BRIGE: An Interdisciplinary Research and Education Program for Engineering Biodegradable Metallic Implants and Biomimetic Interfaces

全世界每年在外科手术中使用数以百万计的医疗植入物和器械（如螺钉、钢板、销钉、导线、缝合锚），传统上这些部件仅限于永久性金属（如不锈钢、钛合金）和聚酯基可吸收聚合物。由于与这些传统材料相关的临床问题，一类新的可生物降解金属材料，即镁基合金，已被积极追求。镁（Mg）在骨科应用中特别有吸引力，因为它具有与皮质骨相当的模量和强度。控制镁与生物环境的界面是目前限制这种可生物降解金属在医疗设备和植入物中广泛应用的关键挑战。因此，长期研究的目标是确定各种体液环境中Mg降解的基本原理，并设计其与组织的界面。这些知识将使研究人员能够设计具有可调降解特性的生物可降解金属植入物/设备，与新组织生长相适应。这个为期两年的bridge项目将特别关注如何在可生物降解的金属植入物和周围组织之间创建一个仿生界面，以达到双重目的：(1)增强组织整合和再生；(2)同时以确定的可编程方式调节金属植入物的降解。知识价值：生物可降解镁植入物的想法在一个世纪前就被抛弃了，因为它们的降解速度很快。金属合金设计和加工的最新进展使人们对镁基材料和器件重新产生了兴趣。最近的研究主要集中在通过添加合金元素（例如稀土元素）来减少Mg的降解，但它们的长期毒性是一个问题。该项目的新颖之处在于使镁的降解可调且具有生物相容性，而无需添加合金元素。具体来说，该项目将开发一个仿生纳米复合涂层库，以控制材料-结构降解-愈合关系，从而管理组织再生，并使用该纳米复合涂层库建立预测模型，以指导可调节降解的医疗植入物/设备的设计。我们推测，纳米结构的类骨复合材料可以减缓镁的生物降解速度，这也会促进骨整合，加速镁与骨组织界面的愈合。该项目将产生基础知识，推动生物可降解植入物/设备的设计，并将生物降解的概念从传统的聚合物领域转变为智能金属的新时代。该项目的成功将导致生物材料的一场革命，特别是通过开发新的工程策略来控制降解，从而释放生物可降解金属的全部潜力。更广泛的影响：本研究将为生物可降解金属植入物/设备的实际设计指南奠定基础。这将提高美国企业在医疗植入物行业的竞争力。PI将利用在该项目中获得的知识开发UCR跨学科材料科学与工程项目的研究生和本科生课程和模块；她的首要任务是建立一个跨学科的生物材料设计课程。她还将与UCR合作？将她的研究整合到一个新的推广计划中，NanoDays。纳米日是一项旨在提高公众对纳米技术认识的全国性计划，ALPHA中心将利用它作为一种工具，激励更多来自南加州内陆的年轻人——一个高度多样化的地区，在经济机会和教育成就方面落后于加州的大部分地区——追求科学和工程领域的研究。PI和她的学生将在社区中积极工作，通过外联、指导和作为年轻女性的榜样，激励更多的年轻人追求工程事业

PI: LiuProposal Number: 1125801Millions of medical implants and devices (e.g., screws, plates, pins, wires, suture anchors) are used each year worldwide in surgery, and traditionally the components have been limited to permanent metals (e.g., stainless steel, titanium alloys) and polyester-based absorbable polymers. Because of clinical problems associated with these traditional materials, a novel class of biodegradable metallic materials, i.e., magnesium based alloys, has been actively pursued. Magnesium (Mg) is particularly attractive for orthopedic applications because it has comparable modulus and strength to cortical bone. Controlling the interface of magnesium with the biological environment is the key challenge that currently limits this biodegradable metal for broad applications in medical devices and implants. Therefore, the long-term research objective is to determine the fundamentals of Mg degradation in a variety of bodily fluid environments and engineer its interface with tissues. This knowledge will enable researchers to design biodegradable metallic implants/devices with tunable degradation properties compatible with new tissue growth. This two-year BRIGE project will particularly focus on how to create a biomimetic interface between the biodegradable metallic implant and surrounding tissue for the dual purposes of (1) enhancing tissue integration and regeneration and (2) simultaneously mediating the degradation of the metallic implant in a deterministic programmable fashion.INTELLECTUAL MERIT: The idea of biodegradable Mg implants was discarded a century ago because of their rapid degradation. Recent advances in the design and processing of metal alloys has revived interest in Mg-based materials and devices. Most recent research has focused on decreasing Mg degradation through the addition of alloying elements (e.g., rare earth elements), but their long-term toxicity is a concern. The novelty of this project is to make Mg degradation tunable and biocompatible without adding alloying elements. Specifically, this project will develop a library of biomimetic nanocomposite coatings on Mg to control the material-structure degradation-healing relationships that manage tissue regeneration, and to use this nanocomposite library to build a predictive model that will guide the design of medical implant/devices with tunable degradation. It is hypothesized that the biodegradation rate of Mg could be moderated when coated with nanostructured bone-like composites, and this would also promote osseointegration to accelerate healing at the interface of Mg and bone tissue. This project will produce fundamental knowledge that will advance the design of biodegradable implants/devices and transform the concept of biodegradation from traditional polymer domain to a new era of smart metals. The success of this project will lead to a revolution in biomaterials - specifically unlock the full potential of biodegradable metals through developing novel engineering strategies to control the degradation.BROADER IMPACTS: This research will build the foundation for practical design guidelines for biodegradable metallic implants/devices. These, in turn, will increase the competitiveness of U.S. companies in the medical implant industry. The PI will use the knowledge developed in this project to develop graduate and undergraduate courses and modules in UCR's interdisciplinary Materials Science and Engineering program; her first priority is to establish an interdisciplinary Biomaterials Design course. She also will team up with UCR?s ALPHA Center (Academy of Learning through Partnerships for Higher Achievement) to integrate her research into a new outreach initiative, NanoDays. NanoDays is a national program designed to increase public awareness of nanotechnology, and the ALPHA Center will use it as a tool to inspire more young people from inland Southern California - a highly diverse region that lags behind much of California in economic opportunity and educational achievement - to pursue studies in science and engineering fields. The PI and her students will work actively in the community to inspire more young people to pursue engineering careers through outreach, mentoring, and serving as role models to young women