Polycarbonate urethane – poly (2-ethyl 2-oxazoline) based electrospun graft material for tympanic membrane perforation therapy

To apply regenerative treatment for tympanic membrane (TM) perforation to patients with severe calcification of the TM, cholesteatomas, or tumors localized to the tympanic cavity. Controlled clinical pilot study. General hospitals. Forty-five patients (age: 8-85; M = 19, F = 26) were selected from patients with or without TM perforation for the regenerative treatment. Twenty-five patients had cholesteatomas, 3 had tumors, and 17 had severe TM calcification. Patients were classified into three groups based on TM perforation size: less than 1/3 of the TM as Grade I (n = 5), 1/3 to 2/3 as Grade II (n = 19), and over 2/3 as Grade III (n = 21). Twenty patients who underwent standard tympanoplasty type I were selected as historical controls. Materials for the TM repair included gelatin sponge with basic fibroblast growth factor and fibrin glue. After lesions were removed through the TM perforation, gelatin sponge immersed in basic fibroblast growth factor was placed over the perforation. Fibrin glue was then dripped onto the sponge. Treatment efficacy was evaluated 6 months posttreatment. Complete closure of the TM perforation was achieved in 91% (n = 41/45) of the patients in this regenerative treatment. Improvement in average hearing levels and air-bone gap were much better with this treatment than in the historical control group. This new regenerative therapy is useful not only for patients with simple TM perforations but also for those with cholesteatomas, tumors, or severe calcification without requiring conventional surgical procedures. This regenerative therapy is an easy, safe, cost-effective, and minimally-invasive treatment.

To determine the clinical efficacy and safety of growth factors in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs). Databases, including PubMed, EMBASE, Cochrane library, Ebsco, Ovid, Scopus, and Web of Science, were searched for articles in any language about studies on the treatment of TM perforations with growth factors. Inclusion criteria were: (1) randomized controlled trials (RCTs); (2) only patients with TM perforations included; and (3) any kinds of growth factors or related products were used as an intervention. Exclusion criteria were: (1) study was not reported as a full paper, only as an abstract; (2) review studies and case reports; and (3) an inability to extract valid data. Outcomes of interest included perforation closure rate, closure time, hearing improvement, and complications. Nineteen RCTs with a total of 1335 participants were included. Growth factors effectively increased the rate of perforation closure [risk ratio (RR): 1.21 95% confidence interval (1.12, 1.30), p < 0.01] and shortened closure time [mean difference (MD): - 16.71 (-22.74, - 10.15), p < 0.01]. There was no significant difference in hearing improvement [MD: 0.10 (- 0.50, 0.70), p = 0.74] or complications [RR: 1.49 (0.96, 2.32), p = 0.07] between the growth factor intervention group and the control group. Growth factors are effective and safe in the treatment of TM perforations. However, better designed clinical trials should be carried out in the future to obtain more robust findings about the effectiveness of growth factors in the treatment of TM perforations.

Conclusion: Acellular dermal matrix (ADM) can be used as a substitute for tympanic membrane (TM) reconstruction. Objective: To investigate the effectiveness of ADM in the treatment of TM perforations. Methods: Fifty guinea pigs were used to create TM perforations. The perforations of the left TM were repaired with ADM by patch technique in 28 guinea pigs and by underlay technique in 22 guinea pigs. The right ears were used as the control group by establishing TM perforation but without TM reconstruction. The morphological and structural status of the grafts was observed by immunohistochemistry and scanning electron microscopy. Results: There was no statistically significant difference in TM perforation closure between the ADM patch technique group and the ADM underlay technique group, but these groups had a higher success rate in closing TM perforation than the control group. The healed TMs with ADM had the same characteristics as normal TM on histological examination.

