Treatment Of Tympanic Membrane Perforations Research Articles

In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions.

Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP.

A Study on Regenerative Treatment for Tympanic Membrane Perforation in a Clinic

A Study on Regenerative Treatment for Tympanic Membrane Perforation in a Clinic

Impact of titanium-prepared platelet-rich fibrin in type 1 fascia graft tympanoplasty on graft survival and hearing outcomes.

Type 1 fascia graft tympanoplasty (T1FGT) is the mainstay surgical approach for the treatment of tympanic membrane perforations. The most widely used graft material is temporal muscle fascia, and graft take rates are reported differently. The methods to enhance graft take are still being investigated. Aim: The aim of our study was to investigate the effect of titanium-prepared platelet-rich fibrin (T-PRF) on graft take and hearing outcomes in T1FGT. Fifty-seven ears eligible for T1FGT were involved in the study and prospectively evaluated. T-PRF was applied with T1FGT in 27 ears. Thirty ears in the other group underwent only T1FGT. The patients underwent an otomicroscopic and audiometric examination in preoperative and postoperative 2nd week, 1st month, and 6th month. Both groups were evaluated in terms of hearing levels, infection, and graft take rates. Two patients in the T1FGT + T-PRF group and seven patients in the T1FGT group had postoperative perforation (graft take rate: 92.6% versus 76.7%). The graft take rate was found to be increased in the T-PRF group although the difference was not statistically significant. In the T1FGT group, the percentage of infection was higher than in the T1FGT + T-PRF group. When the preoperative and postoperative 6th-month audiometry was compared, a statistically significant hearing gain was obtained for both groups. In the treatment of tympanic membrane perforations, T-PRF applied over the fascia graft was shown to increase graft take rates and decrease the probability of infection. Further studies with larger samples are needed to demonstrate the effects of PRF.

Janus membranes with asymmetric cellular adhesion behaviors for regenerating eardrum perforation.

The tympanic membrane plays an important role in the human hearing system, which is easily perforated under unfavorable conditions, leading to loss of hearing and otitis media. Many autologous materials and artificial materials have been used to repair a perforated tympanic membrane, but these materials sometimes can cause severe hearing loss because of their adhesion to the ossicle during the healing process and the postoperative process. Herein, we report Janus membranes with asymmetric cellular adhesion behaviors for regenerating the eardrum. These Janus membranes are constructed by co-depositing a tannic acid (TA)/3-aminopropyltriethoxysilane (APTES) coating on one surface of the polypropylene microfiltration membrane. Cellular experiments indicate that the Janus membranes have good biocompatibility and asymmetric cellular adhesion properties. The repair of the tympanic membrane perforation experiment and laser Doppler vibrometer (LDV) measurements prove that the hydrophilic surface of Janus membranes repairs perforated eardrums, and meanwhile the hydrophobic surface can avoid adhering to the inner ear tissue for reducing hearing loss. The Janus membranes have good prospects in the treatment of tympanic membrane perforation.

Self‐Adhesive Silicone Microstructures for the Treatment of Tympanic Membrane Perforations

Bioinspired Adhesives Novel material architectures for accelerated healing - silicone microstructures are proposed as bioinspired non-chemical adhesive for repairing tympanic membranes. The novel patch adapts and adheres to the injured eardrum and supports scarless healing. Handling by the surgeon is improved and allows for a new paradigm in out-patient treatment. More details can be found in article number 2100057 by Eduard Arzt and co-workers.

Self‐Adhesive Silicone Microstructures for the Treatment of Tympanic Membrane Perforations

Inspired by the gecko foot, polymeric microstructures have demonstrated reliable dry adhesion to both stiff objects and sensitive surfaces such as skin. Microstructured silicone patches are proposed, herein, for the treatment of tympanic membrane perforations with the aim of serving as an alternative for current surgical procedures that require anesthesia and ear canal packing. Sylgard 184 PDMS micropillars of 20 μm in diameter and 60 μm in length are topped by a Soft Skin Adhesive (SSA) MG7‐1010 terminal layer, of about 25 μm thickness. The adhesion is evaluated by specially designed tack tests against explanted murine eardrums and, for comparison, against a rigid substrate. Functional effects are evaluated using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAE). The adhesion strength of the microstructure and unstructured controls to explanted murine tympanic membranes is comparable (typically 12 kPa), but the microstructured patches are easier to handle by the surgeon. For the first time, partial recovery of hearing performance is measured immediately after patch application. The novel patches adhere without the need for further fixation, removing the need for ear canal packing. The proposed material design holds great promise for improving clinical treatments of tympanic membrane perforations.

