Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation.

Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.

Chondrocytes from congenital microtia possess an inferior capacity for in vivo cartilage regeneration to healthy ear chondrocytes.

The remnant auricular cartilage from microtia has become a valuable cell source for ear regeneration. It is important to clarify the issue of whether the genetically defective microtia chondrocytes could engineer cartilage tissue comparable to healthy ear chondrocytes. In the current study, the histology and cell yield of native microtia and normal ear cartilage were investigated, and the biological characteristics of derived chondrocytes examined, including proliferation, chondrogenic phenotype and cell migration. Furthermore, the in vivo cartilage-forming capacity of passaged microtia and normal auricular chondrocytes were systematically compared by seeding them onto polyglycolic acid/polylactic acid scaffold to generate tissue engineered cartilage in nude mice. Through histological examinations and quantitative analysis of glycosaminoglycan, Young's modulus, and the expression of cartilage-related genes, it was found that microtia chondrocytes had a slower dedifferentiation rate with the decreased expression of stemness-related genes, and weaker migration ability than normal ear chondrocytes, and the microtia chondrocytes-engineered cartilage was biochemically and biomechanically inferior to that constructed using normal ear chondrocytes. This study provides valuable information for the clinical application of the chondrocytes derived from congenital microtia to engineer cartilage. Copyright © 2016 John Wiley & Sons, Ltd.

Dynamometric Analysis of Normative Auricular Stiffness and Comparison With Operated Prominent Ears.

AIM: Stiffness of the auricular cartilage is the main determining factor for the choice of operative technique of the prominent ear deformity. The aim of this study is to evaluate the stiffness of normal appearing ears objectively and quantitatively, compare the results with the operated prominent ear patients, and present prospective short-term dynamometric evaluation of the operated prominent ear patients. PATIENTS AND METHODS: A total of 190 volunteers without ear deformities were recruited and 9 age groups were formed: group (5-9), group (10-14), group (15-19), group (20-24), group (25-29), group (30-34), group (35-39), group (40-49), and group (50+). Total 28 ears (14 patients) with otoplasty were included in the study as group (operated 5-9) and group (operated 10-14). In addition, 3 patients with prominent ear deformity were prospectively followed for dynamometric changes that occur with otoplasty operation. The auriculocephalic angle (ACA) was measured once and auricle to scalp distance was measured at 4 different standardized levels. Ear stiffness was measured on each ear individually at 4 different points over the antihelix using digital computer-aided dynamometry. Each ear was compared in terms of ACA, distance, and dynamometric values. FINDINGS: Dynamometric values tend to increase with age, which increase and peak around 35 years of age and declines after 40 years of age. Measurements of the first 2 age groups were statistically different compared with the other groups. Postoperative dynamometric measurements (DNM) of group (operated 5-9) were similar with normative values of group (5-9) and postoperative satisfaction visual analogue scale (VAS) score was 92.8%. Postoperative DNM of group (operated 10-14) were higher compared with normative values of group (10-14) for each different measuring level and the postoperative satisfaction VAS score was 75.3. A total of 3 patients with prominent ears had lower dynamometric values preoperatively; these values approached closer to normative values of their age group postoperatively. CONCLUSIONS: Results show that auricular cartilage stiffens and malleability decreases with increased age. This stiffness peaks in the 35-39 age group and declines after 40 years of age. Dynamometric values increase, at all levels, suggesting increased cartilage stiffness is related to age. In the scope of these results, cartilage sparing techniques are more suitable for 5 to 14 years of age and cartilage-cutting techniques are more suitable for older patients.

Sound transmission by cartilage conduction in ear with fibrotic aural atresia.

A hearing aid using cartilage conduction (CC) has been proposed as an alternative to bone conduction (BC) hearing aids. The transducer developed for this application is lightweight, requires a much smaller fixation force than a BC hearing aid, and is more convenient to use. CC can be of great benefit to patients with fibrotic aural atresia. Fibrotic tissue connected to the ossicles provides an additional pathway (termed fibrotic tissue pathway) for sound to reach the cochlea by means of CC. To address the function of fibrotic tissue pathway, BC and CC thresholds were measured in six ears with fibrotic aural atresia. The relationship between the CC thresholds and the results of computed tomography was investigated. In the ears with the presence of a fibrotic tissue pathway, the CC thresholds were lower than the BC thresholds at 0.5 and 1.0 kHz. At 2.0 kHz, no significant difference was observed between the BC and CC thresholds. The current findings suggest that sound in the low to middle frequency range is transmitted more efficiently by CC via a fibrotic tissue pathway than BC. The development of hearing devices using CC can contribute to rehabilitation, particularly in patients with fibrotic aural atresia.

