Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL. NAD+ decreases in cochlear after noise trauma, and nicotinamide supplementation boosts NAD+ and prevents neuroexcitatory in cochlear by round window administration. Personalized porous gelatin methacryloyl (PGMA) achieves long term drug release in cochlear, and nicotinamide encapsulated PGMA enhances mitochondria and synapse function, and protects noise induced hearing loss in mice.image