Chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a leading global cause of potentially preventable hearing loss in children and adults, associated with socioeconomic deprivation. There is an absence of consensus on the definition of CSOM, which complicates efforts for prevention, treatment, and monitoring. CSOM occurs when perforation of the tympanic membrane is associated with severe or persistent inflammation in the middle ear, leading to hearing loss and recurrent or persistent ear discharge (otorrhoea). Cholesteatoma, caused by the inward growth of the squamous epithelium of the tympanic membrane into the middle ear, can also occur. The optimal treatment of discharge in CSOM is topical antibiotics. In resource-limited settings where topical antibiotics might not be available, topical antiseptics are an alternative. For persistent disease, surgery to repair the tympanic membrane or remove cholesteatoma might offer long-term resolution of otorrhoea and potential improvement to hearing. Recent developments in self-fitted air-conduction and bone-conduction hearing aids offer promise as new options for rehabilitation.

Decellularized tympanic membrane scaffold with bone marrow mesenchymal stem cells for repairing tympanic membrane perforation.

BACKGROUND: Tympanic membrane perforation (TMP) is a common disease in otology, and few acellular techniques have been reported for repairing this condition. Decellularized extracellular matrix (ECM) scaffolds have been used in organ reconstruction. OBJECTIVE: This study on tissue engineering aimed to develop a tympanic membrane (TM) scaffold prepared using detergent immersion and bone marrow mesenchymal stem cells (BMSCs) as repair materials to reconstruct the TM. RESULTS: General structure was observed that the decellularized TM scaffold with BMSCs retained the original intact anatomical ECM structure, with no cell residue, as observed using scanning electron microscopy (SEM), and exhibited low immunogenicity. Therefore, we seeded the decellularized TM scaffold with BMSCs for recellularization. Histology and eosin staining, SEM and immunofluorescence in vivo showed that the recellularized TM patch had a natural ultrastructure and was suitable for the migration and proliferation of BMSCs. The auditory brainstem response (ABR) evaluated after recellularized TM patch repair was slightly higher than that of the normal TM, but the difference was not significant. CONCLUSION: The synthetic ECM scaffold provides temporary physical support for the three-dimensional growth of cells during the tissue developmental stage. The scaffold stimulates cells to secrete their own ECM required for tissue regeneration. The recellularized TM patch shows potential as a natural, ultrastructure biological material for TM reconstruction.

Mesenchymal Stem Cells for Treatment of Delayed-Healing Tympanic Membrane Perforations Using Hyaluronate-based Laminas as a Delivery System: An Animal Model With Histopathologic Study.

HYPOTHESIS: Bone marrow derived-mesenchymal stem cells (BM-MSCs) improve the healing of chronic tympanic membrane perforations (cTMPs) in an animal model. BACKGROUND: cTMPs generate significant morbidity and reduced quality of life, usually requiring surgical assistance. With growing interest in alternative therapies, we sought to evaluate the effect of BM-MSC-therapy on the healing of cTMPs. METHODS: Sixty cTMPs were established in C57Bl/6 mice and randomized into four groups: hyaluronate scaffold as graft plus BM-MSCs (n = 19 ears), scaffold plus cell culture media (n = 16), scaffold plus phosphate-buffered saline (PBS, n = 12), and no intervention (n = 13). Hyaluronate scaffolds with or without BM-MSCs were applied on 8-week perforated eardrums. After a blinded assessment of perforation sizes at baseline and 2 weeks after treatment, mean perforation reduction rates (%) were compared. Histology characterization was then performed. RESULTS: Mean perforation size reduction rates were significantly higher for cTMPs that received scaffolds plus BM-MSCs (Student's t test, p = 0.0207, 12.3% [95% CI: 7.8-16.7]) and scaffolds plus cell culture media (p = 0.0477, 11.3% [95% CI: 4.4-18.2]) when compared with no intervention (4.2% [95% CI: 1.2-7.2]). This was not observed when treating eardrums with scaffolds plus PBS (7.3% [95% CI: 2.7-11.9]). On histology, BM-MSC-treated eardrums demonstrated restoration of the trilaminar configuration and reduced inflammatory changes, while other groups developed tissue architecture disorganization and hypercellular infiltrates surrounding the perforation site. CONCLUSIONS: BM-MSCs and cell culture media equivalently increased cTMP healing rates. Cell-based therapy conferred a restoration of the trilaminar configuration of the eardrum with relatively compact and organized fibrous layers.

