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

非技术摘要人们常说，有些东西要么是解决方案的一部分，要么是问题的一部分，但在伤口敷料的情况下，它们往往都是！虽然伤口敷料是愈合的基本技术，因为它们可以保护愈合的伤口并保持湿润，但它们也是细菌附着和生长的绝佳场所。当细菌聚集在一起并附着在一个表面上时，无论是愈合的烧伤表面还是绷带表面，它们都能形成生物膜感染，用常规抗生素治疗变得非常困难。该项目支持基于医院环境中已经使用的材料开发防止生物膜的先进材料。生活在生物膜中的细菌需要能量和营养物质，生物膜越大，周围环境就越难将这些物质传递给细菌。通过消除一种关键的能量来源，一种称为丙酮酸的分子，生物膜无法生长，并且更容易治疗。通过设计一种能够破坏丙酮酸盐的材料，该研究项目限制了生物膜在伤口敷料上生长的能力，并使感染更容易治疗。该项目的方法和结果被整合到佛蒙特大学生物材料设计和测试的研究生课程中。研究生还通过为将工程与生活联系起来创建一个设计驱动的材料活动来参与社区外展，这是一个针对中学适龄女孩和非二元青年的课后计划。这些教育活动为中学生提供了以有趣和创造性的方式接触先进工程思想的机会，使他们对工程职业产生早期兴趣。最后，专业发展课程佛蒙特大学本科生谁作为课外活动的导师加强工程教育，科学交流，并在佛蒙特州的职业人才库导师多年来。技术摘要NSF项目旨在创建一个新的水凝胶材料，对抗细菌生物膜感染。生物膜是附着于表面的细菌聚集体，由于其对抗菌剂的非凡先天抗性，是伤口发病和死亡的主要原因。水凝胶伤口敷料在促进伤口愈合方面至关重要，但它们容易被细菌定植，这需要频繁更换敷料，显著阻碍愈合，并可能导致败血症、截肢或死亡。这项研究通过结合酶和非酶的生物膜预防手段来增强伤口敷料材料藻酸盐，藻酸盐是一种由褐藻制成的天然聚合物。丙酮酸被假设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量来源，因此消耗丙酮酸有助于防止细菌产生三维生物膜结构。该项目在材料设计方面雄心勃勃，通过创建酶促和仿生，非酶促的海藻酸盐水凝胶配方，螯合丙酮酸盐，并测试每种材料的性能和生物膜预防。该项目的研究成果和基于设计的方法被整合到佛蒙特大学生物材料设计和测试的研究生课程中。研究生通过为将工程与生活联系起来（LEL）创建一个设计驱动的材料活动来参与社区外展，LEL是一个针对中学适龄女孩和非二元青年的课后计划。这些教育活动为中学生提供了一个有趣和创造性的方式接触先进的工程思想，以培养对工程职业的早期兴趣。最后，佛蒙特大学本科生的专业发展课程，作为LEL课后活动的导师，加强了工程教育，科学交流，该项目由生物材料计划和刺激竞争力研究的既定计划（EPSCoR）共同资助。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，被认为值得支持。

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.