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by Alexandra Taylor Published on 1st Oct 2015
by Alexandra Taylor Published on 1st October 2015
123,000 people in the US are currently on a waiting list for an organ transplant. Every day, an average of 21 patients pass away without receiving one. Even for the lucky recipients, there is an ever-present risk that their bodies will reject the organs. Medication to reduce this risk is expensive but wholly necessary. As lifespans lengthen, more people require life-saving transplants, and the crisis is only expected to worsen. A method must be found that can deliver safe, reliable transplants to patients in need. Regenerative medicine hopes to answer such problems. Scientists in this field seek to restore organ function by utilizing the body’s healing mechanisms. In recent years, new technology has offered a compelling solution. 3-D printing of organ tissue, or bioprinting, works by arranging the body’s own cell lines along three-dimensional structures to produce functional organs. There is no risk of rejection, and thus no risk of costly anti-rejection treatment. Technical Difficulties Many obstacles prevent this field from being fully realized. Human organs present a variety of highly specific cell types that are hard to mimic. Pancreas and liver cells, for example, are highly complex and notoriously difficult to grow outside of the human body. Tissues fall under one of three categories: flat, such as skin; tubular, as in blood vessels; or hollow, like the bladder. Certain complex tissues are delicate and risk collapsing under their own weight. Hydrogels can be used to hold these structures in suspension. They must walk a fine line between being sturdy enough to provide structure, yet permeable enough to allow cell migration and the development of vascular networks. The scaffolding that cells grow on, sometimes referred to as the extracellular matrix, presents its own challenges. Polymers and ceramics can mimic the basic arrangement, but such structures are intricate and difficult to faithfully reproduce. They require an extremely high resolution, akin to a high pixel density along three dimensions. Doris Taylor, of the Texas Heart Institute, has devised a solution: by removing the living cells from pig hearts and other pre-existing tissue, researchers can obtain a collagen matrix which they can then re-populate with a patient’s cells. By working off of a pre-formed scaffold, the printing process is simplified. Once the scaffolding is in place, cells must be introduced and begin to specialize. Induced pluripotent stem cells are the cells of choice, since they can be easily obtained from a patient’s skin sample. The scaffolding is populated with stem cells and loaded into a bioreactor, which provides an environment in which the vascular network can develop. Provided with the correct nutrients, the cells will take on the desired form and function. Bioprinting has come a long way since its inception. Multilayered skin grafts have been used to treat burns; tracheal splints have repaired airways; heart tissue and cartilage have been printed on demand. With luck, bone, kidney, and liver transplants are not so far off. Promising Developments The Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina, is at the forefront of the bioprinting field. The institute started off printing the relatively simple human bladder in 2001. Since then, Wake Forest scientists have successfully transplanted muscle, bone, skin, and ears in animal models. In addition to bladders, they have produced skin, cartilage, and urine tubes for human patients. Dr. Anthony Atala, director of the institute, cautions that bioprinting of complex 3-D organs is still decades—as opposed to years—away. The institute is making progress, however, in printing with multiple cell types, strengthening resolution, and printing blood vessels into tissue. While currently they are only able to print the top two layers of skin to treat burn wounds, eventually this will likely expand to include hair follicles and fat tissue. Epibone, as its name suggests, focuses on printing 3-D human bone replacements. This small company uses a patient’s stem cells to grow bone along a customized scaffold. While at this time the technology has only been tested on animals, it has acquired generous start-up funding. Last year, the company received a $350,000 grant from Breakout Labs, a nonprofit fund started by Peter Thiel. In the future, Epibone hopes to treat conditions ranging from complex fractures to bone loss, without the risk associated with artificial implants. Looking Forward Well-placed excitement surrounds 3-D bioprinting. It is difficult to find fault with a field that strives to provide long and healthy lifespans for all of its patients. Realistic expectations are important when dealing with technology of such promise. Dr. Atala gave a TED talk in 2011 which many felt suggested that bioprinting was much more sophisticated than it actually was, and the field suffered as a result. Bioprinting complex organs, especially the heart, liver, and kidneys, remains a distant goal. Dr. Atala is outspoken about the fact that, as long as patients receive all of the organ transplants they need, the mechanism by which this occurs is irrelevant. With enough fine-tuning, the reliable, standardized production offered by bioprinting seems to hold the most promise. With any luck, this “vision zero”—no patient lying in wait for an organ transplant—exists in our not-too-distant future.