EUROPEAN  TISSUE  REPAIR  SOCIETY

Dr Marco Romanelli
Department of Dermatology
University of Pisa, Italy

Marco Romanelli is a strong supporter of the ETRS and has been a member since 1989. He is a consultant dermatologist, also trained in research and his interests include vascular leg ulcers, foot ulcers in diabetic patients and tissue engineering. He has developed a wound clinic and laboratory in the University Hospital at Pisa and has published many original papers, books and book chapters in the field of cutaneous tissue repair. He has presented at wound meetings nationally and internationally.

As the current President of the European Pressure Ulcer Advisory Panel (EPUAP), Dr Romanelli organised a very successful meeting in Pisa. He is a board member of AIUC, the Italian Association for Cutaneous Ulcers, and is currently co-ordinating relations with foreign societies in tissue repair. He is keen on imparting and developing education of wound healing along with research. He supports a cohesive integrated wound 'family'. To this end he will actively help the ETRS Board to work well with other organisations. His experience and interests will aid the ETRS Board in improving education of wound care.
Marco is based at the University of Pisa - his alma mater, living with his family in the city.

Marco Romanelli with his team in Pisa

Dr Bernard Coloumb

Dr Bernard Coulomb
INSERM 532, Institut de Recherche sur la Peau
Pavillon Bazin, Hôpital Saint-Louis, Paris

I am in charge of an INSERM cell biology research group in the Skin Research Institute at Saint-Louis Hospital in Paris (Head of Department: L. Dubertret). As a basic researcher, I have been working on in vitro skin reconstruction for nearly twenty years. Using technology developed by E. Bell in 1979-81 in animals, we initially developed human skin models which contributed to our understanding of human skin physiology, pharmacology and pathophysiology. We also demonstrated that these human skin equivalents are useful modular tools for the investigation of wound healing. We observed the important role of dermal fibroblasts in epidermal behavior and the modulation of fibroblast functions by both the extracellular matrix and the epidermis. In parallel, we investigated the possibility of using living reconstructed skin to graft patients with giant nevi or burn injuries. These clinical investigations showed that fibroblasts are key elements in dermal substitutes, promoting rapid reorganization of a functional dermis.

This experience in clinical research made me more aware of the importance of close interactions between basic researchers and clinicians. It also underlined the crucial role of the medical staff, who may need to modify their working practices in order to help validate new processes. I also had to deal with the legal aspects of clinical investigations. In addition, my research work led me to participate in and co-ordinate projects (some with industrial partners) sponsored by the European Community. I realized the added potential of exchanges between different countries, and between academia and industry.

I would like to serve on the Board of ETRS, as this society strikes a balance between clinicians and researchers, is multidisciplinary, and can federate Societies in different countries through its annual international meetings. Through my experience in dermatological tissue engineering, I would particularly like to help to promote ETRS, especially by actively contributing to meeting organization. I also feel that ETRS, in association with other Societies involved in wound healing (already linked through the journal Wound Repair and Regeneration), should lobby for more investment in training course and expertise.

Professor Karin Scharfetter-Kochanek

Professor Karin Scharfetter-Kochanek
Department of Dermatology and Allergology,
University of Ulm, Germany

The interest of my group is 1) to characterize the role of reactive oxygen species in impaired wound healing as well as in actinic injury and 2) to study specific adhesion signalling receptors in tissue repair. Based on the improved mechanistic understanding we intend to develop strategies to reduce the enhanced ROS-concentration. For this purpose we have been using a combined genetic and biochemical approach to study and to confirm the deleterious role of enhanced ROS concentrations in chronic wounds and the involvement of adhesion molecules responsible for the enhanced neutrophil influx in acute and chronic wounds. We will search for strategies to inhibit adhesion molecules mainly responsible for the emigration of ROS-releasing neutrophils, and to define efficient delivery strategies for antioxidant agents.

We strongly believe that the hostile microenvironment of the chronically disturbed wound healing status in decubital ulcers and chronic venous leg ulcers is due to the enhanced release of neutrophil-derived reactive oxygen species, which in conjunction with increased iron-levels result in the generation of highly toxic hydroxyl radicals.

