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Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.
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Microfracture is a common technique that uses bone marrow components to stimulate cartilage regeneration. However, the clinical results of microfracture range from poor to good. To enhance cartilage healing, several reinforcing techniques have been developed, including porcine-derived collagen scaffold, hyaluronic acid, and chitosan. Autologous collagen-induced chondrogenesis (ACIC) is a single-step surgical technique for cartilage regeneration that combines gel-type atelocollagen scaffolding with microfracture. Even though ACIC is a relatively new technique, literature show excellent clinical results. In addition, all procedures of ACIC are performed arthroscopically, which is increasing in preference among surgeons and patients. The ACIC technique also is called the Shetty-Kim technique because it was developed from the works of A.A. Shetty and S.J. Kim. This is an up-to-date review of the history of ACIC.
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Cartilagem Articular , Fraturas de Estresse , Humanos , Fraturas de Estresse/cirurgia , Condrogênese , Colágeno/uso terapêutico , AciclovirRESUMO
BACKGROUND: Knee pain is one of the commonest symptoms in patients who attend the Orthopaedic outpatient clinics. Chondral defects result in a painful knee. Incidence of chondral defect is reported to be between 5 and 10% over the age of 40. It is well documented that chondral defects can lead to osteoarthritis. Early detection of these lesions and cartilage repair surgery can delay the onset of osteoarthritis. The purpose of this study is to highlight the incidence, associations and correlations between opposing cartilage defects in patients who present to the knee clinic with pain. METHODS: A retrospective analysis was carried out on patients who had Magnetic Resonance Imaging scans for painful knees between June 2017 and May 2019. About 227 consecutive knees were studied for the incidence of chondral defects, number of lesions, grade and size of lesion, geographical location and associated pathology in the knee. RESULTS: All the 227 patients had chondral lesions. Most patients had 2-3 lesions (66.1%) with patellar lesions (76.6%) being the commonest followed by medial femoral condyle (59.9%). Significant correlation was found in grade and size between opposing surface lesions in patella-trochlea, Medial Femoral Condyle-Medial Tibial Plateau and Lateral Femoral Condyle-Lateral Tibial Plateau. Females were more predisposed to patella lesions. Significance between age and lesions were established. CONCLUSION: Incidence of cartilage defects in the knee is very high. Kissing lesions must be considered when treating cartilage lesions. Volume index could be a promising method to quantify lesions.
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Doenças das Cartilagens , Cartilagem Articular , Traumatismos do Joelho , Osteoartrite , Feminino , Humanos , Adulto , Estudos Retrospectivos , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Traumatismos do Joelho/complicações , Traumatismos do Joelho/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/patologia , Imageamento por Ressonância Magnética/métodos , DorRESUMO
Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.
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Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/cirurgia , Sangue Fetal , Transplante de Células-Tronco Mesenquimais/métodos , Artroscopia , Resultado do TratamentoRESUMO
BACKGROUND: Appropriate animal models of osteoarthritis (OA) are essential to develop new treatment modalities for OA. A combination of surgical and chemical induction could be appropriate for OA models. METHODS: Rabbit knee OA models developed by surgical induction (anterior cruciate ligament transection [ACLT]), chemical induction (monosodium iodoacetate [MIA] injection), and a combination of both were compared to assess compositional and structural destruction of the knee joint. Twenty-one New Zealand white rabbits were randomly divided into 3 groups to induce OA (group 1: ACLT, n = 3; group 2: MIA [3, 6, 9 mg] injection, n = 9; group 3: ACLT + MIA [3, 6, 9 mg] injection, n = 9). RESULTS: In all groups, the Modified Mankin score was significantly higher in the osteoarthritis-induced knee than in the control. Modified Mankin scores were compared by category. The ACLT group was observed to score high in cartilage structure. In the MIA group, chondrocytes and matrix staining showed higher scores, and the ACLT+MIA group scored higher in all categories for cartilage structure, chondrocytes, matrix staining, and tidemark integrity. The ACLT + 3 mg MIA showed definite OA characteristics such as cartilage surface destruction and degeneration of cartilage layers, and the ACLT + 6 mg MIA and ACLT + 9 mg MIA showed more prominent OA characteristics such as cartilage surface destruction, matrix disorganization, and osteophyte formation. CONCLUSION: The combination of MIA injection and ACLT could be an appropriate method for OA induction in rabbit models.