Bioprinted Collagen-Based Cell-Laden Scaffold With Growth Factors for Tympanic Membrane Regeneration in Chronic Perforation Model.

With the recent development of bioprinting technology, various attempts have been made to replace bioprinting technologies and regenerative medicine are more directed towards transplantation/reconstructive surgeries only with the implantation of scaffolds. The purpose of this study is to determine whether the growth factors, human umbilical cord serum (hUCS) and bFGF (basic fibroblast growth factor), have a synergistic effect on eardrum regeneration, when used with a cell-printed scaffold in a chronic tympanic membrane perforation (TMP) model. In this study, in vitro cellular activities for bioprinted cell-laden collagen scaffolds using human adipose stem cells (hASCs) and supplemented with 10 [Formula: see text]/mL hUCS and 10 ng/mL bFGF were performed. The mixture of the growth factors in the cell-laden structures effectively affects various in vitro cellular responses including the proliferation of hASCs and the migration of keratinocytes due to the synergistic effect of the growth factors and hASCs. For the in vivo evaluation, a rat TMP model was used, and the TMP regeneration was assessed by otoscopic examination, hearing threshold measurement, and histologic examination. Although the cell-laden structure containing hUCS was more enhancing effect compared to the structure with bFGF, more synergistic effect in the structure using hUCS/bFGF was observed. Based on the results, we believe that the cell-laden structure incorporating hUCS and bFGF can induce significant regeneration of chronic tympanic membrane perforation.

[Spontaneous course of traumatic tympanic membrane perforations]. / Spontaner Heilungsverlauf traumatischer Trommelfellperforationen.

BACKGROUND: Traumatic eardrum perforation is a common presentation in otorhinolaryngologic practices and emergency clinics. A consistent management strategy (active intervention vs. watchful waiting) is, however, still lacking. OBJECTIVE: In the following study, the outcome of watchful waiting is analyzed and presented. MATERIALS AND METHODS: A collective of 272 patients presenting at two different specialist ENT practices within days of traumatic tympanic membrane perforation from June 2002 to March 2019 were analyzed. Treatment was non-surgical, with prospective monitoring. Whereas antibiotics were not given at all in one practice, they were given only upon signs of infection in the other practice. The outcome was evaluated retrospectively on the basis of patient files. RESULTS: The collective consisted of 185 males and 87 females. Mean age was 30 years (range: 7 months to 82 years). The perforations were most commonly located in the upper anterior and lower posterior quadrants. According to Griffin grading, the size was grade I in 97%. The three most common causes were impact to the ear, barotrauma, and foreign bodies. Under a watchful waiting regimen, 95% of the patients presenting for follow-up checks showed complete closure. CONCLUSION: Watchful waiting can be assessed as appropriate in traumatic eardrum perforation, provided otorhinolaryngologic follow-up is ensured. An exception is blast injury, which is now much less common in Central Europe, as this is associated with a risk of secondary cholesteatomas. In these rare cases, active treatment with surgical exploration of the middle ear including relining the perforation is indicated.

Necessities, opportunities, and challenges for tympanic membrane perforation scaffolding-based bioengineering.

