suMMARy wiTh oPTions foR CheMokine TheRAPies of buRn And ChRoniC skin wounds

This thesis focuses on the evaluation of growth factors, cytokines and chemokines present in the wound environment of burn, chronic and surgical wounds. The first chapters describe a differential expression of these mediators in wound exudates isolated from the 3 different wound types. Our results indicate that development of a universal therapy for these wounds is not an option. Since surgical wounds often heal by first intention we were mainly interested in burn and chronic wounds, which provide difficulties in closing. Our results in conjunction with clinical observations indicate that in chronic wounds granulation tissue formation needs to be stimulated whereas in burn wounds excess granulation tissue formation and inflammation rather should be prevented since this frequently leads to excessive scar formation. In this last chapter, we focus on chemokines which may stimulate processes like granulation tissue formation, inflammation and scar formation. Consequently, a stimulatory cocktail of these chemokines would be favoured for chronic wounds while inhibition of these chemokines, e.g. by means of an inhibitory cocktail, would be indicated for burn wounds. Finally, we emphasize the potential role of skin substitutes in facilitating closure of different wounds. This final chapter first discusses current therapies for burn and chronic wounds. Then, we use the knowledge obtained in chapters 2-9 to propose potential new therapies for burn and chronic wounds. Currently the " gold standard " treatment for full thickness burn wounds is transplantation with an autologous, meshed split-thickness graft. This is an adequate procedure to close the injury. However, it is very problematic in severely burned patients due to limited availability of donor sites with healthy skin. Moreover, severe scarring of the donor sites may occur. The burn wounds heal with an irregular mesh pattern and often hypertrophic scarring. These scars are defined as raised, but staying within the confines of the original lesions (1). Hy-pertrophic scarring causes a cosmetic problem but also impairs skin function by reduced scar elasticity and scar contractures. Contractures place patients at risk for additional medical problems including interference with skin and graft healing. Functionally, contractures of the lower extremities interfere with mobility, seating, and ambulation. Contractures of the upper extremities may affect activities of daily living, such as grooming, dressing, eating, and bathing, as well as fine motor tasks (42). Several reports describe that a lack of dermal tissue in the wound is one of the main factors responsible for scarring (1-3). This is …