epidermal-growth-factor and Tympanic-Membrane-Perforation

To review the history of moist therapy used to regenerate traumatic tympanic membrane perforations.. Literature review.. The literature on topical agents used to treat traumatic tympanic membrane perforations was reviewed, and the advantages and disadvantages of moist therapy were analysed.. A total of 76 studies were included in the analysis. Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic Solution, and insulin solutions) to the moist edges of traumatic tympanic membrane perforations shortened closure times and improved closure rates.. Dry tympanic membrane perforation edges may be associated with crust formation and centrifugal migration, delaying perforation closure. On the contrary, moist edges inhibit necrosis at the perforation margins, stimulate proliferation of granulation tissue and aid eardrum healing. Thus, moist perforation margins upon topical application of solutions of appropriate agents aid the regeneration of traumatic tympanic membrane perforations.

Topics: Epidermal Growth Factor; Fibroblast Growth Factor 2; Hyaluronic Acid; Intercellular Signaling Peptides and Proteins; Myringoplasty; Ofloxacin; Ointments; Regeneration; Solutions; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

To perform a contemporary review of experimental studies to describe the effects of various novel adjuvant therapies in enhancing tympanic membrane (TM) perforation healing.. A PubMed search for articles from January 2000 to June 2012 related to TM perforation, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to TM healing.. Many studies have assessed the efficacy of biomolecules or growth factors, such as epidermal growth factors and basic fibroblast growth factors, in TM regeneration with significant success. More recent strategies in TM tissue engineering have involved utilizing bioengineered scaffold materials, such as silk fibroin, chitosan, calcium alginate, and decellularized extracellular matrices. Most scaffold materials demonstrated biocompatibility and faster TM perforation healing rates.. Although several studies have demonstrated promising results, many questions still remain, such as the adequacy of animal models and long-term biocompatibility of adjuvant materials. As well, further studies comparing various adjuvant substances and bioscaffolds are required prior to clinical application.

Topics: Animals; Biocompatible Materials; Chemotherapy, Adjuvant; Disease Models, Animal; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fibroins; Humans; Needs Assessment; Randomized Controlled Trials as Topic; Risk Assessment; Tissue Engineering; Tissue Scaffolds; Treatment Outcome; Tympanic Membrane Perforation; Wound Healing

Basic scientific research has demonstrated that epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA) and transforming growth factor-alpha (TGF-alpha) are induced by acute tympanic membrane (TM) perforation. The expression of these growth factors peaks during the inflammatory phase and then declines, suggesting their involvement in the healing process of the TM. Expression of EGF receptor, bFGF receptor, PDGF receptor and keratinocyte growth factor (KGF) receptor in the TM has also been reported. Identification of these receptors indicates that the target cells in the TM may be stimulated during the process of healing by the corresponding exogenous growth factor in vivo. Some reports from animal studies showed encouraging effects of EGF, bFGF and PDGF-AA in terms of accelerated or enhanced healing of acute and chronic TM perforations without significant adverse effects. Two reports of clinical trials of topical application of EGF or bFGF for TM perforations revealed mixed results. In this article special considerations for future directions of research into growth factors are discussed and related articles on healing of skin wounds and other lesions are reviewed. Further experimental and clinical studies on the mechanism of action of growth factors, timing of application, selection (either singly or in combination), delivery mode, dose and safety aspects, as well as more clinical trials, are warranted, and will pave the way for clinical application.

Topics: Animals; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Growth Substances; Humans; Platelet-Derived Growth Factor; Transforming Growth Factors; Tympanic Membrane Perforation; Wound Healing

Recent experiments have shown the healing potential of growth factors in tissue repair. Epidermal interference and fibroblast growth factors in the healing of acute and chronic tympanic membrane perforations are reviewed and discussed.

Topics: Acute Disease; Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factor 2; Growth Substances; Humans; Regeneration; Tympanic Membrane Perforation

An immense amount of knowledge has been gained over the last decade in the realm of polypeptide growth factors. Only recently has this new information made an impact in otolaryngology. This article is a brief overview of peptide growth factors in relation to wound healing and otolaryngology.

