Influence of oxygen on wound healing

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

Quantifying bacterial bioburden during negative pressure wound therapy: does the wound VAC enhance bacterial clearance?

The bacterial colonization of a wound is a recognized detrimental factor in the multifactorial process of wound healing. The harmful effects on wound healing are recognized to correspond to a level of > 10(5) colonies of bacteria per gram of tissue. Negative pressure wound therapy has become an accepted treatment modality for acute and chronic wounds with accelerated healing rates observed. It has been previously reported that this therapy enhances bacterial clearance, which may account for the wound healing effects noted. We retrospectively reviewed 25 patients' charts undergoing Wound VAC (Vacuum Assisted Closure Device; KCI International, San Antonio, TX) therapy with serial quantitative cultures and found that there is not a consistent effect of bacterial clearance with the Wound VAC. Furthermore, bacterial colonization increased significantly with Wound VAC therapy and remained in a range of 10(4)-10(6). Despite this finding, the beneficial effects of this treatment modality on wound healing were noted in most cases.     

Wundmanagement in der gegenwärtigen Herzchirurgie

Postoperative wound healing disorders after cardiac surgery are rare but nevertheless represent a problem in the treatment of patients with cardiac diseases. Therapeutic approaches to wound healing disorders are often time-consuming and stressful for the patient and are often associated with significantly increased costs. Deep thoracic wound healing disorders with or without infections are associated with increased mortality; therefore, optimized concepts of wound healing treatment are absolutely necessary and should be practiced by everybody who is involved in the treatment of these patients. The simultaneous treatment of other chronic wound disorders, which is often necessary in these patients, must also be mastered by cardiac surgeons This article outlines specific concepts to treat typical wound healing disorders after cardiac surgery. Moreover, the different strategies of modern wound healing concepts are discussed and the application of modern wound therapy systems is outlined.     

Epidermal growth factor therapy and wound healing--past, present and future perspectives

The role ofepidermal growth factor (EGF) has been extensively investigated in normal and pathological wound healing. It is implicated in keratinocyte migration, fibroblast function and the formation of granulation tissue. Since the discovery of EGF, the first growth factor to be isolated, over 45 years ago, growth factor therapy has progressed into clinical practice in the treatment ofwounds. The investigation EGF in wound healing has progressed from the treatment of acute wounds, to its limited effect in chronic wounds. EGF is readily degraded in the chronic wound environment, but with the recent focus of research in new drug delivery systems that are able to protect and stabilise the protein, the potential healing effects of EGF are at the forefront of research. In this review, the history of EGF and wound healing research is considered, as are current and future therapeutic options.     

Organization of wound healing services: The Danish experience and the importance of surgery

Thomas K. Hunt is a general surgeon. Through his basic wound healing research and clinical work with wound patients he has been a great inspiration for my work in wound healing. In order to fulfill Dr. Hunt's vision, the clinical wound healing arena must be organized in an optimal way, and this article focuses on different options. Multidisciplinary wound care teams or centers focusing on all types of problem wounds have proved to be most effective at providing treatment and care for patients with problem wounds. The ultimate model is an outpatient clinic and an inpatient ward joined within a departmental structure, which represents an integrated part of an accepted national expert program on wound healing. Different types of center models can be established with different advantages and disadvantages. Currently, the wound care arena is being organized in Denmark and the model is described in this article. Of all specialties involved in treatment of wounds, surgery is of vital importance. "Wound healing is the keystone on which surgery is founded" (Thomas K. Hunt). This has long been understood in relation to acute wounds, while the importance of surgery in the treatment of chronic wounds has been less widely recognized. Surgical procedures directly related to the wound consist of debridement of all types of problem wounds and, in more specialized procedures such as skin transplantation, different types of flap constructions, bone surgery, and tendo-Achilles lengthening. Arterial reconstruction is a type of surgery that indirectly, through improved tissue perfusion, improves healing of problem wounds. This study concludes that multidisciplinary specialized wound healing concepts integrated into the national health care system as accepted expert functions would be the ideal way to organize wound healing to best benefit patients and society. Emphasis is on the importance of surgical procedures in wound healing and care. The models described can be applied with minor adjustments to both industrialized and developing countries.     

