Improving the Skin‐Conformability of Wearable Continuous Glucose Monitors With Synthetic Hydrogel Electrodes

ABSTRACT Synthetic bioelectronics is rapidly advancing, propelled by breakthroughs in synthetic biology and bioelectronics. This convergence is key to next‐generation wearable and implantable devices, enabling seamless integration with living systems. Here, we introduce an enzymatic hydrogel electrode (GelZymes) developed via a synthetic bioelectronic strategy to overcome the mechanical and interfacial limitations of conventional enzyme electrodes. GelZymes deliver two core advances: i) a monolithic and scalable 3D architecture that unifies the enzyme membrane and electrode, simplifying fabrication and eliminating interfacial instability; and ii) tissue‐like viscoelasticity—combining stretchability and adhesiveness—rarely achievable with rigid enzyme membranes. GelZymes are synthesized through three steps: engineering a stretchable, mixed‐conducting 3D hydrogel; implementing an enzyme‐compatible, cascading crosslinking scheme to immobilize enzymes within the network; and balancing the trade‐off between electronic/ionic conductivity and the density of redox‐active enzyme sites to maximize bio‐electrochemical performance. We further show that GelZymes enable a shift from invasive, tissue‐interfaced biosensing to noninvasive, tissue‐integrated biosensing, offering a practical pathway to bridge current biosensor technologies with living systems.