Topics: Animals; Bone and Bones; Epidermal Growth Factor; Growth Substances; Humans; Platelet-Derived Growth Factor; Transforming Growth Factor beta; Tympanic Membrane Perforation; Wound Healing

To compare the outcomes of epidermal growth factor (EGF) and gelatin sponge patch treatments for traumatic tympanic membrane perforations.. Prospective, randomized, controlled.. University-affiliated teaching hospital.. In total, 141 perforations encompassing >50% of the eardrum were randomly divided into 3 groups: EGF (n = 47), gelatin sponge patch (n = 47), and observation (n = 47). The edges of the perforations were not approximated. The closure rate, mean closure time, and infection rate were evaluated at 6 months and the related factors analyzed.. A total of 135 perforations were analyzed. At 6 months, the closure rates were 97.8%, 86.7%, and 82.2% in the EGF, gelatin sponge patch, and spontaneous healing groups, respectively (. As compared with spontaneous healing, daily application of EGF and gelatin sponge patching reduced the closure time of traumatic tympanic membrane perforations. EGF treatment had a higher closure rate and shorter closure time but resulted in otorrhea. By contrast, gelatin sponge patches did not improve the closure rate or cause otorrhea but required repeated patch removal and reapplication. Thus, the appropriate treatment should be selected according to patient need.

Topics: Adult; Epidermal Growth Factor; Female; Gelatin Sponge, Absorbable; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Tympanic Membrane; Tympanic Membrane Perforation

Traumatic tympanic membrane perforations (TMPs) tend to spontaneous healing, however, large TMPs usually fail to healing. Clinical and experimental studies had demonstrated that growth factors accelerated the healing of large TMPs. The aim of this study was to compare the effects of growth factors and 0.3% (w/v) ofloxacin drops n the healing of human large TMPs.. A total of 184 human large traumatic TMPs were randomly assigned to receive epidermal growth factor (EGF) treatment, fibroblast growth factor-2 (FGF-2) treatment, 0.3% (w/v) ofloxacin drops treatment, and conservative observation (only).. A total of 180 patients were analyzed in this study at the 6-month follow-up. The closure rates of the perforations in the EGF, FGF-2, 0.3% (w/v) ofloxacin drops, and conservative observation groups were 91.11%, 93.18%, 95.65%, and 82.22%, respectively, the closure rates did not significantly differ among the groups (P = .165). Similarly, pairwise comparisons did not reveal any significant between-group differences (P > .0083). However, the difference of the mean closure time was significant among the 4 groups (P < .001), pairwise comparisons showed that closure time was significantly longer in the observational group than in the other 3 groups (P < .001). Nevertheless, no significant difference in mean closure time was evident between any 2 treated groups (P > .0083). The mean hearing gain after 6 months was 11.49 ± 5.88 dB for the EGF group, 10.89 ± 5.16 dB for the FGF-2 group, 10.54 ± 5.56 dB for the ofloxacin group, and 9.29 ± 5.36 dB for the observation group. Differences in hearing improvement rates among the 4 groups were not statistically significant (P = .283).. Epidermal growth factor, FGF-2, and 0.3% (w/v) ofloxacin drops accelerated the closure of large TMPs compared with conservative treatment. Surprisingly, neither the closure rate nor closure time differed significantly among the 3 treated groups. Further experimental studies to demonstrate whether 0.3% (w/v) ofloxacin per se accelerates the healing of TMPs will be interesting in the future.

Topics: Administration, Topical; Adult; Conservative Treatment; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Hearing Tests; Humans; Intercellular Signaling Peptides and Proteins; Male; Ofloxacin; Recovery of Function; Time Factors; Treatment Outcome; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

