Smart wearable biosensors: a transformative synergy between diagnosis and treatment of disease.

Smart wearable biosensors represent a significant paradigm shift from one-time sample analysis to real-time biochemical monitoring at the body interface. Besides the flexible design of the device or wireless readout, their clinical utility will also require the reliability of the entire sensing pathway under real physiological conditions. This pathway involves biofluid access to clinical interpretation. Despite rapid progress, many wearable biosensor platforms remain limited by weak biofluid-blood correlation, receptor degradation, biofouling, motion artefacts, sensor drift and insufficient patient-level validation. Thus, a chemistry-to-clinics approach is crucial to assess the analytical reliability and translational readiness of recognition elements, sensing materials, and engineered biointerfaces. Enzymes, antibodies, aptamers, nucleic-acid systems, molecularly imprinted polymers, and nanozymes are discussed within the context of selectivity, stability, antifouling behaviour and suitability for continuous monitoring of sweat, interstitial fluid, tears, wound exudate and breath condensate. The functionality of carbon nanostructures, metal-based nanomaterials, hydrogels, MXenes, metal-organic frameworks and self-powered interfaces are evaluated in terms of their applications in amplification, mechanical conformity, biofluid handling and signal stability. Artificial intelligence is positioned as a support layer for signal correction, calibration, classification, multimodal fusion and predictive interpretation, rather than as a substitute for robust sensing chemistry. This review provides a critical chemistry-to-clinical perspective on smart wearable biosensors and outlines the validation, manufacturing, cybersecurity, post-market surveillance and benchmarking requirements needed for their translation into reliable diagnostic and therapeutic-monitoring technologies.