Atelocolageno combinado con microperforaciones para el tratamiento de lesiones condrales severas en la rodilla / Atelocollagen matrix combined with microfractures in severe knee articular cartilage injuries

Introducción: En la actualidad existen diferentes métodos y técnicas de preservación articular. La utilización de una matriz de atelocolágeno combinada con microperforaciones otorga un soporte adecuado para la inducción de la condrogénesis a partir de las células mesenquimales provenientes de la médula ósea. El objetivo de nuestro trabajo es describir la técnica quirúrgica y presentar los resultados de una serie de pacientes con lesiones condrales severas, tratados con microperforaciones asociado a una matriz de atelocolágeno. Material y Método: Se evaluaron los pacientes intervenidos quirúrgicamente por lesión de cartílago grado IV de más de 3 cm2 a los que se le aplicó matriz de atelocolágeno combinado con microperforaciones. El mínimo seguimiento fue de 24 meses. En pacientes con deseje o inestabilidad asociada se realizaron procedimientos combinados en el mismo acto quirúrgico. Describimos la técnica quirúrgica, resultados funcionales pre y postoperatorios con las escalas de Lysholm, IKDC y Escala Visual Análoga (EVA) del dolor fueron. Se realizó una evaluación radiográfica. Analizamos las complicaciones del procedimiento. Resultado: Fueron operados 12 pacientes. A uno se le realizó un reemplazo articular de su rodilla a los 10 meses de la cirugía y fue considerado falla con finalización del seguimiento. Once fueron evaluados clínicamente, nueve hombres y dos mujeres, con una edad promedio de 48 años y seguimiento promedio de 34 meses. Ocho procedimientos en cóndilo interno, 2 en cóndilo externo y 4 en tróclea. La mediana de la escala de IKDC pre/post operatorio fue 41/55 (p 0.016), Lysholm 35/82 (p 0.004) y EVA 9/3 (p 0.002). La evaluación radiológica no evidenció cambios degenerativos. Se registró 1 artrofibrosis post operatoria. Conclusión: En nuestra serie, el tratamiento con atelocolágeno combinado con microperforaciones mejoró la clínica de los pacientes con lesión severa del cartílago articular de rodilla. Tipo de trabajo: Serie de casos Nivel de Evidencia: IV

ntroduction: Different surgical approaches are currently available to treat knee chondral defects. The technique used in this article combines microfractures with the use of an injectable atelocollagen matrix (Cartifill). The matrix covers the defect and improves the mechanical stability of the blood clot and maintains the chondrogenic progenitor cells and growth factors in the defective area. The aim of our study is to evaluate and describe the results in a series of patients treated with atelocollagen matrix and microfractures. Material and Methods: All patients treated with atelocollagen matrix due to a cartilage lesion with a minimum follow-up of 24 months were evaluated. Patients undergoing associated surgeries (osteotomies, meniscectomies, mosaicplasty, ligament reconstruction) in the same surgical procedure were included in the study. Clinical function was assessed before and after surgery with the International Knee Documentation Committee (IKDC), the Lysholm score and the Visual Analogue Scale (VAS). Radiographic control was requested according to availability. Results: Twelve patients met the inclusion criteria. Three women. Average age of 50 years. Eight applications in medial condyle, 2 in lateral condyle and 4 in trochlea. One post-operative arthrofibrosis was recorded. One of the patients underwent an articular replacement of his knee 10 months after the surgery with finalization of follow-up. The pre / post-operative average was 39/52 (IKDC), 37/76 (Lysholm) and 8.5 / 3.5 (VAS). Conclusion: In our series, atelocollagen matrix combined with microfractures improved the clinical symptoms of patients with severe knee articular cartilage injury. However, a better selection of patients who require this procedure should be applied in future interventions. Type of Study: Case Series. Level of Evidence: IV

Implantación de condrocitos autólogos versus microfracturas para el tratamiento de lesiones del cartílago en la rodilla / Autologous chondrocytes implantation versus microfracture for the treatment of knee cartilage lesions

