Evaluation of a Photopolymerized Gelatin Hydrogel Network with bFGF-Loaded Alginate Microspheres for Tympanic Membrane Perforation Repair in Rats

Tympanic membrane perforation (TMP) often leads to hearing loss and requires effective repair strategies. However, existing surgical options are invasive and lack ideal biomaterials for scaffold-based healing. Herein, we present a custom-engineered mechano-acoustic responsive hydrogel incorporating bFGF-loaded sodium alginate microspheres, designed for controlled drug release and tissue regeneration under dual stimulation: vibrational simulation and low-frequency acoustic waves (generated by radio devices) — representing its first transition from in vitro characterization to in vivo regenerative application. This polymer-based scaffold exhibits robust adhesion, biocompatibility, and mechanoresponsive release behavior. A rat acute TMP model was employed to evaluate the hydrogel's therapeutic efficacy. Compared with control and blank hydrogel groups, the bFGF-loaded mechanoresponsive hydrogel (SGM) noticeably accelerated tympanic membrane closure, reduced local inflammation, and enhanced early auditory recovery, as confirmed by otoscopic inspection, ABR tests, histological staining, and TEM imaging. Our findings demonstrate that the SGM hydrogel effectively promotes functional tissue regeneration and early hearing restoration in vivo. This work highlights the potential of polymer-based, stimuli-responsive biomaterials in advancing minimally invasive strategies for TMP treatment and offers valuable insights for future tissue engineering applications in otolaryngology.