Semiconducting polymers with mixed electron-ion conductivity, known as mixed conductors, show great promise for creating wearable and implantable devices that interface with the human body. These materials transport charge with electrons like conventional computing technology, but also with ions the way nerves in our body do, making them ideal for interfacing between conventional electronics and living tissue. Research has shown that such devices could be used for health monitoring, for example, by continuously measuring concentrations of biomolecules in a patient’s blood or the electrical signals in their skin produced by heart activity, like an electrocardiogram.
Mixed conducting materials also have potential as medical treatments, with studies highlighting the possibilities of exploiting their optoelectronic response. When exposed to near-infrared light these implantable bioelectronics produce electrical signals, which research shows can stimulate nerves and promote cell growth, for wound healing, for instance.
There is, however, a major compatibility issue for such bioelectronic implants: the human body recognises them as “foreign” and launches immune cells against them. This inflammatory response leads to fibrotic (scar) tissue growth around the implant, as the immune system attempts to seal it off from the rest of the body. This impacts the polymer’s interface with the body, reducing its functionality and ultimately leading to device failure. The immune response can also cause local and systemic side effects for patients.
Now, a research team led by scientists at The University of Chicago has incorporated compounds with known immunomodulating properties into a semiconducting polymer often used for research on implantable bioelectronics, to see if they could improve its immune compatibility. The team used the resources of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.
The structure of semiconducting polymers is generally a backbone of aromatic rings, which control how fast electrons travel along the polymer, along with side chains that further impact the material’s electrical properties and characteristics like solubility. The team created a polymer with a modified backbone by replacing a third of the occurrences of the aromatic compound thiophene with the very similar aromatic compound selenophene, which has displayed antioxidant and immunomodulatory effects in studies.
They also produced two other novel polymers by modifying the backbone – by incorporating selenophene – and adding one of two previously reported immunomodulatory compounds to the side chains. The three novel polymers, along with the original polymer as a control, were implanted into mouse models.
Analysis after four weeks showed that the build-up of collagen, the main component of tissue, around the modified polymers was reduced by up to 70%, compared with the control. The best results were seen with the polymers with both modified backbones and side chains. Further tests found that biomarkers linked to inflammation and immune cell recruitment were reduced in the mice implanted with the modified polymers, while anti-inflammatory biomarkers increased, compared with the control.
These results show that the modifications reduced the mice’s immune response to the polymers, the researchers say.
Tests showed that the electrical performance of the novel semiconducting polymers was comparable with that of the unmodified semiconducting polymer. The addition of selenophene in the polymer backbone was found to even improve some electrical properties, such as electron mobility.
To further explore how the immune modulating adaptions changed their structure and electrical properties, the team performed grazing-incidence X-ray diffraction on the polymers. This work was carried out at the on beamline 8-ID-E of the APS.
The scattering measurements showed that replacing some of the thiophene in the polymer backbone with selenophene decreased the spacing, or “packing distance,” between the polymer’s layers, and made the polymer structure more crystalline. Both these improvements in structural ordering are known to improve electrical performance. Conversely, the adaptations to the polymer side chains were found to decrease crystallinity and increase packing distance.
These X-ray findings likely explain the specific changing behaviors in electrical performance seen with the different modifications, and the overall comparable performance of the new polymers to the original polymer.
As a final test of the novel polymers, the team used them to create ECG devices, which they implanted in mice models. After four weeks the modified polymers provided better ECG readouts than the control polymer, which the researchers say shows the benefits of their immune-compatible designs.
Next the team plans to trial the modified polymers on brain tissue, to explore their potential for treating neurological conditions. – Michael Allen
See: N. Li1, S. Kang1,2, Z. Liu1, S. Wai1, Z. Cheng1, Y. Dai1, A.Solanki1, S. Li1, Y. Li1, J. Strzalka3, M.J.V. White1, Y-H Kim4, B. Tian1, J.A. Hubbell1,5, S. Wang1,3,6, “Immune-compatible designs of semiconducting polymers for bioelectronics with suppressed foreign-body response,” Nat. Mater. (2025)
Author affiliations: 1University of Chicago; 2Soongsil University; 3Argonne National Laboratory; 4Gyeongsang National University; 5New York University; 6CZ Biohub Chicago, LLC.
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.
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