RESUMO
BACKGROUND: Degenerative knee osteoarthritis (KOA) shows an increase in morbidity with improvement in the living conditions and extended lifespans. Treatment for degenerative KOA has been gaining attention since it significantly affects the life of the elderly population and is also associated with increased expenses for medical services and high socioeconomic costs. Treatments for degenerative KOA include nondrug therapy, drug therapy, and surgical treatment. For cases that show little response to conservative treatment but have not involved severe deformation of the knee, procedures such as arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation can be performed. However, effective treatment is required for patients experiencing sustained knee pain after surgery. Although studies confirming the therapeutic effects of acupuncture or thread-embedding acupuncture (TEA) treatment for degenerative KOA have been reported, clinical studies on a combination of TEA and electroacupuncture (EA) in patients complaining of knee pain after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation have not yet been reported. Therefore, this study aimed to evaluate the effectiveness and safety of this combination treatment in patients with persistent knee pain after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation. METHODS/DESIGN: This study has been designed as a 2-group, parallel, single-center, randomized, controlled, assessor-blinded trial. Thirty-six patients with degenerative KOA who complained of pain even after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation will be randomized to either the (TEAâ+âEAâ+âUsual care) group or the (Usual care only) group in a 1:1 ratio. The patients in the (TEAâ+âEAâ+âUsual care) group will receive TEA treatment once a week for 4 weeks for a total of 4 sessions and EA twice a week for a total of 8 sessions while continuing usual care. The (Usual care only) group will only receive usual care for 4 weeks. To assess the efficacy of the TEA and EA combination treatment, the visual analogue scale, the Korean version of the Western Ontario and McMaster Universities Osteoarthritis Index, the EuroQol 5-Dimension 5-Level, and the doses of the rescue drug taken will be evaluated at baseline (1W) and weeks 2 (2W), 4 (4W), 6 (6W), and 8 (8W). The primary efficacy endpoint is the mean change in visual analogue scale at week 4 (4W) compared to baseline. Adverse events will be assessed at every visit. DISCUSSION: This study will provide useful data for evaluating the clinical efficacy and safety of TEA and electroacupuncture combination treatment for improving pain and quality of life after surgery for degenerative KOA. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea (CRIS- KCT0004804), March 6, 2020.
Assuntos
Terapia por Acupuntura/métodos , Dor Musculoesquelética/terapia , Osteoartrite do Joelho/terapia , Polidioxanona/administração & dosagem , Artroscopia , Transplante Ósseo , Cartilagem/transplante , Condrócitos/transplante , Terapia Combinada , Eletroacupuntura , Humanos , Dor Musculoesquelética/etiologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/cirurgia , Medição da Dor , Projetos Piloto , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Método Simples-CegoRESUMO
Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.
Assuntos
Terapias Complementares/métodos , Osteoartrite do Joelho/terapia , Fatores Etários , Condrócitos/transplante , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Transplante Autólogo/métodos , Resultado do Tratamento , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
BACKGROUND: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. METHODS: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. RESULTS: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. CONCLUSIONS: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
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Condrócitos/transplante , Proteoma/metabolismo , Proteômica/métodos , Líquido Sinovial/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Mapas de Interação de Proteínas , Transplante Autólogo , Adulto JovemRESUMO
PURPOSE: The purpose of the present study was to evaluate the effects of pulsed electromagnetic fields (PEMFs) on clinical outcome in patients who underwent arthroscopic matrix-assisted autologous chondrocyte implantation (MACI) for chondral lesions of the knee. METHODS: Thirty patients affected by grade III and IV International Cartilage Repair Society chondral lesions of the knee underwent MACI. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 h per day for 60 days) or control group . Clinical outcome was evaluated through International Knee Documentation Committee (IKDC) subjective knee evaluation form, Visual Analog Scale, Short Form-36 (SF-36) and EuroQoL before surgery and 1, 2, 6, and 60 months postoperative. RESULTS: Mean size of chondral lesion was 2.4 ± 0.6 cm2 in the PEMFs group and 2.5 ± 0.5 cm2 in the control one. No differences were found between groups at baseline. IKDC score increased in both groups till 6 months, but afterward improvement was observed only in the experimental group with a significant difference between groups at 60 months (p = 0.001). A significant difference between groups was recorded at 60 months for SF-36 (p = 0.006) and EuroQol (p = 0.020). A significant pain reduction was observed in the experimental group at 1-, 2- and 60-month follow-up. CONCLUSION: Biophysical stimulation with PEMFs improves clinical outcome after arthroscopic MACI for chondral lesions of the knee in the short- and long-term follow-up. Biophysical stimulation should be considered as an effective tool in order to ameliorate clinical results of regenerative medicine. The use of PEMFs represents an innovative therapeutic approach for the survival of cartilage-engineered constructs and consequently the success of orthopaedic surgery. LEVEL OF EVIDENCE: II.
