Biomimetic Zwitterionic Functional Materials for Immunomodulation

非技术综述目前，无污染材料或免疫调节剂很多。非污染材料可以有效地抵抗复杂介质中的非特异性相互作用，但具有惰性，不具有任何免疫抑制特性。同时，免疫调节药物或分子能够特异地相互作用和调节生物系统，但缺乏隐蔽性。对于许多应用来说，这两个功能是非常理想的。然而，当这两种材料和药物一起使用时，会损害它们的功能。在本项目中，将开发和研究一种能够直接调节免疫反应的无药物隐形生物材料，从而在一个生物材料中实现这两种功能。这项工作的成功不仅将为生物材料的基本设计提供新的见解，而且对药物和基因输送、癌症免疫治疗和细胞治疗等应用具有深远的影响。对该项目的支持将为研究生和本科生提供高度跨学科的研究机会，特别是代表不足的学生。这项工作的知识将通过组织的国际会议、教授的新课程和开展的推广活动来传播。技术SUMMARY磷酸丝氨酸(PS)是一种天然的免疫信号分子，在生理条件下起到免疫抑制的作用。由于两性离子磷酸丝氨酸模拟聚合物(ZPS)带负电荷而不具有隐身特性，因此人们认为ZPS在一种生物材料中可以同时实现隐身和免疫抑制。本项目的目的是研究ZPS的双重功能特性，并研究其免疫调节功能的机制。此外，还将探讨ZPS在药物传递中的重要性和潜在应用。这项拟议工作的成功将阐明如何将生物特性整合到惰性生物材料中或赋予活性生物材料隐形性能的概念。它不仅将为生物材料的基本设计提供新的见解，而且还将丰富免疫调节生物材料的武器库，用于广泛的生物医学应用。这项工作的知识将通过举办国际会议、教授新课程和开展外联活动来传播。PI将通过组织或联合组织国际会议、编辑特刊和吸引学生参与，继续促进两性离子生物材料领域的发展。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL SUMMARY At present, there are many non-fouling materials or immunomodulatory drugs. Non-fouling materials can effectively resist nonspecific interactions in complex media, but are inert without any immunosuppressive properties. At the same time, immunomodulatory drugs or molecules are capable of specifically interacting and regulating biologic systems, but lack stealth properties. For many applications, these two functions are highly desirable. However, these two types of materials and drugs compromise their functions when they are used together. In this project, a drug-free stealth biomaterial capable of directly regulating the immune response will be developed and studied so that both functions will be achieved in one biomaterial. The success of this work will not only provide new insights into the fundamental design of biomaterials, but also have far-reaching implications for applications including drug and gene delivery, cancer immunotherapy and cell therapy. Support of this project will provide highly interdisciplinary research opportunities to graduate and undergraduate students, particularly under-represented students. Knowledge from this work will be disseminated through international conferences organized, new courses taught, and outreach activities engaged.TECHNICAL SUMMARYPhosphoserine (PS), an immune-signaling molecule in nature, serves as an immunosuppressant under physiological conditions. It is hypothesized that zwitterionic phosphoserine-mimic polymer (ZPS) will be able to achieve both stealth and immunosuppressive properties in one biomaterial since PS is negatively charged without stealth properties. The aims of this project are to examine the dual-functional properties of ZPS and investigate the mechanisms accounting for its immunomodulatory functions. Moreover, the importance and potential application of ZPS in drug delivery will be explored. The success of the proposed work will elucidate the concept about how to integrate biological properties into inert biomaterials or endow active biomaterials with stealth properties. It will not only provide new insights into the fundamental design of biomaterials, but also enriches the arsenal of immunomodulatory biomaterials for a broad range of biomedical applications. Knowledge from this work will be disseminated through international conferences organized, new courses taught, and outreach activities engaged. The PI will continue to promote the field of zwitterionic biomaterials through organizing or co-organizing international conferences, editing special issues and engaging student participations.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.