Electrospun PLA-gelatin composite scaffolds loaded with 3D-derived extracellular vesicles for repairing tympanic membrane perforation in rats.

BACKGROUND

The tympanic membrane is an oval, funnel-shaped, translucent structure that plays a crucial role in the auditory system. Individuals suffering from tympanic membrane perforation often experience symptoms such as a sensation of fullness in the ear, hearing impairment, and other discomforts, all of which significantly diminish the quality of life. Currently, autologous temporalis myofascia is the commonly utilized material for repair; however, it is limited by its scarce availability, the need for secondary surgical intervention, and suboptimal recovery outcomes. This study explores the effects of 3D EVs on tympanic membrane perforation repair, both in vivo and in vitro, using a novel electrospun PLA-gelatin composite scaffold. The composite scaffold is designed to mimic the architecture of the tympanic membrane's fibrous layer, enhancing the scaffold's tensile strength, promoting collagen fiber formation, and providing a favorable environment for cellular adhesion and migration, ultimately facilitating tympanic membrane repair.

METHODS

The mechanical properties of the scaffolds were first evaluated, with morphological analysis performed using scanning electron microscopy. Subsequently, the ability of 3D EVs to promote the proliferation and migration of tympanic membrane fibroblasts was assessed through in vitro cellular assays. Finally, the PLA-gelatin composite scaffold loaded with 3D EVs was implanted at the site of tympanic membrane perforation in rats to assess the in vivo repair efficacy.

RESULTS

In vitro experiments demonstrated that the EVs effectively promoted the proliferation and migration of tympanic cells while enhancing the expression of genes and proteins associated with tympanic membrane repair. In vivo experiments showed that PLA-Gel+EVs scaffold repaired tympanic membrane perforation in rats and promoted the repair of tympanic membrane perforation. The collagen production in the exosome group was significantly greater than in the control group, indicating that the effect of exosome in promoting the repair of tympanic membrane perforation was better.

CONCLUSION

The incorporation of EVs significantly accelerates the healing process of tympanic membrane perforations, offering a promising new approach for treating tympanic membrane injuries.