Laboratory-grown elastic ear cartilage moves closer to clinical reality

Swiss researchers have engineered elastic cartilage from patients’ own ear cells with mechanical properties close to natural tissue, although stabilisation of elastin remains a critical hurdle before clinical translation

For more than 30 years, scientists have sought to fabricate a human ear in the laboratory from a patient’s own living cells. In 2016, Professor Marcy Zenobi-Wong at ETH Zurich demonstrated a three-dimensionally printed ear that attracted international attention. Researchers at ETH Zurich, working with colleagues at the Friedrich Miescher Institute and the Cantonal Hospital of Lucerne, both in Switzerland, have now reported a further step towards functional reconstruction.

Using human ear cartilage cells, the team produced elastic cartilage in vitro with mechanical characteristics similar to those of natural ear tissue. The engineered construct displayed stability comparable to that of a human ear and, after implantation beneath the skin of rats, retained both shape and elasticity for six weeks.

The clinical need is substantial with severe burns, trauma and other accidents frequently leading to partial or complete loss of the external structures of the ear. In addition, congenital malformation of the outer ear – known as microtia – affects approximately four in every 10,000 children. At present, reconstruction typically relies on rib cartilage harvested from the patient. Surgeons then carve this tissue to approximate the shape of an ear. Although established practice, this approach can cause pain, thoracic scarring and deformation, and the reconstructed ear often proves to be stiffer than its natural counterpart.

“We aren’t implanting soft tissue in the hope that it remains stable in the body. Instead, we want to achieve that stability in the laboratory,” said Dr. Philipp Fisch, senior researcher in the Tissue Engineering and Biofabrication Group at ETH Zurich and lead author of the study. His statement captured the central objective of the work – to create a construct that already possesses the structural integrity required for long-term function before the potential trauma of surgical implantation.

A principal obstacle lies in elastin, the protein that confers flexibility and recoil to ear cartilage. To recreate the tissue of the ear faithfully, researchers must not only induce cells to synthesise elastin but also ensure correct assembly into a stable, long-lasting network. A precise biological ‘blueprint’ for this process remains elusive. Without that blueprint, elastin may form incompletely or degrade, and so would compromise durability.

The team began with cartilage remnants removed during corrective ear surgery. From a fragment roughly three millimetres in diameter, they could isolate about 100,000 cells. However, fabrication of a full-sized ear requires several hundred million cells. The researchers therefore expanded the cells in a nutrient solution culture. They also designed a tailored culture environment to deliver oxygen and nutrients deep within the printed construct and to promote uniform maturation throughout the tissue.

To stimulate proliferation while preserving cellular identity, the group tested a range of growth factors. They sought to prevent the cartilage cells from adopting behaviour typical of fibroblasts. Fibroblasts primarily produce type I collagen and can form scar-like tissue. Such a shift would yield fibrocartilage, which contains type I collagen and lacks the stiffness and elastic qualities characteristic of cartilage in the ear, which is rich in type II collagen and elastin.

After expansion, the cells were embedded in a bioink – a gel-like carrier material suitable for three-dimensional bioprinting. A printer then shaped the bioink into ear-like structures. Immediately after fabrication, the constructs remained soft and immature.

“While the input material is crucial, so too is the tissue’s ability to develop,” Fisch explained. The constructs were therefore placed in an incubator for several weeks to permit maturation under controlled conditions. Continuous nutrient supply aimed to promote deposition of type II collagen, elastin and glycosaminoglycans, sugar-like molecules that bind water and contribute to cartilage resilience. Fisch noted that success depended on a combination of four elements.

“We optimised cell proliferation, adjusted the material properties, increased the cell density and controlled the maturation environment more effectively,” he added.

After approximately nine weeks of laboratory pre-maturation, the researchers implanted the constructs beneath rat skin and monitored their development. Six weeks later, the artificial ears had maintained form and exhibited mechanical properties close to those of native cartilage.

“Despite this major success, elastin remains a challenge for us, as we were not able to mature it fully,” Fisch said.

“We observed changes in the tissue. That clearly shows that we need to stabilise it further.” His remarks underline the central scientific issue – without a robust elastin network, then long-term structural fidelity cannot be guaranteed.

Only a small number of research groups worldwide pursue fabrication of elastic ear cartilage, and each experimental cycle can last three to four months. Progress therefore demands patience, precise optimisation and iterative refinement. The controlled formation of a durable elastin network represents the decisive step if artificial ears are to maintain shape and function for years after implantation in a human.

“We’ve been working on this problem in our group for more than ten years. When it comes to biofabrication of tissue – or tissue engineering as it’s also known – swift progress is rare to see,” Fisch said.

Fisch expressed cautious optimism about the next phase: “If all goes well, we hope to find the blueprint for the elastin network within the next five years,” he said. Subsequent steps would include structured clinical studies and formal regulatory approval before any transition to routine surgical practice.

“Our current study provides a good guide to the current state of research. It shows how close we already are to recreate the human ear – and what’s still missing,” Fisch concluded.

For further reading please visit: 10.1002/adfm.202530253