Acute Tympanic Membrane Perforations Research Articles

The importance of mechanical and biological cues of tympanic membrane grafts to ensure optimal regeneration

Chronic suppurative otitis media (CSOM) is often associated with permanent tympanic membrane (TM) perforation and conductive hearing loss. The current clinical gold standard, using autografts and allografts, suffers from several drawbacks. Artificial replacement materials can help to overcome these drawbacks. Therefore, scaffolds fabricated through digital light processing (DLP) were herein created to support TM regeneration. Various UV-curable printing inks, including gelatin methacryloyl (GelMA), gelatin-norbornene-norbornene (GelNBNB) (crosslinked with thiolated gelatin (GelSH)) and alkene-functionalized poly-ε-caprolactone (E-PCL) (crosslinked with pentaerythritol tetrakis(3-mercaptopropionate) (PETA4SH)) were optimized regarding photo-initiator (PI) and photo-absorber (PA) concentrations through viscosity characterization, photo-rheology and the establishment of working curves for DLP. Our material platform enabled the development of constructs with a range of mechanical properties (plateau storage modulus varying between 15 and 119 kPa). Excellent network connectivity for the GelNBNB and E-PCL constructs was demonstrated (gel fractions >95 %) whereas a post-crosslinking step was required for the GelMA constructs. All samples showed excellent biocompatibility (viability >93 % and metabolic activity >88 %). Finally, in vivo and ex vivo assessments, including histology, vibration and deformation responses measured through laser doppler vibrometry and digital image correlation respectively, were performed to investigate the effects of the scaffolds on the anatomical and physiological regeneration of acute TM perforations in rabbits. The data showed that the most efficient healing with the best functional quality was obtained when both mechanical (obtained with the PCL-based resin) and biological (obtained with the gelatin-based resins) material properties were taken into account.

Thymosin beta-4 – A potential tool in healing middle ear lesions in adult mammals

Acute tympanic membrane perforations primarily occur due to injury or infection in humans. In acute cases, nearly 80–94 % of the perforations heal spontaneously. In chronic cases, non-surgical treatment becomes significantly limited, and the perforation can be restored only by myringoplasty. In addition to classical grafts such as the fascia or cartilage, promising results have been reported with various biological materials including silk or acellular collagen. However, despite of all the efforts, healing remains insufficient. Consequentially, a need for substances which actively promote tympanic cell migration and proliferation is deemed essential.In our study, we utilized Thymosin beta-4 (TB4), a 43aa peptide possessing many regenerative properties in various organ systems. Our aim was to reveal the impact of externally administered TB4 regarding impairments of the middle ear, particularly the tympanic membrane. We harvested tympanic membranes from adult mice and treated these with TB4 or PBS on both collagen gel matrixes and in the form of floating, ex vivo explants. Cell migration and proliferation was measured, while immunocytochemical analyses were performed to determine cell type and the nature of the targeted molecules.We discovered the peptide affects the behavior of epidermal and epithelial cells of the tympanic membrane in vitro. Moreover, as our initial results imply, it is not the differentiated, yet most likely the local epidermal progenitor cells which are the primary targets of the molecule.Our present results unveil a new, thus far undiscovered field regarding clinical utilization for TB4 in the future.

Epidermal Growth Factor Application versus Observation on Healing of Acute Tympanic Membrane Perforations: A Randomized Open Label Clinical Trial

ABSTRACT Objective: To compare the effect of topical epidermal growth factor (EGF) instillation versus observation alone on healing of acute tympanic membrane perforations in terms of closure and hearing test results. Methods:  Design: Randomized, Open label, Clinical Trial Setting: Tertiary Government Training Hospital Participants: Seventeen (17) ENT-HNS OPD patients aged between 18 to 65 years old diagnosed with acute tympanic membrane perforation were included in the study. Group A underwent observation while group B was treated with recombinant human EGF solution. Follow- up was on a weekly basis (7th, 14th, 21st and 28th days) where video otoscopy for documentation and measurement of perforation using ImageJTM software was done. Pure tone audiometry was used to compare hearing improvement pre and post study in both observation and treatment groups. Results: At baseline, there was no significant difference in the sizes of perforations: 24.20 ± 9.95 (treatment) vs. 32.64 ± 11.62 (observation) with a p-value of .131. Following treatment, mean changes in perforation size were significantly greater in the treatment group compared to the observation group from baseline to day 7 (M = -9.08, n = 15.11 vs. M = -1.06, n = 31.58); p = .009; day 7 to 14 (M = -6.37, n = 13.78 vs. M = -0.79, n = 30.79); p = .003; and from day 14 to 21 (M = -5.65, n = 10.89 vs. M = -0.72, n = 30.07); p = .004 but not from day 21 to 28 (M = -4.16, n = 13.99 vs. M = -0.36, n = 29.71; p = .021. From baseline pure tone averages, four participants with mild hearing loss and two with moderate hearing loss achieved normal hearing in the treatment group (while one each with moderate and severe hearing loss did not improve). None of the observation group participants had improved hearing. Conclusion: Based on our limited experience, topical EGF can be used for traumatic tympanic membrane perforation and otitis media with dry ear perforation during the acute phase or within 3 months of perforation.

Minimally invasive trans-tympanic eustachian tube occlusion animal model

ObjectiveEustachian tube dysfunction is believed to be involved in the pathogenesis of many middle ear diseases including chronic suppurative otitis media. We aimed to describe a simple and reliable animal model of Eustachian Tube obstruction to further research into middle ear disorders. Study designProspective cohort study in animals. SettingUniversity laboratory. Subjects and methods30 mice C57Bl/6J (n = 15) and CBA/CaJ (n = 15) aged 6–8 weeks received transtympanic Eustachian tube occlusion on left ear trough an acute tympanic membrane perforation using thermoplastic latex used in dental procedures (gutta percha). Control mice (n = 6) received tympanic membrane perforation only. At two and four weeks, the mice were observed for signs of Eustachian tube dysfunction and compared to control ears. ET dysfunction was defined as presence of effusion in the middle ear. Results100% (n = 30) of the treated ears had otoscopic signs of Eustachian tube dysfunction at two weeks and the endpoint time of four weeks, compared to 0% in control mice (0/6). Temporary head tilt lasting up to 2 days were observed in 3 mice (10%). No other potential adverse events were recorded. No bacterial growth was determined in the middle ear fluid. ConclusionWe describe a technically easy and reliable method for Eustachian tube occlusion in mice with an excellent success rate and minimal morbidity.

Histopathological Evaluation of Platelet-Rich Plasma Effect in Acute Tympanic Membrane Perforation.

The online version contains supplementary material available at 10.1007/s12070-021-02912-2.

Animal Model of Chronic Tympanic Membrane Perforation.

Chronic tympanic membrane perforations (TMP) can be a source of significant morbidity from hearing loss, recurrent middle ear infections, changes in lifestyle, and risk of cholesteatoma formation. Laboratory experiments of TMP have been fraught by the rapid and high rate of spontaneous healing observed in animal models. There is controversy on the minimal time that perforations in animal models must have in order to be considered chronic TMP and thus have clinical relevance, with authors suggesting time periods of perforation patency of 8-12 weeks. In this article, we sought to create a clinically significant experimental model that could yield a high rate of perforation patency for at least 8 weeks. Animals undergoing acute TMP were exposed to three different experimental situations to delay the healing of the perforation: fractionated radiation, topical lipopolysaccharide application, and a combined dexamethasone and mitomycin C (DXM/MC) solution. In our study, the use of DXM/MC reliably produced TMP lasting at least 8 weeks in 86.48% of the cases without the need to reopen the perforation, infolding the edges of the membrane, or using physical barriers to prevent TMP closure. Histologically, the resulting perforated tympanum showed hyaline changes of the remnant tympanum and hyperkeratosis of the squamous epithelia of the external auditory canal. We believe that this model is reproducible and has potential use in experiments of delayed healing of TMP. Anat Rec, 303:619-625, 2020. © 2019 American Association for Anatomy.

