Neuroelectrodes coated with a heparan sulfate mimetic demonstrate neuroprotective and neurotropic effects

Chronically stable neuroelectrodes increasingly rely on biomimetic strategies to reduce host inflammation and glial scar formation. Here, we report the first use of a heparan sulfate mimetic (HM), F6, as a biological dopant within a poly(3,4-ethylenedioxythiophene):p-toluene sulfonate (PEDOT:PTS) matrix for neuroelectrode coatings. F6 is a sulfated polyanion with neuromodulatory potential. Electrochemical polymerization produced PEDOT:PTS:F6 coatings with enhanced charge storage capacity, reduced impedance, and controlled F6 release relative to PEDOT:PTS and platinum (Pt)/iridium (Ir) electrodes. In vitro , PEDOT:PTS:F6 significantly reduced astrocytic and microglial reactivity, calcium influx markers, and pro-inflammatory chemokines, while increasing neural density and neurite outgrowth. These outcomes were supported by the downregulation of pro-gliosis proteins and growth factor binding consistent with true heparan sulfate mimicry. In vivo , 8-week implantation studies confirmed improved electrode performance and reduced peri-implant neurodegeneration. Overall, this work establishes F6 as a promising biological dopant to enhance longevity, biocompatibility, and the neural integration of next-generation neural interfaces for clinical translation.