Resumen: Objetivo: Comparar la eficacia clínica y la seguridad de la terapia de microfracturas (MF) versus implantación de condrocitos autólogos en membrana (MACI) en el manejo de lesiones condrales de rodilla ≥ 3 cm2 y el seguimiento a 12 meses postratamiento. Material y métodos: Se realizó un estudio de cohorte retrospectiva, de Enero de 2016 a Diciembre de 2017. Se incluyeron pacientes con una o varias lesiones condrales en rodilla ≥ 3 cm2 para comparar la terapia MF versus MACI para la reparación de lesión condral. Se realizaron valoraciones clínicas y funcionales previas al tratamiento quirúrgico y 12 meses posteriores, con medición de los arcos de movimiento, escala EVA, Oxford e índice de Lequesne. Resultados: Se incluyeron 12 pacientes en MF y 12 pacientes en MACI. La lesión más frecuente se localizó en la patela en ocho pacientes (67%). Se demostró incremento en los arcos de movimiento, así como mejoría en la comparación entre el nivel basal y en el seguimiento a 12 meses: en EVA, MF mostró 48.4% y MACI 57.5% (p ≤ 0.05); escala de Oxford: MF 32.65% y MACI 51.04% (p ≤ 0.05); índice de Lequesne: MF 40.12% y MACI 50%. Se presentaron dos casos de derrame articular en MACI, que se resolvieron con la realización de artrotomías. Conclusión: En este estudio se demostró mejoría significativa en MACI con alivio del dolor, funcionalidad y arcos de movimiento en comparación con el tratamiento de MF en lesiones ≥ 3 cm2 del cartílago articular de rodilla después de un año de seguimiento.

Abstract: Objective: To compare the clinical efficacy and safety of microfracture therapy (MF) versus implantation of autologous chondrocytes (MACI) in the management of chondral lesions of the knee ≥ 3 cm2 and follow up to 12 months post treatment. Material and methods: A retrospective cohort study was conducted from January 2016 to December 2017. Patients with one or more chondral lesions in knee ≥ 3 cm2 were included to compare MF versus MACI therapy for the repair of chondral lesion. Clinical and functional evaluations were carried out prior to the surgical treatment and 12 months later, with measurement of the range of motion, EVA, Oxford scale and Lequesne index. Results: Twelve patients were included in MF and 12 patients in MACI. The most frequent lesion was located in the Patella in eight patients (67%). It showed an increase in the arcs of motion, as well as improvement in the comparison between baseline and follow-up at 12 months: in EVA, MF demonstrated 48.4% and MACI 57.5% (p ≤ 0.05); Oxford scale: MF 32.65% and MACI 51.04% (p ≤ 0.05); index of Lequesne: MF 40.12% and MACI 50%. Two cases of joint effusion were presented in MACI, which were resolved with the realization of arthrotomies. Conclusion: In this study, significant improvement was demonstrated in MACI with pain relief, functionality, and range of motion compared to the treatment of MF in lesions ≥ 3 cm2 of the articular cartilage of the knee after one year of follow-up.

Platelet rich plasma associated with heterologous fresh and thawed chondrocytes on osteochondral lesions of rabbits / Associação de plasma rico em plaquetas e condrócitos heterólogos frescos e descongelados em lesão osteocondral de coelhos

Chondrocytes obtained from stifle joint of New Zealand White rabbits were cultivated. Half of cells were maintained in culture for later implantation and the others frozen during six months to evaluate viability. A circular osteochondral defect was created in the right stifle of other twenty seven rabbits. The control group (CG) received no treatment. The thawed (TH) and fresh (FH) heterologous groups received, respectively, an implant of cultivated thawed or fresh heterologous chondrocytes associated with platelet rich plasma (PRP). The CG group showed greatest pain and lameness compared to the other groups seven days after the implantation. Microscopically, at 45 and 90 days, the TH and FH groups showed filling with cartilaginous tissue containing chondrocytes surrounded by a dense matrix of glycosaminoglycans. In the CG group, healing occurred with vascularized fibrous connective tissue without integration to the subchondral bone. Cryopreserved heterologous chondrocytes were viable for implantation and healing of osteochondral lesions; the association with PRP allows the fixation of cells in the lesion and offers growth factors which accelerates repair with tissue similar to articular hyaline cartilage.

