Image credit: Illus_man / Shutterstock.com
Around the world hundreds of thousands of people await a life-saving organ transplant, yet, many of those awaiting will not receive a donation in time and those that do will face years if not a lifetime of immune-suppressing drugs treatment to prevent organ rejection.
However, a team of Bioengineers has developed a pioneering approach for bioprinting tissues which would mean overcoming a major barrier concerning the 3D printing of organs.
This exciting new breakthrough could mean an acceleration into the future of organ replacement. One in which anyone requiring a transplant would not have to rely on the selflessness of a willing donor, but rather be the recipient of a personalized organ generated from their own cells. This smart advance would also mean the risk of organ rejection is drastically reduced.
Bioengineers Jordan Miller and Kelly Stevens of Rice University and the University of Washington (UW) respectively led the research team which included associates from Rowan University, Duke University, and Nervous System, a design firm based in Massachusetts. Their latest research and development allows for an innovative technique that would enable the creation of complex, rhizomatic vascular networks that mimic the body’s systems for carrying blood, lymph, air, and other important fluids.
“One of the biggest roadblocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues,” said Miller, who is an associate professor at the Brown School of Engineering, Rice University. “Further, our organs actually contain independent vascular networks — like the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver. These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way.”
Multivascularization is an important factor in the process because form and function often go hand in hand. Kelly Stevens, investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine stated, “Tissue engineering has struggled with this for a generation.” With one of the key issues being how to marry the structure and arrangement of the tissue with how it should act in the body.
With this work we can now better ask, ‘If we can print tissues that look and now even breathe more like the healthy tissues in our bodies, will they also then functionally behave more like those tissues?’ This is an important question, because how well a bioprinted tissue functions will affect how successful it will be as a therapy.
Kelly Stevens, Investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine
Therefore, the main drivers of fine-tuning the bioprinting methodology is to produce capable working organs and tissues to alleviate the pressure applied on various healthcare systems around the world – as the demand for organ donation exceeds what is possible to deliver – and to also find a way around the issue of the aforementioned organ rejection. “We envision bioprinting becoming a major component of medicine within the next two decades,” Miller said.
Another issue to overcome is that the functionality of certain organs, such as the liver, are extremely difficult to compensate for if they start to fail in the body. “The liver is especially interesting because it performs a mind-boggling 500 functions, likely second only to the brain,” Stevens said. “The liver’s complexity means there is currently no machine or therapy that can replace all its functions when it fails. Bioprinted human organs might someday supply that therapy.”
The technique of bioprinting stems from the technology of 3D printing and uses bioinks that are made up of living cells to print tissues layer by layer. Then, to add support to the structured cells a scaffold or template is required to fabricate complex biological structures. Miller and Steven’s team created an open-source bioprinting technology they called the “stereolithography apparatus for tissue engineering,” or SLATE. This system produces soft hydrogels one layer at a time via additive manufacturing.
Printing layers from a solution of liquid pre-hydrogels and then solidifying them by exposing them to blue light. As each layer is solidified in turn, an overhead arm raises the expanding 3D gel just enough to introduce the liquid to the next image from the projector. One of the major insights of Miller and Bagrat Grigoryan, a Rice graduate student and co-author of the study, was the amalgamation of food dyes that absorb blue light into the solution. Thus, confining the solidification to a very fine layer and enable the system to generate pliable water-based, biocompatible gels with an exquisite internal architecture in just a few minutes.
During tests of a lung mimicking structure the researchers discovered that the tissues were robust enough to withstand simulations of blood flow and pulsatile breathing. They found that red blood cells could absorb oxygen as they flowed through a network of blood vessels surrounding the air sac - a movement of oxygen similar to the gas exchange that occurs in the lung’s alveolar air sacs.
Co-founders of Nervous System Jessica Rosenkrantz and Jesse Louis-Rosenberg worked with Miller directly on the study’s intricate lung mimicking structure. “When we founded Nervous System, it was with the goal of adapting algorithms from nature into new ways to design products,” Rosenkrantz said. “We never imagined we’d have the opportunity to bring that back and design living tissues.”
These unique developments and advances currently being made to assist in the printing of intricate and functioning tissues are extremely exciting, yet, it will still take some time for us to witness the successful bioprinting of entire organs suitable for transplantation. Progress is still needed to take the research beyond the small, relatively simple tissue structures to large, complex complete organs in areas such as vascular network integration. However, the latest innovations and data have been made widely and publicly available and Miller remains optimistic stating, “Making the hydrogel design files available will allow others to explore our efforts here, even if they utilize some future 3D printing technology that doesn’t exist today.”