From Fundamentals to Applications: A Comprehensive Review of Enzymatic Biofuel Cells

ABSTRACT Enzymatic biofuel cells represent a promising class of bioelectrochemical systems that employ redox enzymes as catalysts to convert the chemical energy of bio‐derived fuels into electrical energy under mild and environmentally benign conditions. Unlike conventional fuel cells, EBFCs operate with high substrate specificity and biocompatibility, enabling applications ranging from sustainable energy generation to wearable and implantable biomedical devices. Recent advances in nanostructured electrode design, redox polymer mediators, and protein engineering have significantly enhanced electron transfer efficiency, power density, and operational stability. Hybrid configurations integrating supercapacitors, microfluidics, and flexible substrates further demonstrate EBFC potential in powering self‐sustained biosensors and controlled drug‐delivery systems. Nonetheless, critical challenges remain, including limited enzyme lifetime, restricted direct electron transfer due to structural constraints, mediator leaching, and difficulties in scaling for real‐world deployment. Future research directions emphasize the development of genetically engineered enzymes with improved durability, multifunctional nanostructured electrodes for higher loading and electron mobility, and hybrid bioelectronic platforms capable of delivering stable outputs for long‐term biomedical and environmental applications. This review highlights the fundamental principles, key components, technological advances, and persisting challenges in EBFCs, offering insights into pathways that can bridge laboratory‐scale prototypes to practical, sustainable, and clinically relevant power solutions.