Cultivaram-se condrócitos obtidos da articulação do joelho de coelhos. Metade das células foi mantida em cultura para posterior implantação, e a outra metade foi congelada durante seis meses com a finalidade de avaliar a viabilidade. Criou-se um defeito circular osteocondral no joelho direito de outros vinte e sete coelhos. O grupo controle (GC) não recebeu tratamento. Os grupos descongelado (TH) e fresco (FH) receberam, respectivamente, implantes heterólogos de condrócitos cultivados descongelados e frescos, associados com PRP. O grupo GC apresentou maior dor e claudicação em comparação com os outros grupos aos sete dias após o implante. Microscopicamente, aos 45 e 90 dias, os grupos TH e FH mostraram preenchimento da falha com tecido cartilaginoso contendo condrócitos circundados por uma matriz densa de glicosaminoglicanos. Nesse período, no grupo CG, a cura ocorreu com tecido conjuntivo fibroso vascularizado e sem integração com o osso subcondral. Condrócitos heterólogos criopreservados foram viáveis para implantação e tratamento de lesões osteocondrais; a associação com o PRP permitiu a fixação de células na lesão e ofereceu fatores de crescimento que aceleraram a reparação com o tecido semelhante à cartilagem hialina articular.

Clinical and experimental approaches to knee cartilage lesion repair and mesenchymal stem cell chondrocyte differentiation

Cartilage has poor regeneration capacity due to the scarcity of endogenous stem cells, its low metabolic activity and the avascular environment. Repair strategies vary widely, including microfracture, autologous or allogenic tissue implantation, and in vitro engineered tissues of autologous origin. However, unlike the advances that have been made over more than two decades with more complex organs, including vascular, cardiac or bone tissues, similar advances in tissue engineering for cartilage repair are lacking. Although the inherent characteristics of cartilage tissue, such as the lack of vascularity and low cellular diversity, suggest that it would be one of the more simple tissues to be engineered, its functional weight-bearing role and implant viability and adaptation make this type of repair more complex. Over the last decade several therapeutic approaches and innovative techniques show promise for lasting and functional regeneration of hyaline cartilage. Here we will analyze the main strategies for cartilage regeneration and discuss our experience.

Transplante autólogo de condrócitos / Autologous chondrocyte implantation

Esta revisão da literatura descreve o processo do transplante autólogo de condrócitos em todas as suas etapas, indicações clínicas, técnica operatória, técnica laboratorial, reabilitação e resultados clínicos. Desde 1994, quando a técnica de ACI foi descrita pela primeira vez, este procedimento foi aprimorado e tornou-se uma das mais importantes alternativas cirúrgicas para o tratamento das lesões condrais do joelho. Nivel de Evidência II, Prospectivo Comparativo.

This literature review article describes the autologous chondrocyte implantation (ACI) process - its stages, clinical indications, surgical technique, laboratory protocol, rehabilitation and clinical outcomes. Since 1994, when the ACI was described for the first time, the procedure has improved to become one of the most important surgical alternatives for the treatment of chondral lesions of the knee.

Transplante autólogo de condrócitos: relato de três casos / Autologous chondrocyte implantation: series of 3 cases

A cartilagem hialina recobre as superfícies articulares e tem um papel importante na redução da fricção e da carga mecânica das articulações sinoviais, como o joelho. Este tecido não é suprido de vasos, nervos ou circulação linfática, o que pode ser uma das razões pela qual a cartilagem articular tem uma péssima capacidade de cicatrização. As lesões condrais, quando atingem o osso subcondral (lesão osteocondral), não cicatrizam e podem progredir para artrose com o passar do tempo. Em pacientes jovens, o tratamento dos defeitos condrais do joelho ainda é um desafio, principalmente as lesões maiores de 4cm. Uma das opções de tratamento nesses pacientes é o transplante autólogo de condrócitos, que por não violar o osso subcondral e por reparar o defeito com tecido semelhante à cartilagem hialina, teria a vantagem teórica de ser mais biológico e mecanicamente superior, quando comparado a outras técnicas. Descreveremos nesse artigo a experiência do Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Universidade de São Paulo (IOT-HCFMUSP) com o transplante autólogo de condrócitos (ACI), através do relato de três casos.

