Laboratory for Biomaterials and Bioengineering, Department of Mining, Metallurgical and Materials Engineering & University Hospital Research Center, Laval University, Québec, Canada.
Acta Biomater. 2010 May;6(5):1800-7. doi: 10.1016/j.actbio.2010.02.027. Epub 2010 Feb 20.
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.
几十年来，金属生物材料的设计、开发和使用一直集中在这些材料一旦植入人体后的耐腐蚀性上。最近，可降解金属生物材料（DMMs）已被提议用于某些特定应用，包括儿科、骨科和心血管应用。DMMs 预计将在提供一定时间的结构支撑后，通过腐蚀而消失，具体时间取决于应用部位。在过去的几十年中，针对传统耐腐蚀性金属生物材料，已经提出并详尽研究了广泛而全面的体外、体内和某些情况下的离体测试。因此，美国、日本和欧洲的标准化和监管机构已经开发出用于许可耐腐蚀金属作为“生物材料”使用的测试。对于 DMMs 则并非如此。一旦植入，这种新型生物材料预计将在降解时以潜在可调降解速率支持患病组织或器官的愈合过程。为耐腐蚀金属开发的测试不能简单地应用于 DMMs。在某些情况下，这些测试可以进行调整，但 DMMs 的预期独特特性也应该激发并导致新的特定测试的设计和开发。当前的挑战是如何评估周围组织和器官对降解产物存在的耐受性。这项工作正是专注于这个主题。简要回顾了通常用于评估传统耐腐蚀性金属生物相容性的测试。然后，提出基因调控作为评估 DMMs 生物相容性的一种新颖方法。这种方法似乎可以预测在与 DNA 损伤密切相关的降解产物存在下的细胞行为。已经发现许多基因与毒性和炎症反应有关，表明它们作为评估降解产物毒性的生物标志物的作用。最后，总结了一些可能作为降解产物毒性生物标志物应用的基因家族。