Tympanic membrane (TM) perforation is a global clinical dilemma. It occurs as a consequence of object penetration, blast trauma, barotrauma, and middle ear diseases. TM perforation may lead to otitis media, retraction pockets, cholesteatoma, and conductive deafness. Molecular therapies may not be suitable to treat perforation because there is no underlying tissue matrix to support epithelium bridging. Chronic perforations are usually reconstructed with autologous grafts via surgical myringoplasty. Surgical treatment is uncomfortable for the patients. The grafting materials are not perfect because they produce an opaque membrane, fail in up to 20% of cases, and are suboptimal to restore acoustic function. Millions of patients from developing parts of the world have not got access to surgical grafting due to operational complexities, lack of surgical resources, and high cost. These shortcomings emphasize bioengineering to improve placement options, healing rate, hearing outcomes, and minimize surgical procedures. This review highlights cellular, structural, pathophysiological, and perforation specific determinants that affect healing, acoustic and surgical outcomes; and integrates necessities relevant to bioengineered scaffolds. This study further summarizes scaffolding components, progress in scaffolding strategies and design, and engenders limitations and challenges for optimal bioengineering of chronic perforation.

Traumatic perforations of the tympanic membrane: immediate clinical recovery with the use of bacterial cellulose film / Perfurações traumáticas da membrana timpânica: recuperação clínica imediata com o uso de fragmento de celulose bacteriana

Abstract Introduction: Perforation of the tympanic membrane is a reasonably frequent diagnosis in otorhinolaryngologists' offices. The expectant management is to wait for spontaneous healing, which usually occurs in almost all cases in a few weeks. However, while waiting for healing to be completed, the patients may experience uncomfortable symptoms. Although some research suggests the use of various materials to aid in the recovery of the tympanic membrane, none presented robust evidence of improvement in the cicatricial process. Nevertheless, the occlusion of the perforation with some material of specific texture and resistance can alleviate the patients' symptoms and accelerate the healing process. Objective: To evaluate the clinical (symptomatic and functional) improvement after the placement of bacterial cellulose film (Bionext®) on tympanic membrane perforations (traumatic). Methods: We evaluated 24 patients, victims of traumatic perforations of the tympanic membrane, who were evaluated in the Otorhinolaryngology Emergency Room. Following otoscopy and audiometric examination was performed, before and after the use of cellulose film occluding the tympanic membrane perforation. Results: Twenty-four patients were included, whose degree of overall discomfort caused by the tympanic membrane perforation and the presence of symptoms of autophonia, ear fullness and tinnitus were investigated. The mean score attributed to the overall annoyance caused by tympanic membrane perforation was 7.79, decreasing to a mean value of 2.25 after the film application. Symptom evaluation also showed improvement after using the film: autophonia decreased from a mean value of 6.25 to 2.08, tinnitus from 7 to 1.92 and ear fullness from 7.29 to 1.96. The auditory analysis showed mean threshold values still within the normal range at low and medium frequencies, with slight hearing loss at acute frequencies, but with significant improvement at all frequencies, with the exception of 8000 Hz, after film use. Conclusion: The use of bacterial cellulose film fragment on traumatic perforations of the tympanic membrane promoted immediate functional and symptomatic recovery in the assessed patients.

Resumo Introdução: A perfuração da membrana timpânica é uma condição clínica relativamente frequente em consultórios de otorrinolaringologistas. A conduta é quase sempre expectante, aguardando cicatrização espontânea, que costuma ocorrer na quase totalidade dos casos em algumas semanas. No entanto, enquanto não se completa, os pacientes mantêm sintomas desconfortáveis. Embora algumas pesquisas sugiram o uso de materiais diversos para auxiliar na recuperação da membrana timpânica, nenhuma apresentou evidência substancial de melhoria no processo cicatricial. Por outro lado, a oclusão da perfuração com alguns materiais de textura e resistência específicas poderia aliviar os sintomas dos pacientes durante o processo cicatricial. Objetivo: Avaliar a melhoria clínica (sintomática e funcional) após a colocação de película de celulose bacteriana (Bionext®) sobre a perfuração da membrana timpânica (traumática). Método: Foram avaliados pacientes com perfurações traumáticas da membrana timpânica que deram entrada no pronto-socorro de otorrinolaringologia. Eles foram avaliados em relação a suas queixas e exame audiométrico, antes e após a aplicação de película de celulose que oclui a perfuração da membrana timpânica. Resultados: Foram incluídos 24 pacientes, nos quais foram pesquisados o grau de incômodo global causado pela perfuração da membrana timpânica e a presença de sintomas de autofonia, plenitude auricular e tinnitus. A média da nota atribuída ao incômodo global causado pela perfuração foi de 7,79; caiu para valor médio de 2,25 após a aplicação da película. A avaliação dos sintomas também apresentou melhoria após uso da película, autofonia caiu de valor médio de 6,25 para 2,08; zumbido de 7 para 1,92 e plenitude auricular de 7,29 para 1,96. A análise auditiva apresentou um valor médio de limiares ainda dentro da normalidade em frequências baixas e médias, com perda de audição leve em frequências agudas, porém com melhoria significante em todas as frequências, com exceção de 8000 Hz, após a colocação da película. Conclusão: A aplicação de fragmento de película de celulose bacteriana sobre perfurações traumáticas da membrana timpânica promoveu recuperação funcional e sintomática imediata nos pacientes estudados.

