- Email: [email protected]
Arthroscopic Matrix-Induced Autologous Chondrocyte Implantation: 2-Year Outcomes
Arthroscopic Matrix-Induced Autologous Chondrocyte Implantation: 2-Year Outcomes Jay R. Ebert, B.Sc., Ph.D., Michael Fallon, M.B.B.S., F.R.A.N.Z.C.R., Timothy R. Ackland, Ph.D., F.A.S.M.F., David J. Wood, B.Sc., M.B.B.S., M.S., F.R.C.S., F.R.A.C.S., and Gregory C. Janes, M.B.B.S., F.R.A.C.S.
Purpose: To determine the safety and efficacy of a new arthroscopic technique for matrix-induced autologous chondrocyte implantation (MACI) for articular cartilage defects in the knee. Methods: We undertook a prospective evaluation of the first 20 patients treated with the MACI technique (including 14 defects on the femoral condyle and 6 on the tibial plateau), followed up for 24 months after surgery. A 12-week structured rehabilitation program was undertaken by all patients. Patients underwent clinical assessment (Knee Injury and Osteoarthritis Outcome Score, Short Form 36 Health Survey, visual analog pain scale, 6-minute walk test, knee range of motion) before surgery and at 3, 6, 12, and 24 months after surgery and underwent magnetic resonance imaging (MRI) assessment at 3, 12, and 24 months after surgery. MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score. Results: A significant improvement (P ⬍ .05) was shown throughout the postoperative time line for all Knee Injury and Osteoarthritis Outcome Score subscales, the physical component score of the Short Form 36 Health Survey, the frequency and severity of knee pain, and the 6-minute walk test. An improvement in pertinent morphologic parameters of graft repair was observed to 24 months, whereas a good to excellent graft infill score and MRI composite score were observed at 24 months after surgery in 90% and 70% of patients, respectively. Conclusions: We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period. Level of Evidence: Level IV, therapeutic case series.
M
atrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, showing good outcomes.1-6 It is a 2-stage
procedure involving an initial arthroscopic harvest of healthy cartilage, isolation and expansion of chondrocytes ex vivo, and subsequent reimplantation of the cells into the knee as a cell-scaffold construct. This
From the School of Sport Science, Exercise and Health (J.R.E., T.R.A.) and School of Surgery (J.R.E., D.J.W.), University of Western Australia, Crawley, Australia; Perth Radiological Clinic (M.F.), Subiaco, Australia; and Perth Orthopaedic and Sports Medicine Centre (G.C.J.), West Perth, Australia. The authors report the following potential conflict of interest or source of funding in relation to this article: Hollywood Private Hospital Research Foundation (RF31 and RF050), National Health and Medical Research Council (ID1003452), and Genzyme. Received December 16, 2010; accepted December 5, 2011. Note: To access the supplementary tables (Tables 2 and 3) accompanying this report, visit the [Month] issue of Arthroscopy at www.arthroscopyjournal.org. Address correspondence to Jay R. Ebert, B.Sc., Ph.D., School of Sport Science, Exercise and Health (M408), University of Western Australia, 35 Stirling Highway, Crawley, 6009, Australia. E-mail: [email protected] © 2012 by the Arthroscopy Association of North America 0749-8063/10752/$36.00 doi:10.1016/j.arthro.2011.12.022
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ARTHROSCOPIC MACI matrix can subsequently be cut to the exact size of the defect and fixed in place with fibrin glue, which has been shown to support migration and proliferation of human chondrocytes.7,8 One of the disadvantages of the MACI technique versus other osteoarticular transplantation systems (OATS) and microfracture techniques is that MACI requires a second surgery and an arthrotomy for implantation of the matrix.9-12 This arthrotomy may lead to a range of associated complications, such as arthrofibrosis, decreased range of movement, pain, and scarring.13 However, the MACI procedure lends itself to an arthroscopic implantation technique, decreasing the associated comorbidity of arthrotomy while allowing for faster postoperative rehabilitation because of reduced pain and muscular deficits.13 With the aforementioned proposed benefits of an arthroscopic procedure, several arthroscopic MACI techniques have already been described, with a variety of associated technical difficulties and results reported.13-18 The purpose of this study was to determine the safety and efficacy of a new arthroscopic MACI technique for treating articular cartilage defects in the knee. We hypothesized that this surgical technique would be safe and effective in the treatment of articular cartilage defects of the femoral condyles and tibial plateau. METHODS Patients A consecutive series of 20 patients, amenable to the arthroscopic technique, underwent arthroscopic MACI between June 2006 and September 2009. Initially, patients were identified as being suitable for MACI. This included being aged 15 to 65 years and deemed able to follow the structured postoperative rehabilitation program. Patients were excluded if they had a body mass index (BMI) greater than 35, had ligamentous instability, had undergone a prior extensive meniscectomy, had ongoing progressive inflammatory arthritis, or had varus/valgus lower limb malalignment (as indicated by a tibiofemoral anatomic angle ⬎3°). The orthopaedic specialist initially evaluated the patient for joint malalignment, and should further investigation have been warranted, long leg alignment radiographs (Maquet views) were obtained. Preoperatively, all patients had persistent pain associated with grade III or IV chondral lesions, assessed with the International Cartilage Repair Society chondral defect classification system.19 This was confirmed in all patients by preoperative magnetic reso-