Sympathetic denervation impairs epidermal healing in cutaneous wounds

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

Topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway

Impaired wound healing is one of a variety of severe diabetic complications and involves many factors, including consistent oxidative stress, prolonged inflammation, impaired angiogenesis, and delayed re-epithelialization. Despite the severe negative impacts that impaired wound healing has on patients’ lives, detailed mechanisms and effective therapies are still not fully developed. In this study, we aim to investigate the potential effects and mechanisms of topical administration of pterostilbene and resveratrol on burn wound healing in diabetes. Our in vitro experiments in human umbilical vein endothelial cells showed that long term exposure of hyperglycemia induces oxidative stress and suppression of hypoxia inducible factor1α (HIF1α) signaling pathway, and pterostilbene treatment completely, while resveratrol treatment partly, reversed this effect. Further in vivo experiments in diabetic rats showed that topical administration of pterostilbene exhibited stronger efficacy than resveratrol in normalizing oxidative stress, HIF1α activity, and accelerating burn wound healing in diabetes. We conclude that topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway; thus, pterostilbene may be a potential candidate for clinical treatment of burn wound healing in diabetes.     

The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.     

Contribution of osteopathic medicine to care of patients with chronic wounds

Since its inception, osteopathic medicine has been concerned with the lymphatic system. Research has demonstrated the effectiveness of lymphatic osteopathic manipulative treatment (OMT) techniques in affecting fluid management and immune function. Many of the functions provided by the lymphatic system and augmented by OMT are necessary for proper wound healing. The authors highlight the unique contribution of the lymphatics to wound healing, as well as the unique contribution of OMT to lymphatic-directed treatment of patients with chronic wounds. The authors propose that this information be used as a basis for research into the effects of OMT on chronic wound healing in patients.     

The effects of pH on wound healing,biofilms, and antimicrobial efficacy

It is known that pH has a role to play in wound healing. In particular, pH has been shown to affect matrix metalloproteinase activity, tissue inhibitors of matrix metalloproteinases activity, fibroblast activity, keratinocyte proliferation, microbial proliferation, and also immunological responses in a wound; the patient's defense mechanisms change the local pH of a wound to effect microorganism invasion and proliferation; this pH change has been found to affect the performance of antimicrobials, and therefore the efficacy in biological environments directly relevant to wound healing. Based on the available body of scientific evidence to date, it is clear that pH has a role to play in both the healing of and treatment of chronic and acute wounds. It is the purpose of this review to evaluate the published knowledge base that concerns the effect of pH changes, the role it plays in wound healing and biofilm formation, and how it can affect treatment efficacy and wound management strategies.     

Allogeneic keratinocyte for intractable chronic diabetic foot ulcers: A prospective observational study

Chronic diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are often difficult to treat. The application of newly developed dressing material in patients with chronic DFUs has been reported to be effective. The purpose of this study was to evaluate the usefulness of allogeneic keratinocyte treatment for chronic DFUs. We performed weekly allogeneic keratinocyte treatment for up to 12 weeks in 71 patients with intractable DFUs. We investigated healing rate, wound‐healing velocity, and time to 50% wound size reduction and analysed factors affecting ulcer healing. Fifty‐six patients (78.8%) had complete wound healing. Forty‐six patients (64.7%) showed complete healing within an average of 6.1 weeks, and 10 patients (14.1%) showed partial healing with an average 35.5% reduction vs initial size at the end of follow up. The 10 patients who showed partial healing continued to receive treatment after the 12‐week study period. The mean time to complete wound healing was 7.8 weeks. Fifteen patients (21.1%) experienced treatment failure because of infection, local necrosis, no change in ulcer size, or osteomyelitis during the follow‐up period. No adverse events were observed. Allogeneic keratinocyte treatment is effective for chronic, difficult‐to‐treat DFUs.     

Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing

Superficial skin erosion wounds are very common in the clinic, and conventional treatments are not always effective; thus, effective and novel therapy is needed. Cold atmospheric plasma (CAP) has been recognised as a promising approach to wound healing. The purpose of this study is to show the potential clinical application of CAP for the healing of different kinds of superficial skin wounds. Seven patients with different kinds of superficial skin wounds (two patients with pyoderma gangrenosum, two patients with trauma would, one patient with giant genital wart, one patient with diabetic foot, and one patient with chronic eczema) were recruited to this study. All patients accepted and received CAP treatment every other day till the wound healed. The expected results were complete wound healing after CAP treatment. All patients achieved complete wound healing after several rounds (range from two to eight) of CAP treatment, and there was no side effect observed. CAP may provide a new and effective choice to solve the problem of the healing of superficial wounds that are not only caused by trauma but also because of eczema. CAP has certain value in the treatment of superficial skin diseases in the future.     

