By Puja Bhattacharjee

The Centers for Disease Control and Prevention (CDC) estimates that each year, about 2,650 babies are born with a cleft palate and 4,440 babies are born with a cleft lip with or without a cleft palate in the U.S. It is a birth defect where a missing bone in the upper palate leaves the newborn with a hole between the nose and the mouth.

Pediatricians do not have a lot of options to fill that hole right now. Metal implants need to be replaced later as the child grows. Allograft, or grafting bone tissue from cadavers, risks complications and infections since children have weaker immune systems. And growing up with a physical defect is painful for any child.

Now researchers at Northwestern University are experimenting with a 3D printable version of hydroxyapatite, a naturally occurring mineral of calcium, extensively used in dental implants and bone grafts for the last six years. Ramille Shah, a researcher and professor in the field of biomaterials engineering and 3D-printing, initiated the idea to 3D print hydroxyapatite. Known as hyperelastic bone, the new 3D printable hydroxyapatite may hold the key to permanently fixing cleft palate in children and many other cranial and facial defects.

Shah started her tenure-track position at Northwestern in 2009 and, soon after, invested in a 3D-Bioplotter, a 3D printer for biomaterials used in medicine. Shah’s focus was musculoskeletal tissue engineering, including bone.

Soon after the acquisition of her bioplotter, Shah and her group soon realized the limited number of biomaterials that were compatible with 3D printing. They then started off on a quest to expand the “biomaterial toolbox available for extrusion-based 3D printing.”  Adam Jakus, one of her graduate students at the time,  joined in this endeavor. Before coming to Northwestern, Jakus was researching energetic materials (such as explosives) at Georgia Tech. He adapted the processes that are relatively common in energetic materials research, to making a 3D printable ink from hydroxyapatite.

Biomaterials such as hydroxyapatite are brittle and not surgically friendly as a result. Surgeons dislike that, says Jakus. When the team made this ink five years ago and 3D printed it, they expected it to be brittle. But to their delight it was elastic. “When we started studying it more, putting it inside mice, rats and monkeys, it started regenerating bone very quickly too. So, everything about it started to turn out great.”

Curious, the team studied why the usually brittle hydroxyapatite was displaying such unexpected mechanical properties. Hydroxyapatite constitutes 90-95 percent (by weight) of the 3D printed material. The remaining 5-10 percent is a polymer with elastic properties (polycaprolactone or polylactic coglycolic acid). “After 3D printing, the polymer coats these hard particles and acts as a bridge between them. It’s like these particles are connected by rubber bands. What also makes it elastic is there is room for the particles to move,” says Jakus. That’s because the material is porous.

They also found that when it is cast into a sheet, the material is less elastic than in the 3D printed form – 3D printing gives it the unique properties. Usually 3D printing is used to create things out of existing materials. Shah and Jakus used 3D printing to create new materials and impart new properties.

“We can take advantage of the ink properties and “act” of 3D printing (extrusion and solidification) to induce/control micro and nano-structure in the resulting printed material,” says Jakus. “Thus, something that is normally very brittle, like a ceramic, can be made to be elastic. We apply this process to imparting new mechanical, biological, electrical, optical, thermal, and/or physical properties to 3D-printed materials.” Hyperelastic bone is just one of the applications.

They implanted it in the skull of an injured monkey 14 months ago. No adverse effects were observed and they saw significant tissue infiltration and the start of new bone formation within the hyperelastic bone implant as early as 4 weeks after implantation.

“If you were to come in several years later, you will find no trace of the original materials. Once implanted, the polymer degrades into lactic acid and glycolic acid. These are the same acids in sore muscles after a workout,” says Jakus.

Jakus says that the value of the material is in its simplicity and unique properties. It is made of simple materials already commonly used in a lot of medical devices. It is easy to make and surgically friendly. “When you think of translational medicine, you need all those things. It is cheap to make, which in health care is paramount,” says Jakus.

For now, Shah and Jakus have established basic research on this material. The next step is to translate and commercialize it so that it eventually gets to patients. That will require data from additional trials in animal models for different applications before they can go to human trials, a step that will require significant funding. The target is to generate enough data to get FDA approval for the technology. Next, the team will focus on integrating bone with other complex tissue systems.

Meanwhile, Shah and Jakus have launched a startup called Dimension Inx LLC to help commercialize the 3D ink technology which they have been developing in the lab. “The startup has been formed to bring the technology of academia out of the lab and into the real world,” says Jakus. “It is a long road ahead because it (hyperelastic bone) is a medical product. There are a lot of regulations that we need to pass before it can be used in humans. The startup will help with the approval process as well as help in quality control and scale-up (for) production,” says Shah.

Jakus says that the company will be producing inks that ‘anyone with the appropriate 3D printing technology can 3D print into what they need. “Together, Ramille and I have a lot of experience in 3D printing and additive manufacturing,” says Jakus. He added that the company can offer advice tailored to the needs of the customers.

The startup will have a non-biomedical side to it, too. Shah and Jakus have developed new methods to 3D print metals and alloys that are faster and better than existing 3D printing methods. “We also have ceramics for structural or energy applications. The company is pursuing a comprehensive way to 3D print almost all material with the same approach. One 3D printer can print hyperelastic bone then you swap out the ink and it can print metals or alloys,” says Jakus.

SHyNE, the multi-disciplinary Soft and Hybrid Nanotechnology Experimental Resource has helped bring a litany of Northwestern’s nanotechnology applications and innovations together for research projects such as the one Shah and Jakus are pursuing.

“Our lab specializes in materials development and 3D printing. We do not specialize in how to electrically and optically characterize material systems. We do not have the equipment to do it. That’s when we use SHyNE,” Jakus says. He went through the SHyNE website to figure out which instruments and individuals of expertise are available at Northwestern to help them to do those things. “No matter how good you are, you are going to need someone with some other expertise to help you with something to make it worthwhile. That is why there are so many authors on the hyperelastic bone paper. It’s hard finding facilities, instruments, experts if you are blindly looking,” he adds.

This article was originally written for the Soft and Hybrid Nanotechnology Experimental Resource (SHyNE) website by SHyNE intern and Medill Reports reporter Puja Bhattacharjee