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nance imaging (MRI) assessment and was later confirmed at the time of first-stage arthroscopic chondral biopsy. Preoperative MRI was used to approximately assess the location, size, and severity of the chondral defect, as well as any other soft-tissue damage incorporating the menisci or ligamentous structures. Once patients were identified as being suitable for MACI, on the basis of the aforementioned criteria, we would then consider whether they might be suitable for an arthroscopic approach. The arthroscopic approach was considered in all patients who had isolated lesions on the weight-bearing surface of either the femoral or tibial condyle (medial or lateral) unless their lesions were at the external periphery of the condyle, because these lesions might be problematic with the arthroscopic technique we are using because of the potential interference of the menisci with the inflatable portion of the indwelling catheter. The arthroscopic approach was likewise not considered for patients with patella, trochlea, or multiple lesions, because they were considered beyond the current capabilities of this technique. Therefore, over the recruitment period (June 2006 to September 2009), a total of 61 patients underwent MACI grafting (20 of whom underwent the arthroscopic technique). One of the advantages of planning and performing the arthroscopic technique is that it may be converted to a mini-open technique at any stage during the operation. Among all patients in whom we embarked on the arthroscopic technique (n ⫽ 20), none required conversion to an open technique during the course of the procedure. Among the 20 patients, the matrix was implanted in 11 medial femoral condyles, 3 lateral femoral condyles, 2 medial tibial plateaus, and 4 lateral tibial plateaus (Table 1). The mean defect size was 2.72 cm2 (range, 1.00 to 5.00 cm2) (Table 1). At the time of implantation, the mean age of patients was 34 years (range, 16 to 57 years) and mean BMI was 26.6 (range, 21.1 to 34.8) (Table 1). Of the 20 patients recruited into this prospective trial, 14 (70%) had been treated previously with 1 or more surgical procedures to address knee pain and/or symptoms, including arthroscopy with chondral debridement with or without the removal of a loose body (n ⫽ 10), partial meniscectomy (n ⫽ 6), anterior cruciate ligament reconstruction (n ⫽ 3), and MACI through an open arthrotomy 6 years previously that failed. Six patients had not undergone any prior surgery in the designated knee, apart from the arthroscopic biopsy. Patients provided written informed consent before study enrollment, and ethics approval was obtained from the University of Western Australia
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J. R. EBERT ET AL. TABLE 1.
Descriptive Parameters for Patient Cohort That Underwent Arthroscopic MACI
Patient No.
Gender
Defect Location
Knee
Age (yr)
Weight (kg)
BMI
Defect Size (cm2)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean Range
F M F M M F M M F F M M M F M F M F F F
MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC LFC LFC LFC MTP MTP LTP LTP LTP LTP
R L R R R L R R L L R R L L R R L R L L
36 22 41 18 20 46 57 37 52 42 37 21 29 23 39 35 23 16 42 50 34 16-57
58.8 74.2 65.0 99.0 70.0 97.0 107.9 78.0 78.0 60.5 88.0 93.0 95.0 80.0 82.4 66.0 70.5 55.8 74.0 83.7 78.8 55.8-107.9
22.7 24.2 23.9 31.2 21.1 34.8 33.3 24.6 28.7 23.1 28.4 29.0 26.0 32.0 26.0 21.6 24.7 21.3 23.6 32.3 26.6 21.1-34.8
1.76 3.40 3.20 5.00 5.00 1.50 3.00 1.65 1.50 5.00 2.10 1.00 3.00 1.50 3.75 3.20 3.78 2.38 1.20 1.50 2.72 1.00-5.00
Prior Procedures DOS (yr) 1 1 1 0 0 0 1 0 1 1 0 4 4 0 3 1 2 2 0 0 1 0-4
17 6 15 2 2 1 1 5 1 4 1 8 9 2 1 10 11 6 5 5 6 1-17
Abbreviations: DOS, duration of symptoms; F, female; L, left; LFC, lateral femoral condyle; LTP, lateral tibial plateau; M, male; MFC, medial femoral condyle; MTP, medial tibial plateau; R, right.
and Hollywood Private Hospital Human Research Ethics Committees. Surgical Technique Surgery was performed by 2 orthopaedic surgeons, operating within the same hospital. Initially, an arthroscopic surgery was undertaken to harvest a fullthickness area of healthy articular cartilage (200 to 300 mg) from a non–weight-bearing area of the knee (the trochlear notch or the medial or lateral femoral condylar ridge). This was performed with the patient under general anesthesia with a thigh-high tourniquet.20 At this time, the site, geometry, and containment of the defect were further assessed, as was the integrity of the menisci and ligamentous structures. The suitability of the chondral defect for second-stage arthroscopic implantation was also further assessed at this time. The cartilage biopsy specimen was then sent to the laboratory (Genzyme, Perth, Australia), whereby chondrocytes were isolated from the cartilage tissue, cultured for approximately 4 to 8 weeks, and seeded onto a type I/III collagen membrane (ACI-Maix; Matricel GmbH, Herzogenrath, Germany) 3 days before second-stage reimplantation. At the time of second-stage graft implantation, standard arthroscopy with anteromedial and anterolateral
portals was performed by use of Ringer lactate solution to irrigate the joint. The cartilage defect was prepared by removing all damaged cartilage down to, but not through, the subchondral plate. The edges of the defect were debrided to ensure a well-defined and contained defect. The resultant defect was then “mapped” in several planes by use of the end of a graduated arthroscopy probe (Smith & Nephew, Memphis, TN) (Fig 1), and the membrane was initially oversized and cut based on these approximated measurements (Fig 2). After graft preparation, we converted to performing a “dry” arthroscopy of the knee by draining all irrigation fluid. An arthroscopic “sucker” was used to dry the defect bed, while an adrenaline-soaked patty was pressed onto the subchondral bone to further dry it and prevent any bleeding. The graft was introduced into the knee through a large-bore arthroscopic cannula, with an 8-mm inner diameter, with no valves (ConMed Linvatec, Largo, FL), and positioned within the defect by use of the probe (Fig 3). Care was taken to ensure that the membrane was oriented correctly. Dots were placed with a surgical marker on the different edges of the graft to assist with orientation within the knee (Fig 3). Graft size was reassessed to ensure an exact fit, and further graft trimming was performed if required. The large cannula facilitated multiple passes of the graft in and out of the
ARTHROSCOPIC MACI
FIGURE 1. The chondral defect was initially mapped in several planes arthroscopically for MACI graft shaping, by use of the graduated arthroscopic probe.
