Products & Technology Wound Inflammation and the Role of A
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Products & technology Wound inflammation and the role of a multifunctional polymeric dressing Temporary inflammation is a normal response in acute wound healing. However, in chronic wounds, the inflammatory phase is dysfunctional in nature. This results in delayed healing, and causes further problems such as increased pain, odour and Intro high levels of exudate production. It is important to choose a dressing that addresses all of these factors while meeting the patient’s needs. Multifunctional polymeric Authors: Keith F Cutting membrane dressings (e.g. PolyMem®, Ferris) can help to simplify this choice and Authors: Peter Vowden assist healthcare professionals in chronic wound care. The unique actions of xxxxx Cornelia Wiegand PolyMem® have been proven to reduce and prevent inflammation, swelling, bruising and pain to promote rapid healing, working in the deep tissues beneath the skin[1,2]. he mechanism of acute wound healing — the vascular and cellular stages. During is a well-described complex cellular vascular response, immediately on injury there is T interaction[3] that can be divided into an initial transient vasoconstriction that can be several integrated processes: haemostasis, measured in seconds. This is promptly followed inflammation, proliferation, epithelialisation by vasodilation under the influence of histamine and tissue remodeling. Inflammation is a key and nitric oxide (NO) that cause an inflow of blood. component of acute wound healing, clearing An increase in vascular permeability promotes damaged extracellular matrix, cells and debris leakage of serous fluid (protein-rich exudate) into from zones of tissue damage. This is normally a the extravascular compartment, which in turn time-limited orchestrated process. Successful increases the concentration of cells and clotting progression of the inflammatory phase allows factors. The resulting stagnation of flow and blood healing to enter the proliferative phase, where clotting assists in limiting the spread of microbes cellular ingrowth and the formation of a new that may have entered the site of injury[5]. The shift extracellular matrix progresses the wound of fluid (plasma proteins) into the extravascular towards healing. compartment increases the osmotic pressure and Inflammation describes a localised physical draws more fluid from the vascular bed. condition where the affected part of the body In cellular response, when platelets becomes reddened, swollen, hot and often painful. (thrombocytes) come into contact with exposed This reaction is a biological response to impending collagen in the vessel wall, a platelet plug is damage, in which the objective is to counter formed (haemostasis). This process heralds harmful stimuli and initiate the healing process. the inflammatory response that typifies the One of the underlying mechanisms responsible body’s reaction to injury. Platelet adhesion and for the failure of wounds to heal is an out-of- aggregation then follow, and the platelets and control inflammatory response that is self- neutrophils trapped within the clot initiate sustaining[4]. Persistent wound inflammation is a a coagulation cascade and send signalling recognised and damaging feature of the chronic molecules to attract a variety of cells to the site wound environment and is frequently associated of injury[6,7]. with wound ischaemia and infection. Together Through a process of chemotaxis, the these factors are the major cause of non- or recruitment of leucocytes signals activation delayed wound healing. of host defence systems. With the appearance Keith F Cutting is Visiting Professor, of monocytes and tissue macrophages Faculty of Society and Health, Inflammation and tissue repair approximately 48 hours post-injury, the Buckinghamshire New University, UK To understand the role of inflammation in tissue neutrophils phagocytose bacteria and cell debris Peter Vowden is Consultant Vascular repair, it is important to differentiate between using three stages: recognition and adherence, Surgeon, Bradford Royal Infirmary, UK acute and chronic inflammatory responses. engulfment and intracellular killing[5,8]. Intracellular Cornelia Wiegand is Scientific Associate, Department of killing is accomplished through production Dermatology, University Hospital Acute wound inflammation of a number of endogenous oxidising agents, Jena, Germany Two components constitute acute inflammation including hydrogen peroxide, hypochlorous Wounds International 2015 | Vol 6 Issue 2 | ©Wounds International 2015 | www.woundsinternational.com 41 Products & technology acid and NO. Other inflammatory mediators (e.g. as they are removed by scavaging macrophages histamine) give rise to the four cardinal signs of (apoptosis)[12]. Controlled inflammation as seen inflammation: erythema, swelling (tissue oedema), in the acute wound is a regulated phase of the heat and pain. healing process where cells, in response to infection The pain experienced is also a consequence of or trauma, attempt to neutralise the cause of the increased pressure in the tissues and expression event and then repair the tissue damage. These of bradykinin (vasodilation, vascular permeability, effector cells are then removed as part of the release of NO and increase in prostaglandins) and resolution process[8]. For successful wound healing, leukotrienes[5]. The production of leukotrienes, the inflammatory response must be ‘switched off’ synthesised by leucocytes, is associated with and moved into the resolution phase – a prolonged expression of histamine and prostaglandins. or excessive inflammatory phase causes tissue Prostaglandins enhance the action of histamine damage and delays healing. and sensitise neurones to noxious stimuli[9]. Two important pro-inflammatory cytokines Chronic wound inflammation (proteins that have a specific effect on interactions In chronic wounds, the inflammatory phase is and communications between cells) are tumour dysfunctional in nature. Unregulated proteolytic necrosis factor-α (TNF-α) and interleukin 1 (IL-1). activity is driven by expression of pro-inflammatory Both TNF-α and IL-1 cause endothelial cells to cytokines that, in turn, down-regulates expression express adhesion molecules and release other of TIMPS and the denaturing of growth factors[13]. cytokines and reactive oxygen species (ROS), Chronic wounds are those that do not heal otherwise known as free radicals, which are within an expected timeframe and have not antimicrobial in action but can also be harmful to responded to ‘standard’ care practices. The factors mammalian cells. that are responsible for delayed healing are listed NO and ROS have multiple roles in inflammation in Table 1. According to Moore, a chronic wound is and regulation of immune responses[10]. NO relaxes characterised by an out-of control inflammatory smooth muscle and antagonises leukocyte and response that is self-sustaining and results in the platelet adhesion to the vascular wall and regulates formation of an aberrant extracellular matrix[14]. leucocyte recruitment. ROS are oxygen-containing This describes what is happening ‘under the molecules, which are released from neutrophils surface’, where a persistent state of inflammation during normal metabolic activity or in phagocytic with high levels of pro-inflammatory cytokines, metabolic burst[11]. proteases and neutrophils are the result of a Proteases (proteins that lyse other proteins) dependent host-centred pathological process. are present in the acute wound where the matrix More recent work suggests that biofilm may metalloproteases (MMPs) and the serine proteases, be responsible for this persistent inflammatory e.g. elastase, predominate. Some level of MMP state[15]. Although skin has evolved several defence expression is found in any repair or remodelling mechanisms such as acidic pH, a high salt content, process, or where there is diseased or inflamed or the synthesis of antimicrobial peptides[16], tissue. During early inflammation, monocytes, these are impaired as soon as skin integrity is activated by platelet-derived growth factor and disrupted. The longer wound healing is delayed, transforming growth factor-b, express proteases. the more likely it becomes that contamination These proteases assist in the removal of damaged will proceed to colonisation and subsequently extracellular matrix, wound cleansing and result in wound infection. All chronic wounds are cleaving a path for angiogenic incursion. A major polymicrobial. The main bacterial species found are function is to regulate the balance between tissue the aerobes Staphylococcus aureus, Pseudomonas synthesis and tissue degradation. MMP activity is aeruginosa, and Proteus mirabilis, as well as the balanced by the expression of tissue inhibitors of anaerobes Bacteroides, Propionibacterium, and metalloproteases (TIMPs), ensuring that level and Clostridium species[16,17]. duration of MMP activity is kept in check. It is easy to acknowledge that bacteria play an Until recently, inflammation has been considered important role in driving chronic inflammation and a passive process that resolves as the pro- chronic wounds, but how do bacteria and host inflammatory mediator signals subside[8]. Catabasis interact? During wounding, microbes enter the (Greek κατα βαίνω go down, or decrease in disease) body, forming the ‘wound microbiota’ [Figure 1]. describes a guided process of returning to a non- In the case of normal wound healing, bacterial inflammatory state through mediators such as contamination is resolved rapidly, skin integrity