Round-window delivery of lithium chloride regenerates cochlear synapses damaged by noise-induced excitotoxic trauma via inhibition of the NMDA receptor in the rat.

Noise exposure can destroy the synaptic connections between hair cells and auditory nerve fibers without damaging the hair cells, and this synaptic loss could contribute to difficult hearing in noisy environments. In this study, we investigated whether delivering lithium chloride to the round-window can regenerate synaptic loss of cochlea after acoustic overexposure. Our rat animal model of noise-induced cochlear synaptopathy caused about 50% loss of synapses in the cochlear basal region without damaging hair cells. We locally delivered a single treatment of poloxamer 407 (vehicle) containing lithium chloride (either 1 mM or 2 mM) to the round-window niche 24 hours after noise exposure. Controls included animals exposed to noise who received only the vehicle. Auditory brainstem responses were measured 3 days, 1 week, and 2 weeks post-exposure treatment, and cochleas were harvested 1 week and 2 weeks post-exposure treatment for histological analysis. As documented by confocal microscopy of immunostained ribbon synapses, local delivery of 2 mM lithium chloride produced synaptic regeneration coupled with corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response wave 1. Western blot analyses revealed that 2 mM lithium chloride suppressed N-methyl-D-aspartate (NMDA) receptor expression 7 days after noise-exposure. Thus, round-window delivery of lithium chloride using poloxamer 407 reduces cochlear synaptic loss after acoustic overexposure by inhibiting NMDA receptor activity in rat model.

Improved in vitro biocompatibility of surface-modified hydroxyapatite sponge scaffold with gelatin and BMP-2 in comparison against a commercial bone allograft.

This study aims to demonstrate the morphology and in vitro biocompatibility of neat and surface-modified hydroxyapatite sponge scaffold (SM-HASS) which was fabricated using a sponge replica method, and compared with the commercially available demineralized freeze-dried bone allograft (DFDBA). Surface-modifications were done by coating the surface area of the neat hydroxyapatite sponge scaffold (HASS) with either gelatin alone (HASS/G) or gelatin and BMP-2 growth factor (HASS/G+B). Scanning electron microscope (SEM), Fourier transform infrared (FTIR), porosity, pore size distribution, and compressive strength analyses showed that the addition of gelatin in HASS/G produced a morphologically and structurally similar scaffold to that of the allograft. The addition of BMP-2 improved the biocompatibility of the HASS/G+B in vitro using MC3T3-E1 cells which showed better cell viability, proliferation, and cell adhesion than on the allograft. Therefore, hydroxyapatite scaffold coated with gelatin polymer and gelatin with BMP-2 growth factor showed comparable performance against commercially available DFDBA from cadaver with regards to structure and in vitro biocompatibility.