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Artroscopia , Cartilagem Articular/lesões , Condrócitos/transplante , Traumatismos do Joelho/cirurgia , Articulação do Joelho/cirurgia , Magnetoterapia/métodos , Adolescente , Adulto , Cartilagem Articular/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
Treatment of hip cartilage disease is challenging, and there is no clear algorithm to address this entity. Biomarkers are arising as promising diagnostic tools because they could play a role in the early assessment of the prearthritic joint and as a prognostic factor before and after treatment. The potential effect of biomarkers may be used to categorize individuals at risk of evolving to severe osteoarthritis, to develop new measures for clinical progression of the disease, and to develop new treatment options for the prevention of osteoarthritis progression. A trend toward a less invasive biological treatment will usher in a new treatment era. With the growth of surgical skills in hip arthroscopy, cartilage restoration techniques are evolving in a fast and exponential manner. Biological and surgical treatments have been proposed to treat these pathologies. Biological treatments include platelet-rich plasma, stem cells or bone marrow aspirate concentration, hyaluronic acid, losartan, and fish oil. Surgical treatments include microfracture alone or augmented, direct repair, autologous chondrocyte implantation, matrix-induced chondrocyte implantation, autologous matrix-induced chondrogenesis, mosaicplasty, osteochondral allograft transplantation, and stem cells implanted in matrix (stem cells in membranes/expanded stem cells). This article reviews new evidence available on treatment options for chondral lesions and early osteoarthritis of the hip. [Orthopedics. 2016; 39(4):e715-e723.].
Assuntos
Terapia Biológica/métodos , Doenças das Cartilagens/terapia , Articulação do Quadril/cirurgia , Osteoartrite do Quadril/terapia , Animais , Artroscopia/métodos , Biomarcadores/metabolismo , Doenças das Cartilagens/diagnóstico , Cartilagem Articular/cirurgia , Condrócitos/transplante , Condrogênese , Progressão da Doença , Humanos , Osteoartrite do Quadril/diagnóstico , Plasma Rico em PlaquetasRESUMO
OBJECTIVE: The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model. METHODS: Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry. RESULTS: Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (â¼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced. CONCLUSION: The results further demonstrate the positive effects of rhAC treatment on chondrocyte growth and phenotype in vitro, and reveal for the first time the in vivo effects of the treated cells on cartilage repair.
Assuntos
Ceramidase Ácida/farmacologia , Cartilagem Articular/lesões , Condrócitos/efeitos dos fármacos , Condrócitos/transplante , Animais , Cartilagem Articular/patologia , Cartilagem Articular/fisiologia , Contagem de Células , Células Cultivadas , Condrócitos/metabolismo , Meios de Cultivo Condicionados , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Glicosaminoglicanos/biossíntese , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Regeneração/efeitos dos fármacos , Alicerces Teciduais , Cicatrização/efeitos dos fármacos , Microtomografia por Raio-XAssuntos
Terapia por Acupuntura/métodos , Distinções e Prêmios , Cartilagem Articular/cirurgia , Condrócitos/transplante , Articulação do Joelho/cirurgia , Cervicalgia/terapia , Doenças das Cartilagens/cirurgia , Dor Crônica/terapia , Humanos , Sociedades Médicas , Transplante Autólogo , Pontos-GatilhoRESUMO
OBJECTIVE: To trace the pathological changes of the cultured autologous chondrocytes mass after implanted in cartilage defects and investigate the pathophysiological mechanisms of the antologous chondrocytes mass transplantation in the repair of cartilage defects. METHODS: Twenty-four New Zealand white rabbits of 4 to 6 month-old and weighing more than 3.0 kg (female and male was unrestricted) were randomly divided into experiment group and the control group. For 12 rabbits of experiment group, the cartilage defects were repaired with the autologous chondrocytes mass and sealed with one piece of periosteum. Firstly, cartilage tissue of 10 to 30 mg was obtained from the shoulder of the rabbits after anaesthetized by 1 mg/kg 20% sumianxin. Then, chondrocytes were isolated from the cartilage tissue with 0.2% type II collagenase digestion and were cultured in DMEM/F-12 supplemented with 20% fetal bovine serum (FBS), 50 microg/ml ascorbic acid-2-phosphate, 0.4 mM proline, 5 microg/ml insulin and 1 mM non-essential amino acids (NEAA) in flasks in vitro. The cells were harvested until a thin film of the cells covered the bottom of the flask could be seen with naked eyes. Then the film was collected with a curled glass stick and formed a solid mass. On this time, the animal was anaesthetized again and the full-thickness cartilage square defect of 4.0 mm x 6.0 mm was fabricated in the patellar grove of