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Although in the last few years in general the biocompatibility of biomaterials has significantly improved, unwanted tissue reactions are often observed resulting in early resorption of the biomaterial, loosening of the implant or in a chronic (immunologic) response. From immunologic studies it is known that inflammatory reactions can be modulated by use of (anti) growth factors or anti-inflammatory drugs. Before this can be employed the role of individual factors (humoral and cellular) involved in the inflammatory reaction against biomaterials has to be studied. In this part of the study the role of macrophages is studied with and without depletion by use of the liposomes-mediated macrophage suicide technique. Crosslinked dermal sheep collagens were used as biodegradable test materials. The results showed that macrophage depletion increases vascularization, and decreases the infiltration of granulocytes into the collagens. The foreign body reaction, i.e. the infiltration of macrophages and giant cells was significantly inhibited, resulting in a strongly delayed degradation time of the biomaterials. However, macrophage depletion did not inhibit attraction of fibroblasts and even resulted in increased formation of autologous rat-collagen, which improved the biocompatibility and the function of the biomaterials as a tempory scaffold.

One of the major clinical complications in the biomedical application of synthetic materials is the incidence of implant-associated infections. Such infections are very often induced by Staphylococcus aureus. To obtain information on tissue reactions and minimal bacterial challenge needed to create an infection related to untreated implant surfaces, we injected polyurethane tubing segments with a series of Staphylococcus aureus. The segments were subcutaneously implanted in rats. Implantation periods varied from 2, 5 and 10 days to 3 weeks. Specimen were evaluated using light and transmission electron microscopy. At least 0.25×104 of Staphylococci aureus were needed to clearly recognize that bacteria had been injected in the polyurethane tubing segments. The evidence was indirect, showing high infiltration and activation of neutrophils and macrophages, but not bacteria. Furthermore, 0.25×106S. aureus were needed to induce a persistent specific inflammatory reaction with high concentrations of lymphocytes, i.e. mainly plasma-cells, at 3 weeks. The results indicate that this model functioned well to obtain the wanted information. Results are discussed with respect to (a-) specific inflammatory reactions occurring with (bacterial-challenged) biomaterials. Ultimately, our goal is to develop infection-resistant materials, for which the in vivo model developed may be used to qualify the processed materials