Cellulose-Based Fibrous Materials From Bacteria to Repair Tympanic Membrane Perforations.

Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated with surgical procedures. The success rate of the treatment could be improved by novel bioengineering approaches. In fact, a successful restoration of a damaged TM needs a supporting biomaterial or scaffold able to meet mechano-acoustic properties similar to those of the native TM, along with optimal biocompatibility. Traditionally, a large number of biological-based materials, including paper, silk, Gelfoam®, hyaluronic acid, collagen, and chitosan, have been used for TM repair. A novel biopolymer with promising features for tissue engineering applications is cellulose. It is a highly biocompatible, mechanically and chemically strong polysaccharide, abundant in the environment, with the ability to promote cellular growth and differentiation. Bacterial cellulose (BC), in particular, is produced by microorganisms as a nanofibrous three-dimensional structure of highly pure cellulose, which has thus become a popular graft material for wound healing due to a number of remarkable properties, such as water retention, elasticity, mechanical strength, thermal stability, and transparency. This review paper provides a comprehensive overview of the current experimental studies of BC, focusing on the application of BC patches in the treatment of TM perforations. In addition, computational approaches to model cellulose and TM are summarized, with the aim to synergize the available tools toward the best design and exploitation of BC patches and scaffolds for TM repair and regeneration.

Butterfly Cartilage Tympanoplasty as an Alternative to Conventional Surgery for Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis.

To compare the effectiveness of butterfly cartilage tympanoplasty (BCT) with that of conventional surgical approaches in the treatment of tympanic membrane perforations. A systematic search was performed by screening the PubMed, Embase, and Cochrane Library databases up to October 31, 2020. Two coauthors independently identified studies in accordance with the selection criteria. Data were pooled and analyzed via Review Manager version 5.3 and Stata version 12.0 software. The postoperative outcomes were measured and expressed as odds ratios (ORs) and standardized mean differences (SMDs). Additionally, heterogeneity was assessed through the I2 statistic. A total of 15 articles were eligible for final inclusion. The OR values for the graft uptake rate, compared to conventional tympanoplasty, were 1.12 (95%CI: 0.56-2.22, I2 = 52%, P = .75) and 1.22 (95%CI: 0.58-2.59, I2 = 0%, P = .60), and the OR compared to fat plug myringoplasty was 3.02 (95%CI: 1.04-8.77, I2 = 0%, P = .04). The qualitative analysis of the hearing results reflected significant postoperative auditory gains with no significant differences between the BCT and control groups, indicating satisfactory and similar postoperative hearing improvement. Moreover, the operation time was shortened (SMD = -2.19, 95%CI: -2.79 to -1.59, I2 = 82%, P < .05), and the postoperative pain was less with the BCT approach. Butterfly cartilage tympanoplasty has satisfactory efficacy in terms of anatomical and functional results in small to medium perforations. It reduces operation time and postoperative pain. However, the effectiveness on large perforation requires further assessment by well-designed studies.

The effectiveness and safety of growth factors in the treatment of tympanic membrane perforations: a systematic review and meta-analysis of randomized controlled trials.

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.

Treatment of tympanic membrane perforation with topical epidermal growth factor: progress towards clinical application

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Chronic otitis media is a widespread disease of developing countries, especially of the lower socio-economic group. Medical cost in hospitals associated with tympanoplasty for treating CSOM is very high. Our study investigates the efficacy of epidermal growth factor along with chemical cautery in healing of chronic tympanic membrane perforation on an outpatient department (OPD) basis. Hence providing a cheaper and cost effective treatment alternative to the patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A total number of 70 patients with signs of COM attending ENT OPD were selected. The patients were randomly assigned into 2 groups each with a sample size of 35. Otoendoscopy and pure tone audiometry was performed. Group A was treated with EGF with chemical cautery and group B was treated with only chemical cautery. Both groups were followed up after 15 days, one month and second month of the procedure in ENT outpatient clinic.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The success rate of these non-healing perforation was found to be significantly higher in group A (29 [82.86%]) compared with group B (17 [65.71%]) with P value of 0.0070*.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study shows a statistically significant result with topical application of epidermal growth factor in small to medium non-healing central tympanic membrane perforation. Due to the promising result of epidermal growth factor, it could be considered as office myringoplasty. &lt;/p&gt;

