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

职业：用于控制蛋白质吸附和生物活性的生物陶瓷的设计

• 批准号: 9875326
• 负责人: Sandra Burkett
• 金额: --
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 1999-07-22
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9875326&HistoricalAwards=false
• 关键词: CAREER; Design; Bioceramics; Controlled; Protein

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.

9875326 BurkettThe本学院早期职业发展项目的主要研究目标是发展蛋白质吸附陶瓷表面的表面化学和拓扑结构对蛋白质构象，方向和空间排列的影响方面的基本理解。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。 将制备一系列沸石和分子筛材料，使得表面几何形状和表面化学组成系统地和独立地变化，并且将在分子水平上研究这些参数中的每一个对蛋白质吸附的影响。 研究活动包括选择，合成和表征适当的沸石和分子筛;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;以及选择和表征代表一系列大小，形状和电子电荷的蛋白质，并有用于模型研究的先例或与未来应用相关。所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、拓扑学和微观结构性质的影响之间的相关性应为开发生物学非天然陶瓷材料类别作为生物医学用途的新候选者提供合理的基础;例如需要通过控制骨诱导蛋白和细胞的粘附来促进新骨沉积和结合到整形外科植入物上的新涂层。 研究活动和教育工作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视角。 教育部分涉及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一个连贯一致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在表面化学和拓扑结构对蛋白质构象，方向和空间排列的影响方面，对陶瓷表面上的蛋白质吸附有基本的了解。 为了使蛋白质在吸附到表面时发挥功能，它必须不仅保持活性位点处氨基酸的三维构象，而且使该位点可接近外部环境。 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递送。 特别感兴趣的是生物医学应用的陶瓷材料的设计和评价的影响，因为蛋白质吸附是植入的生物医学材料的初始生物反应，因此是材料的活性和生物相容性的关键决定因素。