State of the art regeneration of the tympanic membrane.

PURPOSE OF REVIEW: One of the most common diseases of the tympanic membrane is a perforation, and tympanoplasty is one of the more common procedures in otolaryngology. Tympanic membrane regeneration and bioengineering aim to improve the success rate of the procedure, increase the availability of different scaffolds and provide innovative tools that will simplify the surgical technique and make it accessible for surgeons with varying expertise level. This review aims to raise awareness of current tissue engineering developments in tympanic membrane regeneration and how they may augment current clinical practices. We focus here on achievements in tympanic membrane cell cultures and on innovations in development of new scaffolds and growth factors that enhance regeneration of patient's native tympanic membranes. RECENT FINDINGS: In recent years, great achievements were reached in the field of tympanic membrane regeneration in the three hallmarks of bioengineering: cells, scaffolds and bioactive molecules. New techniques for modeling normal tympanic membrane proliferation were developed, as well as for isolation and expansion of normal tympanic membrane keratinocytes from miniature samples of scarred tissue. Ongoing clinical trials aim to seal the perforation by applying different scaffolds infiltrated by growth factors on the tympanic membrane. SUMMARY: Research efforts in tympanic membrane regeneration continue to seek the ideal single tissue-engineered substitute. Recent advances in tympanic membrane bioengineering include new types of scaffolds that may augment and provide a safe and effective alternative to the current gold-standard autograft. New bioactive molecules may simplify the surgical procedure and reduce surgical time by augmenting the native tympanic membrane regeneration. Several groups of bioengineering scientists and neurotologists are continuing to move forward and develop new strategies, seeking to create a fully functional tissue-engineered tympanic membrane.

Hyaluronic acid in otology: Its uses, advantages and drawbacks - A review.

OBJECTIVES: Review of the literature for studies involving the use of hyaluronic acid (HA) in otology. METHODS: Pubmed and OvidMedline were searched using a combination of the following words in different variations: hyaluronic acid, hyaluronate, otolaryngology, otology, ear, tympanic membrane, perforation, tympanostomy, tympanoplasty, myringoplasty, packing, middle ear, cochlea, gene delivery, gene therapy, cochlear implant, hearing loss, meniere, vertigo, otitis and cholesteatoma. RESULTS: The papers relevant for this review were triaged based on abstracts and titles and were then categorized based on topic/disease entity/procedure. The papers were read and summarized in order to use their findings in this review. CONCLUSIONS: HA is being recently used as adjuvant therapy for multiple inflammatory conditions and in tissue repair. These immunomodulatory properties and biocompatibility have interested researchers specially in the field of otology for repair, gene delivery, immunomodulation etc. Recent data in the field show optimistic results for the use of HA in several conditions especially tympanic membrane perforations and gene delivery. It also establishes the role of HA as ancillary treatment in many other otologic pathologies. This review presents the most recent findings on the use of HA in otology. The results could be used to guide clinical practice and incite further research based on the presented results of the literature.

Update on treatment options for blast-induced hearing loss.

