A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement
Technical Report,30 Sep 2014,29 Sep 2015
Regents of the University of Michigan Ann Arbor United States
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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.