Human adipose tissue mesenchymal stem cells use in a cartilage repair experimental model

Orientador: João Batista de MirandaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: Por ser um tecido avascular, a cartilagem articular tem capacidade limitada de reparação. Lesões neste tecido tem sido diagnosticadas cada vez com maior frequência. Diversos métodos de tratamento estão disponíveis, mas nenhum promove a formação de tecido de reparação com estrutura e função semelhantes aos da cartilagem hialina original. Há aproximadamente duas décadas, o implante de condrócitos autólogos cultivados em laboratório, conhecido pela sigla inglesa ACI (Autologous Chondrocyte Implantation) tem sido considerado um dos melhores métodos de tratamento das lesões condrais, mas uma das principais limitações do seu uso é a utilização de condrócitos adultos: são necessários dois tempos cirúrgicos; pode causar dano articular na área doadora; requer um tempo de cultura em laboratório muito longo e ainda corre-se o risco destas células sofrerem o processo de de-diferenciação; o tecido de reparação formado na lesão se comporta como cartilagem hialina transitória, sofrendo hipertrofia com o tempo. O desenvolvimento da Engenharia de Tecidos e da Medicina Regenerativa tem levado ao uso de células mesenquimais como uma forma de contornar estes problemas. As células mesenquimais extraídas do tecido adiposo parecem ser uma fonte promissora para esse tipo de terapia. Métodos: Trinta joelhos de quinze ovelhas adultas foram alocados aleatoriamente em um grupo teste (grupo CÉLULAS: esponjas contendo células mesenquimais) e dois grupos controles: grupo ESPONJA (esponjas sem células) e grupo VAZIO (grupo controle com as lesões vazias, sem implantes). Uma lesão com dez centímetros de diâmetro e espessura parcial foi criada no côndilo femoral medial, evitando a penetração na cartilagem calcificada e o sangramento do osso subcondral. De acordo com o processo aleatório de alocação, este defeito foi tratado conforme um dos três grupos descritos anteriormente. Depois de seis meses, os animais foram sacrificados. Foram realizadas avaliações macroscópicas e histológicas. O desfecho principal foi a escala histológica semi-quantitativa da International Cartilage Repair Society (ICRS 1). Resultados: Todos os animais completaram o seguimento. Não houve eventos adversos graves. O grupo CÉLULAS apresentou maior valor da escala ICRS 1 (8,3 ± 3,1 DP) em relação aos dois grupos controle (ESPONJA = 5,6 ± 2,2 DP; VAZIO = 5,2 ± 2,4 DP; p = 0,033). Conclusão: O uso das células mesenquimais do tecido gorduroso promoveu a formação de um tecido de reparação melhor nas lesões da cartilagem hialina do joelho de ovelhas adultasAbstract: Background: Articular cartilage has limited healing capacity. Lesions in this tissue have been diagnosed with increasing frequency. Several methods to treat it have been developed, but repair tissue is different from native hyaline cartilage. Autologous Chondrocyte Implantation (ACI) has been recognized as one of the best strategies in the treatment of articular cartilage lesions nowadays, but one major limitation of this technique is the use of adult autologous chondrocytes, which require a two-time surgery, causes donor site morbidity, require a long cell culture time and could evolve with cell dedifferentiation. Stem cells have been evaluated to overcome these problems. Adipose tissue derived mesenchymal stem cells (AT-MSCs) seem to be a promising cell source. Methods: Thirty knees of fifteen female adult sheep were randomly allocated in three groups: Group 1: scaffold with mesenchymal cells; Group 2: scaffold without cells; Group 3: control group with empty untreated lesions. A ten-millimeter size defect was created in the medial femoral condyle, avoiding penetration in the calcified cartilage and bleeding from the subchondral bone. After six months, animals were euthanized and the knees were examined according to macroscopic and histological ICRS 1 scale (primary outcome). Results: All animals completed follow-up. There were no serious adverse events. Group CELLS presented the highest ICRS 1 score (8.3 ± 3.1 SD) against control groups (SCAFFOLD = 5.6 ± 2.2 SD; EMPTY = 5.2 ± 2.4 SD; p = 0.033). Conclusion: AT-MSCs promoted a better healing of partial thickness lesions in the knee of adult sheepDoutoradoFisiopatologia CirúrgicaDoutor em Ciências2011/17596-8FAPES

Opening-wedge high tibial osteotomy with and without bone graft : a prospective randomized clinical trial

