Opportunities and limits of in vitro cytotoxicity test methods exemplified by powder metallurgy titanium alloys

INTRODUCTION: Testing for in vitro cytotoxicity aims at obtaining data for a test material from simplified in vitro systems that can be used to make a prognosis for a key step within the processes occurring after implantation in the human body. Depending on the application of the test specimens, one can choose from a number of different assays to assess its bioacceptance in terms of absence of cytotoxicity. While guidelines (e.g. ISO, ASTM) describe a number of mandatory test procedures for official approval, additional tests have to be performed to properly evaluate the in vitro effects of test specimen on cells. However, in most cases it is difficult to select the appropriate assay. In addition, the conclusions that can be made out of the results are often limited . They give trends rather than enable clear-cut recommendations. In this work we evaluate for the bioacceptance of different Ti alloys by two different assays; the agar overlay test and the extraction test, both described by the ISO 10993-5 guidelines. Opportunities and limits of cytotoxicity testing based on these and other methods will be discussed.