We evaluated the effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on the healing of large traumatic tympanic membrane perforations (TMPs).. Prospective clinical study.. Tertiary university hospital.. A randomized, prospective analysis was performed between June 2013 and August 2014 on the treatment of traumatic TMPs larger than 25% of the TM. Closure rate, closure time, hearing gain, and rate of otorrhea were compared between EGF and bFGF groups, as well as to an observation-only group.. Final analysis was performed on 86 patients at 3 months. The closure rates of perforation in the EGF, bFGF, and observation groups were 86.2%, 89.3%, and 72.4%, respectively. The closure rates in the EGF and bFGF groups were 14% to 17% higher than in the observation group, although the difference was not statistically significant for the total closure rate among the three groups (P = 0.200). The average closure time was significantly longer (P < 0.01) in the observation group than in the EGF and bFGF groups. However, the closure times in the EGF and bFGF groups were not significantly different (P = 0.92). In addition, differences in purulent otorrhea rates among the groups were not statistically significant (P = 0.82).. Both EGF and bFGF can accelerate the closure of human large traumatic TMPs. The healing outcomes among the two growth factors were not significantly different.

Topics: Administration, Topical; Adolescent; Adult; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing; Young Adult

We evaluated the effects of conservative treatment and topical application of epidermal growth factor (EGF) with no scaffold material on the healing of human traumatic tympanic membrane perforations (TMPs).. Prospective, randomised clinical trial.. A prospective analysis was performed between January 2015 and March 2015 for the treatment of human traumatic TMPs. The closure rate, closure time, hearing gain and rate of purulent otorrhoea were compared between the topical application of EGF and conservative treatment.. In total, 97 patients were analysed. The total closure rates did not significantly differ between the observation and EGF groups (83.0% versus 92.0%, P = 0.182). The total average closure time in the observation group was significantly longer than in the EGF group (25.1 ± 10.5 versus 11.7 ± 5.2 days, P = 0.001). When the closure rate was evaluated according to perforation size, no significant difference was seen for medium or large perforations (P = 0.18 and 0.21, respectively). When closure time was evaluated according to perforation size, a significant difference was seen for medium and large perforations (P = 0.001).. This study suggests that topical application of EGF with no scaffold material may significantly shorten the closure time of human traumatic TMPs. Such a shorter recovery time may lead to reduced healthcare costs. This alternative technique to a classic myringoplasty is particularly beneficial and suitable for the closure of large human traumatic TMPs.

Topics: Administration, Topical; Adult; China; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Tympanic Membrane Perforation; Wound Healing; Young Adult

Tympanic membrane perforations are very common and often require surgical treatment. Recent studies have suggested that growth factors may be an effective nonsurgical alternative for treating chronic perforations. The purpose of this study was to assess the efficacy of a platelet releasate in the treatment of chronic nonhealing perforations in the chinchilla model.. Bilateral perforations were created in 47 chinchillas by excising 80% of the tympanic membrane with a thermal myringotomy knife. Bilateral perforations > 50% of its surface area persisted for 10 weeks in 34 animals, and unilateral perforations > 50% of its surface area, in nine animals. Only animals with bilateral chronic perforations were included in this study. After deepithelializing the perforation and packing the middle ear and external ear canals with Gelfoam, we treated the perforations with either platelet releasate or buffered saline. Each animal served as its own control.. The tympanic membranes were evaluated over a 12-week period by microscopy, photography, tympanometry, and histology. No statistical difference between treated and control ears in the incidence of perforation closure was evident. Histologically, the treated tympanic membranes consistently had a thicker fibrous layer than the controls.. These data suggest that platelet releasate is not effective in enhancing closure of chronic tympanic membrane perforations in the chinchilla model.

Topics: Animals; Chinchilla; Epidermal Growth Factor; Tympanic Membrane Perforation; Wound Healing

Topics: Adult; Epidermal Growth Factor; Female; Hearing; Humans; Male; Middle Aged; Regeneration; Retrospective Studies; Tympanic Membrane Perforation

Chronic tympanic membrane (TM) perforations can cause otorrhea. To date, various types of tissue engineering techniques have been applied for the regeneration of chronic TM perforations. However, the application of nanofibers with radially aligned nanostructures and the simultaneous release of growth factors have never been applied in the regeneration of chronic TM perforations. Here, epidermal growth factor (EGF)-releasing radially aligned nanofibrous patches (ERA-NFPs) are developed and applied for the regeneration of chronic perforated TMs. First, radial alignments and the presence of EGF in the ERA-NFPs are analyzed. EGF is confirmed to be released from the ERA-NFPs until 8 weeks. In an in vitro study, cell viability assay, immunocytochemistry, and wound-healing assay indicate rational enhancement of healing by the combination of radial alignments and EGF release. The effect of ERA-NFPs on TM cells is revealed by quantitative real-time polymerase chain reaction. An in vivo animal study shows that the ERA-NFPs effectively stimulates the healing of the chronic TM perforations. The TMs healed by ERA-NFPs show histological properties similar to those of normal TMs. These results indicate that ERA-NFPs may be an efficient platform for the regeneration of chronic TM perforations, laying the foundation for nonsurgical treatments of chronic otitis media.

