In Response to: Heparin Binding–Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice

Dear Editor,

Iwould like to address the article entitled “Heparin binding-epidermal growth factor-like growth factor for the regeneration of chronic tympanic membrane perforations in mice” by Santa Maria et al. ¹

I agree with the authors in that, because this is an important area of research, this model will provide a new and effective method for the clinical treatment of chronic tympanic membrane perforation (TMP) with chronic suppurative otitis media (CSOM). The animal model of chronic TMP with dry, large perforation+Eustachian tube (ET) dysfunction+CSOM was first published by the authors. This model is more akin to clinical chronic TMP than to previous reported models of chronic TMP. Some studies have found that the previous published animal models of chronic TMP were not actually real chronic TMP, they could have been nonhealing subacute or chronic traumatic TMP.^2,3 This particular animal model is very useful for the study and development of bioscaffold materials or growth factors in human chronic TMP. However, the animal model requires further improvement.

First, most patients had a chronic TMP duration of more than 6 months in clinic, and perforations with a duration of less than 3 months are not strictly chronic TMP.^4–7 Some studies reported that a few traumatic TMPs still healed spontaneously after 3 months postinjury.^8,9 Chronic TMP with a duration of less than 3 months could be subacute or chronic traumatic TMP. Lou et al. reported that the single application of fibroblast growth factor 2 in subacute or chronic traumatic TMP had a high success rate. ¹⁰ In addition, although the authors reported a success rate of 92% in the single dose heparin binding-epidermal growth factor treatment group and a 38% success rate in the control (polymer only) group, it is almost impossible to close using polymer only without excision of the perforation edge in chronic subtotal perforation in a clinical setting. Therefore, some models do not represent complete chronic TMP in this study. Second, most chronic TMPs are usually accompanied by myringosclerosis or tympanosclerosis, with the exception of dry large perforation+ET dysfunction+CSOM, and sclerotic lesions approaching the edge can affect the success rate of myringoplasty.^11,12

In short, the animal model of chronic TMP is very good, and is similar to human chronic TMP. However, the duration of most of clinical chronic TMPs is much longer (i.e., greater than 6 months) and is accompanied by myringosclerosis or tympanosclerosis. Although the perforation edge microscopically shows a mucosal layer migrated laterally to be directly adjacent to the keratinocyte layer with a thickened fibrous layer in the animal model, this model is not completely equal to clinical chronic TMP with CSOM. It would be better if the authors could develop the animal model of chronic TMP so that the perforation fails to close in less than 6 months and is accompanied by myringosclerosis to compare the therapy effects of different growth factors. Otherwise, the success of the future transition to human clinical trials may be doubtful and even potentially risky.