A study to compare the outcomes of CO2 laser assisted myringoplasty versus conventional type1 tympanoplasty in small central tympanic perforations

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The standard treatment of tympanic membrane perforation is conventional surgical closure using myringoplasty or a tympanoplasty type 1. In this study the role of cabon dioxide (CO&lt;sub&gt;2&lt;/sub&gt;)-laser-assisted de-epitheliazation of perforation margins and application of bioinert silastic sheet. Success rate was compared with conventional microscopic surgery.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This was a comparative study containing 60 patients with small dry tympanic membrane perforation (diameter 1-3 mm). The causes of tympanic membrane perforations were mainly traumatic or the eardrum did not heal after spontaneous perforation caused by an acute otitis media or after surgery. The procedure was performed under local anaesthesia. CO&lt;sub&gt;2&lt;/sub&gt; (acupulse) applied along the edge of the perforation until complete de-epitheliazation and application of bioinert silastic sheet in small dry perforation. Closure of eardrum perforation was monitored using an otoendoscope. Success rate of the CO&lt;sub&gt;2&lt;/sub&gt; laser myringoplasty was compared with conventional type 1 tympanoplasty. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Complete eardrum closure occurred in 24 cases (80%), 06 patients (20%) had a residual perforation. The success rate of this procedure is lower than conventional type 1 tympanoplasty, which is 90-94%. There were no complications during and after the treatment.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; A closure rate of 80% (24/30) was achieved with a CO&lt;sub&gt;2&lt;/sub&gt;-laser-assisted de-epitheliazation. This procedure can be offered carefully to selected cases with perforation size &amp;lt;3 mm, where the CO&lt;sub&gt;2&lt;/sub&gt; facility is available before they undergo formal conventional microscopic surgery.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation

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.

Surgical treatment of tympanic membrane perforation in children: Success rate and hearing outcome

Surgical treatment of tympanic membrane perforation in children: Success rate and hearing outcome

Fabrication of tissue-engineered tympanic membrane patches using 3D-Printing technology

In recent years, scaffolds produced in 3D printing technology have become more widespread tool due to providing more advantages than traditional methods in tissue engineering applications. In this research, it was aimed to produce patches for the treatment of tympanic membrane perforations which caused significant hearing loss by using 3D printing method. Polylactic acid(PLA) scaffolds with Chitosan(CS) and Sodium Alginate(SA) added in various ratios were prepared for artificial eardrum patches. Different amounts of chitosan and sodium alginate added to PLA increased the biocompatibility of the produced scaffolds. The created patches were designed by mimicking the thickness of the natural tympanic membrane thanks to the precision provided by the 3D printed method. The produced scaffolds were analyzed separately for chemical, morphological, mechanical and biocompatibility properties. Scanning electron microscope (SEM), Fourier-transform infrared (FT-IR) spectroscopy was performed to observe the surface morphology and chemical structure of the scaffolds. Mechanical, thermal and physical properties, swelling and degradation behaviors were examined to fully analyze whole characteristic features of the samples. Cell culture study was also performed to demonstrate the biocompatibility properties of the fabricated scaffolds with human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). 15 wt % PLA was selected as the control group and among all concentrations of CS and SA, groups containing 3 wt% CS and 3 wt% SA showed significantly superior and favorable features in printing quality. The research continued with these two scaffolds (3 wt% CS, and 3 wt% SA), which showed improved print quality when added to PLA. Overall, these results show that PLA/CS and PLA/SA 3D printed artificial patches have the potential to tissue engineering solutions to repair tympanic membrane perforation for people with hearing loss.

Effect of Local Estrogen on Repairing Tympanic Membrane Perforation.

