Developing Rational Design Principles for Textured Medical Device Surfaces

制定纹理医疗器械表面的合理设计原则

• 批准号: 2037856
• 负责人: Dacheng Ren
• 金额: $ 10万
• 依托单位: Syracuse University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2037856&HistoricalAwards=false
• 关键词: Developing; Rational; Design; Principles; Textured

Non-technical Summary: Each year, millions of medical devices with different surface textures are used to provide life support, mitigate failing body parts, or for cosmetic purposes. Recent research has revealed that surface topography has profound impact on microbe-material interactions and thus the safety of implanted medical devices. However, the mechanisms of such interactions and how to rationally design surface topographies to prevent infection while promoting host tissue integration are not well understood. This study is motivated by this knowledge gap and the recent reports of breast implant associated anaplastic large cell lymphoma (BIA-ALCL). BIA-ALCL is a well-recognized complication that has devastating impact on affected individuals, which has led to a decision of the Food and Drug Association (FDA) in 2019 to remove certain breast implants from the market. Despite this well-recognized challenge, the cause of BIA-ALCL remains elusive and a guideline for effectively regulating such devices is still missing. Through a prior Scholar-in-Residence at FDA project, the PI Ren and FDA co-PI Philips have obtained important new information about how bacteria interact with surface topographies, which led to this proposed new project. Through close collaboration, the team will conduct the first study on how implant surface topography affects bacterial quorum sensing and production of virulence factors, as well as the effects of surface topography on phagocytosis. The findings from this study will not only benefit the safety of breast implants, but also help guide the design and regulation of other devices. Beyond the research itself, the team will leverage this project to recruit young talents especially those from underrepresented groups and jointly advise graduate students. This project will help workforce development and better prepare civilly responsible engineers to solve challenging problems facing our society.Technical Summary:During previous study, the team discovered that surface topographies mimicking the features of ALCL-associated breast implants have significantly higher bacterial loads than the flat control and the surfaces with other recessive patterns tested. In addition, the cell density in recessive wells were about 7 times higher than the flat control based on two-dimensional surface coverage after just 24 hours of culturing. The difference can be even bigger considering the three-dimensional biofilm structure and interaction with host factors, which will be studied in this project. Based on these findings, the team hypothesizes that inappropriate recessive features can promote bacterial biofilm formation, quorum sensing, and associated production of virulence factors. The team further hypothesizes that these topographic features present a physical hindrance for immune cells such as macrophages from reaching bacterial cells and cleaning them from the implant surface, leading to inflammation and subsequently BIA-ALCL. The team will test these hypotheses by conducting complementary experiments and cell tracking to understand how surface topography affects the interaction between bacteria and host cells. This new information will fill an important knowledge gap, and provide critical insights for understanding device-associated complications and the design of safer medical devices. The results will help FDA to better prepare for reviews of emerging technologies involving smart biomaterials. The team will also leverage this project to motivate students for research, especially individuals from underrepresented groups.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.

非技术总结：每年都有数百万种具有不同表面纹理的医疗设备用于提供生命支持，减轻身体部位的衰竭或美容目的。最近的研究表明，表面形貌对微生物-材料相互作用具有深远的影响，从而影响植入式医疗器械的安全性。然而，这种相互作用的机制以及如何合理设计表面形貌以防止感染，同时促进宿主组织整合还没有得到很好的理解。这项研究的动机是这种知识差距和乳房植入体相关的间变性大细胞淋巴瘤（BIA-ALCL）的最新报告。BIA-ALCL是一种公认的并发症，对受影响的个体具有破坏性影响，这导致美国食品药品监督管理局（FDA）在2019年决定将某些乳房植入体从市场上移除。尽管存在这一公认的挑战，BIA-ALCL的病因仍然难以捉摸，并且仍然缺少有效监管此类器械的指南。通过之前的FDA驻校学者项目，PI Ren和FDA合作PI Philips获得了关于细菌如何与表面形貌相互作用的重要新信息，从而导致了这个拟议的新项目。通过密切合作，该团队将首次研究植入物表面形貌如何影响细菌群体感应和毒力因子的产生，以及表面形貌对吞噬作用的影响。这项研究的发现不仅有利于乳房植入体的安全性，而且有助于指导其他器械的设计和监管。除了研究本身，该团队还将利用该项目招募年轻人才，特别是那些来自代表性不足的群体的人才，并共同为研究生提供建议。该项目将帮助劳动力发展，更好地培养有公民责任感的工程师，以解决我们社会面临的挑战性问题。技术总结：在之前的研究中，研究小组发现，模拟ALCL相关乳房植入体特征的表面形貌比平坦对照和其他隐性图案的表面具有更高的细菌负荷。此外，在仅仅培养24小时后，隐性威尔斯孔中的细胞密度比基于二维表面覆盖的平坦对照高约7倍。考虑到三维生物膜结构和与宿主因素的相互作用，差异可能更大，这将在本项目中进行研究。基于这些发现，研究小组假设，不适当的隐性特征可以促进细菌生物膜的形成，群体感应和相关的毒力因子的产生。研究小组进一步假设，这些地形特征对免疫细胞（如巨噬细胞）到达细菌细胞并将其从植入物表面清除存在物理障碍，导致炎症和随后的BIA-ALCL。该团队将通过进行补充实验和细胞跟踪来测试这些假设，以了解表面形貌如何影响细菌和宿主细胞之间的相互作用。这些新信息将填补重要的知识空白，并为理解器械相关并发症和设计更安全的医疗器械提供重要见解。这些结果将有助于FDA更好地准备对涉及智能生物材料的新兴技术进行审查。该团队还将利用这个项目来激励学生进行研究，特别是来自代表性不足的群体的个人。这个奖项反映了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。