeks after treatment, the percentage of complete healing, mean healing time, percentage of wound shrinkage, and patient satisfaction were compared. Results: Complete wound healing was achieved in 79 percent of the blood bank platelet concentrate-treated group and 46 percent of the control group (p < 0.05). The times required for complete healing were 7.0 ± 1.9 and 9.2 ± 2.2 weeks in the blood bank platelet concentrate-treated and control groups, respectively (p < 0.05). The degrees of wound shrinkage were 96.3 ± 7.8 and 81.6 ± 19.7 percent for the treated and control groups, respectively (p < 0.05). Patient satisfaction with the blood bank platelet concentrate treatment yielded better results than the control method (mean score, 7.6 ± 1.6 and 5.3 ± 1.4, respectively; p < 0.05). No adverse events related to the study treatment occurred. Conclusions: Treatment of diabetic foot ulcers using a blood bank platelet concentrate showed results superior to control treatment. A blood bank platelet concentrate offers a simple and effective treatment for diabetic foot ulcers.

Journal ArticleDOI
TL;DR: Interestingly and importantly, the patients reported that the new bandage made from modified flax diminished the pain accompanying chronic venous ulceration, the first pilot study report suggesting the benefits of a flax‐based dressing on wound healing.
Abstract: A new flax dressing product was developed based on three components (fibers, oil emulsion, and seedcake extract) from genetically engineered flax plants that were obtained by plant transformation using three genes controlling the synthesis of antioxidative compounds from the phenylpropanoid pathway. Simultaneous flax explant transformation with three genes coding for chalcone synthase, chalcone isomerase, and dihydroflavonol reductase resulted in an accumulation of phenolic acids in the fibers, polyunsaturated fatty acids in the oil, and lignans in the seedcake. The fibers, oil, and seedcake from transgenic flax contained a broad spectrum of antioxidative compounds. They were tested for cytotoxicity, and none were found to have a negative effect on the growth and morphology of Balb/3T3 cells. In this preliminary report, we present pilot data on the effects of using linen dressing treatment on its own or in combination with oil emulsion and/or seedcake extract on chronic wound healing. After a 12-week study, we concluded that an application of a modified flax-dressing (linen) bandage might yield a more rapid rate of healing and reduce the wound exudes and wound size. In several cases, wound healing was completed during the period of investigation. Interestingly and importantly, the patients reported that the new bandage made from modified flax diminished the pain accompanying chronic venous ulceration. Further study is required to determine any definitive effects of flax bandage on wound healing. This is the first pilot study report suggesting the benefits of a flax-based dressing on wound healing.

Journal ArticleDOI
TL;DR: The handling and the different possibilities of use of polihexanide-containing preparations, including the currently approved indications, contraindications and reservations are described.
Abstract: Polihexanide is an antimicrobial compound suitable for clinical use in critically colonized or infected acute and chronic wounds. Its beneficial characteristic is attributable particularly to its broad antimicrobial spectrum, good cell and tissue tolerability, ability to bind to the organic matrix, low risk of contact sensitization, and wound healing promoting effect. In addition, no development of microorganism resistance during polihexanide use has been detected to date, nor does this risk appear imminent. The aim of therapy using polihexanide is to reduce the pathogen burden in a critically colonized or infected acute or chronic wound. An increasing number of articles on the subject of wound antisepsis with polihexanide can be found in the medical literature. However, there is still little published information on the practical use of polihexanide-containing wound antiseptics. The purpose of this review article is to describe the handling and the different possibilities of use of polihexanide-containing preparations, including the currently approved indications, contraindications and reservations. The use of polihexanide is not the only therapeutic option in management of wounds; therefore, priority is also given to prior surgical debridement and clarification of the cause of the underlying disease, including appropriate therapy.

Journal Article
TL;DR: This review article will attempt to provide a concise report of current concepts on the use of APG in treating chronic ulcers by supporting basic science and some clinical studies.
Abstract: The treatment of chronic wounds remains problematic, despite new insight into the cellular and molecular basis of wound healing. Although the aetio-pathogenesis of chronic wounds is said to be multi-factorial, it is evident from literature that effective and adequate wound debridement has produced the most consistent effect in chronic wound treatment. There is a growing body of evidence that suggests that wound healing in chronic diabetic foot ulcers is growth factor dependent and that the therapeutic delivery of these growth factors to wounds topically, has the potential ability to accelerate wound healing in conjunction with conventional wound care. Autologous derived platelet concentrate is activated to release growth factors that are stored in the platelet granules. These secretory proteins include cytokines and growth factors such as transforming growth factor-beta, vascular endothelia growth factor, platelet derived growth factor, and so on. The enhancement of soft tissue healing by the application of autologous derived platelet rich plasma gel (APG) is supported by basic science and some clinical studies. This review article will attempt to provide a concise report of current concepts on the use of APG in treating chronic ulcers.

