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)     

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.     

Wound bed preparation from a clinical perspective

Wound bed preparation has been performed for over two decades, and the concept is well accepted. The ‘TIME’ acronym, consisting of tissue debridement, infection or inflammation, moisture balance and edge effect, has assisted clinicians systematically in wound assessment and management. While the focus has usually been concentrated around the wound, the evolving concept of wound bed preparation promotes the treatment of the patient as a whole. This article discusses wound bed preparation and its clinical management components along with the principles of advanced wound care management at the present time. Management of tissue necrosis can be tailored according to the wound and local expertise. It ranges from simple to modern techniques like wet to dry dressing, enzymatic, biological and surgical debridement. Restoration of the bacterial balance is also an important element in managing chronic wounds that are critically colonized. Achieving a balance moist wound will hasten healing and correct biochemical imbalance by removing the excessive enzymes and growth factors. This can be achieved will multitude of dressing materials. The negative pressure wound therapy being one of the great breakthroughs. The progress and understanding on scientific basis of the wound bed preparation over the last two decades are discussed further in this article in the clinical perspectives.KEY WORDS: Chronic wound, negative pressure therapy, ulcer, wound, wound bed     

Wound bed preparation and a brief history of TIME

Management of chronic wounds has progressed from merely assessing the status of a wound to understanding the underlying molecular and cellular abnormalities that prevent the wound from healing. The concept of wound bed preparation has simultaneously evolved to provide a systematic approach to removing these barriers to natural healing and enhancing the effects of advanced therapies. This brief review of wound bed preparation traces the development of these concepts and explains how to apply systematic wound management using the TIME acronym - tissue (non viable or deficient), infection/inflammation, moisture (imbalance) and edge (non advancing or undermined).     

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.     

Basic of wound healing in thoracic surgery

Wound condition changes from moment to moment. It is important to understand what is happening on the wound to evaluate and treat it. Wound can be classified into low contaminated wound, contaminated wound, colonized wound, critical colonized wound and infected wound by status of bacteria on the wound. Moreover, it can be classified into acute wound, subacute wound, subchronic wound, and chronic wound by time course. Also, wound healing course can be classified into coagulation phase, inflammation phase, proliferation phase and remodeling phase. Moreover, wound healing can be classified into primary wound healing, secondary wound healing and tertiary wound healing according to types of surgical intervention. The TIME principles provide a systematic approach to the management of wounds. TIME leads to an optimal wound bed preparation( WBP). The objectives underpinning TIME are tissue non-viable or deficient (T), infection or inflammation (I), moisture imbalance (M) and epidermal margin;non advancing or undermined( E).     

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.     

Optimizing healing of the acute wound by minimizing complications

Acute wounds will always be an important source of morbidity and mortality in the United States and around the world. Traumatic injuries and surgical procedures alike will increase in volume, presenting surgeons will challenging wounds and their complications. A rich history of clinical wound management makes it clear that a firm understanding of the mechanism of acute wound healing will allow improved outcomes simply through the rational removal of impediments to acute tissue repair. Proper wound debridement, the application of moist wound dressings, and the management of comorbidities that impair acute wound healing in and of itself will positively affect wound healing. Advances in wound healing research will further improve outcomes, especially in the arenas of wound infection, wound pain, acute wound failure, and excessive scar formation. Wounds are biologically active and wound healing is a dynamic process that can be optimized and sustained by a medically, surgically, and biologically organized approach.     

TIME伤口床准备联合封闭式负压引流用于慢性伤口护理

目的探讨基于TIME原则的伤口床准备联合封闭式负压引流治疗慢性伤口的效果。方法将80例患者随机分为观察组和对照组各40例。观察组采用TIME原则进行伤口床准备,并应用封闭式负压引流,对照组在TIME原则指导下采用传统清创联合无菌敷料换药方法进行伤口护理。比较两组干预前和干预后7d、14d、21d的伤口面积缩小率、深度缩小率、局部症状体征以及观察期内伤口愈合率及所有愈合伤口的愈合时间、伤口换药时数、伤口换药费用。结果观察组伤口面积、深度缩小率和局部症状体征改善显著优于对照组(均P0.01);观察组90d内伤口愈合率显著高于对照组,伤口愈合时间、护理时数和换药费用显著低于对照组(均P0.01)。结论基于TIME原则的伤口床准备联合封闭式负压引流能够显著促进慢性伤口愈合,减少护理工作量及患者经济负担。     

