3D-Printed Organs Are The Future Of Transplantation

Receiving an organ transplant is usually a life-saving event for a patient in need — but now, due to advancements in modern medical technology, this essential procedure may not even require a human donor.

When you think of an organ transplant, you probably envision an organ transfer from one person to another. This may have been the only option for many decades, but 3D bioprinting technology is changing how we think about organ transplantation.

According to the US Health Resources and Services Administration (HRSA), over 105,000 patients across the country are currently on the waiting list to receive an organ transplant¹. With a new person being added to the waitlist every nine minutes, it is clear that human organs are in high demand — and the consequences of these long wait times can be life or death¹.

Due to limited resources and a lack of education about becoming an organ donor, over 6,000 Americans die yearly while waiting for an organ transplant (up to 17 people a day)¹. Looking to find ways to mitigate this health crisis, medical researchers have been investigating alternative options to human organ donations. As a result, the exciting field of 3D bioprinting has taken off.

But can we really 3D-print a working heart, liver, or kidney for those in need? Currently, no — but we aren’t as far off as you may think.

What is organ transplantation?

To better understand the groundbreaking advances of 3D bioprinting, we must first explore the basics of human-organ transplantation.

In most cases, a person requires an organ transplant after the function of their own organ has become too poor for them to experience a decent quality of life. Organ damage of this severity is usually caused by long-term chronic illness or a sudden traumatic injury.

Once a certain level of organ damage occurs, an organ transplant is often the only treatment option available. During an organ transplantation procedure, a healthy organ is removed from the human donor (either living or recently deceased) and is transplanted to replace the damaged organ.

Examples of organs that can be transplanted include²:

• Heart

• Kidneys

• Intestines

• Corneal tissue (in the eye)

• Liver

• Skin

• Lungs

• Vascular tissue (blood vessels)

• Pancreas

• Bone and connective tissue

As an incredibly complex, invasive procedure, an organ transplant is not always guaranteed to be successful. Regardless of the rigorous organ screening and matching before any organ transplant, rejection of the transplant (caused by your immune system attacking the new organ) is still quite a common occurrence².

As a result, people who have received an organ transplant often need to take medications designed to reduce the strength of their immune system for the rest of their life — and while this reduces the risk of their body rejecting the new organ, it increases their risk of becoming ill from dangerous infectious diseases.

Advances in bioprinting — a solution to the transplant epidemic?

While there is a need for increased access to functional organs for patients in need of a transplant, is 3D printing really a viable solution to this massive health problem?

When most people think of 3D printing, we think of hobby projects printing plastic models, not functioning, delicate organs that could be implanted into the body. But, from as early as 1988, researchers have been exploring the potential possibilities of bioprinting — which is now defined as the process of using 3D printing technology with living cells to produce functioning and sustainable tissues and organs³.

The original bioprinting device was made by altering an HP printer to deposit viable cells in a group, and interest and investment in bioprinting led to massive improvements over the next decade³.

In 1999, the first artificial organ outline was successfully bioprinted — a scaffolding of temporary cells 3D printed in the shape of a urinary bladder⁴. Once created, the cell scaffolding was seeded with cells from the intended recipient to reduce the risk of rejection, and then the entire artificial organ outline was implemented into the patient to replace their existing bladder⁴. Ten years later, the transplant recipient had no dangerous complications related to the procedure⁵.

Now, over 20 years later, interest in bioprinting is growing rapidly. In 2021, the global 3D printing market was valued at over 1.7 billion USD, and current projects show that investment and advances in this technology could cause the 3D printing market to more than double in value by 2030⁶.

How bioprinting works

To start the process of bioprinting any tissue or organ, a team of medical researchers and scientists must start with digital images of the patient’s current, poorly functioning organ. This imaging is most commonly done through CT and MRI scans to get a full three-dimensional view of the organ to be replaced. Once completed, the 3D imaging is uploaded to computer software to build a blueprint plan.

Using the wireframe created using digital software and advanced cellular knowledge of each unique tissue and organ, researchers create a slice-by-slice model of the intended organ⁷. Each slice is used as a blueprint for the 3D bioprinting device when it begins the process of creating the actual tissue.

Then, depending on the type of tissue being created, a variety of bioprinting techniques can be used to create the final product. Examples of the most commonly used bioprinting techniques include⁷:

Ink-based bioprinting

Similar in style to traditional inkjet printing technologies, ink-based bioprinting is a precise process that involves depositing specific amounts of “bio-ink” onto a culture dish. Bio-ink is a substance created of live cells and biopolymer gels to improve adhesion⁸.

To create the desired size and shape of the droplet, the bio-link is passed through a piezoelectric sensor as it is printed. Detailed computer programs and specifically designed bioprinting machines are needed to successfully build viable tissue using this bioprinting technique.

Laser-assisted bioprinting (LAB)

During laser-assisted bioprinting, a laser is used as the primary energy source for depositing droplets on the biomaterials into the culture medium. In most cases, a LAB setup includes three essential components:

• A pulsing laser source for energy

• A ribbon coated with biomaterial (sometimes donor cells) deposited on a metal film

• The receiving substrate

Laser-assisted bioprinting most commonly uses nanosecond lasers with UV wavelengths.

Pressure-assisted (extrusion) bioprinting

For most bioprinting projects, the biomaterial used to make the viable tissue is a liquid or paste. Because of this, pressure or extrusion-based bioprinting techniques can be used to create the desired shapes as the tissue is printed.

