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

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 Fe 3 O 4 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.

Versatile Poly(3,4-ethylenedioxythiophene) Polyelectrolytes for Bioelectronics by Incorporation of an Activated Ester

“…Previous reports of PEDOT-S and structural analogues have demonstrated conductivities ranging from ∼0.1 to 40 S cm −1 , depending on the polymer structure and synthesis protocol. 26,43 PEDOT-S synthesized via DHAP demonstrated a conductivity of 13.2 ± 1.4 S cm −1 , which is within error to the original report by Konradsson et al 18 Both PEDOT-NHS-10 and PEDOT-NHS-50 had lower conductivities of 4.9 ± 0.3 and 4.3 ± 0.5 S cm −1 , respectively, but higher conductivity than other reports of PEDOT-S (Figure 1f and Table S1). The relatively similar conductivity between the three materials is consistent with prior reports of sulfonated PEDOT-based copolymers, where the incorporation of hydrophobic comonomers did not show severe deleterious effects on electronic properties.…”

“…Many conductive polymers such as PEDOT-S and PEDOT:PSS have been incorporated into biomaterials for various bioelectronic applications; 15,22,43,50 however, their lack of chemical handles for functionalization has required the use of rudimentary blending and soaking procedures. 35,51 The physical entrapment of conductive polymers within a biomaterial, rather than chemical binding, allows for the potential loss of the polymer over time and therefore decreased bioelectronic performance or increased toxicity to the cellular environment.…”

PEDOT-NHS as a Versatile Conjugated Polyelectrolyte for Bioelectronics

“…17 Previous reports of PEDOT-S and structural analogues have demonstrated conductivities ranging from ~0.1 -40 S cm -1 , depending on the polymer structure and synthesis protocol. 26,43 PEDOT-S synthesized via DHAP demonstrated a conductivity of 13.2  1.4 S cm -1 , which is within error to the original report by Konradsson et al 18 Both PEDOT-NHS-10 and PEDOT-NHS-50 had lower conductivities of 4.9  0.3 S cm -1 and 4.3  0.5 S cm -1 , respectively, but higher conductivity than other reports of PEDOT-S (Table S1). The relatively similar conductivity between the three materials is consistent with prior reports of sulfonated PEDOT-based copolymers, where the incorporation of hydrophobic comonomers did not show severe deleterious effects on electronic properties.…”

“…PEDOT-S and PEDOT:PSS have been incorporated into biomaterials for various bioelectronic applications, 15,22,43,45 however their lack of chemical handles for functionalization has required the use of rudimentary blending and soaking procedures. 36,46 The physical entrapment of conductive polymers within a biomaterial, rather than chemical binding, allows for potential loss of the polymer over time and therefore decreased bioelectronic performance or increased toxicity to the cellular environment.…”

Protein-Based Flexible Conductive Aerogels for Piezoresistive Pressure Sensors

“…This can be achieved either by polymerization of the respective monomer in the presence of PNFs, , or by complexation with electrically conductive polyelectrolytes, − in both cases giving electrically conductive hybrid materials. Herein we employ poly­(4-(2,3-dihydrothieno­[3,4- b ]-[1,4]­dioxin-2-yl-methoxy)-1-butanesulfonic acid (PEDOT-S) , as a conductive polymer to functionalize hybrids between gelatin and lysozyme protein nanofibrils (LPNF). PEDOT-S has been investigated as a functionalization agent for PNFs, − DNA, and liposomes to prepare electrically conductive hybrids materials.…”