One Cell of An Idea
Much of the reporting on 3-D printing has focused on the production of low volume batches of physical components, providing a convenient solution for both industrial businesses and at-home hobbyists. A developing frontier is the use of specially-equipped printers to create living tissue. The current use is primarily for producing strips of tissue that can be used in testing, but making full-scale implantable organs is the longer-term vision.
In a state-of-the-art clean room, a scientist clad in a full-body containment suit, a hair net and blue gloves is preparing some printing cartridges — filled not with ink but a viscous milky liquid. Next to her sits a computer connected to a machine that resembles a large ice-cream dispenser, except that each of its two nozzles is made of a syringe with a long needle. Once the scientist clicks on the “run program” button, the needles extrude not a vanilla or chocolate-flavored treat, but a paste of living cells. These bioinks are deposited in precise layers on top of each other and interspersed with a gel that forms a temporary mold around the cells. Forty minutes later, the task is finished. Depending on the choice of bioink and printing pattern, the result could have been any number of three-dimensional biological structures. In this case, it is a strand of living lung tissue about 4cm in length and containing about 50m cells.
Since its inception in 2007, researchers at San Diego-based Organovo have experimented with printing a wide variety of tissues, including bits of lung, kidney and heart muscle. Now the world’s first publicly traded 3D bioprinting company is gearing up for production. In January samples of its first product — slivers of human liver tissue — were delivered to an outside laboratory for testing. These are printed in sets of 24 and take about 30 minutes to produce, says Keith Murphy, the firm’s chief executive. Later this year Organovo aims to begin commercial sales. Each set consists of a plate with 24 wells containing a piece of liver tissue 3mm square and 0.5mm deep. Although prices have not been fixed, a set of tissues like this can sell for $2,000 or more for laboratory use. It might seem expensive, but it could save pharmaceutical companies a lot of money. This is because Organovo’s research indicates that the slivers of liver respond to drugs in many ways like a fully grown human liver would. If this is confirmed by outside testing, researchers could use the printed tissues to test the toxicity of new drugs before deciding whether to embark on expensive clinical trials with patients.
Organ and tissue structures vary in complexity, and some are much harder to make than others. From an architectural standpoint, flat structures, like skin or cartilage, are less complex than tubular ones, such as blood vessels or windpipes, says Dr. Atala. Hollow, non-tubular organs, like the bladder, stomach or uterus, are trickier. But the most complex are relatively solid organs, such as the heart, liver or kidneys, which consist of many more cells and an extensive vascular structure. So far, surgeons have been able to implant a variety of engineered flat, tubular and hollow tissues into patients, including skin, cartilage and muscle. Dr. Atala has also successfully implanted lab-grown bladders and urethras into young patients. But solid organs are another matter. “That”, he says, “is really the next frontier.” All tissue engineers have the same goal — to create human organs for transplant — but their approaches differ. In particular, they are divided on how much of a support structure or scaffold they need to provide for the cells, and what building materials are the most suitable…
Several laboratories are currently working on developing bioprinters that could print skin cells directly onto wounds and burn injuries. At Wake Forest, researchers use a printer in conjunction with a laser to scan the size and depth of an injury. It produces a topological 3D map of the wound, which is used to determine how much material to deposit at any one spot, explains John Jackson, a member of Wake Forest’s skin-printing team. Although the majority of bioprinters at Wake Forest are inkjet based, the researchers opted for a pressurized version. This is because of the difficulty of getting cells through the inkjet nozzle. “You get a lot of clogs,” says Dr. Jackson. With the system they have chosen the researchers can change nozzle sizes, and the machine can print up to eight different types of cell. Recent studies on animals have shown that it is successful in printing precise layers of cells and cell types onto wounds. The process takes about 20-30 minutes for a wound that is around 10cm in length and width and up to 1cm deep. The current treatment for burn patients is to take skin grafts from other areas of their body and transplant them onto the wounds. But the supply of skin from the body is limited, and the graft has to be prepared for transplantation. So, asks Dr. Atala, why not save a step and print skin cells directly onto the patient? “The patient itself is the best incubator,” he believes. This process might also work for people with diabetes and for the elderly, whose wounds often do not heal well. Dr Jackson hopes, if things go according to plan, that the skin printer could be used in clinical trials within three or four years.