Artificial bone seemed to be a settled issue in academia; there was a sense that nothing was left to be invented. But then Northwestern University materials scientists began talking to surgeons. Over the course of 100 interviews they realized that far from being satisfied with the available options, surgeons wanted much more. Bone graft material, the surgeons complained, was too brittle. It could not be squeezed into tight spaces to allow for minimally invasive surgeries and it did not integrate well with existing tissue, sometimes creating problems with growth and healing.
So the researchers, led by assistant professor Ramille Shah and her postdoctoral fellow Adam Jakus, developed a synthetic “hyperelastic” bone tissue that can be produced with 3D printable ink. In several experiments with rodents and a rhesus macaque, the material appeared to be able to fuse with new natural bone. It is strong enough to be used in a femur and flexible enough to be squeezed through a small incision, the two say in their results published Wednesday in Science Translational Medicine.
The synthetic bone is still years from being tested in people. But if it continues to perform well it could be considered for use in spinal fusion, bone fractures, anterior cruciate ligament (ACR) or rotator cuff injuries, or craniofacial procedures, Shah said at a news conference introducing the work. The hope is that the material will also be shown to grow with the patient, meaning it could be used in children as well as adults.
This compilation shows hyperelastic artificial bone being 3D-printed into various forms. Later, the video shows how this synthetic bone might be squeezed through a tiny opening during minimally invasive surgery. Credit: Adam E. Jakus, PhD
The team’s insight came from the idea of combining materials used in bioengineering with production approaches from industry, says Jakus, who has an academic background in metallurgy and explosive materials. He says he was inspired by the extrusion process used to manufacture goods ranging from bricks to toilets. He combined elements of that technical process with materials often used in medicine, including hydroxyapatite, a form of calcium commonly found in bone. The team’s printer extrudes layer upon layer of a compound made of hydroxyapatite and a biodegradable polyester that binds the layers of ink together.
The researchers can print their hyperelastic bone with a 3D printer—so there is no need to heat the material, which would make it brittle and kill antibiotics added to prevent infection. The ink can be stored for as long as a year, and the process is fast and viable on a large scale; body parts are printable in minutes to hours, Jakus says. He and Shah hope this will make manufacturing cheap enough to someday be feasible within hospitals and in disadvantaged parts of the world.
Laura Niklason, vice chair of anesthesia at Yale University who was not involved with the work, says she is impressed with their results. “From what I can see, this is a really marvelous material because it’s both strong and pliable,” she says. Niklason particularly noted the team’s experiment in which a monkey with thinning patch of skull received a graft of hyperelastic bone. Unsure of the size of the damage before surgery, the researchers printed out a too-large piece of bone and then the surgeon cut it down to fit. Within a month it had integrated into the monkey’s existing skull bone, the research showed. “The results you see in primates tend to translate very well to results you see in humans,” she says, adding that the work “requires more proving out, but I would say this is exciting and encouraging.” The next challenge, says Niklason—whose own research focuses on the heart and lungs—will be to find a way to print functional, weight-bearing connective tissue like heart muscles, tendons and ligaments.
Jakus says that when the team first printed the synthetic material they were stunned by its mechanical properties, ease of printing and ability to integrate into living bone. “The biological effects were quite astounding,” he says. In the lab the researchers cultured the hyperelastic bone along with human stem cells, capable of transforming into other cell types. Jakus says they were surprised that within a week the stem cells had turned into bone cells and begun manufacturing their own minerals.
In another experiment to test the material’s promise, the team printed a human jawbone in under three hours. And in yet another, they reported that the synthetic material rapidly integrated with a mouse’s tissue when injected under its skin, with no evidence of immune rejection. The artificial bone was also able to fuse two vertebrae and replace part of a rat’s femur, reportedly showing that it could support the equivalent of 150 pounds of weight in a human. Adding a growth factor to the hyperelastic bone promoted healthy growth, the research reports. The substance is made of materials that have already been FDA-approved and extensively tested, Jakus says.
Tiny holes inherent to the material allow blood vessels and other cells to integrate into the artificial bone, transforming it into living, growing tissue, the researchers say. Although they have yet to prove exactly how the hyperelastic bone integrates itself, Jakus says he thinks it works because the bone is similar to, but not exactly like, real bone—a flaw that may make it more effective. “To some degree it emulates natural bone, but it’s not quite close enough,” he says. “Cells might view this as maybe incomplete bone, so it spurs them to remodel it into natural bone.”
Naresh Thadhani, professor and chairman of the School of Materials Science and Engineering at the Georgia Institute of Technology, was not involved in the research but says he has enjoyed watching Jakus’ ideas progress since the younger man was a doctoral student in his lab. “They’ve come a long way,” he says. The material is promising, Thadhani adds, but he is also interested in the broader innovation that Shah and Jakus are pursuing: developing different inks for different biomedical and industrial purposes.
The team hopes its printable ink concept will have applications ranging from energy to electronics, as well as bioengineering. Shah says they have a full portfolio of different substance types, including metals and carbon-based materials. On its own, Jakus says, the hyperelastic bone “is an amazing material and fantastic for clinical bone surgical use. But it’s [also] part of a larger system that’s elevating 3D-printing beyond novelty.”