Comparative Outcomes of Delayed i-PRF Combination with Nanofracture in the Treatment of Large Chondral Defects in the Knee

<i>Background and Objectives</i>: This study aimed to evaluate whether delayed intra-articular application of injectable platelet-rich fibrin (i-PRF) improves clinical and radiologic outcomes compared to nanofracture alone. <i>Materials and Methods</i>: A total of 76 patients with ICRS Grade III-IV femoral condyle or trochlear cartilage defects larger than 2 cm² were enrolled in this prospective controlled study. Patients were allocated into two groups: Group 1 (<i>n</i> = 40) underwent nanofracture followed by delayed intra-articular i-PRF injection at three weeks postoperatively, while Group 2 (<i>n</i> = 36) underwent nanofracture alone. Preoperative MRI was evaluated using the AMADEUS grading system. Clinical outcomes-including WOMAC and IKDC scores-were assessed at baseline and at 6, 12, and 24 months postoperatively. MOCART 2.0 scoring was used to evaluate cartilage repair at ≥12 months follow-up. <i>Results</i>: Both groups demonstrated significant functional improvement according to the IKDC and WOMAC scores. However, Group 1 showed a significantly greater improvement in WOMAC total score at final follow-up (Group 1: 20.1 ± 4.3 vs. control: 23.2 ± 3.4; <i>p</i> = 0.0008). No statistically significant differences were found between groups in IKDC score (<i>p</i> = 0.238), Tegner score (<i>p</i> = 0.776), or time to return to daily activities (<i>p</i> = 0.401). Baseline demographic, radiological, and intraoperative variables were comparable between groups (<i>p</i> > 0.05 for all). Radiologic outcomes based on the mean MOCART 2.0 scores were 57.1 and 50, respectively, in group 1 and group 2 (<i>p</i> = 0.0316). These results showed significantly improved results in group 1 according to the MRI evaluation. <i>Conclusions</i>: In patients with large chondral defects (>2 cm²), delayed intra-articular i-PRF injection following nanofracture may improve mid-term functional and radiological outcomes, particularly in pain and symptom relief. This regenerative strategy enhances cartilage repair potential during the early healing phase without adding surgical complexity.