Regeneration Of Tympanic Membrane Perforations Research Articles

Alginate hydrogel-PCL/gelatin nanofibers composite scaffold containing mesenchymal stem cells-derived exosomes sustain release for regeneration of tympanic membrane perforation

Exosomes are among the most effective therapeutic tools for tissue engineering. This study demonstrates that a 3D composite scaffold containing exosomes can promote regeneration in rat tympanic membrane perforation (TMP). The scaffolds were characterized using scanning electron microscopy (SEM), degradation, PBS adsorption, swelling, porosity, and mechanical properties. To confirm the isolation of exosomes from human adipose-derived mesenchymal stem cells (hAMSCs), western blot, SEM, and dynamic light scattering (DLS) were performed. The Western blot test confirmed the presence of exosomal surface markers CD9, CD81, and CD63. The SEM test revealed that the isolated exosomes had a spherical shape, while the DLS test indicated an average diameter of 82.5 nm for these spherical particles. MTT assays were conducted to optimize the concentration of hAMSCs-exosomes in the hydrogel layer of the composite. Exosomes were extracted on days 3 and 7 from an alginate hydrogel containing 100 and 200 μg/mL of exosomes, with 100 μg/mL identified as the optimal value. The optimized composite scaffold demonstrated improved growth and migration of fibroblast cells. Animal studies showed complete tympanic membrane regeneration (TM) after five days. These results illustrate that a scaffold containing hAMSC-exosomes can serve as an appropriate tissue-engineered scaffold for enhancing TM regeneration.

Efficacy of Human Epidermal Growth Factor in the Regeneration of Tympanic Membrane Perforation

Introduction: Majority of tympanic membrane perforations require myringoplasty for closure. Recently, epidermal growth factor (EGF) has been shown to promote the healing of tympanic membrane perforations. Aim: The aim of this study was to find out a simple nonsurgical outpatient procedure to close one-quadrant tympanic membrane perforations that could reduce the hospital stay, medical cost, and morbidity in these patients. Materials and Methods: An interventional prospective randomized clinical study was done on 120 patients at our tertiary hospital. The allocation ratio was 3:1. Pure-tone audiometry, otomicroscopy, and otoenodoscopic recording were performed in all eligible patients who consented to take part in the study. Ninety cases received EGF gel application, whereas 30 controls received antibiotic ofloxacin application. Trichloroacetic acid chemical cautery and fibrin glue application were done in patients of both groups. Results: The closure rate was 97.7% in the EGF group and 70% in the ofloxacin group. The time taken for closure of perforations was 10 to 14 days in the EGF group and 3–4 weeks in the ofloxacin group. Hearing gain was observed in healed perforations of both groups. Conclusion: EGF application enhances the healing effect of one-quadrant nonhealing tympanic membrane perforations. It showed encouraging results and reliable safety in the regeneration of tympanic membrane. Clinical Significance: Apart from its use in single quadrant perforation, EGF may be considered for treating residual perforations after failed tympanoplasty.

Chitosan/PEI patch releasing EGF and the EGFR gene for the regeneration of the tympanic membrane after perforation.

Damage to the eardrum causes acute pain and can lead to chronic otitis media if it develops into chronic tympanic membrane (TM) perforations. Chronic TM perforations are usually treated with surgical methods such as tympanoplasty and myringoplasty. However, these surgeries are not only complicated and difficult but also cost a lot of money. Our research team developed chitosan patches (E-CPs) that release epidermal growth factor (EGF) as a patch therapy to replace surgical methods. However, there was a limitation in the healing ratio of the treatment compared to the surgical methods. In this study, we developed EGF and epidermal growth factor receptor (EGFR) gene-releasing polyethyleneimine (PEI)/chitosan patches (EErP-CPs) to increase the regeneration of TM perforations. The addition of PEI increased the adhesion and migration ability of TM cells on the patches. The simultaneous release of the EGF and the EGFR gene further enhanced TM cell proliferation, adhesion and migratory ability. It was confirmed that the EGF protein and EGFR gene were released for 30 days; however, EGF was released and increased TM cell viability almost immediately after treatment and EGFR took a minimum of 3 days before showing its effect on improved cell viability. It was also shown that EErP-CPs are more hydrophilic and have more positive charge than E-CP because of added amine groups from PEI. In conclusion, the developed EErP-CPs resulted in the improved healing of TM perforations and can potentially be applied to the regeneration of both chronic and acute tympanic membrane perforations.