PURPOSE OF REVIEW: The incidence of blast injuries has increased, and the ear is the highest risk organ. Ear injury induced by blast exposure is important in both military and civilian conditions. The permanent hearing loss caused by blast exposure is associated with a decline in the quality of life. In this review, I describe recent therapeutic strategies for each of the ear pathologies caused by blast exposure. RECENT FINDINGS: For tympanic membrane perforation after blast exposure, basic fibroblast growth factor (bFGF) has been used as a less invasive treatment to repair the tympanic membrane. The closure rates of tympanic membrane perforations treated with bFGF were reported to be comparable to those following conventional tympanoplasty.For sensorineural hearing loss after blast exposure, treatment with neurotrophic factors, such as nerve growth factor (NGF) or neurotrophin-3, antioxidants, and Atoh1 induction have recently been applied, and some of them were considered for clinical application. SUMMARY: Recent advances of therapeutics for blast-induced hearing loss, based on their pathologies, have been outlined. There are several promising therapeutic approaches for both middle and inner ear disorders after blast exposure; however, further research is needed to establish new treatments for blast-induced hearing dysfunction.

Endoscopic tympanoplasty with limited tympanomeatal flap elevation in pediatric cases: comparison of anatomic and audiological results of grafts.

OBJECTIVES: The anatomical and functional success rates of tragal cartilage perichondrium and temporal muscle fascia, in pediatric patients who underwent endoscopic type 1 tympanoplasty with limited tympanomeatal flap elevation, were compared. METHODS: In total, 35 pediatric patients (21 females, 14 males; mean age 11.0 ± 1.5 years; range 8-14 years) who underwent transcanal endoscopic type 1 tympanoplasty with limited elevation of the tympanomeatal flap were included in this study. Patients in group A received a tragal cartilage perichondrium graft and those in group B received a temporal muscle fascia graft. The groups were compared with respect to the pre- and postoperative air-bone gap (ABG) and tympanic membrane status. RESULTS: The mean preoperative and postoperative ABG were 27.0 ± 9.2 and 9.0 ± 8.5 dB in group A, and 26.8 ± 8.8 and 11.6 ± 9.2 dB in group B, respectively. The group differences in pre- and postoperative ABG values were not significant (p = 0.882 and p = 0.417, respectively). However, in both groups, the postoperative ABG was significantly lower than the preoperative ABG (both p = 0.0001). The graft retention rate was 100% in group A and 88.2% in group B; the difference was not statistically significant (p = 0.134). There was also no statistically significant difference between the pre- and postoperative bone conduction values of the patients at 0.5, 1, 2, 3 or 4 kHz (all p > 0.05). CONCLUSIONS: Our study demonstrated that in pediatric patients undergoing endoscopic tympanoplasty, both the tragal cartilage perichondrium and the temporal muscle fascia can be used successfully and safely as grafts in endoscopic type 1 tympanoplasty performed by limited tympanomeatal flap elevation.

A novel gel patch for minimally invasive repair of tympanic membrane perforations.

OBJECTIVE: Evaluate the efficacy of a photocrosslinkable gel patch for repairing tympanic membrane (TM) perforations using a minimally invasive procedure. METHODS: 38 adult male chinchillas underwent bilateral TM perforation via CO2 laser (n = 76 TMs). Eight weeks post-perforation induction, either a gel patch (n = 26) or EpiDisc (n = 12) was applied to the perforation through the ear canal. Perforation margins were not abraded prior to gel patch application in order to make the procedure minimally invasive. During the study, the application process was refined, and 9 of 26 gel-treated TMs received a second gel-patch augmentation. Perforations were observed for 14 weeks post-treatment to determine healing rates, after which animals were euthanized and their TMs and cochlea removed for histological analysis. RESULTS: 38 perforations (50%) persisted for 8 weeks without manipulation. Healing rates stabilized within three weeks post-treatment. Of the gel-treated TMs, 14 TMs healed after one application, 7 TMs healed after a second application, and 5 TMs did not heal, yielding an 81% total healing rate. Six of 12 EpiDisc-treated TMs healed (50%). There was no statistical difference (p = 0.06) in perforation size between gel-treated (25.1 ± 12.5% total TM area) and Epidisc-treated (36.4 ± 22.5). The largest perforation healed with gel patch was 60% total TM area. Histological analysis showed gel-treated TMs to have trilaminar regeneration with substantial lamina propria thickness. Gel-treated TMs had thickness of statistical equivalence to untreated TMs (47.1 ± 29.0 and 54.8 ± 12.1 µm, respectively (p = 0.40)). EpiDisc-treated TMs showed a cell monolayer of substantially less thickness (9.04 ± 6.26 µm, p < 0.05) than gel-treated TMs. No evidence of ototoxicity was present in cochlea from either gel patch or Epidisc treatment. CONCLUSIONS: The gel is promising regarding thickness and trilaminar regenerated tissue, perhaps due to the biomechanical properties of the gel, and further refinements in the material and technique are anticipated to increase ease and efficacy of treatment while minimizing complications.