distal femur, and then the cellular mass was transplanted into the defect covered by one piece of periosteum which obtained from the upper anterior of tibia and sealed with the femoral condyles. For 12 rabbits of the control group, the defects were sealed with one piece of periosteum only. The animals were sacrificed in the 1st, 3rd, 6th and 12th weeks after the operation respectively. The histologic sections were stained with safranin O-fast green, hematoxylin-eosin (H&E) and picric acid-Sirius red and immunostained for type II collagen and aggrecan. RESULTS: In the 1st week, the transplanted cells oriented to articular surface differentiated to matured hyaline chondrocytes and excrete large amount cartilage matrix. In the 3rd week, the trend was more obvious and the periosteum was union to the cell mass. In the 12th week, the defects were repaired with hyaline-like cartilage tissue, and in the 24th week, the repair tissue turned to matured hyaline cartilage. In the control group, the defects were repaired with fibrocartilage tissues. CONCLUSION: It was evidenced that the defects were repaired by the autologous chondrocytes mass transplantation. The procedure was gradual and initialed from up toward joint to down to the deep of the defect.
Assuntos
Cartilagem Articular/cirurgia , Condrócitos/transplante , Articulação do Joelho/cirurgia , Animais , Cartilagem Articular/patologia , Feminino , Articulação do Joelho/patologia , Masculino , Coelhos , Transplante AutólogoRESUMO
Meckel's chondrocytes, derived from the ectomesenchyme, have the potential to transform into other phenotypes. In this study, we transplanted cell pellets of Meckel's chondrocytes into isogenic mouse spleens and analyzed their phenotypic transformation into osteogenic cells using histological and immunohistochemical methods. With the increasing duration of transplantation, chondrocytes were incorporated into splenic tissues and formed a von Kossa-positive calcified matrix containing calcium and phosphoric acid, similar to that of intact bone. Type I, II, and X collagens, and the bone-marker proteins osteocalcin, osteopontin, osteonectin, and bone morphogenetic protein-2 (BMP-2) were immunolocalized in the matrix formed by the transplanted chondrocytes. Osteopontin and osteonectin were detected in the calcified matrix at earlier stages than osteocalcin and BMP-2. Type II collagen was expressed during the first week of transplantation, and type X collagen-positive cells appeared scattered during the initial stage of calcification, these collagens being later replaced by type I collagen formed by osteocyte-like cells. Electron microscopic observations revealed that chondrocytes surrounded by the calcified matrix transformed into spindle-shaped osteocytic cells accompanying the formation of bone-type thick-banded collagen fibrils. These results suggest that phenotypic switching of Meckel's chondrocytes can occur under in vivo conditions at a cellular morphological level.
Assuntos
Condrócitos/citologia , Condrócitos/transplante , Osteogênese , Proteínas/metabolismo , Baço/citologia , Animais , Cálcio/metabolismo , Condrócitos/ultraestrutura , Colágeno/metabolismo , Microanálise por Sonda Eletrônica , Matriz Extracelular/metabolismo , Imunofluorescência , Camundongos , Peroxidase/metabolismo , Fósforo/metabolismo , Baço/enzimologia , Baço/ultraestrutura , Coloração e Rotulagem , Cloreto de Tolônio/metabolismoRESUMO
The present study investigated the effects of hyperbaric oxygen (HBO) and platelet-derived growth factor-BB (PDGF-BB) in chondrocyte transplantation. In vitro, chondrocytes were treated with HBO, PDGF-BB, and HBO combined with PDGF-BB (H+P). Cell growth was analyzed using cell counting, MTT assay, and FACS analysis. mRNA expression of the PDGF-alpha receptor (PDGFR-alpha) and beta receptor (PDGFR-beta) was detected by RT-PCR. Protein expression of PDGFR-beta was detected by Western blotting. In vivo, chondrocytes and PDGF-BB were suspended in alginate as a transplantation system. Cartilage defects were grafted with this system and with or without HBO treatment. Released PDGF-BB concentration was quantified by ELISA. After 8 weeks, animals were sacrificed and the repaired tissues were examined. In vitro data suggested that each treatment increased cell growth via the up-regulated mRNA expression of PDGFR-alpha and increased cell accumulation in the S-phase. The H+P treatment was more additive in cell growth and in mRNA and protein expression of PDGFR-beta than HBO or PDGF-BB. In vivo results suggested that PDGF-BB delivery lasted for more than 5 weeks. Scoring results showed that each treatment significantly increased the cartilage repair. Safranin-O and type II collagen staining confirmed the hyaline-like cartilage regeneration in the repaired tissues. In situ up-regulation of PDGFR-beta expression partially explains the additive effect of H+P treatment in cartilage repair. Accordingly, H+P offers a potential treatment method for cartilage repair.
