Precise Inner Ear Delivery of Injectable GelMA Hydrogel Containing Andrographolide Promotes Repair of Diabetic Hearing Loss

Abstract

Given the poor efficacy of conventional oral medications in treating inner ear disorders due to the presence of the Blood-Labyrinth Barrier (BLB) in the inner ear, we designed an inner ear injectable Andro@GelMA hydrogel for the repair of Diabetic Hearing Loss (DHL). Natural protein-derived materials, such as collagen and gelatin, hold broad prospects in tissue engineering and regenerative medicine. Specifically, Gelatin Methacryloyl Acetate (GelMA), a photosensitive polymer obtained by modifying gelatin with methacrylic anhydride, inherits the high biocompatibility of collagen, making it an ideal drug delivery carrier. In this study, FTIR, XRD, SEM, and rheological tests demonstrated that hydrogen-bonding linkages formed between Andrographolide (Andro) and GelMA, thereby enhancing cross-linking degree and structural stability. Additionally, in vitro and in vivo tests confirmed that the Andro@GelMA hydrogel could achieve controllable sustained release by adjusting the cross-linking degree. Furthermore, in vitro cellular experiments showed strong protective effects on auditory cells, while animal experiments verified that this local delivery system significantly improved the therapeutic efficacy of DHL and promoted the regeneration of damaged inner ear hair cells compared to the control group.