Bioengineers have been able to create heart tissue and structures using 3D printers. They aim to create better In vitro The platforms will be used for the discovery of new therapeutics in heart disease. This is the leading cause for death in the United States and accounts for one out of every five deaths. They will also use 3D printed cardiac tissues to test which treatments work best for each patient. Another goal is to develop implantable tissue that can repair or replace damaged or faulty structures in a patient’s lungs or heart.
In a recent paper, Nature Materials Researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences have developed a new hydrogel infused with gelatin fibres to enable 3D printing of a functioning heart ventricle which mimics the beating of a human’s heart. Researchers found that the fiber-infused ink (FIG), which mimics the beating of a heart, allows cells in a heart ventricle printed as a 3D object to align themselves and beat together in harmony.
People have been replicating organ structures and functions in order to test the safety and efficacy of drugs and predict what may happen in clinical settings.”
Suji choi, SEAS research associate and first author.
But until now, 3D printing techniques alone have not been able to achieve physiologically-relevant alignment of cardiomyocytes, the cells responsible for transmitting electrical signals in a coordinated fashion to contract heart muscle.
The project was started to address the shortcomings of 3D printing biological tissues, says Kevin “Kit”, Tarr Family professor of Bioengineering, Applied Physics, head of the Disease Biophysics Group, and senior author.
The innovation comes from the inclusion of fibers into a printable printer ink. Choi says that “FIG ink can flow through the printing nozzle, but once the structure has been printed, it retains its 3D form.” Choi says that because of the properties, it is possible to print ventricle structures and other complex shapes in 3D without having to use extra scaffolds or support materials.
Choi used a rotary-jet spinning technique, developed by Parker’s lab, to create microfibers using a similar approach as cotton candy. Luke MacQueen (a postdoctoral research fellow and co-author in the paper) proposed that fibers made by the rotaryjet spinning technique could then be added to a 3D printer ink.
Parker says that when Luke developed the concept, he had the vision of expanding the spatial scales of 3D printers, by lowering the lower limit to the nanometer level. “The advantage of producing the fibers with rotary jet spinning rather than electrospinning” – a more conventional method for generating ultrathin fibers – “is that we can use proteins that would otherwise be degraded by the electrical fields in electrospinning.”
Choi spun gelatin fibers using the rotary jet, resulting in a material that looked similar to cotton. Next, she used sonification – sound waves – to break that sheet into fibers about 80 to 100 micrometers long and about 5 to 10 micrometers in diameter. She then dispersed these fibers in a hydrogel.
“This concept is broadly applicable – we can use our fiber-spinning technique to reliably produce fibers in the lengths and shapes we want,” Choi says. The most challenging part of this project was finding the ideal ratio between the fibers and the hydrogel to ensure fiber alignment and overall structural integrity.
Choi arranged the cardiomyocytes to align with the direction of fibers within the FIG ink as he printed 2D or 3D structures. Choi controlled the way the heart muscle cell alignment by controlling the printing direction.
She found that when she applied electrical stimulation on 3D-printed FIG structures, it caused a coordinated wave contraction in line with the direction of these fibers. Choi says that it was “very exciting” to watch the ventricle pump in a structure shaped like a heart.
She found that by experimenting with different printing formulas and directions, she was able to create even stronger contractions in the ventricle shapes.
She says, “Compared to a real-life heart, our model of the ventricle has been simplified and miniatureized.” The team now works on building more realistic heart tissues, with thicker muscles walls to pump fluids more powerfully. Although not as strong or durable as real heart tissue the 3D ventricle can pump 5-20 more fluid volumes than previous 3D heart chambers.
The technique can be used to create heart valves, miniature hearts with dual chambers and more.
Parker says that “FIGs is only one of the tools we’ve developed for additive manufacture.” As we continue to develop human tissue for regenerative therapy, other methods are being developed. The goal is not to be tool driven – we are tool agnostic in our search for a better way to build biology.”
Additional authors include Keel Yong Lee, Sean L. Kim, Huibin Chang, John F. Zimmerman, Qianru Jin, Michael M. Peters, Herdeline Ann M. Ardoña, Xujie Liu, Ann-Caroline Heiler, Rudy Gabardi, Collin Richardson, William T. Pu, and Andreas Bausch.
This work is sponsored by SEAS. The National Science Foundation via the Harvard University Materials Research Science and Engineering Center.
Harvard John A. Paulson School of Engineering and Applied Sciences
Choi, S., et al. (2023). The 3D-printed ventricles are aligned by fibre-infused gel scaffolds. Nature Materials. doi.org/10.1038/s41563-023-01611-3.