During this process, a screw or plunger pressure chamber is used to compress the biomaterial into a microscale nozzle to create the needed droplet of cells. A 3D structure is achieved after layers and layers of biomaterial deposits.

Stereolithography

Developed in the late 1980s, stereolithography is a nozzle-free approach to bioprinting. This technology relies heavily on the type of polymers used in the tissue construction, which must solidify after exposure to a light source.

Using a series of micromirrors, a stereolithography device controls the light intensity on the substrate, allowing for the creation of specific shapes and structures. Currently, stereolithography has the highest fabrication accuracy of all freeform 3D printing technologies.

Promising 3D-printed organ projects

As we can see, the world of bioprinting is complex and diverse. As the technology continues to expand and grow, we get ever closer to building the first standalone bioprinted organ.

To date, no research team has printed a fully self-sustainable organ capable of long-term implantation because it is difficult to create tissues thick enough to withstand the pressures and strain of the human body.

However, recent developments in bioprinting have led to exciting discoveries and advances, including:

Kidney — 2016, Harvard University

One of the essential organs for human life, our kidneys maintain our fluid balance and facilitate waste filtration from our blood. Due to the complexity of kidney tissue, creating a functional copy using bioprinting techniques has proven a challenge.

However, in 2016, a team of scientists at Harvard developed a new bioprinting technique capable of producing proximal tubules (a small section of the nephron, the functional unit that makes up our kidneys)⁹.

Ovaries — 2017, Northwestern University in Chicago

As an essential component of the female reproductive system, women living with damaged or poorly functioning ovaries are likely to struggle when trying to conceive.

Committing to tackling this problem with artificially created tissue, a team of researchers at Northwestern University used bioprinting techniques to create scaffolding for ovaries implanted in infertile mice. Over time, cells within the mouse’s body created working ovaries which enabled three infertile mice to become pregnant and give birth to healthy babies¹⁰.

Cornea — 2018, Newcastle University

Located at the front of the eye, our cornea is essential for focusing light on our retina to produce clear images of our surroundings. Human organ transfer is currently the only viable option to maintain a person’s vision when the cornea becomes damaged due to injury or disease.

Looking to explore other alternatives, a team at Newcastle University successfully bioprinted a human cornea using a unique bio-ink in a circular formation¹¹. While this project was a proof of concept, it is an exciting step toward the successful long-term implantation of bioprinted corneas.

Skin — 2019, Rensselaer Polytechnic Institute

As the human body's largest organ, our skin is a living protective barrier that keeps our vital organs safe from the elements. Full of nerves and tiny blood vessels, our skin is more complex than it appears, posing a serious challenge for researchers looking to help those needing functional skin grafts.

In 2019, a team at Rensselaer Polytechnic Institute had a breakthrough, producing the first “living” sample of bioprinted skin, which included its own vascular function¹².

Heart — 2019, Tel Aviv University

Often considered the most important organ in the human body, a strong, healthy heart is needed to supply our body’s cells with blood and oxygen.

As a breakthrough project from a team of researchers at Tel Aviv University, the first functional mini-heart was bioprinted using cells from a human donor¹³. While this miniature model is not fit for use as an implantable organ, it is a stepping-off point for researchers as they continue to improve their cardiac 3D printing techniques.

The lowdown

As exciting as these amazing breakthrough projects are, we are still some way off from bioprinting organs to reduce the burden of the organ transplant epidemic.

Currently, one of the biggest challenges preventing bioprinted organ transplants is the unique, complex vasculature of every organ in the human body. While trial projects have produced bioprinted organs with their own vascular functions, integrating a bioprinted organ into the body and successfully connecting its blood vessels is proving to be very difficult. Requiring extreme precision in the design and printing of the tissue is just one of many issues blocking advancements in this exciting technology.

Add to the mix difficulties in standardizing bio-ink and cellular substrates, limited access to the correct materials, and possible technological issues with bioprinters, and it is clear that bioprinting is not a simple solution to the global organ-donation shortage.

But, despite the challenges ahead, many people still view bioprinting as a medical revolution. Capable of reducing organ donation waitlists and saving billions of dollars in organ-failure care, there are plenty of benefits to be found if we can crack the 3D organ printing code. We may just need to wait until we see more people walking around with artificially printed organs!

Sources:

1. Organ donation statistics | Health Resources & Services Administration

2. Organ transplantation | MedlinePlus

3. Development of 3D bioprinting: From printing methods to biomedical applications (2020)

4. A record of firsts | Wake Forest Institute for Regenerative Medicine

5. The history of bioprinting | 3D Printing Center

6. 3D bioprinting market size, share & trends analysis report by technology (magnetic levitation, inkjet-based), by application (medical, dental, biosensors, bio-inks), by region, and segment forecasts, 2022 - 2030 | Grand View Research

7. Recent advances in bioprinting techniques: approaches, applications and future prospects (2016)

8. Bioinks for 3D bioprinting: an overview (2018)

9. Bioprinting of 3D convoluted renal proximal tubules on perfusable chips (2016)

10. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice (2017)

11. 3D bioprinting of a corneal stroma equivalent. (2018)

12. Skin bioprinting: the future of burn wound reconstruction? (2019)

13. 3D printing of personalized thick and perfusable cardiac patches and hearts (2019)

Claire Bonneau is a medical writer and certified trauma operating room nurse.