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.

非技术总结：截至2017年2月，FDA已收到359份乳房植入体相关间变性大细胞淋巴瘤（BIA-ALCL）的医疗器械报告（MDR），其中包括9例死亡。在231份提供了植入物表面信息的报告中，203份报告为毛面植入物，28份报告为光滑植入物。假设BIA-ALCL可能是由乳房植入体上的细菌定植和生物膜（附着细胞的多细胞结构）形成引起的。然而，目前尚不清楚毛面种植体为何与ALCL有特定关联。也不知道如何提高这些植入物的安全性。这一挑战主要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方面的知识差距，以及缺乏设计生物膜形貌的指导原则。锡拉丘兹大学和FDA的团队将合作应对这一挑战，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对表面形貌做出反应，以及如何设计新的表面以防止细菌附着。该项目的结果将为FDA提供关于哪些类型的表面更可能被定殖的新知识和有价值的信息，这将有助于FDA对新型抗生物膜形貌的监管。除了研究，该团队还将利用该项目促进学生培训，特别是来自代表性不足群体的个人;并教育下一代工程师成为解决具有挑战性的技术和社会问题的领导者，以改善人类健康和福祉。技术概述：细菌通过鞭毛，皮利和其他因素如粘附素附着在植入的医疗设备上。微生物的附着导致随后形成生物膜，生物膜是由附着细胞分泌的细胞外基质组成的表面附着的多细胞结构。生物膜感染很难治疗，因为生物膜细胞对抗菌剂和消毒剂的耐受性极高（与它们的抗生素对应物相比高达1000倍）。由于基质材料的性质如表面化学、硬度、疏水性、粗糙度、形貌和电荷影响细菌粘附，因此可以通过调整这些性质来抑制生物膜形成。然而，以前的研究生物膜控制通过改变表面形貌主要是经验性的，缺乏一个机械的理解细菌如何作出决定之间的共生生长和生物膜形成的表面形貌的传感和响应。此外，迄今为止的工程化地形基本上是静态的，不能移动。即使少量细菌细胞附着，它们也可以繁殖并逐渐克服大多数抗生物膜地形。为了更有效地控制生物污垢，重要的是设计新的动态材料，可以根据环境线索改变表面形貌。动态材料既可以防止初始细菌粘附，又可以破坏已建立的生物膜，使定殖者分散成寄生形式，在那里它们可以被宿主免疫系统和抗生素治疗根除。该团队假设，特定的微米级表面形貌可以合理设计，以抑制细菌生物膜的形成，同时促进哺乳动物细胞的粘附。还假设所建立的生物膜可以在需要时通过按需触发通过这种表面形貌的动态变化来去除。该团队将通过研究细菌对不同表面形貌的反应来验证这些假设，使用大肠杆菌，铜绿假单胞菌和金黄色葡萄球菌作为模型物种。该奖项反映了NSF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而被认为值得支持。