For almost as long as surgeons have been transplanting organs such as hearts, livers, and lungs, they’ve been frustrated by the scarcity of available organs, and have imagined a future where artificial organs might ease the shortage. One local transplant surgeon, Massachusetts General Hospital’s Joseph Vacanti, has spent more than twenty years working toward that vision, experimenting with various types of support structures that might allow specialized cells such as hepatocytes (liver cells) to grow and function outside an actual organ. And now the firm commercializing his technology, BioEngine, may be within striking distance of the goal.
Within two years, the Boston-based company expects to get clearance from the Food and Drug Administration for the first human pilot studies of an “artifical liver”—an implantable device that would boost liver function as a bridge to transplantation, according to CEO Gary Woolf. The two-year-old company had to throw out its first prototypes for the device and start over with a new design and a new manufacturing technology, but it’s currently building the first set of test devices based on the new design and gearing up to implant them in pigs. Woolf is in high spirits about the company’s progress and about the technology’s extended future. “If we can make this work, it will change everything,” he says.
I visited Woolf and BioEngine vice president of operations Brian Orrick yesterday at their Newbury Street offices, which are shared between BioEngine, sister company Alito Scientific (developer of a device to supplement lung function), and Shiboomi, Woolf’s business incubator. Woolf explained that from the time of Vacanti’s earliest tissue-engineering experiments with Harvard researchers Judah Folkman and Robert Langer (who is now at MIT, and is an Xconomist), the surgeon’s goal was to create three-dimensional structures that could provide a foothold for human cells—both specialized cells like hepatocytes and the surrounding support cells that keep them alive. But to survive and to do their jobs, cells need to constantly exchange nutrients, oxygen, wastes, and other molecules with the blood, and it turned out that that requires each cell to be very close—within a hundred micrometers—to a blood vessel. So the challenge became creating a structure with a dense, highly intricate vasculature.
In normal, living organs, incoming vessels branch into smaller vessels that continue to branch off, eventually forming networks of tiny capillaries only tens of micrometers wide. These capillaries then rejoin like streams flowing into rivers and eventually emerge from an organ as veins. Woolf and Orrick showed me examples of the company’s first-generation prototype for an artificial vasculature, a sheet of clear, flexible polymer bearing a grid-like mesh of progressively smaller channels. BioEngine worked extensively with Draper Laboratories in Cambridge, where Orrick was a member of the technical staff, to adapt a process called MEMS lithography to create the patterned silicon wafers that served as the molds for the polymer sheets.
Unfortunately, Orrick explains, blood tended to clot up as it flowed through the narrowing channels in these sheets. The problem appears to be one of geometry, Orrick says; cells in the natural bloodstream flow through tubes—i.e., structures with circular cross-sections—whereas the lithographic process could only be used to form molds for channels with flat walls and floors and a fixed depth. “You want your wide channels to be deep and your narrow channels to be shallow,” says Orrick.
So Vacanti’s team started over, partnering with Pittsburgh high-tech machining company ExOne to develop a different approach to making the molds for the polymer sheets. ExOne uses techniques such as electrolytic dissolution, laser ablation, and ultrasonic grinding to create tiny metal parts bearing 3-D patterns. In BioEngine’s case, the company used its tools to create molds for polymer disks bearing a lacework pattern of rounded-out grooves resembling the capillary networks of real liver tissue.
It’s that new design that BioEngine hopes to test soon in animals; in lab tests so far, blood doesn’t clot up in the redesigned channels, Woolf says. Before implantation, many of the patterned polymer disks will be stacked together, alternating with layers of hepatocytes. The stack will form a cylindrical device that can be implanted alongside a patient’s ailing liver (or in place of a portion of it).
BioEngine suffered a blow in April when Larry Rhoades, CEO of ExOne and an innovative scientific and engineering advisor to the Vacanti project, fell ill and died during a scuba trip in Hawaii. But Rhoade’s passing has only pushed the team to move faster, Woolf says. “He was a great man, a joy to be around, and we have an even greater motivation to keep pushing now, because he was such a light bulb for us,” says Woolf.
For Alito Sciences, BioEngine’s sister company, Vacanti’s team is developing an almost identical “lung assist” device, without the embedded cells. It turns out that the artificial blood vessels are very good at allowing oxygen to pass into the blood and carbon dioxide to escape. An implanted device fed via catheter with oxygen could help people with chronic obstructive pulmonary disease, cystic fibrosis, or other lung afflictions. That device, too, should be ready for testing on humans within two years, Woolf says.
Eventually, the privately-held, angel-funded company plans to address the transplant-shortage crisis even more directly by testing implantable liver-assist devices made of biodegradable polymers that will simply dissolve over time, leaving nothing but a permanent new organ. “Dr. Vacanti’s philosophy is that when mankind has a problem, it engineers a solution,” says Woolf. “When you need more housing for people, you don’t wait for old houses to open up. You build new ones.”