Collaborative Research: Predicting the Mechanical Properties of Biomimetic Apatite Crystals Due to Co and Cr Ion Substitutions

非技术摘要：当植入物，如钴和铬制成的髋关节植入物降解时，它们可以将这些重金属原子释放到周围的骨骼中。其中一些原子可以进入骨骼本身；更具体地说，它们可以进入骨骼的坚硬部分，这部分由一种名为磷灰石的矿物组成。这些原子进入磷灰石可以改变你骨骼的工作方式，使它们更有可能断裂。然而，因为你骨骼中的磷灰石矿物非常小，所以很难研究这些重金属离子去了哪里，它们是如何影响骨骼强度的。因此，该项目的目标是使用计算机建模和使用非常强大的X射线的实验相结合的方法来计算出磷灰石矿物中的金属原子的位置，并确定它们是否会使骨骼更容易破碎。通过将计算机模型和实验相结合，将开发出一种技术，使研究人员能够了解金属原子与骨磷灰石是如何相互作用的，并预测这些原子如何影响数百万接受含钴和铬植入物的人的骨强度。结合这项研究，主要研究人员将努力创造环境，让学生对自己的科学能力更有信心。这将通过为学生提供在实验室工作的机会，通过教授面向广泛受众的包容性课程，以及通过为那些不经常看到像他们这样的人(女性和少数族裔)担任科学角色的学生充当榜样来实现。技术摘要：含钴和铬的种植体的降解与重金属离子的释放和骨折风险的增加有关。由于骨主要由具有高阳离子取代倾向的磷灰石矿物组成，很可能是骨基质吸收了这些离子，导致晶体结构和力学性能发生显著变化。主要研究人员假设，钴(Co)和铬(Cr)在种植体附近的骨骼中的结合在促进骨折方面发挥了重要作用。然而，由于纳米磷灰石的研究难度较大，在这一过程中还存在一些悬而未决的问题，包括钴和铬如何取代成磷灰石，离子对磷灰石力学性能的影响，以及钴和铬的浓度对骨折的影响。为了回答这些问题，我们将建立一个基于从头算的钴、铬取代磷灰石晶体模型，以预测纳米尺度下磷灰石晶体的结晶学和力学性能的变化。这些预测将通过使用仿生磷灰石系统和高能同步X射线衍射技术的实验方法来验证。这些数据将被结合在一起，创建多尺度的磷灰石晶体模型，以研究由于钴和铬替代而导致的断裂起始过程。这项研究的结果可以为数百万接受钴铬植入物的北美人带来好处，因为它为治疗开发创造了一条新的途径，可以最大限度地减少这一已经处于危险之中的人群的骨折。此外，它们还将促进磷灰石生物材料的可调性，用于未来的骨移植和支架应用。与这项研究相结合的是一项旨在提高各种学生在科学领域的自我效能感的教育计划。这将通过为本科生和研究生提供实验室机会，开发与文化相关的包容性科学课程，并为代表性不足的学生充当榜样来实现。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Non-technical Abstract:When implants, like hip implants made of cobalt and chrome degrade, they can release atoms of those heavy metals into the surrounding bone. Some of those atoms can make their way into the bone itself; more specifically they can get inside the hard part of your bones which is made up of a mineral called apatite. The movement of these atoms into the apatite can change the way your bones work, making them more likely to break. However, because the apatite minerals in your bones are extremely small, it has been very difficult to study where these heavy metal ions go and how they affect bone strength. The goal of this project is therefore to use a combination of computer modelling and experiments using very powerful X-rays to figure out where the metal atoms go in the apatite mineral and determine whether or not they make the bone more breakable. By combining computer models and experiments, techniques will be developed that allow researchers to understand how metal atoms interact with bone apatite and predict how those atoms affect bone strength in the millions of people with cobalt and chromium containing bone implants. Integrated with this research, the principal investigators will strive to create environments that make students more confident about their scientific abilities. This will be done by providing opportunities for students to work in the lab, by teaching inclusive classes that reach broad audiences, and by acting as role models for students who do not often see people like them (women and racial minorities) in scientific roles. Technical Abstract:Degradation of cobalt (Co) and chromium (Cr) containing implants are associated with release of heavy metal ions and an increase in bone fracture risk. Since bone is primarily composed of apatite mineral which exhibits a high propensity for cationic substitutions, it is likely that the bone matrix is absorbing these ions resulting in significant changes in crystal structure and mechanics. The principal investigators hypothesize that the incorporation of cobalt (Co) and chromium (Cr) in the near-implant bone plays a significant role in promoting fracture. However, due to the difficulty in studying nano-sized apatites, there remain several unanswered questions relative to this process including how Co and Cr substitute into apatite, how the ions affect the apatite mechanical properties, and what Co and Cr concentrations are needed to affect bone fracture. To answer these questions, an ab initio-based model of apatite crystals with Co and Cr substitutions will be developed to predict the change in crystallographic and mechanical properties of apatite crystals at the nanoscale. These predictions will be validated by experimental approaches using biomimetic apatite systems and high-energy synchrotron X-ray diffraction techniques. These data will be combined to create multiscale models of apatite crystals to study fracture initiation processes due to Co and Cr substitutions. The results from this study can benefit millions of North Americans with cobalt-chrome implants by creating a new avenue for treatment developments to minimize fracture in this already at-risk population. In addition, they will facilitate the tunability of apatite biomaterials for future bone graft and scaffolding applications. Integrated with the research, is an educational plan which seeks to increase self-efficacy in the realm of science for a variety of students. This will be accomplished by providing lab access to undergraduate and graduate students, developing culturally relevant inclusive scientific courses, and acting as role models for under-represented students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.