Healing Of Tympanic Membrane Perforations Research Articles

Local Alpha1-Antitrypsin Accelerates the Healing of Tympanic Membrane Perforation in Mice.

Most tympanic membrane (TM) perforations heal spontaneously, but 10%-20% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1-antitrypsin (AAT) is a circulating tissue-protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution. This study aimed to examine the effects of local clinical-grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation. Wild-type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9 × 10-3 mL at 20 mg/mL on days 0, 1, and 2; n = 15/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post-injury, and TMs were excised for gene analysis by RT-PCR. There were no adverse reactions in hAAT-treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median: 4 and 9, respectively). According to gene expression analysis, VEGF, TGFβ, and collagen-5A1 were induced earlier in AAT-treated mice (day 4-5 compared with day 9). Additionally, IL-10 expression levels were higher and IL-6 levels were lower in treated versus untreated mice. A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro-dosing in the format of a single local application. NA Laryngoscope, 134:3802-3806, 2024.

Advancement in Tympanic Membrane Repair: Exploring the Potential of Platelet Rich Fibrin.

To assess the effectiveness of the autologous plasma-rich fibrin plug technique for repairing small tympanic membrane perforations. Platelet rich fibrin (PRF) is also called second generation platelet rich plasma due to its high amount of growth factors which could be used in tympanic perforation closure. Being autologous, it is readily available with no immunogenic reactions. PRF membrane has a strong elastin fibrin structure containing growth factors and hence can be considered as an ideal sealing material or an adjuvant to the graft in repairing tympanic membrane perforations. Ours is a prospective study. A total of 52 patients with dry small tympanic membrane perforation were included in the study. In this technique, 10ml of blood is withdrawn from the patient, processed in a centrifuge machine, and platelet-rich fibrin (PRF) is separated from the mixture for use in the repair of small tympanic membrane defects. Out of the 52 patients, 42 experienced successful repair (full closure) of the tympanic membrane. The mean time of closure of the perforation was around 2weeks. However, five of them encountered failure. Although the size of the perforation decreased compared to the preoperative size. Additionally, two patients developed granulations on the tympanic membrane. No major side effects were noted. Autologous PRF is a product derived from whole blood through the process of centrifugation. It is safe and effective in promoting the natural process of wound healing by incorporating a high concentration of platelet-derived growth factors as well as fibrin into the graft mixture. This facilitates the rapid healing of tympanic membrane perforation.

Controlled Release of Mesenchymal Stem Cell-Conditioned Media from a Microsphere/Gel-Based Drug Delivery System for Wound Healing of Tympanic Membrane Perforations

Chronic tympanic membrane (TM) perforation increases patient susceptibility to infection, hearing loss, and other side effects. Current clinical treatment, surgical grafting, can result in detrimental side effects including nerve damage, dizziness, or hearing loss. Therefore, it is essential to develop novel therapeutic procedures that can induce or accelerate healing in minimally or noninvasive approaches. Cell-free therapies have safety advantages over stem cells and are logistically favorable for clinical use. The regenerative potential by mesenchymal stem cell-conditioned media (CM) has been promising. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres with CM encapsulated have been developed as a cell-free alternative regenerative treatment for TM perforation. The results suggest that the PLGA microspheres were capable of encapsulating and releasing CM for up to 21 days. The in vitro scratch wound proliferation assays showed increased wound healing ability of CM-loaded microspheres. In vivo guinea pig models treated with CM drops and CM-loaded microspheres using a thermoresponsive gel carrier demonstrated potential for wound healing in TM perforation. These studies provide a basis for further examination of the delivery of stem cell CM and investigation of time-dependent wound healing, long-term ototoxicity, and hearing restoration.

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

The significance of plasminogen activation during the tympanic membrane (TM) healing is known mainly from studies performed on knock-out mice. In the previous study, we reported activation of genes coding proteins of plasminogen activation and inhibition system in rat’s TM perforation healing. The aim of the present study was the evaluation of protein products expressed by these genes and their tissue distribution using Western blotting and immunofluorescent method, respectively, during 10-day observation period after injury. Otomicroscopical and histological evaluation were employed to assess the healing process. The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) were significantly upregulated in the proliferation phase, with subsequent gradual attenuation during remodeling phase of healing process, when keratinocyte migration was weakening. The expression of plasminogen activator inhibitor type 1 (PAI-1) also showed the highest levels during the proliferation phase. The increase of tissue plasminogen activator (tPA) expression was observed during the whole observation period, with the highest activity during the remodeling phase. Immunofluorescence of these proteins was present mainly in migrating epithelium. Our study found that plasminogen activation (uPA, uPAR, tPA) and inhibitory (PAI-1) molecules form a well-structured regulatory system of the epithelial migration that is critical to the healing of TM after its perforation.

