RESUMEN

BACKGROUND: Microfracture has the most extensive clinical application because of its advantages of a single operation, unified process, and low operation cost. Because research on the repair mechanism of microfractures in the treatment of cartilage defects is not in-depth, this study aimed to elucidate the mechanism. PURPOSE: To identify the characteristic cell subsets at different repair stages after microfracture, systematically analyze the repair process of the defect area after microfracture, and investigate the mechanism of fibrocartilage repair. STUDY DESIGN: Descriptive laboratory study. METHODS: Full-thickness articular cartilage defects and microfractures was established in the right knee of Bama miniature pigs. Single-cell transcriptional assays were used to identify the characteristics of cells isolated from healthy articular cartilage and regenerated tissues. RESULTS: Microfractures induced mature fibrous repair in the full-thickness cartilage defect six months after surgery, while early stages of repair occurred within six weeks. Based on single-cell sequencing results, eight subsets and specific marker genes were identified. Two processes may occur after microfracture: normal hyaline cartilage regeneration and abnormal fibrocartilage repair. Regulatory chondrocytes, proliferative chondrocytes and cartilage progenitor cells (CPCs) may play important roles in the normal regeneration process. During abnormal repair, CPCs and skeletal stem cells may have different functions, and macrophages and endothelial cells may play important regulatory roles in the formation of fibrochondrocytes. CONCLUSIONS: Using single-cell transcriptome sequencing, this study investigated the tissue regeneration process and identified key cell subsets after microfracture. CLINICAL RELEVANCE: These results provide future targets for optimizing the repair effect of microfracture.

Asunto(s)

RESUMEN

BACKGROUND: The short-term safety and efficacy of stromal vascular fraction (SVF) in treating knee osteoarthritis (KOA) have been extensively studied but the mid-term and long-term prognoses remain unknown. METHODS: 126 KOA patients were recruited and randomly assigned to SVF group and hyaluronic acid (HA) group (control group). The scores of visual analogue scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were assessed and compared between the two groups 1, 2, 3, and 5 years after treatment. The endpoint was defined as surgeries related to KOA or clinical scores exceeding the patient acceptable symptom state (PASS). RESULTS: The VAS and WOMAC scores in the SVF group were significantly better than those in the HA group during the 5-year follow-up after treatment. The average responsive time to SVF treatment (61.52 months) was significantly longer than HA treatment (30.37 months). The adjusted Cox proportional hazards model showed that bone marrow lesion (BML) severity, body mass index (BMI) and treatment were independent risk factors and that the use of SVF reduced the risk of clinical failure by 2.602 times. The cartilage volume was reduced in both the SVF and control groups at 5 years but reduced less in the SVF group. CONCLUSIONS: Up to 5 years after SVF treatment, acceptable clinical state was present for approximately 60% of patients. BML severity and BMI were independent predictors of the prognosis. TRIAL REGISTRY: This study was retrospectively registered at Chinses Clinical Trial Registry with identifier ChiCTR2100052818 and was approved by ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, number 2013-X-063.

Asunto(s)

RESUMEN

BACKGROUND: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. PURPOSE: To determine whether implantation of a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. RESULTS: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P < .05). There were no differences between the groups in adverse events. CONCLUSION: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. REGISTRATION: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

