Artificial Intelligence-Empowered 3D and 4D Printing Technologies toward Smarter Biomedical Materials and Approaches

In the last decades, 3D printing has played a crucial role as an innovative technology for tissue and organ fabrication, patient-specific orthoses, drug delivery, and surgical planning. However, biomedical materials used for 3D printing are usually static and unable to dynamically respond or transform within the internal environment of the body. These materials are fabricated ex situ, which involves first printing on a planar substrate and then deploying it to the target surface, thus resulting in a possible mismatch between the printed part and the target surfaces. The emergence of 4D printing addresses some of these drawbacks, opening an attractive path for the biomedical sector. By preprogramming smart materials, 4D printing is able to manufacture structures that dynamically respond to external stimuli. Despite these potentials, 4D printed dynamic materials are still in their infancy of development. The rise of artificial intelligence (AI) could push these technologies forward enlarging their applicability, boosting the design space of smart materials by selecting promising ones with desired architectures, properties, and functions, reducing the time to manufacturing, and allowing the in situ printing directly on target surfaces achieving high-fidelity of human body micro-structures. In this review, an overview of 4D printing as a fascinating tool for designing advanced smart materials is provided. Then will be discussed the recent progress in AI-empowered 3D and 4D printing with open-loop and closed-loop methods, in particular regarding shape-morphing 4D-responsive materials, printing on moving targets, and surgical robots for in situ printing. Lastly, an outlook on 5D printing is given as an advanced future technique, in which AI will assume the role of the fifth dimension to empower the effectiveness of 3D and 4D printing for developing intelligent systems in the biomedical sector and beyond.