Using fibroblast cell lines with stably transfected expression cassettes for various antioxidant enzymes, we found that imbalanced overexpression of manganese superoxide dismutase upon challenge with neutrophil-released ROS resulted in an enhanced synthesis and release of matrix-degrading metalloproteinases. This is most likely due to an imbalanced increase in MnSOD activity as the activities of catalase and glutathion peroxidase did not change eventually leading to an enhanced release of hydrogen peroxide (H₂O₂). H₂O₂ is able to activate AP-1 with subsequent activation of the collagenase (MMP-1) promoter. Thus, imbalanced overexpression of antioxidant enzymes such as MnSOD may be detrimental for tissue repair. In fact, in normal but not in chronically disturbed wound healing antioxidant adaptive mechanisms exist with a concomitant induction of both manganese superoxide dismutase and glutathion peroxidase which protects the fibroblasts from the oxidative attack of activated neutro-phils. Currently, there is evidence that such antioxidant mechanisms are significantly compromised by the pro-oxidant hostile microenvironment of chronic wounds. A variety of laboratories including ours searches for strategies to rebalance the prooxidant microenvironment to a more favourable state which finally may promote wound healing.

Selected literature of my group on injury and tissue repair:

• Scharffetter-Kochanek K, Meewes C, Eming S, Dissemond J, Hani N, Wenk J, Wlaschek M, Brenneisen P (1999) Chronische Wunden und Wachstumsfaktoren. Z Hautkr 74: 664-672.
• Wenk J, Foitzik A, Achterberg V, Sabiwalskiy A, Dissemond J, Meewes C, Reitz A, Brenneisen P, Wlaschek M, Meyer-Ingold W, Scharffetter-Kochanek K (2001) Selective pick-up of increased iron by deferoxamine coupled cellulose abrogates the iron-driven induction of matrix-degrading metalloproteinase-1 (MMP-1) and lipid peroxidation in human dermal fibroblasts in vitro - A new dressing concept. J Invest Dermatol 116: 833-839.
• Wenk J, Brenneisen P, Wlaschek M, Poswig A, Briviba K, Oberley TD, Scharffetter-Kochanek K (1999) Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the AP-1 mediated induction of matrix-metalloprotease-1/MMP-1. J Biol Chem 274: 25869-76.
• Brenneisen P, Wenk J, Wlaschek M, Krieg T, Scharffetter-Kochanek K (2000) Activation of p70 ribosomal protein S6 kinase is an essential step in the DNA damage-dependent signaling pathway responsible for the ultraviolet B-mediated increase in interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts. J Biol Chem 275: 4336-4344.
• Brenneisen P, Wenk J, Klotz OL, Wlaschek M, Briviba K, Krieg T, Sies H, Scharffetter-Kochanek K (1998) Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts. J Biol Chem 273: 5279-5287.
• Poswig A, Wenk J, Brenneisen P, Wlaschek M, Hommel C, Quel G, Faisst K, Dissemond J, Briviba K, Krieg T, Scharffetter-Kochanek K (1999) Adaptive antioxidant response of manganese superoxide dismutase and glutathione peroxidase following repetitive UVA irradiation. J Invest Dermatol 112: 13-18.
• Scharffetter-Kochanek K, Lu H, Norman K, van Nood N, Munoz F, Grabbe S, McArthur M, Lorenzo I, Kaplan S, Ley K, Smith CW, Montgomery CA, Rich S, Beaudet AL (1998) Spontaneous skin ulceration and defective T cell function in CD18 null mice. J Exp Med 188: 119-131.
• Sixt M, Hallmann R, Wendler O, Scharffetter-Kochanek K, Sorokin LM (2001) Cell adhesion and migration properties of {Beta}2-integrin negative, polymorphonuclear granulocytes (PMN) on defined extracellular matrix molecules: Relevance for leukocyte extravasation. J Biol Chem 276: 18878-18887.
• Walzog B, Weinmann P, Jeblonski F, Scharffetter-Kochanek K, Bommert K, Gaehtgens P (1999) A role for beta(2) integrins (CD11/CD18) in the regulation of cytokine gene expression of polymorphonuclear neutrophils during the inflammatory response. FASEB J 13: 1855-1865.
• Jung U, Norman KE, Scharffetter-Kochanek K, Beaudet AL, Ley K (1998) Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo. J Clin Invest 102: 1526-1533.

Professor Dr Horst D. Becker
Chirurgische Univesitätsklinik
University of Tübingen, Germany

Professor Becker is the president of the section wound healing of the German Surgery Wound Society, trying to reunify the different scientific societies which are dealing with wound healing in Germany.
From 1987 to 1989 a major interest into the path of physiology of wound healing was established at the University of Tübingen. After this a wound healing centre was set up which is visited by more than 1000 patients per year. The research focused interest on signal transduction during the early period of wound healing and the effect of growth factors in wound healing in the chronic wound. An intense operation was set up with the University of California, San Francisco and Professor T. K. Hunt.

Professor Becker feels that the ETRS must play a major role in supporting research and wound healing, especially in the chronic wound and standardising the clinical treatment of the chronic wound. He feels that it is very important that people from basic science and from clinical backgrounds cooperate in this Institution on a European level.