joint for fine-tuning without damaging it. Once we were satisfied with membrane fit and orientation, the graft was folded away from the defect to allow for the introduction of the fibrin glue through a 19-gauge needle (Becton and Dickinson, Franklin Lakes, NJ) through the most appropriate portal. An even spread of glue was achieved by use of the arthroscopic probe, and the graft was then replaced over the glue. Application of even pressure over the graft for 30 seconds is required to ensure uniform graft stability, before the fibrin glue becomes adherent. This was achieved with a Silastic Foley catheter (Cook Urological, Spencer, IN) (Fig 4). The end of the catheter was
FIGURE 2. After chondral defect measurement, the MACI graft was initially oversized and cut based on the approximated arthroscopic measurements.
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FIGURE 3. After initial sizing of the MACI graft, the membrane was introduced into the knee through a large-bore arthroscopic cannula and care was taken to ensure that it was placed and oriented correctly over the subchondral bed.
introduced into the knee through the most appropriate portal, while visualization was maintained through the opposite portal. Once centered over the graft, the balloon was then inflated with saline solution instilled into the end of the catheter outside of the knee, to distribute 30 seconds of even pressure over the area of the membrane. The transparent Silastic allows visualization of the graft underneath (Fig 4). After uniform membrane fixation, the knee was put through several cycles of knee flexion and extension under visualization to ensure graft stability. Any area
FIGURE 4. Once membrane sizing was satisfactory and an even spread of fibrin glue had been placed over the subchondral bed, even pressure over the graft was achieved by use of the balloon end of a Silastic Foley catheter (inset), inflated over the graft for 30 seconds.
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inadequately fixed had fibrin glue reapplied before closure of the portals. The arthroscopy portals were then closed in standard fashion without drainage. Postoperative Rehabilitation After hospital discharge, patients underwent a coordinated outpatient rehabilitation program of progressive exercise and graduated weight bearing over a period of 12 weeks, and further education and advice were provided up to the 12-month time point (Table 2, online only, available at www.arthroscopyjournal.org).21,22 Clinical Assessment Three subjective questionnaires were used to evaluate patient outcome before surgery and at 3, 6, 12, and 24 months after surgery: (1) the Knee Injury and Osteoarthritis Outcome Score (KOOS)23 to assess knee pain, symptoms, activities of daily living (ADLs), sports and recreation, and knee-related quality of life; (2) the Short Form 36 Health Survey (SF-36), which evaluated the general health of the patient, producing a mental component score and a physical component score24; and (3) a visual analog scale (VAS) that assessed the frequency and severity of knee pain on a scale from 0 to 10. Two functional tests were used by an independent therapist to evaluate functional status preoperatively and at 3, 6, 12, and 24 months after surgery: (1) the 6-minute walk test21,25 to assess the maximum comfortable distance the patient could walk in a 6-minute period and (2) assessment of maximal active knee flexion and extension range of motion (ROM), by use of a plastic goniometer. Defect size was calculated based on the dimensions of the chondral graft at the time of second-stage implantation, whereas the number of prior cartilage repair procedures and the duration of symptoms were obtained through a thorough patient history. MRI Assessment High-resolution MRI was conducted at 3, 12, and 24 months after surgery with a Siemens Symphony 1.5-T scanner (Siemens, Erlangen, Germany). Standardized proton density and T2-weighted fat-saturated images were obtained in the coronal and sagittal planes (slice thickness, 3 mm; field of view, 14 to 15 cm; 512 matrix in at least 1 axis for proton density images with minimum 256 matrix in 1 axis for T2weighted images). Additional axial proton density fatsaturated images were also obtained (slice thickness, 3 to 4 mm; field of view, 14 to 15 cm; minimum 224 matrix in at least 1 axis).
