Recent Advances in 4D Printing: A Review of Current Smart Materials, Technologies, and Drug Delivery Systems.

Research on shape memory materials (SMM) or smart materials, along with advancements in printing technology, has transformed three-dimensional (3D) printing into what we now refer to as 4D printing. In this context, the addition of time as a fourth dimension enhances 3D printing. 4D printing involves the creation of 3D-printed objects that can change their shapes into complex geometries when influenced by external stimuli such as temperature, light, or pH over time. Currently, the use of smart materials in 4D printing is being explored extensively across various fields, including automotive, wearable electronics, soft robotics, food, mechatronics, textiles, biomedicine, and pharmaceuticals. A particular focus is on designing and fabricating smart drug delivery systems (DDS). This review discusses the evolution of 3D printing into 4D printing, highlighting the differences between the two. It covers the history and fundamentals of 4D printing, the integration of machine learning in 4D printing, and the types of materials used, such as stimuli-responsive materials (SRMs), hydrogels, liquid crystal elastomers, and active composites. Moreover, it presents various 4D printing techniques. Additionally, the review highlights several smart DDS that have been fabricated using 4D printing techniques. These include tablets, capsules, grippers, scaffolds, robots, hydrogels, microneedles, stents, bandages, dressings, and other devices aimed at esophageal retention, gastro-retention, and intravesical DDS. Lastly, it elucidates the current limitations and future directions of 4D printing.