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Extracellular vesicles (EVs), as extracellular membrane particles, play a crucial role in intercellular signaling. Research suggests that EVs may be used as biomarkers for specific organs (such as the inner ear) or as drug delivery systems. The molecules released by EVs under stress and healthy conditions are different, and these active molecules can recognize the body's disease state. Research has shown that EVs can be used to deliver drugs to structurally complex organs, such as cochlear sensory hair cells and the brain, as they can cross the blood-labyrinth and blood-brain barrier. In this review, we summarize the biological composition and biogenesis of EVs, separation techniques, characterization methods, potential therapeutic applications as drug delivery carriers, drug loading methods, and potential applications in the treatment of the inner ear within the auditory system.

Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin‐induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin‐induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin‐induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1‐NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin‐induced SGNs damage, offering promising therapeutic targets for SNHL mitigation. [ABSTRACT FROM AUTHOR]

Photonic crystals are a new class of optical microstructure materials characterized by a dielectric constant that varies periodically with space and features a photonic bandgap. Inspired by natural photonic crystals such as butterfly scales, a series of artificial photonic crystals are developed for use in integrated photonic platforms, biosensing, communication, and other fields. Among them, colloidal photonic crystals (CPCs) have gained widespread attention due to their excellent optical properties and advantages, such as ease of preparation and functionalization. This work reviews the classification and self‐assembly principles of CPCs, details some of the latest biomedical applications of large‐area, high‐quality CPCs prepared using advanced self‐assembly methods, summarizes the existing challenges in CPC construction and application, and anticipates future development directions and optimization strategy. With further advancements, CPCs are expected to play a more critical role in biosensors, drug delivery, cell research, and other fields, bringing significant benefits to biomedical research and clinical practice. [ABSTRACT FROM AUTHOR]

In the past 20 years, the research about gene therapy on hereditary diseases has been deepening.As a safe vector, recombinant adeno-associated virus (rAAV) viruses are widely used in basic and clinical studiesof genetic diseases. Hereditary hearing loss, including nonsyndromic and syndromic hearing loss, is mainly causedby genetic or chromosomal abnormalities. Since the first deafness gene was discovered in 1997, 123 nonsyndromicdeafness genes and more than 40 syndromic deafness genes have been identified in the past twenty-four years.Hereditary deafness is characterized by a high clinical incidence in the population and lack of effectivelytreatments. Fortunately, with the development of molecular biology technology and the progress of gene therapy,recombinant AAV-mediated gene therapy has been widely used in the basic research of deafness treatment. Thisreview will address the concepts, strategies and applications of recombinant AAV-mediated gene therapies forhereditary diseases, especially for hereditary deafness.

The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super‐aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co‐cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region‐specific organoids and these organoids are assembled in the nanofiber‐combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4‐ethylenedioxythiophene) (PEDOT)‐integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre‐coating with polydopamine. The obtained PEDOT/IKVAV‐integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV‐integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV‐integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB‐derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long‐segment neural defects. [ABSTRACT FROM AUTHOR]

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four‐transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV‐ie‐mediated Gpm6b overexpression promoted SC‐derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re‐entry cell cycle and facilitating the SC‐to‐HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans‐differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV. [ABSTRACT FROM AUTHOR]

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).