Enzymatic In Situ Polymerization for Soft Bioelectronic Interfaces—Advancing Tissue-Compatible Conductors in Vivo

The field of bioelectronics aims to integrate electronics with biological systems, unlocking new possibilities for diagnostics and therapies. A critical challenge in this domain is the mechanical mismatch between rigid electronic components and the soft, dynamic nature of biological tissues. To address this, researchers are developing soft, flexible bioelectronic devices using advanced microfabrication and printing techniques. Inspired by natural processes where biological systems polymerize small molecules into complex functional structures, we utilize thiophene-based monomer systems and enzymatic pathways to synthesize organic conductors in vivo. This approach enables the in-situ formation of conducting polymer-based gels within the nervous systems of zebrafish, medicinal leeches, and murine brains. These conductive gels exhibit excellent biocompatibility and mechanical properties that closely align with native tissue characteristics. Moreover, our findings demonstrate that these organic conductors can be selectively formed around hyperexcitable brain regions or areas with altered metabolism, effectively modeling neurological disorders. This method offers a novel solution to the limitations of conventional bioelectronic interfaces, allowing the development of soft, tissue-compliant, and biocompatible electronic interfaces, for applications in healthcare, bioengineering, and beyond.