Topics: Animals; Cell Survival; Drug Liberation; Epidermal Growth Factor; Female; Gene Expression Regulation; Guided Tissue Regeneration; Microscopy, Electron, Scanning; Nanofibers; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Tympanic Membrane Perforation

Damage to the eardrum causes acute pain and can lead to chronic otitis media if it develops into chronic tympanic membrane (TM) perforations. Chronic TM perforations are usually treated with surgical methods such as tympanoplasty and myringoplasty. However, these surgeries are not only complicated and difficult but also cost a lot of money. Our research team developed chitosan patches (E-CPs) that release epidermal growth factor (EGF) as a patch therapy to replace surgical methods. However, there was a limitation in the healing ratio of the treatment compared to the surgical methods. In this study, we developed EGF and epidermal growth factor receptor (EGFR) gene-releasing polyethyleneimine (PEI)/chitosan patches (EErP-CPs) to increase the regeneration of TM perforations. The addition of PEI increased the adhesion and migration ability of TM cells on the patches. The simultaneous release of the EGF and the EGFR gene further enhanced TM cell proliferation, adhesion and migratory ability. It was confirmed that the EGF protein and EGFR gene were released for 30 days; however, EGF was released and increased TM cell viability almost immediately after treatment and EGFR took a minimum of 3 days before showing its effect on improved cell viability. It was also shown that EErP-CPs are more hydrophilic and have more positive charge than E-CP because of added amine groups from PEI. In conclusion, the developed EErP-CPs resulted in the improved healing of TM perforations and can potentially be applied to the regeneration of both chronic and acute tympanic membrane perforations.

Topics: Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Chitosan; Drug Carriers; Epidermal Growth Factor; Polyethyleneimine; Rats; Rats, Sprague-Dawley; Regeneration; Tympanic Membrane; Tympanic Membrane Perforation

Topics: Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

Topics: Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

The 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.. Seventy 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.. HGF 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.. High 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.

Topics: Animals; Biomarkers; Blotting, Western; Epidermal Growth Factor; Hepatocyte Growth Factor; Male; Random Allocation; Rats; Rats, Wistar; Tympanic Membrane Perforation; Vascular Endothelial Growth Factor A; Wound Healing

That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.. A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.. The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks.. The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.. This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

Topics: Animals; Chronic Disease; Drug Delivery Systems; Epidermal Growth Factor; Fibroblast Growth Factor 2; Heparin-binding EGF-like Growth Factor; Hydrogels; Male; Mice; Mice, Inbred CBA; Polymers; Tympanic Membrane Perforation; Wound Healing

To investigate the effect of hyaluronic acid (HA) associated to fat graft on growth factors expression during the healing process of tympanic membrane (TM) perforations in guinea pigs using the hyaluronic acid fat graft myringoplasty (HAFGM) technique.. Prospective randomized animal study.. Thirty guinea pigs were divided equally into three groups: group I (control group), group II (fat graft myringoplasty technique), and group III (HAFGM technique). TMs were perforated on day 1 and then sampled on days 0, 3, 8, and 21 and tested for the expression of: epidermal growth factor (EGF), insulin-like growth factor (IGF), tumor necrosis factor α (TNF α), vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF). Five perforated TMs were taken at day 0 from group I to serve as a reference level.. Group III showed an increased expression of all tested growth factors, except for KGF. EGF was highest in the early healing process; then IGF peaked at day 8 with statistically significant increase compared to groups I and II. TNF α in group III was significantly higher than group I throughout the study, with a peak level at day 21. VEGF was significantly higher in group III compared to group I at days 3 and 21. Neovascularization and scarless TM closure was obtained in group III, while spontaneous closure was associated with thin-layered and scarred TM in group I.. HA association to fat graft in perforated TM increases the expression of the endogenous growth factors, suggesting that such an association is advantageous for healing.. N/A.