Efficacy of Human Epidermal Growth Factor in the Regeneration of Tympanic Membrane Perforation

Introduction: Majority of tympanic membrane perforations require myringoplasty for closure. Recently, epidermal growth factor (EGF) has been shown to promote the healing of tympanic membrane perforations. Aim: The aim of this study was to find out a simple nonsurgical outpatient procedure to close one-quadrant tympanic membrane perforations that could reduce the hospital stay, medical cost, and morbidity in these patients. Materials and Methods: An interventional prospective randomized clinical study was done on 120 patients at our tertiary hospital. The allocation ratio was 3:1. Pure-tone audiometry, otomicroscopy, and otoenodoscopic recording were performed in all eligible patients who consented to take part in the study. Ninety cases received EGF gel application, whereas 30 controls received antibiotic ofloxacin application. Trichloroacetic acid chemical cautery and fibrin glue application were done in patients of both groups. Results: The closure rate was 97.7% in the EGF group and 70% in the ofloxacin group. The time taken for closure of perforations was 10 to 14 days in the EGF group and 3–4 weeks in the ofloxacin group. Hearing gain was observed in healed perforations of both groups. Conclusion: EGF application enhances the healing effect of one-quadrant nonhealing tympanic membrane perforations. It showed encouraging results and reliable safety in the regeneration of tympanic membrane. Clinical Significance: Apart from its use in single quadrant perforation, EGF may be considered for treating residual perforations after failed tympanoplasty.

Case study of a hydrostatic pressure-induced traumatic chronic tympanic membrane perforation with purulent otorrhea and spontaneous closure

<p>Tympanic membrane (TM) perforations are ruptures of the membrane separating the middle and outer ear which heal spontaneously in 78.7-94% of cases. However, with large perforations and infection, the spontaneous closure rate diminishes.Chronic TM perforations are thought to rarely close spontaneously and are often treated with a myringoplasty which has a variable success rate, potential risks, and a significant recovery period during which patient activity is notably limited. Significant controversy exists over the indication for surgical intervention in the case of grade 3, chronic TM perforation with a history of infection. The aim of this case study is to provide insight into the typical progression and potential spontaneous resolution of such cases. Moreover, there is a lack of publicly available reference images outlining the progress of TM perforation healing, so detailed time-stamped photos are included. The investigators imaged, at regular intervals, a 23-year-old male’s mid-anterior chronic grade 3 TM perforation who presented with an outer and middle ear infection with purulent otorrhea. The result indicates that chronic grade 3 TM perforations with a history of infection still have potential to spontaneously close. Given the risks and inconvenience of a myringoplasty, further consideration should be taken before recommending this procedure in these cases.</p>

Role of healing promoting factors in healing of tympanic membrane perforations

Background and Aim Some healing promoting factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), hyaluronic acid (HA), and platelet-rich plasma (PRP), have been in use nowadays to assist healing eardrum perforations. Several trials have been conducted to assess their effectiveness. This meta-analysis was conducted to find out the prognostic effects of these factors. Materials and methods The search methods consist of electronic databases and literature references for published and unpublished studies, besides the reference lists of all relevant studies. Selection criteria All types of studies (randomized controlled trials, prospective, retrospective, or case–control). Data collection and analysis Eighteen articles were included after screening by titles and/or abstracts and full-text assessment. They were categorized according to the used healing promoting factor. Data were extracted and analyzed via Cochrane Collaboration's Review Manager Software. Results EGF and FGFs significantly improved the rate of closure, healing duration, and increased hearing gain. On the contrary, the overall effects of HA and PRP were nonsignificant in this respect. Conclusion EGF and FGF can increase the rate of closure of tympanic membrane perforations, shorten healing duration, and improve hearing gain. PRP and HA do not have a significant effect. This can be attributed to heterogeneity of the studies included to assess the role of each of these two factors.

