4D hydrogels: fabrication strategies, stimulation mechanisms, and biomedical applications

Shape-morphing hydrogels have emerged as a promising biomaterial due to their ability to mimic the anisotropic tissue composition by creating a gradient in local swelling behavior. In this case, shape deformations occur due to the non-uniform distribution of internal stresses, asymmetrical swelling, and shrinking of different parts of the same hydrogel. Herein, we discuss the four-dimensional (4D) fabrication techniques (extrusion-based printing, dynamic light processing, and solvent casting) employed to prepare shape-shifting hydrogels. The important distinction between mono- and dual-component hydrogel systems, the capabilities of 3D constructs to undergo uni- and bi-directional shape changes, and the advantages of composite hydrogels compared to their pristine counterparts are presented. Subsequently, various types of actuators such as moisture, light, temperature, pH, and magnetic field and their role in achieving the desired and pre-determined shapes are discussed. These 4D gels have shown remarkable potential as programmable scaffolds for tissue regeneration and drug-delivery systems. Finally, we present futuristic insights into integrating piezoelectric biopolymers and sensors to harvest mechanical energy from motions during shape transformations to develop self-powered biodevices.