Enzymatically stable, non-cell adhesive, implantable polypyrrole/thiolated hyaluronic acid bioelectrodes for in vivo signal recording.

Implantable bioelectrodes have attracted significant attention for precise in vivo signal transduction with living systems. Conductive polymers, including polypyrrole (PPy), have been widely used as bioelectrodes due to their large surface areas, high charge injections, and versatilities for modification. Especially, several natural biopolymers, such as hyaluronic acid (HA), can be incorporated into conductive polymers to produce biomimetic electrodes with better biocompatibility. However, HA-incorporated PPy electrodes (PPy/HA) frequently lose their original performances after implantation in the body because of the deterioration of material properties, such as degradation of natural biopolymers in the electrode. Here, thiolated HA (HA-SH) was synthesized and introduced into PPy electrodes (PPy/HA-SH) to enhance the enzymatic stabilities of PPy electrodes against hyaluronidase (HAase) and endow these electrodes with robust resistances to non-specific cell adhesion, thereby enabling prolonged signal transmission. Unlike PPy/HA, PPy/HA-SH resisted cell adhesion even in the presence of HAase. Subcutaneous implantation studies revealed that PPy/HA-SH formed less fibrotic scar tissue and permitted more sensitive and stable signal recording for up to 15 days after implantation as compared to PPy/HA. These findings hold significance for the design and advancement of biocompatible implantable bioelectrodes for a wide range of applications, such as neural electrodes, cardiac pacemakers, and biosensors.

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 (i.e., PPy/HA) characterized by low biofouling. However, as HA is readily degraded by enzymes (i.e., 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-1), 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.