RESUMEN

OBJECTIVE: To analyze the clinical outcomes, knee function, and activity level of patients after treatment of full-thickness cartilage defects involving the patellofemoral compartment of the knee with cryopreserved osteochondral allograft. DESIGN: Nineteen patients with cartilage defects involving the patellofemoral compartment were treated. The average age was 31 years (range 15-45 years), including 12 females and 7 males. Patients were prospectively followed using validated clinical outcome measures including Veterans RAND 12-item Health Survey (VR-12), International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Tegner activity scale. Graft incorporation was evaluated by magnetic resonance imaging (MRI) or second-look arthroscopy. RESULTS: The cartilage defects included the patella (n = 16) and the femoral trochlea (n = 3). Mean VR-12 scores increased from 31.6 to 46.3 (P < 0.01), mean IKDC increased from 40.0 to 69.7 (P < 0.01), mean KOOS increased from 53.9 to 80.2 (P < 0.01), and mean Tegner scores increased from 3.0 to 4.9 (P < 0.01), at average follow-up of 41.9 months (range 24-62 months). Of the 3 patients who underwent second-look arthroscopy, all demonstrated a well-incorporated graft. Mean MOCART score for the 6 patients with follow-up MRI was 62.5 (range 25-85). The reoperation rate was 21.1% and 2 patients (12.5%) experienced progressive patellofemoral osteoarthritis requiring conversion to patellofemoral arthroplasty. CONCLUSION: Patients with unipolar cartilage defects involving the patellofemoral compartment of the knee can have positive outcomes at minimum 2-year follow-up after surgical treatment with a cryopreserved osteochondral allograft when concomitant pathology is also addressed, but the reoperation rate is high and bipolar cartilage lesions may increase the failure rate.

Asunto(s)

RESUMEN

OBJECTIVE: To assess the development of kissing lesions 12 months after the generation of full-thickness chondral defects. DESIGN: Eight minipigs were randomized into 2 groups: the Φ8.5 mm full-thickness chondral defect group (8.5FT group) and the Φ6.5 mm full-thickness chondral defect group (6.5FT group). The Φ8.5 mm or Φ6.5 mm full-thickness chondral defects were prepared in the medial femoral condyle. Knee magnetic resonance imaging (MRI) was performed before sacrifice. India ink staining was performed to macroscopically assess kissing lesions. Histologic staining (hematoxylin-eosin [HE], safranin O/fast green, toluidine blue staining) and immunohistochemistry (collagen I, collagen II, collagen X, MMP-3) were performed. Microcomputed tomography analysis was completed to assess subchondral bone alterations. RESULTS: Obvious kissing lesions were observed on the tibial plateau. Knee MRI demonstrated high cartilage signal intensity in the medial femoral condyle and opposite tibial plateau. HE staining demonstrated cartilage fibrillation and prominent cell death. The depletion of safranin O, toluidine blue staining, and collagen II was observed in the kissing lesion areas. The kissing lesion areas demonstrated increased collagen I, Collagen X, and MMP-3 expression. The 8.5FT group showed a significantly lower mean trabecular number (2.80 1/mm) than the control group (3.26 1/mm). The 6.5FT group showed a significantly increased mean trabecular thickness (0.54 mm) and a decreased mean trabecular number (2.71 1/mm) compared to the control group (0.32 mm; 3.26 1/mm). CONCLUSIONS: Obvious kissing lesions were observed on the tibial plateau. Knee MRI demonstrated high cartilage signal The presented findings support the development of kissing lesions caused by full-thickness chondral defects.

Asunto(s)

RESUMEN

The purpose of this study is to determine whether full-thickness tibiofemoral cartilage defects are predictive of incident radiographic OA, progression of radiographic OA, and progression to severe radiographic OA. Participants in the OA Initiative (n = 1317, 38.1% male, mean age 60.9 years SD 9.2) with baseline MRIs and Kellgren-Lawrence (KL) OA grade 0-3 (none to moderate OA) were included. All participants had follow-up radiographs at mean 4.9 years (max 8.0). The effect of full-thickness defect presence, size, and location on risk of incident OA (KL grade 2+), overall progression of OA (increase in KL grade 1+ points), or compartment-specific OA progression was assessed with Cox proportional hazards modeling with adjustment for demographic factors, weight, and knee alignment. The yearly incidence of tibiofemoral OA was 0.3% (CI 0.2-0.4%); defect presence, size, and location were not associated with incident OA risk. The yearly rate of OA progression was 3.8% in participants without tibiofemoral full-thickness defects, 6.7% with medial defects, and 6.3% with lateral defects. Medial bipolar (kissing) lesions were an independent risk factor for OA progression as well as medial compartment progression. Lateral tibial-sided full-thickness defects increased risk of lateral progression (increase in lateral OARSI grade). In older adults, isolated full-thickness cartilage defects do not increase short-term risk of incident OA. However, in the setting of preexisting mild or moderate OA, medial bipolar (kissing) defects increase risk of overall OA progression (KL grade) as well as progression of medial compartment OA. Lateral tibial defects increase risk of lateral compartment OA progression. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Asunto(s)