Assuntos
Condrócitos/transplante , Oxigenoterapia Hiperbárica , Fator de Crescimento Derivado de Plaquetas/uso terapêutico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/biossíntese , Animais , Becaplermina , Cartilagem/lesões , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Colágeno Tipo II/biossíntese , Proteínas Proto-Oncogênicas c-sis , RNA Mensageiro/metabolismo , Coelhos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Regulação para CimaRESUMO
This study introduces an implantable scaffold-free (SF) cartilage tissue construct that is composed of chondrocytes and their self-produced extracellular matrix (ECM). Chondrocytes were isolated from the articular cartilages from knees of domestic pigs (2-week old) and monolayer-cultured for 3-4 days in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum and 50 microg/mL of ascorbic acid. Briefly treated with 0.25% trypsin-ethylenediaminetetraacetic acid (EDTA), an intact chondrocytes/ECM membrane, as a cell sheet was released from the plate bottom and subsequently centrifuged into a pellet-type construct. Each was grown in vitro for up to 5 weeks and subjected to various assays at different time points (1, 7, 14, 21, and 35 days). For in vivo implantation, full-thickness defects (n = 4) were manually created on the femoro-patellar groove of the left porcine knee and 1-week-cultured SF construct was implanted as an allograft for a month. One defect (#1) was an empty control and the remaining three received different recipes; construct only (#2) or 0.25% trypsin/EDTA-treated first and then construct and collagen gel (#3) or construct and collagen gel (#4). While the total cell numbers significantly increased by 2 weeks and then remained stable, cell viability stayed in the mid-70% range through the entire culture period. Biochemical assay found continuous glycosaminoglycan (GAG) accumulation. Histology exhibited that cell distribution was even in the construct and GAG intensity became stronger and uniform with time. Real-time reverse transcription polymerase chain reaction (RT-PCR) results showed that phenotypic stability peaked at 2 weeks, which was arable to that of freshly isolated chondrocytes. Upon analysis of the retrieved implants, some promising results were witnessed in the defects (#3) retaining not only their intact mass but also chondrocytic morphology with lacuna formation.
Assuntos
Cartilagem Articular/citologia , Condrócitos/transplante , Engenharia Tecidual/métodos , Animais , Contagem de Células , Sobrevivência Celular , Matriz Extracelular/metabolismo , Expressão Gênica , Glicosaminoglicanos/metabolismo , Masculino , Suínos , Transplante Homólogo , TransplantesRESUMO
OBJECTIVE: To explore the feasibility of repairing the articular cartilage with allo-articular chondrocytes embedded in alginate gel. METHODS: Allo-articular chondrocytes were isolated from three adult New zealand rabbits. The cells were cultured in DMEM/F-12 supplemented with 20% fetal bovine serum (FBS). Chondrocytes of 2nd - 3rd passage were harvested and were diluted to 5.0 x 10(7) cells/ml with 1.2% alginate. Then alginate gel was formed by 102 mM CaCl(2). The gels were cultured subsequently for 1 week and then transferred to the full-thickness defects in the femoral condyles of adult rabbits. In control group the defects were left untreated. The animals were sacrificed in the 3rd and 6th month after operation respectively. The specimens were decalcified with 50% formic acid. The histologic sections were stained with safranin O-fast green, hematoxylin-eosin (H&E) and picric acid-Sirius red and immunohisto-stained for type II collagen and aggrecan. The repairing efficiency was evaluated according to Wakitani scoring. RESULT: In the experiment group all 8 defects acquired repair, 7/8 were repaired with mature hyaline cartilage tissue, and 1/8 was with fibrocartilage tissue for less cell-gel inputted. The thick of repaired tissues were closed to the normal and the tissue integrated smoothly with cartilage around the defects. Safranin O staining of the matrix acted in accordance with the normal and immunostaining for type II collagen and aggrecan showed positive. Picric acid-Sirius red staining showed that the chondrocytes lined in lines and the collagen aligned like Gothic architecture structure by polarization microscopy. There was no evidence of residue of alginate and inflammation in 3rd month specimens and no obvious deterioration at 6th month. But in control group, only a small amount of fibrous, fibrocartilage, or hyaline-like tissue was seen on the surface of the defects. Wakitani scoring showed 1.75 points for the experiment group and 7.65 for the control group. CONCLUSION: It is a promising way to repair the articular cartilage with homogeneous articular chondrocytes embedded in alginate gel.
