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Bioprinting can be defined as the computer-aided manufacturing of cells and tissues to create organs. It produces 3D tissue-like structures by printing cells and biomaterials one layer over the other.
I used to play very carelessly as a child, falling down constantly and always getting hurt. My mother used to scold me: “You’ll never get new body parts, so take care of the ones you have!”
Well, the joke’s on her, because I can now 3D print my own body parts!
3D printing started with architects making miniature prototypes, but now fields like construction, manufacturing and logistics all utilize 3D printing. This led to a natural question: Can this technology also be used to print cells, tissues or organs?
YES, it can, and this exciting field is known as bioprinting.
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What Is 3D Printing?
3D printing is the process of converting three-dimensional digital files into their physical forms using “printing ink”. Multiple layers of this “ink”, a type of printing material, are laid successively on top of each other. Adding layers of the material allows designers to create complex structures and geometries.
Bioprinting is an organic extension of 3D printing, where living tissue and/or organs are printed. Cells are layered over each other, resulting in 3D biological structures. The desired tissue/organ is designed using computer-aided software, after which it is printed into reality.
3D-bioprinted tissues are very similar to our living tissues/organs, with minute cellular details, such as microvascular networks and cellular junctions that link cells together; even these microscopic details can be bioprinted accurately.
The printed structure is then subjected to tissue remodeling and is allowed to mature in a specialized vessel known as a bioreactor. Once mature, these organs are then capable of withstanding blood flow.
Also Read: Could We Produce Organs In Space?
How Is Bioprinting Done?
The process of bioprinting involves 4 basic steps:
- Scanning the tissue to be 3D bioprinted
- Selection of bioink
- The bioprinting stage
- Incubating the 3D bioprinted organ
Tissue engineers will scan a healthy body part to create a digital design. Imaging technologies like a CT (computed tomography) or MRI (magnetic resonance imaging) scan are used, depending on what information is required.
It is important that the organ closely matches its recipient; computer-aided software is used to model the tissue precisely. This software generates a set of instructions for the 3D printer to create the replica.
Based on the tissue being printed, the printing materials will be selected. Just as conventional printers need ink cartridges, bioprinters use a special type of bioink. Bioink contains living cells, such as stem cells, mixed with microgels that provide a suitable environment (water, oxygen, nutrients) for the cells to remain alive.
Consider a patient who has been badly burned and is suffering from intense burn wounds. Stem cells called mesenchymal stroma cells might be the bioink used to regenerate that patient’s burnt skin.
Once the object to be bioprinted is scanned, instructions for the printer have been generated, and the bioink has been selected, the actual process of bioprinting can begin.
Based on the tissue/organ and material selected, the right bioprinting strategy is decided upon. There are three approaches to this, which will be outlined later in this article.
The bioprinted tissue/organ is incubated in a bioreactor, which stimulates the environment in which the tissue/organ normally lives. After its time in the bioreactor, the organ can be used for transplantation or research work. This step depends on the complexity of the tissue/organ and is not always required.
Also Read: What Is An Organ-On-A-Chip?
Approaches To 3D Printing
There are three approaches to bioprinting:
1. Biomimicry: In this approach, the part to be replicated is bioprinted around a scaffold. The idea here is that the function of the body part can be replicated if the form or structure is the same as the original. Tissues that are bioprinted using this approach require a bioreactor for further maturation.
2. Autonomous self-assembly: In this approach, embryonic organ development occurs, followed by tissue replication. The idea here is that if the correct embryonic elements are in place, natural development will follow, without the need for a scaffold. Cells and supporting structures will self-organize and interact with each other to form the final body part. The first biological blood vessel was bioprinted using this approach.
3. Mini tissues: This approach is a combination of the other two. These “mini tissues” are the structural and functional units of a tissue, and such mini tissues are added to the bioink and printed.
Mini tissues have anywhere between 500 and 10,000 cells cultured under specific conditions that allow them to live and adhere to each other. These cultured cells make up the bioink.
Many layers of the mini tissues are bioprinted together, after which they self-assemble into the target organ.
Three Bioprinting Techniques
- Inkjet bioprinting
- Laser printing
Inkjet bioprinters are the most commonly used type of printers. They work in a manner very similar to our conventional 2D inkjet printers, where the desired volumes of bioink are expelled onto pre-defined spots of a substrate.
Inkjet bioprinters most often use heat (200-300°C) to produce bursts of pressure that push the bioink out of the printer nozzle in the form of droplets. Another type of inkjet bioprinter creates pulses using piezoelectric pressure.
Certain piezoelectric elements, such as crystals or ceramics, compress and bend when an electrical charge is applied to them, thus squeezing out precise amounts of bioink onto the receiving substrate.
Microextrusion 3D bioprinters print biological materials in the form of tiny beads that flatten out on a surface due to high pressure. In this manner, it prints successive layers of beads, with each layer acting as a base for the next one, until a 3D structure is eventually generated.
A laser printer makes use of a metal ribbon coated with biological materials, such as cells, a laser and a receiving substrate, and is usually glass covered with a laser-absorbing material.
The laser vaporizes the biological materials on the metal ribbon, which then flow in droplet form onto the receiving substrate. This receiving substrate supports the cells and allows them to grow.
Refer to the articles here and here if you are interested in knowing more about different types of bioprinting and the advantages of using each of the abovementioned bioprinters.
Bioprinting has revolutionized the healthcare sector. A patient’s cell samples can now be cultured to create individualized bioink that can then be used to 3D print tissues and organs. Since these cells are taken from the patient receiving the organ, the chances of organ transplant rejection are very low.
Bioprinted organs can also be used for drug testing purposes, thus reducing the use of animal testing.
Bioprinting is an economical, accurate and relatively easy method of manufacturing tissues/organs that effectively solves the problem of donor organ shortages and donor rejection in one fell swoop.
Areas for improvement in this technology are the feasibility, speed, accessibility, toxicity and bio-compatibility of the process, but the future is looking bright!
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References (click to expand)
- Derakhshanfar, S., Mbeleck, R., Xu, K., Zhang, X., Zhong, W., & Xing, M. (2018, June). 3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances. Bioactive Materials. Elsevier BV.
- Vyas, D., & Udyawar, D. (2018, June 5). A Review on Current State of Art of Bioprinting. 3D Printing and Additive Manufacturing Technologies. Springer Singapore.
- Bishop, E. S., Mostafa, S., Pakvasa, M., Luu, H. H., Lee, M. J., Wolf, J. M., … Reid, R. R. (2017, December). 3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends. Genes & Diseases. Elsevier BV.
- Murphy, S. V., & Atala, A. (2014, August). 3D bioprinting of tissues and organs. Nature Biotechnology. Springer Science and Business Media LLC.
- Ngo, T. D., Kashani, A., Imbalzano, G., Nguyen, K. T. Q., & Hui, D. (2018, June). Additive manufacturing (3D printing): A review of materials, methods, applications and challenges. Composites Part B: Engineering. Elsevier BV.
- Mironov, V., Reis, N., & Derby, B. (2006, April). Review: Bioprinting: A Beginning. Tissue Engineering. Mary Ann Liebert Inc.
- Gungor-Ozkerim, P. S., Inci, I., Zhang, Y. S., Khademhosseini, A., & Dokmeci, M. R. (2018). Bioinks for 3D bioprinting: an overview. Biomaterials Science. Royal Society of Chemistry (RSC).