While the number of patients waiting for organ transplantation is continuously increasing, the number of organ donors is always far less than that. For replacing the insufficiency of organ donors, three dimensional (3D) printing technology began to be used in the bioindustry.

Through 3D bioprinting, bones, ears, exoskeleton, blood vessels, tissues, and organs can be produced. The bioindustry fields utilizing the technology are body transplantation, anatomical model, and pharmaceutical industry research. In general, 3D printing types include laser, inkjet, and extrusion, and among these, inkjet-based printers are the most used for bioprinting.

The process of inkjet-based 3D bioprinting is as follows: (1) Create blueprints of the tissue or organ. (2) Extract stem cells from the patient and differentiate them into cells of a specific tissue or organ. (3) Fill the printer's bioink with the differentiated cells, vascular cells, and other necessary media. (4) Put the bioprinted result in a bioreactor to look at the reaction. (5) Transplant into the patient.

Since it is the transplantation of organs made by culturing cells extracted from the patient's body, rather than human-to-human transplantation, side effects and secondary infections can be significantly reduced. Other advantages include that it is possible to produce a personalized organ, saving time as a result, and available regardless of location.

However, as the human body constantly changes, the tissues or organs that are transplanted in the body must also be able to transform itself according to environmental factors. Four-dimensional (4D) bioprinting is a technology currently being developed to satisfy this aspect. 4D printing is the first technology known in 2013 by Prof. Skylar Tibbits of MIT Self-Assembly Lab in the United States, and in 2014, Korea Institute of Science and Technology Information (KISTI) selected 4D printing as one of the top 10 promising technologies.

▲ 4D printing is creating something that can be self-assembled through a 3D printer.

4D printing is about creating a "smart material" that can be self-transformed or self-assembled by various energy sources such as temperature and humidity even after the production through a 3D printer. In other words, the concept of time (one dimension) has been added to 3D (three-dimensional) printing.

In terms of self-assemblable, 4D printing is a necessary technology, especially in the bioindustry. This is because, in general, natural biomolecules recognize other biomolecules and make changes such as synthesis and migration. To be specific, in the process of cell formation, polymers (including nucleic acids, proteins, polysaccharides, lipids, etc.) are made from simple precursors, and then larger and more complex structures such as macromolecular systems and organelles are formed. The polymers contain the information necessary for them to be self-formed into macromolecular systems.

A typical example is when a single DNA strand recognizes the opposite single DNA strand, and the two join to form a double-stranded DNA. Another example could be the case when many proteins and ribonucleic acid molecules self-assemble to form ribosomes. Moreover, the cases where the antibody recognizes and binds to a specific antigen and the fiber synthesis of flagella protein are also great examples of self-assembly.

Stimulants that activate self-assembly include physical stimulants such as temperature, humidity, light, magnetic field, electric field, chemical stimulants such as pH and ionic concentration, and biological stimulants such as glucose and enzymes. A number of elements can be used as a stimulator of 4D bioprinting results.

4D printing has tremendous potential as it can be used in various fields such as tissue regeneration in the bioindustry (making and transplanting scaffold proteins necessary for tissue regeneration), medical device manufacturing, drug administration, and medical diagnosis. Besides, the advantages of 4D bioprinting are that the size of the initial product can be reduced as much as possible to minimize the scar at the site of transplantation, and new complex structures can be created using lower-level molecules.

However, as there are a wide variety of stimulants and directions, 4D bioprinting technology is still only at an early stage. This is because all possibilities caused by biosynthetic and molecular biology principles must be considered, and side effects and secondary problems such as secondary infection must be identified.

Last year, a Korean bio company released the first 4D bioprinter product to which human organ regeneration technology was applied, and showed demonstrations such as printing artificial skin. I hope that it was a successful first step in 4D printing technology. Also, in the future, we all hope that the number of patients leaving the world waiting for donors would be zero as artificial organ transplant treatments significantly improve.


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