Clinical analysis of 15 patients with relapsing auricular polychondritis.

Relapsing polychondritis (RP) is a rare autoimmune disorder of unknown etiology. The disease is characterized by episodic inflammation and destruction of cartilaginous and connective tissue structures, including the ear, eye, nose, larynx, trachea, bronchi, joints, skin, heart valves, and aorta. As the symptoms of RP are diverse and complex, it is easily misdiagnosed. The aim of this paper was to improve the understanding of the clinical features of RP, thereby facilitating its early diagnosis. Fifteen patients with RP were analyzed retrospectively and the relevant literature reviewed. The number of patients presenting with auricular chondritis was 13, while two presented with polyarthritis. Among them, the treatment of 2 RP patients with respiratory tract involvement failed and 1 patient died. Eleven patients with RP (73 %) were initially misdiagnosed. RP involves cartilage and connective tissue. The prognosis for patients with respiratory tract involvement is poor. RP causes episodic and progressive inflammation of cartilage throughout the body and is associated with a variety of clinical manifestations. Early diagnosis of RP depends on a thorough understanding of its clinical features.

Tissue engineering: revolution and challenge in auricular cartilage reconstruction.

External ear reconstruction for congenital deformity such as microtia or following trauma remains one of the greatest challenges for reconstructive plastic surgeons. The problems faced in reconstructing the intricate ear framework are highly complex. A durable, inert material that is resistant to scar contracture is required. To date, no material, autologous or prosthetic, is available that perfectly mimics the shapely elastic cartilage found in the ear. Current procedure involves autologous costal cartilage that is sculpted to create a framework for the overlying soft tissues. However, this is associated with donor-site morbidity, and few surgeons worldwide are skilled in the techniques required to obtain excellent results. Various alloplastic materials have therefore been used as a framework. However, a degree of immunogenicity and infection and extrusion are inevitable, and results are often disappointing. Tissue-engineered cartilage is an alternative approach but, despite significant progress in this area, many problems remain. These need to be addressed before routine clinical application will become possible. The current tissue-engineered options are fragile and inflexible. The next generation of auricular cartilage engineering is promising, with smart materials to enhance cell growth and integration, and the application of stem cells in a clinical setting. More recently, the authors' team designed the world's first entirely synthetic trachea composed of a novel nanocomposite material seeded with the patient's own stem cells. This was successfully transplanted in a patient at the Karolinska Hospital in Sweden and may translate into a tissue-engineered auricle in the future.

Complications of ear rings.

In this paper the complications of ear piercing are considered and the treatment of resultant deformities is described.

Condritis bilateral de pabellón auricular / No disponible

No disponible

Non-surgical correction of congenital deformities of the auricle: a systematic review of the literature.

BACKGROUND: Splinting is an elegant non-surgical method to correct ear deformities in the newborn. Since the late 1980s, many authors demonstrated that permanent correction occurs by forcing the ear into the proper position for several weeks. The external ear anomalies suitable for splinting have a common feature that no skin or cartilage is absent; the protruding, lop and Stahl's ears are good examples of these anomalies. Surprisingly, this technique is relatively unknown to plastic surgeons and is hardly ever communicated to the general public. PURPOSE OF STUDY: To review the literature on non-surgical correction of ear deformities, focussing on indications, technique, results and possible complications. METHODS: A systematic literature search was performed in July 2008 using PubMed. Twenty papers were suitable for review. RESULTS: Splinting can be performed in many ways, provided that the ear is permanently kept in the desired shape without distorting it. It is disputable until what age splinting therapy can reasonably be offered--opinions vary from 'newborn only' to well up to 3 or 6 months of age. A rigid fixation seems to allow correction in older children. The time needed to splint for permanent correction depends upon the age at the time of starting the treatment. For a newborn, 2 weeks often suffice, whereas for older children splinting time becomes more variable--up to 6 months. Most patients we treated had lop, Stahl's or prominent ears. In a case series in Japan, cryptotia was the most frequent deformity encountered. Most authors made their own judgement on the results, categorising their outcomes from poor to excellent, or asked a lay opinion. Fair-to-excellent results were reported in 70-100% of the cases. The results tended to be poor in older children. Recurrence was seldom described clearly in the literature and was probably listed as poor result. No serious complications occurred and skin irritation was seen sporadically. CONCLUSIONS: Ear splinting is an elegant technique that should be practised on a wider scale than is done today. Hopefully this article will challenge authors to perform prospective studies specifically addressing the relation between patient age, degree of deformity, stiffness of the cartilage, the time needed to splint and the treatment outcome.

