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Osteochondritis dissecans (OCD) is a developmental condition of subchondral bone that may result in secondary separation and instability of the overlying articular cartilage, which in turn may lead to degeneration of the overall joint and early osteoarthritis. Biphasic scaffolds have been developed to address defects of the entire osteochondral unit by reproducing the different biological and functional requirements and guiding the growth of both bone and cartilage.To evaluate midterm clinical and imaging results after cell-free osteochondral scaffold implantation for the treatment of knee OCD.Case series; Level of evidence, 4.Twenty-seven patients (8 women, 19 men; mean age, 25.5 ± 7.7 years) were treated for knee OCD, with International Cartilage Repair Society (ICRS) grade 3 to 4 lesions with a mean size of 3.4 ± 2.2 cm2 (range, 1.5-12 cm2), and prospectively evaluated for up to 5 years using the ICRS classification system and the Tegner score. Eighteen patients underwent magnetic resonance imaging (MRI) at 24 and 60 months of follow-up, and the graft was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score for the cartilage layer, while a specific score was used for subchondral bone.All patients significantly improved their clinical scores at each follow-up until their final evaluation. The mean International Knee Documentation Committee (IKDC) subjective score improved from 48.4 ± 17.8 to 82.2 ± 12.2 at 2 years (P < .0005), and it then remained stable for up to 5 years postoperatively (90.1 ± 12.0). The mean Tegner score increased from 2.4 ± 1.7 preoperatively to 4.4 ± 1.6 at 2 years (P = .001), with a further increase up to 5.0 ± 1.7 at 5 years of follow-up (P < .0005 vs preoperatively), reaching almost the preinjury level (5.7 ± 2.2). The MOCART score showed stable results between 24 and 60 months, whereas the subchondral bone status significantly improved over time. No correlation was found between MRI findings and clinical outcomes.This 1-step cell-free scaffold implantation procedure showed good and stable results for up to 60 months of follow-up for the treatment of knee OCD. MRI showed abnormalities, in particular at the subchondral bone level, but there was an overall improvement of features over time. No correlation was found between imaging and clinical findings.