2012|13 Annual Report Fraunhofer IGB

62 1 MEDICINE BIOMIMETIC, ANTIBACTERIAL BONE IMPLANTS FOR THE PREVENTION OF LOCAL INFECTIONS Dr. rer. nat. Iris Trick, Prof. Dr. Christophe Drouet* Prevention of bone infections by antibacterial implants Hospital-acquired bone infections, for example, as a result of surgery, are a serious and costly problem, making the preven- tion of such infection a matter of the highest priority. Cal- cium phosphate (CaP) apatites are highly suitable candidates for the preparation of biomaterials for bone repair. However, although CaP compounds have been the subject of the ex- tensive industrial research and development, there are still no technological concepts for equipping calcium phosphates with antibacterial properties. Since the use of antibiotics is prob- lematic, due to the development of bacterial resistance, other strategies must be found, compared and developed. French-German research alliance BioCapabili The binational BioCapabili project involves the collaboration between the Fraunhofer IGB and the CIRIMAT Carnot Institute in France, in order to equip bioactive, biomimetic CaP apatite with various antimicrobial compounds and fully investigate them. Antibiotics were not used. CaP apatites were developed in the CIRIMAT “Phosphates, Pharmacotechnics and Biomate- rials“ working group, with a focus on their synthesis, charac- terization and surface reactivity. Alternative surface modiﬁca- tions as well as biological characterization were carried out at the Fraunhofer IGB. Methods Calcium phosphates crystallized in the apatite structure have a similar construction to the mineral content of bone. In order to produce new formulations of nanocrystalline biomimetic apatites with antibacterial properties we modiﬁed the com- position of the apatite. A second approach was to functional- ize the hydrated surface layer of nanoscale CaP apatite with active agents. Various methods were employed to modify preferably the surface of the nanocrystals (e.g. using a dialy- sis membrane), or the entire crystal. The surface adsorption of organic or organic-inorganic compounds on the surface of the CaP crystals was also investigated. We were able to show antibacterial effects for various different pathogens and with various test parameters. We compared the concentration-de- pendency of the antibacterial effect with regard to cytotoxic- ity and antibacterial properties. The best formulations were subsequently tested in vivo for osteoconduction. Results Several new formulations of chemically-modiﬁed (with or without surface modiﬁcations) nanocrystalline apatites were synthesized and fully characterized. The conditions enabling us to obtain single-phased apatite systems were retained and tests for antibacterial effects and cytotoxicity were carried out. Non-doped systems served as a reference. The apatite nanocrystals obtained showed high surface reactivity, espe- cially through a hydrated surface layer. The inﬂuence of syn- thesis parameters, particularly the amount of antibacterial agent used per formulation and subsequent treatments was thoroughly investigated, especially in view of future possible areas of application. All the systems developed in the project were screened for antibacterial properties and cytotoxicity and the results were compared to determine the most promising formulations for future development to an industrial level. Fig. 5 shows several selected screening results. The ﬁgure shows the reduction fac- tor RF, which is calculated from the starting cell count used and the re-cultivable cells (RF =log (starting cell count) – log 32

2012|13 Annual Report Fraunhofer IGB

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