Clinical challenges and opportunities related to the biological responses experienced by indwelling and implantable bioelectronic medical devices

Implantable electrodes have been utilized for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. While the underlying science related to the application of electrodes is a mature field, preclinical and clinical studies have demonstrated that there are still significant challenges in vivo associated with a lack of control over tissue-material interfacial interactions, especially over longer time frames. Herein we discuss the current challenges and opportunities for implantable electrodes and the associated bioelectronic interfaces across the clinical landscape with a focus on emerging technologies and the obstacles of biofouling, microbial colonization, and the foreign body response. Overcoming these challenges is predicted to open the door for a new generation of implantable medical devices and significant associated clinical impact.

Statement of significance

Implantable electrodes have been utilised for decades to stimulate, sense, or monitor a broad range of biological processes, with examples ranging from glucose monitoring devices to cochlear implants. Next-generation bioelectronic implantable medical devices promise an explosion of new applications that have until this point in time been impossible to achieve. However, there are several persistent biological challenges hindering the realisation of these new applications. We present a clinical perspective on how these biological challenges have shaped the device market and clinical trial landscape. Specifically, we present statistical breakdowns of current device applications and discuss biofouling, the foreign body response, and microbial colonisation as the main factors that need to be addressed before a new generation of devices can be explored.