Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells

Abstract

The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.

Current advances in biomaterials for inner ear cell regeneration

“…Recent studies have shown that the combination of graphene oxide and hydrogels can promote the expansion of SGN growth cones and the outgrowth of neurites (Shi et al, 2023). Graphene substrates have also been revealed to promote the proliferation and HC differentiation of inner ear Lgr5+ progenitor cells, despite having no effect on cell viability (Ding et al, 2022). MXene, an emerging two-dimensional layered material with a structure similar to that of graphene, has been used in a wide range of applications since its discovery (Naguib et al, 2011) due to its excellent hydrophilicity and electrical conductivity (Naguib et al, 2021).…”

“…CI technology has restored partial hearing in patients with SNHL over the past few decades; however, challenges still remain (Naples and Ruckenstein, 2020). Research on coating materials for CI electrodes has never stopped, and these coating materials, especially topologically structured (Clarke et al, 2011;Tuft et al, 2014a;Mattotti et al, 2015;Cai et al, 2016;Leigh et al, 2017;Xu et al, 2018;Truong et al, 2021) or conductive materials (Wei et al, 2021;Ding et al, 2022;Hu et al, 2022;Liao et al, 2022;Zhang et al, 2022), can be used as interfaces to promote axonal regrowth of degenerated SGNs.…”

Graphene Hybrid Inner Ear Organoid with Enhanced Maturity

“…Ding et al demonstrated that graphene can induce the differentiation of inner ear progenitor cells into hair cells without the use of chemical factors. 32 Myosin7a+ cells were observed to be more prevalent on graphene substrates than on TCPS, suggesting that graphene may facilitate the differentiation process. In another study, computer simulations have also shown that the electric field on graphene, with a surface charge density of approximately −4 × 10 −4 C/m 2 , is nearly 2−3 times higher than that on TCPS (graphene, 0.8 V/μm; TCPS, 0.1 V/μm).…”

“…One possible mechanism is that the electrical properties of graphene may enhance the maturity of inner ear organoids. Ding et al demonstrated that graphene can induce the differentiation of inner ear progenitor cells into hair cells without the use of chemical factors . Myosin7a+ cells were observed to be more prevalent on graphene substrates than on TCPS, suggesting that graphene may facilitate the differentiation process.…”