Topics: Adipose Tissue; Animals; Biomarkers; Disease Models, Animal; Epidermal Growth Factor; Graft Survival; Guinea Pigs; Hyaluronic Acid; Intercellular Signaling Peptides and Proteins; Male; Myringoplasty; Neovascularization, Physiologic; Otoscopy; Random Allocation; Reproducibility of Results; Sensitivity and Specificity; Somatomedins; Surgical Flaps; Tumor Necrosis Factor-alpha; Tympanic Membrane; Tympanic Membrane Perforation; Vascular Endothelial Growth Factor A; Wound Healing

Most chronic tympanic membrane (TM) perforations require surgical interventions such as tympanoplasty because, unlike with acute perforations, it is very difficult for the perforations to heal spontaneously. The purpose of this study was to develop novel therapeutic techniques and scaffolds that release growth factors to treat chronic TM perforations. We evaluated the cell proliferation effects of the epidermal growth factor (EGF) and fibroblast growth factor (FGF) on in vitro cultures of TM cells using an MTT assay. They both showed similar efficacy, so we used EGF because of its lower cost. We then constructed an EGF-releasing chitosan patch scaffold (EGF-CPS) based on previous studies. We analyzed its toxicity and strength, and we studied it using scanning electron microscopy. EGF was released from the EGF-CPS for 8 weeks in an in vitro system. In animal studies, the EGF group, which was treated with EGF-CPS, showed healing in 56.5% of the animals (13/23), while the control group, which did not receive any treatment, revealed 20.8% healing (4/24) (p=0.04). Transmission electron microscopic studies of regenerated eardrums in the EGF group showed much greater preservation of histological features, and TMs of the EGF group were thinner than spontaneously healed TMs. In conclusion, this novel EGF-CPS can be used as a nonsurgical intervention technique for treatment of chronic TM perforations.

Topics: Animals; Cell Survival; Chitosan; Epidermal Growth Factor; Female; Rats; Rats, Sprague-Dawley; Tympanic Membrane Perforation; Wound Healing

Topics: Animals; Chitosan; Epidermal Growth Factor; Female; Tympanic Membrane Perforation

Topics: Animals; Chitosan; Epidermal Growth Factor; Female; Tympanic Membrane Perforation

Topics: Epidermal Growth Factor; Humans; Recombinant Proteins; Tympanic Membrane; Tympanic Membrane Perforation

Topics: Adolescent; Adult; Aged; Endoscopes; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Treatment Outcome; Tympanic Membrane Perforation; Young Adult

Office treatment for chronic tympanic membrane (TM) perforations has limitations, and alternative methods to myringoplasty are sometimes needed. Serum lacks antigenicity and contains a large variety of growth factors known to modulate proliferation of various tissues to promote wound healing effects. Our purpose was to evaluate the feasibility of autologous serum eardrops therapy with a chitin membrane for closing TM perforations.. In the outpatient clinic, the perforation margin was cauterized with silver nitrate, and the perforation was covered with a chitin membrane. Patients were instructed to apply autologous serum eardrops daily. Patients were examined every 2 weeks, and the procedure was repeated.. We treated 19 sequential patients with chronic TM perforation in 1 ear between October 2005 and September 2007. Closure of the TM was achieved in 11 (58%) of 19 ears, and reduction of the perforation size was observed in 2 ears (11%). Closure rates for small, medium, and large perforations were 57 (8 of 14), 0 (0 of 1), and 75% (3 of 4), respectively. Closure rates for perforations attributable to intratympanic dexamethasone treatment, after myringoplasty and chronic otitis media were 67 (2 of 3), 67 (2 of 3), and 54% (7 of 13), respectively. Time for closure took from 15 to 175 days, with an average of 68 days (5.9 clinic visits). During autologous serum eardrop therapy with a chitin membrane, no remarkable side effects in the treated ears were observed. Measurement of the concentration of the epidermal growth factor, transforming growth factor beta1, fibronectin, and interleukin 6 in the serum showed no decrease in 14 days, suggesting activity remained stable in that period.. Autologous serum eardrops therapy with a chitin membrane, which requires no surgical intervention, was found to be a promising office-based technique for the closure of chronic TM perforations because of its ease, safeness, and feasibility. However, additional studies are needed to independently analyze the specific benefits of the serum drops and the chitin membrane.

