, 2025-04-18 10:04:00
We’ve come a long way from the Vacanti mouse.
Back in the mid-90s, Charles Vacanti and other researchers experimented with cartilage regeneration and, with the help of a biodegradable mold and bovine cells, grew cartilage the size and shape of a human ear under the skin of a nude mouse, making it look like it had an ear growing out of its back. Along with the cartilage, one of the first internet memes was born.
The work to create viable human tissue from scratch — whether that’s cells or an entire organ — has not stopped. With cell-based “bioinks” and three-dimensional (3D) bioprinters, researchers are creating viable tissue with multiple applications.
Unlike the everyday 3D printers in homes and schools, the inks, or bioinks, contain a mix of human cells and materials that mimic necessities such as extracellular fluids or cartilage proteins.
“Bioprinting is well described as being the living form of 3D printing,” said Mark Skylar-Scott, PhD, an assistant professor of bioengineering at Stanford University, Stanford, California. “Instead of plastic, you can write materials that are biomaterials, living materials, cells, into complex 3D shapes so that you can produce tissue function.”
This technology could someday transform organ and tissue transplants, allowing patients to receive 3D-bioprinted body parts without waiting for a donor or requiring immunosuppressive drugs. 3D bioprinting could also speed up preclinical research by providing new models of disease that make animal testing obsolete.
Here’s where 3D bioprinting is and where it’s going.
How 3D Bioprinting and Bioinks Work
In 2004, the advent of 3D bioprinting opened a new era in tissue engineering, a field that had begun in the 1980s. In the early days, tissue engineers added cells to sponge-like scaffolding, created conditions for growth, and observed how the tissue took shape (sometimes using an ear mold inside a mouse).
“With cell-based products, all of this was really being done by hand, and there was really no way to automate it,” said Anthony Atala, MD, chair and professor in the Department of Urology and director of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina.
Now, 3D bioprinting allows scientists to mold tissues and organs from the bottom up instead, with reproducible results that can be scaled up for eventual use in medicine.
“3D bioprinting is an advanced manufacturing tool for making the next generation of medical implants,” said Lawrence Bonassar, the Daljit S. and Elaine Sarkaria professor in biomedical engineering at Cornell University, Ithaca, New York. “What is very different about this technology than previous versions is that it allows for the precise assembly of complicated implants.”
To make bioink for the bioprinter, scientists need two things. One is a sample of living cells. They use human-induced pluripotent stem cells, which can morph into different cell types. Researchers can culture these cells quickly in bioreactors under tightly controlled conditions. The rise in stem cell research over the past two decades aided advancement in 3D bioprinting, said Skylar-Scott.
The other key ingredient in bioink is material that can do three things: Mimic the extracellular matrix that supports living cells, flow through the nozzle of a 3D bioprinter, and stay in place once printed into the desired shape. These materials must behave like solids at rest and liquids under pressure, like toothpaste, which stays stiff in the tube until you squeeze it onto your brush, said Skylar-Scott.
Advances in material science and colloidal physics have given researchers a repertoire of hydrogel polymers that meet these requirements, said Skylar-Scott. Many bioinks for soft tissues contain naturally derived hydrogels, like collagen protein, or synthetic ones, like polyethylene glycol.
Each organ requires a slightly different cocktail to mimic its extracellular matrix. For bioprinting bone, for example, bioinks often contain powdered ceramics like alumina or zirconia that can be mixed with a liquid and hardened after printing.
Researchers are using varied combinations of cells and supporting materials to recreate different body parts.
From the Lab to the Clinic
Someday, 3D bioprinters might be standard operating room equipment, just like scalpels.
“The futuristic goal is that we could take the cells from the patient who needs a transplant, reprogram them in the stem cell for the organ that is needed, and then print it through 3D bioprinting, grow it, and transplant it to the human subject,” said Mohammad Fazle Alam, PhD, a research scientist in bioprinting at the University of Illinois Chicago.
The timeline will vary by body part. While all tissues are complex, obviously some are more challenging to recreate than others, said Atala. Flat structures like skin are the simplest. Next are tubular structures like blood vessels. Next are hollow, nontubular organs like the bladder and stomach. Solid internal organs like the heart, liver, and kidneys will be the hardest to bioprint thanks to their intricate structures and blood vessel networks.