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Cartilagem Articular , Osteoartrite do Joelho , Animais , Coelhos , Ligamento Cruzado Anterior/cirurgia , Modelos Animais de Doenças , Ácido Iodoacético , Articulação do JoelhoRESUMO
Articular cartilage has unique biological and biomechanical characteristics. Damage to this tissue fails to heal spontaneously, leading to progressive arthritis. Cartilage repair techniques have been looked forward to in the treatment of significant cartilage injuries. Cell-based regenerative techniques like the two-staged cultured chondrocytes and single-stage mesenchymal cell transplantation have been tried with varying results and limitations. We study the outcomes of cultured bone marrow derived MSCs in the treatment of articular cartilage defects of the knee in comparison to autologous cultured chondrocyte implantation (ACI). Both cultured MSC and ACI treatment methods resulted in significant improvements in patient reported outcome measures (PROMs). There was no difference in the PROMs, MOCART scores, T2∗ mapping and dGEMRIC values between the groups. Use of cultured MSCs leads to good clinical outcomes similar to ACI and represents a promising treatment to restore the articular cartilage in the knee.
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OBJECTIVE: Skin grafts after negative pressure wound therapy (NPWT) and acellular dermal matrix (ADM) usage have both been useful for treating diabetic foot amputation. We hypothesised that injectable ADM combined with NPWT would be more useful than NPWT only for healing after amputation in patients with diabetic foot ulcers (DFUs). The aim of this study was to investigate the clinical outcomes of injectable ADM combined with NPWT in patients with DFU who have undergone amputation. METHOD: This retrospective study reviewed patients with infected DFUs who were administered NPWT. Patients were divided into two groups: Group 1 included patients who were treated with NPWT only, while Group 2 included patients who were treated with injectable ADM combined with NPWT. Clinical results including the number of NPWT dressing changes, wound healing duration, and full-thickness skin graft (FTSG) incident rate between the two groups were compared. RESULTS: A total of 41 patients took part in the study (Group 1=20, Group 2=21). The mean number of NPWT dressing changes was significantly lower in Group 2 (8.71±3.77) than in Group 1 (13.90±5.62) (p=0.001). Mean wound healing period was shorter in Group 2 (3.17±1.36 weeks) than in Group 1 (5.47±1.68 weeks) (p=0.001). Finally, the rate of patients who underwent FTSG for complete wound closure was 85% in Group 1, whereas it was only 14.3% in Group 2. CONCLUSION: In this study, the use of injectable ADM combined with NPWT in patients with DFU who underwent amputation favoured complete wound healing, without the need to resort to the use of skin grafts.
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Derme Acelular , Diabetes Mellitus , Pé Diabético , Tratamento de Ferimentos com Pressão Negativa , Amputação Cirúrgica , Pé Diabético/cirurgia , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Estudos RetrospectivosRESUMO
Osteonecrosis of femoral head (ONFH) is a disease of the femoral head and can cause femoral head collapse and arthritis. This can lead to pain and gait disorders. ONFH has various risk factors, it is often progressive, and if untreated results in secondary osteo-arthritis. Biological therapy makes use of bone marrow concentrate, cultured osteoblast and mesenchymal stem cell (MSC) obtained from various sources. These are often used in conjunction with core decompression surgery. In this review article, we discuss the current status of cell therapy and its limitations. We also present the future development of biological approach to treat ONFH.
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Articular cartilage injuries are common. The diagnosis of these injuries is often delayed and may lead to early osteoarthritis. Treatment depends on many factors but mainly on the stage and size of the lesion. The anatomy of articular cartilage is complex, and it is an avascular, aneural, and alymphatic structure. Recently, more emphasis is laid on its anatomy and biomechanics to understand the regeneration process of articular cartilage.
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Previously, most fractures have been treated through bone reduction and immobilization. With an increase in the patients' need for an early return to their normal function, development in surgical techniques and materials have accelerated. However, delayed union or non-union of the fracture site sometimes inhibits immediate return to normal life. To enhance fracture healing, diverse materials and methods have been developed. This is a review on the current modalities of fracture healing enhancement, which aims to provide a comprehensive knowledge regarding fracture healing for researchers and health practitioners.
