Design of next-generation degradable polymer materials with immunoregulatory properties

合成聚合物材料提供优化的性能，使多样化的医疗设备技术成为可能。虽然这些设备是医学进步的基础，但其临床应用充满了挑战：患者经常会遇到不良副作用，需要后续治疗、设备拆卸和持续治疗。其中许多是由与材料组成有关的炎症引起的，这突显了开发能够提供对不受欢迎的免疫细胞行为的内在控制的新型聚合物的必要性。拟议的研究计划将满足这一需求，从生物学中获得灵感，建立一系列能够提供有效的炎症调节剂的可降解聚合物材料。我们的实验室最近开发了免疫调节材料，方法是将人体固有调节系统的分子直接构建到可降解的聚合物骨架中，展示了在随时间分解的材料中传递调节构件的效用。根据我们在可降解聚酯材料方面的专业知识，我们将应用这种方法来构建材料家族，该材料家族的灵感来自于细胞用来自我调节多种细胞类型的炎症的稳定小分子。使用这些分子，我们将产生一个在不同生物材料应用中具有实用价值的调节聚合物文库。这将通过建立一种多元化的合成和分析方法来实现，使我们能够测试更多的配方，提取更多信息进行彻底优化。但在实践中，人体免疫系统和材料表面的相互作用在生物上是复杂的。我们最近的工作强调了这种复杂性在不同的时间点，并激发了对材料的需求，这些材料可以像免疫系统一样改变它们的调节行为。基于对细胞刺激做出反应的其他材料应用方面的专业知识，我们将设计材料组合物，当炎症细胞也指示它们时，这些材料组合物可以放大我们材料家族的调节靶点的释放。拟议的研究计划将利用学科领域、技能和人员身份的多样性来实现这些目标。这将促进自然科学和工程领域高素质人员(HQP)的有效技能发展；受训人员将从事跨越聚合物开发、数据分析和利用免疫学工具构建生物材料的多种技术。研究团队的跨学科性质将很好地转化为生物技术新兴领域所需的批判性思维。提出的研究目标和HQP的协作团队的组合将加强Discovery研究在材料设计方面的翻译，使下一代可降解医疗设备成为可能。通过为未来基于新型聚合物的医疗设备的商业化提供坚实的基础，该计划支持了加拿大作为医疗设备技术的始终如一的创新者的地位。

Synthetic polymer materials provide optimized properties that enable diverse medical device technologies. While foundational to medical advances, the clinical application of these devices is fraught with challenges: patients frequently encounter undesired side effects that require follow-up treatments, device removal, and ongoing therapies. Many of these are caused by inflammation related to material composition, highlighting the need for novel polymer development that can provide inherent control of undesired immune cell behaviour. The proposed research program will address this need, taking inspiration from biology to build a family of degradable polymer materials that can deliver potent regulators of inflammation. Our lab recently developed immune regulatory materials by building molecules of the body's inherent regulatory systems directly into degradable polymer backbones, demonstrating the utility of delivering regulatory building blocks in materials that break down over time. From our expertise in degradable polyester materials, we will apply this approach to build family of materials inspired by the stable small molecules cells use to self-regulate inflammation in multiple cell types. Using these molecules, we will generate a library of regulatory polymers with utility in diverse biomaterial applications. This will be achieved by building a multiplexed approach to synthesis and analysis, allowing us to test more formulations and extract more information for thorough optimization. In practice, the interaction of the body's immune system and material surfaces is biologically complex. Our recent work highlights this complexity at different time points and motivates the need for materials that can change their regulatory behaviour as the immune system does. Building from expertise in other material applications that respond to cellular stimuli, we will design material compositions that can amplify the release of regulatory targets of our material family when inflammatory cells instructs them too. The proposed research program will draw from diversity in subject areas, skills, and personnel identity to achieve these goals. This will facilitate effective skill development for highly qualified personnel (HQP) in natural science and engineering; trainees will engage in multiple techniques that cross polymer development, data analysis, and harnessing the tools of immunology to build biomaterials. The interdisciplinary nature of the research team will translate well to the critical thinking required in emerging areas of biotechnology. The combination of proposed research goals, and a collaborate team of HQP, will potentiate translation of this Discovery research in material design, enabling next-generation degradable medical devices. By providing a strong foundation to future commercialization of medical devices based on new polymers, this program supports Canada's position as a consistent innovator in medical device technologies.