ów Summary Summary

Due to the increasing ages of the Western populations and to the increasing technical possibilities, biomaterials are increasingly used in the clinic. Examples of biomaterials are hip and breast prostheses, artificial heart valves, wound dressings, nerve guides or drug delivery systems. However, unwanted foreign body reactions still occur, leading to implant failure, infections and the necessity for re-operations. Biocompatibility, defined as the ability of a biomaterial to perform with an appropriate host response in a specific application [,2], could possibly be improved by interfering in the Íbreign body reaction, e.g., by inhibiting macrophage (M@) attraction and activation, or by inhibiting giant cell formation and activation. But first, the cascade of the foreign body reaction should be understood. The subjects described in this thesis concern the Íundamental understanding and the modulation of the foreign body reaction to the biodegradable biomaterial hexamethylenediisocyanate crosslinked dermal sheep collagen (HDSC) in AO rats at the f evel of the T cell and and its M@-activating cytokine interferon-y(IFN-y) (chapters 2 to 4). Furthermore, the role of IFN-y was studied in IFN-y-receptor knock-out mice (chapter 5). Finally, the foreign body reaction to HDSC in rats and mice was compared and attempts were made to understand and to enhance the reaction in mice (chapter 6 andT). Although in biomaterial-research, the involvement of T cells is often neglected, it was demonstrated in this study that T cells play an important role in the foreign body reaction to HDSC in rats (chapter 2). The lack of T cells in athymic nude rats delayed the foreign body reaction to HDSC for approximately 3 weeks. In control rats, some T cells (less than 17o) were detected in or near the HDSC disk. It could be questioned whether these T cells have a specificity against the biomaterial. Probably, the T cells involved in the foreign body reaction have a more regulatory function, for example, production of IFN-y to induce activation of MA. In chapters 3 and 4, it was studied whether IFN-y is involved in the foreign body reaction to HDSC in rats. Local application of neutralizing antibodies against IFN-yclearly delayed the foreign body reaction. Cellular ingrowth, expression of MHC class II, which is involved in antigen presentation, and degradation of HDSC were pa \4, of r