Introduction
Current cartilage repair strategies and tissue engineering
Scaffolds available for clinical application
A bilayer collagen type I–III membrane
Collagen type I gel
Hyaluronan-based polymer
Fibrin
Synthetic copolymer
Clinical outcomes of articular cartilage repair with scaffolds
Authors | Study design | Scaffold, Technique etc |
N
| Follow-up | IKDC score | Lysholm score | Cincinnati knee score | ICRS Functional score, evaluation form | VAS etc | Other clinical outcomes |
---|---|---|---|---|---|---|---|---|---|---|
Manfredini et al. [65] | Prospective, non-randomised | Hyaluronan (Hyalograft C) vs. ACI (Carticel) | 10 vs. 17 | 1 year | – | – | – | 77 vs. 75 NS preoperative: 53 vs. 54 NS Post-operative values in both groups significantly improved compared with preoperative values (p = 0.005, 0.001) | – | HSS score; Excellent or Good: 90 vs. 88% NS |
Marcacci et al. [69] | Prospective, uncontroled | Hyaluronan (Hyalograft C), Arthroscopic technique | 70 | Minimum of 2 years | Objective; Normal or Nearly normal: 89%. Post-operative values significantly improved compared with preoperative values (p < 0.0005). Subjective; Post-operative values significantly improved compared with preoperative values (p < 0.0005) | – | – | – | EQ-VAS; Post-operative values significantly improved compared with preoperative values (p < 0.0005) | – |
Ossendorf et al. [84] | Prospective, uncontroled | Polymer (Bio-Seed-C) | 40 | 2 years | IKDC SF-36 current health assessment; Post-operative values significantly improved compared with preoperative values (p < 0.05) | Mean score increased from 46 to 81 in patients with posttraumatic and/or mild degenerative defects and from 47 to 79 in patients with osteoarthritic degeneration, (p < 0.007) | Statistically significant improvements were observed (p < 0.05) | – | – | KOOS; The patient’s status had improved significantly (p < 0.05) |
Retrospective, cross-sectional | Hyaluronan (Hyalograft C) | 15 | 3–42 months | – | – | – | – | – | Brittberg score; Excellent or Good: 80% | |
Behrens et al. [6] | Prospective, uncontroled | Porcine collagen I/III matrix (Chondro-Gide) | 11 | 5 years | – | Post-operative values significantly improved compared with preoperative values (p = 0.04) | – | Post-operative values significantly improved compared with preoperative values (p = 0.03) | – | Tegner activity score; There was no significant improvement. Meyer score; Post-operative values significantly improved compared with preoperative values (p = 0.007) |
Gobbi et al. [36] | Case series | Hyaluronan (Hyalograft C) for damaged articular surface of the patellofemoral joint | 32 | 2 years | Subjective; 74 preoperative: 43, Objective; Normal or Nearly normal: 91% Post-operative values significantly improved compared with preoperative values (p < 0.0001) | – | – | – | EuroQol-EQ-5D questionnaire; 53% and 90% of patients had no pain and morbility problems | – |
Marlovits et al. [71] | Retrospective, cross-sectional | Hyaluronan (Hyalograft C) | 9 | 2 years | 2.62 ± 0.65 | KOOS; pain 68 ± 24; symptoms 62 ± 15; ADL 75 ± 22; sport 53 ± 29; QOL 70 ± 22 | ||||
Nehrer et al. [82] | Prospective, case series | Hyaluronan (Hyalograft C) | 36 | 3 years | Excellent or Good: 87%, average: 60 ± 25 preoperative: 39 ± 19, Post-operative values significantly improved compared with preoperative values (p < 0.02) | 81 ± 19 preoperative: 58 ± 14, Post-operative values significantly improved compared with preoperative values (p < 0.05) | 7 ± 3 preoperative: 3 ± 2 | – | – | – |