Journal ArticleDOI
TL;DR: The aim of the clinical investigation was to analyse the spectrum of microbial colonization of patients with a chronic leg ulcer in a specialized dermatological outpatient wound clinic, and to compare them with the results of comparable data already collected 5 years ago.
Abstract: Background In nearly every chronic wound different bacteria species can be detected. Nevertheless, the presence of such microorganisms is not necessarily obligatory associated with a delayed wound healing. But from this initially unproblematic colonization an infection up to a sepsis can arise in some patients. The aim of our clinical investigation was to analyse the spectrum of microbial colonization of patients with a chronic leg ulcer in our specialized dermatological outpatient wound clinic, and to compare them with the results of comparable data already collected 5 years ago. Objectives In our retrospective investigation the results of bacteriological swabs were documented in 100 patients with a total of 107 chronic leg ulcers. All patients visited the specialized wound outpatient clinic, Department of Dermatology, University of Essen in Germany. Methods A total of 60 patients were female, 40 were male. The mean age was 65 years. Altogether a total of 191 bacterial isolates and 25 different bacterial species could be identified. Results The most often detected species were Staphylococcus aureus (n = 60), Pseudomonas aeruginosa (n = 36) as well as Proteus mirabilis (n = 17). In 10 patients (10%) we identified a colonization with methicillin resistant S. aureus (MRSA). Merely in 6 patients the taken swabs were sterile. Five years ago a comparable investigation was already carried out in our wound outpatient clinic. At that time we could detect in particular more frequent MRSA (21.5% vs. 10%) and rarely P. aeruginosa (24.1% vs. 33.6%). Conclusion The results of our investigation demonstrate the current spectrum of the bacterial colonization in patients with chronic leg ulcers in a university dermatological wound centre in comparison to the last 5 years. In our institution we were able to demonstrate a shift of the detected bacterial species from gram-positive in direction to gram-negative germs. Beside the already known problems with MRSA, in future therapeutic strategies in patients with chronic leg ulcers the increasing amount of gram-negative bacteria and especially of P. aeruginosa should considered.

Journal ArticleDOI
TL;DR: Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity and protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations.
Abstract: Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity. Samples for determination of plasma and tissue concentrations were simultaneously collected over 12 h under steady-state conditions. Tissue concentrations were corrected for percent in vivo recovery by the retrodialysis technique. Plasma samples were also collected for determination of protein binding at 1, 6, and 12 h postdose for each patient. Protein binding data were corrected using a fitted polynomial equation. The mean patient weight was 95.1 kg (range, 63.6 to 149.2 kg), the mean patient age was 63.5 ± 9.4 years, and 75% of the patients were males. The mean values for the plasma, thigh, and wound free area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) were 2.65 ± 0.33, 2.52 ± 1.15, and 2.60 ± 1.02 μg·h/ml, respectively. Protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations. Exposure values for thigh tissue and wound tissue were similar (P = 0.986). Mean steady-state tissue concentrations for the thigh and wound were similar at 0.12 ± 0.02 μg/ml, and clearance from the tissues appeared similar to that from plasma. Tissue penetration ratios (tissue fAUC/plasma fAUC) were 99% in the thigh and 100% in the wound (P = 0.964). Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity.

Journal ArticleDOI
TL;DR: In this article, the authors developed a six species mathematical model of wound healing angiogenesis and used it to investigate the effectiveness of hyperbaric oxygen therapy (HBOT), compare the response to different HBOT protocols and study the effect of HBOT on the healing of diabetic wounds that fail to heal for a variety of reasons.

Journal ArticleDOI
TL;DR: It is suggested that platelet gel is mostly effective within the first 2 weeks of treatment while a prolonged treatment does not provide any significant advantage versus the current best practice approach to chronic wounds protocols.
Abstract: Although platelet gel is considered one of the most popular tools in the treatment of chronic ulcers, current consensus on its use is not unanimous. A prospective randomised trial was carried out at the Plastic Surgery Unit of the ‘Salvatore Maugeri’ Foundation Hospital of Pavia (Italy). The study involved 13 patients affected by spinal cord injury with 16 pressure sores over a period of 20 months. The ulcer was considered the experimental unit of the study irrespective of the number of ulcers per patient. Each consecutive ulcer was randomised to be treated either with allogenic platelet gel or with current best practice approach to chronic wounds dressing protocol. At the end of the treatment 15 ulcers out of 16 improved clinically. No statistically significant difference was demonstrated in volume reduction between the two groups, although a statistically significant difference could be demonstrated in the onset time of granulation tissue proliferation as in the wounds treated with platelet gel the healing process was triggered earlier. Our study suggests that platelet gel is mostly effective within the first 2 weeks of treatment while a prolonged treatment does not provide any significant advantage versus the current best practice approach to chronic wounds protocols.

Journal ArticleDOI
TL;DR: Copious exudate is a product of the normal wound healing process but variations in the colour, consistency, odour and amount can indicate disruption to the normal healing process.
Abstract: Exudate is a product of the normal wound healing process. It is usually clear or amber coloured but variations in the colour, consistency, odour and amount can indicate disruption to the normal healing process. Certain types of chronic wound commonly seen in the community can be associated with the production of excessive exudate. Copious exudate can be distressing for patients and expensive for community health-care providers. Effective management depends on the accurate diagnosis and treatment of the underlying condition and skill in selecting the most appropriate dressing regime.

Journal ArticleDOI
TL;DR: This review examines clinical chronic wound research and recommends a path toward proteomic investigation for the discovery of medically significant targets.
Abstract: Chronic wounds, such as venous and diabetic leg ulcers, represent a significant health and financial burden to individuals and healthcare systems. In worst-case scenarios this condition may require the amputation of an affected limb, with significant impact on patient quality of life and health. Presently, there are no clinical biochemical analyses used in the diagnosis and management of this condition; moreover few biochemical therapies are accessible to patients. This presents a significant challenge in the efficient and efficacious treatment of chronic wounds by medical practitioners. A number of protein-centric investigations have analyzed the wound environment and implicated a suite of molecular species predicted to be involved in the initiation or perpetuation of the condition. However, comprehensive proteomic investigation is yet to be engaged in the analysis of chronic wounds for the identification of molecular diagnostic/prognostic markers of healing or therapeutic targets. This review examines clinical chronic wound research and recommends a path toward proteomic investigation for the discovery of medically significant targets. Additionally, the Supporting Information documents associated with this review provide the first comprehensive summary of protein-centric, small molecule and elemental analyses in clinical chronic wound research.