Reply

Abstract

We are writing in response to a letter written by Dr George Tysowsky at Ivoclar Vivadent, Inc, to you at The Journal of Prosthetic Dentistry in reference to our recently published article, “In Vitro Cytotoxicity Of Traditional Versus Contemporary Dental Ceramics” (J Prosthet Dent 2003;90:452-8). In that letter, Dr Tysowsky expressed his “strong” disagreement with our conclusions about one lithium-disilicate material, IPS Empress 2, that we tested. In particular, Dr Tysowsky claimed that “it is inappropriate to make a definitive conclusion on biocompatibility on the basis of a single screening evaluation,” in reference to the in vitro method we used to evaluate various ceramic materials in cell culture. We make several points in response to this letter. First, contrary to Dr Tysowsky's claim, we did not conclude that Empress 2 had poor biocompatibility. Our conclusion was that “[Empress 2] exhibited cytotoxicity that would not be deemed biologically acceptable on the basis of prevailing empirical standards for dental alloys and composites.” We stand by this conclusion, which is strongly supported by the data presented in the article. The Empress 2 product was markedly cytotoxic initially, but improved with time. On an aggressive perturbation of the surface, the cytotoxicity was evident again. In a screening test such as ours, this marked cytotoxicity would be the basis for termination of development of a new product, or at least very close scrutiny. In the development of new products, given a choice between the cytotoxicity exhibited by this material and lower cytotoxicity of other nascent materials, most manufacturers would proceed with the less cytotoxic material. This is our experience, and the data support our conclusion. We acknowledge that we used an in vitro test, for which we have no apologies, because these types of tests are currently the best, first evaluation of new materials. Dr Tysowsky also emphasized that the Empress 2 product has been evaluated by independent toxicologic laboratories and clinical trails. Although we are not able to view these data, we acknowledge their existence, and we do not imply that Empress 2 was not biologically evaluated before marketing. We cannot explain any differences between these other tests and ours because, to our knowledge, these other data have not been published in a peer-reviewed journal. The methods we used (which we stand by) are published in our article for scientific scrutiny. We encourage the publication of all biologic data on materials to further intellectual discussion and improvement of in vitro biocompatibility testing methods. The results of our in vitro study are “after-the-fact” in that we applied our in vitro test to materials that are either on the market or under consideration for the market. The selection of these materials helps provide a relevance to our work. The cytotoxicity of Empress 2 in our methods may indeed be contrary to known clinical experience. This type of paradox is well known in the biocompatibility field. These “disagreements” of data do not imply that in vitro tests are wrong, nor that the clinical studies are correct. In our eyes, they provide an opportunity to ask intellectual questions that will further our understanding of the biologic response to materials. It may be, for example, that more subtle biologic effects of a material are discovered in in vitro testing that are not discernable in clinical trials. In vitro tests such as ours may point out new areas for scrutiny in future clinical trials. Finally, we do not contest the “biologic safety” of Empress 2, and we are sure that Ivoclar Vivadent has tested this material for biologic safety. However, we also believe that every material deserves continuing scrutiny for all properties, including biologic effects. It is our job to provide this scrutiny. Dr Tysowsky points out in his letter that “it is inappropriate to make a definitive conclusion on biocompatibility based on a single screening evaluation.” We would amend this idea to say that it is also inappropriate to assume that once a material has passed current regulatory tests, additional assessments of its biologic effects are not necessary. Our study showed some dramatic biologic differences between Empress 2 and other ceramic materials. Our results clearly demonstrate the need to assess the biologic properties of new materials, including ceramics, and that ceramics are not all the same biologically any more than they are all the same in transverse strength. We stand by our tests, and we hope to discover the mechanisms responsible for these differences in future studies. We thank The Journal of Prosthetic Dentistry for allowing us to respond, and we thank Dr Tysowsky for his interest and his comments. We are grateful for the dialogue.