Negative pressure wound therapy: An update

Purpose: To get the maximum benefit of vacuum-assisted closure (VAC) in the management of acute and chronic wounds without abuse or misuse. Methods: Fourty one patients were included in the study. Among them, 9 patients had chronic wounds and the rest 32 patients had acute wounds. In acute wounds, 19 patients had co-morbid conditions. Seven patients had gaped wounds, 4 patients had necrotizing fasciitis and 2 patients had enterocutaneous fistula. Results: The hospitalization period varied from 1 to 6 weeks. The follow-up period was up to 6 months. No mortality was recorded during this study. All skin grafts showed complete healing. Necrotizing fasciitis was managed with good outcome. Wounds with enterocutaneous fistula have improved. In chronic wounds, good healing and excellent outcome were obtained. Conclusion: The VAC therapy is an essential element for the management of problematic acute and chronic wounds.     

Whole genome microarray data of chronic wound debridement prior to application of dermal skin substitutes

Clinical consensus is that debridement is necessary for successful application of dermal skin substitutes (DSS) to chronic wounds. The aim here was to identify commonly expressed genes associated with wound healing in untreated acute wounds and chronic wounds treated with wound debridement followed by DSS. Cutaneous biopsies were taken at two time points from untreated acute and chronic wounds and from chronic wounds treated with DSS following debridement. Microarray analysis identified significant differences (p < 0.05) related to proliferation (HIPK2, LGR4, FGFR1, SRRT), migration (RHOC, PRPF40A, FGFR1), differentiation (TCF4, COL13A1, GNPTAB, HUWE1, FGFR1), angiogenesis (HIPK2, CASP8), extracellular matrix organization (VWA1), and apoptosis (BBC3, HIPK2, KLF11, PSME3, MSFD10, TOP2A, MLH1, CASP8, PDIA3, XAF1) when comparing untreated chronic wounds to chronic wounds treated with DSS, with similar expression levels compared to untreated acute wounds. Chronic wounds treated with debridement followed by DSS resemble untreated acute wounds at a genomic level. These novel findings, albeit with limited clinical specimen numbers, strengthen the recommendation to transform chronic into acute wounds prior to application of DSS.     

Biofilms in chronic wounds

Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference ( p <0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.     

A Pilot Study of Noninvasive Methods to Assess Healed Acute and Chronic Wounds

BACKGROUND: A variety of instruments are available that can objectively assess physical parameters of the skin such as strength, firmness, elasticity, hydration, and color, often undetected by clinical assessment. OBJECTIVE: To assess the physical properties of healed acute and chronic wounds using several noninvasive instruments. METHODS: Four patients with healed acute wounds and four patients with healed chronic wounds were studied using ballistometric, impedance, levarometric, and spectrophotometric measurements. RESULTS: In general, scars were harder, less elastic, dryer, and more erythematous than control skin. These differences were more pronounced in healed chronic wounds. CONCLUSION: A scar from an acute surgical wound becomes softer, more elastic, dryer, less erythematous, and less pigmented as it ages. In contrast, chronic wound scars become harder as they age. These different properties of healed acute wounds and healed chronic wounds may be a result of the different healing processes in each wound type.     

Negative pressure wound therapy via vacuum assisted closure following partial foot amputation: what is the role of wound chronicity?

