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Background: The treatment of larger osteochondral lesions of the talus remains an operative challenge. In addition to micro fracturing and osteochondral transplantation one promising strategy could be the operative repair with a cell-free multilayered nano-composite scaffold with the potential to regenerate bone and cartilage in one treatment., Methods: In this prospective case series four consecutive patients who suffered from a single osteochondral lesion (≥1.5cm 2 ) on the medial talus were enrolled. The repair potential of the implant was assessed using MRI based biochemical, compositional MR sequences (T2 mapping) as well as semi-quantitative morphological analyses (MOCART score) at 18 months follow-up after the surgery. The clinical outcome was determined at 6-, 12-, 18-, and 24 months follow-up by using the Ankle Disability Index and the AOFAS score., Results: At 18 months after the surgery, the clinical outcome was significantly improved compared to the preoperative baseline. Global T2 relaxation times of the repair tissue were significantly increased compared to the healthy control cartilage., Conclusions: Osteochondral repair with a cell-free, biomimetic scaffold provides good clinical, short-term results. However, biochemical MR imaging provides strong evidence for limited repair tissue quality at 18 months after the implantation., Level of Evidence: IV., (Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)