Research SummaryIntroduction The research in the laboratory for Tissue Repair and Gene Therapy broadly aims at creating better treatment for both acute and chronic wounds. By combining the most advanced methods for wound treatment with genetic manipulation of the cells in the wound. Our work allows us to gain new insight into how wounds heal. We are also using gene therapy as a powerful tool to stimulate healing or inhibit scar formation. The overall objective of our research program is to gain a better understanding of the molecular and cellular effects and interactions on wound repair in normal and impaired wounds. Our laboratory has had several firsts in the field of wound healing research and gene therapy: We were first to demonstrate the feasibility and utility of treating a wound in a liquid tissue culture like environment in vivo (Breuing et al. 1992, J Surg Res). Our laboratory demonstrated for the first time that single cell suspensions of keratinocytes can be directly transplanted to a wound and we used marker genes to demonstrate that the transplanted cells actually survived (Vogt et al. 1994, PNAS). Our laboratory performed the first successful direct in vivo gene transfer to wounds (Andree et al. 1994, PNAS). We have also been able to develop new methods for controlled gene delivery: Microseeding is a mechanical method that can be combined with any other vector system (Eriksson et al. 1998 J Surg Res.). We have also developed a gene switch that allows us to turn genes on and off and to regulate their level of expression (Yao et al. 1998 Hum Gene Ther), which allows a better and more controlled therapy. This gene switch has been used by several thousand laboratories. Currently, we are in the process of investigating how to normalize wound healing in diabetes by using gene delivery of proteins that stimulate wound healing. The overall goal of the laboratory is to do translational research, which will benefit our patients with wounds. We also want to educate plastic surgeons, research fellows and students in the art of scientific investigation. Tissue Repair Our research methodology spans a wide spectrum from molecular biology, cell biology, tissue engineering experimentation, small and large in vivo experiments. Therefore we use a sealed chamber to control and study the wound environment. This chamber functionally becomes an in vivo incubator. With use of this model, the wound micro-environment can readily be monitored and modified in a specific fashion like a tissue culture in vivo. Thus, the wound healing process can be modulated repetitively by targeted delivery of therapeutic genes into the wound microenvironment using and assessing various in vivo and ex vivo gene delivery techniques as well as daily wound fluid collection, monitoring of wound contraction, histology and immunohistochemistry. Current experiments deal with both wounds that heal normally and that have impaired healing. We are particularly interested in diabetic wound healing. Gene Therapy Gene Therapy is a promising approach to overcome some of the obstacles mentioned above. It is defined by the insertion and expression of a foreign gene in cells or tissue of a host organism. The goal of this procedure is to express transgenes such as growth factors or host defense peptides. Gene Therapy is a highly targeted powerful way of delivering therapeutic peptides to the interior of the wound. Several different vector systems are being used and are tailored to the specific need of the experimental situation. We are using the gene switch which allows us to control both the beginning and the end of gene expression as well as the amount of protein expressed. Our research focuses on the potential impact of Gene Therapy to Wounds. Currently, we analyze the impact and interaction of various Growth Factors and Host Defense Peptides in chronic, acute and infected wounds. Skin Transplantation By enclosing the wound in a sealed transparent chamber, transplantation of individual cells, groups of cells or skin particles to the wound can be carried out. Our laboratory was first to transplant both single cell suspensions and minced skin to this tissue culture like wound environment. Transplantation of cells and skin particles is one of the methodologies that are being used in the laboratory (Vogt et al. 1994, PNAS, Svensjo et al. 2002, J Surg Res) in order to accelerate healing and minimize donor sites. Back to the top | 
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