Bioprinted materials can be used to repair damaged organs

A 3D printer prints out a heart. belekekin / 
Bioprinting, a type of 3D printing, uses cells and other biological materials as “inks” to fabricate 3D biological structures. Bioprinted materials have the potential to repair damaged organs, cells, and tissues in the human body. In the future, bioprinting may be used to build entire organs from scratch, a possibility that could transform the field of bioprinting.

Materials That Can Be Bioprinted

Researchers have studied the bioprinting of many different cell types, including stem cells, muscle cells, and endothelial cells.

Several factors determine whether or not a material can be bioprinted. First, the biological materials must be biocompatible with the materials in the ink and the printer itself. In addition, the mechanical properties of the printed structure, as well as the time it takes for the organ or tissue to mature, also affect the process. 

Bioinks typically fall into one of two types:

• Water-based gels, or hydrogels, act as 3D structures in which cells can thrive. Hydrogels containing cells are printed into defined shapes, and the polymers in the hydrogels are joined together or "crosslinked" so that the printed gel becomes stronger. These polymers can be naturally derived or synthetic, but should be compatible with the cells.
• Aggregates of cells that spontaneously fuse together into tissues after printing.

How Bioprinting Works

The bioprinting process has many similarities with the 3D printing process.

Bioprinting is generally divided into the following steps: 

• Preprocessing: A 3D model based on a digital reconstruction of the organ or tissue to be bioprinted is prepared. This reconstruction can be created based on images captured non-invasively (e.g. with an MRI) or through a more invasive process, such as a series of two-dimensional slices imaged with X-rays.   

• Processing: The tissue or organ based on the 3D model in the preprocessing stage is printed. Like in other types of 3D printing, layers of material are successively added together in order to print the material.
• Postprocessing: Necessary procedures are performed to transform the print into a functional organ or tissue. These procedures may include placing the print in a special chamber that helps cells to mature properly and more quickly.

Types of Bioprinters

As with other types of 3D printing, bioinks can be printed several different way. Each method has its own distinct advantages and disadvantages.

• Inkjet-based bioprinting acts similarly to an office inkjet printer. When a design is printed with an inkjet printer, ink is fired through many tiny nozzles onto the paper. This creates an image made of many droplets that are so small, they are not visible to the eye. Researchers have adapted inkjet printing for bioprinting, including methods that use heat or vibration to push ink through the nozzles. These bioprinters are more affordable than other techniques, but are limited to low-viscosity bioinks, which could in turn constrain the types of materials that can be printed.
• Laser-assisted bioprinting uses a laser to move cells from a solution onto a surface with high precision. The laser heats up part of the solution, creating an air pocket and displacing cells towards a surface. Because this technique does not require small nozzles like in inkjet-based bioprinting, higher viscosity materials, which cannot flow easily through nozzles, can be used. Laser-assisted bioprinting also allows for very high precision printing. However, the heat from the laser may damage the cells being printed. Furthermore, the technique cannot easily be "scaled up" to quickly print structures in large quantities.

• Extrusion-based bioprinting uses pressure to force material out of a nozzle to create fixed shapes. This method is relatively versatile: biomaterials with different viscosities can be printed by adjusting the pressure, though care should be taken as higher pressures are more likely to damage the cells. Extrusion-based bioprinting can likely be scaled up for manufacturing, but may not be as precise as other techniques.
• Electrospray and electrospinning bioprinters make use of electric fields to create droplets or fibers, respectively. These methods can have up to nanometer-level precision. However, they utilize very high voltage, which may be unsafe for cells.

Applications of Bioprinting

Because bioprinting enables the precise construction of biological structures, the technique may find many uses in biomedicine.

Researchers have used bioprinting to introduce cells to help repair the heart after a heart attack as well as deposit cells into wounded skin or cartilage. Bioprinting has been used to fabricate heart valves for possible use in patients with heart disease, build muscle and bone tissues, and help repair nerves.

Though more work needs to be done to determine how these results would perform in a clinical setting, the research shows that bioprinting could be used to help regenerate tissues during surgery or after injury. Bioprinters could, in the future, also enable entire organs like livers or hearts to be made from scratch and used in organ transplants.

4D Bioprinting

In addition to 3D bioprinting, some groups have also examined 4D bioprinting, which takes into account the fourth dimension of time. 4D bioprinting is based on the idea that the printed 3D structures may continue to evolve over time, even after they have been printed. The structures may thus change their shape and/or function when exposed to the right stimulus, like heat. 4D bioprinting may find use in biomedical areas, such as making blood vessels by taking advantage of how some biological constructs fold and roll.

The Future

Although bioprinting could help save many lives in the future, a number of challenges have yet to be addressed. For example, the printed structures may be weak and unable to retain their shape after they are transferred to the appropriate location on the body. Furthermore, tissues and organs are complex, containing many different types of cells arranged in very precise ways.

Current printing technologies may not be able to replicate such intricate architectures.

Finally, existing techniques are also limited to certain types of materials, a limited range of viscosities, and limited precision. Each technique has the potential to cause damage to the cells and other materials being printed. These issues will be addressed as researchers continue to develop bioprinting to tackle increasingly difficult engineering and medical problems.

References

• Beating, pumping heart cells generated using 3D printer could help heart attack patients, Sophie Scott and Rebecca Armitage, ABC.
• Dababneh, A., and Ozbolat, I. “Bioprinting technology: A current state-of-the-art review.” Journal of Manufacturing Science and Engineering, 2014, vol. 136, no. 6, doi: 10.1115/1.4028512.
• Gao, B., Yang, Q., Zhao, X., Jin, G., Ma, Y., and Xu, F. “4D bioprinting for biomedical applications.” Trends in Biotechnology, 2016, vol. 34, no. 9, pp. 746-756, doi: 10.1016/j.tibtech.2016.03.004.
• Hong, N., Yang, G., Lee, J., and Kim, G. “3D bioprinting and its in vivo applications.” Journal of Biomedical Materials Research, 2017, vol. 106, no. 1, doi: 10.1002/jbm.b.33826.
• Mironov, V., Boland, T., Trusk, T., Forgacs, G., and Markwald, P. “Organ printing: computer-aided jet-based 3D tissue engineering.” Trends in Biotechnology, 2003, vol. 21, no. 4, pp. 157-161, doi: 10.1016/S0167-7799(03)00033-7.
• Murphy, S., and Atala, A. “3D bioprinting of tissues and organs.” Nature Biotechnology, 2014, vol. 32, no. 8, pp. 773-785, doi: 10.1038/nbt.2958.

• Seol, Y., Kang, H., Lee, S., Atala, A., and Yoo, J. "Bioprinting technology and its applications." European Journal of Cardio-Thoracic Surgery, 2014, vol. 46, no. 3, pp. 342-348, doi: 10.1093/ejcts/ezu148.
• Sun, W., and Lal, P. “Recent development on computer aided tissue engineering – a review.” Computer Methods and Programs in Biomedicine, vol. 67, no. 2, pp. 85-103, doi: 10.1016/S0169-2607(01)00116-X.