A tiny minority of infants – one to 10 per 10 000 births – are born without an outer ear (auricle). For them and their parents, the congenital disfigurement called microtia is a catastrophe. The birth defect that occurs when the external ear fails to develop normally, and as a result, is small and improperly formed. Occasionally, besides the aesthetic issue, microtia also involves hearing loss.

Since the “bones” of the outer ear are in fact flexible cartilage and not bone tissue, the customary technique for microtia reconstruction is to use costal cartilage harvested from the patient’s costal cartilage — which prolong the ribs forward and contribute to the elasticity of the walls of the thorax. But this method involves pain and discomfort as well as  a risk of further complications. In addition, constructing an ear that is identical to the other one depends on both the surgeon’s creativity and high-level surgical skills.

But now, researchers at the Technion-Israel Institute of Technology in Haifa and Sheba Medical Center at Tel Hashomer (near Tel Aviv) have developed an efficient technology for the fabrication of custom-made functional aesthetic implants for the rehabilitation of congenitally deformed ears.

The Israeli researchers’ breakthrough has just been reported in the journal Biofabrication under the title “Human-engineered auricular reconstruction (hEAR) by 3D-printed molding with human-derived auricular and costal chondrocytes and adipose-derived mesenchymal stem cells.” 

It was achieved through a collaborative project between Prof. Shulamit Levenberg of the Technion’s Faculty of Biomedical Engineering and Dr. Shay Izhak Duvdevani, a senior physician in the otorhinolaryngology head and neck surgery department and head of the tissue engineering lab at Sheba Medical Center.

In the current study, the researchers applied new technologies for tissue engineering that were developed in Levenberg’s lab under the leadership of Dr. Shira Landau to fabricate a biodegradable auricle scaffold that formed stable, custom-made neocartilage implants. 

The unique scaffold, which allows for the formation of an aesthetic and stable auricle, is 3D-printed and based on a computerized tomography (CT) scan. It is biodegradable and forms chondrocytes – the cells responsible for cartilage formation – and mesenchymal stem cells. The scaffold has pores of varying sizes, allowing for cell attachment to form stable cartilage.

3D printing can be applied to fabricate complex water-soluble moldדץ After they are printed, in a grid pattern, the desired material is cast into the mold, and the entire construct is freeze-dried to achieve pores within the material; the mold is then washed with water, leaving behind both large pores from the 3D printing process and small pores from the freeze-drying step. This approach has a significant advantage compared to direct printing since the mechanical properties of the material are highly controllable, which allows for precise printing and the fabrication of fine details. A full-sized pediatric ear requires 450 million expandable cells responsible for cartilage formation. 

According to the researchers, engineering an auricle from the patient’s own cells will reduce the suffering and risk caused to children as a result of harvesting their costal cartilage. Furthermore, it will allow the surgery to be performed on children as young as six years old, rather than the currently accepted practice of waiting until they are 10. Performing the surgery at a younger age is likely to minimize the psychological effects of microtia on children.

The researchers monitored cartilage formation within the auricle construct in the lab for between 10 days and six weeks and then implanted it in a murine (mouse) model. Mice are the most commonly used animal model for studying human disease because they are biologically very similar to humans and get many of the same diseases and can be genetically manipulated to mimic virtually any human disease or condition.

After the procedure, the graft integration was successful, and the prosthetic ear showed good biomechanical function. The technique could be used to produce an aesthetic outer ear for adults or children who lost theirs due to disease or physical trauma and were not born with a congenital defect. 

“One of the challenges in the study was to find a suitable 3D printing method, since fabricating an ear necessitates the use of biodegradable materials that break down in the body without harming it but have an extremely accurate external structure and small pores,” explained Levenberg. “We demonstrated all of this in the present research, and estimate that it will be possible to tailor our technology to other applications, such as reconstruction of thenose and fabrication of various orthopedic implants.”

“In the present study,” concluded Duvdevani, “we achieved a significant breakthrough by integrating medicine and research and collaboration among doctors and researchers. This research is another milestone in the transition to advanced technologies in medicine, where the use of 3D printing and tissue engineering will play a significant part and provide patients with an optimal, state-of-the-art response.”