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Consolidação da Fratura , Fraturas Ósseas , Osso e Ossos , Fraturas Ósseas/cirurgia , HumanosRESUMO
BACKGROUND: Venous blood drained from the knee joint after total knee arthroplasty (TKA) using a hemovac line is a potential source of bone marrow components, including stem cells, from the cutting surface of cancellous bones of the knee joint. However, the function of mesenchymal stem cells (MSCs) in patients with osteoarthritis (OA-MSCs) can be disrupted by inflammation of the joint. Further, to override the invasive nature of the currently used methods to obtain stem cells, their functional modification is necessary for therapeutic applications. METHODS: The effects of signal transducer and activator of transcription 3 (STAT3) signaling suppression on MSCs (iSTAT3-MSCs) were evaluated by comparative analyses of the characteristics of OA-MSCs and iSTAT3-MSCs from 20 patients who underwent TKA. RESULTS: OA-MSCs and iSTAT3-MSCs were adherent, with fibroblast-like appearance and high rates of expression of MSC-specific markers, including CD73, CD90, and CD105 (>90%). Both OA-MSCs and iSTAT3-MSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic cells; however, iSTAT3-MSCs showed higher levels of osteogenic and chondrogenic differentiation markers than OA-MSCs. Additionally, the anti-inflammatory and chondroprotective cytokine levels were higher in iSTAT3-MSCs than in OA-MSCs. CONCLUSIONS: These findings indicate that iSTAT3-MSCs after TKA are potentially effective for stem cell therapy in the context of bone and cartilage disorders.
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BACKGROUND: Patellar tendinopathy is a common cause of limitations in daily life activities in young and/or active people. The patellar tendon consists of a complex of collagen fibers; therefore, collagen could be used as a scaffold in the treatment of patellar tendinopathy. PURPOSE: To evaluate the healing capacity of injected atelocollagen as a treatment scaffold for patellar tendon defect and, hence, its potential for the treatment of patellar tendinopathy. STUDY DESIGN: Controlled laboratory study. METHODS: After receiving a full-thickness patellar tendon defect, 24 New Zealand White rabbits were divided into a control group (without treatment) and an experimental group that received an atelocollagen injection into the defect. Six rabbits from each group were subsequently used for either histologic scoring or biomechanical testing. The Mann-Whitney U test was used to compare histologic evaluation scores and load to failure between the 2 groups. Statistical significance was set at P < .05. RESULTS: The experimental group showed excellent repair of the damaged patellar tendon and good remodeling of the defective area. In contrast, the control group showed defective healing with loose, irregular matrix fibers and adipose tissue formation. A statistically significant difference was found between the 2 groups in both histologic scores and biomechanical tests at postoperative week 12. CONCLUSION: Injection of atelocollagen significantly improved the regeneration of damaged patellar tendons. CLINICAL RELEVANCE: Atelocollagen gel injections could be used to treat patellar tendinopathy in outpatient clinic settings.
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Ligamento Patelar , Tendinopatia , Animais , Colágeno , Patela , Ligamento Patelar/cirurgia , CoelhosRESUMO
BACKGROUND: With increasing life expectancy, stem cell therapy is receiving increasing attention. However, its application is restricted by ethical concerns. Hence a need exists for design of safe procedures for stem cell procurement. Here, we investigated whether hemovac blood (HVB) is an appropriate stem cell source. METHODS: HVB concentrates (HVBCs) from 20 total knee arthroplasty (TKA) patients and bone marrow aspirate (BMA) concentrates (BMACs) from 15 patients who underwent knee cartilage repair were comparatively evaluated. A bone marrow aspiration needle was inserted into the anterior superior iliac spine. Aspiration was performed using a 50-mL syringe, including 4 mL of anticoagulant, followed by centrifugation to obtain BMACs. To obtain HVBCs, blood was aspirated from the hemovac immediately after TKA surgery. Different cell types were enumerated. Isolation of BMA and HVB mononuclear cells was performed using density gradient centrifugation. Non-hematopoietic fibroblast colonies were quantified by colony forming unit-fibroblast assay surface marker analysis of HVB, HVBC, BMA, and BMAC was performed via flow cytometry. Mesenchymal stem cells (MSCs) isolated from HVBCs and BMACs were examined for osteogenic, adipogenic, and chondrogenic differentiation potential. Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The number of cells from HVB and HVBC was significantly lower than from BMA and BMAC; however, the number of colonies in HVBC and BMAC did not differ significantly (P>0.05). Isolated cells from both sources had a fibroblast-like appearance, adhered to culture flasks, and formed colonies. Under different culture conditions, MSC-specific surface markers (CD29, CD44, CD90, CD105), osteogenic markers [RUNX2, osteopontin, osteocalcin, and alkaline phosphatase (ALP)] and adipogenic markers (PPARγ and C/EBPα) were expressed. Moreover, SOX9, type II collagen, and aggrecan were significantly upregulated upon chondrogenic differentiation. CONCLUSIONS: HVB from TKA patients is a useful source of stem cells for research.
