Biomimetic Zwitterionic Functional Materials for Immunomodulation

目前，有许多非污染材料或免疫调节药物。无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，但没有任何免疫抑制特性。同时，免疫调节药物或分子能够特异性地相互作用和调节生物系统，但缺乏隐形特性。对于许多应用，这两个功能是非常需要的。然而，这两种类型的材料和药物在一起使用时会损害它们的功能。在该项目中，将开发和研究能够直接调节免疫反应的无药物隐形生物材料，以便在一种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础设计提供新的见解，而且对药物和基因递送，癌症免疫治疗和细胞治疗等应用具有深远的影响。该项目的支持将为研究生和本科生，特别是代表性不足的学生提供高度跨学科的研究机会。这项工作的知识将通过组织国际会议、教授新课程和开展外联活动来传播。技术概述磷酸丝氨酸（PS）是自然界中的一种免疫信号分子，在生理条件下可作为免疫抑制剂。假设两性离子磷酸丝氨酸模拟聚合物（ZPS）将能够在一种生物材料中实现隐形和免疫抑制性质，因为PS带负电荷而没有隐形性质。本研究的目的是探讨ZPS的双重功能特性，并探讨其免疫调节功能的机制。此外，ZPS在药物传递中的重要性和潜在的应用进行了探讨。这项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特性的概念。它不仅将为生物材料的基本设计提供新的见解，而且还丰富了免疫调节生物材料的军火库，用于广泛的生物医学应用。将通过组织国际会议、教授新课程和开展外联活动传播这项工作的知识。PI将继续通过组织或共同组织国际会议，编辑特别问题和吸引学生参与来促进两性离子生物材料领域。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 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.