The Influence of Ciprofloxacin-Dexamethasone Ear Drops on Perforation Closure Rates After Endoscopic Tympanoplasty.

Topical ciprofloxacin and dexamethasone have both been shown to disrupt healing of tympanic membrane perforations in animal models. There have been no clinical studies evaluating the effect of ciprofloxacin-dexamethasone (CD) ear drops on success of tympanoplasty. We compare perforation closure rates in pediatric endoscopic tympanoplasty with and without use of postoperative CD. Retrospective comparative cohort study. Tertiary referral centre. One hundred sixty-two totally endoscopic tympanoplasties with porcine-derived collagen graft in children, mean age 12.0 years (range 2.3-17.9 yrs). Prescription of CD versus no ear drops in the immediate postoperative period. Perforation closure rate 2 months after totally endoscopic tympanoplasty. Postoperative CD was given to 65 (40%) ears and no drops given to the remainder. Overall, successful closure of tympanic membrane perforation was achieved in 140 (86%) of ears. The closure rate was not significantly different in those ears given CD postoperatively than those not given CD (54/65 [83%] vs 86/97 [89%], Fisher's p = 0.35). Multiple logistical regression revealed no confounding effect of other variables on outcome including age, revision surgery, graft position, or type of postoperative packing material. Our results reveal no harm or benefit with prescription of drops containing ciprofloxacin and dexamethasone on success of perforation closure after tympanoplasty. Allocation to treatment in this retrospective study was nonrandomized and was predominantly based on a change in practice. No other variables are known to have influenced this finding but a randomized prospective study could be justified for more reliable evidence.

Panel 1: Biotechnology, biomedical engineering and new models of otitis media

ObjectiveTo summarize recently published key articles on the topics of biomedical engineering, biotechnology and new models in relation to otitis media (OM). Data sourcesElectronic databases: PubMed, Ovid Medline, Cochrane Library and Clinical Evidence (BMJ Publishing). Review methodsArticles on biomedical engineering, biotechnology, material science, mechanical and animal models in OM published between May 2015 and May 2019 were identified and subjected to review. A total of 132 articles were ultimately included. ResultsNew imaging technologies for the tympanic membrane (TM) and the middle ear cavity are being developed to assess TM thickness, identify biofilms and differentiate types of middle ear effusions. Artificial intelligence (AI) has been applied to train software programs to diagnose OM with a high degree of certainty. Genetically modified mice models for OM have further investigated what predisposes some individuals to OM and consequent hearing loss. New vaccine candidates protecting against major otopathogens are being explored and developed, especially combined vaccines, targeting more than one pathogen. Transcutaneous vaccination against non-typeable Haemophilus influenzae has been successfully tried in a chinchilla model. In terms of treatment, novel technologies for trans-tympanic drug delivery are entering the clinical domain. Various growth factors and grafting materials aimed at improving healing of TM perforations show promising results in animal models. ConclusionNew technologies and AI applications to improve the diagnosis of OM have shown promise in pre-clinical models and are gradually entering the clinical domain. So are novel vaccines and drug delivery approaches that may allow local treatment of OM. IMPLICATIONS FOR PRACTICE: New diagnostic methods, potential vaccine candidates and the novel trans-tympanic drug delivery show promising results, but are not yet adapted to clinical use.

Role of Stem Cells in Healing of Tympanic Membrane Perforations

AbstractBackground: Stem cells are biological cells found in all multicellular organisms, that can divide (through mitosis) and differentiate into diverse specialized cell types and can self-renew to produce more stem cells. Currently, surgery is the treatment of choice for repairing the perforation. However, surgery is time-consuming and expensive, and there is a risk of complications. Repairing a perforation by office techniques has been successful for a few cases for small traumatic perforations.Aim of Study: In this study we aimed to study the role of stem cell therapy in management of tympanic membrane perforations by otoscopic examination, microscopic, endo-scopic examination and audiological assessment.Patients and Methods: Thirty patients included in our prospective study in Al-Zahra University Hospital and Shebin El-Kom Teaching Hospital from April 2014 up to December 2018. These patients were operated for simple myringoplasty with stem cell technique. These patients followed-up with otomicroscopic examination of the perforation, tympanometry and pure tone audiometry.Results: There were female patients much more than male patients. The mean age of the patients was 31.9±8.2 years. There is highly significant improvement in the air bone gap and ear canal volume differences before and 3 months after the operation. Doctor satisfaction was 96.7% while patient satisfaction was 94.1%. 96.7% of cases had successful results of perforation closure. Of 30 patients operated by stem cells therapy under complete aseptic techniques 29 patients TM perforations had completely healed after first trial (success rate 96.7%) and one case failed (failure rate 3.3%).Conclusion: Stem cells therapy is a new effective technique more safer successful, economic, easier to operate and time consuming than the traditional tympanoplasty. When the perforation is small to medium size maximum 4 X 4mm and dry since more than one month. This technique is better and to avoid complications and side effects of general anaethesia.