Introduction:Tympanoplasty is a surgical treatment of tympanic membrane perforation. Many efforts have been made to increase the success rate of tympanoplasty. Some studies confirmed the positive role of estrogen in wound healing. The current study was conducted to evaluate the effect of topical estrogen on the success rate of tympanoplasty.Materials and Methods:A total of 85 patients were randomly assigned to the case and control groups. Otomicroscopic examination was performed before and 3 months following the operation. At the final stage of tympanoplasty, gelfoam was placed on the lateral side of the graft. It was soaked in dexamethasone in the control group and combination of dexamethasone and estradiol valerate solution in the case group. Hearing thresholds were measured by audiometric tests pre- and postoperatively. Hearing levels were assessed as the mean air conduction (AC) at 500, 1000, and 2000 Hz. The graft status was evaluated using otomicroscopic examination 3 months following the operation. Results:Otomicroscopic examination revealed successful graft healing in 23 of 37 and 29 of 36 patients in the control and case groups, respectively. A higher rate (80.55%) of graft repair was observed in the estradiol group, compared to that (62.16%) reported for the control group; however, the difference was not statistically significant (P=0.08). The average improvement values of the AC levels were 20.45 and 24.7 dB in the control and case groups, respectively (P=0.3). Statistical analysis among the subgroup of patients with small perforations showed that the success rate of tympanoplasty was significantly higher in the estradiol group, compared to that reported for the control group (P=0.03). Conclusion:Although topical estrogen was generally ineffective in increasing the success rate of tympanoplasty, it improved the success rate among patients with small tympanic membrane perforations.

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis.

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.

The Management of Tympanic Membrane Perforation With Endoscopic Type I Tympanoplasty.

The objective of this study is to describe what we consider to be the state-of-the-art procedure for the treatment of tympanic membrane perforations, and to present the results attained in our institution. A retrospective cohort study, using data of Verona University Hospital, Italy. This medical record includes the data of 98 patients who underwent 100 transcanal endoscopic type I tympanoplasties from November 2014 to October 2017. Tertiary referral center University Hospital of Verona, Italy. Were enrolled 109 patients, that underwent endoscopic type I tympanoplasty in the period considered. Out of the selected patients, 11 (10.1%) were lost to long-term follow-up, and were therefore excluded from our study. Other exclusion criteria were surgical approaches that included other procedures. Patients whose follow-up was shorter than 6 months were excluded from this study. The technique is based on an endoscopic placement of underlay graft of temporal fascia or tragal cartilage. We consider the data of four surgeons from Verona University ENT department. In the study we considered the reduction of the Air Bone Gap as functional outcome and the integrity of the reconstruction as anatomical outcome of success. No major intraoperative complications were observed. The closure rate was 86%. The mean surgery time was 48.6 minutes. The air bone gap was improved within 20 DB HL in 89% of patient. Only 8% of patients needed revision surgery, and none needed a third surgical evaluation. Endoscopic ear surgery is by now a reality that has replaced in many cases exclusive microscopic ear surgery. Transcanal endoscopic type I tympanoplasty can be considered nowadays as an alternative technique for tympanic membrane perforations.

Palisade cartilage fascia tympanoplasty: our experience

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Cartilage tympanoplasty is one of the procedures performed for treatment of tympanic membrane perforation, more so in those cases associated with eustachian tube dysfunction, or failed previous temporalis fascia type 1 tympanoplasty. Palisade cartilage tympanoplasty, initially described by Heerman utilizes strips of conchal cartilage to reconstruct the tympanic membrane.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A retrospective study which was presented with 64 patients who underwent palisade cartilage- fascia type I tympanoplasty and compared their hearing outcome after three years of post-operative period. Indication to perform a cartilage-fascia tympanoplasty was either an atelectatic middle ear or large perforation of the drum or residual or recurrent perforation following previous temporalis fascia myringoplasty. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Average pre-operative hearing loss was 37.38±15.04 dB, while post-operative hearing loss was 20.47±8.85 dB, giving an average gain of 17.03 dB. Of 64 patients, 93.7% patients had fully healed neotympanum.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Palisade cartilage fascia tympanoplasty is an effective method to ensure graft uptake and at the same time achieve competitive hearing gain. The reliability of this technique lies in its use for recurrent and residual perforations of the tympanic membrane as well as in cases associated with eustachian tube dysfunction.&lt;/p&gt;

