A Model for the Human Inner Ear, Built on a Chip

By: Wynne Parry | June 02, 2026 | 10 min. read |

Miller School researchers are developing an organoid-on-a-chip system to model inner ear development and explore how damaged sensory hair cells might be regenerated.

The anatomical structure of the human ear, sound wave and ear with middle ear, otitis, auditory canal, auditory canal and cochlea nerve, 3d illustration

During embryogenesis, molecular signals establish the basic architecture of the inner ear, designating one half dorsal and the other ventral. This asymmetry then guides formation of the two organs it contains, the cochlea below, the vestibular system on top.

Researchers at the University of Miami Miller School of Medicine, led by Pei-Ciao Tang, Ph.D., a research assistant professor in the Miller School’s Department of Otolaryngology — Head and Neck Surgery, are recreating this spatial division with an organoid-on-a-chip system. Microfluidic channels in the chip expose human, stem cell-derived organoids to the distinct chemical environments that drive this patterning in vivo.

Dr. Diane Jung with Dr. Pei-Ciao Tang in the lab, both flashing the U hand sign — Dr. Pei-Ciao Tang (left, with Dr. Diane Jung) is studying how hair cells develop, and how to regenerate them.

“Our project will provide invaluable insight into how the hair cells responsible for hearing and balance develop and, potentially, how to regenerate them,” Dr. Tang said. “A glimpse of this process could contribute to new therapeutic strategies for hearing loss and vestibular disorders.”

Recreating Inner Ear Development on a Chip

Dr. Tang and Miller School colleagues Ashutosh Agarwal, Ph.D., an associate professor of engineering at the University of Miami and director of engineering and applied physics for the Desai Sethi Urology Institute, and Derek Dykxhoorn, Ph.D., professor in the Dr. John T. Macdonald Foundation Department of Human Genetics, and colleagues from outside the University of Miami have received an approximately $2.5 million, five-year RO1 grant from the U.S. National Institutes of Health (NIH).

Studio portrait of Dr. Derek Dykxhoorn wearing round eyeglasses, a white lab coat, and a dark patterned tie against a light gray background. The coat features UHealth branding, indicating affiliation with an academic medical center. — Dr. Derek Dykxhoorn

Dr. Ashutosh Aagarwal, in black shirt and coat, smiling in a science lab — Dr. Ashutosh Agarwal

The research team aims to reliably induce the formation of cochlear tissue, which has proven more difficult to generate than that of the vestibular system. Meanwhile, they intend to use the more accessible vestibular system to investigate sensory hair cell development and the possibility of restoring hair cells lost due to damage, injury or aging.

“Fooling” an Organoid

Research on the development of inner ear structures, which are deeply embedded within the temporal bone and nearly impossible to access without damaging, has relied heavily on pre-clinical models and, more recently, human stem cells. Conventional stem cell models, however, do not replicate the chemical gradients that partition the developing inner ear in two.

To create a system that did, Dr. Tang sought help from Dr. Agarwal, whose lab specializes in human organs-on-chips. These microscale devices mimic organs within physiological conditions.

Infographic from University of Miami Miller School of Medicine showing an NIH-funded inner ear-on-a-chip model that uses stem cell–derived organoids and microfluidic gradients to simulate cochlear and vestibular development, study hair cell regeneration, and advance hearing loss treatment research.

“On the basic level, the challenge was how do you fool an organoid into believing it’s part of a growing organism?” Dr. Agarwal said. “The answer is by exposing it to two very different chemical environments, which is exactly what happens in development.”

During fetal development, cells encounter signals called morphogens, which prompt them to choose a fate, such as that of a cochlear versus vestibular hair cell. The morphogens’ concentrations vary with location, shaping the structure of the human inner ear and many other aspects of our anatomy.

A Chip Designed for Two Fates

Dr. Agarwal’s lab designed a chip that holds an organoid, measuring 0.5 to two millimeters (0.02 to 0.08 inches) positioned between two parallel microfluidic channels, each delivering a distinct chemical environment.

One channel supplies the morphogen SHH along with inhibitors of the WNT and BMP signaling pathways, a combination intended to drive ventralization and promote cochlear development. The other channel delivers a growth medium that allows the organoid to default to its baseline trajectory of dorsalization and a vestibular fate.

If we can identify the key pathways that drive hair cell fate, we may be able to enhance hair cell regeneration by modulating them. This would give us targets for therapeutic approaches to address disorders of the inner ear.
Dr. Derek Dykxhoorn

While researchers have established reliable methods for deriving the vestibular system from stem cells, they have struggled to do the same for the cochlea. Consequently, part of the team’s work focuses on inducing cochlear tissue. Other components of the project center on its more tractable counterpart, the vestibular system.

Some evidence suggests this balance organ has a limited capacity to regenerate sensory hair cells. In the cochlea, hair cells lost to damage caused by prolonged noise exposure, ototoxic medications or simply age, do not grow back. Hearing loss is permanent.

The vestibular system appears different. Some studies, including the team’s preliminary experiments, have found evidence of regeneration among its hair cells.

Pursuing the Possibility of Regeneration

Very little is known about the mechanisms that control this process, according to Dr. Dykxhoorn. However, some evidence suggests DNA methylation may limit it by suppressing key regulators of cell fate needed to regrow hair cells, he said.

To explore how epigenetics regulates the formation of hair cells and perhaps their capacity for regeneration, Dr. Tang will map chromatin accessibility and its downstream effects on gene expression in the organoids. She will apply the same approach after exposing the organoids to an aminoglycoside antibiotic, a class of drugs known to destroy hair cells. The goal is to identify developmental pathways involved in responding to the injury. She and Dr. Dykxhoorn will then test any candidates using CRISPR-based tools to switch their genes on or off.

“If we can identify the key pathways that drive hair cell fate, we may be able to enhance hair cell regeneration by modulating them,” Dr. Dykxhoorn said. “This would give us targets for therapeutic approaches to address disorders of the inner ear.”

The organoid-on-a-chip’s potential applications extend well beyond the inner ear. Morphogen gradients drive cell fate decisions across an embryo, leading to the emergence of the nervous system, the limbs and more.

“If we can create a gradient across a three-dimensional organoid, our approach could be widely applicable for studying patterning during human development,” Dr. Tang said.