Bzzz. In the lab at Organovo, two machines labeled “Ruby”, and “Zorg” come to life. These machines resemble desktop printers, but they are far more sophisticated than that. Ruby and Zorg are two of Organovo’s 3-D bioprinters. Instead of ink they use cells, and instead of printing on a flat surface, they print 3-D organs. The bioprinted organs are not yet able to function as a living organs, but researchers are on the brink of a discovery that will change the future of organ transplantation.
Organ transplants are performed as a last resort when a patient’s organ has become too damaged to function successfully. The diseased organ is removed, and replaced with a donor’s healthy organ. Each individual has a cellular blueprint that is unique, so when the immune system detects the foreign cells of a donor’s organ it is designed to attack them. The recipient of an organ transplant must take immunosuppressants to counteract the body’s natural response to the foreign cells. Immunosuppressants cost between $20,000 and $30,000 per year, and are required to be taken for the rest of the recipient’s life. These drugs are highly toxic and cause many undesirable side effects, including high blood pressure, lymphoma, and osteoporosis. The only time patients are not required to take immunosuppressants is when the new organ has cells that are identical to the recipient’s cells. This can be accomplished by an identical twin donating an organ, or a process called regenerative medicine.
Regenerative medicine is the process of engineering a new organ from the cells of the patient. By using the patient’s cells, there is no need for immunosuppression, and no chance of the body rejecting the organs. Anthony Atala, M.D., the director for Regenerative Medicine at Wake Forest School of Medicine, started working on building bladders in 1990. He used a small biopsy of the patient’s cells to grow enough cells to cover a biodegradable mold shaped like a bladder. This bladder was placed in a patient’s body in 1999, and in 2006 the transplant was still successful. The regenerative medicine procedure has a high success rate with bladders, and other simple organs, such as tracheas, but the more complicated organs require a more complex solution.
The complex solution has come in the form of 3-D bioprinting. Bioprinting began in 2000, when Thomas Boland, a bioengineer at Clemson University found an old printer in his lab. He emptied the printer’s ink cartridge, replacing the ink with collagen, then printed his initials on a piece of black silicon. After using cells in a two dimensional printer, Boland decided to try it in 3-D. After making some modifications to desktop printers, Boland was creating complex living structures. Scientists began to print a variety of organs, including kidneys, livers, and a meniscus. They quickly learned that although the printed organs look like functioning organs, most are not able to be transplanted into the body. A printed meniscus is too weak to be put into the knee. Menisci receive a lot of pounding throughout the day, so overtime they become stiff. A printed menisci has not had the same environment that another menisci has had, so it lacks the strength needed to function properly.
Another concern with bioprinted organs is the lack of a vascular system that is required in complex organs. All cells in an organ must be within the width of a few human hairs away from a capillary in order to get the blood and nutrients needed to survive. The challenge lies in the complexity and intricacy of the network of vessels and capillaries. There have been several attempts to find a vascularization technique that is successful in printed organs. One attempt has been to print the organ with a filler in place of the vascular network. Once the organ has been printed, the fillers are removed, leaving channels for the vessels. Another method is printing the channels into the organ. However, printing such small channels is a challenge, and making them stable after printing is difficult. Dr. Jennifer Lewis has been able to print microvascular channels as small as 10 microns in diameter. Lewis has prevented the collapsing of the channels using “fugitive ink”, and ink designed to melt away after the pattern of the vascular channels has been formed.
Both the filler system, and the system of printing a vascular system into the organ have been somewhat successful. The vascular system that each method makes is able to provide blood to most cells in the printed organs. However, neither method has been able to provide blood and nutrients to every cell in the organ. Every cell must be able to survive in order for the organ to survive. Jordan Miller, an assistant professor of bioengineering at Rice University, has created a new technique for building the complex vascular systems. Miller calls his technique “3-D sacrificial molding”. 3-D sacrificial molding prints the organs with large channels going through them. The channels are then lined, and blood is guided through them. The goal of this method is to trigger the organ to form its own capillary network. The advantage of this process is that it does not take as much time as placing each sphere of cells in its place. The disadvantage is that scientists cannot control the placement of the cells.
The challenge of creating a functioning vascular system for these organs is one of the final hurdles that must be cleared before bioprinted organs are able to be used in transplants. However, the bioprinters and the organs they have created have many other uses that have made a big difference in medicine. Bioprinted livers are being used to test the safety of drugs on human livers. The Food and Drug Administration says that the effect of a drug on the liver is the most common reason for the drug to be considered unsafe. By testing the drugs on a bioprinted organs instead of animals, researchers are able to skip the step of animal testing, thus saving the lives of countless animals. Testing drugs on the printed livers will reduce the time and money needed to guarantee drug safety. Bioprinted organs are also being used by medical students. The bioprinters are able to create healthy organs, but also organs with tumors. Medical students can practice cutting a tumor out of a bioprinted organ before they attempt surgery on a living person.
While bioprinted organs have been an incredible advancement in medicine, there is still so much room for growth. “Getting to a whole organ-in-a-box that’s plug-and-play and ready to go, I believe that could happen in my lifetime” says Sharon Presnell, chief technology officer at Organovo. Once printed organs are able to be made with vascular systems, they will be able to be used for transplants. The 121,000 patient’s on UNOS waitlist will decrease dramatically, and people will no longer need to wait for years in order to resume a healthy life. The incredible advances in engineering have already saved many lives, and I am looking forward to seeing the tremendous impact it will continue to have throughout my lifetime.