Collaborative Research: Nucleation of Calcium Phosphate Biomaterials

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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.