Functionalized Biomimetic Scaffolds for Human‐Derived Auditory Neural Circuit Construction

ABSTRACT Damage to auditory circuits results in sensorineural hearing loss. However, the scarcity of human inner ear tissue significantly hinders the development of therapies to preserve auditory function, creating a critical need for reliable in vitro models. While human‐derived neural circuits offer therapeutic promise, generating high‐purity, functionally mature spiral ganglion neurons (SGNs) and achieving their oriented integration remain substantial challenges. In this study, we successfully differentiated human induced pluripotent stem cells (hiPSCs) into SGN‐like neurons that closely resemble in vivo counterparts. Using electrically conductive biomimetic scaffolds with highly ordered topological structures promoted SGN‐like neurons maturation, growth orientation. Furthermore, by co‐culturing SGN‐like neurons with denervated cochlear tissues, we established a human‐derived in vitro model capable of mimicking the auditory neural circuit. We efficiently recapitulated an in vitro auditory neural circuit on biomimetic scaffolds, elucidated transcriptional changes underlying SGN‐like neurons' maturation, and reproduced the protective phenotypes against cisplatin‐induced auditory circuit damage. These results demonstrate that the constructed human‐derived in vitro neural circuit model is a reliable platform for drug screening with broad application prospects.