Relationship between in vitro apatite-forming ability measured using simulated body fluid and in vivo bioactivity of biomaterials.

In a large number of studies, it has been assumed that the in vitro apatite-forming ability measured by simulated body fluid (SBF) test is a predictor of in vivo bioactivity. Several researchers have argued in favor and against this assumption; but the actual experimental evidence is not yet fully examined. The purpose of this study is to review the currently available evidence that supports or rejects the above-mentioned assumption. Ultimately, it is important that SBF tests could simulate the actual physiological conditions experienced by biomaterials within the human body. Given that in vivo animal experiments provide the best pre-clinical test conditions, all studies in which both in vitro apatite forming ability and in vivo performance of two or more biomaterials are compared were found by searching the literature. From all studies that satisfied the inclusion criteria (33), in 25 studies in vitro apatite-forming ability could predict the relative performance of the tested biomaterials in vivo. In 8 studies, in vitro performance did not correctly predict the relative in vivo performance. In majority of failure cases (i.e. 5/8), none of the compared biomaterials formed apatite, while all compared biomaterials showed bioactive behavior in vivo. It is therefore concluded that, in majority of cases, the SBF immersion test has been successful in predicting the relative performance of biomaterials in vivo. However, the details of the test protocols and the (expected) mechanisms of bioactivity of tested biomaterials should be carefully considered in the design of SBF immersion tests and in interpretation of their results. Certain guidelines are devised based on the results of this review for the design of SBF immersion test protocols and interpretation of the test results. These guidelines could help in designing better SBF test protocols that have better chances of predicting the bioactivity of biomaterials for potential application in clinical orthopedics.