Assuntos
Alginatos/uso terapêutico , Transplante de Células/métodos , Condrócitos/transplante , Articulação do Joelho/cirurgia , Alginatos/química , Animais , Cartilagem Articular/citologia , Cartilagem Articular/lesões , Cartilagem Articular/cirurgia , Células Cultivadas , Condrócitos/química , Condrócitos/citologia , Estudos de Viabilidade , Feminino , Fêmur/lesões , Fêmur/cirurgia , Géis , Masculino , Coelhos , Transplante Homólogo , Resultado do TratamentoRESUMO
Autologous chondrocyte implantation is an advanced, cell-based orthobiological technology used for the treatment of chondral defects of the knee. It has been in clinical use since 1987 and has been performed on 12 000 patients internationally; but despite having been in clinical use for more than 15 years, the evidence base for rehabilitation after autologous chondrocyte implantation is notably deficient. The authors review current clinical practice and present an overview of the principles behind autologous chondrocyte implantation rehabilitation practices. They examine the main rehabilitation components and discuss their practical applications within the overall treatment program, with the aim of facilitating the formulation of appropriate, individualized patient rehabilitation protocols for autologous chondrocyte implantation.
Assuntos
Condrócitos/transplante , Traumatismos do Joelho/reabilitação , Articulação do Joelho/cirurgia , Fenômenos Biomecânicos , Terapia por Estimulação Elétrica , Terapia por Exercício/métodos , Humanos , Traumatismos do Joelho/cirurgia , Articulação do Joelho/fisiologia , Aparelhos Ortopédicos , Propriocepção , Recuperação de Função Fisiológica , Transplante AutólogoRESUMO
OBJECTIVE: To critically analyze the existing literature relating to autologous chondrocyte implantation (ACI) and thereby to ascertain whether the technique is clinically effective and safe. METHODS: Using predefined criteria, we searched a number of automated databases, such as MEDLINE, EMBASE, Cochrane, CRD, etc., for relevant articles, which were then analyzed by two independent reviewers. RESULTS: Three clinical trials and nine case series were evaluated. The clinical trials yielded no evidence that ACI was superior to the therapeutic alternatives with which it was compared. In contrast, the case series revealed an improvement in patients. However, as with the clinical trials, the follow-up periods were usually very short. In general, few adverse effects were observed, indicating that ACI is a safe technique. CONCLUSION: Available data afford no evidence that ACI is more effective than other conventional techniques in treating chondral lesions of the knee.
Assuntos
Condrócitos/transplante , Cartilagem Articular/cirurgia , Humanos , Articulação do Joelho/cirurgia , Estilo de Vida , Osteoartrite do Joelho/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Resultado do TratamentoRESUMO
The treatment of unicompartmental osteoarthritis and focal chondral pathologic conditions in the knee in active aging athletes has captured the interest of patients, clinicians, basic scientists, and medical industry researchers. Most would agree that a biologic solution to treating hyaline cartilage injuries and degeneration would be optimal over prosthetic joint arthroplasty. Articular cartilage resurfacing techniques and biologic surgical methods continue to evolve and have gained more acceptance in orthopedic practice. A consensus exists for the ultimate goal of achieving a more predictable and durable result after surgical tissue repair or regeneration. Numerous promising approaches are now on the horizon and although the final word is far from in, the integration of many of the anticipated advances in molecular medicine, biomedical engineering, polymer chemistry, cell biology, and clinical orthopedics contributes to an exciting and rapidly evolving field. This article reviews the current concepts of the biologic approach to articular cartilage pathologic conditions and discusses future trends and novel technologies.
