Kavish Saini, Downingtown STEM Academy, Downingtown, Pennsylvania, USA
Over 17 people die each day waiting for an organ donor, according to the HRSA (U.S. Health Resources & Services Administration) in 2020. With over 100,000 patients currently waiting for a transplant in the U.S. alone, waiting for a matching organ donor is no longer the most accessible solution (HRSA, 2021). Thankfully, more advanced medical technology has slowly started to establish its presence. Bioprinting is no exception to these revolutionary technologies.
Bioprinting Basics
Bioprinting has made dramatic leaps in progress during the past few years. As a branch of additive manufacturing, bioprinting uses biological materials to cultivate biomolecules for use in medical settings as replacements for human cells (Zhang et al., 2017). 3D printing makes this technology possible. These machines mainly use extrusion-based printing, a process involving the controlled expulsion of melted materials (often plastic) in layers stacked upon each other to form any structure or item imaginable (Papaioannou et al., 2019). Bioprinting uses the same technology, but it extrudes cells and different types of biomaterials instead of plastic. They both use computer programs to help guide their printing processes.
Due to the complexity of specific organs/tissues and the needs of the patients, many different printing methods have emerged. The three main types of bioprinting are extrusion-based, inkjet-extrusion, and laser-assisted (Kačarević et al., 2018). Many companies are currently researching these processes as the mainstream solution for hospitals and pharmaceutical companies.
Figure 1. Simplified diagram of an extrusion bioprinter
The extrusion-based printing style is similar to standard 3D Printers. Using a syringe filled with biomaterials, the bio-ink is pushed into a flat surface, liquid bath, or scaffolds (premade structures to help the printed cells further grow into a specific form) as seen in Figure 1 (Leberfinger et al., 2017). These prints are constructed by a single continuous string that is around 100 to 400 nanometers thick (depending on the required resolution). The advantage of extrusion-based printing is that a print can have a very high cell density compared to other methods, which is helpful in certain types of tissues and organs. Its design is straightforward to not only manufacture but maintain as well. However, the nozzle limits the printing resolutions, causing these prints to be less refined than other methods, preventing them from being used in more detail-oriented organs.
The biomaterials for extrusion printing are very vast; for example, printed facial tissues can be composed of Hyaluronic acid, Gelatin, Glycerol, and Fibrinogen (Leberfinger et al., 2017). Despite the significant variation in biomaterials, all materials are a form of viscous hydrogels (Derakhshanfar et al., 2018). Because of the force applied when the syringe is trying to push the gel out, it can damage any other type of highly viscous biomaterial.
Figure 2. Simplified diagram of an inkjet bioprinter
The mechanism of ink-jet printing is very similar to that of extrusion printing. However, instead of pressure, it uses a thermal component to induce the material to bubble, expelling the biomaterials into a substrate plate or scaffold. Some methods use a piezoelectric element to create acoustic waves to help dispel the biomaterials instead. This was one of the first methods used to print out live cells, and scientists found that, unlike the extrusion methods, the biomaterials used for inkjet printers need to be highly hydrated due to the temperature used to control the fluid (between 100-300 C) (Xie et al., 2020). Inkjet generally offers a high resolution along with other advantages such as higher print speeds, the ability to print high viscosity biomaterials, and high fabrication speeds. However, the low cell concentration of the ink is held back by the low droplet maneuverability and unreliable cell encapsulation. Ink-jets are used similarly to extrusion printing for soft tissue development (Derakhshanfar et al., 2018).
Figure 3. Simplified diagram of a laser-assisted bioprinter
Laser-Assisted Bioprinting (known as LAB) is a printing method unique to the inkjet and extrusion-based system (Xie et al., 2020). Instead of having physical control of the biomaterial (which can damage more sensitive materials), it uses a laser to pulse a beam onto a triple-layered structure to “dot” the substrate plate with the desired shape of the bio-ink. This “sandwiched” structure consists of an energy-absorbing layer, a donor layer, and the bio-ink layer. When the laser flashes onto a particular spot, it is first absorbed by the energy absorbing layer (often made of metals such as titanium or gold). This thermally excites the donor layer, which will bubble up on the bio-ink layer below, and controllably eject a tiny droplet of the bio-ink onto the substrate (similarly to the inkjet). This allows for many types of material to be used since there is no chance of it being damaged by physical expulsion. However, the lack of a nozzle can cause the resolution quality not to be as fine as some of the other controlled methods.
