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However, traditional fiber devices, typically composed of rigid, dry, and non\u2010living materials, are intrinsically different from the soft, wet, and living essence of biological tissues, thereby posing grand challenges for long\u2010term, reliable, and seamless interfacing with biological systems. Hydrogel fibers have recently emerged as a promising candidate, in light of their similarity to biological tissues in mechanical, chemical and biological aspects, as well as distinct fiber geometry. In this review, a comprehensive overview of recent progress in hydrogel fibers\u2010based biointerfacing technology is provided. It thoroughly summarizes the manufacturing strategy and functional design, especially for hydrogel fibers with distinct optical and electron conductive performance, as well as responsiveness to triggers including thermal, magnetic field and ultrasonic wave, etc. Such unique attributes enable various biomedical applications, which are also examined in detail. 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