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Engineering immunomodulatory biomaterials for type 1 diabetes

Abstract

A cure for type 1 diabetes (T1D) would help millions of people worldwide but remains elusive to date. Tolerogenic vaccines and β-cell replacement therapy are complementary therapies that seek to address aberrant T1D autoimmune attack and subsequent β-cell loss. However, both approaches require some form of systemic immunosuppression, imparting risks to the patient. Biomaterials-based tools enable localized and targeted immunomodulation, and biomaterial properties can be designed and combined with immunomodulatory agents to locally instruct specific immune responses. In this Review, we discuss immunomodulatory biomaterial platforms for the development of T1D tolerogenic vaccines and β-cell replacement devices. We investigate nanoparticles and microparticles for the delivery of tolerogenic agents and autoantigens and as artificial antigen-presenting cells, and we highlight how bulk biomaterials can be used to provide immune tolerance. We examine biomaterials for drug delivery and as immuno-isolation devices for cell therapy and islet transplantation and explore synergies with other fields for the development of new T1D treatment strategies.

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Fig. 1: Immunomodulation biomaterial vaccines.
Fig. 2: Temporal sequence of host immune response to islet transplants.
Fig. 3: Immunomodulatory biomaterial approaches for islet and β-cell transplantation.

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Acknowledgements

The authors are grateful for funding from the US National Institutes of Health (NIH) grants DK104208 and DK100654 (C.L.S.), DE027301, DK098589 and AI133623 (B.G.K.) and DK108736 (C.L.S. and B.G.K.), as well as from Juvenile Diabetes Research Foundation (JDRF) grants 3-SRA-2017-347-M-B and 3-SRA-2018-683-S-B (C.L.S.). J.M.S. is supported by the NIH training grant DK108736.

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C.L.S. and B.G.K. conceived the manuscript; C.L.S. designed the figures; and all authors made substantial contributions to the content, writing, and editing of the manuscript.

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Correspondence to C. L. Stabler or B. G. Keselowsky.

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Stabler, C.L., Li, Y., Stewart, J.M. et al. Engineering immunomodulatory biomaterials for type 1 diabetes. Nat Rev Mater 4, 429–450 (2019). https://doi.org/10.1038/s41578-019-0112-5

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