CAREER: Design of Bioceramics for Controlled Protein Adsorption and Biological Activity

这个教师早期职业发展项目的主要研究目标是根据表面化学和拓扑结构对蛋白质构象、取向和空间排列的影响，对蛋白质在陶瓷表面的吸附有一个基本的了解。蛋白质-沸石相互作用为研究表面化学和拓扑结构对蛋白质吸附的影响提供了一个模型系统。我们将制备一系列分子筛和分子筛材料，使它们的表面几何结构和表面化学组成发生系统而独立的变化，并在分子水平上研究这些参数对蛋白质吸附的影响。研究活动包括选择、合成和表征合适的沸石和分子筛；通过透射电子显微镜和原子力显微镜对这些材料进行详细的表面表征；以及选择和表征用于研究的蛋白质，这些蛋白质代表一系列大小、形状和电荷，并具有在模型研究中使用或与未来应用相关的先例。观察到的蛋白质构象和取向效应与底层陶瓷基质的物理化学、拓扑和微结构特性的影响之间的相关性应该为开发一类生物非天然陶瓷材料作为生物医学应用的新候选材料提供合理的基础；例如，需要新的涂层通过控制骨诱导蛋白和细胞的黏附来促进新骨与骨科植入物的沉积和结合。研究活动和教育努力的统一主题是在生物医学材料设计、合成和开发的多学科领域内培养分子观点。教育部分包括在麻省理工学院材料科学与工程系的本科生和研究生课程中建立连贯、协调的生物医学材料教育努力。该学院早期职业发展项目的主要研究目标是根据表面化学和拓扑结构对蛋白质构象、取向和空间排列的影响，对蛋白质在陶瓷表面的吸附有一个基本的了解。为了使蛋白质在吸附到表面时发挥作用，它的位置不仅必须保持活性部位的氨基酸的三维构象，而且还必须使外部环境能够接触到该部位。蛋白质-沸石相互作用为研究表面化学和拓扑结构对蛋白质吸附的影响提供了一个模型系统。这些研究的结果与涉及吸附蛋白质的各种应用有关，包括生物催化、生物传感、蛋白质结晶以及药物和疫苗输送。尤其令人感兴趣的是对生物医学应用的陶瓷材料的设计和评估的影响，因为蛋白质吸附是对植入的生物医学材料的初始生物反应，因此是材料活性和生物兼容性的关键决定因素。

9875326BurkettThe primary research goal of this Faculty Early CAREER Development project is to develop a fundamental understanding of protein adsorption on ceramic surfaces in terms of the effects of surface chemistry and topology on protein conformation, orientation, and spatial arrangement. Protein-zeolite interactions provide a model system for studying the effects of surface chemistry and topology on protein adsorption. A series of zeolite and molecular sieve materials will be prepared such that surface geometry and surface chemical composition are varied systematically and independently, and the effects of each of these parameters on protein adsorption will be studied at the molecular level. The research activities involve selection, synthesis, and characterization of appropriate zeolites and molecular sieves; detailed surface characterization of these materials by transmission electron microscopy and atomic force microscopy; and selection and characterization of proteins for study that represent a range of sizes, shapes, and electronic charges, and have precedent for use in model studies or are relevant to future applications. Correlation of the observed protein conformational and orientational effects with the influence of physicochemical, topological, and microstructural properties of the underlying ceramic matrix should provide a rational basis for the development of classes of biologically non-native ceramic materials as new candidates for biomedical use; for example, there is a need for new coatings that promote deposition and bonding of new bone to orthopedic implants by controlling the adhesion of osteoinductive proteins and cells. The unifying theme within the research activities and the educational efforts is cultivation of a molecular perspective within the multidisciplinary field of biomedical materials design, synthesis, and development. The educational component involves establishment of a coherent, concerted educational effort in biomedical materials within the undergraduate and graduate curricula in the Department of Materials Science and Engineering at MIT. The primary research goal of this Faculty Early CAREER Development project is to develop a fundamental understanding of protein adsorption on ceramic surfaces in terms of the effects of surface chemistry and topology on protein conformation, orientation, and spatial arrangement. In order for a protein to function while adsorbed to a surface, it must be situated not only such that the three-dimensional conformation of amino acids at the active site is retained, but also such that the site is accessible to the external environment. Protein-zeolite interactions provide a model system for studying the effects of surface chemistry and topology on protein adsorption. Results from these studies are relevant to a variety of applications that involve adsorbed proteins, including biocatalysis, biosensing, protein crystallization, and drug and vaccine delivery. Of particular interest are the implications for the design and evaluation of ceramic materials for biomedical applications, since protein adsorption is the initial biological response to an implanted biomedical material and is thus a critical determinant of the material's activity and biocompatibility.