1. Academic Validation
  2. Ti3 C2 Tx MXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids

Ti3 C2 Tx MXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids

  • Adv Sci (Weinh). 2022 Sep 18;e2203557. doi: 10.1002/advs.202203557.
Zhong Zhang 1 2 Shan Gao 1 Yang-Nan Hu 1 Xin Chen 1 Cheng Cheng 1 Xiao-Long Fu 1 3 Sha-Sha Zhang 1 Xin-Lin Wang 1 Yu-Wei Che 1 Chen Zhang 4 Ren-Jie Chai 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, P. R. China.
  • 2 Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Suzhou, 215123, P. R. China.
  • 3 Shandong Provincial Hospital, Shandong First Medical University, Jinan, 250021, P. R. China.
  • 4 Department of Neurobiology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100069, P. R. China.
Abstract

Organoids have certain cellular composition and physiological features in common with real organs, making them promising models of organ formation, function, and diseases. However, Matrigel, the commonly used animal-derived matrices in which they are developed, has limitations in mechanical adjustability and providing complex physicochemical signals. Here, the incorporation of Ti3 C2 Tx MXene nanomaterial into Matrigel regulates the properties of Matrigel and exhibits satisfactory biocompatibility. The Ti3 C2 Tx MXene Matrigel composites (MXene-Matrigel) regulate the development of Cochlear Organoids (Cochlea-Orgs), particularly in promoting the formation and maturation of Organoid hair cells. Additionally, regenerated hair cells in MXene-Matrigel are functional and exhibit better electrophysiological properties compared to hair cells in Matrigel. MXene-Matrigel potentiates the amycin (mTOR) signaling pathway to promote hair cell differentiation, and mTOR signaling inhibition restrains hair cell differentiation. Moreover, MXene-Matrigel facilitates innervation establishment between regenerated hair cells and spiral ganglion neurons (SGNs) growing from the Cochlea modiolus in a co-culture system, as well as promotes synapse formation efficiency. The 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.

Keywords

MXenes; co-culture; cochlea organoids; differentiation; functional hair cells; modiolus.

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