CAREER: Metabolite-Depleting Materials as an Anti-Biofilms Strategy

职业：代谢物消耗材料作为抗生物膜策略

• 批准号: 2341706
• 负责人: Amber Doiron
• 金额: $ 59.86万
• 依托单位: University of Vermont & State Agricultural College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2029-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341706&HistoricalAwards=false
• 关键词: CAREER; Metabolite; Depleting; Materials; Anti

Non-Technical AbstractIt is often said that something is either part of the solution or part of the problem, but in the case of wound dressings, they are often both! While wound dressings are an essential technology for healing because they protect the healing wound and keep it moist, they also make an excellent place for bacteria to attach and grow. When bacteria group together and attach to a surface—whether it is the surface of a healing burn or the surface of a bandage—they can form a biofilm infection that becomes very difficult to treat with normal antibiotics. This project supports the development of advanced materials that prevent biofilms, based on materials that are already used in the hospital setting. Bacteria that live in biofilms require energy and nutrients, and the larger the biofilm becomes, the more difficult it is for the surroundings to deliver these to the bacteria. By eliminating a key source of energy, a molecule called pyruvate, the biofilm is not able to grow and is much more easily treated. By designing a material capable of destroying pyruvate, this research project limits the ability of biofilms to grow on wound dressings and makes infections easier to treat. Methods and results from this project are integrated into a graduate-level course at the University of Vermont on biomaterials design and testing. Graduate students also engage in community outreach by creating a design-driven materials activity for Linking Engineering to Life, an afterschool program for middle school-aged girls and non-binary youth. These educational activities provide middle schoolers with exposure to advanced engineering ideas in a fun and creative way so they develop an early interest in engineering careers. Finally, a professional development course for University of Vermont undergraduate students who act as mentors for after-school activities strengthens engineering education, scientific communication, and mentorship in the Vermont career talent pool for many years to come.Technical AbstractThis NSF project aims to create a new hydrogel material that combats bacterial biofilm infections. Biofilms, aggregates of bacteria attached to surfaces, are the primary cause of wound morbidity and mortality due to their extraordinary innate resistance to antimicrobial agents. Hydrogel wound dressings are critical in promoting the healing of wounds, yet they are susceptible to colonization by bacteria, which necessitates frequent dressing changes, significantly impedes healing, and can result in sepsis, amputation, or death. This research enhances the wound dressing material alginate, a natural polymer made from brown seaweed, by incorporating enzymatic and non-enzymatic means of biofilm prevention. Pyruvate is hypothesized to be a main energy source for anaerobic Staphylococcus aureus and Pseudomonas aeruginosa bacteria in biofilms, so depleting pyruvate helps prevent bacteria from creating the three-dimensional biofilm structure. This project is ambitious in its approach to materials design by creating both enzymatic and biomimetic, non-enzymatic formulations of alginate hydrogels that sequester pyruvate and testing each for material properties and biofilm prevention. Research findings and the design-based methodology from this project are integrated into a graduate-level course at the University of Vermont on biomaterials design and testing. Graduate students engage in community outreach by creating a design-driven materials activity for Linking Engineering to Life (LEL), an afterschool program for middle school-aged girls and non-binary youth. These educational activities provide middle schoolers with exposure to advanced engineering ideas in a fun and creative way to develop an early interest in engineering careers. Finally, a professional development course for University of Vermont undergraduate students who act as mentors for LEL after-school activities strengthens engineering education, scientific communication, and mentorship in the Vermont STEM workforce for years to come.This project is jointly funded by the Biomaterials Program and the Established Program to Stimulate Competitive Research (EPSCoR).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.

非技术摘要人们常说，某件事要么是解决方案的一部分，要么是问题的一部分，但就伤口敷料而言，它们往往两者兼而有之。虽然伤口敷料是愈合的一项重要技术，因为它们可以保护正在愈合的伤口，并且可以保护愈合的伤口。当细菌聚集在一起并附着在表面上时（无论是正在愈合的烧伤表面还是绷带表面），它们也会形成生物膜感染，从而使其保持湿润。用普通抗生素治疗变得非常困难。该项目支持开发预防生物膜的先进材料，该材料基于医院环境中已使用的材料。生物膜中的细菌需要能量和营养，而生物膜越大，周围环境就越困难。通过消除一种称为丙酮酸的关键能量来源，生物膜无法生长并且更容易处理。通过设计一种能够破坏丙酮酸的材料，该研究项目限制了生物膜的能力。在伤口敷料上生长并使感染更容易治疗。该项目的方法和结果被纳入佛蒙特大学生物材料设计和测试的研究生课程中。研究生还通过创建设计驱动的方式参与社区推广。 “将工程与生活联系起来”的材料活动，这是一项针对中学生和非二元青年的课外计划。这些教育活动以有趣和创造性的方式让中学生接触先进的工程理念，从而培养他们对工程职业的早期兴趣。最后，为大学提供专业发展课程佛蒙特州本科生在课外活动中充当导师，在未来的许多年里加强佛蒙特州职业人才库中的工程教育、科学交流和指导。技术摘要该 NSF 项目旨在创造一种新型水凝胶材料，以对抗细菌生物膜感染。生物膜是附着在表面的细菌聚集体，是伤口发病和死亡的主要原因，因为它们对抗菌药物具有非凡的先天抵抗力，对于促进伤口愈合至关重要，但它们很容易定植。该研究通过结合酶促和非酶促方法增强了伤口敷料海藻酸盐（一种由棕色海藻制成的天然聚合物）。生物膜预防丙酮酸被重新捕获为生物膜中厌氧金黄色葡萄球菌和铜绿假单胞菌的主要能源。消耗丙酮酸盐有助于防止细菌形成三维生物膜结构。该项目在材料设计方法上雄心勃勃，通过创建可隔离丙酮酸盐的酶促和仿生、非酶促藻酸盐水凝胶配方，并测试每种配方的材料特性和生物膜预防。该项目的研究成果和基于设计的方法被纳入佛蒙特大学关于生物材料设计和测试的研究生课程中，研究生通过创建一个项目来参与社区外展。连接工程与生活 (LEL) 的设计驱动材料活动，这是一项针对中学生和非二元青年的课外计划。这些教育活动以有趣和创造性的方式让中学生接触先进的工程理念，以培养他们的能力。最后，为担任 LEL 课外活动导师的佛蒙特大学本科生开设的专业发展课程将在未来几年加强对佛蒙特州 STEM 劳动力的工程教育、科学交流和指导。由生物材料联合资助计划和刺激竞争性研究的既定计划 (EPSCoR)。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。