Biomimetic polypyrrole/hyaluronic acid electrodes integrated with hyaluronidase inhibitors offer persistent electroactivity and resistance to cell binding.

Conductive polymers, including polypyrrole (PPy), have garnered much attention as bioelectrodes because of their high conductivity, low interfacial resistance, environmental stability, and biocompatibility. In particular, the introduction of high-molecular weight hyaluronic acid (HA) into PPy enables the fabrication of biomimetic and biocompatible electrodes (, PPy/HA) characterized by low biofouling. However, as HA is readily degraded by enzymes (, hyaluronidase (HAase)) in a biological milieu, PPy/HA substantially loses its original properties, including resistance to cell adhesion and electrical activity. We found that HAase treatment of PPy/HA substantially degraded the HA moieties in PPy/HA, resulting in increased water contact angles, increased impedance, and conversion of non-cell adhesive to cell adhesive surfaces. Hence, it is desirable to mitigate HA degradation to achieve persistent performance of PPy/HA electrodes. Accordingly, we incorporated glycyrrhizin as an HAase inhibitor (HI) into PPy/HA electrodes. HI-incorporated PPy/HA (PPy/HA/HI) successfully prevented the degradation of the HA moiety and non-specific cell adhesion on the electrodes, in the presence of HAase (2.5 U mL), without cytotoxicity. These excellent properties allowed for maintenance of the electrical sensitivity of PPy/HA during cell culture with HAase. Altogether, biomimetic PPy/HA, which is resistant to degradation by HAase, may serve as an effective platform for the development of reliable and biocompatible bioelectrodes.