Endoscopic observation of different repair patterns in human traumatic tympanic membrane perforations / Observação endoscópica de diferentes padrões de reparo em perfurações humanas traumáticas da membrana timpânica

Abstract Introduction: In the last decade, there has been an increasing use of biomaterial patches in the regeneration of traumatic tympanic membrane perforations. The major advantages of biomaterial patches are to provisionally restore the physiological function of the middle ear, thereby immediately improving ear symptoms, and act as a scaffold for epithelium migration. However, whether there are additional biological effects on eardrum regeneration is unclear for biological material patching in the clinic. Objective: This study evaluated the healing response for different repair patterns in human traumatic tympanic membrane perforations by endoscopic observation. Methods: In total, 114 patients with traumatic tympanic membrane perforations were allocated sequentially to two groups: the spontaneous healing group (n = 57) and Gelfoam patch-treated group (n = 57). The closure rate, closure time, and rate of otorrhea were compared between the groups at 3 months. Results: Ultimately, 107 patients were analyzed in the two groups (52 patients in the spontaneous healing group vs. 55 patients in the Gelfoam patch-treated group). The overall closure rate at the end of the 3 month follow-up period was 90.4% in the spontaneous healing group and 94.5% in the Gelfoam patch-treated group; the difference was not statistically significant (p > 0.05). However, the total average closure time was significantly different between the two groups (26.8 ± 9.1 days in the spontaneous healing group vs. 14.7 ± 9.1 days in the Gelfoam patch-treated group, p < 0.01). In addition, the closure rate was not significantly different between the spontaneous healing group and Gelfoam patch-treated group regardless of the perforation size. The closure time in the Gelfoam patch-treated group was significantly shorter than that in the spontaneous healing group regardless of the perforation size (small perforations: 7.1 ± 1.6 days vs. 12.6 ± 3.9, medium-sized perforations: 13.3 ± 2.2 days vs. 21.8 ± 4.2 days, and large perforations: 21.2 ± 4.7 days vs. 38.4 ± 5.7 days; p < 0.01). Conclusion: In the regeneration of traumatic tympanic membrane perforations, Gelfoam patching not only plays a scaffolding role for epithelial migration, it also promotes edema and hyperplasia of granulation tissue at the edges of the perforation and accelerates eardrum healing.

