Hydrogel-based wearable electrochemical biosensors (HWEBs) are emerging biomedical devices that have recently received immense interest. The exceptional properties of HWEBs include excellent biocompatibility with hydrophilic nature, high porosity, tailorable permeability, the capability of reliable and accurate detection of disease biomarkers, suitable device-human interface, facile adjustability, and stimuli responsive to the nanofiller materials. Although the biomimetic three-dimensional hydrogels can immobilize bioreceptors, such as enzymes and aptamers, without any loss in their activities. However, most HWEBs suffer from low mechanical strength and electrical conductivity. Many studies have been performed on emerging electroactive nanofillers, including biomacromolecules, carbon-based materials, and inorganic and organic nanomaterials, to tackle these issues. Non-conductive hydrogels and even conductive hydrogels may be modified by nanofillers, as well as redox species. All these modifications have led to the design and development of efficient nanocomposites as electrochemical biosensors. In this review, both conductive-based and non-conductive-based hydrogels derived from natural and synthetic polymers are systematically reviewed. The main synthesis methods and characterization techniques are addressed. The mechanical properties and electrochemical behavior of HWEBs are discussed in detail. Finally, the prospects and potential applications of HWEBs in biosensing, healthcare monitoring, and clinical diagnostics are highlighted.
