Presently, large groups of patients with various diseases are either intolerant, or irresponsive to drug therapies and also intractable by surgery. For several diseases, one option which is available for such patients is the implantable neurostimulation therapy. However, lacking closed-loop control and selective stimulation capabilities, the present neurostimulation therapies are not optimal and are therefore used as only ‘third’ therapeutic options when a disease cannot be treated by drugs or surgery. Addressing those limitations, a next generation class of closed-loop controlled and selective neurostimulators generically named bioelectronic medicines seems within reach. A sub-class of such devices is meant to monitor and treat impaired functions by intercepting, analyzing and modulating neural signals involved in the regulation of such functions using just one neural interface for those purposes. The primary objective of this review is to provide a first broad perspective on this type of single-interface devices for bioelectronic therapies. For this purpose, the concept, clinical applications and preclinical studies for further developments with such devices are here analyzed in a narrative manner.

Bioelectronic medicines record biological signals and provide electrical stimulation for the treatment of diseases. Advanced bioelectronic therapies require the development of electrodes that match the softness of the implanted tissues, as the present metal electrodes do not meet this condition. The objective of the present work was to investigate whether the electroconductive polymer polypyrrole (PPy) could be used for fabricating such electrodes, as PPy is several orders softer than metals. For this purpose, we here investigated if electrodes made using coatings and films of PPy doped with naphthalin-2-sulfonic acid (PPy/N) are capable to record and elicit by stimulation cardiac monophasic action potentials (MAPs) and if PPy/N is also biocompatible. The results of this study showed that the tested PPy/N electrodes are capable of recording MAPs almost identical to the MAPs recorded with platinum electrodes and eliciting stimulation-evoked MAPs almost identical to the spontaneous MAPs. In addition, we show here that the cell cultures that we used for biocompatibility tests grew in a similar manner on PPy/N and platinum substrates. We, therefore, conclude that PPy/N coatings and films have recording and electrical stimulation capabilities that are similar to those of platinum electrodes and that PPy/N substrates are as biocompatible as the platinum substrates.

Flexible electrode materials with tailored electrical and mechanical properties are essential for reliable electrocardiographic (ECG) sensing. In this work, p-toluenesulfonic-acid-doped polypyrrole (PPy–TSA) films were modified using polymeric and inorganic fillers, as well as their combinations (polyethylene glycol, graphene, carbon nanotubes, and zeolite), to tune their functional performance. The reference PPy–TSA film exhibits typical morphological and chemical characteristics of doped polypyrrole and serves as a reliable baseline for comparison. All composite films retain electrical conductivity within the range required for ECG applications while showing improved mechanical compliance (i.e., enhanced ability to conform to the skin and sustain deformation). Based on the optimized balance between electrical and mechanical properties, flexible ECG electrodes were fabricated using the TSA-doped PPy-based composite film. ECG recordings obtained with the several proposed electrodes show good agreement with those acquired using a commercial ECG electrode, demonstrating the potential of PPy-based composite films for flexible bioelectronic sensing applications.

Plasma medicine is a field of research that focuses on the sterilization of bacteria, wounds and cancer treatment, tissue regeneration and other biomedical applications using plasma. Dielectric barrier discharge microplasma was used for biomedical applications such as sterilization of bacteria and skin treatment for transdermal drug delivery. In this study, we investigated the feasibility of using microplasma for improving blood coagulation parameters. Blood samples collected from one dog and one cat were treated with microplasma, and the blood coagulation effect of this treatment was compared with the effect achieved by treating the blood with air flow only. The microplasma electrodes were energized using a negative pulse voltage power supply and environmental air was used as discharge gas. The microplasma treatment produced clear coagulation effects that increased proportionally with treatment time, discharge voltage and frequency. In contrast, the treatment with air flow only had no coagulation effects after the same treatment time as for the microplasma treatment. The observed blood coagulation effects induced by microplasma treatment could be attributed to the reactive oxygen and nitrogen species generated by microplasma. The blood sample subjected to microplasma treatment had a slight temperature increase (≈4 °C) confirming the nonthermal operation. In conclusion, this study shows promising results that suggest the potential of using microplasma treatment as a tool for improving blood coagulation parameters. Furthermore, microplasma’s suitability for portability and integration indicates the potential for developing a compact microplasma device tailored for use by first responders in cases of bleeding.