Clinical REVIEW Current advances in modern wound healing Under normal circumstances, wounds are expected to heal within a reasonable period of time through a series of a regulated cascade of events. However, when the cascade becomes interrupted, wounds fail to heal in a timely manner, resulting in chronic non-healing wounds (ulcers). Over the years, a variety of measures have been attempted in the treatment of non-healing wounds, including a range of different dressing products, drugs and devices. However, not all wounds respond to the above modalities of treatment and, consequently, non-healing, refractory wounds continue to be a significant burden in the hospital as well as the community. Wai-Ping Linda Fan, Mamun Rashid, Stuart Enoch discusses some of the aetiological chronic non-healing wounds (Lazarus KEY WORDS factors of non-healing wounds, the et al, 1994). A chronic wound may be Complex wounds essential scientific aspects, the current defined as one that has not adequately Recent advances treatment options and the potential re-epithelialised within 6–8 weeks Novel therapies future advances in the management of (Enoch and Price, 2004). Although chronic wounds. a variety of measures have been Stem cell therapy attempted in the treatment of non- Gene therapy A systematic approach healing wounds, some wounds are refractory to all forms of treatment to research, a and result in chronic wounds. multiprofessional approach ecent advances in molecular to management and a Scientific enquiry into the many biology, nanotechnology and willingness to consider the aspects of chronic wound healing is far Rfunctional genomics, coupled patient’s perspective are from complete, and, consequently, the with an increased understanding of the some of the important knowledge base is continually being pathophysiology of chronic wounds enriched by input from clinicians and have resulted in the development changes that have paralleled researchers. A systematic approach to of novel therapies such as tissue technological advances and research, a multiprofessional approach engineered substitutes and growth expertise, which, as ever, to management and a willingness to factors. In addition, promising have been the prime drivers consider the patient’s perspective are developments in the areas of stem of progress. some of the important changes that cells and gene therapy have given have paralleled technological advances rise to new hope in modulating and expertise, which, as ever, have non-healing wounds. This article Acute wound healing, triggered been the prime drivers of progress. In by tissue injury, comprises a addition to providing an overview of complex systemic cascade of the different types of common ulcers events that includes inflammation, and types of wounds healing, this neovascularisation, collagen synthesis, article discusses some of the recent granulation tissue formation, developments in the management epithelialisation and wound of chronic wounds and the potential remodelling (Clark, 1996). Normally, future advances. wounds are expected to heal within a Wai-Ping Linda Fan is a Foundation Year 2 student, reasonable period of time that ranges Common types of chronic wounds Department of Accident and Emergency, Royal Preston Hospital; Mamun Rashid is Core Surgical Trainee, from about 7–14 days. However, Common types of chronic wounds Department of ENT Surgery, Tameside General Hospital, when the above cascade becomes arise from one of the following Manchester; Stuart Enoch is Speciality Registrar, Burns and interrupted at any of the stages of the aetiologies: venous, arterial, Plastic Surgery, University Hospitals of South and healing process, the wounds will fail neuropathic or pressure. The other Central Manchester to heal in a timely manner, resulting in important causes include malignancy, 22 Wounds uk, 2010, Vol 6, No 3 Clinical REVIEW regulated cascade of events, as Table 1 happens in acute wound healing, and Important characteristics of some common types of ulcers thus become recalcitrant or chronic wounds. In most chronic wounds, the healing process seems to be halted during the inflammatory or Type of ulcer Aetiology Site Salient features proliferative phases (Lazarus et al, 1994). Disturbance in the action Venous 8 Incompetent valves 8 Medial gaiter area 8 May be painful; particularly and balance between components in perforating veins of the leg if long-standing and such as growth factors, cellular and with atrophie blanche 8 Venous extracellular elements contribute hypertension 8 Usually shallow towards a non-healing wound (Table 8 May be 8 Irregular, sloping edges 4). Additionally, accumulation of secondary to DVT 8 Characterised by pigmentation in necrotic tissue or slough promotes and/or the surrounding skin