The role of simple office-based surgery in small central tympanic membrane perforation

ObjectiveThe aim of this study was to evaluate the outcome of simple office-based surgery in small central tympanic membrane (TM) perforation.BackgroundThe purpose of closure of TM perforations is to restore the continuity of the TM in order to improve hearing and decrease the risk of middle ear infections. Rapid and cost-effective procedures like chemical cauterization and fat plug myringoplasty have been found to be effective in healing small central perforations with significant hearing improvement.Patients and MethodsOur prospective study was carried out on 40 patients aged more than 15 years with dry small central persistent perforation during the period spanning from April 2017 to March 2018, divided in two groups: group A (20 patients underwent fat graft myringoplasty) and group B (20 patients underwent chemical cautery of the edge of perforation).ResultsOur study included 26 male patients and 14 female patients; the mean age was 27.2 ±9.3 years. Our study showed a 70% success rate in the healing of TM perforation in group A while there was a 55% success rate in group B.ConclusionFrom our study, we found that the two procedures are easy to perform, reliable with a satisfactory outcome, simple, rapid, risk free, and also lessen the financial burden and morbidity on the patient.

Novel transparent collagen film patch derived from duck’s feet for tympanic membrane perforation

To increase healing rate of tympanic membrane (TM) perforations, patching procedure has been commonly conducted. Biocompatible, biodegradable patching materials which is not limited across cultures is needed. The authors evaluated the effectiveness of novel transparent duck’s feet collagen film (DCF) patch in acute traumatic TM perforation. This procedure was compared with spontaneous healing and paper patching. Cell proliferation features were observed in paper and DCF patches. Forty-eight TMs of 24 rats were used for animal experiment, perforations were made on each TMs, and divided into three groups according to treatment modality. Sixteen were spontaneously healed, 16 were paper patched and 16 were DCF patched. The gross and histological healing results were analyzed. Both paper and DCF patch showed no cytotoxicity, but cell proliferations were more active in DCF than paper in early stage. In animal study, the healing of TM perforations were completed within 14 days in all three groups, but found to be faster in DCF patch group than paper patch or spontaneous healing group. The DCF patches were transparent and size of DCF patches were gradually decreased, so there were no need to remove the DCF patches to check the wound status or after the completion of healing. According to this result, authors concluded that DCF patch is transparent, biocompatible and biodegradable material, and can induce fast healing in acute traumatic TM perforations.

A Comparative Study of Endoscopic Myringoplasty vs Conventional Myringoplasty

ABSTRACT Objective To evaluate the efficacy of endoscopic myringoplasty and comparison with conventional myringoplasty. Materials and methods Sixty cases of clinically diagnosed chronic suppurative otitis media with dry central perforation were taken into account of which 30 cases were undergone endoscopic myringoplasty and 30 cases undergone conventional myringoplasty. All patients were followed up on 3rd, 7th, 15th day, 6th weeks, 3rd and 6th months after surgery. Results The tympanic membrane's perforation healing rate was 86% (26/30), in conventional group of myringoplasty and 83% (25/30) in endoscopic group of myringoplasty and average hearing gain in conventional group was 13.96 dB and in endoscopic group was 15.03 dB. Conclusion The surgical outcome of endoscope assisted myringoplasty in terms of graft uptake and hearing improvement was comparable to the conventional microscope assisted myringoplasty, but in terms of cosmesis and postoperative recovery patients in the endoscope group had better results. How to cite this article Kumar M, Kanaujia SK, Singh A. A Comparative Study of Endoscopic Myringoplasty vs Conventional Myringoplasty. Int J Otorhinolaryngol Clin 2015;7(3): 132-137.