Orientador: João Batista de MirandaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Introdução: A técnica de abertura de cunha medial apresenta vantagens em relação às outras de osteotomia valgizante da tíbia, o que a tem tornado muito popular. Sua desvantagem é a criação de uma falha óssea na tíbia proximal, o que poderia possibilitar perda de correção ou retardo de consolidação. O uso de enxerto ósseo autólogo da crista ilíaca tem sido preconizado para diminuir o risco destas complicações. Entretanto, nenhum estudo clínico comparou a evolução clínica entre pacientes com e sem o uso do enxerto ósseo. Hipótese: Não há necessidade de enxerto ósseo na osteotomia de abertura medial, fixada com placa-calço igual ou menor que 12,5 mm. Desenho do estudo: Estudo clínico controlado, duplo-cego, randomizado. Métodos: Foram realizadas 46 osteotomias entre Abril de 2007 e Novembro de 2008. As osteotomias foram divididas aleatoriamente por um programa de computador em dois grupos de 23 joelhos cada. No grupo A, foi usado enxerto autólogo da crista ilíaca para preencher o espaço. No grupo B, o espaço foi deixado sem preenchimento. O enxerto foi coletado nos dois grupos, para garantir o mascaramento tanto dos pacientes quanto dos avaliadores. Avaliações clínicas foram realizadas a cada duas semanas até que sinais clínicos de consolidação estivessem presentes. Resultados: As varáveis demográficas foram similares nos dois grupos. A média de tempo para consolidação no grupo A foi de 12,4 semanas (IC 11,2 - 13,6), e no grupo B foi de 13,7 semanas (IC 12,5-14,9), sem diferença estatística (p=0,130). Perda de correção ocorreu em um paciente no grupo A (4,35%) e em dois pacientes no grupo B (8,7%). Conclusão: Nesta amostra, o tempo de consolidação das osteotomias foi similar nos grupos com e sem enxerto ósseoAbstract: Background: Medial opening-wedge has gained popularity among other techniques of high tibial osteotomy with many advantages. The disadvantage of this method is the creation of a gap, with the possibility of collapse or delayed bone healing, and the need to harvest iliac crest bone graft. The filling of the gap is recommended, but no reports have compared grafted and ungrafted osteotomies. Hypothesis: There is no need for graft to achieve bone union in medial opening-wedge high tibial osteotomy when 12,5 mm or less spacer plate is used. Study design: Double-blinded randomized controlled clinical trial. Methods: Forty-six opening-wedge high tibial osteotomies were carried out. They were randomly divided by software in two groups of 23 knees: group A filled with autologous bone graft and group B unfilled. Bone graft was taken in all cases to ensure blindness of patients and investigators. Clinical evaluations were performed each two weeks until signs of bone union were achieved. Results: Demographic variables were similar in both groups. Mean time to bone union in group A was 12.4 weeks (CI 11.2-13.6) and in group B was 13.7 weeks (CI 12.5-14.9), without significant difference (p=0.130). Signals of loosening of screws occurred in one patient (4,35%) in group A, against two patients (8,7%) in group B. Conclusion: In this series both groups achieved bone union in similar timesMestradoCirurgiaMestre em Cirurgi

Total Knee Arthroplasty in Valgus Knee

Total knee arthroplasty in valgus knee deformities continues to be a challenge. It comprises only 10% of patients who undergo total knee arthroplasty. The surgeon should be aware of the technical aspects that differentiate it from the varus deformity: surgical exposure, bone cuts, ligament balancing, gap balancing, joint line obliquity, patellar tracking, preserving fibular nerve function, and selection of the implant. The aim of this chapter is to provide step-by-step comprehensive knowledge about different surgical techniques for the correction of severe valgus deformity in total knee arthroplasty

Primary Total Knee Arthroplasty

This book presents a compilation of topics related to primary total knee arthroplasty. The chapters cover, in a clear and didactic way, the current themes, written by experts from the area, from different parts of the world. Topics related to the three surgical phases (before surgery, during surgery, and after surgery) are discussed here. This is very important because the surgeon is not a ""factory worker."" First of all, it is a medicine doctor who has to feel and understand the particularities of each patient. Demographic studies show an aging population. Osteoarthritis and inflammatory diseases are becoming much more prevalent. In addition, a worldwide epidemic of trauma has led to the need for arthroplasties much more frequently. Therefore, total knee arthroplasty will be an increasingly important subject

Proposal for a New Histological Scoring System for Cartilage Repair

OBJECTIVE: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results. METHODS: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson’s trichrome staining. RESULTS: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair. DISCUSSION: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue. CONCLUSION: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system

Superior Dislocation of the Patella in a Young Patient without Osteophytes: A Case Report with Discussion about Differential Diagnosis

We report a case of superior dislocation of the patella in a young woman without degenerative changes. We retrospectively analyzed the clinical and imaging data obtained from the patient. This article describes a rare case of patellar dislocation following a bicycle fall in a 19-year-old woman without any history of patellofemoral complaints. Our literature search yielded 28 case reports; however, most reports describe older individuals with osteoarthritis. Only two reports have previously described this lesion in young patients without osteophytes, but some features, like an increase of the patella tilt, may raise doubts about whether it would be better to classify them as a vertical dislocation of the patella, another quite rare lesion, or just as a variant of a superior dislocation

Opening-wedge High Tibial Osteotomy With And Without Bone Graft.

Medial opening-wedge has gained popularity in comparison to other techniques of high tibial osteotomy. This technique involves the creation of a gap in the tibia. Filling the gap with autologous iliac bone graft was recommended in the classic description, to prevent complications such as correction loss or delayed bone union. No previous reports have compared grafted and nongrafted osteotomies. This study hypothesized that the use of autologous bone graft in medial opening-wedge high tibial osteotomy (MOWHTO) less than 12.5 mm is unnecessary. A prospective randomized clinical trial was conducted. Forty-six opening-wedge high tibial osteotomies were carried out between April 2007 and December 2008. All had fixation with a type of Puddu stainless steel plate and screws. Patients were randomly divided by software analysis into two groups: group A had osteotomies that were filled with autologous bone graft and group B had osteotomies that were unfilled. Autologous iliac bone graft was harvested in both groups. Clinical and radiographic evaluations were performed twice monthly by blinded investigators. The rates of complications were compared between the groups. There was no difference in demographic data. Mean time to clinical bone union in group A was 12.4 weeks (confidence interval [CI] 11.2-13.6) and in group B was 13.7 weeks (CI 12.5-14.9), but this difference was not significant (P = 0.13). Signals of correction loss occurred in one patient (4.35%) in group A, and in two patients (8.70%) in group B. All osteotomies had achieved bone union. It was concluded that time to bone union was not statistically different between the group with bone graft and the group without graft.35301-