Biomimetic Zwitterionic Functional Materials for Immunomodulation

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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.