Speaker
Description
Introduction
Shape changes during heart development, known as looping, are crucial for its morphogenesis [1]. Conventional bioprinting techniques produce static structures that bypass the shape-morphing cascades, essential for tissue maturation during development. 4D materials that can undergo shape changes due to external stimuli such as magnetic fields, light, etc., can play a key role in mimicking these dynamic shape changes, which is critical in understanding heart development [2]. They can also regulate the spatial arrangement of cells in 3D-engineered cardiac structures. Magnetic bioinks for 4D shape-morphing have been studied before and proven to improve hydrogel cell-seeding efficiency [3]. However, the complexity of motion that can be achieved with this technology has been restricted.
Herein, we have developed controlled geometries using collagen-based magnetic inks and actuated them by an external magnetic field to mimic the cardiac shape changes occurring at the embryonic stage. Further, we have studied the patterning and assembly of human iPSC-cardiomyocytes encapsulated in the ink. We believe that the 4D shape-morphing due to the programmed magnetic actuation would improve the functionality of the human iPSC-cardiomyocytes.
Methods
Fe3O4 magnetic nanoparticles (MNPs) of varying concentrations (0-5 mg/ml) were mixed with 4.8 mg/ml of neutralized collagen to form the acellular bioink. We conducted biocompatibility and rheology analysis with these concentrations to determine the optimal MNP concentration for further studies. 5 mg/ml of the MNP was chosen to print multimeric geometries with collagen and magnetic ink in a 0.5% agarose support bath. The constructs were then actuated with the help of an external magnetic field built within an in-house 3D bioprinter with an integrated magnetic probe with XYZ control. Further, the viability of the human iPSC-cardiomyocytes encapsulated within the bioinks in a support bath was determined by a live-dead assay. Conjugation of the Fe3O4 to collagen was prepared for docking using UCSF Chimera, followed by docking with Autodock Vina.
Results
The developed collagen-based magnetic ink exhibited superior printability and rheological properties. As shown in Figure 1C, upon programmed magnetic actuation, the multimeric U-shaped geometry bends or forms a closed loop mimicking the shape changes like bending, buckling, and twisting that happen during embryonic cardiac looping. The straight tube with magnetic ends buckles together to form a U-like geometry, with the tail ends attracted to the magnetic probe.
Discussion
The programmed magnetic actuation to the multimeric geometries replicated the embryonic shape change during cardiac looping. Ongoing work involves the actuation of the human iPSC-cardiomyocytes encapsulated within the magnetic bioink, which is believed to enhance its functionality.
References
[1] J. Männer, J Cardiovasc Dev Dis 2024, 11, 252.
[2] A. Pramanick, T. Hayes, V. Sergis, E. McEvoy, A. Pandit, and A. C. Daly, Advanced Functional Materials 2025, 35, 2414559.
[3] J. Chakraborty, J. Fernández-Pérez, M. T. Ghahfarokhi, K. A. van Kampen, T. ten Brink, J. Ramis, M. Kalogeropoulou, R. Cabassi, C. de J. Fernández, F. Albertini, et al., CR-PHYS-SC 2024, 5, DOI 10.1016/j.xcrp.2024.101819.
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