Petrified auricular cartilages pointing the diagnosis of post-partum hypopituitarism in an encephalopathic patient.

True ossification of ear auricles is exceptional. We present the first case linking this finding to post-partum hypopituitarism. A 57-year-old female presented with a 2-day history of fever, headache and behavioural disturbances. Brain magnetic resonance imaging was normal. Since cerebral spinal fluid could not be obtained, she was treated empirically for a meningitis. A urinary tract infection was subsequently identified as the cause of fever but when she improved she remained apathetic. At this time petrified auricles were noticed; histological examination revealed true ossification. Endocrinological screening showed partial hypopituitarism and thyroid autoimmune disorder. Initial symptoms could be dated to the birth of her last child 15 years before, with breast feeding difficulties, loss of body hair, and transient amenorrhoea. The absence of overt peripartum bleeding, resumption of menses 1 year later, preservation or recovery of some hypophyseal function, and presence of an associated autoimmune thyroid disorder and of hypophyseal tissue in a normal sella turca, all suggest lymphocytic hypophysitis rather than Sheehan syndrome as the primary disorder. Of the 15 patients reported to date with auricular ossification, two had Addison disease. The present case suggests that low cortisol is the key factor in this clinical finding.

An animal study on cartilage healing using auricular cartilage as a model.

We investigated the effect of different surgical procedures on cartilage healing, using auricular cartilage as a model, which would be useful to create a rationale for septal cartilage surgery. Different kinds of manipulations were performed on the auricular cartilage of six female New Zealand white rabbits. Histopathological investigations were performed under light microscopy 4 months postoperatively. The autologous cartilage grafts survived well under the forehead skin regardless of the presence of the perichondrium. The response of perichondrium to either incomplete or complete trauma was not only new cartilage formation but also ossification. When incomplete incisions were made on the non-perichondrial side, new cartilage formation was stimulated whereas ossification was induced when there was perichondrium on the cartilage. If the cartilage with perichondrium was sliced into small pieces and planted back in its original place, many ossification areas occurred. The crushed cartilage was usually absorbed but sometimes replaced by bony plates. The traumatized cartilage with perichondrium undergoes ossification. This finding may be important clinically in that surgeons should not traumatize septal cartilage with perichondrium and work under the perichondrium. This ossification of traumatized cartilage may later result in thickening of the septal cartilage which we sometimes face in revision surgery.

Ingeniería de tejidos y osteoartritis / Tissue engineering and osteoarthritis

Las lesiones de cartílago articular predisponen al desarrollo precoz de osteoartritis. La mayoría de las técnicas quirúrgicas actuales para el tratamiento de lesiones condrales dan lugar a la formación de fibrocartílago con propiedades bioquímicas y biomecánicas inferiores a las del cartílago articular. La ingeniería de tejidos puede ofrecer una alternativa moderna para el tratamiento de estas lesiones y de esta forma prevenir el desarrollo de osteoartritis en pacientes jóvenes activos. Existen diferentes alternativas en cuanto al tipo de células para implantar como tratamiento, ya sean el actual uso de condrocitos autólogos o células troncales mesenquimales. La otra variable es el tipo de andamio sobre el cual cultivar o sembrar la células para su implante: materiales sintéticos biocompatibles y bioabsorbibles, los derivados de fibrina o de colágeno de diferentes fuentes (bovina, porcina, de cola de rata, etc.), en forma de geles, esponjas, mallas, etc., y todas ellas con o sin la adición de factores de crecimiento. En la actualidad, el uso de condrocitos autólogos es una realidad, ya sea inyectados en suspensión bajo un parche de periostio o sembrados en colágeno. Casi todos los investigadores y las empresas de biotecnología están buscando técnicas para las que no se requieran dos intervenciones quirúrgicas, por lo cual muy probablemente habrá que pensar en células troncales y con sistemas de implantación artroscópicos (AU)