Hyaline cartilage in the surface of synovial joints plays an important role in lowering stress and attrition in joints such as the knee. This tissue has no blood vessels, nerves, nor lymphatic drainage, which in part explains why articular cartilage has such poor capacity for healing. Chondral lesions reaching the subchondral bone (osteochondral lesions) do not heal and may progress to osteoarthritis as time passes. In young patients, treatment of such defects is challenging, especially in lesions larger than 4 cm. One option in young adults is the autologous chondrocyte implantation, capable of filling the defect with tissue similar to hyaline cartilage without violating the subchondral bone. Theoretically, it has biological and mechanical advantages over other surgical options. In this paper, we describe the experience with this procedure in a series of 3 cases at the Institute of Orthopedics and Traumatology, University of São Paulo.

Tratamiento quirúrgico de la osteocondritis disecante de rodilla / Surgical treatment of osteochondritis dissecans

La OCD (osteocondritis disecante) de rodilla es diagnosticada con mayor frecuencia en pacientes adultos jóvenes. Sin tratamiento, la OCD puede llevar al desarrollo de una artrosis precoz. Este artículo discute la presentación clínica de pacientes con OCD de rodilla, métodos de evaluación, haciendo principal hincapié en el tratamiento quirúrgico. La indicación quirúrgica se basa en la estabilidad de la lesión, la maduración esquelética y los síntomas clínicos. El reestablecimiento de la superficie articular, estimular la vascularización, lograr la fijación y reducción del fragmento osteocondral acompañado de una movilidad articular precoz son los objetiivos primarios cuando se preserva el fragmento osteocondral. Cuando el fragmento no puede ser preservado, el tratamiento se focaliza en la reparación del defecto mediante técnicas de reconstrucción como ser: microfractura, OATS, transplante osteocondral e injerto de condrocitos autólogos.

Autologous chondrocyte implantation for traumatic large cartilage defect.

OBJECTIVE: The authors report the immediate result (6 months) after Autologous Chondrocyte Implantation (ACI) in clinical and anatomic result with MRI. This is the first report ofACI that provides chondrocyte cells from a domestic lab. MATERIAL AND METHOD: ACI was done in a two-stage procedure, first stage via arthroscope to harvest cartilage and detect pathology. The authors found deep cartilage defect at grade 4 according ICRS, area 2.5 cm2 and near total meniscus tear. Meniscal repair and cartilage shaving were done. Harvesting 300 mg of cartilage was done in this stage. Four weeks later, the secondACl was done. Lateral para-patellar was used. Periosteum was used as chondrocyte suspension and by suture to the healthy cartilage, using prolene interrupted suture in conjunction with fibrin glue to seal the pocket after injecting the cell. Range of motion exercise started on day 2, assisted with continuous passive motion machine. Running and jumping were restricted for 9 months. RESULTS: No complication was found, full range of motion and walking was done at 7-8 weeks post operative. Visual analogue scale improved from 3 points to 0 point. MRI shows evidence of 100% filling of the repair tissue in defect site associated with hypertrophy of the repair tissue above chondral surface. CONCLUSION: Immediate result of ACI shows improvement in clinical and anatomic that present with MRI. Further follow up and case series is needed

Defectos osteocondrales tratados con inoculacion de celulas progenitoras o condrocitos autologos. Modelo en conejos / Osteochondral defects treated with autologous chondrocyte implantation or progenitor cells. Rabbit model

