>> Research Projects >> ”Living” Cochlear Implants and Hearing Loss Prevention

1. Towards the development of a "living" cochlear implant

We are aiming at developing the first tissue engineered “living” cochlear implant to benefit patients with hearing loss.

Loss of cochlear hair cells has been associated with the degeneration of auditory nerve fibers, due to the loss of endogenous trophic support from hair cells. This peripheral degeneration can then lead to loss of central auditory nuclei and successive impairments of auditory function. There is growing evidence that treatment with neurotrophic agents, such as glial-cell derived neurotrophic factor (GDNF), brain-derived neurotrophic factor ( BDNF ), neurotrophin 3 (NT-3), etc., enhances survival or neurogenesis in the auditory system. Some studies have demonstrated that neurotrophins are sufficient to maintain survival of auditory neurons after loss of hair cells, with the caveat that cessation of neurotrophin treatment may lead to accelerated neuronal loss compared to untreated cochleas. Thus, there is a critical need for long-term delivery of neurotrophic agents to auditory neurons in the diseased ear. Conventional delivery strategies utilizing degradable polymer carriers, microwicks, or miniosmotic pumps with catheters have been problematic due to uneven delivery profiles, limited temporal delivery profiles, and difficulty with retrieval.

To achieve long-term sustained delivery of neurotrophins and therefore prevent secondary nerve degeneration caused by hair cell loss in deaf patients, two types of "living" cochlear implants have been developed by Dr. Wen and both devices were submitted for patent approval. (Due to patent application, two papers are on hold for submission.) One type of "living" cochlear implant is specially designed for patients who need a new cochlear implant. The other type of device is designed for patients having cochlear implants in place. The long-term delivery of neurotrophins is made possible by both devices.

This project pioneers the development of a sustained, targeted delivery paradigm for hearing loss prevention and functional restoration based upon a novel design, which allows unlimited time delivery of neurotrophins into the diseased inner ear. Meanwhile, from the perspective of understanding the pathologies associated with auditory diseases and establishing effective therapies, the devices may serve as a scientific tool to examine cell behaviors in different in vivo microenvironments, and to help identify the key proteins and receptors involved in cochlear pathologies.

2. Resorbable, Drug Eluting, Pressure Equalizer (PE) Tubes

Pressure equalization tubes (PE tubes) or tympanostomy tubes are effective in reducing the frequency of ear infections and antibiotic use. A PE tube is placed in an incision (myringotomy) made in the tympanic membrane. The device bypasses a dysfunctional eustachian tube by ventilating the middle ear, provides drainage for middle ear fluid, and provides a portal for ototopical therapy. Its documented efficacy is a major reason that PE tube insertion is one of the most common surgical procedures performed in the United States. Most PE tubes maintain ventilation for approximately 1 year, but with a great degree of variability. Many of the complications are associated with prolonged tube ventilation. PE tubes that do not extrude may form tympanosclerosis or granulation tissue that can become quite vascular and cause recurrent bleeding. An atrophic portion of the tympanic membrane may develop at the site of tympanostomy tube placement. Persistent eustachian tube dysfunction may cause this atrophic portion of the tympanic membrane to retract and cause epithelial entrapment, an early nidus for cholesteatoma formation Tympanic membrane perforations may also cause hearing loss or provide an avenue for water exposure or infection. Additional surgery is frequently required to close the hole.

In view of the complications associated with prolonged PE tube ventilation, there may be value in developing a biodegradable PE tube [Read Full Paper]. A bioresorbable PE tube would not rely on squamous epithelial accumulation to mediate tube extrusion. Our hypothesis is that a bioresorbable ear tube made of a aliphatic polyester can be made to maintain middle ear ventilation for a predetermined duration, then degrade to permit the eardrum’s hole to close in a manner that is substantially equivalent to existing FDA-approved class II tympanostomy devices. We are now developing drug eluting tube for the enhanced performances in the body.