Inner ear disorders are among the predominant etiology of hearing loss. The blood-labyrinth barrier limits the ability of drugs to attain pharmacologically effective concentrations within the inner ear; consequently, delivering drugs systemically is insufficient for effectively treating inner ear disorders. Hence, it is imperative to create efficient, minimal or non-invasive methods for administering drugs to the inner ear. However, the development of such a system is hindered by three main factors: anatomical unavailability, the lack of sustained drug delivery, and individual variability. Advances in biomaterials technology have created new opportunities for overcoming existing barriers, offering great hope for the effective treatment of inner ear disorders. Hydrogel- and nanoparticle-based drug delivery systems can carry drugs to targeted designated anatomical locations in the inner ear for long-term, sustained release. Furthermore, a range of devices, including microneedles, micropumps, and cochlear implants, when paired with biomaterials, enhance the delivery of drugs to the inner ear, making the treatment of inner ear disorders more effective. Therefore, biomaterial-based drug delivery systems offer the possibility for extensive clinical uses and promise to restore hearing to millions of patients with inner ear disorders.

Cochlear implants can directly activate the auditory system’s primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration.

The hypothalamus is a central regulator of systemic energy balance and glucose homeostasis, yet how type 2 diabetes (T2D) alters its cellular and regulatory landscape remains incompletely understood. Here, we integrated single-nucleus RNA sequencing (snRNA-seq) with bulk ATAC-seq to characterize hypothalamic remodeling in an HFD/STZ-induced T2D mouse model. High-resolution snRNA-seq revealed pronounced cell type-specific alterations involving several neuronal subpopulations, including Gal.Nts.Npy, Nxph4.Adcyap1, and Lmx1a.Gpr149.Tcf4 neurons, together with substantial changes in oligodendrocyte-lineage cells. Increased Npy expression was accompanied by greater tissue-level chromatin accessibility at the Npy locus, providing convergent evidence for activation of the hypothalamic Npy regulatory axis. Pseudotime analysis further showed increased representation of a transcriptionally distinct Cntnap2-positive oligodendrocyte-lineage state, together with reduced representation of canonical myelination-associated states. Ligand–receptor analysis predicted reduced signaling across selected neuron–oligodendrocyte interactions and altered communication among glial populations. Collectively, these findings reveal coordinated neuronal, oligodendrocyte-lineage, intercellular signaling, and chromatin-accessibility alterations in the diabetic hypothalamus, and identify the Npy regulatory axis and Cntnap2-positive oligodendrocyte-lineage state as candidate features for further mechanistic investigation.

Background: Sensorineural hearing loss (SNHL) is increasingly recognized as a disorder involving not only hair-cell damage but also selective degeneration of spiral ganglion neurons (SGNs). Recent single-cell, molecular, and functional studies have refined the classical type I/type II classification of SGNs by identifying distinct Ia, Ib, and Ic subtypes within type I neurons. This review aims to synthesize current evidence on how SGN vulnerability is shaped by the interaction between subtype identity, life stage, and injury context. Methods: We conducted a critical narrative review of recent studies on SGN heterogeneity and subtype-specific vulnerability across development, maturity, and aging, with particular attention to molecular profiling, functional studies, and emerging therapeutic strategies. Results: SGN degeneration in SNHL is not uniform. During development, the available evidence mainly supports the vulnerability of subtype specification, synaptogenesis, and activity-dependent maturation, rather than direct selective degeneration of mature Ia/Ib/Ic identities. In the mature cochlea, subtype-specific differences in synaptic architecture, ion-channel composition, and metabolic demand appear to shape responses to noise, ototoxic drugs, and ischemic stress, with Ic-related populations often showing greater vulnerability. During aging, cumulative mitochondrial dysfunction, oxidative stress, chronic inflammation, and declining neurotrophic support may progressively unmask differences in subtype resilience and contribute to age-related auditory decline. Conclusions: A lifespan-oriented and subtype-informed framework may improve the current understanding of selective SGN degeneration and support the development of more precise neuroprotective and reparative strategies for SNHL.

Precision prevention and control of genetic diseases represent a major public health challenge. This paper provides a structured narrative review of advances in molecular diagnostic technologies across the preconception, preimplantation, and prenatal stages over the past five years. In the preconception phase, next-generation sequencing has become central to carrier screening, while long-read sequencing significantly enhances detection capabilities for complex variants. In the preimplantation phase, research has increasingly focused on non-invasive preimplantation genetic testing, leveraging maternal contamination quantification algorithms and deep learning models to address DNA contamination challenges. During the prenatal phase, stratified diagnostic strategies combining chromosomal microarray analysis and whole-exome sequencing have improved the diagnostic evaluation of fetal structural anomalies. Simultaneously, non-invasive prenatal testing is expanding to include microdeletion/duplication and monogenic disease screening, though positive screening results still require invasive diagnostic confirmation. Future trends lie in multi-technology integration, multi-omics data fusion, and artificial intelligence-assisted decision-making, aiming to enhance resolution while balancing health-economic considerations and ethical standards.