Engineering vascularized inner ear organoids: Challenges and advances in recapitulating the cochlear microenvironment.

The inner ear is a highly specialized structure responsible for auditory and vestibular functions; however, research progress has been limited by its deep anatomical location and the difficulty of obtaining human tissue samples. Recent advances in inner ear organoids (IEOs) and organoid-on-a-chip technologies offer powerful platforms for studying hearing loss mechanisms and testing therapies. This review outlines progress in generating IEOs from human pluripotent stem cells, including differentiation into hair cells and spiral ganglion neuron-like cells, and improvements in 3D culture, co-culture, and microfluidics. Special attention is given to the reconstruction of the blood-labyrinth barrier (BLB) within organoids, focusing on vascular formation, barrier integrity, and drug delivery limitations. Drawing from advances in brain and kidney organoid models, we explore strategies to improve vascularization using microfluidic technologies. Ultimately, building vascularized IEOs that recapitulate the cochlear microenvironment offers significant potential for drug screening, disease modeling, and regenerative therapies.