MRI evaluation used in this study assessed 8 pertinent parameters of graft repair (Table 3, online only, available at www.arthroscopyjournal.org) that have been previously outlined.26 Some modification was required to allow for discrepancies in MRI equipment and sequence protocols. MRI parameters (signal intensity, graft infill, border integration, surface contour, structure, subchondral lamina, subchondral bone, and effusion) were selected to best describe the morphology and signal intensity of the repair tissue. These parameters were scored individually from 1 to 4 (1, poor; 2, fair; 3, good; and 4, excellent) in comparison with the adjacent native cartilage. For the scoring parameter “graft infill,” an additional score of 3.5 was awarded for a fifth level (very good) corresponding with “graft hypertrophy,” as indicated by previous work.26,27 An MRI composite score was also calculated by multiplying each individual score by a weighting factor25 and adding the scores together. This composite score was, therefore, also scored from 1 to 4 (1, poor; 2, fair; 3, good; and 4, excellent). MRI evaluation was performed by an independent, experienced musculoskeletal radiologist, blinded to the clinical details and clinical outcome assessment. Data and Statistical Analysis A 1-way repeated-measures analysis of variance was used to investigate the progression of clinical (subjective and functional) outcomes over time. The number and percentage of grafts evaluated as good or excellent within each of the 8 pertinent parameters of graft repair, as well as the MRI composite score, at 3, 12, and 24 months after surgery were calculated and presented in table format. With regard to the MRI scoring system, intraobserver reliability assessment by use of the Spearman rank order () correlation was undertaken for the 8 pertinent MRI scores, as well as the MRI composite score, by use of 20 randomly selected images filtered through a second time to the radiologist. Statistical analysis was performed with SPSS software (version 17.0; SPSS, Chicago, IL), and statistical significance was determined at P ⬍ .05. RESULTS Clinical Assessment There was a significant improvement (P ⬍ .05) throughout the preoperative and postoperative time line for all 5 subscales of the KOOS, the physical component score subscale of the SF-36, the frequency and severity of knee pain as assessed by the VAS, and
ARTHROSCOPIC MACI TABLE 4.
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Summary of Analysis of Variance Results for Clinical Outcomes Throughout Preoperative and Postoperative Time Line
Variable KOOS Pain Symptoms ADLs Sports QOL SF-36 PCS MCS VAS Frequency Severity 6-min walk test (m) ROM (°) Knee flexion Knee extension
Before Surgery
3 mo
6 mo
12 mo
24 mo
P Value
58.06 (5.57) 59.46 (4.38) 73.24 (4.85) 27.88 (5.13) 24.86 (3.86)
76.17 (3.07) 83.93 (2.57) 85.76 (1.99) 24.87 (6.78) 42.54 (5.54)
80.92 (2.75) 87.5 (1.94) 87.69 (2.39) 32.37 (7.01) 48.03 (5.37)
80.07 (3.24) 85.3 (2.15) 89.67 (2.68) 51.05 (6.53) 51.97 (4.81)
86.81 (2.04) 85.94 (2.43) 94.61 (1.21) 67.19 (5.38) 56.25 (6.02)
⬍.0001 ⬍.0001 .008 ⬍.0001 ⬍.0001
38.51 (2.52) 49.79 (1.79)
39.43 (2.81) 53.2 (2.17)
43.84 (1.86) 55.47 (1.67)
47.21 (1.87) 53.66 (1.89)
49.98 (1.64) 55.19 (1.09)
.001 .194
6.53 (0.70) 5.48 (0.55) 501.6 (15.3)
3.68 (0.63) 3.26 (0.48) 570.6 (17.0)
2.66 (0.55) 2.24 (0.48) 599.5 (12.3)
2.45 (0.48) 2.21 (0.35) 592.2 (17.2)
2.56 (0.63) 1.94 (0.28) 587.1 (13.6)
.001 ⬍.0001 ⬍.0001
141.4 (1.5) ⫺1.3 (0.5)
141.2 (1.2) ⫺1.3 (0.4)
141.1 (1.8) ⫺1.2 (0.4)
141.3 (1.1) ⫺1.1 (0.4)
.614 .126
139.5 (1.8) ⫺0.25 (0.3)
NOTE. Data are shown as mean (SE). Abbreviations: ADLs, activities of daily living; KOOS, Knee Injury and Osteoarthritis Outcome Score; MCS, mental component score; PCS, physical component score; QOL, quality of life; ROM, range of motion; VAS, visual analog scale.
the 6-minute walk test (Table 4). Post hoc dependent t tests indicated that the improvement in knee pain, symptoms, and ADLs occurred predominantly in the first 3 months after surgery and was then maintained to 24 months. No significant improvement (P ⬎ .05) was observed for knee flexion and extension ROM or for the mental component score subscale of the SF-36 (Table 4) over the preoperative and postoperative period. MRI Assessment Intraobserver reliability for the defined MRI scoring method was evaluated by having the single radiologist score a repeat series of 20 MRI scans. This evaluation
indicated a significant correlation (P ⬍ .01) between radiologic scores within each of the 8 pertinent MRI scoring variables (signal intensity, ⫽ 1.00; graft infill, ⫽ 0.949; border integration, ⫽ 0.982; surface contour, ⫽ 1.00; structure, ⫽ 0.840; subchondral lamina, ⫽ 1.00; subchondral bone, ⫽ 0.920; and effusion, ⫽ 0.993), as well as the MRI composite score ( ⫽ 0.811), for the 20 randomly selected image pairs. At 3 months after surgery, 60% of grafts (n ⫽ 12) showed good to excellent filling of the chondral defect (Table 5) whereas signal intensity was described as good to excellent in only 5% (n ⫽ 1). Good to excellent scores were observed in 65% of grafts (n ⫽ 13)
TABLE 5. Number of Grafts at 3, 12, and 24 Months After Surgery Rated as Good to Excellent or Poor to Fair for MRI Composite Score and Each of 8 Individual MRI Parameters in Comparison With Adjacent Native Cartilage Postoperative Time Point 3 mo
12 mo
24 mo
Rating Good to excellent Poor to fair Good to excellent Poor to fair Good to excellent Poor to fair
Signal Border Surface Subchondral Subchondral Graft Infill Intensity Integration Contour Structure Lamina Bone
Effusion
MRI Composite Score
12 (60%)
1 (5%)
12 (60%) 11 (55%) 13 (65%)
17 (85%)
14 (70%)
20 (100%) 14 (70%)
8 (40%) 17 (85%)
19 (95%) 13 (65%)
8 (40%) 9 (45%) 7 (35%) 14 (70%) 13 (65%) 15 (75%)
3 (15%) 20 (100%)
6 (30%) 13 (65%)
0 (0%) 6 (30%) 20 (100%) 16 (80%)
3 (15%) 18 (90%)
7 (35%) 15 (75%)
7 (35%) 7 (35%) 5 (25%) 14 (70%) 13 (65%) 15 (75%)
0 (0%) 20 (100%)
7 (35%) 11 (55%)
0 (0%) 18 (90%)
4 (20%) 14 (70%)
2 (10%)
5 (25%)
0 (0%)
9 (45%)
2 (10%)
6 (30%)
6 (30%)
7 (35%)
5 (25%)
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J. R. EBERT ET AL. TABLE 6.
