Nanoengineering conductive soft interfaces for electrogenic cell interactions: a review of materials, fabrication and...

Conductive soft materials are emerging as critical platforms for interfacing with electrogenic cells, such as neurons and cardiomyocytes. Unlike rigid metal electrodes, these materials offer tuneable conductivity for reliable electrical communication, tissue-like softness for mechanical compliance, and chemical or bioactive functionalities for effective integration with biological systems. However, achieving an optimal balance between the material properties required to control biological functionality, including conductivity, modulus, bending stiffness, charge injection capacity and biocompatibility, remains a significant challenge that is strongly dependent on the fabrication pathway selected. The array of advanced biofabrication methodologies available to researchers continues to expand rapidly, enabling both 'top down' approaches that start with bulk materials and 'bottom up' approaches that enable more precise formation of structures from molecular building blocks. To equip researchers with a practical toolkit for understanding the design trade-offs involved in creating effective bio-interfaces for translation into the clinic in areas such as neuroengineering and cardiac modelling, here we provide a comprehensive review of the interdependencies between material properties, fabrication techniques and functionalisation strategies for these materials, highlighting how they can impact upon the ability to communicate with and control cell behaviour. We first provide an overview of the key interaction mechanisms between electrogenic cells and conductive artificial materials, then introduce some key classes of conductive soft materials, highlighting the impact of their material properties on controlling interactions with electrogenic cells. We then discuss how these material properties are critical for optimising fabrication techniques, with a focus on identifying the strengths and limitations of the array of biofabrciation techniques in the context of specific bioelectronic applications. Subsequently, strategies for tailoring post-fabrication surface chemistry to enhance cell adhesion, growth pathways and prevention of foreign body responses are discussed. Finally, we conclude with a consideration of where these strategies are being employed in both emerging applications (in vitroandin vivo) and clinical translation to create soft conductive bioelectronic devices to address challenges in health and society, highlighting emerging opportunities and potential new directions for the future.