The heart represents one of the most ambitious goals for researchers working to create 3D-printed organs.
Cambridge University Department of Engineering
When physicians run out of treatment options they look to a nascent field known as bioengineering. Specialized scientists apply engineering principles to biological systems, opening up the possibility of creating new human tissue, organs, blood and even corneas such as the one shown here. Waiting lists for organ transplants continue to be lengthy so the race to save lives with bioengineered body parts is on. Here’s a look at some of the most notable achievements in recent years.
Fraunhofer Institute for Interfacial Engineering and Biotechnology
Producing small amounts of artificial skin to graft on patients and use for toxicity testing has been possible for years. Human skin cells are cultivated in the lab and then embedded in a collagen scaffold. In 2011, the Fraunhofer Institute for Interfacial Engineering and Biotechnology introduced a system that can rapidly manufacture two-layer artificial skin models. Their Tissue Factory has the capacity to make 5,000 skin sheets in a month.
Princeton University / Frank Wojciechowski
Reproducing 3-D biological structures, particularly the complex human ear, presents significant challenges for bioengineers. A team at Princeton University led by mechanical and aerospace engineering associate professor Michael McAlpine used 3-D printing technology to make a functional ear from calf cells and electronic materials. The ear that debuted in May 2013 is no mere replacement -- it can pick up radio frequencies well beyond the range that human ears normally detect.
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Surgeon Anthony Atala directs the Wake Forest Institute for Regenerative Medicine and is known for growing new human cells, tissues and organs -- particularly ones that advance urology. Atala and his team’s bioengineered bladders succeeded in clinical trials. The bladders were constructed from patients’ cells that were grown over two months on a biodegradable scaffold and then implanted. Patients included children with spina bifida who risked kidney failure. It’s been several years since then and the results are positive. “These constructs appear to be doing well as patients get older and grow,” Atala told the NIH Record.
Massachusetts General Hospital/PNAS
Being able to make blood vessels in the lab from a patient’s own cells could mean better treatments for cardiovascular disease, kidney disease and diabetes. In 2011, the head of California-based Cytograft Tissue Engineering reported progress in a study where three end-stage kidney disease patients were implanted with blood vessels bioengineered in the lab. After eight months the grafts continued to work well, easing access to dialysis. Then this month a team at Massachusetts General Hospital found a way to encourage stem-like cells to develop into vascular precursor cells, a key step on the way to becoming blood vessel cells. They generated long-lasting blood vessels in living mice.
Ott Lab / Massachusetts General Hospital
Artificial heart devices have been surgically implanted since the 1980s, but no device has been able to replace the human heart as effectively as a healthy biological one. After all, a human heart pumps 35 million times in a single year. Recently scientists have made advances in adding more biological material to artificial heart devices. In May the French company Carmat prepared to test an artificial device containing cow heart tissue. At Massachusetts General Hospital, surgeon Harald C. Ott and his team are working on a bioartificial heart scaffold while MIT researchers recently printed functional heart tissue from rodent cells.
Wake Forest University Baptist Medical Center
Bioengineers are working on it, but the liver is one of the largest, most challenging organs to recreate. In 2010 bioengineers at Wake Forest University Baptist Medical Center grew miniature livers in the lab using decellularized animal livers for the structure and human cells. This month, a team from the Yokohama City University Graduate School of Medicine published results of a study where they reprogrammed human adult skin cells, added other cell types, and got them to grow into early-stage liver “buds.” Currently the scientists can produce about 100 of them, but the study’s lead author Takanori Takebe told the Wall Street Journal that even a partial liver would require tens of thousands.
Harvard Apparatus Regenerative Technology
In April, after an international team of surgeons spent nine hours operating on her at Children's Hospital of Illinois in Peoria, 32-month old Hannah Warren became the youngest patient to ever receive a bioengineered organ. Scientists had made a windpipe for her using her own bone marrow cells. Born without a trachea, she needed help breathing, eating, drinking and talking. Harvard Bioscience created the custom scaffold and bioreactor for the experimental procedure. Sadly Hannah died on July 7 due to complications from a more recent surgery on her esophagus. Despite the high risks, bioengineers say they will continue to move ahead.
