EAGER: Biocompatibility of nanocrystalline YSZ transparent cranial implant

非技术描述：该项目的总体目标是开发新一代透明陶瓷，可用于取代传统的不透明颅骨植入物（由钛和聚合物材料制成）。这种新的植入物被称为“大脑之窗”（WttB）平台，允许对大脑进行非侵入性的反复光学检查，因此，它是新兴的基于激光的诊断（例如，光遗传学）和治疗（例如，光动力疗法）脑病和神经系统疾病的关键推动者，如脑癌、中风、创伤性脑损伤、帕金森病等。该项目特别侧重于评估低温“老化”和陶瓷植入物周围生物膜形成的潜在问题。该项目的广泛影响在于它为神经科学社区提供了额外的好处，该社区旨在促进理解和改善脑部疾病管理，从而提高生活质量并降低医疗保健成本。此外，这种新型光陶瓷材料在科学和技术上取得的进步有可能扩展到许多其他领域，包括医疗激光、国防、能源等。该项目还为本科生和研究生提供研究机会，特别是在STEM领域和代表性不足的少数族裔，为他们作为独立的、全球参与的工程师进行创新做好准备。技术细节：虽然传统的颅骨植入材料提供了植入后所需的机械性能和可接受的生物相容性，但没有一种材料能提供高断裂韧性和光学透明度的独特组合，使医生能够连续诊断和治疗各种脑病和神经疾病。最近对透明纳米晶氧化钇稳定氧化锆（nc-YSZ）在动物模型上的可行性研究表明，对大脑进行非侵入性光学询问是可能的。由于在其他类型的YSZ植入物中已经报道了由于相变不稳定导致的老化引起的降解，因此需要对透明nc-YSZ材料进行类似的独立评估。此外，这些植入物的光学透明度允许激光介导控制来阻止甚至恢复过度的污垢（生物膜形成），这是将这种材料用于诸如此类的生物医学应用的另一个潜在障碍。因此，该项目的第一个目标是研究长期老化是否会限制透明nc-YSZ作为医疗材料的使用。第二个目标是测量nc-YSZ样品上生物膜形成的程度，并探索使用亚治疗激光照射方法来补救这种问题，如果它出现的话。这项工作的意义在于基于陶瓷的WttB平台的潜力，通过促进新兴光遗传神经技术的临床转化，该平台最终可能会提高对大脑的理解。这项研究是及时的和变革性的，属于大脑计划的目标。同时，它也为本科生和研究生提供研究机会。该项目利用了一些成熟的项目和学生组织，如加州少数民族参与联盟（CAMP）、加州大学高级学位卓越领导力（UC LEADS）和西班牙裔专业工程师协会（SHPE）。

NON-TECHNICAL DESCRIPTION: The overall goal of this project is to develop a new generation of transparent ceramics, which may be used to replace traditional, opaque cranial implants (made from titanium and polymer-based materials). This new implant, which is referred to as a Window to the Brain (WttB) platform, allows for non-invasive optical interrogation of the brain on a recurring basis and, thus, serves as a critical enabler of emerging laser-based diagnostic (e.g., optogenetics) and therapy (e.g., photodynamic therapy) of brain pathologies and neurological disorders, such as brain cancer, stroke, traumatic brain injury, Parkinson's disease, etc. In particular, this project focuses on assessing potential problems of low temperature "ageing" and biofilm formation around the ceramic implant. The broad impact of this project lies in the added benefit it provides to the neuroscience community, which aims to advance understanding and improve brain disease management, thus improving quality of life and reducing healthcare costs. Furthermore, the advances made in the science and technology of novel opto-ceramic materials such as this has potential to extend to numerous other fields, including medical lasers, defense, energy, etc. This project also provides research opportunities to undergraduate and graduate students, particularly in the STEM field and for underrepresented minorities, preparing them to innovate as independent, globally-engaged engineers. TECHNICAL DETAILS: While traditional cranial implant materials provide the mechanical properties and acceptable biocompatibility necessary after implantation, none provide the unique combination of high fracture toughness and optical transparency that would enable physicians to diagnose and treat continuously various brain pathologies and neurological disorders. A recent feasibility study of a transparent nanocrystalline yttria-stabilized-zirconia (nc-YSZ) on an animal model showed that non-invasive optical interrogation of the brain is possible. Since aging-induced degradation has been reported in other types of YSZ implants as a result of phase change destabilization, independent assessments of a similar kind are required for transparent nc-YSZ materials. Furthermore, the optical transparency of these implants allows for laser-mediated controls to arrest and even revert excessive fouling (biofilm formation), which is another potential impediment for the use of this material for biomedical applications such as this. Therefore, the first goal of this project is to investigate if long term ageing could limit the use of transparent nc-YSZ as a medical material. The second goal is to measure the extent of biofilm formation on nc-YSZ samples and explore the use of sub-therapeutic laser irradiation approaches to remedy such a problem if it arises. The significance of this work lies in the potential of the ceramic-based WttB platform which may eventually allow advancements in the understanding of the brain, by facilitating the clinical translation of emerging optogenetic neurotechnologies. This research is timely and transformational and falls under the objectives of the BRAIN Initiative. As well, it is providing research opportunities to undergraduate and graduate students. This project is leveraging well-established programs and student organizations such as the California Alliance for Minority Participation (CAMP), UC Leadership Excellence through Advanced Degrees (UC LEADS), and the Society for Hispanic Professional Engineers (SHPE).