9 February 2024 | Maria Kalogeropoulou, Pedro J Díaz-Payno, Mohammad J Mirzaali, Gerjo J V M van Osch, Lidy E Fratila-Apachitei and Amir A Zadpoor
Four-dimensional (4D) printing is an emerging technology that has the potential to revolutionize tissue engineering and regenerative medicine (TERM). It builds upon 3D printing by introducing time as the fourth dimension, enabling the transformation of 3D printed scaffolds into new, distinct, and stable states upon application of one or more stimuli. This review summarizes the current developments in 4D printing for TERM, focusing on methods to achieve temporal shape changes in printed constructs. The review critically examines printing methods, types of stimuli, shape-shifting mechanisms, and cell-incorporation strategies. It also discusses the challenges and future research directions of this biofabrication technology.
The most common 4D printing methods for TERM are stereolithography (SLA) and extrusion bioprinting, followed by fused deposition modelling (FDM). Shape-shifting mechanisms used in 4D printing include shape-memory and differential swelling. Shape-memory mechanisms often use synthetic materials such as polylactic acid (PLA), poly(glycerol dodecanoate) acrylate (PGDA), or polyurethanes. Differential swelling-based 4D transformations use acrylate combinations of alginate, hyaluronan, or gelatin.
TERM applications include bone, vascular, and cardiac tissues. The field has great potential for further development by considering the combination of multiple stimuli, the use of a wider range of 4D techniques, and the implementation of computational-assisted strategies. The review highlights the use of various stimuli such as hydration, temperature, and light to trigger shape transformations in 4D (bio)printed scaffolds. The shape-shifting mechanisms include shape-memory and differential swelling, with the latter being particularly effective for creating tubular or curved structures. The review also discusses the challenges and future directions of 4D printing in TERM, emphasizing the need for further research to optimize the technology for clinical applications.Four-dimensional (4D) printing is an emerging technology that has the potential to revolutionize tissue engineering and regenerative medicine (TERM). It builds upon 3D printing by introducing time as the fourth dimension, enabling the transformation of 3D printed scaffolds into new, distinct, and stable states upon application of one or more stimuli. This review summarizes the current developments in 4D printing for TERM, focusing on methods to achieve temporal shape changes in printed constructs. The review critically examines printing methods, types of stimuli, shape-shifting mechanisms, and cell-incorporation strategies. It also discusses the challenges and future research directions of this biofabrication technology.
The most common 4D printing methods for TERM are stereolithography (SLA) and extrusion bioprinting, followed by fused deposition modelling (FDM). Shape-shifting mechanisms used in 4D printing include shape-memory and differential swelling. Shape-memory mechanisms often use synthetic materials such as polylactic acid (PLA), poly(glycerol dodecanoate) acrylate (PGDA), or polyurethanes. Differential swelling-based 4D transformations use acrylate combinations of alginate, hyaluronan, or gelatin.
TERM applications include bone, vascular, and cardiac tissues. The field has great potential for further development by considering the combination of multiple stimuli, the use of a wider range of 4D techniques, and the implementation of computational-assisted strategies. The review highlights the use of various stimuli such as hydration, temperature, and light to trigger shape transformations in 4D (bio)printed scaffolds. The shape-shifting mechanisms include shape-memory and differential swelling, with the latter being particularly effective for creating tubular or curved structures. The review also discusses the challenges and future directions of 4D printing in TERM, emphasizing the need for further research to optimize the technology for clinical applications.