Bioengineering applications for hearing restoration: emerging biologically inspired and biointegrated designs.

Cochlear implantation has become the standard of care for hearing loss not amenable to amplification by bypassing the structures of the cochlea and stimulating the spiral ganglion neurons directly. Since the first single channel electrodes were implanted, significant advancements have been made: multi-channel arrays are now standard, they are softer to avoid damage to the cochlea and pre-curved to better position the electrode array adjacent to the nerve, and surgical and stimulation techniques have helped to conform to the anatomy and physiology of the cochlea. However, even with these advances the experience does not approach that of normal hearing. In order to make significant advances in performance, the next generation of implants will require novel interface technology. Advances in regenerative techniques, optogenetics, piezoelectric materials, and bioengineered living scaffolds hold the promise for the next generation of implantable hearing devices, and hope for the restoration of natural hearing.

Biopreservation of living tissue engineered nerve grafts.

Tissue engineered nerve grafts (TENGs) built from living neurons and aligned axon tracts offer a revolutionary new approach as "living scaffolds" to bridge major peripheral nerve defects. Clinical application, however, necessitates sufficient shelf-life to allow for shipping from manufacturing facility to clinic as well as storage until use. Here, hypothermic storage in commercially available hibernation media is explored as a potential biopreservation strategy for TENGs. After up to 28 days of refrigeration at 4℃, TENGs maintain viability and structure in vitro. Following transplantation into 1 cm rat sciatic defects, biopreserved TENGs routinely survive and persist for at least 2 weeks and recapitulate pro-regenerative mechanisms of fresh TENGs, including the ability to recruit regenerating host tissue into the graft and extend neurites beyond the margins of the graft. The protocols and timelines established here serve as important foundational work for the manufacturing, storage, and translation of other neuron-based tissue engineered therapeutics.