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Engineering complexity into protein-based biomaterials for biomedical applications

Nature Reviews Materials (2025)Cite this article

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Abstract

Protein-based biomaterials are growing in popularity for biomedical applications, in part owing to their innate ability to interface with biological systems. These materials, in the form of fibres, nanoparticles and hydrogels, have shown promise as drug delivery vehicles, tissue scaffolds and vaccines. Moreover, the explosion of protein engineering tools and the inception of de novo protein design have transformed our ability to explore new protein structures, enabling the creation of novel materials with diverse properties and furthering their customization for various applications. In this Perspective, we explore the coming of age of protein engineering technologies and their impact on biomaterials. Starting with naturally sourced materials, we highlight common protein building blocks and fabrication methods, as well as recent applications of each. We subsequently explore rationally designed materials and conclude by discussing the potential impacts that de novo design will have on the biomaterials field.

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Fig. 1: Overview of the three approaches to designing protein-based materials.
Fig. 2: Examples of methods used to fabricate and design protein-based biomaterials.
Fig. 3: Functionalizing protein-based biomaterials for therapeutic effects.

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Acknowledgements

The authors acknowledge support for this work in the form of two Graduate Research Fellowships Program Awards (DGE-2140004 to N.E.G. and C.M.H.) from the National Science Foundation, a Maximizing Investigators’ Research Award (R35GM138036 to C.A.D.) and Other Awards (P01AI167966 and 1U19AI181881 to N.P.K.) from the NIH, and an Award (HR00112420369 to C.A.D.) from the Defense Advanced Research Projects Agency.

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  1. These authors contributed equally: Nicole E. Gregorio, Cyrus M. Haas.

Authors and Affiliations

  1. Department of Bioengineering, University of Washington, Seattle, WA, USA

    Nicole E. Gregorio & Cole A. DeForest

  2. Department of Chemical Engineering, University of Washington, Seattle, WA, USA

    Cyrus M. Haas & Cole A. DeForest

  3. Institute of Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA, USA

    Cyrus M. Haas & Cole A. DeForest

  4. Institute for Protein Design, University of Washington, Seattle, WA, USA

    Cyrus M. Haas, Neil P. King & Cole A. DeForest

  5. Department of Biochemistry, University of Washington, Seattle, WA, USA

    Neil P. King

  6. Department of Chemistry, University of Washington, Seattle, WA, USA

    Cole A. DeForest

  7. Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA

    Cole A. DeForest

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Gregorio, N.E., Haas, C.M., King, N.P. et al. Engineering complexity into protein-based biomaterials for biomedical applications. Nat Rev Mater (2025). https://doi.org/10.1038/s41578-025-00861-8

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