Breakthrough: 'Living' Ear, Bone and Muscle 3D-Printed
Scientists have created a bio-sponge that allows nutrients and oxygen to flow freely to living cells printed anywhere in the structure.
Organ printing is getting closer and closer to reality.
In a breakthrough study, researchers at Wake Forest Institute for Regenerative Medicine announce that they've used an advanced 3-D printer to create sections of bone, muscle and cartilage that all functioned like the real thing when implanted in animals.
The advance could make it possible to custom print replacement body parts and organs for anyone.
The idea of printing tissue is not new. For years now, scientists have been using bioprinters to precisely lay down cells in specific patterns with the goal of creating a piece of bone or organ.
But the technology has not made its way into mainstream medicine because of the limitations that still exit.
In the human body, cells grow and thrive thanks to blood vessels that supply them with oxygen and nutrients.
But when living cells are printed, they must be suspended in some kind of biologically compatible matrix until they can grow and develop into the final body part.
Keeping them alive has been a challenge since these structures lack blood vessels, which are too small and delicate to be printed.
And even if scientists have figured out a way to keep cells alive, the resulting structures have proved unstable and too fragile to be implanted into a living being.
At Wake Forest, a research team led by Anthony Atala, developed a matrix embedded with microchannels - a sort of bio-sponge - that allows nutrients and oxygen to flow freely to the cells anywhere in the structure.
To make a specific kind of tissue, the scientists shaped the bio-sponge, which is made from a biodegradable material, into the custom form. Next, they infused it with a water-based gel that contained the living cells.
The cells were allowed to grow and then the structure was implanted in an animal. Over time, the matrix biodegraded and the cells took hold on their own in the desired shape.
In the study, the scientists found that after two months the ears, implanted in mice, had kept their shape.
Muscles cells prompted nerve formation in rats and bone implants actually triggered the formation of blood vessels after five months.
Eventually, such tissues will need to be studied in humans. Because this research was funded in part by the US Army, it's only a matter of time before this kind of technology will be used to help people, perhaps starting with soldiers injured on the battlefield.
A completed ear structure was printed with the Integrated Tissue-Organ Printing System.
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.
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.
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.
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.
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.
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.
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.
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.
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.