Enzymatically Polymerized Glycolated Conductive Polymers as Soft Electrodes for Neural Bioelectronic Interfaces

Organic bioelectronics relies on materials capable of efficiently transducing signals between ionic biological environments and electronic devices. Conducting polymers are particularly attractive for this purpose due to their mixed ionic-electronic conductivity, mechanical compliance, and chemical tunability. Among them, bis-ethylenedioxythiophene-thiophene (ETE)-based polymers can be synthesized in situ via mild enzymatic reactions, enabling seamless and substrate-free integration with biological systems. Here, we investigate the impact of hydrophilic side-chain engineering on the physicochemical, electrochemical, and biological properties of ETE-based polymers by comparing two polymers which differ only by the presence of a triethylene glycol side chain between the ETE core and the terminal carboxylic group. We show that glycolation leads to increased film hydration and surface roughness without a measurable change in elastic modulus, suggesting competing effects from molecular ordering and ionic cross-linking. In a neuronal cell model, the glycolated polymer exhibits markedly enhanced cytocompatibility and cell adhesion, likely driven by its increased surface roughness and matrix topography. By combining electrochemical quartz crystal microbalance with dissipation monitoring, in-operando UV-vis spectroscopy, and electrochemical atomic force microscopy, we correlate ionic transport, swelling behavior, and nanomechanical responses, revealing enhanced electrochemically induced swelling in the glycolated polymer. Finally, when implemented as active channel materials in organic electrochemical transistors, both polymers display comparable performance, although the glycolated polymer shows slightly reduced cycling stability. These findings highlight the complex trade-offs introduced by side-chain glycolation and provide design guidelines for enzymatically synthesized conducting polymers in bioelectronic interfaces.