Decellularized equine carotid artery layers as matrix for regenerated neurites of spiral ganglion neurons

Abstract

Today’s best solution in compensating for sensorineural hearing loss is the cochlear implant, which electrically stimulates the spiral ganglion neurons in the inner ear. An optimum hearing impression is not ensured due to, among other reasons, a remaining anatomical gap between the spiral ganglion neurons and the implant electrodes. The gap could be bridged via pharmacologically triggered neurite growth toward the electrodes if biomaterials for neurite guidance could be provided. For this, we investigated the suitability of decellularized tissue. We compared three different layers (tunica adventitia, tunica media, and tunica intima) of decellularized equine carotid arteries in a preliminary approach. Rat spiral ganglia explants were cultured on decellularized equine carotid artery layers and neurite sprouting was assessed quantitatively. Generally, neurite outgrowth was possible and it was most prominent on the intima (in average 83 neurites per spiral ganglia explants, followed by the adventitia (62 neurites) and the lowest growth on the media (20 neurites). Thus, decellularized equine carotid arteries showed promising effects on neurite regeneration and can be developed further as efficient biomaterials for neural implants in hearing research.

Development of Neuronal Guidance Fibers for Stimulating Electrodes: Basic Construction and Delivery of a Growth Factor

“… Xie et al (2012) showed that a BDNF reservoir leads to a long distance axonal growth of hippocampal neurons along an ordered channel system. Further studies support the successful guidance of SGNs along ordered structures and their positive effect on the length of the neurites ( Leigh et al, 2017 ; Yilmaz-Bayraktar et al, 2020 ). Whereas other studies have reported a neuroregenerative effect of BDNF, based on increasing lengths of neurites ( Gao et al, 2016 ; McGregor and English, 2019 ), we were not able to confirm this in the present work nor in former BDNF delivery experiments ( Schmidt et al, 2018 ).…”

“…Even though not investigated in this study, a BDNF concentration gradient emanating from the polymer fibers could be a conceivable method for not only enhancing the survival rate of the SGNs, but also for guiding their neurites along the fibers and finally towards the surface of the implant. Several studies have demonstrated neuronal growth towards a neurotrophin concentration gradient ( Xie et al, 2012 ; Li H. et al, 2017 ; Yilmaz-Bayraktar et al, 2020 ). Xie et al (2012) showed that a BDNF reservoir leads to a long distance axonal growth of hippocampal neurons along an ordered channel system.…”

“…Due to this gap, electrical signals with stronger intensity have to be used and spatial spreading of the stimulation signal occurs ( Wilson, 2017 ). This leads to an overlap in the addressed SGNs and reduces focused neuronal stimulation which in turn leads to discriminated frequency resolution ( Stöver and Lenarz, 2009 ; Shibata et al, 2011 ; Li H. et al, 2017 ; Yilmaz-Bayraktar et al, 2020 ). In a more favourable situation, the neurites resprouting from the SGNs would overcome this gap to get into close contact with the electrode in order to achieve a much more specific electrical stimulation.…”

“…Despite the fact that the development of neuronal guidance conduits for peripheral nerves has made considerable progress ( Houshyar et al, 2019 ), and that there is strong research on regenerative scaffolds for the treatment of spinal cord injury, only limited research has been carried out with regard to scaffolds guiding resprouting neurites of SGNs to the implant. Decellularized equine carotid arteries showed promising effects on neurite regeneration ( Yilmaz-Bayraktar et al, 2020 ). Calcium phosphate hollow nanospheres coated on a CI and delivering GDNF were proposed to help close the anatomical gap between auditory neurons and electrodes ( Li H. et al, 2017 ).…”

Oriented polyaniline/poly‐l‐lactic acid/gelatin nanofiber scaffolds promote outgrowth of spiral ganglion neurons

“…It has also been reported that decellularized equine carotid arteries showed positive effects on neurite regeneration. 29 However, the disadvantage is that these materials are less stable and homogeneous, may also damage electrodes and increase current diffusion. Some studies have also attempted to use cochlear electrode coatings as a drug delivery system, for example by adding drugs such as dexamethasone for therapeutic purposes.…”