Acute Otitis Media in Childhood - Use of Guidelines for Diagnosis and Treatment in Emergency Rooms

Background: AOM is characterized by its high prevalence and morbidity but low lethality. It is estimated that 70% of children will have had one episode prior to completing five years of age Compliance with the guidelines for acute otitis media (AOM) may avoid complications. This study aimed at determining whether pediatricians follow the guidelines for AOM management. Methods: A prospective, cross-sectional study involving pediatricians working in emergency centers in Recife. A specific questionnaire was used to collect data. Results: Of the 71 pediatrics interviewed around 98% gave importance to crying/irritability and otalgia when diagnosing otitis and all recognized the significance of otorrhoea. All the professionals gave importance to bulging tympanic membrane, 98.6% to acute tympanic membrane perforation, 97.1% to purulent effusion and 46.5% to bilateral hyperemia of the tympanic membrane. Regarding antibiotic therapy, 70.4% used standard doses of amoxicillin as first-line treatment (81.7% prescribing for 10 days). Furthermore only 47.9% double the dose in case of therapeutic failure. Conclusion: Pediatricians working in emergency departments need to be better informed about the guidelines to decrease inappropriate prescription of antibiotics for AOM. We believe that adoption of the “wait and see” strategy, even in emergency rooms, would be an important means of reducing the inadequate prescription of antibiotics in cases of AOM, thus contributing towards reducing bacterial resistance.

Evaluation of the regenerative capacity of the tissues of the external auditory canal and tympanic membrane in patients with chronic otitis media

Relevance: It is noted that the condition of the skin, the external auditory canal bone, the eardrum residues, that is, the tissues, from which the graft must first receive nutrition, largely determine the myringoplasty result. Purpose: to assess the regenerative ability of the external auditory canal and tympanic membrane tissues in patients with chronic otitis media. Materials and Methods: The migration ability of the external auditory canal and tympanic membrane tissues study was carried out in 98 patients with acute tympanic membrane perforation using a tissue staining test. In patients with chronic otitis media the staining test was performed before the operation. The external auditory canal skin in the bone part and the tympanic membrane residues were taken in patients of all groups in myringoplasty for immunohistochemistry. The quantitative assessment of the biomolecular markers expression was performed by the digital image analyzing. It was obtained by a Leica DMLS microscope with software (Germany) and a JVC digital camera (the magnification of 200 times and a minimum number of view fields 5 in each microslide) using «positive pixel count» and morphometry software Aperio Image Scope. Results: It was noted that in cases where the perforation was not closed, the migration ability of the tissues was impaired. A correlation was established between the regenerative ability of the epithelium by determining tissue biomarkers and migration ability. A high EGF level indicates a good regenerative ability and a positive test with staining. A low EGF level is noted in a negative test with staining. The state of the migratory ability of the external auditory canal epithelium and the tympanic membrane epithelium may indirectly indicate the regenerative ability of tissues and affect the tympanoplasty result. The staining test can serve as a prognostic criterion for the myringoplasty result, because it evaluates the regenerative ability state of the external auditory canal epithelium and eardrum epithelium.

A rare cause of acute tympanic membrane perforation: a case report

<p class="abstract">This is a case report of 57yrs old gentleman who presented to accident and emergency department with complaints of sudden onset of left earache, tinnitus, feeling of fullness in the ear which he claimed to start following an episode of sudden sneezing, while he was trying to blow his nose by pinching it with 2 fingers. The tympanic membrane was ruptured. He was managed conservatively with analgesics. Spontaneous and complete healing of the perforated tympanic membrane occured within one month of follow up. It was shown that an episode of sneezing with nose closed can build up such a high pressure in the middle ear which can perforate a tympanic membrane.</p>

Platelet-Rich Plasma Application for Acute Tympanic Membrane Perforations.