Resumo Introdução: Na última década, houve um uso crescente de placas biomateriais na regeneração de perfurações traumáticas da membrana timpânica. As principais vantagens das placas de biomateriais são restaurar provisoriamente a função fisiológica da orelha média, assim melhoram imediatamente os sintomas da orelha e atuam como um suporte para a migração do epitélio. No entanto, não se sabe se há efeitos clínicos adicionais na regeneração do tímpano em relação ao fragmento de material biológico. Objetivo: Avaliar a resposta de cicatrização para diferentes padrões de reparo em perfurações de membrana timpânica traumáticas humanas por meio de observação endoscópica. Método: Foram alocados 114 pacientes com perfurações de membrana timpânica traumáticas sequencialmente para dois grupos: o de cicatrização espontânea (n = 57) e o tratado com esponja de Gelfoam (n = 57). A velocidade de fechamento, o tempo de fechamento e a taxa de otorreia foram comparados entre os grupos aos três meses. Resultados: Foram analisados 107 pacientes nos dois grupos (52 no de cicatrização espontânea e 55 no tratado com esponja de Gelfoam). A velocidade global de fechamento no fim do período de seguimento de três meses foi de 90,4% no grupo de cicatrização espontânea e de 94,5% no grupo tratado com esponja de Gelfoam; a diferença não foi estatisticamente significativa (p > 0,05). No entanto, o tempo total médio de fechamento foi significativamente diferente entre os dois grupos (26,8 ± 9,1 dias no de cicatrização espontânea versus 14,7 ± 9,1 dias no tratado com esponja de Gelfoam, p < 0,01). Além disso, a velocidade de fechamento não foi significativamente diferente entre o grupo de cicatrização espontânea e o grupo tratado com esponja de Gelfoam, independentemente do tamanho da perfuração. O tempo de fechamento no grupo tratado com esponjas de Gelfoam foi significativamente menor do que no grupo de cicatrização espontânea, independentemente do tamanho da perfuração (pequenas perfurações: 7,1 ± 1,6 dias vs. 12,6 ± 3,9, perfurações de tamanho médio: 13,3 ± 2,2 dias vs. 21,8 ± 4,2 dias e grandes perfurações: 21,2 ± 4,7 dias vs. 38,4 ± 5,7 dias; p < 0,01). Conclusão: Na regeneração de PMT traumáticas, a esponja de Gelfoam não só desempenha um papel de estrutura para a migração epitelial, mas também promove edema e hiperplasia de tecido de granulação nas bordas da perfuração e acelera a cicatrização do tímpano.

Efficacy of EGF and Gelatin Sponge for Traumatic Tympanic Membrane Perforations: A Randomized Controlled Study.

OBJECTIVE: To compare the outcomes of epidermal growth factor (EGF) and gelatin sponge patch treatments for traumatic tympanic membrane perforations. STUDY DESIGN: Prospective, randomized, controlled. SETTING: University-affiliated teaching hospital. SUBJECTS AND METHODS: 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. RESULTS: 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 (P = .054). The mean ± SD closure time was 11.12 ± 4.60, 13.67 ± 5.37, and 25.65 ± 13.32 days in the EGF, gelatin sponge patch, and spontaneous healing groups, respectively (P < .001). In addition, the presence of infection was not significantly associated with rate of closure in any group. CONCLUSIONS: 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.

Repair of Tympanic Membrane Perforations with Customized Bioprinted Ear Grafts Using Chinchilla Models.

The goal of this work is to develop an innovative method that combines bioprinting and endoscopic imaging to repair tympanic membrane perforations (TMPs). TMPs are a serious health issue because they can lead to both conductive hearing loss and repeated otitis media. TMPs occur in 3-5% of cases after ear tube placement, as well as in cases of acute otitis media (the second most common infection in pediatrics), chronic otitis media with or without cholesteatoma, or as a result of barotrauma to the ear. About 55,000 tympanoplasties, the surgery performed to reconstruct TMPs, are performed every year, and the commonly used cartilage grafting technique has a success rate between 43% and 100%. This wide variability in successful tympanoplasty indicates that the current approach relies heavily on the skill of the surgeon to carve the shield graft into the shape of the TMP, which can be extremely difficult because of the perforation's irregular shape. To this end, we hypothesized that patient specific acellular grafts can be bioprinted to repair TMPs. In vitro data demonstrated that our approach resulted in excellent wound healing responses (e.g., cell invasion and proliferations) using our bioprinted gelatin methacrylate constructs. Based on these results, we then bioprinted customized acellular grafts to treat TMP based on endoscopic imaging of the perforation and demonstrated improved TMP healing in a chinchilla study. These ear graft techniques could transform clinical practice by eliminating the need for hand-carved grafts. To our knowledge, this is the first proof of concept of using bioprinting and endoscopic imaging to fabricate customized grafts to treat tissue perforations. This technology could be transferred to other medical pathologies and be used to rapidly scan internal organs such as intestines for microperforations, brain covering (Dura mater) for determination of sites of potential cerebrospinal fluid leaks, and vascular systems to determine arterial wall damage before aneurysm rupture in strokes.