Topics: Administration, Topical; Adolescent; Aged; Chitin; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fibronectins; Humans; Interleukin-6; Male; Middle Aged; Polymers; Serum; Transforming Growth Factor beta1; Tympanic Membrane Perforation; Young Adult

The aims of the present study were to determine the effect of epidermal growth factor (EGF) and pentoxifylline on subacute tympanic membrane (TM) perforations and to quantify the healing rate of such perforations treated with these drugs alone or in combination.. It is known that EGF modulates in vitro and in vivo proliferation of epithelial and endothelial cells. Pentoxifylline is a methylxanthine that has been used to treat experimental skin flaps and venous leg ulcers. Data in the literature regarding this subject are contradictory, and quantitative data regarding the effects of EGF and pentoxifylline on TM perforation healing are scarce.. We studied 50 chinchillas submitted to TM perforation. On postoperative Day 30, eight were selected for histologic analysis. Of the remaining 42, those presenting little or no healing were distributed into four groups: control, EGF, pentoxifylline, and EGF combined with pentoxifylline.. Histologic analysis showed that the observation period adopted was sufficient to consider the TM perforations subacute. We found significant differences between the study groups and the control group in the healing rate of subacute TM perforations during a 30-day period (analysis of variance; p < 0.001), which was 30.3% for the EGF group, 3.6% for the pentoxifylline group, 16.5% for the EGF-pentoxifylline group, and 8.7% for the control group.. The use of EGF promoted healing of subacute TM perforations in chinchillas, and the use of pentoxifylline did not. The combination of the two had no synergistic effect on the healing of these perforations.

Topics: Analysis of Variance; Animals; Anti-Bacterial Agents; Chinchilla; Drug Therapy, Combination; Epidermal Growth Factor; Female; Male; Pentoxifylline; Treatment Outcome; Tympanic Membrane; Tympanic Membrane Perforation; Vasodilator Agents; Wound Healing

The aim of this study was to evaluate the effects of an alginate matrix releasing epidermal growth factor on healing after acute tympanic membrane perforation in rats.. A total of 20 male rats were divided into two groups. In each animal, a randomly chosen tympanic membrane was perforated by heat. A piece of alginate matrix (control group) or alginate matrix loaded with 0.25 microg epidermal growth factor (EGF group) was then placed on the perforation. The rat ears were examined after days 3, 6, 9, and 14 and every week thereafter for a total of 11 weeks. Each matrix was removed on day 9. To examine the status of the tympanic membranes on day 14, one randomly chosen membrane from each group was histopathologically examined.. By day 6, complete closure of the tympanic membrane perforation was achieved in 56% of the EGF group, whereas it was achieved in only 10% in the control group. By day 14, all tympanic membrane perforations were closed in both groups. There were no complications and no significant differences in the histopathologic parameters between the EGF group and the control group.. An alginate matrix seems to be a useful EGF-delivery system to the tympanic membrane.

Topics: Administration, Topical; Alginates; Animals; Biocompatible Materials; Drug Carriers; Drug Implants; Epidermal Growth Factor; Glucuronic Acid; Hexuronic Acids; Male; Materials Testing; Membranes, Artificial; Rats; Treatment Outcome; Tympanic Membrane Perforation; Wound Healing

Topics: Acute Disease; Alginates; Animals; Biocompatible Materials; Drug Carriers; Drug Implants; Epidermal Growth Factor; Glucuronic Acid; Hexuronic Acids; Male; Materials Testing; Membranes, Artificial; Rats; Treatment Outcome; Tympanic Membrane Perforation; Wound Healing

