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TARGETED DELIVERY OF ENCAPSULATED NEURAL PROGENITOR CELLS INTO THE SPIRAL GANGLION NEURONS
DANKOOK INSTITUTE OF MEDICINE AND OPTICS, COLLEGE OF MEDICINE, DANKOOK UNIVERSITY©ö, DEPARTMENT OF OTORHINOLARYNGOLOGY-HEAD & NECK SURGERY, COLLEGE OF MEDICINE, DANKOOK UNIVERSITY©÷
NATHANIEL CARPENA, NATHANIEL CARPENA©ö, CELINE DG ABUEVA©ö, SO-YOUNG CHANG©ö, JI-EUN CHOI©÷, JAE YUN JUNG©÷, LEE MIN YOUNG©÷
¸ñÀû: Cell encapsulation has emerged as a transformative approach for delivering therapeutic cells to specific anatomical sites, such as the spiral ganglion of the inner ear, which is essential for auditory function. Recent innovations incorporate light-activated release systems into encapsulation technologies, enabling precise spatial and temporal control over cell deployment. Additionally, modifying the encapsulation polymer with a targeting moiety enables accurate targeting of specific areas of the cochlea. By combining advanced targeting strategies, light-responsive systems, and bioactive capsule modifications, this method offers a promising platform for developing precise and effective interventions for sensorineural hearing loss and other auditory disorders. ¹æ¹ý:Neural progenitor cells (NPCs) were encapsulated in a polymer matrix composed of a polyethylene glycol (PEG) backbone functionalized with a hydrophobic dye molecule sensitive to near-infrared (NIR) light for controlled release. The polymer was modified with a nerve growth factor (NGF) peptide to enhance the targeting of the spiral ganglion region of the cochlea. Cell viability after encapsulation was confirmed using live/dead staining. Encapsulated cells were delivered into the Scala tympani (ST) of nude mice via the round window membrane (RWM), with NIR laser (808 nm) applied post-delivery to trigger cell release. For comparison, non-encapsulated NPCs were injected either into the ST or directly into Rosenthal¡¯s canal. Delivery efficiency and targeting specificity were assessed using histology and fluorescence imaging, comparing encapsulated and non-encapsulated NPCs. °á°ú:Encapsulated neural progenitor cells (NPCs) retained high viability after encapsulation, as confirmed by live/dead staining. In vivo delivery of encapsulated cells into the ST resulted in successful localization to Rosenthal¡¯s canal, with a more uniform distribution observed across the apex, middle, and basal turns of the cochlea. Controlled release was achieved using NIR laser, with no damage observed to surrounding cochlear structures. In contrast, non- encapsulated NPCs delivered into the ST were predominantly localized to the basal turn and showed significant off-target distribution into surrounding cochlear structures. Direct delivery of non-encapsulated NPCs into Rosenthal¡¯s canal caused localized damage to the modiolus, with the majority of cells confined to the basal turn and limited migration to the middle or apical turns. Encapsulation with NGF modification not only improved targeting specificity and reduced off- target cell migration but also minimized tissue damage, enabling more precise and effective NPC delivery into the cochlea. °á·Ð:NGF-modified, NIR-sensitive encapsulation of neural progenitor cells enables precise, controlled, and minimally invasive delivery to the spiral ganglion within the cochlea. This approach ensures uniform distribution across cochlear turns, minimizes off-target cell migration and reduces tissue damage compared to non-encapsulated delivery methods. These findings highlight the potential of this encapsulation system for targeted therapeutic interventions in the inner ear.


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