Liquid ozone therapies for the treatment of epithelial wounds: A systematic review and meta-analysis

Ozonated water and ozonated oils are emerging as potential therapies for wound care, but their efficacy has not been appropriately evaluated. The aim of this systematic review and meta-analysis was to evaluate the therapeutic potential of topical ozone in the treatment of mammalian wounds. A structured search of five scientific databases returned a total of 390 unique studies. Of these, 22 studies were included in this review. Four studies provided enough data to be included in a meta-analysis evaluating the time to complete wound healing. All studies were randomised controlled trials of humans or other mammalian animals that reported clinical signs of wound healing. Each study was critically analysed by a six-point assessment of the risk of bias. Wounds treated with topical ozone had a greater reduction in wound size than similar wounds treated with controls or standard of care in all studies. Those treated with ozonated liquids also had a shorter time to wound healing by approximately one week. In conclusion, topical ozone contributed to enhanced wound healing in all studies. While additional human experiments would be helpful to quantify ozone's specific effects on wound healing compared to standard treatment, topical ozone should be considered as part of an overall wound management strategy.     

分期中药熏洗对混合痔术后创面愈合的干预研究

目的：探讨分期辨证应用中药熏洗对混合痔术后创面的影响及安全性评价。方法：80 例混合痔术后患者随机分为治疗组和对照组各 40 例。对照组应用康复新液熏洗,治疗组按疮疡祛腐期、生肌长肉期和收口敛皮期三个阶段辨证应用中药四黄祛毒汤加味熏洗。观察两组患者术后平均出院时间和平均创面完全愈合时间,以及术后创面恢复过程中第 5 天、第 10 天和第 15 天时,患者疼痛评分,创面渗出情况,创面愈合情况评分,并观察不良反应。结果：治疗组出院时间和创面完全愈合时间均短于对照组（P<0.05）。治疗组术后第 10 天较对照组疼痛评分明显降低（P<0.05）。治疗组术后第 10 天和第 15 天时创面愈合情况评分优于对照组（P<0.05）。术后第 10 天和第 15 天时,中度的创面渗出患者较轻度渗出患者的单位面积创面完全愈合时间短（P<0.05）。结论：分期辨证使用中药熏洗可有效促进混合痔术后创面愈合,且安全性好。维持中度创面渗出水平,保持创面湿润,可能更有利于创面愈合。     

Prediction and monitoring the therapeutic response of chronic dermal wounds

A significant proportion of chronic wounds fail to heal in response to treatment of underlying pathologies combined with good wound care practice. Current prognostic tests to identify these wounds rely on the use of algorithms based on clinically measurable parameters such as wound dimensions and wound duration. Venous leg ulcers may be stratified into healing/non healing at 24 weeks of compression therapy and diabetic foot ulcer treatment outcome assessed using a 3-parameter algorithm. Accurate and reproducible measurement of wound area is required for these algorithms to have clinical utility. Whilst a number of attempts have been made to develop computerised wound-assessment techniques, wound tracing by clinicians combined with planimetry remains the standard methodology. Once treatment has been initiated, it is important to continuously monitor the wound to assess efficacy of treatment. This can be achieved by measuring wound area change over the first weeks of treatment to identify whether re-assessment of treatment strategy is required. A number of algorithms for assessing rate of wound area change have been evaluated to determine a surrogate endpoint for healing. Retrospective analysis of large patient groups indicates that approximately 75% correct prediction of healing outcome can be achieved.     

肛肠病术后应用康复新液促进创面愈合的临床观察

为观察肛肠病术后应用康复新液促进创面愈合的临床疗效,将120例肛肠病术后患者随机分为治疗组和对照组,对照组采用常规换药,治疗组在常规处理基础上加用康复新液,比较两组创面愈合时间、创缘水肿差异。结果显示,治疗组创面愈合时间明显短于对照组．创面水肿临床发生率明显低于对照组。结果表明,康复新液对肛肠病术后创面有良好的促进愈合和降低水肿作用。     

A new concept of a multidisciplinary wound healing center and a national expert function of wound healing.