CASE-CONTROL STUDY IS BEST FOR BASIC FIBROBLAST GROWTH FACTOR REPAIRING HUMAN CHRONIC TYMPANIC MEMBRANE PERFORATION

To the Editor: We would like to address the article entitled “Application of regenerative treatment for tympanic membrane perforation with cholesteatoma, tumor, or severe calcification” by Kanemaru et al. (1). The study is excellent. This study suggested that gelatin sponge with basic fibroblast growth factor (b-FGF) is useful not only for patients with simple tympanic membrane perforations (TMPs) but also for those with cholesteatomas, tumors, or severe calcification without requiring conventional surgical procedures (1). However, the confounding factors and short follow-up times affected the assessment of effect of b-FGF repairing chronic TMPs. This is a single institution and none clinical controlled trial. In this study, the regenerative treatment for TMP with cholesteatoma, tumor, or severe calcification included the use of a gelatin sponge immersed in b-FGF and fibrin glue. Whether bFGF alone is sufficient for the repair of chronic TMPs or whether it is necessary to add one of these other materials is unclear. Previous clinical studies have shown that the use of a gelatin sponge alone facilitates the healing of chronic TMPs (2). In addition, in the clinical studies of b-FGF on human traumatic TMPs, early studies have shown that a single application of b-FGF improves the closure rate and shortens the closure time of traumatic TMPs compared with spontaneous healing (3). However, in subsequent controlled studies, groups treated with topical application of b-FGF did not have a better closure rate or shorter closure time than patients in the ofloxacin otic group (4). Clinical and experimental studies have shown that topical application of ofloxacin otic solution aids the healing of the eardrum (5–7). Thus, a clinical case-control study comparing the curative effects of bFGF-immersed gelatin sponge with those of ofloxacin otic solution for the treatment of chronic TMPs is needed. If the healing rates of the two treatments are similar, then the topical application of b-FGF cannot be recommended. On the other, traumatic TMPs was different from TMPs with chronic suppurative otitis media, recent studies have demonstrated that topical application of EGF can promote the healing of traumatic human TMPs (8) but this is not the case for chronic TMPs (9). The biological half-life of b-FGF is short, only 12 hours (10). Clinical studies on using b-FGF to treat traumatic TMPs have shown that daily continuous application of b-FGF keeps the eardrum moist, which promotes healing of the TMP (3,4). The authors (1) have described the use of a b-FGF-infiltrated gelatin sponge during 3 weeks of treatment. Although this material slowly releases b-FGF, most of the b-FGF will flow into the nasopharynx, through the Eustachian tube, with only a small amount remaining in the middle ear. In addition, most gelatin sponge-infiltrated b-FGF dries out within 3 to 4 days (3). Thus, whether only one application of b-FGF can promote chronic TMP healing remains to be verified. In addition, the follow-up time was short. The authors reported the success rate of 91% at 6 months (1). However, Hakuba et al. investigated chronic TMPs treated with atelocollagen immersed in b-FGF, and reported a success rate of 92.0% at 6 months (11) but 66.0% at 1 year (12). Thus, the long-term advantages of bFGF await clarification. The authors did not describe whether the severe calcification needs to be removed for the TMPs with severe calcification. Clinical studies have shown that severe calcification is related to a high risk of healing failure in TMPs treated with b-FGF (12,13). In summary, while b-FGF may indeed be an excellent biological material for the repair of human chronic TMPs, this must still be demonstrated in case-control trials conducted at multiple centers with a large number of patients and in studies with a longer follow-up.

The short- and long-term adverse effects of FGF-2 on tympanic membrane perforations.

The objective of this study was to investigate the short- and long-term adverse effects of fibroblast growth factor-2 treatment of tympanic membrane perforations. A total of 134 patients with traumatic tympanic membrane perforations were randomly divided into two groups: an observational group and a fibroblast growth factor-2 treatment group. The closure rate, closure time and principal side-effects were compared between the groups at 6 and 12 months. At 6 months, 131 patients were examined to determine healing outcomes and short-term side-effects. The total closure rate differed significantly between the fibroblast growth factor-2 and observational groups (95.5% vs 73.4, p #x003C; 0.01). The fibroblast growth factor-treated group exhibited a significantly shorter closure time than the observational group (11.9±3.1 days vs 52.6 ± 18.1 days, p = 0.00). Three patients with secondary otitis media with effusion, and three with reperforations, were noted in the fibroblast growth factor-2 group. We additionally performed long-term follow-up on 89.1% of the patients in the observational group and 92.5% of the patients in the fibroblast growth factor-2 group; follow-up was performed 16-42 months after perforation closure. Only a small perforation of the pars flaccida developed in the fibroblast growth factor-2 group. No middle ear cholesteatoma was noted in either group. This study suggests that the topical application of fibroblast growth factor-2 to human traumatic tympanic membranes is safe. Otorrhoea was the most common short-term side-effect; other less common side-effects included otitis media with effusion and reperforation. No serious long-term side-effects were found.