Spiral ganglion neurons (SGN) carry auditory information from sensory hair cells (HCs) to the brain. These auditory neurons, which are the target neurons of cochlear implants, degenerate following sensorineural hearing loss (SNHL). Prosthetic devices such as cochlear implants function by bypassing lost HCs and stimulating the residual SGNs, allowing restoration of hearing in deaf patients. Emerging cell-replacement therapies for SNHL include replacing damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells constitutes a major prerequisite towards cell replacement for auditory nerve recovery. Human dental pulp stem cells (hDPSCs) extracted from human wisdom teeth are self-renewing stem cells that originate from the neural crest during development. In this study, we developed a stepwise in vitro guidance procedure to differentiate hDPSCs into ONPs and then to SGNs. The procedure relies on the modulation of BMP and TGF-β pathways for neurosphere formation as a first step, then a differentiation step based on two culture paradigms exploiting major signaling pathways (Wnt, Shh, RA) and neurotrophic factors involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers over the course of in vitro differentiation. The use of atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties compared to their in vivo SGN counterparts. Furthermore, neurites extended between hDPSC-derived ONPs and rat SGN explants 4-6 days after co-culturing, suggesting the formation of neuronal contacts. These data indicate that the in vitro differentiated cells closely replicate the phenotypic and nanomechanical characteristics of human SGNs, advancing our culture differentiation system to the level to be used in next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.

The rheological properties of the periodontal ligament are key parameters to understand the homeostatic stability of the tooth supporting apparatus. The objective of this study is to lay new insights on the rheological properties and structural information of different regions in murine periodontal ligament by using atomic force (AFM) and multi-photon microscopy (MPM). A significant variation in elasticity of different regions was measured. The elasticity of periodontal ligament showed a significant tendency to become softer towards the furcation, the nearest area to the center of resistance of the tooth. This can open a new prospective for connecting the rheological adaptation of periodontal ligament to the tooth geometry that defines the center of resistance. Another important finding revealed by the second harmonic generation (SHG) signal exhibited by collagen fibers and measured by MPM is that the orientation of fibers in the furcation region can both provide space for tooth vertical movement with high compressive loads and prevent horizontal tooth movement. Additionally, it was found that the dispersion of the angles at different levels of cutting indicates homogeneity in the directionality of fibers across different regions. These results provide an accurate description of the rheological properties and structural information of periodontal ligament, which can serve as a base for comparison with other local and systemic diseases that may influence the periodontal ligament.

Optical Second Harmonic Generation (SHG) is obtained from adsorbed gold nanoparticles with an average diameter of 16 nm at the air / aqueous solution interface in reflection. A detailed analysis of the depth profile of the SHG intensity detected shows that two contributions appear in the overall signal, one arising from the air / aqueous solution interface that is sensitive to the gold nanoparticles surface excess and one arising from the bulk aqueous phase. The latter is an incoherent signal also known as Hyper Rayleigh scattering. The results are in agreement with an analysis involving Gaussian beam propagation optics and Langmuir isotherm. It also reveals discrepancies for the largest concentrations used and proposes a new route for the design of soft metasurfaces.

The degeneration of spiral ganglion neurons (SGNs), which convey auditory signals from hair cells to the brain, can be a primary cause of sensorineural hearing loss (SNHL) or can occur secondary to hair cell loss. Emerging therapies for SNHL include the replacement of damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells is a prerequisite for successful replacement of the auditory nerve. In this study, we derived ONP and SGN-like cells by a reliable and reproducible stepwise guidance differentiation procedure of self-renewing human dental pulp stem cells (hDPSCs). This in vitro differentiation protocol relies on the modulation of BMP and TGFβ pathways using a free-floating 3D neurosphere method, followed by differentiation on a Geltrex-coated surface using two culture paradigms to modulate the major factors and pathways involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers during the time course of hDPSCs differentiation. Atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties as their in vivo SGN counterparts. Furthermore, spiral ganglion neurons from newborn rats come in close contact with hDPSC-derived ONPs 5 days after co-culturing. Our data demonstrate the capability of hDPSCs to generate SGN-like neurons with specific lineage marker expression, bipolar morphology, and the nanomechanical characteristics of SGNs, suggesting that the neurons could be used for next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.

We investigate anatase TiO 2 doping with Au to determine the change in the band gap energy and optoelectronic properties using experimental and theoretical analysis. The structural analysis using XRD patterns revealed that the synthesized materials primarily exhibited an anatase phase of TiO 2 , with no impurity peaks observed. However, as the concentration of Au increased, additional diffraction peaks corresponding to Au crystalline phases were detected, indicating successful doping. Furthermore, the crystallite size was found to decrease with increasing Au concentration. We observe that the band gap reduces through substitution of Au into the TiO 2 lattice from 3.09 eV to 2.78 eV, demonstrating the feasibility of bandgap tuning of the TiO 2 system. A redshift for Au doped TiO 2 is observed from absorption spectroscopy and optical absorption intensity using hybrid density functional theory, facilitating visible light absorption, although with potential electron-hole recombination limitations. To enhance a visible light photocatalytic activity for water splitting, we extend our work to explore the impact of N and Au codoping into TiO 2 lattice. It reveals that the combination between N and Au leads to a suitable reduction in the band gap width of pure TiO 2. Interestingly, Au-N codoping may decrease the effect of photogenerated carriers, produce a new optical absorption feature in the visible region, and enhance the photocatalytic performance of TiO 2. This codoping configuration is also a promising photocatalyst for the decomposition of water using visible light without inducing unoccupied states.