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

我们经常说，某件事要么是解决方案的一部分，要么是问题的一部分，但在伤口敷料的情况下，它们往往是两者！虽然伤口敷料是一项重要的愈合技术，因为它们可以保护愈合的伤口并保持伤口湿润，但它们也为细菌的附着和生长提供了绝佳的场所。当细菌聚集在一起并附着在一个表面上——无论是愈合烧伤的表面还是绷带的表面——它们会形成生物膜感染，这种感染很难用普通抗生素治疗。该项目支持开发防止生物膜的先进材料，基于已经在医院环境中使用的材料。生活在生物膜中的细菌需要能量和营养物质，生物膜越大，环境就越难以将这些物质输送给细菌。通过消除一种关键的能量来源，一种叫做丙酮酸的分子，生物膜就不能生长，而且更容易处理。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在伤口敷料上生长的能力，使感染更容易治疗。这个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。研究生们还通过创建设计驱动的材料活动来参与社区外展活动，将工程与生活联系起来，这是一个针对中学女生和非二元青年的课后项目。这些教育活动以有趣和创造性的方式为中学生提供了接触先进工程思想的机会，从而使他们对工程职业产生了早期的兴趣。最后，为佛蒙特大学的本科生开设了一门专业发展课程，这些学生作为课后活动的导师，加强了工程教育、科学交流和佛蒙特州未来多年的职业人才库的指导。技术摘要：这个NSF项目旨在创造一种新的水凝胶材料来对抗细菌生物膜感染。生物膜是附着在表面的细菌聚集体，由于其对抗菌剂的特殊先天耐药性，是伤口发病率和死亡率的主要原因。水凝胶伤口敷料对促进伤口愈合至关重要，但它们容易被细菌定植，这就需要频繁更换敷料，严重阻碍愈合，并可能导致败血症、截肢或死亡。本研究通过结合酶和非酶的生物膜预防手段，增强了伤口敷料海藻酸盐，一种由褐海藻制成的天然聚合物。据推测，丙酮酸是厌氧金黄色葡萄球菌和铜绿假单胞菌在生物膜中的主要能量来源，因此消耗丙酮酸有助于阻止细菌形成三维生物膜结构。该项目在材料设计方面雄心勃勃，通过创建酶和仿生，非酶褐藻酸盐水凝胶配方来隔离丙酮酸，并测试每种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。研究生通过为连接工程与生活（LEL）创建设计驱动的材料活动来参与社区外展，LEL是一个针对中学女生和非二元青年的课后项目。这些教育活动以有趣和创造性的方式为中学生提供了接触先进工程思想的机会，从而培养了他们对工程职业的早期兴趣。最后，为佛蒙特大学的本科生开设了一门专业发展课程，这些学生作为LEL课后活动的导师，加强了未来几年佛蒙特州STEM劳动力的工程教育、科学交流和指导。该项目由生物材料计划和促进竞争性研究的既定计划（EPSCoR）共同资助。该奖项反映了美国国家科学基金会的法定使命，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.