Microstructural scaffold (patch) insertion without autologous cell implantation for repairing symptomatic chondral knee defects

4.1 In a randomised controlled trial of 38 patients with cartilage knee defects, autologous matrix-induced chondrogenesis (AMIC) techniques (sutured [n=13] or glued [n=15]) were compared with microfracture (MFx; n=10). In the interim analyses, the mean modified Cincinnati scores (assessing knee function [6 to 30 points], clinical pathology [0 to 20 points], and highest activity level without pain [0 to 50 points]; a maximum possible score of 100 points) increased significantly from baseline values of 47±20 to 82±14 (p<0.001) for the sutured AMIC group, 47±15 to 67±27 (p=0.02) for the glued AMIC group and 37±14 to 68±17 (p=0.002) for MFx group respectively at 1‑year follow-up. There were no statistically significant differences between the groups. At 2 years, mean scores increased significantly from baseline to 88±9 (p<0.001) for the sutured group, to 85±18 (p<0.001) for the glued AMIC group and to 83±8 (p<0.001) for the MFx group. There were no statistically significant differences between the groups. In a case series of 27 patients with 32 chondral lesions treated with AMIC, the mean Cincinnati scores improved significantly from baseline (46±18 to 66±23; p<0.05) at 1 year and further increased (to 74±23) at 2 years (level of significance not given). Non-significant declines in scores were reported at 36‑month follow-up (62±26) and 48‑month follow-up (37±9).

4.2 In the randomised controlled trial of 38 patients with cartilage knee defects comparing AMIC techniques (sutured [n=13] or glued [n=15]) against MFx (n=10), pain (measured on a visual analogue scale [VAS], 0 [no pain] to 100 [severe pain]) was rated less severe by patients at 1- and 2‑year follow-up compared with baseline and was similar between the groups. At 1‑year follow-up, pain decreased significantly from baseline for sutured AMIC (46±19 to 14±13; p<0.001), glued AMIC (48±20 to 16±13; p< 0.001) and MFx (54±21 to 19±17; p=0.002), and was further reduced at 2‑year follow-up without statistical significance (9±6 for sutured AMIC; 10±13 for glued AMIC; 5±3 for MFx). In a case series of 57 patients, knee pain (measured with a VAS) decreased significantly from baseline at 1‑year follow-up (7.0±1.8 to 2.7± 2.4; p<0.001) and at 2‑year follow-up (2.0±2.1; p<0.003). The mean VAS improvement from baseline to 1‑year follow-up was 4.2±2.6 (p<0.001), from 1- to 2‑year follow-up was 0.5±2.3 (p=0.003), and from baseline to 2‑year follow-up was 4.7±2.7 (p<0.001).

4.3 In the randomised controlled trial of 38 patients with cartilage knee defects comparing AMIC techniques (sutured [n=13] or glued [n=15]) against MFx (n=10), at 1‑year follow-up, patients in all groups (n=30) rated their functional status as improved (n=24) or stable (n=6; using the International Cartilage Repair Society [ICRS] Cartilage Injury Standard Evaluation Form 2000). At 2 years, patients in all groups rated their functional status as improved (n=12), stable (n=13) or deteriorated (from normal to nearly normal; n=2). Surgeon-rated assessments, based on the modified ICRS score (with respect to functional status, classification of the knee and crepitation using parts 3, 4 and 7 of the ICRS form), reported improvement in clinical symptoms and function and found no differences between the groups at 1- and 2‑year follow-up. In the case series of 27 patients, mean ICRS scores improved significantly from baseline (31±15 to 59±24; p<0.05) at 1 year and further increased (to 68±22) at 2 years (level of significance not given). Scores declined non-significantly at 36‑month follow-up (54±25) and 48‑month follow-up (37±4).

4.4 In a randomised controlled trial of 80 patients with cartilage knee defects comparing a chitosan-based scaffold (n=40) with MFx alone (n=39), at 1‑year follow-up, there were no significant differences in clinical benefit between the scaffold and MFx groups (measured on Western Ontario and McMaster Universities Osteoarthritis Index subscales for pain, stiffness and function), but significant improvement (p<0.0001) from baseline was seen for both groups. There were no significant differences in quality-of-life scores (measured with SF‑36 health survey, higher positive scores indicating better results) between the scaffold and MFx treatment groups at 1‑year follow-up; both the physical component scores (13.02 in the scaffold group versus 14.76 in the MFx group; p=0.41) and the mental component scores (3.54 in the scaffold group versus 0.84 in the MFx group; p=0.22) were similar.

