INTRODUCTION: The advent of 3D printing has revolutionized biomedical engineering, yet limitations in creating dynamic human tissues remain. The emergence of 4D printing, which introduces time as a fourth dimension, offers new possibilities by enabling the production of adaptable, stimuli-responsive structures. A thorough literature search was performed across various databases, including Google Scholar, PubMed, Scopus, and Web of Science, to identify pertinent studies published up to 2025. The search parameters were confined to articles published in English that concentrated on peer-reviewed clinical studies. AREAS COVERED: This review explores the transition from 3D to 4D printing and focuses on stimuli-responsive materials, particularly hydrogels, which react to environmental changes. The literature search examined recent studies on the interaction of these materials with biological stimuli, emphasizing their application in tissue engineering and drug delivery applications. EXPERT OPINION: 4D printing, combined with smart materials, holds immense promise for advancing biomedical treatments, including customized therapies and regenerative medicine. However, technological challenges must be addressed to realize its full potential.