Assuntos
Terapia Biológica/tendências , Doenças das Cartilagens/terapia , Cartilagem Articular/lesões , Artroplastia/tendências , Cartilagem Articular/fisiopatologia , Cartilagem Articular/cirurgia , Condrócitos/transplante , Substâncias de Crescimento/uso terapêutico , Humanos , Regeneração , Engenharia TecidualRESUMO
Osteoarthritis represents an advanced stage of disease progression caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and noninflammatory pathways. The burden of this disease will increase in direct proportion to the increase in the older adult population. Research on current and experimental treatment protocols are reviewed, including the effect of hyaluronic acid in both in vitro and in vivo studies, autologous chondrocyte and osteochondral plug implantation, and gene therapy. Disease-modifying osteoarthritis drugs and in vivo studies of glucosamine and chondroitin sulfate are reviewed.
Assuntos
Osteoartrite/tratamento farmacológico , Adjuvantes Imunológicos/farmacocinética , Adjuvantes Imunológicos/uso terapêutico , Antraquinonas/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Camellia sinensis , Cartilagem Articular/transplante , Condrócitos/transplante , Condroitina/uso terapêutico , Previsões , Terapia Genética , Glucosamina/uso terapêutico , Humanos , Ácido Hialurônico/farmacocinética , Ácido Hialurônico/uso terapêutico , Osteoartrite/cirurgia , Fitoterapia , Extratos Vegetais/uso terapêuticoRESUMO
Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid-polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1alpha (IL-1alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin-transferrin-selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically (hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically (glycosaminoglycan content). The presence and distribution of IL-1alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1alpha that may inhibit cartilage tissue formation in autologous transplant models.
Assuntos
Materiais Biocompatíveis/farmacologia , Condrócitos/citologia , Implantes Experimentais , Interleucina-1/metabolismo , Ácido Láctico/farmacologia , Poliésteres/farmacologia , Ácido Poliglicólico/farmacologia , Polímeros/farmacologia , Implantes Absorvíveis/veterinária , Animais , Técnicas de Cultura de Células , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/transplante , Cartilagem da Orelha/citologia , Interleucina-1/farmacologia , Masculino , Suínos , Fatores de Tempo , Engenharia Tecidual/métodos , Transplante AutólogoAssuntos
Condrócitos/transplante , Custos Hospitalares/legislação & jurisprudência , Oxigenoterapia Hiperbárica/economia , Programas Nacionais de Saúde/economia , Análise Custo-Benefício/legislação & jurisprudência , Alemanha , Humanos , Programas Nacionais de Saúde/legislação & jurisprudência , Transplante AutólogoRESUMO
Symptomatic chondral lesions in the knee remain a problem for young sportsmen and pose a difficult management issue for orthopedic surgeons and patients alike. Damaged articular cartilage has a limited potential for healing and can lead to premature arthritis. Articular defects larger than 2 mm to 4 mm in diameter rarely heal. Neither articular cartilage possesses a lymphatic drainage, a sufficient blood supply, nor neural elements. Also, they are sheltered even from immunological recognition, because of the extracellular matrix surrounding the chondrocyte.
Assuntos
Doenças das Cartilagens/cirurgia , Cartilagem Articular , Condrócitos/transplante , Adulto , Transplante de Células/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante AutólogoRESUMO
In this study, we investigated the possible use of calcium alginate as a matrix for cartilage generation with autogenous chondrocytes, and examined whether the generated cartilage could keep its original volume over time when used as an implant for filling and contour restoration in the host body. Biodegradable, biocompatible, and injectable calcium alginate impregnated with isolated autogenous chondrocytes from the auricle was injected into the gluteus muscle of 12 New Zealand White rabbits. The volume of injected calcium alginate was always 3 mL, and the density of chondrocytes was 10 x 10(6) cells per milliliter. At 4 weeks (short-term period, n = 6) and 20 weeks (long-term period, n = 6) after injection, the histologic findings and the volume of the generated cartilaginous nodules were analyzed. At the time of harvest, 10 of the 12 specimens revealed findings characteristic of natural cartilage. However, histologic examination demonstrated scanty vascular and fibrous tissue ingrowth. Many osteoid matrices, including marrow-like cells, were noted in the vicinity of the neocartilage. The approximate original volume of the injected material was maintained over 20 weeks. These results suggest that although complete cartilage replacement was not always achieved, calcium alginate-autogenous chondrocytes may represent an injectable implant that can generate new autogenous fibro-osteo-cartilaginous tissue for volume augmentation.