Pediatric Tympanostomy Tube Removal Technique and Effect on Rate of Persistent Tympanic Membrane Perforation.

Tympanostomy tube removal is a commonly performed pediatric procedure. Few studies have evaluated whether removal technique influences the likelihood of the tympanic membrane (TM) to heal. To determine whether the technique used for tympanostomy tube removal affects the likelihood of persistent TM perforation healing in children. Retrospective case series with medical chart review in a tertiary care pediatric health system of 247 children undergoing tympanostomy tube removal (341 ears) between 2010 and 2013 by 1 of 4 different techniques: (1) tube removal only; (2) freshening TM perforation edges; (3) performing patch myringoplasty; or (4) both freshening edges and performing patch myringoplasty. Rate of persistent TM perforation after tympanostomy tube removal using the different removal techniques. Secondary outcomes included associations between persistent TM perforation and patient and tympanostomy tube characteristics. The overall persistent TM perforation rate was 10% (34 of 341 ears). Tube removal technique did not significantly influence likelihood for the TM to heal: perforations persisted in 11 of 97 ears (11%) with tube removal only, 6 of 68 ears (9%) with freshened TM perforation edges, 7 of 57 (12%) with patch myringoplasty, and 10 of 119 (8%) with both edges freshened and patch myringoplasty (P = .81). The mean (SD) age of patients with a persistent perforation at the time of tympanostomy tube removal was 8.5 (3.9) years vs 6.5 (3.2) years for those without a persistent perforation (P = .01). In patients with trisomy 21, there was a significantly higher rate of persistent TM perforation (OR, 8.65; 95% CI, 2.13-34.74; P = .002). Short-acting tubes were found to have a significantly lower rate of persistent TM perforation (13 of 194; 7%) than longer-acting tubes (9 of 41; 22%) (OR, 0.26; 95% CI, 0.09-0.71; P = .002). No reduction in persistent TM perforation rate was found following tympanostomy tube removal if TM edges were freshened and/or a patch myringoplasty was performed. Increased pediatric age, longer-acting tympanostomy tubes, and history of trisomy 21 may negatively influence likelihood of closure.

Pediatric Tympanostomy Tube Removal: Does Technique Affect the Rate of Persistent Tympanic Membrane Perforation?

Objectives: Determine whether various techniques used to promote tympanic membrane (TM) perforation closure at the time of ventilation tube removal impact the likelihood of TM perforation healing in children. Methods: A retrospective chart review was conducted of 265 children (341 ears) who underwent tympanostomy tube removal at a tertiary care pediatric hospital between January 2010 and November 2013. Techniques performed at the time of ventilation tube removal included tube removal only, freshening the perforation edges, performing paper patch myringoplasty, or both freshening edges and paper patch myringoplasty. Results: The persistent TM perforation rate was 9.97% (34/341). Technique was not found to significantly influence the likelihood for the TM to heal ( P = .81), with 11/86 (12.7%) having persistent perforations with tube removal only, 6/62 (9.7%) with freshened perforation edges, 7/50 (14.0%) with paper patch myringoplasty and 10/109 (9.2%) with both edges freshened and paper patch myringoplasty. There was no significant interaction between technique and age, tube retention length, number of previous ventilation tubes placed, or type of tube removed. Additionally, no significant difference in TM perforation rate was observed for number of previous tympanostomy tubes, tube duration, previous adenoidectomy, or indication for tube removal. Factors associated with higher rates of persistent perforation included older age, longer-acting ventilation tubes, and trisomy 21. Conclusions: There is no reduction in persistent TM perforation rate following ventilation tube removal if edges are freshened and/or a paper patch myringoplasty is performed. Increased pediatric age, longer-acting tympanostomy tubes and history of trisomy 21 may negatively influence the likelihood of closure.

Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice

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.

