A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement
Abstract
The chief aim of our study is restoration of hearing by regeneration of peripheral auditory neurons. The study takes a systematic approach in three objectives aiming to push human stem cells toward an auditory neural fate, embed the cells on a functionalized scaffold, and implant the device in a deafened animal model. In the first year of the project grant, we have addressed three key tasks: (1) derivation of sensory neurons from human pluripotent stem cells (hPSCs), (2) development of implantable nanofibrous substrates, and (3) optimization of the deafness model. We have established and compared several methods for generating glutamatergic sensory neurons including (i) standard SMAD inhibition, (ii) Neurog1-overexpression in otic precursors, and (iii) neurogenesis in inner ear organoids. Neural progenitors adhere and mature on nanofibrous scaffolds. New methods were developed to bundle cell-seeded scaffolds in small, defined polymer sheaths. Surgical approaches were generated to facilitate implantation in chemically deafened guinea pigs. Initial results show improved electrically-evoked auditory brainstem responses in cell-seeded implants compared to control, cell-free implants.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1005930
Entities
People
- Keith R. Duncan
Organizations
- Board of Regents of the University of Michigan