Assessing the biocompatibility of degradable metallic materials: state-of-the-art and focus on the potential of genetic regulation.

For decades, the design, development and use of metallic biomaterials has focused on the corrosion resistance of these materials once implanted in the human body. Recently, degradable metallic biomaterials (DMMs) have been proposed for some specific applications, including paediatric, orthopaedic and cardiovascular applications. DMMs are expected to disappear via corrosion after providing structural support for a certain period of time depending on the application site. Over the past decades, a wide-ranging and comprehensive set of in vitro, in vivo and for some cases also ex vivo tests have been proposed and exhaustively investigated for conventional corrosion-resistant metallic biomaterials. Standardization and regulatory bodies in the United States, Japan and Europe have therefore developed tests to license corrosion-resistant metals for use as "biomaterials". This is not the case for DMMs. Once implanted, this new class of biomaterials is expected to support the healing process of a diseased tissue or organ while degrading at a potentially adjustable degradation rate. The tests developed for corrosion-resistant metals cannot simply be transposed to DMMs. These tests can in some cases be adapted, but the expected unique properties of DMMs should also inspire and lead to the design and the development of new specific tests. The current challenge is how to assess the tolerance of surrounding tissues and organs to the presence of degradation products. This work precisely focuses on this topic. The tests usually used to assess the biocompatibility of conventional corrosion-resistant metals are briefly reviewed. Then, genetic regulation is proposed as an original and novel approach to assess the biocompatibility of DMMs. This method appears to predict cell behaviour in the presence of degradation products that are closely related to DNA damage. Various genes have been related to the toxicity and inflammatory responses, indicating their role as biomarkers to assess the toxicity of degradation products. Finally, some gene families that have the potential to be applied as biomarkers of degradation product toxicity are summarized.