When a ruptured or degenerating disc causes chronic back pain, treatment is limited. At worst, patients undergo surgery to fuse vertebrae together and then have limited flexibility. Over the past several years artificial discs have emerged as an alternative, but they can wear out as they work. In 2011, a research team from Cornell University bioengineered implants using gel and collagen seeded with rat cells that were then successfully placed into rat spines. This summer Duke bioengineers took things further, coming up with a gel mixture they think can help regenerate tissue when injected into the space between discs.
Little by little, bioengineered intestines are being grown in the lab to diagnose digestive disorders and to help patients born without a piece of intestine. In 2011, Cornell biological and environmental engineering assistant professor John March began collaborating with Pittsburgh-based pediatric surgeon David Hackam on a small artificial intestine using collagen and stem cells. Then last year in Switzerland, EPFL professor Martin Gijs led a project in the Laboratory of Microsystems to create a miniature intestinal wall from cultured epithelial cells and electronics called NutriChip to identify foods that cause inflammation. Scientists at Harvard’s Wyss Institute also made a “gut-on-a chip” to mimic the real thing using intestinal cells in a tiny silicon polymer device.
University of California, San Francisco
One in 10 American adults will have some level of chronic kidney disease, according to the Centers for Disease Control and Prevention. Currently around 600,000 patients in the U.S. have chronic kidney failure. Most rely on dialysis while a fraction of them actually get transplants. Scientists from the University of California, San Francisco are on a mission to create a sophisticated artificial kidney device made with human kidney cells, silicon nanofilters and powered by blood pressure. The project, led by UCSF nephrologist William Fissell and bioengineering professor Shuvo Roy, aims to begin testing the kidney device in 2017.
An ambitious 3D-printed heart project aims to make a natural organ replacement for patients possible within a decade. But the researcher heading the effort also believes 3D-printing technology must harness the self-organizing power of biology to get the job done.
The idea of a 3D-printed heart grown from a patient's own fat stem cells comes from Stuart Williams, executive and scientific director of the Cardiovascular Innovation Institute in Louisville, Ky. His lab has already begun developing the next generation of custom-built 3-D printers aimed at printing out a complete heart with all its parts -- heart muscle, blood vessels, heart valves and electrical tissue.
"We can print individual components of the heart, but we're building next-generation printers to build the heart from the bottom up," Williams said.
The heart represents one of the most ambitious goals for researchers working to create 3D-printed organs within the field of regenerative medicine. The ability of 3-D printing to build human tissue by laying down living cells layer by layer has already allowed researchers to create small chunks of organs such as livers and kidneys -- often by using stem cells extracted from fat or bone marrow as the source material. [7 Cool Uses of 3-D Printing in Medicine]
Williams and the Cardiovascular Innovation Institute have started out by first using 3-D printing to create individual parts of what they have deemed the "bioficial" heart. That piecemeal approach could eventually allow researchers to print and piece together a fully functional heart within a week.
"I took a step back and looked at my colleagues, and said, 'Why don’t we build it like a large airplane?'" Williams told LiveScience. "Separate the organ into separate components, figure out the best way to make the components, and then put them together."
But building full-size organs also requires researchers to print human tissue in a way that includes the intricate networks of tiny blood vessels that keep the organs healthy. Williams envisions 3-D printing as an ideal way to make smaller blood vessels — he and his colleagues have already built large blood vessels for transplant use in surgeries using methods other than 3-D printing.
Still, 3-D printers can only do so much bioengineering when working at the tiniest scales. The best printers may only print structures with the size of millimeters, whereas the smallest blood vessels can have a width of just a few microns, Williams explained, where 1 millimeter is equal to 1,000 microns.
That's why 3-D printing may only get researchers partway toward the goal of creating a complete heart. Instead, researchers will have to rely upon the natural self-organizing tendency of cells to knit together blood vessels and eventually connect everything within a 3D-printed organ — a process that could take place within 24 hours.
"We will be printing things in the order of tens of microns or more like hundreds of microns, and then cells will undergo their biological developmental response in order to self-organize correctly," Williams said.
Most researchers don't expect full-size, 3D-printed organs to become reality anytime within the next 10 or even 15 years, but the Cardiovascular Innovation Institute continues to forge ahead with its goal of building a 3D-printed heart within a decade. Williams expects the next generation of "bioprinters" to begin rolling out in December.
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