To assess the efficacy of the application of platelet-rich plasma (PRP) in the healing process of acute tympanic membrane perforations (TMPs). Acute TMPs were made in both the ears of 12 New Zealand rabbits. Plasma gel was applied at the right tympanic membrane (TM) of the same animal until the perforations were closed. The left TM was left untreated. On days 1, 4, 7, 10, 13, 16, 21, 28, and 35, the TMs were monitored to check the closure of perforations. The days of perforation closure for the 2 groups were compared using the paired t-test. The animals were sacrificed 2 months after making the perforations. Seven histopathological parameters were reviewed by 2 blinded pathologists: acute inflammation, chronic inflammation, edema in the lamina propria, congestion in the lamina propria, sclerosis, fibroblastic reaction, and an increase in the thickness of the squamous epithelial layer. The presence or absence of each histological parameter in both groups was compared using the Pearson Chi-square test. The average number of days for closure in the plasma gel group was 12 (range 8-18 days) and that in the control group was 17.7 (range 8-31 days). The difference was statistically significant (p=0.0145). There was no sclerosis or fibroblastic reaction in any of the specimens. No statistically significant difference was seen between the 2 groups with respect to acute inflammation, chronic inflammation, edema in the lamina propria, congestion in the lamina propria, and an increase in thickness of the squamous epithelial layer (p>0.05). Platelet-rich plasma fastens TMP closure; in long term, the eventual outcome is both microscopically and macroscopically same for the control as well as study groups in a rabbit traumatic TMP model. We believe that this study will encourage the clinical use of PRP for acute TMPs and trigger clinical studies in this field.

Application of a Collagen Patch Derived from Duck Feet in Acute Tympanic Membrane Perforation.

We investigated the utility of the duck-feet collagen extraction patching procedure in the traumatic tympanic membrane (TM) perforation via a comparison with spontaneous healing or paper patch. Fifty-six ears of adult male Sprague-Dawley rats, each weighing in the range of 250 to 300 g, were used for the animal studies. Sixteen rats had one-side ear in the control group and the opposite-side ear in the treated groups. The remaining twelve rats had a one-side ear with the duck-feet collagen patch and the opposite-side ear with a paper patch. The proliferating cell nuclear antigen (PCNA) expression cells were calculated among the 200 basal cells, and the expression percentage was identified as the labeling index. The healing of the perforation in the duck-feet collagen patch group was confirmed to be more rapid compared to the healing of the other groups. PCNA staining was observed in the migrating portion of PCNA enhanced cell to collagen scaffold in Post operative day (POD) 7 of collagen patch group. Thus, the adhesive effect of the duck-feet collagen patch to perforated margin was better than that of the paper patch. After completing the healing process, the collagen patch shrank and detached from the tympanic membrane (POD 14). In this study, we confirmed that the use of a duck-feet collagen patch had the advantage of early healing, inducing natural TM contour, and disappearing ability after the patch effect is complete.

Single Administration of a Sustained-Release Formulation of KB-R7785 Inhibits Tympanic Membrane Regeneration in an Animal Model.

A pressure equalization tube placed within the tympanic membrane is the only clinically available method for inhibiting tympanic membrane regeneration. Problems associated with this include associated otorrhea, biofilm formation, medial migration of the tube, tube retention, induction of granulation tissue, and a small but significant rate of cholesteatoma. We aimed to demonstrate that a single administration of a sustained-release polymer formulation of KB-R7785 maintains tympanic membrane perforation for at least 6 months. Sustained-release KB-R7785 was delivered within a novel polymer hydrogel to 20 mice with bilateral acute tympanic membrane perforations (a total of 40 perforations). The perforations were monitored at 3-month intervals until 9 months. At 3 months, 90% of perforations were open (n=36/40). At 6 months, 75% of perforations were open (total n=30/40). At 9 months, 22.5% of perforations were open (total n=6/40). The majority of tympanic membrane perforations (75%) were open (not healed) beyond 6 months and close (fully healed) prior to 9 months (77.5%). Once healed, tympanic membranes resembled their normal histological appearance. This study demonstrates that a single administration of a sustained-release polymer formulation of KB-R7785 inhibits tympanic membrane regeneration for 6-9 months.

Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

ObjectiveTo evaluate histologically the progressive development and underlying mechanisms of chronic tympanic membrane perforation (TMP) in a rat model using a two-weeks ventilation tube (VT) treatment combined with topical application of mitomycin C/dexamethasone (VT-M/D), compared with normal tympanic membrane and acute TMPs. MethodsFifty male Sprague-Dawley rats were divided into three experimental groups: a normal control group (n = 5), an acute TMP group (n = 5) (i.e. 3 days post-myringotomy) and a VT-M/D group (n = 40). The TMs were regularly assessed by otoscopy. The normal control animals were sacrificed on day 0 and the acute TMP group was sacrificed 3 days post-myringotomy for histological and immunohistochemical evaluations. The VT-M/D group was sacrificed at various time points - 14 and 17 days, 3, 4, 6, 8 and 10 weeks. ResultsOn longitudinal histological examination, compared with normal TM and acute TMP, the perforation edges at the later time points illustrated thickened stratified squamous epithelium rimming around the edges, significant increase in keratin and collagen deposition, increased macrophage infiltration as well as reduced cellular proliferation. Three phases of TMP healing process were identified - the acute healing phase (3–17 days), the transition phase (3–4 weeks) and the chronic phase (6–10 weeks). ConclusionBased on the histological results of this study, the progressive development of chronic TMPs appeared to be associated with increased epidermal thickening, collagen and keratin deposition, macrophage infiltration and reduced cellular proliferation. After the 3–4 weeks of transition phase, the TMPs seemed to have transformed into a non-healing chronic TMP between 6 and 10 weeks.

Topikal dekspantenol uygulaması akut kulak zarı perforasyonlarının iyileşmesini hızlandırmaktadır: Deneysel bir çalışma

Topikal dekspantenol uygulaması akut kulak zarı perforasyonlarının iyileşmesini hızlandırmaktadır: Deneysel bir çalışma

In Reply: Treatment for Acute Tympanic Membrane Perforation.

First of all, we would like to thank you for your interesting comments to our study. Our study was concerning to the application of synthetic bio-material patch. As your recommendation, natural healing rate of acute tympanic membrane perforation is very high [1,2], and moist environment of middle ear accelerate healing process [3,4]. In our study, the patient with small size perforation (under 25% of perforation) was 35% of silk patch group. The other patients had relative large perforation with margin’s eversion or inversion. So, the confusion about natural hearing process of small perforation might be resolved. Additionally, we thought that the perforation pattern was more important than the perforation’s size. Slit pattern’s perforation was relatively better healing condition.

Treatment for Acute Tympanic Membrane Perforation.

Treatment for Acute Tympanic Membrane Perforation.

A prospective cohort study of the silk fibroin patch in chronic tympanic membrane perforation.

Silk fibroin patching has been used to repair acute tympanic membrane perforations. Here, we describe the advantages and outcomes of this technique for chronic tympanic membrane perforations. Individual cohort study. Forty patients were enrolled; half underwent perichondrium myringoplasty, and the silk fibroin patch technique was applied in the remaining patients. We compared the closure, otorrhea, and complication rates; closure time; postoperative hearing gain; and patient satisfaction between the two groups. Demographic data (gender, site, age, duration, preoperative air-bone gap, and perforation size and location) were not significantly different between the two groups. The closure rates and times, complication rates, and postoperative hearing gains were also similar in both groups. The mean operative time, otorrhea rate, and complication rate were also significantly better in the silk fibroin patch group. The intraoperative dizziness scores were higher in the conventional perichondrium myringoplasty group. Success rates were similar for the silk fibroin patch technique and conventional perichondrium myringoplasty; however, patching was an easier, faster procedure. Our results suggest that the silk fibroin patch technique is a suitable treatment for chronic tympanic membrane perforation. 2b Laryngoscope, 126:2798-2803, 2016.

