4D Printing in Regenerative Medicine: Bio-Inspired Applications for Dynamic Tissue Repair
Guihua Liu, Jinan Wu, Yang Yang, Junsi Luo, Xiaoli Xie
Abstract
4D printing, as an advanced evolution of 3D bioprinting, introduces time as an active design dimension, enabling printed constructs to undergo programmed morphological or functional transformations in response to external or endogenous stimuli. By integrating stimuli-responsive smart materials with precise additive manufacturing, 4D printing provides a bio-inspired strategy to overcome the inherent limitations of static scaffolds and to achieve spatiotemporal dynamic matching with the evolving biological microenvironment during tissue regeneration. Over the past decade, significant progress has been made in applying 4D printing to structurally and functionally complex tissues, including bone, muscle, vasculature, nerve repair, wound closure, and other emerging biomedical scenarios. Rather than emphasizing shape change alone, recent advances demonstrate that 4D-printed constructs can emulate key biological processes such as morphogenesis, contraction, directional guidance, electrophysiological signaling, and microenvironment-responsive regulation, thereby enhancing tissue integration and functional recovery. This review systematically summarizes materials, stimulus-response mechanisms, and representative applications of 4D printing from a bio-inspired perspective, while critically discussing current challenges related to material performance, mechanistic understanding, manufacturing precision, and clinical translation. Finally, future perspectives are outlined, highlighting the importance of interdisciplinary integration, intelligent manufacturing, and clinically oriented evaluation frameworks to advance 4D printing toward personalized and precision regenerative medicine.