Engineering Complex Anisotropic Scaffolds beyond Simply Uniaxial Alignment for Tissue Engineering

Abstract Anisotropic microarchitectures arising from an aligned organization of threadlike extracellular matrix (ECM) components or cells are ubiquitous in the human body, such as skeletal muscle, corneal stroma, and meniscus, for executing tissue‐specific physiological functions. It is widely recognized that tissue engineering, whereby growing the implanted or endogenous cells in anisotropic scaffolds with geometrical resemblance to the ECM of targeted tissues, represents a promising solution for the structural and functional restoration of these anisotropic tissues. However, remarkable challenges remain in recapitulating the anisotropic complexities of native tissues beyond simply uniaxial alignment. Through unremitting endeavors over the past decade, some innovative bioengineering approaches are developed to tackle these challenges. This review focuses on the recent progress in modular assembly and 3D printing techniques exploited to construct complex anisotropic scaffolds with a key highlight on their accessibility and features for different types of anisotropies, based on understanding the whole picture of anisotropies beyond simply uniaxial alignment in native tissues, which are geometrically divided into three categories. Finally, the applications of these complex scaffolds in anisotropic tissue engineering, either in vitro modeling or in vivo regeneration, are explored.