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  • Review Article
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Macroscale biomaterials strategies for local immunomodulation

Nature Reviews Materials volume 4, pages 379–397 (2019)Cite this article

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Abstract

The immune system plays key roles in tissue homeostatic and disease processes, and manipulation of innate and adaptive immune responses is of great promise for a wide array of human afflictions, including tissue repair and regeneration, cancer, autoimmune syndromes and chronic infections. Systemic approaches to immunomodulation can correct both hypoactive and hyperactive immunity; however, they typically interfere with the homeostatic role of the immune system at nontarget sites, are associated with lifelong comorbidities and potentially fatal side effects. To overcome these issues, macroscale delivery devices can be placed at sites of interest in the body and engineered to locally control the pharmacokinetics of immunomodulatory agents, including small molecules, macromolecules and cells. In this Review, we outline important cellular targets of immunotherapies in tissue repair and cancer and discuss how macroscale delivery devices can be designed to modulate the release of molecular factors to impact immune cell behaviour, control the fate of delivered therapeutic cells or directly recruit, house and modulate host cells for immunotherapy applications.

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Fig. 1: The local immune microenvironment and priming of adaptive immune responses.
Fig. 2: Cellular targets for immunotherapy in tissue repair and regeneration.
Fig. 3: Cellular targets for cancer immunotherapy.
Fig. 4: Biomaterial scaffolds as biomolecule carriers.
Fig. 5: Biomaterials-assisted cell delivery.
Fig. 6: Biomaterial niches for host–cell modulation.

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Acknowledgements

The authors’ research is supported by grants from the National Cancer Institute (5U01 CA214369; 5R01 CA223255), National Institute of Biomedical Imaging and Bioegineering (5R01 EB023287) and National Institute of Dental and Craniofacial Research (2R01 DE013349). The authors thank M. Brennan and A. Elosegui-Artola for helpful discussions.

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Authors and Affiliations

  1. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Maxence O. Dellacherie, Bo Ri Seo & David J. Mooney

  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

    Maxence O. Dellacherie, Bo Ri Seo & David J. Mooney

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  1. Maxence O. Dellacherie
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  2. Bo Ri Seo
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  3. David J. Mooney
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Contributions

M.O.D. and B.R.S. researched data and wrote the manuscript. M.O.D., B.R.S. and D.J.M. discussed the content and reviewed and/or edited the manuscript.

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Correspondence to David J. Mooney.

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Competing interests

Novartis, sponsored research: D.J.M. Agnovos, consulting: D.J.M. Amgen, sponsored research: D.J.M. Samyang Corp., consulting: D.J.M. Decibel, sponsored research: D.J.M. Merck, sponsored research: D.J.M. Immulus, equity: D.J.M.

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Dellacherie, M.O., Seo, B.R. & Mooney, D.J. Macroscale biomaterials strategies for local immunomodulation. Nat Rev Mater 4, 379–397 (2019). https://doi.org/10.1038/s41578-019-0106-3

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