This type of regenerative medicine is in the developmental stage, and the driving force behind this innovation is “a real human need,” Lewis said.
The cause of this discrepancy is “a combination of people who experience catastrophic health events, but their organs are not of sufficient quality to donate, or they are not on the organ donor list to begin with, and the fact that it’s actually very difficult to find a good match” so that the patient’s body doesn’t reject the transplanted organ, Lewis said.
And while living donors are an option, “operating on someone who doesn’t need it” is a big risk, said Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine. “So living related donors are usually not the way to go, because then you’re taking an organ from someone else who might need it, especially now that we’re aging longer.”
Every day, 17 people die while waiting for an organ transplant, according to the Health Resources & Services Administration. And every nine minutes another person is added to the waiting list, the agency says. More than 90% of people on the transplant list in 2021 needed a kidney.
“About a million people in the world need a kidney, so they have end-stage kidney disease and need dialysis,” Lewis said. “Once you’re on dialysis, you basically have five years to live, and every year your death rate increases by 15%. Dialysis is very hard on your body, so it’s really motivating to take on this great challenge. of organ printing.”
“There’s no practical reason why someone who needs a kidney – or a lung, a heart, a liver – can’t get one,” he said. she adds. “We are using technology to solve this problem.”
Print Organs 101
To begin the process of bioprinting an organ, doctors typically start with a patient’s own cells. They take a small needle biopsy of an organ or perform minimally invasive surgery that removes a small piece of tissue, “less than half the size of a postage stamp,” Atala said. “By taking this little piece of tissue, we are able to separate the cells (and) we grow and expand the cells outside the body.”
This growth occurs inside a sterile incubator or bioreactor, a pressurized stainless steel vessel that helps cells stay nourished with nutrients – called “media” – doctors feed them every 24 hours, because cells have their own metabolism, Lewis said. Each type of cell has a different medium, and the incubator or bioreactor acts as an oven-like device mimicking the internal temperature and oxygenation of the human body, Atala said.
“Then we mix it with this gel, which is like a glue,” Atala said. “Every organ in your body has the cells and the glue that holds it together. Basically, it’s also called ‘extracellular matrix.'”
This glue is Atala’s nickname for bioink, a printable mixture of living cells, water-rich molecules called hydrogels, and growth media and factors that help cells continue to proliferate and differentiate, Lewis said. The hydrogels mimic the extracellular matrix of the human body, which contains substances such as proteins, collagen and hyaluronic acid.
The non-cellular sample part of the glue can be made in the lab and “will have the same properties as the tissue you’re trying to replace,” Atala said.
The biomaterials used should generally be non-toxic, biodegradable and biocompatible to avoid a negative immune response, Lewis said. Collagen and gelatin are two of the most commonly used biomaterials for tissue or organ bioprinting.
The printing process
From there, doctors load each bioink – based on how many cell types they want to print – into a print chamber, “using a printhead and nozzle to extrude an ink and build the material layer by layer,” Lewis said. . Creating tissue with custom properties is made possible by programming printers with a patient’s imaging data from X-rays or scans, Atala said.
“With a color printer, you have several different cartridges, and each cartridge prints a different color, and you choose your (final) color,” Atala added. Bio-printing is the same; you’re just using cells instead of traditional inks.
The length of the printing process depends on several factors, including the organ or tissue being printed, the fineness of the resolution and the number of printheads needed, Lewis said. But it usually lasts a few to several hours. The time from biopsy to implantation is about four to six weeks, Atala said.
The ultimate challenge is “getting the organs to work as they should,” so accomplishing that “is the holy grail,” Lewis said.
“Just like if you were to take an organ from a donor, you have to immediately put that organ in a bioreactor and start perfusing it, otherwise the cells die,” she added. Perfusing an organ involves supplying it with a fluid, usually blood or a blood substitute, by circulating it through blood vessels or other pathways.
Depending on the complexity of the organ, it’s sometimes necessary to further mature the tissue in a bioreactor or other drive connections, Lewis said. “There are just a number of plumbing issues and challenges to get this printed organ to actually work like a human organ would in vivo (i.e. in the body). And honestly, it doesn’t. has not yet been fully resolved.”
Once a bioprinted organ is implanted in a patient, it will naturally degrade over time – which is normal since that’s how it’s designed to work.
“You’re probably wondering, ‘Well, so what happens to the fabric? Is it going to fall apart?’ Actually, no,” Atala said. “These glues dissolve and the cells feel that the bridge is giving way; they feel that they no longer have a solid base. So the cells do what they do in your own body, which is to create their own bridge and create their own glue.”
Atala and Lewis are conservative in their estimates of the number of years remaining before fully functioning bioprinted organs can be implanted in humans.
“The field is changing rapidly, but I mean, I think we’re talking about a decade and more, even with all the huge progress that’s been made,” Lewis said.
“I learned so many years ago never to predict because you will always be wrong,” Atala said. “There are so many factors in terms of manufacturing and (US Food and Drug Administration regulations). Ultimately our interest, of course, is to make sure the technologies are safe first and foremost. for the patient.”
Whenever bioprinting organs become an available option, affordability for patients and their caregivers should not be an issue.
They will be “accessible for sure”, Atala said. “The costs associated with organ failure are very high. Just keeping a patient on dialysis costs more than a quarter of a million dollars a year just to keep a patient on dialysis. So it’s much cheaper to create an organ that you can implant in the patient.”
Some of the major costs of organ transplantation today are “the harvesting of the organ from the donor, the transportation costs, then, of course, the surgery that the recipient undergoes, and then all the care and monitoring”, Lewis said. “Some of that cost would still be in play, even if it were bioprinted.”
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