PurposeTo determine the clinical and radiographic efficacy of chitosan-glycerol phosphate/blood implant versus hyaluronic acid-based cell-free scaffold in patients with focal osteochondral lesion of the knee joint.MethodsClinical data of 46 patients surgically treated using either chitosan-glycerol phosphate/blood implant (25 patients, Group 1) or hyaluronic acid-based cell-free scaffold (21 patients, Group 2) in combination with microfracture were retrospectively evaluated. All lesions were Outerbridge grade III or IV with a mean lesion size of 3.30.7cm(2). The mean follow-up time was 24.4 months. Visual analogue scale (VAS), Lysholm knee score, and Tegner activity scale were the instruments to evaluate the clinical status. Magnetic resonance observation of cartilage repair tissue (MOCART) system was used to analyze the characteristics of repair tissue.ResultsNo significant differences were detected between the groups regarding VAS, Lysholm, and Tegner scores at any time interval during the whole follow-up. The mean post-operative VAS and Lysholm scores at the latest follow-up was significantly better in cases with the lesion size3cm(2) in Group 1 (p=0.001, p<0.001, respectively). However, no significant differences according to the lesion size were detected in Group 2 (n.s.). Complete repair with the filling of the defect was achieved in 7 (28%) of the knees in Group 1 and it was 7 (33.3%) of the knees in Group 2 according to MOCART system at the latest follow-up.ConclusionSingle-stage regenerative cartilage surgery using chitosan-glycerol phosphate/blood implant combined to microfracture for focal osteochondral lesions of the knee revealed similar clinical and radiographic outcomes with hyaluronic acid-based cell-free scaffold at short-term follow-up. However, clinical outcomes of hyaluronan scaffold were less sensitive to defect size than chitosan. With the advantages of no hypertrophic repair tissue formation as well as no need to arthrotomy during surgery, chitosan is an effective choice especially in patients with the lesion size3cm(2).Level of evidence III.