Written by: David Han ‘24
Edited by: Jasmine Shum ‘24
Every year, more than 100,000 people in the US take a spot on the national organ transplant waiting list [1]. In 2020, however, only 39,000 people received a transplant, marking a large difference between the availability of organs versus the demand [1]. One of the reasons for this discrepancy is because the donor and recipient need to have a strong histocompatibility. Otherwise, if the cells from one person differ too much from the cells of another, then the recipient’s immune system will attack the donor’s organ and destroy it. Scientists have figured out ways to reduce the risk of transplant rejection through pre-screening and immunosuppressive drugs, but what if there was a way to bypass the donor entirely? Can organs be grown from a petri dish, or even manufactured? Enter 3D bioprinting, a rapidly advancing technology that has widespread applications to the field of regenerative medicine, therapeutics, and drug development.
Many people are probably familiar with 3D printing, a process in which a machine melts plastic and deposits it onto a surface layer by layer based on computer-generated coordinates. Bioprinting is similar in concept, the biggest difference being that the “ink” for the printer is organic material. The first bioprinter was invented in 2003 by Thomas Boland, who needed to create a bioink that consisted of nutrients, cells, and a structural medium to hold it all together [2]. Since then, bioprinting has come a long way in terms of the types of tissues that can be printed and the amount of complexity that can be attained within tissues. However, as one might imagine, being able to encapsulate all of the intricacies of an organ like the kidney, for example, is no easy task. Not only does a printed organ need to have networks of veins and arteries to keep the cells alive, but it also needs to have working neuronal connections to the brain in order to adapt to different physiological conditions. Another aspect to consider is whether simply stacking cells together in the shape and composition of an organ is enough to actually gain all the functionality of a naturally grown organ.
Different bioprinting methods reflect this uncertainty. A biomimicry approach involves reproducing physiologically accurate compositions of tissue on the microscale; scientists measure the total cellular makeup of a subsection of the organ and try to precisely copy it into the printer’s instructions [3]. This method is most similar to traditional 3D printing in that the full organ would be printed in one go. Alternatively, an autonomous self-assembly approach utilizes the components of developing tissues to signal and organize the growth of the organ on its own [3]. Think of this like baking; if all the right ingredients are in the right place, then with a little heat, they can combine together and make something completely new. The third approach is to create the functional components of an organ, called mini tissues, and use either biomimicry or self-assembly to join the units together [3]. This is analogous to building a car; each component is added into the frame individually until the entire ensemble is complete.
Currently, researchers are still far from printing any organ in full capacity, but there are several interesting projects utilizing bioprinting on a smaller scale. In June 2021, researchers at the University of Birmingham and the University of Huddersfield developed a skin-like substitute that could be 3D printed for the treatment of skin damage [4]. They used a gel within the bioink that enabled each layer of their skin substitute to mix together, aiding in the adhesion of the layers. The researchers chose to design three different layers to match the biological composition of real skin, which allowed their skin substitute to easily integrate with surrounding tissue after implantation on a simulated wound [4]. Yet another very promising use has been the creation of organs-on-a-chip, in which tissue scaffolds simulating the microenvironments of organs are placed on a chip that can be used to study the effects of drugs or other biological agents without the need for live subjects. 3D bioprinting’s ability to incorporate different materials in different spatial positions makes for excellent scaffold construction and control of which cells go where [5].
Researchers are continuing to push towards 3D printed organs too. A team of researchers at Harvard Medical School and Brigham and Women’s Hospital have found a way to increase the lifespan of printed tissues, which they believe is a crucial step towards being able to successfully carry out transplantations with 3D printed organs [6]. The researchers employed a technique called cryobioprinting, in which the printing takes place at very cold temperatures and the tissue is frozen immediately after printing [6]. In order to protect the tissues from damage associated with freezing, they added cryopreservative agents that stopped osmotic shock and the formation of ice crystals. With this new technique, printed tissues can be kept for up to three months as opposed to mere hours or days [6].
Cryobioprinting and other innovative approaches to printing live tissues may be promising solutions to the organ donor shortage. However, there is still a lot of work to be done before that point. Current technologies are mostly limited to printing simpler, relatively uniform biomaterials, which is ideal for structural tissues and the simulation of biological environments in the body but not adequate for organ construction.
References:
[1] “Organ Donation Statistics.” Organ donation statistics, March 2022. https://www.organdonor.gov/learn/organ-donation-statistics.
[2] “Writing the Next Chapter in the History of Bioprinting .” Biolife4D. Accessed April 15, 2022. https://biolife4d.com/writing-next-chapter-history-bioprinting/.
[3] Murphy, Sean V, and Anthony Atala. “3D Bioprinting of Tissues and Organs.” Nature News. Nature Publishing Group, August 5, 2014. https://www.nature.com/articles/nbt.2958/.
[4] Moakes, Richard J. A., Jessica J. Senior, Thomas E. Robinson, Miruna Chipara, Aleksandar Atansov, Amy Naylor, Anthony D. Metcalfe, Alan M. Smith, and Liam M. Grover. “A Suspended Layer Additive Manufacturing Approach to the Bioprinting of Tri-Layered Skin Equivalents.” AIP Publishing. AIP Publishing LLCAIP Publishing, December 1, 2021. https://aip.scitation.org/doi/full/10.1063/5.0061361.
[5] Yi, Hee-Gyeong, Hyungseok Lee, and Dong-Woo Cho. “3D Printing of Organs-on-Chips.” Bioengineering (Basel, Switzerland). MDPI, January 25, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590440/#:~:text=Organ%2Don%2Da%2Dchip,the%20cells%20and%20their%20microenvironments.
[6] Cell Press. “3D-Bioprinted Tissues Can Now Be Stored in the Freezer until Needed.” ScienceDaily. ScienceDaily, December 21, 2021. https://www.sciencedaily.com/releases/2021/12/211221133518.htm.
[7] Agarwal, Swarnima, Shreya Saha, Vamsi Krishna Balla, Aniruddha Pal, Ananya Barui, and Subhadip Bodhak. “Current Developments in 3D Bioprinting for Tissue and Organ Regeneration–A Review.” Frontiers. Frontiers, October 30, 2020. https://www.frontiersin.org/articles/10.3389/fmech.2020.589171/full.