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

摘要：当植入物，如由钴和铬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头中。其中一些原子可以进入骨头本身；更具体地说，它们可以进入骨骼的坚硬部分，该部分由一种叫做磷灰石的矿物质组成。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少，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，这个项目的目标是使用计算机建模和实验相结合，使用非常强大的x射线来找出金属原子在磷灰石矿物中的位置，并确定它们是否使骨头更容易破碎。通过结合计算机模型和实验，研究人员将开发出技术，使他们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含钴和含铬骨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，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，通过教授面向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（妇女和少数民族）担任科学角色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度的阳离子取代倾向，因此骨基质很可能吸收这些离子，导致晶体结构和力学发生重大变化。主要研究人员推测，近种植体骨中钴（Co）和铬（Cr）的掺入在促进骨折中起着重要作用。然而，由于纳米级磷灰石的研究难度较大，在这一过程中，Co和Cr如何替代成磷灰石，离子如何影响磷灰石的力学性能，以及Co和Cr的浓度需要多大才能影响骨折等问题仍未得到解答。为了回答这些问题，我们将建立一个基于从头算的Co和Cr取代磷灰石晶体模型，以预测纳米尺度下磷灰石晶体的晶体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Co和Cr取代引起的断裂起裂过程。这项研究的结果为北美数百万钴铬植入物患者提供了治疗发展的新途径，从而最大限度地减少了这些已经处于危险中的人群的骨折。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。与研究相结合的是一项教育计划，旨在提高各种学生在科学领域的自我效能感。这将通过向本科生和研究生提供实验室通道，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树立榜样来实现。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.