Introduccion: El mejor tratamiento para las lesiones osteocondrales an se desconoce. Los resultados clinicos con el injerto de condrocitos autologos son favorables (90 por ciento exito a 10 años); sin embargo, su capacidad de regenerar un cartilago hialino adulto continua siendo controversial. La capacidad pluripotencial de las células progenitoras determina probablemente la posibilidad de regenerar al cartilago articular y el hueso subcondral subyacente. El objetivo es establecer si la regeneracion del cartílago es hialina luego de la inoculacion de celulas progenitoras adultas o condrocitos autologos en las lesiones osteocondrales de la rodilla. Materiales y metodos: Se utilizaron 10 conejos en los cuales se creo un defecto osteocondral de ambas rodillas. Luego se los dividio en dos grupos: un grupo control, que no recibio tratamiento (10 rodillas izquierdas) y grupo estudio (10 rodillas derechas), dentro del cual 5 recibieron celulas progenitoras autologas y 5, condrocitos autologos. A los ocho meses de la operacion se sacrifico a los animales previa evaluacion con resonancia magnetica tridimensional. Las piezas fueron evaluadas con tincion de hematoxilina-eosina y con inmunohistoquimica para colageno tipo II. Resultados: Los defectos sin tratamiento presentaron un tejido degenerativo fibrocartilaginoso. Los tratados con lineas celulares demostraron un estimulo regenerativo, pero sin evidenciar un cartílago hialino adulto similar al cartílago nativo adyacente. Las celulas progenitoras demostraron una mejor regeneracion del hueso subcondral. Conclusiones: Los tratamientos con líneas celulas demuestran un estimulo regenerativo en las lesiones osteocondrales; sin embargo, no se logra una cartilago articular hialino similar al nativo. Tal vez sea necesario incorporar a estas terapias otras herramientas de la ingeniería de tejidos, como las matrices tridimimensionales y los factores de crecimiento, que puedan lograr una regeneracion ad integrum del cartílago...

Tissue engineering trachea: Malaysian experience

Management of severe tracheal anomalies remains a clinical challenge. Tissue engineering offers new hope in trachea reconstruction surgery. However to date no optimal technique achieved in the formation of human or animal trachea. The main problem lies on the biomaterial used and the complex city of forming trachea in vivo. This study was aimed at creating tissue-engineered trachea cartilage from easily accessible human and animal nasal septum cartilage using internal scaffold and biodegradable human and animal fibrin.

Estudio de la actividad mitotica entre las fases in vitro e in vivo en el trasplante de condrocitos / Mitotic activity in \"in vitro\" and \"in vivo\" chondrocyte transplantation

El trasplante de matrices alogenicas desvitalizadas portadoras de condrocitos autologos, previamente aislados y sembrados sobre ellas, podria ser una solucion al problema de la reparacion de las lesiones del cartilago articular. El presente estudio analiza la actividad mitotica de los condrocitos sembrados en cartilago alogenico desvitalizado e implantados en animales vivos. Se aislaron enzimaticamente condrocitos de cartilago articular de cordero, y se sembraron "in vitro" sobre matriz cartilaginosa alogenica desvitalizada durante 3 semanas. Al final del periodo de cocultivo, se trasplantaron los compuestos de matriz y condrocitos en bolsillos subcutaneos de ratones atimicos. Las muestras experimentales y las de control fueron evaluadas luego de extraidas mediante el estudio histologico y tras la incorporacion de timidina tritiada. Los resultados obtenidos mostraron una disminucion importante de los valores de incorporacion de timidina a partir del tiempo experimental cero (evaluacion preimplante) hasta el dia 28 del implante, seguido por un leve aumento hacia el dia 42 del estudio. La experiencia ha demostrado la tendencia de los condrocitos articulares (cultivados "in vitro" y sucesivamente trasplantados "in vivo" sobre un soporte de matriz cartilaginosa alogenica desvitalizada) de modificar su propia actividad mitotica desde valores muy altos, correspondiendo a los primeros dias experimentales (tipico de las fases "in vitro" de expansion celular) hasta valores muy bajos, similares a la conducta de los condrocitos articulares "in vivo"