A perspective on stem cell therapy for ear disorders.

The use of stem cells in cell-based therapy is an emerging concept for the treatment of ear disorders. Tympanic membrane perforation (TMP) and inner ear disorders are some of the most commonly presented otologic disorders that can benefit from advances in cell-based therapy. Studies have already demonstrated that stem cell-based therapy can potentially be an effective treatment modality for acute and chronic TMP. Recent studies have also shown promise in application of cell-based approach to treat inner ear dysfunction. In this perspective, we will discuss the recent advancements regarding the use of cell-based therapy for ear disorders.

Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor.

OBJECTIVE: The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP). METHODS: The current study was a prospective, multicenter, open-label, single-arm, and exploratory clinical trial to evaluate the safety and efficacy of the TM regeneration procedure (TMRP). Myringotomy was used to mechanically disrupt the edge of the TMP, and a gelatin sponge immersed in bFGF was then placed over the perforation. Fibrin glue was dripped over the sponge as a sealant. TMP closure was examined 4 weeks later and, if insufficient, TMRP was repeated a maximum of three more times. TMP closure and hearing improvement 12 weeks after the final TMRP as well as safety were evaluated. RESULTS: Of the 11 patients with TMP who participated in this study, one who fulfilled the exclusion criteria and did not undergo TMRP and one with cholesteatoma were excluded from the efficacy analysis. TMP closure and hearing improvement 12 weeks after the final TMRP were achieved in eight out of nine patients (88.9%). Mean bone conduction threshold significantly improved 12 weeks after the TMRP compared with baseline (35.7±20.3 vs 29.4±21.0dB, P=0.015). Six out of ten patients receiving TMRP experienced temporary adverse events: appendicitis (serious, severe), otorrhea (mild), otitis media (mild), and sudden hearing loss (mild). However, none were related to the protocol treatment. CONCLUSION: TMP closure and hearing improvement were frequently confirmed following the TMRPs which were safely performed. These favorable outcomes were accompanied with significant improvement of the bone conduction threshold. These promising outcomes would encourage a large-scaled, randomized and pivotal clinical trial in the future. This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000006585).

Conditions of the external and middle ear: an overview of presentation, management and associated complications.

Ear, nose and throat (ENT) presentations to primary care are common and frequently affect military patients. Many patients can be managed in primary care with appropriate treatment, but some presentations require appropriate, timely, and occasionally emergency onward referral for hospital management. This paper discusses the management of common otological presentations including otitis externa (OE), acute otitis media, chronic suppurative otitis media (including cholesteatoma), tympanic membrane (TM) perforations and pinna haematoma.

Histologic changes of mesenchymal stem cell repair of tympanic membrane perforation.

CONCLUSION: Mesenchymal stem-cells are good candidates for cell-therapy of chronic tympanic membranes perforations. OBJECTIVES: To determine the effects of cell-based therapy in tympanic membrane perforations. METHODS: Young C57BL/6 mice were anesthetized with intraperitoneal administration of ketamine and xylazine and randomly divided into three groups (n = 4 ears/group) that underwent bilateral sub-total pars tensa perforations of equal sizes using a sterile 27-gauge needle under a surgical microscope. Six-to-eight hours after injury, one group of mice did not receive treatment (acute perforation control), and the last two groups were treated with BM-MSCs embedded within HA scaffolds previously soaked in PBS to rinse culture media residues to avoid confounders and were euthanized 1 or 2 weeks after treatment. RESULTS: Untreated tympanic membrane perforations developed a hyper-cellular infiltrate surrounding the injury site, while BM-MSC treated eardrums showed a reduced inflammatory response after the first week and a restoration of the trilaminar configuration 2 weeks after treatment, mimicking a normal tympanic membrane.