Recent advances in topical wound care

There are a wide variety of dressing techniques and materials available for management of both acute wounds and chronic non-healing wounds. The primary objective in both the cases is to achieve a healed closed wound. However, in a chronic wound the dressing may be required for preparing the wound bed for further operative procedures such as skin grafting. An ideal dressing material should not only accelerate wound healing but also reduce loss of protein, electrolytes and fluid from the wound, and help to minimize pain and infection. The present dictum is to promote the concept of moist wound healing. This is in sharp contrast to the earlier practice of exposure method of wound management wherein the wound was allowed to dry. It can be quite a challenge for any physician to choose an appropriate dressing material when faced with a wound. Since wound care is undergoing a constant change and new products are being introduced into the market frequently, one needs to keep abreast of their effect on wound healing. This article emphasizes on the importance of assessment of the wound bed, the amount of drainage, depth of damage, presence of infection and location of wound. These characteristics will help any clinician decide on which product to use and where,in order to get optimal wound healing. However, there are no ‘magical dressings’. Dressings are one important aspect that promotes wound healing apart from treating the underlying cause and other supportive measures like nutrition and systemic antibiotics need to be given equal attention.KEY WORDS: Moist healing, topical wound care, wet dressings     

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.     

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.     

Wound bed preparation of difficult wounds: an evolution of the principles of TIME

In the last few years, considerable progress has been made in the treatment of chronic ulcers, thanks to new therapy methods. Wound bed preparation is a modern approach for the removal of local barriers to healing by optimising debridement, reduction of bioburden and exudate management through the TIME principles, which have been introduced by the International Advisory Board on Wound Bed Preparation. However, this protocol does not evaluate the state of the repair process and therefore does not suggest the ideal therapeutic choice for each single patient. The revised TIME-H concept considers also the supposed healing time, H, and gives a score that correlates the wound condition with the incidental concomitance with medical pathologies related to the therapeutic measures, thus guiding the clinician towards a practical and systematic approach in the treatment. By applying this scheme to our situation, the average healing time was considerably reduced. The formulation of the new protocol TIME-H for a critical assessment of treatment scheme, which also includes the general conditions of the patient, represents a more rational and adequate approach for an accurate prognosis and therefore for a more suitable therapeutic choice in the treatment of difficult wounds.     

The use of hyperbaric oxygen therapy to treat chronic wounds: A review

Chronic wounds, defined as those wounds which fail to proceed through an orderly process to produce anatomic and functional integrity, are a significant socioeconomic problem. A wound may fail to heal for a variety of reasons including the use of corticosteroids, formation of squamous cell carcinoma, persistent infection, unrelieved pressure, and underlying hypoxia within the wound bed. Hypoxia appears to inhibit the wound healing process by blocking fibroblast proliferation, collagen production, and capillary angiogenesis and to increase the risk of infection. Hyperbaric oxygen therapy (HBOT) has been shown to aid the healing of ulcerated wounds and demonstrated to reduce the risk of amputation in diabetic patients. However, the causal reasons for the response of the underlying biological processes of wound repair to HBOT, such as the up‐regulation of angiogenesis and collagen synthesis are unclear and, consequently, current protocols remain empirical. Here we review chronic wound healing and the use of hyperbaric oxygen as an adjunctive treatment for nonhealing wounds. Databases including PubMed, ScienceDirect, Blackwell Synergy, and The Cochrane Library were searched for relevant phrases including HBOT, HBO/HBOT, wound healing, and chronic/nonhealing wounds/ulcers.     

