## 4 Discussion  
The main finding of the current study is that voluminous, high quality repair cartilage results from ChondroMimetic treatment of osteochondral defects after 7.9 years, supporting the hypothesis that ChondroMimetic brings consistent and durable long-term structural repair with an appropriate safety profile. Improvements in clinical outcomes were highly significant over the baseline (\(p<0.0065\)) for the 7.9-year follow-up, which suggests a benefit of ChondroMimetic treatment when used as backfill for mosaicplasty donor sites. The use of validated, three-dimensional quantitative MRI [17, 18], which assessed the repair tissue quantity and quality, is a particularly valuable aspect of this study, with a high level of standardization and precision and conducted under Good Clinical Practice guidelines. The high degree of defect filling by new bone and repair cartilage seen in ChondroMimetic defects at 7.9 years (95.2%) is a critical outcome, as any joint resurfacing should aim to reestablish mechanical homeostasis and anatomical shape with an integrated surface, particularly since chondrocyte-mediated biosynthesis, remodeling, and either tissue repair or degradation over time is dependent on the mechanical loading conditions of cartilage [24]. Normal surface morphology and joint articulation would be expected to improve biomechanical conditions and inhibit the degeneration of defect and peri-defect tissues and slow the progression of secondary osteoarthritis [8, 9]. This particular outcome was not fully unexpected, since critical size osteochondral defects in goat knees treated with ChondroMimetic scaffolds yielded similarly striking filling [14]. Furthermore, this level of defect filling is greater than that resulting from another off-the-shelf biological scaffold, BST-CarGel, at 5 year spost-treatment, which produced %Fill of 93.79%, as determined by very similar quantitative MRI methods [13]. Quantitative MRI also identified durable, high quality cartilage repair tissue by T2 relaxation time for ChondroMimetic-treated defects. T2 relaxation time is well known to be sensitive to, and highly dependent on, the extracellular cartilage matrix and particularly the collagen network structure, orientation, as well as macromolecular concentration, and tissue hydration [25, 26, 27, 28, 29]. When acquired under standardized conditions coupled with three-dimensional segmentation of regions of interest, T2 relaxation time has been an effective, quantitative method for comparing repair tissue to native articular cartilage, and/or to repair tissue resulting from another treatment [13, 30, 31]. Here, the determination of the quality of repair is evidenced by the closeness of measured T2 values to that found from the ipsilateral normal articular cartilage (52.3 vs. 52.5 ms, \(p=0.94\)), indicating a near-normal level of tissue quality after 7.9 years. The overall level of repair tissue organization achieved is further evidenced by the T2 standard deviations calculated for each repair tissue volume, which were comparable to native cartilage with a variance that was statistically equal to that of native cartilage. In contrast, a tissue with regions of differing organization, or of mixed hyaline-fibocartilage tissue, would be expected to have a more widespread variance than normal cartilage. When comparing to T2 outcomes resulting from MRI studies with other scaffolds, ChondroMimetic repair tissue demonstrated  
Figure 3: Knee Injury and Osteoarthritis Outcome Scores (KOOS) for ChondroMimetic subjects at a mean follow-up of 7.9 years. Data represents mean + standard deviation (n = 15). a similar closeness to native control cartilage as a study with Hyalograft C [32] in the knee, but was improved compared to the MaioRegen scaffold in the ankle [30], and BST-CarGel in the knee [13], neither of which resulted in T2 relaxation times similarly close to control cartilage.