CAREER: Hybrid Surface Coating Toward Corrosion-Controlled Magnesium-Based Implants

在美国，骨折的发病率正在上升，部分原因是人口老龄化。到2027年，全球骨折固定设备（如医疗植入物）市场预计将达到136亿美元，同期复合年增长率为6.1%。这个学院早期职业发展（Career）奖通过提高可生物降解镁基金属植入物的临床可行性，解决了一个重大的医疗保健挑战。生物可降解植入物在生物医学应用中的应用，包括血管支架和小型骨固定装置，为目前使用的永久性金属植入物提供了一种创新的选择。这些永久性金属植入物通常会引起严重的并发症，可能需要手术干预。虽然可生物降解的镁基植入物很有希望，但在愈合过程完成之前，它们的快速降解破坏了它们的功效。该项目引入了创新的混合涂层，结合了不同的涂层方法和材料，以减轻降解，并允许生物活性剂的可控释放。通过研究生物活性物质如何与包覆镁相互作用，该项目旨在了解降解抑制机制和调节降解速率。此外，将开发一个计算模型来预测降解和药物释放，连接理论和实验。这项研究的意义在于，它有可能通过调整植入物的降解率和使用寿命来彻底改变针对患者的生物医学植入物。成功的结果可能会导致各种种植体的改进，包括骨科、面部、口腔等，使患者有个性化的需求。该项目与美国国家科学基金会的使命一致，即推进科学，促进健康，为国家福利做出贡献。认识到某些群体的代表性不足，该项目包括一个以社区为基础的指导计划，旨在通过实践活动，促进参与和公民参与，让查塔努加和田纳西东南部地区得不到充分服务的西班牙裔儿童接触STEM。PI还计划与首尔大学女工程师协会（Society of Women Engineers）合作，向女高中生介绍生物医学工程研究，鼓励她们参与STEM领域。此外，还将开设“生物材料制造”研究生课程，丰富教育，培养未来的专业人才。本研究项目解决了镁基生物医学植入物快速降解的挑战，阻碍了它们的临床影响。通过采用混合涂层系统，特别是等离子体电解氧化（PEO）与溶胶-凝胶涂层方法相结合，该项目旨在控制降解率并增强智能生物材料的生物活性剂释放。该研究项目将解决在理解涂层镁植入物增强耐腐蚀性背后的机制以及在长时间植入期间有效调节生物活性剂释放方面的空白。两个主要目标指导研究：目标#1侧重于了解生物活性剂与peo涂层镁基质多孔表面的相互作用，通过微观结构演变和电化学腐蚀机制阐明它们作为腐蚀抑制剂的作用。目标#2涉及基于物理建模方法的多功能数值模型的开发，以预测由混合peo基和多层羟基磷灰石（HA）溶胶-凝胶涂层涂覆的镁基质的降解率和生物活性剂释放。该项目的一个成果是有可能沉积薄（100纳米）的后续涂层。这使得沉积的涂层层和降解率之间建立了明确的关系。这种理解对于确保植入物降解的特定时间开始是至关重要的，这是患者特定植入物应用的重要方面。跨学科的方法结合了生物材料加工，腐蚀科学和数值模拟方面的专业知识。预期的结果有可能将镁作为一种可生物降解的金属技术整合到临床环境中，特别是在骨科和颅颌面应用的患者特定设备中。该项目的教育目标是：(1)为11至18岁的西班牙裔儿童开发一个新的社区指导计划，(2)组织讲座、演讲和现场演示，旨在招募更多的女性研究学生，以及(3)开发一门以“生物材料制造”为主题的研究生跨学科课程。这些教育活动将提供STEM接触，社会参与，职业发展和建议，特别是针对查塔努加和田纳西州东南部地区的西班牙裔和女学生。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 SUMMARYThere is an increasing incidence of bone fractures in the United States, which is caused in part by an aging population. The global market for fracture fixation devices (e.g., medical implants) is expected to reach $13.6 billion by 2027, growing at a compound annual growth rate of 6.1% over that time. This Faculty Early Career Development (CAREER) award addresses a significant healthcare challenge by enhancing the clinical feasibility of biodegradable magnesium-based metallic implants. The utilization of biodegradable implants in biomedical applications, including vascular stents and small bone fixation devices, presents an innovative alternative to the currently employed permanent metallic implants. These permanent metallic implants often entail significant complications and may necessitate surgical intervention. Although biodegradable magnesium-based implants hold promise, their rapid degradation undermines their efficacy before the completion of the healing process. This project introduces innovative hybrid coatings, combining different coating methods and materials, to mitigate degradation and allow the controlled release of bioactive agents. By investigating how bioactive agents interact with coated magnesium, the project aims to understand degradation inhibition mechanisms and modulate degradation rates. Additionally, a computational model will be developed to predict degradation and agent release, bridging theory and experiment. The significance of this research lies in its potential to revolutionize patient-specific biomedical implants by tailoring the degradation rates and hence the lifespan of an implant. Successful outcomes may lead to the improvement of a variety of implants including orthopedic, facial, oral, and more, benefiting patients with personalized needs. This project aligns with the NSF's mission by advancing science, promoting health, and contributing to national welfare. Recognizing the underrepresentation of certain groups, the project includes a community-based mentoring program that aims to expose underserved Hispanic children in Chattanooga and the Southeast Tennessee Area to STEM through hands-on activities, fostering engagement and civic involvement. The PI also plans to work with the Society of Women Engineers at the university to introduce female high school students to biomedical engineering research, encouraging their participation in STEM fields. Moreover, a graduate course on "Manufacturing of Biomaterials" will be developed, enriching education and nurturing future professionals.TECHNICAL SUMMARYThis research project addresses the challenge of rapid degradation in magnesium-based biomedical implants, hindering their clinical impact. By employing hybrid coating systems, particularly plasma electrolytic oxidation (PEO) coupled with the sol-gel coating method, the project aims to control degradation rates and enhance bioactive agent release for smart biomaterials. This research project will address gaps in understanding the mechanisms behind enhanced corrosion resistance of coated magnesium implants and the effective regulation of bioactive agent release during prolonged implantation periods. Two primary objectives guide the investigation: Objective #1 focuses on understanding the interaction of bioactive agents with the porous surface of PEO-coated magnesium substrates, elucidating their role as corrosion inhibitors through microstructural evolution and electrochemical corrosion mechanisms. Objective #2 involves the development of a versatile numerical model based on a physical modeling approach to predict degradation rates and bioactive agent release from magnesium substrates coated with hybrid PEO-based and multiple layers of hydroxyapatite (HA) sol-gel coatings. One outcome of the project is the possibility of depositing thin ( 100 nm) subsequent coating layers. That enables the establishment of a clear relationship between the deposited coating layers and degradation rates. This understanding is crucial for ensuring a time-certain commencement of the implant’s degradation, a vital aspect for patient-specific implant applications. The interdisciplinary approach combines expertise in biomaterials processing, corrosion science, and numerical modeling. The anticipated outcomes hold the potential to integrate magnesium as a biodegradable metal technology in clinical settings, particularly for patient-specific devices in orthopedic and craniomaxillofacial applications. The educational objective of the project is to (1) develop a new community-based mentoring program for Hispanic children ages 11 to 18, (2) organize talks, presentations, and live demonstrations aiming at recruiting more female research students, and (3) develop a graduate interdisciplinary course on the topic of “Manufacturing of Biomaterials”. These educational activities will offer STEM exposure, social engagement, career development, and advising, particularly for Hispanic and female students in Chattanooga and the Southeast Tennessee Area.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.