Collaborative Research: Nucleation of Calcium Phosphate Biomaterials

非技术性：这些由材料研究部生物材料项目资助给圣路易斯华盛顿大学和哥伦比亚大学的合作奖项将研究生理条件下基于磷酸钙(CAP)的生物矿物的形成。为了治疗矿化相关的骨病变、促进骨再生和改善肌腱与骨的愈合，需要更好地了解胶原蛋白上实时帽状矿物质的形成。因此，该项目的发现对于理解生物活性骨和肌腱-骨界面的兼容性和强度将是重要的。此外，该项目将提供治疗病理性骨形成的关键信息。这些结果还将广泛应用于生物矿化领域，并将对研究基本过程和开发再生医学应用(例如，人工骨材料的体外合成)的研究人员感兴趣。此外，从这项工作中获得的变革性知识将适用于许多生物、医学、工业、地质和环境过程。拟议的教育和推广计划还将为初中生、高中生、本科生和研究生提供教育和研究机会，同时鼓励传统上代表性不足的群体的学生参与和教育刺激。该项目团队将与圣路易斯地区的中学教师以及华盛顿大学学校合作研究所(ISP)和纽约市地区的外展教育工作者合作。该团队将开发关于晶体形成的研讨会和免费教育工具包，并提供对这些实验与骨形成的相关性的见解。教育工具包将提供给大圣路易斯地区的教师，并在互联网服务提供商网站上列出，以便更好地传播。技术：这个合作项目将研究胶原纤维中磷酸钙(CAP)生物矿物的初始成核和生长，并考虑所涉及的多个长度尺度(即宏观纤维外结构和纳米纤维内区域)。这项工作首次使用基于同步加速器的原位实时小角X射线散射，提供了关于成核位置的粒子尺寸和体积、成核率以及帽核和胶原纤维之间的界面自由能的定量信息。现场广角X射线散射和高分辨率X射线对分布函数将考察多个帽状结晶路径的动力学，包括经典和非经典成核行为，取决于多个成核点的成矿顺序。一旦更好地了解了不同成核点的成核动力学和成核机理，该项目将研究胶原帽复合材料最终产品的后续机械性能。通过开发一种新的结构-功能关系模型，该项目可以为开发更好的生物材料提供指导。该项目的技术影响包括基础科学发现和矿化生物材料的应用。

Non-technical: These collaborative awards funded by the Biomaterials program of the Division of Materials Research to Washington University in St. Louis and Columbia University will investigate calcium phosphate (CaP) based biomineral formation under physiological conditions. A better understanding of real-time CaP mineral formation on collagen is required for treating mineralization-related bone pathologies, in enhancing bone regeneration, and in improving tendon-to-bone healing. Thus, the findings from the project will be important in understanding the compatibility and strength of bioactive bone and tendon-to-bone interfaces. In addition, the project will provide key information in remediating pathologic bone formation. The results will also be broadly applicable in the bio-mineralization field and will be of interest to investigators studying fundamental processes and developing regenerative medicine applications (e.g., in vitro synthesis of artificial bone materials). Furthermore, transformative knowledge obtained from this work will be applicable in many biological, medical, industrial, geological, and environmental processes. The proposed education and outreach plan will also provide educational and research opportunities for middle school, high school, undergraduate and graduate students, while simultaneously encouraging the participation and educational stimulation of students from traditionally underrepresented groups. The project team will collaborate with middle school teachers in the St. Louis area and outreach educators at Washington University's Institute for School Partnership (ISP), and in New York City area. The team will develop workshops and free educational kits on crystal formation, and provide insight into the relevance of the experiments for bone formation. The educational kits will be available for teachers in the Greater St. Louis area, and listed on the ISP website for better dissemination.Technical: This collaborative project will examine the initial nucleation and growth of calcium phosphate (CaP) bio-minerals within collagen fibrils, with consideration of the multiple length scales involved (i.e., macroscale extra-fibrillar structures and nanoscale intra-fibrillar regions). Using synchrotron-based in situ real-time small angle X-ray scattering, the work for the first time, will provide quantitative information on particle dimensions and volumes, nucleation rates, and interfacial free energies between CaP nuclei and collagen fibrils at nucleation sites. In situ wide angle X-ray scattering and high resolution X-ray pair-distribution functions will examine the kinetics of multiple CaP crystallization pathways, involving both classical and non-classical nucleation behaviors, depending on the sequence of mineralization at multiple nucleation sites. Once a better understanding of nucleation kinetics and mechanisms at different nucleation sites is achieved, the project will study the consequent mechanical properties of the final products of collagen-CaP composites. By developing a novel structure-function relationship model, the project can provide a guideline for the development of better biomaterials. The technical impacts of the project encompass both fundamental scientific discovery and applications for mineralized biomaterials.