Promising treatments for closure of tympanic membrane perforation (TMP) have been studied, in search of outpatient, minimally invasive procedures that are effective, safe, affordable and technically feasible.1–5 Among some innovative alternatives, the use of gelfoam™ and atelocollagen™ stand out, in association with fibroblast growth factor (β-FGF),1–4 autologous serum, and chitin membranes.5

The establishment of a therapy developed from tissue engineering for treatment of TMP will probably eliminate the need for conventional surgery. However, it is critical to understand the factors that contribute to the success or failure of TMP treatment.4

An alternative material is cellulosic polysaccharide, obtained by bacterial synthesis. In previous studies, cellulosic polysaccharide proved to be a safe, low-toxicity,6 biocompatible7 product, with the ability to encourage cellular growth and differentiation – a feature that is promising for tissue engineering.8 Preclinical and clinical studies have demonstrated that this biomaterial was effective functioning as a mechanical barrier and as an adjunct in the treatment of ulcerative lesions9 and surgical wounds.10

The objective of this study was to investigate the effect of direct application of a bacterial cellulose (BC) graft on the healing of tympanic membrane perforations, compared with a conventional procedure with autologous fascia.

Forty patients with tympanic membrane perforations caused by otitis media were enrolled in a randomized controlled clinical study of spontaneous demand at Otolaryngology Service in a teaching hospital in Pernambuco state, Brazil, from 2013 to 2014. Patients with marginal, damp or cholesteatomatous perforations were excluded. Patients were randomly allocated to two groups: 20 in an experimental group, who were treated with bacterial cellulose membrane graft, and 20 controls treated conventionally with autologous fascia graft.

This study was approved by the Ethics Committee on Research, Health Sciences Center, Universidade Federal de Pernambuco, under CAAE 21109913.7.0000.5208, Opinion CEP/CONEP No. 527.461 of December 18, 2013.

A total of 40 patients underwent treatment for tympanic membrane perforation; 20 received a BC graft (30% men and 70% women); and 20 – the control group – received an autologous fascia graft (40% men and 60% women). The mean age of the groups was 38.15±12.63, and 34.5±10.16 years, respectively (Table 1).

In the group of patients who received BC graft, 65% of TMPs were in the left ear, while in the group that received an autologous fascia graft, most (55%) TMPs were in the right ear. Perforations were more often of small size, accounting for 70% of cases in each group. Closure occurred in all small perforations treated by BC graft, when compared with fascia graft (92.9%). More than half (66.6%) of medium-sized perforations closed with BC graft (Table 1).

Surgical time for the procedure was statistically significant (p<0.001), when comparing the group that received BC graft (14.06±5.23min) versus autologous fascia graft (76.50±17.92min); and epithelialization time was similar in both groups, corresponding to 30 days (Table 1) (Figs. 1–3).

Figure 1.

Tympanic perforation on otomicroscopy.

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Figure 2.

Otoendoscopy of bacterial cellulose graft over TMP.

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Figure 3.

Tympanic membrane after application of bacterial cellulose graft, on microscopic examination.

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To evaluate tympanic membrane compliance, 14 patients treated with BC graft underwent tympanometry, and of these, 13 (92.9%) had Gt within the normal range (mean Gt=0.86±0.28) and an expected At (−0.58±0.28) (Fig. 4).

Figure 4.

Relationship between material's success and failure versus procedure time.

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The relative risk (RR) of non-closure of tympanic membrane in the group treated with BC graft was lower (50%) than that for the group with autologous fascia graft. The effectiveness was 50%, a result similar for both materials (BC or fascia), despite an absolute risk reduction of 10% for TMP closure in BC group (Table 1).

Conventionally the treatment of TMP involves three steps: pre-operative clinical control, surgical treatment and postoperative follow-up. The main objectives of miringoplasty, in general, are to regenerate the tympanic membrane, reconstruct the sound transmission mechanism, control infection, and improve hearing. In the literature, the success rate varies from 65 to 98%.13,14 In this study, our success rate with the use of BC membrane was 90%, compared to 80% with autologous fascia.4 We must also emphasize that the use of BC represented an efficiency of 50%, i.e. the chance of non-closure of tympanic perforation was reduced by half (RR=0.5) versus temporal fascia. This is in agreement with a previous study, which followed a similar methodology and was conducted in Chinchilla laniger, where the authors obtained a 90% success rate.11

Some factors can influence the success of the surgery or of the graft, as follows: age, perforation location, size of perforation, auditory tube function, status of middle ear mucosa, type of graft used, and surgeon's experience.15 As to the study population, it can be added that the use of BC membrane was effective, regardless of patient's age and location and size of tympanic perforation. No adverse events related to this membrane occurred. It is noteworthy the reduction of a little more than 1h (62.44min) in the time required for the procedure, when comparing BC group versus temporal fascia (control) group, indicating that BC, in addition to being effective, shows a high level of effectiveness and practicality.

The reduction in the operating time using BC membrane is self-explanatory, because there was no need for incisions, removal of fascia, or lifting flaps. From the cost estimate for each procedure (fascia or BC membrane graft), we found a reduction of 13 times in hospital costs with the use of BC membrane; this figure represents a saving of R$ 7,178.8, considering that, with the choice of BC, there is no need for additional tests (hematology and cardiology), hospitalization or general anesthesia. The use of BC also obviates the use of special materials, such as Gelfoam™, suture material and antibiotics; on the other hand, the use of BC avoids complications such as ear pain, bleeding, and hematomas. The patient can resume immediately their daily activities.

To these aspects we can add efficiency, effectiveness and practicality, in addition to security, because this is a low-cytotoxicity and high-biocompatibility material.6,7

As described in the literature, the tympanic membrane should be rebuilt with a connective tissue that allows for, in replacing the eardrum, ensuring its properties: elasticity, strength and ability to vibrate. Many materials have been used in the history of tympanoplasty, including free skin graft, sclera, perichondrium, temporal fascia, cartilage, and fat, among others.16,17 It was observed that these properties were recovered, with proven data corroborated by tympanometry findings; this technique assessed tympanic membrane compliance and showed that most patients (92.9%) had Gt in the normal range and At as expected. Tympanometry, used in this study to evaluate tympanic membrane function, is a classic method applied in clinical practice, by being fast and atraumatic.18

Another important feature, demonstrated in previous studies, refers to BC's ability to function as an inducer of tissue remodeling and, thus, as a promoter of the healing process,8–10 by enabling an intensive process of revascularization19 and epithelialization,11 which may explain the regeneration of the eardrum remains and also the closure of TMP.

The use of a bacterial cellulose graft promoted TMP regeneration, showing it to be an innovative, safe, efficient, effective, minimally invasive, low-cost option.

The authors declare no conflicts of interest.