To evaluate the possible roles of epidermal growth factor(EGF) and its receptor (EGFR) on the chronic tympanic membrane perforations.. A phosphate buffer saline of EGFR was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in guinea pigs. The EGFR of 10 specimens from the acquired middle ear cholesteatoma of the adjacent skin around perforation was examined by immunohistochemical SP method and computer image analysis. Results Complete closure of the tympanic membrane perforations was observed in 82.6% of EGF-treated ears, but only 33.3% in the controls(P < 0. 01). No case was led to middle ear cholesteatoma in the experiment group (0/23). The positive expression in the adjacent skin around perforation was (39.3 -/+ 7.4)%; and the normal external ear skin was (25.4 +/- 3.7)%; There were distinctly significant differences between the adjacent skin around perforation and the normal external ear skin (P < 0. 01).. EGF is effective on closing chronic tympanic membrane perforations in the guinea pigs. Present data suggests that EGF-treated may induce the occurrence of middle ear cholesteatoma.

Topics: Animals; Epidermal Growth Factor; ErbB Receptors; Guinea Pigs; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

The goal of this study was to evaluate the effects of hyaluronic acid, epidermal growth factor, and mitomycin C on the healing of acute experimental traumatic perforations of the tympanic membrane.. Most acute perforations of the tympanic membrane heal spontaneously. However, some form of surgical treatment (i.e., myringoplasty) is needed for nonhealing perforations. Because the closure occurs by squamous epithelial migration, drugs that stimulate this regenerative process may aid in the closure of the perforation, obviating the need for more extensive treatments.. Bilateral perforations of the tympanic membrane were created in 30 rats, divided into three groups (A, B, C). The perforations in the right ears were treated with hyaluronic acid, epidermal growth factor, or mitomycin C. Those in the left ears were left untreated for comparison. To examine the healing process in different periods, 5 animals were killed in each group at days 3, 5, 7, 9 and 14. The other 5 animals in each group were observed daily to determine the duration of perforation closures. Thirty surgical specimens (5 right sides from each group and all 15 left sides in all groups) were histopathologically examined for tympanic membrane thickness, fibroblastic reaction, neovascularization, and crust morphology.. Hyaluronic acid and epidermal growth factor applications significantly shortened the healing in acute experimental traumatic perforations of the tympanic membrane (p = 0.0432); however, the difference between them was not significant (p = 0.3160). On the other side, tympanic membrane perforations treated with topical mitomycin C showed no evidence of closure. There were no significant differences in the histologic parameters between the treated groups and their contralateral control ears.. Hyaluronic acid and epidermal growth factor accelerated the closure of acute tympanic membrane perforations in rats. This may make them clinically useful in augmenting the efficiency of conservative treatments of acute perforations of the tympanic membrane.

Topics: Adjuvants, Immunologic; Animals; Anti-Ulcer Agents; Antibiotics, Antineoplastic; Epidermal Growth Factor; Fibroblasts; Hyaluronic Acid; Mitomycin; Random Allocation; Rats; Regeneration; Tympanic Membrane; Tympanic Membrane Perforation

Large tympanic membrane perforations usually require a surgical tympanoplasty for closure. Reducing surgical costs and risks has encouraged investigators to examine nonsurgical office procedures for healing these perforations. Growth accelerators are the most promising agents. We study here the closure of large acute perforations using weekly applications of 1 mg of 1% hyaluronic acid (HA), 0.4 microg basic fibroblast growth factor (bFGF), or 1.0 microg epidermal growth factor (EGF) directly to the tympanic membranes of the experimental ears. Control ears were treated with 0. 1 mL Vasocidin. Complete closure was obtained in 100% of the ears treated with HA and EGF and 85.7% of those treated with bFGF by day 21, compared with 63.6% of the controls by day 32. Moderate-to-severe ipsilateral and contralateral external canal hypertrophy was noted in 14.2% and 37.5% of the ears treated with bFGF and HA, respectively, but was not seen in ears treated with EGF or in the control group.