MRI-Based Assessment at 24 Months After Surgery for Each of 20 Patients Who Underwent Arthroscopic MACI
MRI Mean MRI Composite Patient Defect Graft Signal Border Surface Subchondral Subchondral Composite Score by Defect No. Location Infill Intensity Integration Contour Structure Lamina Bone Effusion Score Location 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC LFC LFC LFC MTP MTP LTP LTP LTP LTP
4 3.5 4 3.5 3.5 4 3 4 3.5 3 3.5 3 1 4 4 3.5 2 3 4 3
3 2 3 2 3 3 2 4 3 3 3 3 1 4 4 3 3 2 4 3
3 3 3 4 4 1 4 4 3 1 3 3 1 4 4 4 1 2 4 2
3 3 3 4 4 1 2 3 4 1 3 4 1 4 4 4 1 2 3 1
3 3 4 3 3 1 3 3 4 2 4 4 1 4 4 4 1 2 3 3
4 3 4 4 4 3 4 3 4 3 4 4 4 4 4 4 4 4 4 3
1 1 3 3 3 4 1 4 3 1 3 1 1 3 1 2 1 3 3 3
3 2 3 3 4 4 4 4 4 2 4 4 4 4 3 4 3 3 3 3
3.25 3.25 3.45 3.25 3.5 2.7 2.85 3.8 3.45 2.25 3.35 3.2 1.3 3.65 3.8 3.55 2.10 2.25 3.7 3.10
3.19
2.72
3.68 2.75
NOTE. Individual patient scores are shown for the MRI composite score and each of the 8 individual MRI parameters in comparison with the adjacent native cartilage, as well as a mean MRI composite score by defect location. Abbreviations: LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau.
for tissue structure, 60% (n ⫽ 12) for border integration, and 55% (n ⫽ 11) for the tissue surface contour. The subchondral lamina was rated as good to excellent in 85% of grafts (n ⫽ 17) at 3 months, whereas the subchondral bone was rated as good to excellent in 70% (n ⫽ 14). No evidence of moderate to severe knee joint effusion was shown at 3 months after surgery (Table 5). At 12 months after surgery, the percentage of grafts with good to excellent infill had increased to 85% (n ⫽ 17), with 55% (n ⫽ 11) showing complete infill (or graft hypertrophy) in comparison with the adjacent native cartilage. The percentage of grafts with good to excellent scores had also improved for signal intensity (65%, n ⫽ 13), border zone integration (70%, n ⫽ 14), surface contour (65%, n ⫽ 13), tissue structure (75%, n ⫽ 15), and subchondral lamina (100%, n ⫽ 20). Although there remained no evidence of moderate to severe knee joint effusion at 12 months, the percentage of grafts with good to excellent subchondral bone decreased marginally from 3 to 12 months (Table 5). At 24 months after surgery, the percentage of grafts with good to excellent infill had further increased to 90% (n ⫽ 18), with 65% (n ⫽ 13) showing complete infill (or graft hypertrophy). However, the percentage
of grafts with a good to excellent MRI composite score had fallen to 70% (n ⫽ 14), down from 80% (n ⫽ 16) at 12 months. Whereas signal intensity improved and border integration, surface contour, structure, and subchondral lamina were unchanged, the percentage of patients with good to excellent subchondral bone and effusion decreased (Table 5). When assessed by graft location, MACI to the medial tibial plateau provided the best mean MRI composite score (3.68, n ⫽ 2) at 24 months after surgery, followed by the medial femoral condyle (3.19, n ⫽ 11), lateral tibial plateau (2.75, n ⫽ 4), and lateral femoral condyle (2.72, n ⫽ 3) (Table 6). When assessed by defect size (⬎2 cm2 or ⬍2 cm2), 8 of 20 grafts (40%) were less than 2 cm2 and showed a mean MRI composite score at 24 months of 3.09 compared with 12 of 20 grafts (60%) greater than 2 cm2 showing an MRI composite score of 3.08. No significant difference (P ⬎ .05) was observed for tissue infill or the MRI composite score when we compared graft outcome dependent on defect size at 24 months after surgery. Figures 5 and 6 show the successful development of a postoperative MACI graft located on the medial femoral
ARTHROSCOPIC MACI
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FIGURE 5. Proton density fast spin echo magnetic resonance images of MACI graft (between arrows) to medial femoral condyle. The images are from the same patient and are representative of (A) before surgery; (B) 3 months after surgery, with reduced thickness and a hyperintense signal compared with the adjacent native cartilage; (C) 12 months after surgery, with equivalent signal and thickness characteristics to the adjacent native cartilage, good border zone integration, and good surface contour; and (D) 24 months after surgery, with relatively unchanged graft characteristics from 12 months, though with a mild increase in underlying bony edema.
condyle and on the lateral tibial plateau, respectively, for 2 different patients, as assessed with MRI. Complications and Failures Graft hypertrophy was reported in 5% of patients (1 graft) at 3 months after surgery and 20% (4 grafts) at both 12 and 24 months after surgery (Fig 7). All hypertrophic grafts were located on the medial femoral condyle. There was 1 graft failure (5%), as indicated by MRI, on a lesion of the lateral femoral condyle (33%) (Fig 8). DISCUSSION MACI performed as an open procedure has shown good short-term and midterm clinical results in the
treatment of articular cartilage defects in the knee.1-6 However, MACI performed through an open arthrotomy presents with a range of associated potential complications, such as arthrofibrosis, decreased range of movement, pain, and scarring, whereas the advantage of an arthroscopic surgical technique over an open surgical technique has been previously shown for other knee procedures.28,29 MACI lends itself to an arthroscopic implantation technique, decreasing the associated comorbidity of arthrotomy, and although methods of arthroscopically performed MACI remain in their infancy, several have been described, with a variety of associated technical difficulties and results reported.13-18 Marcacci et al.16 described the first arthroscopic MACI technique, whereby cells were seeded onto a
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FIGURE 6. Proton density fast spin echo magnetic resonance images of MACI graft (between arrows) to lateral tibial plateau. The images are from the same patient and are representative of (A) before surgery; (B) 3 months after surgery, with reduced thickness and a hyperintense signal compared with the adjacent native cartilage; (C) 12 months after surgery, with equivalent signal and thickness characteristics to the adjacent native cartilage, good border zone integration, and good surface contour; and (D) 24 months after surgery, with relatively unchanged graft characteristics from 12 months, though with a mild increase in underlying bony edema.
hyaluronic acid scaffold (Hyaff 11, Fidia Advanced Biopolymers Laboratories, Padova, Italy), with circular stamps of this construct placed over the prepared defect site using a circular corer. Satisfactory clinical results were later reported up to 48 months after surgery15 while reducing the associated morbidity of the open technique. However, it has been reported that an even distribution of pressure is required over the graft as the glue sets,14 and there has been no biomechanical testing to evaluate whether this technique provides adequate graft fixation at the time of implantation. Erggelet et al.13 described a transosseous 4-point fixation technique of graft fixation whereby the corners of the graft were secured by needles driven through the defect and fixed to the outer bone surface,
whereas Petersen et al.17 used 2 bioresorbable pins, driven through the graft to anchor it to the subchondral bone. More recently, Zantop and Petersen30 reported a similar technique for arthroscopic matrix-covered microfracture. Longer-term results in a larger patient cohort using these techniques are yet to be reported, although the method of applying an even distribution of pressure over the graft as the fibrin glue sets is not reported. Furthermore, these techniques appear to be technically demanding procedures, whereas with regard to MACI, associated adverse effects may include damage to the immediate area of graft penetration and bleeding, potentially interfering with the regeneration of repair tissue.17 Ronga et al.18 described an arthroscopic MACI technique whereby graft pressure was applied with an
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minor deterioration from before surgery to 3 months after surgery, although significant physical limitation is placed on patients over this early postoperative period.31 The KOOS subscales for sports and recreation and for quality of life continued to improve throughout the 24-month period, as indicated by post hoc testing. However, the KOOS subscales for pain,
FIGURE 7. Proton density fast spin echo magnetic resonance image of 1 of the 4 MACI grafts (between arrows) that showed graft hypertrophy at 24 months after surgery. All hypertrophic grafts were located on the medial femoral condyle.
arthroscopic probe in combination with a valgus knee stress. Although good clinical and radiologic outcomes were attained in this case report up to 12 months after surgery, application of even pressure over the graft while the fibrin glue set could not be enabled with the probe. Furthermore, this reported case involved treatment of a defect on the lateral tibial plateau, and this particular technique would prove difficult in treating lesions on the femoral condyles. Reported arthroscopic implantation techniques fail to show how an even distribution of pressure is provided over the graft as the fibrin sets, which is potentially important in adequate graft adherence.14 Furthermore, currently proposed techniques use needles13 or pins17 driven through the membrane for fixation, which may result in damage to the immediate area of graft penetration and bleeding. Our technique provides an even distribution of pressure through the inflation of the balloon end of a Silastic Foley catheter as the glue sets whereas no additional fixation is required, thereby avoiding bleeding, which may interfere with the regeneration of repair tissue.17 In this study a significant improvement was achieved in all subscales of the KOOS, VAS, and the physical component score subscale of the SF-36 over the 24month assessment period, indicated by a significant time effect for all subjective variables (Table 4). The sports and recreation subscale of the KOOS showed a
FIGURE 8. Proton density fast spin echo magnetic resonance images of failed MACI graft to lateral femoral condyle (between arrows), with full-thickness loss at (A) 3 months after surgery and (B) 12 months after surgery.
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symptoms, and ADLs improved predominantly in the first 3 months, with further minor improvement up to 24 months, showing a good early postoperative improvement. These 24-month KOOS and SF-36 outcomes are comparable, if not superior, to those previously reported for MACI performed through open arthrotomy at 12 and 24 months.22,32 A significant improvement over time was observed for the 6-minute walk test, with improvement up to 6 months, with a mild deterioration through 24 months, although the largest improvement was shown from before surgery to 3 months after surgery (Table 4). This is contrary to many studies that have shown a fall from before surgery to 3 months using both open matrix-induced22 and collagen-covered25 autologous chondrocyte implantation techniques. No significant improvement was observed in active knee flexion or extension ROM over the 24-month period (Table 4), although both full knee flexion and mild knee hyperextension were shown as early as 3 months and were maintained up to 24 months after surgery. Although the degree of knee effusion was not evaluated in this patient cohort, the reduced knee pain and swelling that may accompany the arthroscopic technique, as opposed to an open arthrotomy, could prove pivotal in the early recovery of knee function. Full active knee extension ROM is important in the return of a normal gait pattern, whereas the 6-minute walk test has been reported as a key component of many activities of normal daily living and a foundation for functional independence.25 When we grouped all chondral grafts irrespective of location, MRI-based evaluation at 3 months after surgery showed an immature graft, primarily with respect to tissue infill and signal intensity (Table 5). At 3 months, tissue infill above 50% of the adjacent native cartilage was observed in only 60% of grafts (n ⫽ 12), whereas 70% of grafts (n ⫽ 14) were given an overall MRI composite score rated as good or excellent based on the 8 pertinent parameters of graft repair. Several graft changes were observed in the 12- and 24-month MRI assessments. The percentage of grafts showing good to excellent tissue infill had increased to 85% (n ⫽ 17) at 12 months and 90% (n ⫽ 18) at 24 months, with 13 of these (65%) showing complete infill (or graft hypertrophy) in comparison with the adjacent native cartilage. Although detailed morphologic graft evaluation with MRI after arthroscopically performed MACI is limited, the degree of complete tissue infill presented in the literature after open MACI is varied. Welsch et al.33 showed complete infill in only 4 of 10 patients (40%) at 24 months, in comparison with
Genovese et al.,2 who reported 11 of 12 patients (92%) with complete tissue infill at 5 years, although both of these studies had smaller patient cohorts. Our 12month findings are, however, comparable to the outcomes of Kon et al.,4 who showed complete infill in 65% of patients at a minimum 5-year follow-up, after undergoing a different technique for arthroscopic MACI. At 24 months, 75% of grafts (n ⫽ 15) were isointense or hypointense compared with the adjacent healthy articular cartilage, whereas the percentage of grafts with good to excellent ratings for border integration (70%), surface contour (65%), and structure (75%) had increased. Good reconstitution of the subchondral lamina was observed in all cases, and although the percentage of grafts with a good or excellent MRI composite score had improved to 80% (n ⫽ 16) at 12 months, this fell to 70% (n ⫽ 14) at 24 months (Table 5). This coincided with a deterioration in scores for subchondral bone and effusion between the 3- and 24-month period. Both bone edema and joint effusion may be seen as signs of overloading and, subsequently, an inability of the regenerative tissue up until 12 to 24 months to appropriately transmit forces acting across the tissue,34 especially with the increasing patient activity level throughout this period. Although MRI evaluation as early as 12 months after surgery has been shown to be a reasonable time for assessing graft maturation,35 it should be noted that the repair tissue continues to develop and remodel up to 3 years after surgery.31,36,37 Therefore further improvements in tissue repair would be expected beyond this 24-month assessment of safety and efficacy. At 24 months after surgery, a mean MRI composite score of 3.68 (n ⫽ 2) was observed for MACI grafts located on the medial tibial plateau, with both grafts showing a good to excellent MRI composite score and tissue infill at or above the surface of the adjacent native cartilage (Table 6). For the other defect locations, mean MRI composite scores of 3.19 (medial femoral condyle, n ⫽ 11), 2.75 (lateral tibial plateau, n ⫽ 3), and 2.72 (lateral femoral condyle, n ⫽ 3) were recorded. Although an assessment of this surgical technique based on defect location should be considered with caution because of the low graft numbers, the lowest mean score recorded for the lateral femoral condyle was skewed with a single study graft failure. Among the 20 grafts that underwent MRI evaluation at 24 months after surgery, there was a 20% incidence of graft hypertrophy (n ⫽ 4). The incidence of graft overgrowth after MACI ranges from 13% to
