Engineering anisotropic tissues: from structured scaffolds to magnetic actuation

Tissue engineering emerged in the late 20th century to replicate human tissues in vitro for biomedical applications. Early concepts relied on culturing cells within three-dimensional scaffolds to reproduce in vivo architecture. However, native tissues are not only three-dimensional but also structurally complex, heterogeneous, and often anisotropic - skeletal muscle being an archetypal example. These anisotropic features are not merely structural, as they critically influence tissue mechanics and function. Replicating such multiscale structural and mechanical complexity is therefore critical to engineer physiologically relevant tissue models. After outlining the diversity and functional significance of anisotropic tissues in vivo, this review examines current material- and fabrication-based strategies for anisotropic tissue engineering. Approaches range from surface-engineered 2D substrates and architected polymeric scaffolds to hydrogel-based three-dimensional bioprinting, where micro- and nano-scale control over material properties enables guided cell alignment. In addition, emerging techniques exploit external forces, such as electrical or acoustofluidic stimuli, to induce structural micro-features, while others leverage the intrinsic self-organization capacity of cells. Among these externally driven approaches, magnetic-based strategies are particularly promising due to their ability to provide remote, spatially precise, and dynamically tunable control over tissue organization, both at the microscopic and macroscopic scales. This review highlights their capacity to generate anisotropic architectures unattainable by conventional methods and discusses the key challenges that must be addressed to establish magnetic-based approaches as a promising emerging strategy to expand the design space for engineering functional, anisotropic tissues.