Objective:To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs), prospective and retrospective studies.Data Sources:PubMed, EMBASE, and Cochrane databases were screened from their inceptions to June 2019.Study Selection:Inclusion criteria: 1) English language; 2) observational (retrospective or prospective) or treatment (RCT) studies; 3) reported the outcomes on the application of bFGF in adult or pediatric population. Exclusion criteria: 1) studies without a control group; 2) animal studies, in vitro studies, review studies, and case reports.Data Extraction:Number of patients, cause of TM perforation, perforation size, treatment, mean age, follow-up time, sex, closure rate, healing time, mean air-bone gap improvement.Data Synthesis:A total of 14 studies were included, including seven RCTs and seven non-RCTs with a total of 1,072 participants. The odds ratio for closure rate of bFGF treatment was 7.33 (95% confidence interval [CI], 4.65 to 11.53; p < 0.01; I2 = 44%) and the standardized mean difference (SMD) for healing time was –5.89 (95% CI: –7.85 to –3.93, p < 0.01, I2 = 98%), suggesting bFGF application has a significant effect on closure of TM perforations. However, no significant change in hearing (SMD: 0.08, 95% CI: –0.11 to 0.27, p = 0.39, I2 = 0%) was seen as a result of bFGF treatment.Conclusions:Our meta-analysis has revealed that the application of bFGF can significantly enhance the closure rate as well as shorten the healing time for TM perforations. In terms of hearing, there is as yet no evidence that bFGF has a significant effect. Given its ease, availability, and safety, bFGF can be used effectively for TM repair.

BackgroundMost tympanic membrane (TM) perforations heal spontaneously, but approximately 10-20% remain open as chronic TM perforations. Chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. Traditionally, these perforations must be surgically closed, which is costly and time consuming. Therefore, there is a need for simpler therapeutic strategies. Previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that accelerates cutaneous wound healing in mice. We have also shown that the healing of TM perforations is completely arrested in plg-deficient (plg-/-) mice and that these mice develop chronic TM perforations. In the present study, we investigated the therapeutic potential of local plg injection in acute and chronic TM perforation mice models.MethodsPlg-/- mice and wild-type mice were subjected to standardized TM perforations followed by local injection of plg into the soft tissue surrounding the TM. TM perforations with chronic characteristics were induced by leaving TM perforations in plg-/- mice untreated for 9 days before treatment. The healing process was observed through otomicroscope and finally confirmed by immunostaining. The quality of TM healing was evaluated based on the morphology of the TM.ResultDaily local injections of plg into the soft tissue surrounding the TM restored the ability to heal TM perforations in plg-/- mice in a dose-dependent manner, and potentiated the healing rate and quality in wild-type mice. A single local injection of plg initiated the healing of the chronic-like TM perforations in these mice, resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. However, three plg injections led to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer.ConclusionOur data suggests that plg is a promising drug candidate for the treatment of chronic TM perforations in humans.

ObjectiveTo evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. MethodsThis was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23–78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air–bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. ResultsTotal closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%–91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%–100.0%). The ratio of hearing improvement and the air–bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%–100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. ConclusionThe results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Retrospective study of risk factors for tympanic membrane perforation in the early period after intratympanic steroid injection

Chronic Candida albicans otitis media in children with immunodeficiency.

PurposeInjury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear.MethodsThe middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, ¼ of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated.ResultsThe measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz.ConclusionSize and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.

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

The majority of issues related to patients suffering from conductive hearing loss and repeated otitis media are due to chronic tympanic membrane perforations. This generally requires a surgical procedure called tympanoplasty to seal the perforation where autologous grafts are used to reconstruct the membrane. However, the limitations associated with surgical procedures and the limited graft-material availability often cause difficulties in this route; demanding novel procedures or materials. The basic requirements for a synthetic graft-material for this application cover excellent cell adherence with no immune response and inflammatory actions at the site of implantation along with wound-healing characteristics and sufficient acoustic and mechanical properties. With this aim, an innovative graft material has been developed with polyvinyl alcohol (PVA) as the base component through this work. To ensure better cell adhesion and proliferation, a natural polymer, gelatin, has been cross-linked with PVA through a maleic anhydride (MA) intermediate; with a two-step synthesis protocol. The mechanical strength of graft material has been found to be tunable by adjusting the ratio of gelatin with PVA. Laser Doppler Vibrometry (LDV) has been employed to evaluate its acoustic properties upon exposure to a frequency sweep of 10-8000 Hz. The invitro biocompatibility assays using L929 and RPMI 2650 cells substantiate the material's compatibility; ensuring its potential clinical applications toward chronic tympanic membrane perforations.

