Oral wearable biosensors in saliva: Antifouling interfaces, device integration, calibration and in-mouth validation

Oral wearable biosensors enable repeated measurement of salivary biochemical and physicochemical variables using devices retained on teeth, incorporated into dental appliances or attached to saliva-facing oral surfaces. However, changing saliva composition, fouling, motion, intermittent contact, mechanical loading and temperature can alter the calibration relationship established before use. This Review critically synthesises evidence on these failure mechanisms and the validation requirements needed to support quantitative in-mouth measurement. We first analyse reaction-product passivation, protein and mucin fouling, electroactive interferents, pH and ionic-strength variation, enzyme degradation, microbial adhesion and biofilm formation, together with mechanism-matched protection, selectivity and regeneration strategies. We then consider motion artefacts, unstable sensor-saliva contact, fluid renewal, device deformation and temperature effects. At the device level, we assess how wearable format, anatomical placement and sensing-window design, electrochemical-cell and reference-electrode integration, encapsulation, biocompatibility, miniaturised potentiostats, power supply and wireless readout affect the complete measurement chain. Finally, we examine calibration across buffer, artificial saliva and human saliva, pre- and post-wear checks of calibration validity, validated correction, reference-method agreement, repeated wear, missing data and between-subject variability. Across the reviewed evidence, continued device operation and successful data transfer do not by themselves establish preservation of calibration validity. Progress depends less on isolated gains in sensitivity or detection limits than on mechanism-matched control and evidence that selectivity, response kinetics, reference stability, calibration validity and data completeness are retained during realistic in-mouth use.