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Background: Collagen acts as a scaffold for healing damaged cartilage. This study evaluated the results of an in vivo animal study and provides short-term clinical results on a mixture of atelocollagen and fibrin glue-enhanced microfracture techniques in patients with osteochondral lesions (OCL) of the talus. Methods: This paper contains animal in vivo data and clinical outcomes on the effectiveness of atelocollagen. An in vivo animal study was conducted with full-thickness cartilage defects created in the femoral condyle of 12 rabbits equally divided into 4 groups evaluated at 2, 4, 8, and 12 weeks. Four chondral lesions were created according to one procedure on each rabbit with each lesion treated as follows: (1) microfracture, (2) microfracture and the lesion covered with atelocollagen, (3) microfracture and the lesion covered with mixture of atelocollagen and fibrin glue, and (4) microfracture and the lesion covered with fibrin glue. In the clinical evaluation, 17 patients were treated with a combination of microfracture and atelocollagen injection for symptomatic full-thickness OCL of the talus. They were evaluated by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS), Hannover Ankle Score System (HSS), visual analog scale (VAS), and magnetic resonance imaging (MRI) at baseline and at 12-months follow-up. Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score of the post-op status was compared with the MOCART score and a modified Anderson's score of the pre-op status. Results: In the animal study, subchondral bone and cartilage were generated completely in groups 2 and 3 microscopically. Hyaline-like cartilage was found in the repair tissue. In the clinical evaluation, mean AOFAS improved from 62 to 88, mean HSS improved from 62 to 87, and mean VAS score improved from 64 to 18, respectively (p <0.001). Fifteen patients (89 %) reported good or excellent satisfaction. We defined the improvement of most of the subchondral bone edema and bone cyst as well as a chondral lesion by radiologic evaluation. Conclusions: Rapid regeneration of cartilage was demonstrated in the in vivo animal study, and patients showed significant clinical improvement. Atelocollagen-enhanced microfracture enabled a reasonable treatment of cartilage defects. [ABSTRACT FROM AUTHOR]