Highly oriented hydrogels for tissue regeneration: design strategies, cellular mechanisms, and biomedical applications

Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior.