Huan Wang

The loss of spiral ganglion neurons (SGNs) and hair cells often leads to sensorineural hearing loss (SNHL), whose therapeutic effect depends on the quality and functional integrity of the residual SGNs. Compared with traditional pharmacological therapies, tissue engineering methods have been developed to provide a biomimetic environment for SGN regeneration, but static strategies and non‐responsive scaffolds still limit the therapy efficiency. Here, we present a composite piezoelectric nanofibrous scaffold responsive to acoustic stimulation to promote the growth of SGNs. The oriented nanofibrous scaffold comprising polyaniline (PANI), poly (L‐lactide) (PLLA) and gelatin was fabricated using electrospinning techniques. It was cytocompatible and provided a biomimetic culture environment with controllable electric signals for SGN regeneration. It has been confirmed that the piezoelectric nanofibrous scaffold could not only enhance cell adhesion and directional growth of SGNs, but also generate the electrical signals in response to acoustic stimulation, thereby accelerating the axon growth and functional development of SGNs. Therefore, the piezoelectric nanofibrous scaffolds could provide a new approach for SGN regeneration and a potential therapeutic strategy for SNHL.

The rapid advancements in nanotechnology have promoted transformative breakthroughs in biomedical imaging, with global research in this field exhibiting exponential growth and numerous cutting-edge achievements widely reported. This review systematically summarizes the evolving frontiers of nanomaterial-enabled in vivo bioimaging modalities, offering a perspective across eight distinct classifications: quantum dots, nanogold, nanocarbons, silica-based nanoparticles, superparamagnetic iron oxide nanoparticles, aggregation-induced emission nanoparticles, nanobubbles, and polymeric nanomaterials, and meticulously deconstructing their structure–property paradigms. It demonstrates the synthetic methodologies and surface functionalization strategies of the nanomaterials, establishing novel design paradigms that enable spatiotemporal control of nanomaterials’ performance metrics within pathophysiological microenvironments. We also emphasize the recent advancements and breakthroughs in in vivo biomedical imaging using these nanomaterials, while critically addressing multifaceted challenges such as biosafety and clinical scalability. We believe this review emphasizes the theoretical foundation for the rational design of next-generation nanomaterials, underscores their transformative potential in precision medicine and personalized healthcare management through the interdisciplinary view. We hope this review may bring some inspiration to the researchers in the related fields, and accelerate the translation from laboratory innovation to clinical practice of the nanomaterials.

Nerve guidance conduits play a critical role in bridging nerve gaps and facilitating neural repair. Recent advances highlight that structural optimization and functional enhancement can further enhance the regenerative outcomes. Herein, inspired by the structural features of celery stalks and native nerves, we propose a biomimetic multichannel three-dimensional (3D) MXene nanofiber sponge scaffold for reconstructing large-gap peripheral nerve defects. The scaffold integrates MXene-loaded sacrificial alginate microfibers, a gas-foamed 3D porous nanofiber sponge, and a gelatin methacryloyl hydrogel encapsulating neurotrophic and angiogenic factors. The biomimetic multichannel structure was obtained by sacrificing the alginate microfibers, during which MXene nanosheets were released and deposited onto the channels. Benefiting from the conductive microchannels, the 3D sponge network, and the bioactive hydrogel, the scaffold potently induced the differentiation of rat pheochromocytoma cells and supported endothelial tube formation. Moreover, the scaffold significantly enhanced nerve regeneration and functional motor recovery in rat long-gap nerve defect models. These findings demonstrate a potential strategy for the regeneration of peripheral nerve defects.

Nerve guidance conduits (NGCs) hold considerable value in the field of nerve regeneration, yet current approaches display constraints regarding the diversity of loaded factors and their short sustained-release duration. Herein, a type of multifunctional inverse opal NGC integrating bone marrow mesenchymal stem cells (BMSCs) is presented for peripheral nerve repair. The generation of inverse opal scaffolds leverages the inversion of a monodisperse emulsion droplet template crafted by microfluidic technique. Ascribed to the biocompatibility and the cell-concentrating properties of the inverse opal scaffold, coupled with the inherent capabilities of BMSCs, such an NGC enables the secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor, promoting the migration of rat Schwann cells and differentiation of pheochromocytoma 12 cells. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) further revealed that three-dimensional (3D) BMSC spheroid culture in the inverse opal scaffold significantly upregulated bFGF, PDGF, and VEGF mRNA expression relative to two-dimensional (2D) culture. Further in vivo experimentation confirms the promising efficacy of NGCs loaded with BMSCs in repairing 10 mm sciatic nerve defects. These results underscore the substantial potential of this innovative design for peripheral nerve regeneration.

Hearing loss is becoming a common disease worldwide, affecting individuals across all age groups, from infants to older adults. However, the unique anatomical barriers of the inner ear limit the effectiveness of conventional systemic therapies, highlighting the need for advanced drug delivery strategies. Engineered inner ear drug delivery systems have emerged as promising approaches for improving drug targeting, retention, and therapeutic efficacy. In this review, we provide a comprehensive overview of the advances by integrating 3 major aspects: major administration routes, diverse therapeutic agents, and delivery carriers employed in inner ear treatment. We first introduce systemic administration, trans-tympanic drug delivery, intracochlear drug delivery, and cochlear implantation (CI). We then summarize anti-inflammatory drugs and antioxidants for the treatment of inner ear disorders. Subsequently, we discuss multiple nanocarriers, viral vectors, injectable hydrogels, and other innovative carriers used in inner ear drug delivery, highlighting their design principles and therapeutic applications. We also illustrate recent progress in clinical trials and discuss the difficulties associated with translating experimental systems into clinical applications. Finally, we outline current limitations and future opportunities, together with potential strategies to address these challenges.

Peripheral nerve injury (PNI) presents a significant clinical challenge due to the intrinsic limitations of nerve regeneration and poor functional recovery. Although nerve guidance conduits (NGCs) offer a promising alternative to autografts, their therapeutic efficacy is often constrained by insufficient bioactivity and electrical conductivity. To address these dual deficiencies, we engineered an electroactive living nerve conduit by integrating silk sericin (SS)‐modified carbon nanotubes (SCNTs) with adipose‐derived stem cells (ADSCs). The SCNTs serve as a conductive scaffold, whereas the ADSCs provide a sustained release of neurotrophic factors. This design creates a synergistic microenvironment to promote neuronal maturation and axonal regeneration. In an experimental rat model featuring a 10‐mm sciatic nerve gap, ADSC/SCNT/RAM NGCs demonstrated regenerative performance comparable to autografts, facilitating axon connection and recovery of motor functions. Histological assessment revealed that the implanted ADSC/SCNT/RAM NGCs promoted the most extensive nerve and axon regeneration among all groups, as evidenced by the significantly higher counts of S100 calcium‐binding protein B (S100‐β)‐positive cells (10,152 ± 986.00) and Neurofilament Protein 200 (NF200)‐positive cells (11,517 ± 795.70). Corroborating these histological findings, functional analysis demonstrated that the ADSC/SCNT/RAM group achieved the highest sciatic nerve function index (SFI) at 12 weeks post‐surgery (−58.06 ± 1.46), a value comparable to the Autograft group (−57.73 ± 1.80). This strategy proposes a promising tissue‐engineered alternative to autografts for nerve repair.