Randomised clinical trials (RCTs) to evaluate diabetic foot wound therapies have systematically eliminated large acute wounds from evaluation, focusing only on smaller chronic wounds. The purpose of this study was to evaluate the proportion and rate of wound healing in acute and chronic wounds after partial foot amputation in individuals with diabetes treated with negative pressure wound therapy (NPWT) delivered by the vacuum-assisted closure (VAC) device or with standard wound therapy (SWT). This study constitutes a secondary analysis of patients enrolled in a 16-week RCT of NPWT: 162 open foot amputation wounds (mean wound size = 20.7 cm(2)) were included. Acute wounds were defined as the wounds less than 30 days after amputation, whereas chronic wounds as the wounds greater than 30 days. Inclusion criteria consisted of individuals older than 18 years, presence of a diabetic foot amputation wound up to the transmetatarsal level and adequate perfusion. Wound size and healing were confirmed by independent, blinded wound evaluators. Analyses were done on an intent-to-treat basis. There was a significantly higher proportion of acute wounds (SWT = 59; NPWT = 63) than chronic wounds (SWT = 26; NPWT = 14), evaluated in this clinical trial (P = 0.001). There was no significant difference in the proportion of acute and chronic wounds achieving complete wound closure in either treatment group. Despite this finding, the Kaplan-Meier curves demonstrated statistically significantly faster healing in the NPWT group in both acute (P = 0.030) and chronic wounds (P = 0.033). Among the patients treated with NPWT via the VAC, there was not a significant difference in healing as a function of chronicity. In both the acute and the chronic wound groups, results for patients treated with NPWT were superior to those for the patients treated with SWT. These results appear to indicate that wound duration should not deter the clinician from using this modality to treat complex wounds.     

Infected chronic wounds show different local and systemic arginine conversion compared with acute wounds

BACKGROUND: Several experimental studies have shown the importance of arginine in wound healing. However, little is known about its role in human wound healing. In this study, we investigated arginine metabolism in impaired wound healing. MATERIALS AND METHODS: Twenty patients with chronic wounds and 10 patients with acute wounds were included in a prospective study. Amino acids, nitrate/nitrite, and arginase concentrations were determined in plasma and wound fluid using high-performance liquid chromatography and enzyme-linked immunosorbent assay. Chronic wounds were divided into two groups: noninfected chronic wounds (n = 11) and infected chronic wounds (n = 9), based on quantitative bacterial analysis of wound fluid samples. RESULTS: Plasma arginine levels, next to total plasma amino acid levels, were significantly decreased in patients with infected chronic wounds compared with patients having acute or noninfected wounds. Citrulline and ornithine levels were significantly increased in infected chronic wounds and related to decreased nitrate/nitrite levels, whereas wound fluid arginine levels were similar in all groups. In addition, wound fluid arginase levels of infected chronic wounds were significantly enhanced. CONCLUSIONS: This study demonstrates that patients with infected chronic wounds have decreased plasma arginine levels and suggests enhanced arginine conversion in the wound. In contrast to noninfected chronic wounds, arginine seems to be mainly metabolized by arginase in infected chronic wounds. In conclusion, our hypothesis is that impaired wound healing is related to an altered arginine usage.     

Identification of biomarkers in sequential biopsies of patients with chronic wounds receiving simultaneous acute wounds: A genetic,histological, and noninvasive imaging study

Chronic wounds are common and lead to significant patient morbidity. A better understanding of their pathogenesis and relevant biomarkers are required. We compared acute and chronic wounds in the same individual using noninvasive imaging including spectrophotometric intracutaneous analysis (SIAscopy) and full‐field laser perfusion imaging. Gene expression analysis was also performed on sequential biopsies. Whole genome gene expression microarray analysis (44k), quantitative polymerase chain reaction, and immunohistochemistry were carried out to determine gene expression levels in tissue biopsies. Fifteen Caucasian patients with chronic venous ulcers had biopsies of the wound edges and simultaneously had an acute wound created on their upper arm on days 0, 7, and 14. SIAscopy revealed increased levels of melanin (p < 0.001), reduced levels of collagen (p < 0.001), and hemoglobin (p = 0.022) in chronic wounds. Microarray and subsequent quantitative polymerase chain reaction analysis confirmed an overall differential expression in acute and chronic wounds for several genes. Significantly higher levels of inhibin, beta A (INHBA) expression were confirmed in the dermis of chronic wounds (p < 0.05). Additionally, INHBA and thrombospondin 1 messenger RNA levels significantly correlated with SIAscopy measurements (p < 0.05). This unique study has showed aberrant expression of INHBA in chronic wounds using a sequential biopsy model of chronic vs. acute wounds in the same individual.     