RESUMEN

PURPOSE: To determine: (1) rates and risk factors for progression of lateral and medial full-thickness cartilage defect size in older adults without severe knee osteoarthritis (OA), and (2) whether risk factors for defect progression differ for knees with Kellgren-Lawrence OA grade 3 (moderate) OA versus grades 0-2 (none to mild) OA. METHODS: Three-hundred and eighty adults enrolled in the Osteoarthritis Initiative were included (43% male, mean age 63.0 SD 9.2 years). Ethical approval was obtained at all study sites prior to enrollment. All participants had full-thickness tibial or weight-bearing femoral condylar cartilage defects on baseline knee MRIs. Baseline OA grade was KL grade 3 in 71.3% and grades 0-2 in 21.7% of participants. Repeat MRIs were obtained at a minimum 2-year follow-up. Independent risk of progression in defect size due to demographic factors, knee alignment, OA grade, knee injury and surgery history, and baseline knee symptoms was determined by multivariate Cox proportional hazards and linear regression modeling. RESULTS: The average increase in defect size over 2 years for lateral defects was 0.18 cm2 (SD 0.60) and for medial defects was 0.49 cm2 (SD 1.09). Independent predictors of medical defect size progression were bipolar defects (beta 0.47 SE 0.08; p < 0.001), knee varus (per degree, beta 0.08 SE 0.03; p = 0.02) and increased weight (per kg, beta = 0.01 SE 0.004; p = 0.01). Independent predictors for lateral defect progression were larger baseline defect size (per 1.0 cm2, beta 0.14 SE 0.03; p < 0.001) and tibial sided defects (beta 0.12 SE 0.04) and degrees valgus (per degree, beta 0.04 SE 0.01; p = 0.001). CONCLUSIONS: Medial compartment full-thickness defects progress at a more rapid rate than lateral defects in older adults with minimal to moderate OA. Medial defect progression was greatest for bipolar defects in heavier adults with varus knees. Lateral defect progression was greatest for large tibial-sided defects in adults with valgus knees. LEVEL OF EVIDENCE: II.

Asunto(s)

RESUMEN

BACKGROUND: Although a variety of strategies have been employed for managing articular cartilage defects in the knee, overall outcomes have not been satisfactory. An alternative option may be autologous chondrocyte transplantation (ACT). However, as this method is still under investigation, here we assessed the efficacy of ACT for human knee defect cartilage repair. METHODS: In a randomized clinical trial study, eleven patients (mean age 31.09 years) were enrolled in the study with full thickness cartilage defects in the knee. Arthroscopically, healthy cartilage was obtained, chondrocytes expanded for 2-3 weeks and ACT performed. Clinical status was evaluated before ACT, 6 and 12 months after ACT using the Brittberg-Peterson functional assessment and modified Cincinnati rating score. Magnetic resonance imaging (MRI) findings were evaluated based on the scoring systems used by Sally Roberts and by Henderson. RESULTS: Modified Cincinnati rating indicated significant improvement of clinical score before ACT compared to 6 (p = 0.000) and 12 (p = 0.000) months after ACT (from 2.73 before ACT to 7.27, 8.36 and 9.5 at 6, 12, and 48 months after ACT, respectively). Brittberg-Peterson functional assessment indicated a decline from 79.27 to 25.82 and 19.27 at 6 and 12 months post ACT. Further, statistical test demonstrated significant differences 6, 12 and 48 months post ACT (p = 0.007). Evaluation of MRI revealed a score of 6.5 for Henderson criteria and a score of 2.5 for Robert criteria. CONCLUSIONS: Our study demonstrated that ACT of the knee provides an excellent treatment for full thickness cartilage defects with outstanding clinical and radiological outcomes.