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（如由钴和Chrome制成的髋关节植入物）降解时，它们会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，这是由一种叫做磷灰石的矿物质组成的。这些原子进入磷灰石的运动可以改变骨骼的工作方式，使它们更容易断裂。然而，由于骨骼中的磷灰石矿物质非常小，因此很难研究这些重金属离子的去向以及它们如何影响骨骼强度。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，以确定金属原子在磷灰石矿物中的位置，并确定它们是否使骨骼更容易破碎。通过将计算机模型和实验相结合，将开发技术，使研究人员能够了解金属原子如何与骨磷灰石相互作用，并预测这些原子如何影响数百万人的骨强度，这些人使用含钴和铬的骨植入物。结合这项研究，主要研究人员将努力创造环境，使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，通过教授覆盖广泛受众的包容性课程，以及为那些不经常看到像他们这样的人（女性和少数民族）的学生树立榜样来实现。技术摘要：含钴（Co）和铬（Cr）植入物的降解与重金属离子的释放和骨折风险的增加有关。由于骨主要由磷灰石矿物组成，磷灰石矿物表现出高的阳离子取代倾向，因此骨基质可能吸收这些离子，导致晶体结构和力学发生显著变化。主要研究者假设，种植体附近骨中钴（Co）和铬（Cr）的结合在促进骨折方面起着重要作用。然而，由于在研究纳米尺寸的磷灰石的困难，仍然有几个未回答的问题，相对于这个过程，包括如何钴和铬替代到磷灰石，离子如何影响磷灰石的机械性能，以及什么样的钴和铬浓度需要影响骨折。为了回答这些问题，一个从头算为基础的模型，磷灰石晶体与钴和铬取代将开发预测磷灰石晶体的晶体学和机械性能的变化在纳米级。这些预测将通过使用仿生磷灰石系统和高能同步加速器X射线衍射技术的实验方法进行验证。这些数据将结合起来创建磷灰石晶体的多尺度模型，以研究由于Co和Cr替代而导致的断裂引发过程。这项研究的结果可以使数百万使用钴铬合金植入物的北美人受益，为治疗开发创造了新的途径，以最大限度地减少这一已经处于风险中的人群的骨折。此外，它们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。与研究相结合，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访问，开发文化相关的包容性科学课程，并作为代表性不足的学生的榜样来实现。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.