Collaborative Research: Nucleation of Calcium Phosphate Biomaterials

非技术：该合作奖由圣路易斯华盛顿大学材料研究部生物材料项目和哥伦比亚大学资助，将研究生理条件下基于磷酸钙（CaP）的生物矿物形成。更好地了解胶原蛋白上CaP矿物的实时形成对于治疗矿化相关的骨病理、促进骨再生和改善肌腱-骨愈合是必需的。因此，该项目的研究结果将对理解生物活性骨和肌腱-骨替代品的相容性和强度具有重要意义。此外，该项目将为修复病理性骨形成提供关键信息。结果也将广泛适用于生物矿化领域，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激励。该项目团队将与圣路易斯地区的中学教师和华盛顿大学学校伙伴关系研究所（ISP）的外展教育工作者合作。该团队将开发有关晶体形成的研讨会和免费教育工具包，并提供有关骨形成实验的相关见解。大圣路易斯地区的教师可以使用这些教育工具包，并在互联网服务提供商网站上列出，以便更好地传播。技术：该合作项目将研究胶原原纤维中磷酸钙（CaP）生物矿物的初始成核和生长，并考虑到涉及的多个长度尺度（即宏观尺度的纤维外结构和纳米尺度的纤维内区域）。利用基于同步加速器的实时小角度x射线散射（SAXS），这项工作将首次提供关于CaP核与成核部位胶原原纤维之间的粒子尺寸和体积、成核速率和界面自由能的定量信息。现场广角x射线散射（WAXS）和高分辨率x射线对分布函数（PDF）将研究多种CaP结晶途径的动力学，包括经典和非经典成核行为，这取决于多个成核位点的矿化顺序。一旦对不同成核位点的成核动力学和机制有了更好的了解，该项目将研究胶原- cap复合材料最终产品的机械性能。通过建立一种新的结构-功能关系模型，该项目可以为更好的生物材料的开发提供指导。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: This 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 substitutes. 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). 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) biominerals within collagen fibrils, with consideration of the multiple length scales involved (i.e., macro-scale extrafibrillar structures and nano-scale intrafibrillar regions). Using synchrotron-based in situ real-time small angle X-ray scattering (SAXS), the work will, for the first time, 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 (WAXS) and high resolution X-ray pair-distribution functions (PDF) 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.