Impact of Bioprinting
As mentioned earlier, there are many weaknesses in the current organ transplant method. Over 6,205 people die each year simply waiting for a transplant and with the average wait time at about 3-5 years, this is a problem that needs more attention (HRSA, 2021). Moreover, the process is indirectly discriminatory towards certain patients as those with a blood type of ‘O’ had an 85 month wait time for kidney grafts compared to the 59 month wait time by non ‘O’ blood type recipients (Glander et al., 2010). This fact means an increased death rate for those with certain blood types. While rejection rates have drastically reduced as medicine improved, it still currently sits at about 10-15% (HRSA, 2021).
A surprisingly common issue with transplantation is transporting the organs. Not only do organs have a short shelf life, they are costly to transport. Even then, between 2014-2019, 170 expired in transit and 370 experienced “near misses” (Aleccia, 2020). For a lifesaving process in such high demand but in great shortage, 3D bioprinting presents viable solution.
This technology has the potential to personalize and optimize many current medical procedures. Each printer can print different types of grafts, cartilage, bones, and even certain organs in less than a day. This could be the difference between life and death for certain patients who need an immediate organ transplant. Printed biological organs can drastically cut wait times for all organ recipients and further reduce the risk of transplant rejection. By using cell culture grown from the patients themselves, this technology engineers organs that biologically suit patients, lowering the risk of rejection. The transplant waitlist timing will also be shortened as these organs can be printed in the hospital within a week and then surgically implanted right after (Derakhshanfar et al., 2018).
Furthermore, this technology reduces ethical concerns regarding organ transplants and drug testing. Doctors are no longer faced with the ethical dilemma of taking organs from a healthy person- or picking one patient over another to receive a transplant. Use of 3D-printed organs does not require these ethical considerations. They can completely cut animal testing for new pharmaceutical drugs and ethically produce more dependable test results. Pharmaceutical industries can test dangerous drugs for deadly conditions on printed replicas of organs to test the drugs instead of on desperate patients searching for a cure.
While these machines still have to be perfected to be able to print more complex organs, this idea is feasible and simply requires more time for research and development. Still, there are many working prototypes printing simpler tissues that are already being used in universities and hospitals across the country. 3D bioprinting is on the brink of revolutionizing many aspects of the healthcare and pharmaceutical industry.
References
Aleccia, J. N. (2020, February 27). How lifesaving organs for transplant go missing in transit. Kaiser Health News. Retrieved September 28, 2021, from https://khn.org/news/how-lifesaving-organs-for-transplant-go-missing-in-transit/.
Derakhshanfar, S., Mbeleck, R., Xu, K., Zhang, X., Zhong, W., & Xing, M. (2018). 3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances. Bioactive materials, 3(2), 144–156. https://doi.org/10.1016/j.bioactmat.2017.11.008
Glander, S., Budde, K., Schmidt, D., Fuller, T., Giessing, M., Neumayer, H., Liefeldt, L. (2010), The ‘blood group O problem’ in kidney transplantation—time to change?, Nephrology Dialysis Transplantation, Volume 25, Issue 6, June 2010, Pages 1998–2004,
HRSA Staff, Organ Donation Statistics. Organ Donor. (2021). https://www.organdonor.gov/statistics-stories/statistics.html.
Kačarević, Ž. P., Rider, P. M., Alkildani, S., Retnasingh, S., Smeets, R., Jung, O., Ivanišević, Z., & Barbeck, M. (2018). An Introduction to 3D Bioprinting: Possibilities, Challenges and Future Aspects. Materials (Basel, Switzerland), 11(11), 2199. https://doi.org/10.3390/ma11112199
Leberfinger, A. N., Ravnic, D. J., Dhawan, A., & Ozbolat, I. T. (2017). Concise Review: Bioprinting of Stem Cells for Transplantable Tissue Fabrication. Stem cells translational medicine, 6(10), 1940–1948. https://doi.org/10.1002/sctm.17-0148
Papaioannou, T. G., Manolesou, D., Dimakakos, E., Tsoucalas, G., Vavuranakis, M., & Tousoulis, D. (2019). 3D Bioprinting Methods and Techniques: Applications on Artificial Blood Vessel Fabrication. Acta Cardiologica Sinica, 35(3), 284–289. https://doi.org/10.6515/ACS.201905_35(3).20181115A
Xie, Z., Gao, M., Lobo, A. O., & Webster, T. J. (2020). 3D Bioprinting in Tissue Engineering for Medical Applications: The Classic and the Hybrid. Polymers, 12(8), 1717. https://doi.org/10.3390/polym12081717
Zhang, Y. P., Sun, J., & Ma, Y. (2017). Biomanufacturing: history and perspective. Journal of industrial microbiology & biotechnology, 44(4-5), 773–784. https://doi.org/10.1007/s10295-016-1863-2