4D Printing of Smart Biomaterials: Emerging Applications in Cardiovascular Tissue Engineering

초록

Cardiovascular diseases remain the leading cause of deaths worldwide, which highlights the urgent need for regenerative therapies. Although 3D printing has advanced tissue engineering applications, it is limited to fabricating static structures that lack dynamic adaptability, long-term patency, and adequate vascularization. For example, small-diameter vascular grafts fab- ricated by 3D printing often experience occlusion within months, and thick cardiac patches (> 200 µm) encounter oxygen diffusion barriers that compromise cell survival. These limitations indicate the unmet need for dynamic, patient-specific con- structs in cardiovascular applications. By introducing the temporal dimension, 4D printing enables shape transformation and stimuli-responsiveness, offering unique advantages. This review summarizes recent progress in the use of 4D-printed smart biomaterials across three major categories. First, the fabrication of self-expanding small-diameter vascular grafts with func- tional bioinks to enhance endothelialization. Second, the development of dynamic cardiac patches that synchronize with my- ocardial contraction while promoting cell adhesion, proliferation, and vascularization. Third, the establishment of disease mod- els, including ischemia–reperfusion injury and heart-on-a-chip systems, which provide physiologically relevant platforms for drug screening. Future directions emphasize diversifying smart biomaterials, ensuring long-term safety, refining cell-material interactions, and integrating artificial intelligence (AI) and microfluidics. Overall, these advances demonstrate the potential of 4D printing in cardiovascular research.

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