The use of 3D printers in the medical and dentistry field is vastly growing from dental implants to prosthetics, and models for surgeons to practice on before making cuts on a patient. Researchers have advanced past printing with plastics and metals to printing with cells that form into living human tissues. Although no one has printed fully functional transplantable human organs, scientists are making improvements. Researchers have been developing pieces of human tissue that can be used to test drugs and creating methods to succeed in the challenges of recreating the body’s complex biology. This article will explore some of the milestones achieved by research groups as well as some of the challenges they have faced on the journey to creating 3D printed organs.
Cardiac Cells and Ear Transplants
Thus far, scientists have printed mini organoids and microfluidic models of tissues that are also known as organs on chips. The results from both microfluidics and organoids show encouraging insights into operating like the human body. Pharmaceutical companies created the models and are testing drugs before moving into animal studies, after which they will be moving to clinical trials. One group involved in the clinical trials printed cardiac cells on a chip and attached the cells to a bioreactor before testing the cardiac toxicity of a commonly known cancer drug, doxorubicin. The team revealed that the cells’ beating rate reduced significantly after exposure to the medication.
Robby Bowles, a bioengineer at the University of Utah, stated that other companies had been involved with 3D printing. The companies studied printing 3D ears, transplanting the ears to children who had congenital disabilities such as underdevelopment of the ears. He acknowledged initial attempts of using 3D printing in the medical field.
Organovo Studies
Most recently, researchers have built patches of tissues that emulate fractions of particular organs but haven’t been able to replicate the complexity or cell density of a full organ. Some studies show that even a patch of human tissue could be useful for treatment in patients. However, Organovo, a company that announced its program to design 3D printed liver tissue for human transplants, revealed the results from a previous study. The company presented a successful live implant in a mouse model of genetic liver disease which raised multiple biomarkers that showed improvement in liver function.
Researchers have also made progress with one of the biggest challenges in printing 3D organs by creating blood vessels or arranging of blood vessels in an organ, also known as vasculature. After patches were implanted into the mouse’s liver in the Organovo study, blood was supplied to it by the surrounding liver tissue. Still, an entire organ would need to be prepared for blood flow.
Wyss Institute
In 2018, Sébastian Uzel, Mark Skylar-Scott, and a team at the Wyss Institute were able to 3D print a tiny, beating heart ventricle complete with blood vessels. A few days later after printing the tissue, Uzel says he came into the lab and found a piece of tissue twitching, that was “very terrifying and exciting.”
The team used embedded printing rather than printing the veins in layers, a method in which instead of building from the bottom of a slide upwards, materials are released directly into a bath or matrix. This approach allows researchers to print “free form in 3D,” according to Skylar-Scott, instead of having to print a vascular tree. The matrix, in this case, was cellular material that made up the heart ventricle. This material, a gelatin-like ink, pushed these cells gently out of the way to create a network of channels. Once the printing was completed, the combination was then heated up. This heat caused the cellular matrix to solidify but caused the gelatin to liquify so it could then be washed out, leaving room for blood to flow through.
Challenges
Though there are many advancements in 3D printing organs, scientists remain “a ways away” from printing more intricate tissues and organs that can be transplanted into living organisms, but this is the objective for many scientists to achieve soon according to Bowles. As reported by the United Network for Organ Sharing, there are over 112,000 people in the US waiting for an organ transplant, and 20 of those waiting die each day.
For a long time, biological engineers have attempted to construct 3D structures that they could seed among stem cells that could later develop and form into organs. One reason this could be challenging according to Bowles “to a large extent don’t allow you to introduce the kind of the organization of gradients and the patterning that is in the tissue,”. Bowles also says “there is no control over where the cells go in that tissue.” In contrast to 3D printing which provides researchers with the ability to precisely direct the organization of the cells that could guide better control over organ development.
Another important aspect is that 3D printed organs would need to be created from cells that the patient’s immune system could identify as its own to prevent immune rejection and the need for patients to be prescribed immunosuppressive medication. 3D printed organs could be developed from patient-specific induced pluripotent stem cells. However, the difficult aspect is getting the cells to differentiate into the subtype of mature cells required to form a specific organ. Bowles believes that “the difficulty is kind of coming together and producing complex patternings of cells and biomaterials together to produce different functions of the different tissues and organs.”.
Potential Solutions Moving Forward
To accomplish the emulation of patterns shown in vivo, there are still other methods scientists would have to develop. Scientists can print cells into hydrogels or different environments along with molecular signals and gradients built to influence the cells into arranging themselves into lifelike organs. 3D printing can be used by scientists to create these hydrogels as well.
In the meantime, 3D printing of tissues is helping to expedite basic and clinical research regarding the human body. Though challenges associated with 3D printing remain, it has great potential to create organs and provide lifesaving organ transplants to patients. The advancement of the 3D printing continues to show promising results that could one day be effective in treating patients with critical conditions.
Sources:
- https://www.the-scientist.com/news-opinion/on-the-road-to-3-d-printed-organs-67187?_ga=2.230604892.1926843048.1587572466-1658288134.1587572466
- https://organovo.com/wp-content/uploads/2019/01/ORG-AASLD2017-805_THX_VJ-FINAL.pdf
- https://unos.org/data/transplant-trends/
- https://www.bme.utah.edu/department-directory/#/filter-Faculty
- https://bioe.uic.edu/profiles/alsberg-eben/
- https://www.prellisbio.com/team
- https://lewisgroup.seas.harvard.edu/people/mark-skylar-scott
- https://lewisgroup.seas.harvard.edu/people/s%C3%A9bastien-g-m-uzel
- https://advances.sciencemag.org/content/5/9/eaaw2459