Design of next-generation degradable polymer materials with immunoregulatory properties

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.