Ti ₃C ₂T _xMXene Composite 3D Hydrogel Promotes the Generation of Functional Hair Cells in Cochlea Organoids

Organoids have certain cellular composition and physiological features in common with real organs, making them promising models of organ formation, function, and diseases. However, the most used animal-derived matrices in which they are developed, Matrigel, have limitations in mechanical adjustability and providing complex physicochemical signals. Here, we used Ti3C2TxMXene nanomaterial to modify the property of Matrigel. We showed that the Ti3C2TxMXene Composite Matrigel (MXene-Matrigel) regulated the development of Cochlear Organoids (Cochlea-Orgs), particularly in promoting the formation of functional organoid hair cells. Additionally, using mRNA sequencing, we found that some specific genes of hair cells in the MXene-Matrigel hydrogel are significantly upregulated. Using the whole-cell patch-clamp, we also demonstrated that newly generated hair cells in MXene-Matrigel were functional and exhibited electrophysiological properties comparable to postnatal day2 (P2) mouse cochlea hair cells. Moreover, we successfully developed a co-culture system of Cochlea-Orgs and modiolus. Regenerated hair cells established innervation with spiral ganglion neurons (SGNs) growing from the Cochlea modiolus. And MXene-Matrigel promoted synapse formation efficiency in the co-culture system. Our approach overcomes some limitations of the Matrigel-dependent culture system and greatly accelerates the application of nanomaterials in organoid development and research on therapies for hearing loss.