Fig. 4.

Feasibility, non-invasive monitoring and safety evaluation of the ARTiCAR combined ATMPs implanted in sheep intra-articular defect model. a–e the OAR process after ARTiCAR implant was monitored non-invasively by means of MRI immediately after surgery (a) and at 12 (b) and 26 (c) weeks post implant. The extension of the bone defect (white asterisks) and the ongoing OAR (white arrowheads) are visible. Micro CT-scan (d) followed by 3D surface rendering (e) were performed on freshly explanted joints. f The level of cartilage regeneration was macroscopically assessed based on ICSR score system. g, h Whole explants were sectioned and stained with safranin o - fast green (blue: bone; red: cartilage), imaged at ×4 and stitched together (g) to evaluate the OAR according to the ICRS II score system (g). Scale bar: 1 mm. ICRS II parameters were examined for ARTiCAR and the control groups considered and analyzed by mean of two-way ANOVA followed by Bonferroni post hoc test (h). * = p ≤ 0.1; ** = p ≤ 0.05. Dots represent individual scores, bars represent mean scores and error bars represent standard errors. (i–n) Zones of osteochondral remodeling within the treated defects in animals from AG (I,L), NT (j, m) and ARTiCAR (k, n) groups, either at 12 or 26 weeks post implant. Bone (white asterisks), cartilage (black asterisk), fibrocartilage (black arrow) and subchondral bone (yellow arrow) are shown. Scale bar: 500 µm