HYPOTHESIS: An independent, multidisciplinary wound healing center in an accepted national expert function of wound healing is the optimal way to improve prophylaxis and treatment of patients with problem wounds. DESIGN: A clinical perspective analysis. SETTING: An independent, multidisciplinary wound healing center focusing on all types of problem wounds, organized as a university hospital department, and integrated in an expert function in the national health care organization of Denmark. PATIENTS AND METHODS: Patients with all types of problem wounds referred to and treated in the center during the first years of its existence provided a model for a new multidisciplinary structure for treatment of wound patients in the health care system. RESULTS: During the first 3 years of the fully functioning wound healing center, a total of 23 802 patient consultations were performed in the outpatient clinic, and 1014 patients with problem wounds were hospitalized in the inpatient ward. The surgical concept of the center has resulted in improved healing rates in patients with leg ulcers and decreased rates of major amputations. The outpatient function has resulted in a decrease in the number of patients transported in beds to the center. This structure provides better opportunities for basic and clinical research as well as for establishing expert education for all types of health care personnel. The center's structure has been the background for establishing an expert function in wound healing, allowing the wound healing area area to be fully integrated in the Danish National Health Care System. Overall, the concept and structure of the center have enhanced the knowledge and understanding of wound problems and increased the status of wound healing and patient care. CONCLUSIONS: Establishing multidisciplinary centers integrated into an accepted national expert function of wound healing is an optimal way to improve the clinical outcome of prophylaxis and treatment of all types of problem wounds. This model, with minor adjustments, may be applicable for both industrialized and developing countries.     

An update on wound management

This article provides an update on wound management with wound diagnosis and treatment discussed in terms of the normal cellular events of the wound healing process. The role of growth factors as cell regulators, the importance of wound fluids to wound metabolism, and the deleterious effects of some wound cleansers, disinfectants, and modalities are reviewed. Treatment guidelines are suggested based on negative or positive cellular response to individual management techniques. Wound evaluation, diagnosis, and treatment are considered in terms of a new color concept that simplifies clinical decision making. An explanation of the relatively new microenvironmental dressings designed to maintain wound humidity and speed wound healing is provided. A more physiologic approach to managing the simple and complex wound may prove to speed the process of epithelialization, contraction, and collagen deposition while diminishing the problems associated with delayed or inadequate healing. The wound healing process is subject to manipulation and facilitation by the clinician, a concept that is certain to receive much attention in the next decade. The importance of a scientific approach to this aspect of our discipline cannot be overemphasized.     

Pathophysiology of wound healing and current treatment strategies in a urological context

Acute wound healing is a dynamic, interactive process culminating in the closure of a tissue defect. Chronic wounds result when the healing cascade is impaired. Proteases destroy important growth factors and matrix proteins, inflammation is prolonged, and the normal healing process does not take place within the expected time span. Owing to demographic changes the investigation of age-related pathologies, including treatment-resistant wounds, has become increasingly important. The TIME concept (tissue, infection, moisture imbalance, edge of wound) assesses essential elements in the healing process that can be addressed in the treatment of chronic wounds. Moist wound treatment is standard therapy. Definitive research trials on the level of success that can be achieved with different dressings are still needed. New types of treatment should be selected with due consideration for clinical variables, the patient's quality of life and independence, and cost effectiveness.     

Wound edge biopsy sites in chronic wounds heal rapidly and do not result in delayed overall healing of the wounds

Wound biopsies are an essential diagnostic component in the management of chronic wounds. First, the possibility of malignancy or infection in the wound often requires sampling of the wound edge and its bed. Secondly, several practice guidelines recommend biopsying wounds that have not responded to treatment after 2–6 weeks. However, there has always been a concern that the biopsy may worsen the wound and delay overall healing. In this report, we investigated the safety and effects of wound biopsies on overall chronic wound healing rates (advance of the wound edge per week toward the center) before and after the biopsy was performed. In a cohort of 14 consecutive patients with chronic wounds of the lower extremity, we found that postbiopsy chronic wound healing rates (0.99±1.18 mm/week; mean±SD) were not decreased and were actually higher than prebiopsy chronic wound healing rates (0.49±0.85 mm/week; mean±SD, p <0.05). In addition, we documented that healing of the biopsy sites up to the original wound edge occurred within 6 weeks in 11 of the 14 subjects. Therefore, we conclude that chronic wounds do not worsen after being biopsied and that wound biopsies are a safe procedure that does not delay overall healing of the chronic wound.