Bartlett et al. [5] | Prospective, randomised | Porcine-derived collagen I/III matrix (MACI) vs. ACI with a cover manufactured from Porcine-derived collagen I/III(Matricel) | 47 vs. 44 | 1 year | – | – | 64 vs. 59 NS (modified) preoperative: 45 vs. 41 NS, Post-operative values in both groups significantly improved compared with preoperative values (p = 0.002, 0.01) | – | 4 vs. 4 NS preoperative: 6 vs. 6 NS, Post-operative values in both groups significantly improved compared with preoperative values (p = 0.003, 0.001) | Stanmore functional rating; 2 vs. 2 NS preoperative: 3 vs. 3NS Post-operative values in both groups significantly improved compared with preoperative values (p = 0.02, 0.02) |
Marcacci et al. [68] | Retrospective, case series | Hyaluronan (Hyalograft C) | 141 | Average: 38 months (2–5 years) | Subjective; 92% of patients improved. average: 79 ± 20 preoperative:40 ± 14, Post-operative values significantly improved compared with preoperative values (p < 0.0001). Objective; Normal or Nearly normal: 96% | – | – | Functional status: 71% of the patients could do everything or nearly everything (Levels I and II) | EuroQol-EQ-5D questionnaire; 76% and 88% of patients had no pain and morbility problems. Post-operative values (0.7) significantly improved compared with preoperative values (0.9) (p < 0.0001) | – |
Visna et al. [115] | Prospective, randomised, controlled | Fibrin glue (Tissucol) vs. ablasive technique | 25 vs. 25 | 1 year | Subjective; 76 ± 13 vs. 68 ± 10 Significantly better in ACI in fibrin glue (p < 0.05) preoperative:41 ± 12 vs. 45 ± 11 | 86 ± 9 vs. 74 ± 11 Significantly better in ACI in fibrin glue (p < 0.001) preoperative:48 ± 11 vs. 53 ± 11 | – | – | – | Tegner activity score; 5.9 ± 0.8 vs. 4.2 ± 1.1 Significantly better in ACI in fibrin glue(p < 0.01) preoperative:3.2 ± 0.8 vs. 2.3 ± 1.1 |
Cherubino et al. [22] | Prospective, uncontroled | Porcine collagen I/III matrix (MACI) | 6 | Minimum of 6 months | – | 94 (range, 87–97) preoperative:46.5 (range, 18–67) | Clinical evaluation;8.5(range, 6–10) preoperative:4.7 (range, 2–6) Patients’ evaluation; 8 (range, 6–10) preoperative:2.6 (range, 2–4) | Evaluation form; 4 normal knees and 2 nearly normal knees | – | Tegner activity score; 6.5 (range, 5–7) preoperative:2.6 (range, 1–4) |
Pavesio et al. [85] | Retrospective, case series | Hyaluronan (Hyalograft C) | 67 | Mean:17.5 months | Subjective; 78 ± 18 preoperative: 37 ± 9, Post-operative values significantly improved compared with preoperative values (p < 0.01). Objective; Normal or Nearly normal: 87% | – | – | – | EQ-VAS; 88 ± 14 preoperative: 59 ± 17, Post-operative values significantly improved compared with preoperative values (p < 0.05) | – |
Ochi et al. [83] | Prospective, case series | Collagen I gel (Atelocollagen) with periosteal cover | 28 | 2 years | – | 97 ± 5 preoperative: 71 ± 12, Post-operative values significantly improved compared with preoperative values (p < 0.001) | – | – | – | – |
Authors | Arthroscopic findings, ICRS visual scoring system | Histological findings | Magnetic resonance imaging | Complications | Other findings |
---|---|---|---|---|---|
Manfredini et al. [65] | – | – | Most patients in both groups showed the formation of tissue characteristics similar to the surrounding healthy cartilage. Four patients in ACI group showed hypertrophic growth of the repair tissue | There were no major adverse events observed | – |
Marcacci et al. [69] | A complete coverage with a hyaline cartilage-like tissue with integration with the surrounding cartilage in 12 of 15 patients | Specimens obtained from 2 patients showed hyaline-like cartilage in one patient and fibrocartilage in the other with close integration into the subchondral bone. In one patient, a tidemark was observed | – | There were no major adverse events observed | Results were better in young patients who practiced sport at a highly competitive level |
