Hydrogel-Forming Microneedles for Interstitial-Fluid Biosensing and Therapeutic Monitoring

Hydrogel-forming microneedles (HFMNs) are minimally invasive interfaces that access interstitial fluid (ISF) through skin penetration, swelling-mediated uptake, analyte diffusion, and hydrated sensor integration. This review examines HFMN architectures, skin–device interfaces, ISF transport, molecular-recognition and signal-transduction strategies, analytical performance, benchmarking, wear-associated failure modes, therapeutic monitoring, and translational priorities. The field has expanded from glucose sensing to metabolites, ions, hormones, proteins, nucleic acids, microbial and wound biomarkers, and therapeutic drugs, enabled by advances in hydrogel chemistry, conductive networks, nanostructured electrodes, catalysis, affinity recognition, molecular imprinting, optical readouts, and multiplexed wearables. Performance remains context dependent and requires physiological range, calibration stability, biofouling resistance, reliable insertion, validated ISF-reference correlations, and interpretable thresholds. Evidence is strongest in artificial matrices, ex vivo tissue, and animals, while human validation remains limited. Translation will require standardized mechanics and transport reporting, longer wear studies, sterilization-compatible chemistries, scalable manufacturing, and clinical validation. HFMNs may complement rather than replace blood-based diagnostics.