Hello and welcome. In this presentation I will give you an introduction to chronic wounds and the non-healing properties of these. Bacterial biofilm certainly have responsibility of lack of healing of some chronic wounds, but to witch extend is not fully understood. My name is Klaus Kirketerp-Møller, I am an orthopedic surgeon, and I will give you this brief introduction to bacterial biofilms in chronic wounds. I will introduce you to some of the controversies and challenges we face working with this subject: Bacterial biofilm in chronic wounds. The term “chronic wound” is generally accepted but no simple definition has been agreed upon. “ A wound that do not follow the normal trajectory” has been proposed, but generally a more practical definition has been: “ An ulcer or wound older than three months of age” The socio-economic burden of chronic wounds is immense. It is estimated that between one and two percent of the population has a chronic wound and that 4% of the total cost of healthcare in the western world, is used on wound care. Every chronic wound starts as an acute wound. Most acute wounds do heal uneventful through the well accepted, although not well recognized, phases: inflammation, proliferation and remodeling. A chronic wound is unlikely to occur in an otherwise healthy person. In general one or more physiologic impairments of the patient is a prerequisite but it is possible that the initial trauma is the direct cause of the healing impairment. Every wound treatment must aim at diminishing every contributing factor of non-healing: Edema, infection, dead tissue and impaired blood supply. Edema is in this context increased extracellular or interstitial fluid. Traditionally chronic wounds have been divided in four major groups: Venous leg ulcers, Diabetic Foot ulcers, pressure ulcers and a mixed and more heterogenic group: Others. This group consists of cancer related ulcers, traumatic ulcers, burns and more. The grouping of these wounds has been done due to the main contributing factor. The diabetic foot ulcer occurs on the foot of the diabetic patient and the venous leg ulcer is found in patients with venous insufficiency. Venous insufficiency is due to defects in the small valves in the veins of the lower extremity. These can be destroyed due to deep vein thrombosis, overload due to obesity and many other reasons. The grouping has been practical as the treatment options are guided by the correct diagnosis of the wounds. As the main factor of the non-healing of the venous leg ulcers is edema, managing this with compression therapy is mandatory and usually will lead to healing. In Diabetic foot ulcers poor blood supply, or ischemia and repetitive stress due to neuropathy are the main contributors. Hence restoration of blood-circulation and off-loading usually will result in healing. It is important to recognize that with increasing age and weight of the population in the world some of the conditions normally associated with diseases, as neuropathy and edema will be present in normal persons. As a part of the normal ageing the sensation in the feet decreases and is not uncommon (and therefor normal) that a person at the age of 85 without diabetes can have a foot ulcer. Obesity increases the tissue edema in the lower legs and as a result of this healing is impaired in these persons even without venous insufficiency. You might have noticed that I use the terms “ulcer” and “wounds” interchangeably. Usually the term wound is used when the cause is externally applied, as in traumatic wounds. The term “ulcer” is used when the cause is internally as a cancer ulcer. However in the real world the chronic wounds have both internally and externally contributing factors and the both terms apply. Some chronic ulcers are by definition non-healing unless the underlying cause is eradicated like cancer ulcers with chemotherapy or irradiation, yet new problems can emerge due to damage by the treatment. In diabetes or venous insufficiency the underlying cause cannot be cured, but most chronic wounds will heal when the basic principles are used. But some will not heal despite this and one of the main causes in these situations is the presence of microorganisms. Instantly, when a wound occurs, it is contaminated with microorganisms. Normally these microorganisms are cleared by the innate and adaptive immune defense system. This is dealt with during the normal healing process. If the microorganisms are very virulent or the healing is impaired, like in skin with edema, or healing is disturbed, like in diabetic foot ulcers, the immune defense system cannot eradicate the bacteria. This will result in an infection if the bacteria are very virulent and in colonization with less virulent bacteria.. The chronic wound is constantly exposed to new microorganisms from the environment and the bacterial flora will have the possibility to change over time. The wound bed characteristics can, and will, change over time due to the healing process, treatment and other factors. This will change the environment for the microorganisms and favor different bacteria. In a paper by Gødsbøll et al they found that Pseudomonas aeruginosa containing ulcers were older and larger. The bacteria are very sensible to their environment and will adapt if possible, but they prefer certainly an environment that minimizes their cost and efforts. Fazli et al found that Pseudomanas aeruginosa resided deeper in the chronic wound than Staphylococcus aureus indicating this. The treatment with antibiotics will favor bacteria that are not susceptible and this will again change the bacterial flora in the chronic wounds. Remember that the chronic wounds are constantly challenged with new microorganisms from the environment and during antibiotic treatment non-susceptible microorganisms will take the place rendered free. The use of broad-spectrum antibiotics or prolonged treatment will facilitate growth of other microorganisms like fungi. In 2008 two papers in the same issue of Wound Repair and Regeneration, James et al and Bjarnsholt et al reported of bacterial biofilm in chronic wounds and since it has been generally accepted that bacterial biofilm obstructs healing in some cases. I believe that bacterial biofilm is present in all chronic wounds, but when is it an obstacle in the healing process? I think that an indicator is when all standard treatment options for the relevant ulcer is applied, as indicated above, and the wound is not healing, there is a great risk that the biofilm mode of growth is a contributing factor. Failed antibiotic treatment also indicates that biofilm is present as an obstacle to healing. A comprehensive list of when to suspect biofilm in infections is presented by Høiby et al. There is a paradox: Why does some people develop chronic wounds while others don't? Why can we make some chronic wounds heal by just applying some compression or offloading while others not? Many factors are still not known but by strengthening the immune system and revealing the body from the burden of infection and dead material we can reverse the vicious circle of non-healing illustrated by this treadmill. To summarize, we know that biofilm is present in all chronic wounds but that many of these will heal with specific treatment, targeting the compromising factors. In the cases where biofilm is suspected to be a contributing factor the treatment options are limited, but surgical treatment seems to create a time-slot where the immune system and antibiotic treatment have increased effectiveness. Thank you very much for your attention.