The science of wound bed preparation

The concept of wound bed preparation (WBP) heralded a new era in terms of how we treat wounds. It emphasized the difference between acute and chronic wounds, and it cemented the idea that the processes involved in the healing of acute wounds do not apply completely to the healing of chronic wounds. The arbitrary division of the normal healing process into the phases of hemostasis, inflammation, proliferation, and maturation addresses the events in acute wound healing. We have realized that the impediments to healing in chronic wounds lead to a failure to progress through these phases and are independent factors that make the chronic wound a much more complex condition. A major advance in resolving or addressing the chronic wound has been the concept of WBP. WBP 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. In WBP we can optimize our therapeutic agents to accelerate endogenous healing or to increase the effectiveness of advanced therapies.     

生长因子应用于临床创伤修复--十年的主要进展与展望

目的回顾研究和评价10年来有关生长因子在临床创面治疗中的作用,特别是在中国的应用实践. 方法从文献和互联网检索近10年来发表的有关生长因子在临床治疗急慢性创面的报告,分析其疗效和不良反应. 结果临床应用生长因子显著加速了急慢性创面愈合速度,缩短了愈合时间,提高了愈合质量,尚未见不良反应发生. 结论应用生长因子促进创面愈合已显示出有效性和安全性.为了将来更好地临床应用,尚有一些潜在的问题需要探讨.     

Transdermal CO2 application in chronic wounds

Chronic wounds are a challenge to treatment. In this retrospective study, the effect of transdermal CO2 application on wound healing in chronic ulcers was investigated and compared to the effect of CO2 on acute surgical wounds. Eighty-six patients (52 females and 34 males) with chronic wounds of different origin except arterial occlusive disease were included. In addition, 17 patients (5 females, 12 males) with wide excision wounds after surgical therapy of acne inversa were considered. The indication for CO2 application was a wound at risk for infection. Treatment was performed with a Carboflow device once daily for 30 to 60 minutes. There was clinical evidence of improvement of granulation and reduction of discharge and malodor within 1 week of treatment in both chronic and acute wounds. Only 9 patients, all diabetics, needed an additional systemic antibiosis. The treatment was well tolerated. No adverse effects have been noted. Transdermal CO2 application is a useful method to reduce the risk of infection and improve wound healing in both chronic and certain acute wounds. Systematic prospective trials are needed.     

Wundversorgung und Verbandtechniken

The need for treatment of chronic and infected wounds has increased during recent years due to demographic changes and the increasing number of patients with severe comorbidities. An increasingly larger selection of treatment options as well as wound dressings for the treatment of acute and chronic wounds have become available in recent years. Due to the diversity of increasingly specialized bandages and wound dressings, a standardized, phase-adapted treatment of acute, chronic and infected wounds is useful and recommended. The comprehensive treatment of problematic wounds should also include treatment of any comorbidities present as well as the elimination of noxious agents that may compromise wound healing. For these reasons, treatment of complicated wounds should be interdisciplinary and in close cooperation with the nursing staff. This article presents excerpts from our phase-adapted wound treatment concepts of the “Wound Compendium Boberg”, by which we are able to maintain a standardized and high quality treatment for problematic wounds.     

Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors

To assess the differences in proteolytic activity of acute and chronic wound environments, wound fluids were collected from acute surgical wounds (22 samples) and chronic wounds (25 samples) of various etiologies, including mixed vessel disease ulcers, decubiti and diabetic foot ulcers. Matrix metalloproteinase (MMP) activity measured using the Azocoll assay was significantly elevated by 30 fold in chronic wounds (median 22.8 microg MMP Eq/ml) compared to acute wounds (median 0.76 microg MMP Eq/ml) (p < 0.001). The addition of the matrix metalloproteinase inhibitor Illomostat decreased the matrix metalloproteinase activity by approximately 90% in all samples, confirming that the majority of the activity measured was due to matrix metalloproteinases. Gelatin zymograms indicated predominantly elevated matrix metalloproteinase-9 with smaller elevations of matrix metalloproteinase-2. In addition tissue inhibitor of metalloproteinase-1 levels were analyzed in a small subset of acute and chronic wounds. When tissue inhibitor of metalloproteinase-1 levels were compared to protease levels there was an inverse correlation (p = 0.02, r = - 0.78). In vitro degradation of epidermal growth factor was measured by addition of 125I labelled epidermal growth factor to acute and chronic wound fluid samples. There was significantly higher degradation of epidermal growth factor in chronic wound fluid samples (mean 28.1%) compared to acute samples (mean 0.6%). This also correlated to the epidermal growth factor activity of these wound fluid samples (p < 0. 001, r = 0.64). Additionally, the levels of proteases were assayed in wound fluid collected from 15 venous leg ulcers during a nonhealing and healing phase using a unique model of chronic wound healing in humans. Patients with nonhealing venous leg ulcers were admitted to the hospital for bed rest and wound fluid samples were collected on admission (nonhealing phase) and after 2 weeks (healing phase) when the ulcers had begun to heal as evidenced by a reduction in size (median 12%). These data showed that the elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers (p < 0.01). This parallels the processes observed in normally healing acute wounds. This data also supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.     

Level of Fibronectin mRNA Is Markedly Increased in Human Chronic Wounds

BACKGROUND: Acute wound healing has been extensively investigated over the years, however, little is known about possible healing defects in chronic wounds. Fibronectin (FN) plays a critical role in different phases of wound healing and has been demonstrated to be degraded in chronic wounds by proteases. Fibroblasts cultured from chronic leg ulcers showed a higher level of FN compared to normal fibroblasts. OBJECTIVE: We explored whether the increase in FN protein in chronic wounds is due to increased FN mRNA. In addition, the level of alpha5beta1 integrin FN cell surface receptor was also examined. METHOD: Skin biopsies were taken from normal skin within a few hours of Mohs surgery and from the edge of chronic venous leg ulcers. In situ hybridization was performed to determine the level of FN mRNA. The level of integrin alpha5beta1 was determined by immunohistochemistry. RESULTS: The level of FN mRNA in normal skin and acute wounds was undetectable. In contrast, FN mRNA was heavily induced throughout the dermis of chronic wounds. Immunostaining using a monoclonal antibody against the alpha5 subunit of integrin revealed that chronic wounds and normal skin showed undetectable levels of alpha5beta1 integrin. A large induction of alpha5 was observed in acute wounds. CONCLUSION: For reepithelization to occur, epidermal keratinocytes need to migrate over the wound surface, a process requiring an interaction between FN and its cell surface receptor integrin alpha5beta1. These findings suggest that although FN mRNA is increased in chronic wounds, lack of FN cell surface receptor may prevent migration of epidermal keratinocytes in chronic wounds.     

Acute and chronic wounds: differences in self-reported health-related quality of life

Seventeen patients (10 female) with acute wounds (pilonidal sinus) and 32 patients (19 female) with chronic wounds (venous leg ulcers) attending a specialist wound clinic completed a condition-specific health-related quality of life (HRQoL) tool on two occasions five to seven days apart. The ratings from the two groups were statistically different for two sub-scales, with those with acute wounds rating themselves more positively. There were no differences between the groups for overall HRQoL or satisfaction with HRQoL--although there was a trend for those with chronic wounds to rate their overall HRQoL as higher than those with acute wounds, possibly indicating adaptation to their health status. While possible demographic and aetiological differences must be borne in mind, the tool used in this study appears to be sensitive to different types of wound.     

Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies

Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc-dependent endopeptidases known to be essential for the wound-healing process. MMP-8 (collagenase-2) is a neutrophil-derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP-26 is a more recent and less well-studied member of the MMP family. Our aim was to study the expression of MMP-8 and MMP-26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP-8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP-26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP-26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP-8 and MMP-26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP-26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP-8 and MMP-26 are differentially expressed in acute and chronic wounds.     