012Microvascular Endothelial Cell Migration in Scaffolds of Electrospun Collagen

Introduction:  Chronic, nonhealing wounds are often observed in tissues with poor oxygen supply. Impaired reepithelialization is a hallmark of these wounds; however, the pathogenesis of the retarded reepithelialization in chronic, ischemic wounds remains poorly understood. Transforming Growth Factor beta (TGF‐beta) is involved in both normal and hypoxic wound healing response and exogenous overexpression of Smad3, a TGF‐beta signaling intermediate, has been known to accelerate reepithelialization. In a recent study, Ad‐Smad3 injection in the rabbit ear dermal ulcer model showed enhanced reepithelialization and granulation tissue area suggesting a positive effect of Smad3 on wound healing. However, little is known about the role of Smad3 in the ischemic wound healing process. In this study we examined the effect of Smad3 in an ischemic wound model.
Methods:  Ad‐Smad3 or LacZ (10⁸ pfu/wound) empty vector was injected in either ear of White New Zealand Rabbits. Twenty‐four hours later, these ears were rendered ischemic using an established model and four 7‐mm full‐thickness punch wounds were made on each ear.
Results:  Histological evaluation showed a highly significant increase in reepithelialization, epithelial ingrowth and percentage of epithelialization in Ad‐Smad3 transfected wounds versus ischemic wounds transfected with LacZ‐empty vector (p < 0.01).
Conclusion:  Our data confirm the enhancing effect of Smad3 on reepithelialization in an ischemic wound model. The deficiency in reepithelialization, as evident in chronic ischemic wounds, could thus be ameliorated by excess Smad3. Therapeutic interventions using overexpressed Smad3 may improve wound healing through accelerated epithelialization in chronic wounds.     

创口的处理与难点

外科创口的处理对创口的愈合至关重要。清创是创口处理的重要内容,清创的概念经历了变迁,目前已发展为创面床准备的过程。常用的清创方式有外科手术清创、自溶清创、酶解清创、生物清创、机械清创等,现在主张联合清创。清创方法的选择是创口处理的难点,目的是有效清创、降低风险、促进愈合。清创过程中可根据情况选择合适的消毒剂和抗生素。     

Surfactants: Role in biofilm management and cellular behaviour

Appropriate and effective wound cleaning represents an important process that is necessary for preparing the wound for improved wound healing and for helping to dislodge biofilms. Wound cleaning is of paramount importance to wound bed preparation for helping to enhance wound healing. Surfactant applications in wound care may represent an important area in the cleaning continuum. However, understanding of the role and significance of surfactants in wound cleansing, biofilm prevention and control, and enhancing cellular viability and proliferation is currently lacking. Despite this, some recent evidence on poloxamer‐based surfactants where the surfactants are present in high concentration have been shown to have an important role to play in biofilm management; matrix metalloproteinase modulation; reducing inflammation; and enhancing cellular proliferation, behaviour, and viability. Consequently, this review aims to discuss the role, mode of action, and clinical significance of the use of medically accepted surfactants, with a focus on concentrated poloxamer‐based surfactants, to wound healing but, more specifically, the role they may play in biofilm management and effects on cellular repair.     

Wound duration and healing rates: Cause or effect?

Multiple factors affect the likelihood of a wound healing. One of these factors, wound duration, is well known to be related to healing rates, with numerous publications showing that older wounds are less likely to heal. However, disentangling the effect of this factor on wound healing rates is complex. Is this simply an observation of the obvious; wounds of longer duration will by definition be harder to heal? Or does time represent an independent factor, implying that should treatments be given earlier in the disease process, better outcomes may result? This review summarizes the available evidence of the effects of wound duration on healing rates and examines potential biological aberrations identified in chronic wounds, which may be significant in making chronic wounds difficult to heal. Wounds of longer duration are associated with excessive inflammation, fibroblast senescence, and alterations in wound bed flora, which appears to have a temporal relationship. Early and aggressive treatment of ulcers that fail to respond to standard care may well aid in reducing the burden of wounds that become chronic.     

Cellular events and biomarkers of wound healing

Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.KEY WORDS: Cytokines, growth factors, matrix metalloproteinases, platelet-derived growth factor, wound healingIn the last 30 or so years, researchers have identified several of the cellular and biochemical events associated with wound healing. The process is becoming clearer, with the understanding of the cells and chemicals that help wounds to heal, and of those that inhibit healing. Investigators are trying to analyze the chemicals in chronic wounds in order to determine their condition and fitness for closure. A major advance is the clinical application of some of these chemicals to improve outcomes in wound healing.In this paper we look at the biology of normal and abnormal healing, see if wounds analysis can predict poor healing, and review some literature on the clinical applications of this knowledge.