How far is the real “3D printed heart” from us?

On August 2, a research team led by Adam Feinberg of Carnegie Mellon University announced in a study published in Science that the team designed the FRESH2.0 printing system and successfully used it. A left ventricle with contractile capacity is obtained.

“This is a major contribution of bio 3D printing technology to the scientific development of regenerative medicine and organ remodeling.” Sun Wei, a professor of mechanical engineering at Tsinghua University, told Intellectuals that the construction of functional myocardial tissue containing vascular channels has been a myocardium. Difficulties in tissue engineering. This innovation proves that 3D printing can construct myocardial tissue with microchannels, form intravascular channels through subcutaneous culture, and achieve functional contraction under external stimulation.

“3D printing” was originally obtained by layering the adhesive material as “ink” to obtain three-dimensional objects. In recent years, with the development of technology and the variety of “ink”, 3D printing technology has been applied to more and more fields: Small to clothing toys, large to automotive and aerospace materials. Using bioactive materials such as cells and growth factors as "ink" "3D bio-printing" printed in hydrogels has begun to emerge in the development of drugs and manufacturing organs. Experiments have been successful in repairing knee cartilage defects with 3D bioprinted cartilage tissue. . But so far it has not been possible to build a functional whole organ with 3D printing technology.

In April 2019, the Tal Dvir team at Tel Aviv University (TAU) used the cardiomyocytes and endothelial cells obtained from patient tissue to create the world's first 3D printed complete structure of cherry size in hydrogels added to the cytoplasmic matrix. heart. However, Sun Wei commented that the heart “seems not to be like a god” and does not have the physiological function of the heart.

In the latest study, the Adam Feinberg team designed the FRESH2.0 printing system, which used a printing strategy for cardiomyocytes and collagen to print a left ventricular model and further analyzed the function of the model. Electrophysiological behavior and ventricular contraction associated with arrhythmia.

The FRESH2.0 printing system was developed based on the successful use of collagen. Collagen plays an important role as a "scaffold" in the cytoplasmic matrix to maintain cell structure, provide adhesion, and conduct signals.

Researchers have improved the assembly mechanism of biomaterials in hydrogels—using the pH change to drive the self-assembly of biomaterials. Compared with traditional thermal driving, pH-driven assembly solves the problem of traditional hydrogel softness and insufficient support. It allows the use of a stronger concentration of collagen as an ink to enhance mechanical properties and is more conducive to the manufacture of complex structures. Not only that, the researchers improved the production process of gel particles, reduced the diameter and dispersion of gel particles, and adjusted the shape of the gel particles into a uniform spherical shape, which increased the resolution of printing by an order of magnitude. These two improvements enable the printing of precision collagen in hydrogels.

To demonstrate the functionality of the FRESH2.0 printing system, the researchers first implanted the print into the skin of the mouse and found that it was able to generate a complete vascular network. The system in turn prints a left ventricle with contractile capacity and a tricuspid valve capable of carrying physiological stress, indicating the mechanical integrity of the collagen structure in the human body. The perfusion of the vascular network was verified by perfusion. Finally, the human heart collagen model of the neonatal ratio was printed, thereby demonstrating the ability of FRESH2.0 to print large structures.

So, does this prove that FRESH2.0 can print a full-featured heart? Adam Feinberg said there are still many challenges to overcome, such as the billions of cells needed for printing. At present, FRESH2.0, as a printing system, has the ability to build models and has the potential to be a powerful tool for studying organ structure, mechanical strength and biological properties.

For the future of 3D printing heart, Sun Wei believes, “We may never expect to print a physiologically functional heart directly with 3D printing.” Why?

Sun Wei added that with the development of bio-3D printing technology, the use of novel bio-inks, breakthroughs in stem cells and cell biology, it is possible to print out the biological models needed for cardiac regeneration using bio-3D printing technology, and then on this basis. In the end, through the cross-fusion of cell biology and developmental biology, the heart is finally reconstructed.

"I am optimistic that we will still need 15 years of effort from this day." Sun Wei finally predicted.