Chemical profiling of biological cell / engineering alloy interactions

近年来，在陶瓷、聚合物或复合基生物材料方面取得了许多令人兴奋的进展。然而，绝大多数生物医学植入物仍然是金属基的，覆盖了体内广泛的部位和时间依赖性。例如，钛基合金可用于骨科和骨合成装置，如髋关节和膝关节，骨固定板和螺钉，以及心脏瓣膜，颌面植入物，牙科植入物和潜在的血管支架。尽管有一个巨大的产业致力于植入材料的开发和应用，但我们对生物环境对生物材料表面的反应方式的了解仍然存在明显的差距。因此，需要在分子尺度上继续发展和提高对候选植入材料的理解。该项目的目标是开发强大的方法，使生物医学植入物对软硬组织环境的初始反应能够在分子尺度上进行化学分析。为了实现这一目标，我们建议进行可行性研究，通过建立样品制备程序的微妙发展，使用横截面透射电子显微镜（TEM）来表征生物细胞/工程合金相互作用的最初阶段。在这种情况下，各种微观分析评估技术，包括电子光谱成像（ESI）和能量色散x射线光谱（EDS），将用于化学绘制一系列模型植入模板的腐蚀过程，包括Ti， Ti基合金和NiTi，不锈钢，CoCr和羟基磷灰石，暴露于体外的人类成骨细胞和内皮细胞培养；中间小细胞衍生血小板；血清蛋白和模拟体液重点还将给予环境扫描电子显微镜（ESEM）和光学荧光显微镜的互补技术的评估。方法是结合我们在生物材料沉积，表面改性，细胞培养和材料表征领域的内部专业知识。

There have been many exciting advances in ceramic, polymeric or composite based biomaterials in recent years. However, the vast majority of biomedical implants still remain metallic-based, covering a wide range of sites and time dependencies in the body. Titanium-based alloys, for example, may be used within orthopaedic and osteosynthesis devices such as hip and knee joints, bone fixation plates and screws, along with heart valves, maxillofacial implants, dental implants and potentially vascular stents. Even though there is a huge industry dedicated to the development and application of implant materials, there is still a clear gap in our knowledge as to the way a biological environment responds to a biomaterial surface. Thus, continued development and improved understanding of candidate implant materials on the molecular-scale is required.The project aim is the development of robust methodologies to enable the initial response of biomedical implants to soft and hard tissue environments to be chemically profiled on the molecular scale. To achieve this, we propose to conduct a feasibility study to characterise the very first stages of biological cell / engineering alloy interaction using cross-sectional transmission electron microscopy (TEM), through the subtle development of established sample preparation procedures. In this context, a variety of microanalytical assessment techniques, including electron spectroscopic imaging (ESI) and energy dispersive X-ray spectroscopy (EDS), will be used to chemically map the corrosion processes of a range of model implant templates, including Ti, Ti-based alloys and NiTi, and stainless steel, CoCr and hydroxyapatite, exposed in-vitro to human osteoblast and endothelial cell cultures; intermediate small cell derived platelets; and serum protein and simulated body-fluid. Emphasis will also be given to the assessment by the complementary techniques of environmental scanning electron microscopy (ESEM) and optical fluorescence microscopy. The approach is to combine our in-house expertise in the areas of biomaterials deposition, surface modification, cell culturing and materials characterisation.