Physicians at Weill Cornell Medical College (WCMC) and biomedical engineers at Cornell University have succeeded in building living facsimiles of human ears. They believe that their bioengineering method will finally achieve the goal of providing normal-appearing new ears to children born with a congenital ear deformity. The researchers used three-dimensional (3D) printing and injectable gels made of living cells. Over a three-month period, the ears steadily grew cartilage to replace the collagen used in molding them.

The study’s colead-author is Dr. Jason Spector (director of the Laboratory for Bioregenerative Medicine and Surgery, LBMS; associate professor of plastic surgery at WCMC; and adjunct associate professor in biomedical engineering department at Cornell University). He says, “A bioengineered ear replacement like this would also help individuals who have lost part or all of their external ear in an accident or from cancer.”

Current replacement ears have Styrofoam-like consistency; sometimes, surgeons build ears from ribs harvested from young patients. “This surgical option is challenging and painful for children, and the ears rarely look totally natural or perform well,” says Spector, who is also a plastic and reconstructive surgeon at New York-Presbyterian Hospital/Weill Cornell Medical Center. “Other attempts to ‘grow’ ears have failed in the long term.” In addition to appearing and functioning naturally, these ears can be made quickly — taking a week at most.

Scanning, Printing, Molding

The study’s other lead author is Dr. Lawrence J. Bonassar (associate professor and associate chair of the biomedical engineering department at Cornell University). The deformity he and Spector seek to remedy is microtia, a congenital deformity in which a child’s external ear — typically only one — is not fully developed. Causes for this disorder are not entirely understood, but research has found that it can occur in children whose mothers took an acne medication during pregnancy. The incidence varies from one to four per 10,000 births each year. Many affected children have an intact inner ear but experience hearing loss due to the missing external ear structure, which normally acts to capture and conduct sound.

Spector and Bonassar have been collaborating on bioengineered human replacement parts since 2007, and Bonassar also works with other Weill Cornell physicians. (For example, he and neurological surgeon Dr. Roger Härtl are currently testing bioengineered disc replacements using techniques similar to those described here.) The researchers are developing replacements for human structures primarily made of cartilage: e.g., joints, tracheas, and noses. Cartilage needs no vascularization to survive.

To make the ears, Bonassar and colleagues first combined laser scans and panoramic photos (in just 30 seconds) of ears from twin girls to make a digitized 3D image. Then they converted that into a digitized “solid” ear and used a 3D printer to assemble a mold of it. They injected animal-derived collagen (frequently used in cosmetic/plastic surgery) into the resulting mold, then added ∼250 million human cartilage cells. As the main mammalian structural protein, collagen serves as a scaffold on which cartilage can grow. The high-density collagen gel developed by Cornell researchers resembles the consistency of flexible gelatin when the mold is removed.

“The process is fast,” says Bonassar. “It takes half a day to design the mold, a day or so to print it, and 30 minutes to inject the gel. We can remove the ear 15 minutes later. We trim the ear and then let it culture for several days in a nourishing cell culture medium before it is implanted.”

During a three-month observation period, cartilage grew to replace the collagen scaffold in the ears. “Eventually the bioengineered ear contains only auricular cartilage,” says Spector, “just like a real ear.” Previous bioengineered ears have been unable to maintain their shape/dimensions over time, and their cells did not survive.

Next Steps

These researchers are looking at ways to expand populations of human cartilage cells in vitro so that those cells could be used in ear molds. Spector says the best time to give a bioengineered ear to a child would be at five or six years of age, when most ears are 80% of their adult size. “We don’t know yet if the bioengineered ears would continue to grow to their full size, but I suspect that they will,” he says. “Surgery to attach a new ear would be straightforward: The malformed ear would be removed and the bioengineered ear inserted under a flap of skin.” Spector says that if all future safety and efficacy tests work out, the first such procedure might be possible in as little as three years. “These bioengineered ears are highly promising because they precisely mirror the native architecture of a human ear,” he says. “They should restore hearing and a normal appearance to children and others in need. This advance represents a very exciting collaboration between physicians and basic scientists. It is a demonstration of what we hope to do together to improve the lives of patients with ear deformity, missing ears, and beyond.”

Study coauthors include Dr. Alyssa J. Reiffel, Dr. Karina A. Hernandez, and Justin L. Perez from WCMC’s Laboratory for Bioregenerative Medicine and Surgery; and Concepcion Kafka, Samantha Popa, Sherry Zhou, Satadru Pramanik, Bryan N. Brown, and Won Seuk Ryu from Cornell University’s Department of Biomedical Engineering.

Author Details
Lauren Woods is a senior media associate at Weill Cornell Medical College, 1300 York Avenue, New York, NY 10021; 1-212-821-0560; law2014@med.cornell.edu; www.med.cornell.edu.