Table 2.

Clinical studies on TE of cartilage/OCD of the ankle.

references	biomaterial/treatment approach	defect area/follow-up	procedure	outcome
Giannini et al. [162]	Hyalograft C scaffold seeded with human autologous chondrocytes	ankle/12 and 36 months	patients (n = 46) with a mean age of 31.4 years, post-traumatic talar dome lesions. First procedure: ankle arthroscopy to harvest cartilage. Chondrocytes were cultured on Hyalograft C scaffold. In the second step, the construct was arthroscopically implanted into the lesion site. Patients were evaluated by AOFAS score pre-operatively and at 12 and 36 months post-surgery	the mean pre-operative AOFAS score was 57.2 ± 14.3. After 12 and 36 months, the scores were 86.8 ± 13.4 and 89.5 ± 13.4, respectively. Clinical results were significantly related to the age of patients and to previous operations for cartilage repair. Histological stainings have revealed that hyaline-like cartilage was formed
Giannini et al. [163]	collagen powder/hyaluronan membrane loaded with concentrated BMDCs	ankle/6, 12, 18 and 24 months	patients (n = 23) used collagen/MSCs, and 25 patients used hyaluronan/MSCs for the treatment. Porcine collagen powder (Spongostan Powder) and hyaluronic acid membrane (HYAFF-11) were used. At first, bone marrow was harvested and concentrated. Then, the collagen powder or hyaluronan membrane was mixed with bone marrow and platelet-rich fibrin gel and composites were implanted	for the collagen powder group, the mean AOFAS scores of pre-operation and 24 months post-operation were 62.5 ± 18 and 89.8 ± 9.8, respectively. In the hyaluronic acid group, the scores increased from 66.2 ± 10.5 to 92.8 ± 5.3, 24 months after the surgery. At 2 years follow-up, MRIs showed the restoration of the cartilage layer and subchondral bone of the patients
Giza et al. [164]	collagen type I/III bilayered membrane with autologous chondrocytes	ankle/1 and 2 years	patients (n = 10) with average age of 40.2 years. The size and location of the defects were analysed by ankle arthroscopy, and cartilage was also harvested from the border or the lesion. Expanded chondrocytes were seeded into the collagen membrane. The joint was exposed with a small anterolateral or anteromedial approach, without malleolar osteotomy. The graft was cut and placed into the defect on top of a layer of fibrin sealant	the AOFAS hindfoot scores increased from 61.2 (pre-operative, ranged from 42 to 76) to 74.7 (1 year post-operative, ranged from 46 to 87) and 73.3 (2 year post-operative, ranged from 42 to 90). At 19 months post-operation, MRIs showed the regeneration of articular cartilage and subchondral bone
Aurich et al. [165]	collagen type I scaffold with autologous chondrocytes (MACI)	ankle/mean follow-up 24.5 months	patients (n = 18, with a total of 19 defects) with mean age of 29.2. Arthroscopy was used for the evaluation and debridement on the defects, as well as the harvest of cartilage. Cultured chondrocytes were seeded into the collagen membrane and implanted in the defects, with fibrin as the glue. MOCART score, the pain and disability module of the foot function index (FFI), AOFAS score and the core scale of the foot and ankle module of the American Academy of Orthopaedic Surgeons (AAOS) lower limb outcomes assessment instruments were used	according to AOFAS hindfoot score, 64% were rated as excellent and good, whereas 36% were rated fair and poor. The results correlated with the age of the patient and the duration of symptoms, but not with the size of the lesion. Mean MOCART score was 62.4 ± 15.8 points. There was no relation between MOCART score and the clinical outcome