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Multiscale engineering of immune cells and lymphoid organs

Abstract

Immunoengineering applies quantitative and materials-based approaches for the investigation of the immune system and for the development of therapeutic solutions for various diseases, such as infection, cancer, inflammatory diseases and age-related malfunctions. The design of immunomodulatory and cell therapies requires the precise understanding of immune cell formation and activation in primary, secondary and ectopic tertiary immune organs. However, the study of the immune system has long been limited to in vivo approaches, which often do not allow multidimensional control of intracellular and extracellular processes, and to 2D in vitro models, which lack physiological relevance. 3D models built with synthetic and natural materials enable the structural and functional recreation of immune tissues. These models are being explored for the investigation of immune function and dysfunction at the cell, tissue and organ levels. In this Review, we discuss 2D and 3D approaches for the engineering of primary, secondary and tertiary immune structures at multiple scales. We highlight important insights gained using these models and examine multiscale engineering strategies for the design and development of immunotherapies. Finally, dynamic 4D materials are investigated for their potential to provide stimuli-dependent and context-dependent scaffolds for the generation of immune organ models.

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Fig. 1: The different levels of the immune response.
Fig. 2: Engineering bone marrow niches.
Fig. 3: Engineering thymus tissue.
Fig. 4: Engineering activated T cells.
Fig. 5: Engineering the germinal centre.
Fig. 6: Temperature-responsive, photo-responsive and magnetoresponsive 4D materials.
Fig. 7: Electroresponsive, pH-responsive and cellular 4D materials.

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Acknowledgements

The authors acknowledge financial support from the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (1R01AI132738-01A1 awarded to A.S.), the Innovative Molecular Analysis Technology programme of the US National Cancer Institute (NIH R33-CA212968-01 awarded to A.S.), a US National Science Foundation CAREER award (DMR-1554275 awarded to A.S.), a US Department of Defense Congressionally Directed Medical Research Program (CDMRP) cancer career development award (W81XWH-17-1-0215 awarded to A.S.) and the 3 M Non-Tenured Faculty Award (awarded to A.S.).

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S.K., S.B.S., P.G. and A.S. wrote the article. A.S. edited and reviewed the article. All authors contributed to the discussion of the content.

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Correspondence to Ankur Singh.

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Kim, S., Shah, S.B., Graney, P.L. et al. Multiscale engineering of immune cells and lymphoid organs. Nat Rev Mater 4, 355–378 (2019). https://doi.org/10.1038/s41578-019-0100-9

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