Medial or medio-lateral graft tympanoplasty for repair of tympanic membrane perforation

This study aimed to determine how tympanic membrane (TM) perforations and their closure, using a paper-patch technique, affect middle-ear mechanics and, thus, conductive hearing for different sizes of the TM perforation. Temporal bone (TB) study and prospective clinical trial. Tertiary referral center. Nine patients with chronic otitis media for more than 3 months. The TM perforations were closed with a paper patch in all 9 patients. In 5 of 9 patients, myringoplasty was performed. Matching TM perforations were created in a TB model (n = 8) and closed using the paper patch. Air-bone gap was measured in all 9 patients of the patient cohort with TM perforations before and after closure and in 5 patients after myringoplasty. Stapes velocity and sound pressure difference between the ear canal and middle-ear cavity were measured in TBs with intact TM, with TM perforations, and with the perforations closed by the paper patch. All measurements in the patient cohort and TBs were performed for different sizes of TM perforations to determine if the effects varied as a function of size. Degree of the air-bone gap differed as a function of size of the TM perforations and its recovery after closure, and myringoplasty was independent of the size of the TM perforation in the frequency range of 0.25 to 4 kHz. In the TB measurements, although pressure difference across the TM was almost fully recovered by closing the perforation with a paper patch, recovery of the stapes motion was limited at frequencies above 4.5 kHz for larger sizes of TM perforations. Hearing loss caused by TM perforations depends on the size of the perforation. Hearing returns almost completely across the frequency range after closure except above 4 kHz for larger perforations. This is because the structural damage caused by large TM perforations cannot be completely restored by application of a paper patch.

Background: Tympanic membrane (TM) perforation is a recognised cause of hearing loss in our environment. The integrity of the TM can be compromised by varying aetiological factors which are often preventable. TM perforation occurs in different dimensions which tend to influence the degree of hearing loss. Aim: The aim of this study is to determine the aetiological factors and dimensions of TM perforation among adolescents and adults in Benin City. Methods: This was a 1-year prospective study carried out from 1st July 2014 to 30th June 2015 at the Ear, Nose and Throat Clinic of University of Benin Teaching Hospital. Consecutive patients with TM perforation were examined using a hand-held otoscope as well as Firefly video otoscope and subsequently had an interviewer administered questionnaire. Data were analysed using Statistical Package for Social Sciences (SPSS) version 20 and ImageJ software. Results: One hundred and forty-eight patients with TM perforation in either or both ears were studied. There were 67 (45.3%) males and 81 (54.7%) females; ratio of 1:1.2. Ages ranged from 10 to 64 years, with a mean age of 34.5 ± 15.7 years. Chronic suppurative otitis media (CSOM) was the major cause of TM perforation in this study, 148 (74.0%). The small perforation was predominant, 54 (55.1%) and 48 (47%) in the right and left ears, respectively while the central anterior perforation, 93 (46.5%) occurred commonly. Conclusion: Central and small perforations were the predominant TM perforation while CSOM was the major cause of TM perforation.

PurposeAir-bone gap (ABG) is an essential indicator of middle ear transfer function after myringoplasty. However, there is still uncertainty about the mechanisms behind unexplained ABGs in patients post-myringoplasty. The present study investigated these mechanisms using cadaveric temporal bone (TB) measurement and finite element (FE) modeling.MethodsThree conditions of tympanic membrane (TM) perforation were modeled with a perforated area of 6%, 24%, and 50% of the total TM area to simulate a small, medium, or large TM perforation of TB model. A piece of paper was used to patch the TM perforation to simulate the situation post-myringoplasty. In the FE model for post-operation, the material properties at the perforation area were changed. Measurement of TM vibration at the umbo was undertaken with a laser Doppler vibrometer (LDV).ResultsAs the perforated area increased vibration of the TM at the umbo decreased in both the TB and FE models. But the reduction of TM vibration is more minor in the FE model than in the TB model. After the perforation was repaired, the displacement of TM at the umbo could not be recovered totally in the TB and FE models. In the FE model, the displacement of TM at the umbo decreased markedly when the cone shape of TM flattened, and the reduction was almost the same as that in the TB model in the condition of large perforation.ConclusionThe material properties and the anatomical shape of the repaired TM could influence the TM's modal motion and wave motion. Except for appearance and shape current clinical instruments are unable to resolve factors that affect TM motion. Consequently the ABG seen post-myringoplasty remains unexplained.