Ossendorf et al. [84] | The implanted grafts completely filled the defects and formed a tough hyaline-like cartilage | One repair tissue appeared as a mixed tissue of hyaline-like and fibrous cartilage,whereas 3 biopsies documented the development toward a hyaline repair tissue | Analysis at 6 months and 12 months after implantation showed good defect filling | Of the 79 patients, 5 underwent reoperation comprising synovectomy, debridement, total knee arthroplasty, and removal of graft | – |
– | – | Repair tissue T2 line profiles normalized over time toward the control sites | – | – | |
Behrens et al. [6] | Four of six patients showed tissues that correspond to the genuine cartilage with good integration into the adjacent areas | Specimens obtained from 4 patients showed fibrocartilagenous tissue in 3, and fibrous connective tissue in one | – | There were detachment of the transplat in one knee (9%) and a softer transplant in another (9%) | – |
Gobbi et al. [36] | ICRS scale: Nearly normal: 6 of 6 patients (100%) | Specimens obtained from 6 patients showed hyaline-like cartilage in 4 patients and mixed in the other 2 patients | Improvements with 71.9% of patients having > 50% or complete fill, 75%having normal or nearly normal signal, 90.6% having mild or no effusion, 84.4% having mild or absent subchondral edema.None of the defects treated resulted in graft hypertrophy or delamination | Fibrosis in 1 patient (3%) was documented | – |
Marlovits et al. [71] | – | – | A complete filling in 61.5%; a complete integration in 76.9%; an intact subchondral lamina in 84.6%; intact subchondral bone in 61.5%; isointense signal intensities in 92.3% | A graft failure was found in one patient (11%) with complete dissemination of the transplant | The clinical scores were correlated with the MRI variables |
Nehrer et al. [82] | – | – | – | There were no major adverse events observed | Patients under 30 years of age with single lesions showed significant improvements compared to those over 30 years with multiple defects (p < 0.01) |
Bartlett et al. [5] | ICRS score: Excellent or Good: 66.6 vs. 79.2% NS | Hyaline-like or Hyaline-like with fibrocartilage: 36.4 vs. 43.9% NS | – | The rate of hypertrophy: 3 (6%) vs. 4 (9%)The frequency of re-operation: 9 vs. 9% Wound infection: 1 (2%) | Patients aged less than 35 years had a significantly better clinical outcome compared with those aged more than 35 years (p = 0.03) |
Marcacci et al. [68] | ICRS scale: Normal or Nearly normal: 96.4% | Twelve of 22 patients showed hyaline-like tissue, whereas 6 were classified as mixed tissue, 4 showed a fibrocarilage appearance | – | Nine patients (4.7%) reported adverse events or complications such as arthrosynovitis. There were 10 (5.2%) graft failures | – |
Visna et al. [115] | Average ICRS score in 4 patients after ACI in fibrin glue: 8.5 (6–11) | Specimens obtained from 4 patients after ACI in fibrin glue showed hyaline-like cartilage | – | Five patients had reactive synovitis and 4 had shaving of adhesion | – |
Cherubino et al. [22] | – | – | MRI taken after 6 and 12 months showed the presence of hyaline-like cartilage, with restoration of the articular surface, in all the knees | No complications were observed | – |
Pavesio et al. [85] | Brittberg scale:Normal or Nearly normal: 96.7% | Fourteen of 22 patients showed hyaline-like tissue, whereas 4 were classified as mixed tissue, 4 showed a fibrocarilage appearance | – | Four patients reported fibroarthrosis or periosteal hypertrophy | Longer time points from implantation may be correlated to better histological appearance. The larger the size, the greater the improvement |
Ochi et al. [83] | ICRS scale: Normal or Nearly normal: 93% | Specimens obtained from 2 patients showed hyaline-like cartilage with steady integration into the subchondral bone | – | There were marked hypertrophy of the graft in 3 knees, partial detachment of the periosteum in 4 and partial ossification of the graft in one | – |