4.5 In a retrospective case series of 38 patients (40 knees) treated with AMIC for full-thickness chondral and osteochondral defects of the femoral condyles and patella, International Knee Documentation Committee (IKDC) scores (using the IKDC Subjective Knee Evaluation form 2000, score range 0 to 100, higher scores representing higher levels of function and lower levels of symptoms) improved significantly from baseline to a mean follow-up of 28.8 months in the osteochondral femoral condyle group (from 44±25 to 88±9; p=0.005) and the chondral patella group (from 51±25 to 74±17; p=0.0025). However, improvements in the chondral femoral condyle group were not significant (from 45±26 to 68±14). Significant differences were seen between the 3 groups (p=0.0016). There were no significant differences in outcomes in patients treated with AMIC alone compared with those who also had an osteotomy or realignment procedure. In a case series of 30 patients treated for chondral or osteochondral lesions with a cell-free collagen hydroxyapatite osteochondral scaffold, mean IKDC subjective scores improved significantly from 40.0±15.0 at baseline to 76.5±14.4 (p<0.0005) at 2‑year follow-up and 77.1±18.0 (p<0.0005) at 5‑year follow-up.

4.6 In the case series of 27 patients, mean Lysholm scores (a patient knee functional scoring scale with 8 items and a maximum possible score of 100) improved significantly from baseline (36±21 to 67±28; p<0.05) at 1‑year follow-up and further increased (to 76±24) at 2‑year follow-up (level of significance not given). Non-significant declines in scores were seen at 36‑month follow-up (62±25) and 48‑month follow-up (47±22).

4.7 In the case series of 27 patients, mean Tegner score (a patient activity level scale; score range 0 to 10, with higher scores representing participation in higher-level activities) improved significantly from baseline (not reported) to 3.4 (p<0.05) at 1‑year follow-up and further increased to 4.1 at 2‑year follow-up (level of significance not given). Non-significant decline in scores was seen at 36‑month follow-up (4.0). In the case series of 30 patients with chondral or osteochondral lesions treated with a cell-free collagen hydroxyapatite osteochondral scaffold, mean Tegner score improved significantly from 1.6±1.1 at baseline to 4.0±1.8 (p<0.0005) at 2‑year follow-up and to 4.1±1.9 (p<0.0005) at 5‑year follow-up.

4.8 In a case series of 23 patients with symptomatic knee osteochondritis dissecans, EQ‑VAS score (a measure of patients' own global rating of their overall health, on a scale 0 [worst imaginable health state] to100 [best imaginable health state]) had improved significantly from baseline at 2‑year follow-up (3.15±1.09 to 8.15±1.04; p<0.0005).

4.9 In the case series of 38 patients (40 knees), patient satisfaction (rated on a scale of 0% to 100%, 0 indicating completely dissatisfied and 100 indicating completely satisfied) was high in all subgroups and there was no significant difference between groups (osteochondral femoral group 94±8; chondral patella group 84±24; chondral femoral condyle group 74±43). In the case series of 23 patients with symptomatic knee osteochondritis dissecans, satisfaction was recorded in 85% (absolute numbers not given) of patients.

4.10 In the case series of 30 patients with chondral or osteochondral lesions treated with a cell-free collagen hydroxyapatite osteochondral scaffold, MRI evaluation showed an improvement in both the magnetic resonance observation of cartilage repair tissue (MOCART) score and subchondral bone status (part of MOCART, 5 variables rated on a scale of 1 to 3) at 2- and 5‑year follow-up. At 5‑year follow-up, complete filling of the cartilage was shown in 78% of lesions (absolute numbers not given), complete integration of the graft was detected in 70% of cases, the repair tissue surface was intact in 61% of cases and the structure of the repair tissue was homogenous in 61% of the cases. No correlation was found between MRI findings and clinical outcome. In the randomised controlled trial of 80 patients with cartilage knee defects comparing a chitosan-based scaffold (n=40) with MFx alone (n=39), at 1‑year follow-up, the scaffold group achieved statistical superiority for greater lesion filling (92.8±2.0% versus 85.2±2.1% with MFx; p=0.011) and more hyaline cartilage-like T2 relaxation times (70.5±4.5 milliseconds versus 85.0±4.9 milliseconds with MFx; p=0.033) on MRI analysis.

4.11 The specialist advisers listed key efficacy outcomes as improved clinical benefit, MRI evidence of chondro-regeneration (for example, T2 mapping and d‑GERMIC) and delayed replacement arthroplasty.