Regeneration of Chronic Tympanic Membrane Perforation Using an EGF-Releasing Chitosan Patch

Abstract

Most chronic tympanic membrane (TM) perforations require surgical interventions such as tympanoplasty because, unlike with acute perforations, it is very difficult for the perforations to heal spontaneously. The purpose of this study was to develop novel therapeutic techniques and scaffolds that release growth factors to treat chronic TM perforations. We evaluated the cell proliferation effects of the epidermal growth factor (EGF) and fibroblast growth factor (FGF) on in vitro cultures of TM cells using an MTT assay. They both showed similar efficacy, so we used EGF because of its lower cost. We then constructed an EGF-releasing chitosan patch scaffold (EGF-CPS) based on previous studies. We analyzed its toxicity and strength, and we studied it using scanning electron microscopy. EGF was released from the EGF-CPS for 8 weeks in an in vitro system. In animal studies, the EGF group, which was treated with EGF-CPS, showed healing in 56.5% of the animals (13/23), while the control group, which did not receive any treatment, revealed 20.8% healing (4/24) (p=0.04). Transmission electron microscopic studies of regenerated eardrums in the EGF group showed much greater preservation of histological features, and TMs of the EGF group were thinner than spontaneously healed TMs. In conclusion, this novel EGF-CPS can be used as a nonsurgical intervention technique for treatment of chronic TM perforations.

Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy

“…Dexamethasone is a glucocorticoid with antiinflammatory and immunosuppressant effects [28]. Despite previous reports on the high success rate of using mitomycin C with steroid [13][14][15] in the creation of a chronic TMP animal model, we were unable to replicate the previous reported efficacy of this method. One TMP out of ten stayed patent for seven out of eight weeks, however, this near success rate of 10% is unsatisfactory from a reproducibility point of view.…”

“…Subsequently, a second Gelfoam soaked in dexamethasone (5 mg/ml) was placed on TMP which was left in-situ before removal on day seven. This exact method has been reported to be efficacious by Seonwoo et al [13]. Upon examination by routine otoscopy during the first week, if dexamethasone soaked Gelfoam was found to be absent or displaced from TMP, a new Gelfoam soaked with dexamethasone was re-applied.…”

“…Seonwoo et al [13] utilized topical mitomycin C (0.5 mg/ml) and dexamethasone (5 mg/ml) in rats with a reported chronic TMP success rate of 100% after one week. Cui et al [14] tested topical mitomycin C (0.2 mg/ml) with hydrocortisone (5 mg/ml) in rats having a success rate of 87% after eight weeks.…”

Regeneration of chronic tympanic membrane perforation using 3D collagen with topical umbilical cord serum

“…To enhance the healing of chronic TM perforations, biomolecules including growth factors [12,13], hyaluronic acid [14], and pentoxifylline [15] have been used together with good results. To date, chemically recombinant growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) have been mainly used combined with bioscaffold for TM regeneration [16,17].…”

What is new in tympanoplasty?

“…The 3D graft would be advantageous in revision cases which translate to substantial economic benefits. An artificial tympanic membrane that is transparent is also highly desirable, as it allows direct visualization on the middle ear 8 . A graft available in various thicknesses and sizes can be tailored specifically for perforations of different sizes and for underlying pathology, such as middle ear inflammation and Eustachian tube dysfunction.…”