Abstract: The last few decades have witnessed unprecedented convergence between humans and machines that closely operate around the human body. Despite these a

Abstract: The last few decades have witnessed unprecedented convergence between humans and machines that closely operate around the human body. Despite these advances, traditional machines made of hard, dry and abiotic materials are substantially dissimilar to soft, wet and living biological tissues. This dissimilarity results in severe limitations for long-term, reliable and highly efficient interfacing between humans and machines. To bridge this gap, hydrogels have emerged as an ideal material candidate for interfacing between humans and machines owing to their mechanical and chemical similarities to biological tissues and the versatility and flexibility in designing their properties. In this Review, we provide a comprehensive summary of functional modes, design principles, and current and future applications for hydrogel interfaces towards merging humans and machines. Overview: The main challenges of human–machine interfaces stem from materials. Existing machines largely employ conventional materials, such as metals, silicon, glass, ceramics and plastics, to communicate and interact with human bodies. However, the hard, dry and abiotic nature of these conventional materials is intrinsically contradictory with the soft, wet and living nature of biological tissues. In recent decades, intensive efforts have been devoted to transforming these conventional materials into flexible and stretchable structures to conformally interface with soft and curvilinear biological tissues. However, these structural designs do not alter the materials’ intrinsic properties, which may still hamper their communication and interactions with biological tissues. For example, the integration of conventional materials with tissues usually relies on physical attachment or surgical suturing, methods that face challenges such as non-conformal contact, unstable adhesion, tissue damage and/or scar formation. As another example, the properties of metallic electrodes, such as their high rigidity, low interfacial capacitance and low charge injection capacity, make them far from ideal for the electrical recording and stimulation of soft neural tissues. In addition, biological tissues often recognize these materials, even when in flexible and stretchable structures, as foreign bodies due to their inherently disparate properties, resulting in an adverse foreign-body response, biofouling, and fibrotic encapsulation or fibrosis. Such foreign-body response and subsequent fibrotic isolation from the surrounding tissues can severely compromise the long-term reliability and efficacy of the communication and interactions between humans and machines. Because of their unique similarities to biological tissues and the versatility and flexibility in tailoring their properties, hydrogels have naturally emerged as a promising material candidate to act as an alternative or adjunct to conventional materials for bridging humans and machines.