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Effective engineering approaches for cartilage regeneration involve a combination of cells and biomaterial scaffolds. Multipotent mesenchymal stem cells (MSCs) are important sources for cartilage regeneration. Atelocollagen provides a suitable substrate for MSC attachment and enhancing chondrogenic differentiation. Here, we assessed the chondrogenic potential of adipose tissue derived human MSCs (hMSCs) mixed with atelocollagen gel. We observed cell attachment, viability, and microstructures by electron microscopy over 21 days. The levels of Sox9, type II collagen, aggrecan, type I collagen, Runx2, type X collagen, ALP, Osterix, and MMP13 were measured by RT-qPCR. Cartilage matrix-related proteins were assessed by enzyme-linked immunosorbent assay (ELISA), histology, and immunohistochemistry. hMSCs of all groups exhibited well-maintained cell survival, distribution and morphology. Abundant type II collagen fibers developed on day 21; while Sox9, type II collagen, and aggrecan expression increased over time in the atelocollagen group. However, type I collagen, RUNX2, type X collagen (CoL10A1), Osterix, and ALP were not expressed. These results corroborated the protein expression detected by ELISA. Further, histological analysis revealed lacunae-like structures, while staining demonstrated glycosaminoglycan accumulation. Cumulatively, these results indicate that atelocollagen scaffolds improve hMSC chondrogenic differentiation and are a potential approach for cartilage regeneration.
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Diferenciação Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Colágeno/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Idoso , Agrecanas/metabolismo , Cartilagem/metabolismo , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Colágenos Fibrilares/metabolismo , Humanos , Proteínas Matrilinas/metabolismo , Fatores de Transcrição SOX9/metabolismo , Engenharia Tecidual/métodosRESUMO
Open patellar stabilization surgeries carry a risk of knee stiffness, patello femoral pain, longer time for recovery and poor cosmesis. We describe an arthroscopic assisted minimally invasive technique for patella maltracking which can help eliminate these complications.
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PURPOSE: The autologous collagen-induced chondrogenesis technique is described, and the results of a 6-year follow-up clinical study using this technique are presented. METHODS: 30 patients with International Cartilage Repair Society (ICRS) Grade III/IVa symptomatic chondral defects of the knee treated with enhanced microdrilling using atelocollagen were prospectively examined in this clinical series. The median age of the patients was 39.0 years (range 19-61 years). Patients were followed up to 72 months. Clinical evaluation was performed using functional knee scores and radiologically. Both quantitative and qualitative assessments were performed. RESULTS: Statistically significant and clinically relevant improvement was observed in 2 years and was sustained for the 6 years of the study observation. At 6 years, the mean Lysholm score was 79.7 (SD 6.8) compared to 52.6 (SD 10.7) pre-operatively (p < 0.05). The symptomatic Knee Injury and Osteoarthritis Outcome Score (KOOS) improved from 68.3 (SD 11.4) to 90.2 (SD 4.3) (p < 0.05). The subjective International Knee Documentation Committee (IKDC) also showed improvement from 39.1 (SD 4.1) to 81.6 (SD 7.8) (p < 0.05). The calculated T2* relaxation times were 26.0 (SD 4.2) seconds and 30.3 (SD 6.2) seconds for the repair tissue and native cartilage, respectively. The average magnetic resonance observation of cartilage repair tissue (MOCART) score was 78.5 (SD 9.6) for all lesions. CONCLUSION: The enhanced microdrilling using atelocollagen is an enhancement of the traditional microfracture method using an off-the-shelf product. When used to treat moderate to severe chondral lesions, this enhancement produces hyaline-like cartilage with a corresponding improvement in symptoms. LEVEL OF EVIDENCE: IV.
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Artroplastia Subcondral/métodos , Cartilagem Articular/cirurgia , Condrogênese , Colágeno/uso terapêutico , Articulação do Joelho/cirurgia , Adulto , Cartilagem Articular/patologia , Cartilagem Articular/fisiologia , Condrogênese/efeitos dos fármacos , Análise Custo-Benefício , Seguimentos , Humanos , Articulação do Joelho/patologia , Articulação do Joelho/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Autólogo , Adulto JovemRESUMO
BACKGROUND: Osteochondritis dissecans (OCD) is a pathologic condition accompanied by the gradual destruction of subchondral bone and defects in the overlying articular cartilage.This case series reports the results of allogenic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation for the treatment of osteochondral defect in two cases of juvenile osteochondritis dissecans. CASE PRESENTATION: Two patients with osteochondral defect of the knee recovered from the disease enough to begin major exercise 1 year after hUCB-MSCs implantation. The IKDC, VAS, and Tegner score of the two patients showed an excellent improvement and concurrent arthroscopy was performed; cartilage regeneration of ICRS grade 1 similar to normal was observed. The modified two-dimensional MOCART scores increased in both cases over time. CONCLUSION: This is the first case series detailing the results of treating juvenile OCD lesions using hUCB-MSCs. This could be an option for treating juvenile OCD.