By Dona Suri
It actually finally happened in March 2022.
Reconstructive surgeon Dr Arturo Bonilla of San Antonio, Texas, gave a right ear to a 20-year-old woman who was born without one. The ear was bio-printed using her own cells and precisely matched her left ear. The reconstructive surgery specialist stitched it on and, not only did the transplanted ear firmly integrate with existing tissue, it started regenerating its own cartilage tissue. Months later, the transplant looked like it had always been there.
It was the world’s first transplant using a bioprinter. The device is made by 3DBio. The company also turns harvested human cells and other biomaterials into customized “bioink”. Said Daniel Cohen, the company’s CEO, “We believe that the ear transplant clinical trial can provide us not only with robust evidence about the value of this innovative product, but also demonstrate the potential for the technology to provide living tissue implants in other therapeutic areas in the future.”
“Other therapeutic areas …” Absolutely!
If you read sci-fi comics when you were a kid, then you have always known that this day would come. Remember those obsessed scientists with determined jawlines? They concocted viscous soups in giant test tubes, the soups congealed into full grown female bodies and the scientists zapped them to life.
Of course, Bonilla and Cohen are not yet up to the level of imaginary sci-fi life. But on the other hand, they are way beyond what anybody could have imagined as real life even ten years ago.
What they did was 3D-print a collagen hydrogel scaffold using the patient’s own cartilage cells. Bonilla’s got 11 more patients in the US lined up and he’s going to keep doing transplants and refining the process.
3DBio Therapeutics made history as the first to provide a body part for an actual transplant, but it is not the only company in the field.
Swedish company, Cellink, also makes bioprinters. Their most advanced printer: BIO X6, can print simultaneously with six different bioinks. Currently their printers are installed in more than 1.500 labs across the world.
Obviously, the big interest is in bioprinted organs, such as hearts. More than 100,000 people are on the organ transplant waiting list in the US alone, and on average, 16 lives are lost every day due to the lack of organ transplants. In the future, no waiting. The docs will just print a heart.
Did we say the future? Wrong !
Here’s the April 16, 2019 news release from Tel Aviv University:
“This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers,” says Prof. Tal Dvir of TAU’s School of Molecular Cell Biology and Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology, who led the research for the study. ”This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models,” Prof. Dvir says. “At this stage, our 3D heart is small, the size of a rabbit’s heart,” explains Prof. Dvir. “But larger human hearts require the same technology.”
The 3D bioprinter is, of course, important, but an even bigger breakthrough is the bioink. The TAU researchers separated human fatty tissue’s cellular and non-cellular components, creating stem cells.
Then they reprogrammed the stem cells into either cardiac or endothelial cells. The non-cellular components and programmed cells together formed a hydrogel or bio-ink. The cells were differentiated to cardiac or endothelial cells. This is what made it possible to bioprint an entire heart.
Since then, high-tech medical research labs all over the world have been carrying the process forward.
Bioprinting of the first full-size 3D bioprinted human heart was announced in 2020 — the work of Adam Feinberg and his team from Carnegie Mellon University. It was made from alginate, a soft, natural polymer with properties similar to real cardiac tissue and formed using the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique developed at the CMU lab. This heart was not transplanted into anybody; it was created as a model.
Models are as important as the real thing. Feinberg explained: “The surgeon can manipulate it and have it actually respond like real tissue, so that when they get into the operating site they’ve got an additional layer of realistic practice in that setting”
In 2021, researchers at Boston University used 3D printing technology to develop a miniature replica of a human heart that keeps beating like the real thing.
It’s not just organs. Carcinotech, a med-tech company based at Edinburgh University’s Roslin Innovation Centre, bioprints a personalized, exact 3D model of a cancer patient’s tumor. It’s alive. Multiple cancer drugs are then tested on the model to assess the options that can lead to the best treatment outcome. This shows how bioprinting can be used for drug discovery and make drug testing much faster and more precise.
Both the creation of bioinks and the bioprinting process is extremely complex. In writing about it, the danger is the temptation to skip over the huge challenges involved. An ordinary 3D printer uses plastic filament that the printer heats up and squeezes into whatever shape the program dictates. You can’t do that when the “ink” is alive, and has to be kept alive, during the printing process. Living cells are delicate and imperfect; they die. Rather than try to explain all the difficulties and complications in this post, a better idea is to provide a link to a detailed article that spells it all out. Please read David Levin of Stanford University:
At the moment, it looks like there are two ways to go:
Print the bioink onto scaffolds made of hydrogels
Develop bioinks from materials that gradually degrade as they are replaced by the body’s own tissue.
Hydrogels mimic the body’s own extracellular matrix and provide a supportive environment for cells to grow and differentiate.
Biodegradable inks allow for seamless integration of the bioprinted construct.
So what stand in the way of widespread application of this technology ?
Technical problems
The process is going to need …
- Better bioinks, more compatible with the human body, more amenable to forming complex 3D structures.
- More precise printers that can handle a wide range of materials, including living cells
- More clinical trials to test out safety and efficacy of 3D bioprinted tissues and organs.
Affordability
Bioprinting and bioinks are astronomically costly. Until a way is found to do it relatively cheaply, it is not going to be used outside of lavishly funded research laboratories.
Regulation
The technology is so new that issues of regulation and ethical considerations have hardly been raised. Two candidates for a bioprinted heart: an 80-year old multi-millionaire who can afford it, and a kid with a whole life to look forward to who can’t. Who gets the heart?
Meanwhile, medical technology companies can spot profits even when the money is years in the future. Around the world, more than 180 companies are working to develop more and more sophisticated 3D bioprinters and the bioinks to go with them.
The applications of 3D bioprinting will revolutionize medicine. Think of multilayered skin, bones, muscle structures, blood vessels, retinal tissue and even mini-organs, drug discovery and testing, model-assisted surgery. And they are all realities NOW – being tested out in labs, institutional and commercial, wherever cutting edge research is carried out.