Perforations of the tympanic membrane or “eardrum,” the thin membrane that conducts sound in the ear, can result in severe hearing loss and recurring infections. Worldwide, tympanic membrane perforations occur in about 30 million people, with about four million people in North America and the European Union alone, due to blast and other traumatic injuries, chronic ear infections, and abnormal, noncancerous skin growth behind the eardrum. When these perforations do not heal on their own, they become chronic and require reconstructive “tympanoplasty” to repair these defects. However, commonly used graft materials, including temporalis fascia grafts harvested from tissue beneath the skin that covers the temples, do not ensure full mending. Hence, patients often require revision surgeries and are at risk for long-term hearing loss.
Engineering a permanent regenerative medicine solution
A multidisciplinary team of material scientists and ENT clinicians led by Gliklich Healthcare Innovation Postdoctoral Research Fellow Nicole Black and Core Faculty member Jennifer Lewis at the Wyss Institute, and Aaron Remenschneider and Elliott Kozin at Massachusetts Eye and Ear in Boston has developed an easy-to-use, biomimetic device, termed PhonoGraft. PhonoGraft is a biomimetic graft that has the potential to enable better and longer-lasting tympanic membrane reconstruction than typically used fascia grafts. These grafts, which are manufactured from biodegradable elastomers in the form of biomimetic circular and radial scaffolds to accommodate different ear sizes, function like the native eardrum.
By mimicking the native tympanic membrane, the PhonoGraft effectively conducts sound and promotes remodeling processes in which native tympanic tissue and vasculature grow into the graft, as the graft material slowly biodegrades. This results in tympanic membrane regeneration inside the ear that recapitulates key properties of the original tympanic membrane, including the conduction of sound across a broad range of frequencies important for human hearing, and normal barrier functions against pathogens.
The team has validated PhonoGraft in preclinical in vivo studies using a chinchilla model whose tympanic membrane size and hearing range are akin to humans. PhonoGraft enabled remodeling of native tissue in animals with chronic perforations, including neovasculaturization, as it slowly degrades. By contrast, autologous tissue grafts, which were used as controls in the same study, do not remodel or degrade. Importantly, PhonoGraft restores hearing far more effectively than control grafts, as determined by auditory tests that measure the ability of sound to reach the cochlea, the anatomical structure in the inner ear that produces nerve impulses in response to sound vibrations, as well as to the brain.
The Wyss Institute is currently de-risking this technology and is seeking industrial partners to assist with commercialization and funding efforts.