Combined Basic Fibroblast Growth Factor and Gelatin Sponge Therapy Achieves Near-Normal Tympanic Membrane Regeneration After Blast Injury in Mice

Hypothesis: We hypothesized that combining basic fibroblast growth factor (bFGF) with a gelatin sponge scaffold (bFGF+gel therapy) would correct the regenerative deficits specific to blast injury and achieve near-normal tympanic membrane (TM) regeneration. Background: Blast-induced TM perforation (TMP) is refractory to spontaneous healing. bFGF promotes closure but results in markedly thickened regeneration when used alone. Methods: CBA/J mice were subjected to shockwave blast exposure (330±11.3 kPa). Their ears were randomized into the normal, blast, bFGF, Gel, or bFGF+gel groups (n=6 each). Treatments were administered transtympanically immediately after the blast. TM morphology was assessed endoscopically through day 56 and histologically on day 56. Cochlear function was evaluated using auditory brainstem response and distortion product otoacoustic emission. Results: All groups had TMP closure by day 14. On day 56, the blast and bFGF groups showed significantly greater TM thickness than the normal group, with disorganized collagen fibers and degenerative fibrocytes on transmission electron microscopy. The gel group showed thinner TM than the bFGF group, but had persistent collagen fiber disorganization. The bFGF+gel group had normal TM thickness with a well-organized collagen fiber architecture and preserved fibrocyte morphology, which was superior to that of all blast-exposed groups. The auditory brainstem response and distortion product otoacoustic emission thresholds were elevated for all blast-exposed groups without significant intergroup differences. Conclusion: bFGF+gel therapy achieved near-normal TM regeneration in a mouse model of blast-induced TMP, outperforming the bFGF solution or gelatin sponge alone. Growth factor-based and scaffold-based treatments have potential and require validation in clinically representative models.