Method Matters: Exploring Alkoxysulfonate-Functionalized Poly(3,4-ethylenedioxythiophene) and Its Unintentional Self-Aggregating Copolymer toward Injectable Bioelectronics

Abdelrazek H Mousa; David Bliman; Lazaro Hiram Betancourt; Karin Hellman; Peter Ekström; Marios Savvakis; Xenofon Strakosas; György Marko-Varga; Magnus Berggren; Martin Hjort; Fredrik Ek; Roger Olsson

doi:10.1021/acs.chemmater.1c04342

Method Matters: Exploring Alkoxysulfonate-Functionalized Poly(3,4-ethylenedioxythiophene) and Its Unintentional Self-Aggregating Copolymer toward Injectable Bioelectronics

Chem Mater. 2022 Mar 22;34(6):2752-2763. doi: 10.1021/acs.chemmater.1c04342. Epub 2022 Feb 28.

Authors

Abdelrazek H Mousa^{1

2}, David Bliman^{1

2}, Lazaro Hiram Betancourt^{3

4}, Karin Hellman², Peter Ekström², Marios Savvakis⁵, Xenofon Strakosas⁵, György Marko-Varga⁶, Magnus Berggren⁵, Martin Hjort², Fredrik Ek², Roger Olsson^{1

2}

Affiliations

¹ Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden.
² Chemical Biology & Therapeutics, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
³ Division of Oncology, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden.
⁴ Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, 202 13 Malmö, Sweden.
⁵ Laboratory of Organic Electronics, Department of Science and Technology, Linköping University, 601 74 Norrköping, Sweden.
⁶ Division of Clinical Protein Science & Imaging, Department of Clinical Sciences and Department of Biomedical Engineering, Lund University, 221 00 Lund, Sweden.

Abstract

Injectable bioelectronics could become an alternative or a complement to traditional drug treatments. To this end, a new self-doped p-type conducting PEDOT-S copolymer (A5) was synthesized. This copolymer formed highly water-dispersed nanoparticles and aggregated into a mixed ion-electron conducting hydrogel when injected into a tissue model. First, we synthetically repeated most of the published methods for PEDOT-S at the lab scale. Surprisingly, analysis using high-resolution matrix-assisted laser desorption ionization-mass spectroscopy showed that almost all the methods generated PEDOT-S derivatives with the same polymer lengths (i.e., oligomers, seven to eight monomers in average); thus, the polymer length cannot account for the differences in the conductivities reported earlier. The main difference, however, was that some methods generated an unintentional copolymer P(EDOT-S/EDOT-OH) that is more prone to aggregate and display higher conductivities in general than the PEDOT-S homopolymer. Based on this, we synthesized the PEDOT-S derivative A5, that displayed the highest film conductivity (33 S cm^-1) among all PEDOT-S derivatives synthesized. Injecting A5 nanoparticles into the agarose gel cast with a physiological buffer generated a stable and highly conductive hydrogel (1-5 S cm^-1), where no conductive structures were seen in agarose with the other PEDOT-S derivatives. Furthermore, the ion-treated A5 hydrogel remained stable and maintained initial conductivities for 7 months (the longest period tested) in pure water, and A5 mixed with Fe₃O₄ nanoparticles generated a magnetoconductive relay device in water. Thus, we have successfully synthesized a water-processable, syringe-injectable, and self-doped PEDOT-S polymer capable of forming a conductive hydrogel in tissue mimics, thereby paving a way for future applications within in vivo electronics.