封闭负压引流技术对创面愈合过程纤溶酶原激活剂级联表达的影响

目的研究封闭负压引流技术对急慢性创面纤溶酶原激活剂(plasminogen activator,PA)级联中尿激酶型纤溶酶激活剂(urokinase-type plaminogen activator,uPA)和尿激酶型纤溶酶激活剂受体(urokinase-type plasminogen activator receptor,uPA)表达的影响。方法雄性小家猪5头,背部两侧形成急性创面,分为实验组和对照组,仅实验组动物接受封闭负压引流治疗。分别在治疗前和治疗后第1、3、6、9、12、18、25天于创缘切取标本,用兔抗人uPA和uPAR单克隆抗体按ABC程序进行免疫组织化学染色,并计算uPAA和uPAR的标记指数。人慢性创面6例,清创后进行持续封闭负压引流治疗,在治疗后第13、、5、7天采集创面渗出液,并用ELISA法检测渗出液中uPA和uPAR的含量。结果猪急性创面在封闭负压引流治疗后uPA和uPAR均增加,在第3天达到高峰,然后急速下降,但实验组的基因表达量和染色强度均显著高于对照组。6例人慢性创面进行治疗前uPA和uPAR表达较多,随着治疗时间的延长而逐渐减少。结论封闭负压引流治疗既能上调急性创面伤口周围的表皮角质形成细胞的uPA和uPAR表达,使之迅速增殖迁移;又能通过抑制慢性创面uPA和uPAR表达,从而减少细胞外基质的降解。     

Metalloproteinases in chronic and acute wounds: A systematic review and meta‐analysis

A systematic review and meta‐analysis were undertaken in order to explore the influence of matrix metalloproteinases and their diagnostic methods in chronic and acute wounds. Searches were conducted in the PubMed (Medline) and Embase (Elsevier) databases from inception to late November 2017. We included clinical trials enrolling patients with cutaneous chronic and acute wounds where a validated diagnostic method was employed for metalloproteinases. We excluded in vitro, animal or preclinical studies, nonoriginal articles, and studies without available data for analysis. In addition, references of narrative and systematic reviews were scrutinized for additional articles. Eight studies met the inclusion criteria. Results revealed that the most frequently determined matrix metalloproteinases were MMP‐2 and MMP‐9, and were found in 54.5% of wounds. MMP‐9 was present in more than 50% of the chronic wounds with a range from 37 to 78%. However, metalloproteinases were found in only 20% of acute wounds, and other types of metalloproteinases were also observed (MMP‐2 and MMP‐3). On the basis of the available evidence, high levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies.     

Recent advances on the association of apoptosis in chronic non healing diabetic wound

Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophages and myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.     

Wound bed preparation: a systematic approach to wound management

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; ? the current status of wound bed preparation; ? an analysis of the acute and chronic wound environments; ? how wound healing can take place in these environments; ? the role of wound bed preparation in the clinic; ? the clinical and cellular components of the wound bed preparation concept; ? a detailed analysis of the components of wound bed preparation. (WOUND REP REG 2003;11:1–28)     

Efficacy of a silver lipidocolloid dressing on heavily colonised wounds: a republished RCT

Nearly all open wounds are contaminated by microorganisms. This generally corresponds to simple bacterial growth, without leading to deleterious effects or compromising the progress of the healing process. In acute wounds, the probability of wound infection increases as the level of contamination does. However, it is more complex for chronic wounds, which are able to contain and tolerate large amounts of bacteria, many times higher than the usual threshold level (>105 bacteria/g of tissue) defining infection in acute wounds,1 without inducing local signs. Nevertheless, many clinical and experimental studies indicate that the probability for chronic wounds to heal properly is limited when the bacterial load exceeds this level of contamination; even when body defences are still able to prevent tissue invasion, bacteria can impair wound healing.