Programmable Anisotropic Hydrogels: Materials Design, Fabrication Strategies, and Emerging Biointegrated Applications

Abstract Hydrogels, valued for their intrinsic biocompatibility and tunable mechanical properties, play a pivotal role in bioelectronics, biomedicine, and soft robotics. However, the intrinsic isotropy of conventional hydrogels limits their capacity to mimic the anisotropic architectures and directional functionalities of native tissues─hindering performance in applications requiring unidirectional force transmission, directional charge transport, or guided cell alignment. To address this, anisotropic hydrogels with spatially ordered architectures have emerged as transformative materials. This review systematically summarizes recent advances in the design and fabrication of anisotropic hydrogels, highlighting innovative strategies such as external-field-induced alignment and template-guided assembly, along with the integration of functional materials that enable precise molecular orientation and multiscale structural control. These engineered hydrogels exhibit programmable anisotropic responses─mechanical, electrical, and biological─unlocking new possibilities in flexible biosensing, intelligent actuation, targeted drug delivery, and tissue regeneration. Despite substantial progress, challenges remain in long-term structural stability, scalable manufacturing, biocompatibility of conductive fillers, and implementation of full-lifecycle design. Addressing these limitations through next-generation material innovations and fabrication technologies will be key to realizing the full potential of anisotropic hydrogels in advanced biointegrated systems.