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Immune-compatible designs of semiconducting polymers for bioelectronics with suppressed foreign-body response

Nature Materials (2025)Cite this article

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Abstract

One of the greatest obstacles to achieving implantable electronics with long-term functionality and minimized inflammatory reactions is the immune-mediated foreign-body response (FBR). Recently, semiconducting polymers with mixed electron–ion conductivity have been demonstrated as promising candidates to achieve direct electrical interfacing on bio-tissues. However, there is limited understanding of their immune compatibility in vivo, and strategies for minimizing the FBR through molecular design remain underexplored. Here we introduce a set of molecular design strategies for enhancing the immune compatibility of semiconducting polymers. Specifically, we show that selenophene, when incorporated in the backbone, can mitigate the FBR by suppressing macrophage activation. In addition, side-chain functionalization with immunomodulatory groups decreases the FBR further by downregulating the expression of inflammatory biomarkers. Together, our synthesized polymers achieve suppression of the FBR by as much as 68% (as indicated by the collagen density). In the meantime, these immune-compatible designs still provide a high charge-carrier mobility of around 1 cm2 V−1 s−1. We anticipate that such immune-compatible design principles can be translated to a variety of conjugated polymers to suppress the FBR for implantable applications.

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Fig. 1: Immune-compatible designs of semiconducting polymers with suppressed FBR.
Fig. 2: Reduced collagen deposition and immune cell populations on the polymer films with immune-compatible designs.
Fig. 3: The immune-compatible designs induce more anti-inflammatory macrophages.
Fig. 4: Macrophage activation was suppressed by selenophene through in vitro study.
Fig. 5: OECT characterization and implantable application for the immune-compatible semiconducting polymers.

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Data availability

The data that support the findings of this study are available within this Article and its Supplementary Information. Additional data are available from the corresponding authors upon request. Source data are provided with this paper.

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Acknowledgements

This work is supported by the US National Institutes of Health Director’s New Innovator Award (1DP2EB034563), the National Science Foundation (DMR-2105367), the US Office of Naval Research (N00014-21-1-2266) and the start-up fund from The University of Chicago. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Y.-H.K. acknowledges NRF RS-2023-00301974. S. Wang is a CZ Biohub Investigator.

Author information

Author notes

  1. Seounghun Kang

    Present address: Department of Chemistry, Soongsil University, Seoul, Republic of Korea

  2. These authors contributed equally: Nan Li, Seounghun Kang, Zhichang Liu.

Authors and Affiliations

  1. Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA

    Nan Li, Seounghun Kang, Zhichang Liu, Shinya Wai, Yahao Dai, Songsong Li, Yang Li, Michael J. V. White, Jeffrey A. Hubbell & Sihong Wang

  2. Department of Chemistry, The University of Chicago, Chicago, IL, USA

    Nan Li, Zhe Cheng & Bozhi Tian

  3. Animal Resource Center, The University of Chicago, Chicago, IL, USA

    Ani Solanki

  4. X-Ray Science Division, Argonne National Laboratory, Lemont, IL, USA

    Joseph Strzalka

  5. Department of Chemistry and RIMA, Gyeongsang National University, Jinju, South Korea

    Yun-Hi Kim

  6. Committee on Immunology, The University of Chicago, Chicago, IL, USA

    Jeffrey A. Hubbell

  7. Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA

    Jeffrey A. Hubbell

  8. Department of Chemical and Biomolecular Engineering, Tandon School of Engineering, New York University, New York, NY, USA

    Jeffrey A. Hubbell

  9. Nanoscience and Technology Division and Center for Molecular Engineering, Argonne National Laboratory, Lemont, IL, USA

    Sihong Wang

  10. CZ Biohub Chicago, LLC, Chicago, IL, USA

    Sihong Wang

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Contributions

S. Wang conceived and supervised the research. N.L. and S. Wang designed the experiments. N.L. synthesized and characterized the monomers and polymers. S.K., A.S., N.L., S. Wai, M.J.V.W. and J.A.H. designed and performed the surgical experiments and immune compatibility analysis. S.K. conducted in vitro cell tests. N.L., Z.L., Y.D., Y.L., S.L. and Y.-H.K. fabricated the transistor devices and performed the measurements. N.L., Y.D. and J.S. performed the GIXD characterization. Z.L., S. Wai, Z.C., S.L., N.L. and B.T. conducted the implantable demonstrations. N.L. and S. Wang co-wrote the paper. All authors reviewed and commented on the paper.

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Correspondence to Sihong Wang.

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Li, N., Kang, S., Liu, Z. et al. Immune-compatible designs of semiconducting polymers for bioelectronics with suppressed foreign-body response. Nat. Mater. (2025). https://doi.org/10.1038/s41563-025-02213-x

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