Rational Design of Dynamic Antifouling Material Topographies for Safer Medical Devices

合理设计动态防污材料形貌，提高医疗器械安全性

• 批准号: 1836723
• 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: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1836723&HistoricalAwards=false
• 关键词: Rational; Design; Dynamic; Antifouling; Material

Non-technical Summary: As of February 2017, the FDA had received 359 medical device reports (MDRs) of breast implant associated anaplastic large cell lymphoma (BIA-ALCL), including nine deaths. Among the 231 reports that had information about the implant surface, 203 were reported to be textured implants and 28 were reported to be smooth implants. It has been hypothesized that BIA-ALCL may be caused by bacterial colonization and formation of biofilms (multicellular structures of attached cells) on breast implants. However, it is not clear why textured implants have a specific association with ALCL. It is also not known how to improve the safety of these implants. This challenge is largely due to the knowledge gap in the fundamental understanding of how surface topography affects microbial adhesion and biofilm formation, as well as the lack of guiding principles for the design of antifouling topographies. The teams at Syracuse University and FDA will collaborate to address this challenge and gain critical new knowledge through complementary studies. Specifically, the team will collaborate to investigate how bacteria respond to surface topography during attachment and how to engineer new surfaces to prevent bacterial attachment. The results of this project will provide new knowledge and valuable information to FDA about what types of surfaces are more likely to be colonized, which will be useful for FDA's regulation of novel anti-biofilm topographies. In addition to research, the team will also leverage this project to promote student training, especially the individuals from underrepresented groups; and educate the next generation of engineers to be leaders solving challenging technical and societal problems to improve human health and well being.Technical Summary: Bacteria attach to implanted medical devices using flagella, pili, and other factors such as adhesins. The attachment of microbes leads to the subsequent formation of a biofilm, which is a surface-attached multicellular structure comprised of an extracellular matrix secreted by the attached cells. Biofilm infections are difficult to treat because of extremely high tolerance of biofilm cells to antimicrobials and disinfectants (up to 1000 times higher compared to their planktonic counterparts). Since properties of the substratum material such as surface chemistry, stiffness, hydrophobicity, roughness, topography, and charge affect bacterial adhesion, biofilm formation may be inhibited by tailoring these properties. However, previous research on biofilm control by altering surface topography is largely empirical and lacks a mechanistic understanding of how bacteria make a decision between planktonic growth and biofilm formation by sensing and responding to surface topography. In addition, the engineered antifouling topographies to date are largely static and cannot move. Even if a small number of bacteria cells attach, they can multiply and gradually overcome most anti-biofilm topographies. To more effectively control biofouling, it is important to engineer new dynamic materials that can change surface topography upon an environmental cue. A dynamic material can both prevent initial bacterial adhesion and disrupt established biofilms, causing the colonizers to disperse into planktonic form where they can be eradicated by the host immune system and antibiotic treatment. The team hypothesizes that specific micron-scale surface topographies can be rationally designed to inhibit bacterial biofilm formation while promoting the adhesion of mammalian cells. It is also hypothesized that established biofilms can be removed by dynamic changes in such surface topographies via on-demand triggering when needed. The team will test these hypotheses by studying how bacteria respond to different surface topographies using Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus as model species.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.

非技术摘要：截至2017年2月，FDA已收到359份医疗器械报告（MDR），包括乳腺植入物相关的间变性大细胞淋巴瘤（BIA-ALCL），包括9例死亡。在有关于植入物表面的信息的231个报告中，据报道203个是纹理植入物，据报道有28个是光滑的植入物。已经假设BIA-ALCL可能是由细菌定植和乳腺植入物上生物膜（附着细胞的多细胞结构）形成引起的。但是，尚不清楚为什么纹理植入物与ALCL具有特定的关联。也不知道如何提高这些植入物的安全性。这一挑战在很大程度上是由于对表面形貌如何影响微生物粘附和生物膜形成的基本理解的知识差距，以及缺乏针对反染色地形设计的指导原则。锡拉丘兹大学和FDA的团队将合作解决这一挑战，并通过互补研究获得关键的新知识。具体来说，该团队将合作研究细菌在附着过程中如何应对表面地形以及如何设计新表面以防止细菌附着。该项目的结果将为FDA提供有关哪些类型的表面更可能被殖民的新知识和有价值的信息，这对于FDA的调节对新型抗生物胶片的调节将很有用。除研究外，团队还将利用该项目来促进学生培训，尤其是来自代表性不足小组的个人；并教育下一代工程师是解决具有挑战性的技术和社会问题以改善人类健康和福祉的领导者。技术摘要：使用鞭毛，pili和其他因素（例如粘合剂）附着在植入的医疗设备上的细菌。微生物的附着会导致生物膜的随后形成，该生物膜是由附着的细胞分泌的细胞外基质组成的表面连接多细胞结构。由于生物膜细胞对抗菌和消毒剂的耐受性极高的耐受性（与它们的浮游物质相比，高达1000倍），因此很难治疗生物膜感染。由于基质材料的性质，例如表面化学，僵硬，疏水性，粗糙度，地形和电荷会影响细菌粘附，因此可以通过调整这些特性来抑制生物膜形成。然而，先前通过改变表面地形来控制生物膜控制的研究在很大程度上是经验性的，并且缺乏对细菌如何通过传感和对表面地形反应来做出浮游生物生长和生物膜形成之间做出决策的机械理解。此外，迄今为止，工程的防污式地形在很大程度上是静态的，无法移动。即使少数细菌细胞附着，它们也可以繁殖并逐渐克服大多数抗生物膜的地形。为了更有效地控制生物污染，重要的是要设计新的动态材料，这些动态材料可以在环境提示上改变表面地形。动态材料既可以防止初始细菌粘附，又可以破坏建立的生物膜，从而导致殖民者分散成浮游生物形式，从而可以通过宿主免疫系统和抗生素处理来消除它们。该团队假设特定的微米尺度表面地形可以是合理设计的，可以抑制细菌生物膜的形成，同时促进哺乳动物细胞的粘附。还可以假设，可以通过在需要时通过按需触发来消除建立的生物膜。该团队将通过研究细菌如何使用大肠杆菌，假单胞菌和金黄色葡萄球菌作为模型物种来对不同的表面地形进行反应来检验这些假设。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识优点和广泛的crietia crietia criperia cribity crietia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia criperia recectia recteria rection。

项目成果

How microbes read the map: Effects of implant topography on bacterial adhesion and biofilm formation

• DOI: 10.1016/j.biomaterials.2020.120595
• 发表时间: 2021-01-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Lee, Sang Won;Phillips, K. Scott;Ren, Dacheng
• 通讯作者: Ren, Dacheng