Localized cell and drug delivery for auditory prostheses

Abstract

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness.

Figure 1

Schematic of auditory prostheses in the cochlea and central auditory pathway. The cochlear implant (CI) is used to stimulate cochlear nerve processes from within the cochlea. The auditory brainstem implant (ABI) is composed of a grid of surface electrodes to stimulate the cochlear nucleus. The penetrating auditory brainstem implant (PABI) is better able to access the tonotopic structures of the cochlear nucleus that lie parallel to the surface of the cochlear nucleus. The target of the auditory midbrain implant (AMI) is the inferior colliculus. Reproduced from Lenarz et al. (2006b) with permission from Lippincott Williams & Wilkins.

Figure 2

2A. Anatomical section of guinea pig cochlea showing the scala tympani (ST), the chamber in which cochlear implants are inserted, the Organ of Corti (OC) where the sensory hair cells are found and enervated by spiral ganglion processes, and the spiral ganglion (SG) cell bodies. Electrical stimulation of the spiral ganglion processes or cell bodies can result in neuronal activation. 2B. Section of human cochlea with cochlear implant showing minimal tissue reaction. Small amounts of fibrous tissue were found around the electrode tip along the lateral wall. The implant had been in place for 5 years. 2C. Cochlear sections from another human patient with extensive new bone growth in the scala tympani between the electrode array and Rosenthal's canal, located at the right of the image. In addition, the osseous spiral lamina was fractured due to the implanted electrode. This cochlear implant had been in place for 8 years. Images 2B and 2C have been adapted from Kawano et al. (1998) with permission from Informa Healthcare.

Figure 3

3A. Histological section of inferior colliculus showing the implant track, T, from an auditory midbrain implant that had been in place in a cat for 3 months and electrically stimulated for the final 2 months. Dense tissue around implant track is fibrous encapsulation of electrode and shows increased staining for glial fibrillary acidic protein suggesting the presence of astrocytes around the implant. 3C. Average glial cell density around the probe show elevated glial populations for up to 500 μm from the implant site. The difference is statistically significant for 50–250 μm (*) (4 animals). 3B. The average density of neurons in the tissue surrounding the implant site is lower than in the control, unimplanted inferior colliculus. At 50 μm the difference in neuronal density is statistically significant (*), and around 200 μm from the implant no difference is seen (4 animals). Reproduced from Lenarz et al. (2007) with permission from Lippincott Williams & Wilkins.

Figure 4

4A. Custom-built 4 channel cochlear implant with pharmacological delivery. A hole in the tip of the electrode, indicated by an arrow, is connected via polyimide microtubing to an osmotic pump to infuse drugs into the scala tympani. Reproduced from Shepherd et al. (2002b) with permission from Elsevier. 4B. A different custom-built contoured cochlear implant with integrated drug delivery microcannula for delivery of drugs 3into the basal portion of the cochlea using an osmotic pump. The delivery site and connection point are indicated with arrows. The implant is made of silicone molded to enter the cochlea through the RWM as indicated by “RW”. Reproduced from Rebscher et al. (2007) with permission from Elsevier. 4C. The Contour cochlear implant lead retrofitted with a drug delivery channel along its inner lumen. It can be attached to a mini-osmotic pump to deliver pharmacological agents through ports between electrodes along the implant or at the tip. Reproduced from Paasche et al. (2003) with permission from Lippincott Williams & Wilkins.