Exploring 4D printing of smart materials for regenerative medicine applications

The field of biomaterials has evolved rapidly with the introduction of time as a transformative factor, giving rise to four-dimensional (4D) materials that can dynamically change their structure or function in response to external stimuli. This review presents a comprehensive comparison between traditional three-dimensional (3D) and emerging 4D biomaterials, highlighting the key distinctions in design, adaptability, and functionality. We explore the development of smart biomaterials at the core of 4D systems, including stimuli-responsive polymers, shape-memory materials, and programmable hydrogels. The ability of these materials to undergo controlled transformations under physiological or engineered stimuli offers promising avenues in tissue engineering, drug delivery, regenerative medicine, and soft robotics. By integrating responsiveness and temporal control, 4D biomaterials represent a paradigm shift in biomedical engineering, with the potential to revolutionize patient-specific therapies and next-generation implants. Future challenges and opportunities for clinical translation are also discussed.