“One of the major challenges for the field has been the ability to create three-dimensional structures that are well vascularized, that can stay alive,” said Atala. “I think there are a lot of advances there now that are allowing us to truly break that major logjam that was present in creating tissues of significance.”
Here are a few of the organs and tissues in the works:
Cartilage for transplant. Bonassar’s team at Cornell University uses 3D bioprinting to make auricles — the outer cartilage that gives ears their shape — using bioink made with collagen. Bioprinted ears could be used as implants for children with microtia, a condition that leaves the outer ear underdeveloped.
“The options for those patients are really not very good,” said Bonassar. “They require waiting years until the child is old enough to have surgery and either putting in an inert biomaterial that’s in the right shape but doesn’t really have the right properties of ear cartilage or grafting cartilage from the child’s rib, which requires creating a hole in the ribs and lots of time for surgery.”
In 2022, a 3D-bioprinted ear was implanted into a human for the first time in a clinical trial.
“Breaking the barrier of having a 3D-printed living implant placed in a human is enormous,” said Bonassar. “It sets the precedent and provides a sort of road map for the technology and for how bioprinters and bioinks will be regulated by the FDA [US Food and Drug Administration].”
His team also does 3D bioprinting of the nose and knee cartilage and intervertebral disks. In addition, they are building quality control checks into bioprinters, using sensors that can detect problems, like bacterial contamination, that could threaten the viability of implants.
Bone graft alternatives. Today, when a patient needs a new bone, surgeons have two options. You can take a bone from elsewhere in the body, which can come with complications, or use a cadaver bone, which carries infection risk. 3D bioprinting could eliminate those issues.
“With the bioprinter in the operating room, you could get cells from the patient while you have that operation going on, mix them with your biomaterial, print, and then put the implant in the body,” said Nureddin Ashammakhi, PhD, senior research specialist and lead, Engineering Multicellular Living Systems at Michigan State University, East Lansing, Michigan.
This isn’t limited to orthopedics. On-demand bone bioprinting could be particularly helpful in dentistry, he said.
New hearts to replace tickers running out of time. Skylar-Scott’s research group at Stanford University aims to 3D print a human heart worthy of transplantation. With its complex shape, ventricles, atria, blood vessels, and pumping motions, this is as tricky as it gets.
“Its potential applications are very broad and exciting, but this isn’t something that is off the shelf and ready now,” said Skylar-Scott. “It’s one to two decades away.”
Skylar-Scott sees potential for 3D-bioprinted hearts to help children born with congenital heart conditions or adults with cardiovascular problems someday. Today, whole-heart transplants are rare because donor hearts are in short supply. If a patient needs a new valve, they can get a mechanical or pig-derived valve. However, these replacement valves only last 15-20 years.
“Having something that’s living and can grow with the patient, I think there’s a real potential to improve quality of life,” said Skylar-Scott.
Recreating cancer to see what will kill it. Bioprinting other tissues strictly for lab work could have the most immediate value.
“Besides constructing or printing normal tissues, we could also make tissues of certain diseases, like cancer,” said Ashammakhi. “We can have that model in the lab and use it for testing drugs or following the process of disease progression, so we could, in the future, consult individual patients on the drugs that will be most effective to that type of the disease.”
The rise of 3D bioprinting could also usher in a paradigm shift in medical research. It could reduce or eliminate the use of animal testing — with all its limitations and ethical concerns.
“This way, we can create a mimicking system outside the human body and test the drug,” said Alam.
The Road Ahead
Once the basic science of 3D bioprinting is worked out, regulators will have work to do. For example, they must determine how to ensure safety and quality control for each bioprinted product that reaches patients.
Logistical challenges are another consideration. Sometimes, bioprinted tissue might need to be transported or kept alive outside the body longer than expected — like if a surgical patient gets sick and needs to postpone their procedure, said Atala.
Until then, researchers will keep refining the technology.
“It’s been really amazing to see how the field has grown beyond anyone’s expectations,” said Atala.