Collagen Type II Is Produced in Healing Pars Tensa of Perforated Tympanic Membranes

Type II collagen is synthesized in the tympanic membrane during healing of a perforation. The time course and appearance of Type II collagen regrowth in the newly healed tympanic membrane is the subject of the present study. The arrangement of Type II collagen fibers in the tympanic membrane gives it a unique tensile strength important for sound conduction. Healing after tympanic membrane perforation can cause the tympanic membrane to lose its characteristic. At what phase Type II collagen in tympanic membrane is replaced during healing of a perforation has previously not been studied. Rat tympanic membranes were perforated, and the animals were sacrificed 9 to 16 days after perforation. Tympanic membranes were stained with a Type II collagen antibody. At Day 9, a majority of the tympanic membranes had healed. Keratinizing epithelium and connective tissue had formed, but there was no Type II collagen. At Day 10, all tympanic membranes had healed, and staining for Type II collagen appeared. After Day 10, staining was more intense. Newly formed collagen did not show the parallel bundle arrangement seen in normal tympanic membranes but was more scattered in the tissue. Type II collagen was seen in tympanic membranes only after closure of the perforation. The fiber arrangement after healing was disturbed, which presumably has an impact on the function of the tympanic membrane. Understanding the formation of Type II collagen in the healing of tympanic membrane perforations could enable further research toward treating tympanic membrane perforations.

Effect of local irradiation with 630 and 860 nm low-level lasers on tympanic membrane perforation repair in guinea pigs

In this study, we evaluated the effect of low-level lasers on the healing of tympanic membrane perforation, one of the most common otological pathologies. Twenty-four guinea pigs were randomly assigned to either the experimental or control group. One day after the induction of a 2 mm diameter, centred myringotomy in all animals, the tympanic membranes in the experimental group were irradiated with 630 and 860 nm lasers for 10 days. Two weeks later, histological changes in the membranes were evaluated. Tympanic membrane thickening and inflammatory cell infiltration in the tympanic membranes and surrounding tissues were significantly less in the experimental group (p < 0.001). The distance from the external auditory canal wall to the malleus tip did not differ significantly between the two groups (p = 0.42). The results show that the combined application of 630 and 860 nm lasers had a significant effect on the healing of tympanic membrane perforation, and on the prevention of thick fibrotic or atelectatic neomembrane formation.

Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

Mice deficient in plasminogen, the precursor of plasmin, show completely arrested healing of tympanic membrane (TM) perforations, indicating that plasmin plays an essential role in TM healing. The activation of plasminogen to plasmin is performed by two plasminogen activators (PAs), urokinase-type PA (uPA) and tissue-type PA (tPA). To elucidate the functional roles of PAs in the healing of TM perforations, we investigated the phenotypes of single gene-deficient mice lacking uPA (uPA−/−) or tPA (tPA−/−) after TM perforation. Delayed healing of TM perforations was observed in uPA−/− mice but not tPA−/− mice. The migration of keratinocytes was clearly delayed and seemed to be misoriented in uPA−/− mice. Furthermore, fibrin deposition and the inflammatory response were persistent in these mice. Our findings demonstrate that uPA plays a role in the healing of TM perforations. The observed phenotypes in uPA−/− mice are most likely due to the reduced generation of plasmin.

Impact of basic fibroblast growth factor on healing of tympanic membrane perforations due to direct penetrating trauma: a prospective non‐blinded/controlled study

To investigate the effect of direct application of basic fibroblast growth factor (bFGF) on healing of tympanic membrane perforations due to direct traumatic penetration through the external auditory canal. A prospective non-blinded controlled study. University-affiliated teaching hospital. In total, 104 patients with small [<25%] penetrating perforations were recruited. They were alternatively allocated to two groups: Control (spontaneous healing, n = 51) and FGF treatment (direct application of bFGF drops in the clinic and repeated daily by the patient, n = 53). Perforation closure rate and time and hearing gain were recorded and compared between the two groups. Information on earache, dizziness and facial paralysis was also collected. In total, 93 (89%) patients were finally analysed. The closure rate at 3 m of the perforations in the control spontaneous healing and bFGF treatment groups were 77% and 100%, respectively; the difference was statistically significant (P = 0.01). The average closure time was 43.1 ± 2.5 days (range, 17-57 days) for control patients, which was significantly longer (P < 0.01) than that for the bFGF-treated patients (12.6 ± 1.2 days; range, 3-21 days). The mean hearing improvement at 3 m was not significantly different between the FGF treatment and control groups (1.7 ± 2.4 dB vs 11.5 ± 1.9 dB, P > 0.05). No significant difference was observed in earache, dizziness and facial paralysis between two groups. Direct application of bFGF may offer an effective topical management of penetrating traumatic tympanic membrane perforations, particularly for small-sized perforations.