The effects of different environmental pH on healing of tympanic membrane: an experimental study.

In this study, we investigated the effect of environmental pH on healing of acute rat tympanic membrane perforations. Twenty Wistar albino rats were divided into four groups and used in the study. A large myringotomy was performed in the posteroinferior quadrants of both tympanic membranes. In left ears, topical pH 4 standard calibration solution was used in groups 1 and 3, and pH 7 standard calibration solution was used in groups 2 and 4. Right ears served as controls, and allowed for spontaneous healing. The solutions were applied for 2days in groups 1 and 2, and for 7days in groups 3 and 4. Healing was assessed by macroscopic closure of the tympanic membrane perforation, and histopathological analysis of lamina propria edema, neovascularization, inflammatory cells, and fibroblastic reaction in the temporal bones. pH 7 and pH 4 groups were similar for macroscopic closure of perforation on day 2; however difference was significant on day 7. The fibroblastic activity was significantly less on days 2 and 7 in pH 4 group. On day 7, there were significant differences between pH 4 and pH 7, and pH 7 and control groups for inflammatory cell infiltration. In conclusion, clinical and histopathological results of this study indicated that acidic environmental pH speeded up and shortened wound-healing process. By building up optimum environmental pH, a healthy healing may be achieved in acute tympanic membrane perforations.

Enhanced expression of hepatocyte growth factor in the healing of experimental acute tympanic membrane perforation

ObjectivesThe present study was performed to investigate the expression of hepatocyte (HGF), epidermal (EGF) and vascular endothelial (VEGF) growth factors in the course of healing of experimental tympanic membrane (TM) perforations in rats. The goal was to explain the role of these growth factors in the healing process of TM and to assess the possibility of their future application as healing promoters. MethodsSeventy rats were used, of which 10 served as controls and the others had their TM perforated. The experimental animals were divided into six subgroups on the basis of time points (01, 03, 05, 07, 09, 15 day after injury). Videootoscopy and histology were employed to assess the morphology of the healing process. The expressions of HGF, EGF and VEGF were evaluated using Western blot analysis. Tissue localization of HGF was determined by the immunofluorescence method. ResultsHGF was hardly detectable in normal TM; however, a significant increase was noted in its expression starting from the third day after injury throughout the follow-up period, with the highest level on day 05. The analysis of HGF tissue localization with immunofluorescence revealed diffuse staining in the cytoplasm of proliferating epithelial cells. The expression of EGF was elevated on the first day after injury, not reaching statistical significance, and then returned to the level observed in the control TM. No significant differences were noted in the expression of VEGF. ConclusionHigh expression of HGF during the healing process of acute TM perforations makes it a promising candidate for further studies oriented towards its possible use in augmentation of TM healing.

[The Traumatic Tympanic Membrane Perforation - Aetiology and Therapy].

The use of cotton swabs is well known as a cause of a traumatic membrane perforation. More reasons are known. A detailed description of the aetiology and therapy in Germany does not exist. The treatment consist of a readaptation of the perforation an splinting of the tympanic membrane with paper sheets or silicon foils. 238 patients with an acute tympanic membrane perforation were included in this retrospective study. They were treated between 2005 and 2010. The mean causes of a traumatic tympanic membrane perforation were slaps with the open hand (37.4%), the use of a cotton swab (19.3%) and high diving (13.0%). The perforations have been splinted with paper sheets or silicon foils. The rate of complete wound closure after splinting with different materials are comparable (71.9% and 81.8%). The side effects are low. This is the first study about the aetiology of traumatic tympanic membrane perforations in Germany. There is no statistic difference between the 2 materials for tympanic membrane splinting. A traumatic tympanic membrane perforation should be treatet at least to improve the air conduction threshold.