Articular cartilage lesions predispose to the development of early osteoarthritis. Most current surgical techniques give rise to the formation of fibrocartilage with biochemical and biomechanical properties inferior to those or articular cartilage. Tissue engineering could offer modern alternative to the treatment of these lesions and in this way, prevent the development of early osteoarthritis in young active patients. Different tissue engineering approaches rely on the current use of autologous chondrocytes, or the potential use of mesenchymal stem cells. Other variables rely on the type of scaffold to use such as synthetic biodegradable polymers, fibrin or collagen-derived scaffolds of different sources, bovine, porcine, rat tail, etc, in the form of gels, sponges, mesh, etc, and all of these with or without growth factors. The use of autologous chondrocytes is a reality at the present time, whether injected under a periosteum patch or seeded on collagen. However, most investigators and biotech companies are in search of onestep surgical procedures, for which reason stem cells have to be kept in mind, as well as systems that will allow arthroscopic implantation (AU)

Calcificación de cartílagos auriculares en la insuficiencia suprarrenal / Calcification of auricular cartilages in adrenal insufficiency

El hallazgo de pabellones auriculares duros y rígidos a la palpación es un hecho muy infrecuente y poco conocido. Se debe a la calcificación de los cartílagos auriculares que aparece en enfermedades metabólicas como la insuficiencia suprarrenal o la diabetes. Su etiología y su mecanismo fisiopatológico no están del todo aclarados. También se lo ha relacionado con la exposición al frío o traumatismos del cartílago auricular, pero en un significativo número de casos se produce sin conocimiento de su origen o causa precipitante. Presentamos el caso de un paciente con insuficiencia suprarrenal primaria (enfermedad de Addison) en el que se desarrolló una calcificación auricular bilateral, revisamos la literatura y discutimos las hipótesis fisiopatológicas

Calcification of the auricular cartilages is a very rare finding observed in metabolic disorders like Addison's disease, adrenal insufficiency or diabetes. Its aetiology and physiopathological mechanisms remain unclear. It may be caused by exposure to cold or trauma in the cartilage but in a significant number of cases, ossification occurs without the identification of the precipitating cause or event. We present the clinical and pathologic findings of a patient suffering from Addison's disease who developed auricular bilateral calcification. The literature is reviewed and the physiopathological hypotheses discussed

Osificación bilateral del cartílago auricular / Bilateral ossification of the auricular cartilage

La petrificación auricular es un hallazgo infrecuente en el que las orejas se tornan total o parcialmente rígidas. La causa más frecuente es la calcificación del cartílago auricular e infrecuentemente la osificación auricular. La osificación puede deberse a hipotermia, factores físicos, procesos inflamatorios y distintas endocrinopatías. La hipotermia grave es la causa más frecuente. Se presenta un caso de osificación bilateral del cartílago auricular secundario a hipotermia

Auricular petrification is an infrequent finding in which the ears become completely or partially rigid. The most frequent cause is the calcification of the auricular cartilage and, infrequently, auricular ossification. Ossification may be due to hypothermia, physical factors, inflammatory processes and different endocrinopathies. Severe hypothermia is the most frequent cause. We present a case of bilateral ossification of the auricular cartilage secondary to hypothermia

Risk factors for cartilage infections of the ear.

BACKGROUND: Investigation and case-control study to identify risk factors in a large outbreak in 2003 of auricular chondritis associated with piercing. METHODS: Epidemiologic, environmental, and laboratory (pulsed-field gel electrophoresis) investigation, and case-control study. Telephone interviews were conducted for 15 cases and 61 controls. Odds ratios were determined for risks of infection. RESULTS: Of 15 confirmed cases, nine (60%) were hospitalized (median duration 4.4 days) and treated with intravenous/oral antibiotics. Cases required surgical treatment and multiple antibiotics. Risk factors for infection included piercing location and the use of a contaminated aftercare solution. Pseudomonas aeruginosa isolates, nine from patients and four from the aftercare solution, were indistinguishable by pulsed-field gel electrophoresis; one from the sink at the facility differed by two bands. CONCLUSIONS: This study demonstrates the serious consequences of cartilage piercing, identifies specific risk factors for infection, and suggests the importance of implementation and assurance of safe procedures.

Multiple, bilateral and painful ear nodules of the anthelices: a variant of chondrodermatitis nodularis?

A case of a distinctive clinicopathologic condition of the ear cartilage is presented, characterized by multiple, bilateral and painful nodules of the anthelices without epidermal involvement. Histologically, there was a peri-chondrial lymphohistiocytic infiltrate and a small focus of degenerate, basophilic cartilage as well as cystic chondromalacia containing an amorphous mass. This condition is both clinically and histopathologically distinct from other causes of ear nodules, although the lesions seen in our patient exhibit features of chondrodermatitis nodularis helices and therefore could well be a variant of the latter.