4D Printing in Biomedical Engineering: Advancements, Challenges, and Future Directions

Abstract

4D printing has emerged as a transformative technology in the field of biomedical engineering, offering the potential for dynamic, stimuli-responsive structures with applications in tissue engineering, drug delivery, medical devices, and diagnostics. This review paper provides a comprehensive analysis of the advancements, challenges, and future directions of 4D printing in biomedical engineering. We discuss the development of smart materials, including stimuli-responsive polymers, shape-memory materials, and bio-inks, as well as the various fabrication techniques employed, such as direct-write assembly, stereolithography, and multi-material jetting. Despite the promising advances, several challenges persist, including material limitations related to biocompatibility, mechanical properties, and degradation rates; fabrication complexities arising from the integration of multiple materials, resolution and accuracy, and scalability; and regulatory and ethical considerations surrounding safety and efficacy. As we explore the future directions for 4D printing, we emphasise the need for material innovations, fabrication advancements, and emerging applications such as personalised medicine, nanomedicine, and bioelectronic devices. Interdisciplinary research and collaboration between material science, biology, engineering, regulatory agencies, and industry are essential for overcoming challenges and realising the full potential of 4D printing in the biomedical engineering landscape.

Keywords: 4D printing; biocompatibility; biomedical engineering; fabrication techniques; smart materials.

Figure 1

An overview of the 4D printing process.

Figure 2

Schematics of the fused deposition modelling process.

Figure 3

Schematic representation of the stereolithography process.

Figure 4

Schematic view of the digital light processing technique.

Figure 5

Sketch of the selective laser sintering process.

Figure 6

Schematic of the multi-material jetting process.

Figure 7

Schematic representation of the direct ink writing process.

Figure 8

Selected biomedical applications of 4D printing.

Figure 9

Illustration of the self-folding process of 3D-printed structures and the formation of a T-junction. (a) The initial state of the dried and UV crosslinked hydrogel immediately after water addition. (b) Swelling and detachment of the sample from the substrate. (c) Formation and folding of the T-junction. (d) The final T-junction after water removal and drying. (e) A zoomed view of the junction area. (f,g) Side views of the structure [73].

Figure 10

(a) Various designs of multimaterial grippers fabricated for the study. (b) Illustration depicting the transition from the printed shape to the temporary shape of multimaterial grippers. (c) Sequential snapshots capturing the process of gripping an object using the multimaterial grippers [78].