Self-assembled thiol monolayers as functional coatings for electrodes in stimulus-responsive neurotransmitter delivery

Biomedical electrodes are essential tools in neurotechnology, enabling electrical communication with neural tissues for recording, stimulation, and increasingly, for therapeutic drug delivery. As the field advances toward implantable systems capable of electrically-controlled neurotransmitter release, surface engineering becomes critical to ensure both electrochemical performance and neural compatibility.
This study explores self-assembled monolayers (SAMs) of thiol compounds: 2-thiophenethiol (TT) and 2-mercaptoethanol (ME) as minimal yet functional surface coatings for gold electrodes. By systematically varying the TT:ME ratio, we assessed their impact on surface morphology, electrochemical properties, and neural cell response. The 1:1 (TT:ME) composition emerged as the most effective, offering a favorable balance between charge storage capacity and charge transfer resistance key parameters for developing electrically triggered release platforms. Atomic force microscopy revealed a structured yet uniform surface, conducive to molecular loading and controlled diffusion. Importantly, biological evaluations using primary mesencephalic cultures showed enhanced neurite extension, high neuronal complexity, and reduced astrocytic activation on the 1:1 SAM, indicating a neural-supportive and low-inflammatory profile.These findings highlight the potential of thiol-based SAMs not only as biocompatible electrode coatings but also as enabling surface layers for bioelectronic systems designed to deliver neurotransmitters on demand. This work provides a foundational step toward integrating molecular-level surface control with functional neural interface technologies.