Topics: Adjuvants, Immunologic; Animals; Epidermal Growth Factor; Evaluation Studies as Topic; Female; Fibroblast Growth Factor 2; Guinea Pigs; Hyaluronic Acid; Male; Random Allocation; Treatment Outcome; Tympanic Membrane Perforation; Wound Healing

In the present structural study the authors investigated the border of permanent tympanic membrane (TM) perforations in patients selected for myringoplasty. Furthermore, a panel of monoclonal antibody markers that recognize different epitopes within glycosaminoglycans as well as antibodies to epidermal growth factor and fibronectin were applied to the sections. In half of the specimens the epithelial junction ended at the inside of the perforation border, whereas in the other half it was located at the perforation border itself. In the junctional area the keratinocytes were covered by a thick keratin layer which protruded as a spur centripetally in order to bridge the perforation. Epidermal cells formed papillae and contained remnants of keratinocyte nuclei that showed similarities to those of the skin in inflammatory conditions. The connective tissue layer was fibrous and showed areas containing sclerotic plaques. The inner epithelium of the TM had abundant ciliae, thus supporting the concept that cells of the mucosal lining of the TM are able to differentiate in inflammatory conditions into ciliated cells and secretory cells. The immunoreactivity of hyaluronan and other glycosaminoglycans, the immunoreactivity of epidermal growth factor, and immunoreactivity of fibronectin, all of which are known to occur in healing wounds, were only scantily demonstrated; this could be one reason for the arrested healing and a reason why the natural drive to complete a mature closure is abandoned.

Topics: Biomarkers; Epidermal Growth Factor; Epithelium; Fibronectins; Glycosaminoglycans; Humans; Immunohistochemistry; Keratinocytes; Middle Aged; Tympanic Membrane; Tympanic Membrane Perforation; Wound Healing

Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF-2) have been shown to enhance the healing of traumatic tympanic membrane (TM) perforations. The action of EGF and bFGF in the TM repair process remains unknown. This study was designed to determine the expression of EGF and bFGF in normal and injured TM by immunohistochemistry. EGF was detected in normal TM mainly in the annulus tympani area. After a perforation in the TM posterior/superior quadrant, EGF was detected around the perforated area in polynuclear cells, in pericytes and in basal epithelial cells. EGF was also detected in the antero/superior quadrant in basal epithelial cells and pericytes. The peak of EGF detection was observed 3 days after the perforation. bFGF was not detected in normal TM, but it was expressed 3 days after a traumatic perforation mainly in the perforated area in pericytes and in polynuclear cells. This study suggests that EGF and bFGF are involved in the control of TM acute perforation repair. These findings help to explain the accelerated healing of TM perforations that are seen after application of FGF or EGF, and suggest that antibodies against these growth factors would retard the healing process.

Topics: Animals; Culture Techniques; Ear, Middle; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Guinea Pigs; Immunohistochemistry; Tympanic Membrane; Tympanic Membrane Perforation

In an earlier study, epidermal growth factor (EGF) was shown to be effective in healing chronic tympanic membrane (TM) perforations in the chinchilla. The original protocol required rimming of the perforation's epithelial edge, application of a paper patch, placement of a Gelfoam pledget, and then administration of EGF solution. To develop a simple outpatient method of healing chronic TM perforations, an attempt was made to simplify the treatment protocol while preserving efficacy. In the modified experimental protocol, a large Gelfoam pledget was placed over the chronic perforation in contact with the residual TM, without mechanical disruption of the perforation edge or use of a paper patch. Then EGF in phosphate buffered saline (PBS) was applied to the Gelfoam pledget (50 microL of 0.5 mg EGF/mL PBS). A series of control ears received Gelfoam pledgets and PBS. Complete closure of the TM perforation was achieved in 80 percent (12/15) of treated ears but in only 20 percent (3/15) of controls (p < 0.01), results similar to those obtained with the original protocol. At long-term follow-up, 4 to 9 months after treatment, EGF-healed TMs were histologically similar to normal TMs, both in their overall thickness and in the relative proportions of the three component layers. In contrast, the few spontaneously healed TMs from the control group were less than half the thickness of normal TMs. To ascertain the optimal EGF concentration for therapeutic effect, a dose ranging study was undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Chi-Square Distribution; Chinchilla; Chronic Disease; Epidermal Growth Factor; Male; Myringoplasty; Organ of Corti; Recombinant Proteins; Tympanic Membrane Perforation; Wound Healing