colonisation of bacteria, which varicose veins prevents complete repair of the wound. Finally, condition-specific Arterial 8 Tissue hypoxia and 8 Dorsum of foot, 8 Painful factors, such as peripheral oedema damage secondary to toes, heel and 8 Punched out appearance in sustained venous hypertension, arterial insufficiency bony prominences 8 The affected limb may be painful, ischaemia in peripheral vascular of foot 8 Atherosclerosis cool to touch and hairless disease or neuropathy in diabetes, as 8 The skin may be dusky, thin well as intake of certain drugs (e.g. and shiny non-steroidal anti-inflammatories and steroids), smoking, poor 8 Nail(s) may be brittle or lost in dietary intake and malnutrition also the affected limb contribute to impaired healing (Table Neuropathic 8 Diabetes, spinal 8 Usually on 8 Painless 5) (Edmonds and Foster, 2006; Grey et al, 2006a). cord injury, plantar surface of 8 Surrounding calluses peripheral nerve the foot under 8 Warm limb; good peripheral injury the metatarsal Conventional management of pulses heads or toes difficult-to-heal wounds 8 Surrounding skin may be dry There are some established treatment and fissured due to decreased modalities in the treatment of difficult- sweating to-heal wounds (Humpherys et al, 2007). Some of the commonly used Pressure 8 Tissue compression 8 Most develop on 8 Painful or painless management options for such wounds between a bony the lower half of 8 Surrounding skin may appear are shown in Table 6. prominence and an the torso with inflamed or blistered external force heel ulceration 8 May go very deep extending Current advances/novel therapies becoming the to bone With great strides in technological most common innovations and increased under- standing of the pathophysiology of wound healing, various devices drug-induced ulcers and vasculitis. With great strides (physical modalities) have been Some of the salient features of the in technological developed to aid the management of common types of ulcers are shown in innovations and increased chronic wounds. Table 1. understanding of the Intermittent pneumatic compression (IPC) How do normal wounds heal? pathophysiology of wound Intermittent pneumatic compression Normal wounds heal by a systemic healing, various devices (IPC) is effective for managing cascade of events that includes four (physical modalities) have chronic venous ulcers with severe overlapping, but regulated phases been developed to aid oedema that are resistant to simple (Table 2). the management of compression therapy (Enoch et al, 2006a). A compression pressure of Types of wound healing chronic wounds. 20–120mmHg is provided at preset The salient features of the four intervals to improve venous and recognised types of wound healing are Why don’t some wounds heal? lymphatic flow. It is generally used summarised in Table 3. Some wounds fail to follow the two hours a day for up to six weeks. 24 Wounds uk, 2010, Vol 6, No 3 Clinical REVIEW Hyperbaric oxygen Table 2 Hyperbaric oxygen may be a useful Phases of acute wound healing adjunct in the management of non- healing wounds. As most non-healing tissues are hypoxic, 100% oxygen given in a pressurised chamber may hasten Stages Time after injury Cell type Important features the healing process (Thackham et al, 2008). A systematic review (Wang et al, Haemostasis 8 Immediate 8 Coagulation 8 Loss of structural integrity 2003) on the use of hyperbaric oxygen cascade, platelets triggers the coagulation cascade in wounds identified six controlled trials and inflammatory and constriction of the vessels, involving diabetic ulcers and chronic mediators which further limits blood loss non-healing wounds showing positive 8 Major initial stimulation results. However, its use is restricted for inflammation as special equipment and expertise is required. Inflammatory 8 24–72 hours 8 Neutrophils and 8 Neutrophils phagocytose phase macrophages bacteria and other foreign Biosurgery particles. Macrophages The use of sterile maggots, also known transformed from monocytes as biosurgery, has a selective technique appear to act as the of slough and necrotic tissue digestion key regular cell for repair from wounds without damaging the and stimulate fibroblast division, surrounding healthy tissue (Kumar et collagen synthesis and al, 2004). Along with its antimicrobial angiogenesis effect, biosurgery is best suited for Neuropathic 8 3 days–2 weeks 8 Fibroblasts 8 Fibroblast migration, wounds with slough and infection. extracellular matrix deposition, It is cost-effective and tolerance is formation of granulation tissue excellent (Wollina et al, 2002). Apart and epithelisation from the presence of fistulas and the proximity of the wound to major 8 Fibrin/fibronectin matrix will blood vessels or vital organs,