ARTHROSCOPIC MACI 25% across different postoperative time points.2,6,27,38 The 4 patients with hypertrophic grafts at 12 and 24 months were nonsymptomatic, although they will be closely monitored to ascertain whether symptoms relating to graft “overfill” emerge. There was 1 graft failure (5%) as indicated by MRI at 12 months after surgery, which was observed in a compliant 29-year-old man, with a preoperative BMI of 26.0 and no pre-existing conditions that would warrant study exclusion. Although the reason for this graft failure remains unknown, this patient had undergone failed MACI 6 years prior in the same location, which was performed with an open arthrotomy. Although literature supporting arthroscopic MACI still remains limited, Nehrer et al.5 presented a 2- to 7-year follow-up and reported that 3 of 42 patients (7%) had graft failure, whereas Kon et al.4 outlined graft reabsorption in 2 of 50 patients (5%) at a minimum 5-year follow-up. Although this is a short-term follow-up more focused around the early safety and efficacy of the described arthroscopic MACI technique, it has been reported that graft delamination generally presents within the first 6 months.37 At this stage, outcomes pertaining to graft failure are comparable to those reported. Our study hypothesis was partially supported, whereby our arthroscopically performed MACI surgical technique was shown to be both safe and effective in addressing articular cartilage defects on the femoral and tibial condyles. This was with the exception of 1 failure (5%) on the lateral femoral condyle (33%) in a patient who had undergone failed MACI 6 years earlier through an open procedure. However, this failure rate is comparable to that reported in the literature, and the 12- to 24-month clinical outcomes are at least comparable to those reported in the literature for MACI performed through open arthrotomy, at 24 months and beyond. A number of limitations existed within this study. First, it is a small prospective case series with no comparative cohort and with a relatively short follow-up (24 months). Although the repair tissue produced by MACI requires a longer developmental time line and, therefore, prospective follow-up, the primary aim of this study was to evaluate the early safety and efficacy of the arthroscopic technique. Second, this study presented graft outcomes over varied locations, including the medial and lateral femoral, as well as tibial, weight-bearing condyles. A more comprehensive evaluation of this technique specific to each location is not yet attainable with such a small patient cohort. Third, 40% of the grafts treated in this cohort (8 of 20) were less than 2 cm2 (Table 1) and, therefore, are considered amenable to
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other cartilage repair methods such as OATS and microfracture. However, our preferred method of treatment is MACI to achieve a “hyaline-like” articular cartilage as opposed to the fibrocartilage that is generally the result of microfracture. We also held the view that the MACI procedure was superior to the OATS procedure in that there was virtually no risk of donor-site morbidity and the procedure was less invasive. Fourth, although the morphologic MRI scoring system used within this study has been used previously, new methods have emerged that may assess the biochemical characteristics of repair tissue.39-41 These new methods may be used in a longerterm follow-up to evaluate the “ultrastructure” of the repair tissue.42 Finally, no follow-up arthroscopy or histologic analysis has been undertaken in this case series, which may provide more information on repair tissue structure. However, postoperative arthroscopic biopsy provides ethical barriers, particularly when patients have a good early outcome and remain asymptomatic. CONCLUSIONS We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period. REFERENCES 1. Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/ MACI)—5-Year follow-up. Knee 2006;13:194-202. 2. Genovese E, Ronga M, Angeretti MG, et al. Matrix-induced autologous chondrocyte implantation of the knee: Mid-term and long-term follow-up by MR arthrography. Skeletal Radiol 2011;40:47-56. 3. Gobbi A, Kon E, Berruto M, et al. Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: Results at 5 years’ follow-up. Am J Sports Med 2009;37:1083-1092. 4. Kon E, Di Martino A, Filardo G, et al. Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol 2011;79:382-388. 5. Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R. Treatment of full-thickness chondral defects with hyalograft C in the knee: A prospective clinical case series with 2 to 7 years’ follow-up. Am J Sports Med 2009;37:81S-87S (Suppl 1). 6. Saris DB, Vanlauwe J, Victor J, et al. Treatment of symptomatic cartilage defects of the knee: Characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 2009;37:10S-19S (Suppl 1). 7. Gille J, Meisner U, Ehlers EM, Müller A, Russlies M, Behrens P. Migration pattern, morphology and viability of cells suspended in or sealed with fibrin glue: A histomorphologic study. Tissue Cell 2005;37:339-348.
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8. Kirilak Y, Pavlos NJ, Willers CR, et al. Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and proteaseactivated receptors. Int J Mol Med 2006;17:551-558. 9. Gudas R, Kalesinskas RJ, Kimtys V, et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 2005;21:1066-1075. 10. Hangody L, Vásárhelyi G, Hangody LR, et al. Autologous osteochondral grafting—Technique and long-term results. Injury 2008;39:S32-S39 (Suppl 1). 11. Reddy S, Pedowitz DI, Parekh SG, Sennett BJ, Okereke E. The morbidity associated with osteochondral harvest from asymptomatic knees for the treatment of osteochondral lesions of the talus. Am J Sports Med 2007;35:80-85. 12. Steadman JR, Rodkey WG, Briggs KK, Rodrigo JJ. The microfracture technic in the management of complete cartilage defects in the knee joint. Orthopade 1999;28:26-32 (in German). 13. Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of fullthickness cartilage defects of the knee joint. Arthroscopy 2003; 19:108-110. 14. Carey-Smith R, Ebert JR, Davies H, Garrett S, Wood DJ, Janes GC. Arthroscopic matrix-induced autologous chondrocyte implantation (MACI): A simple surgical technique. Tech Knee Surg 2010;9:170-175. 15. Marcacci M, Kon E, Zaffagnini S, et al. Arthroscopic second generation autologous chondrocyte implantation. Knee Surg Sports Traumatol Arthrosc 2007;15:610-619. 16. Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I. Arthroscopic autologous chondrocyte transplantation: Technical note. Knee Surg Sports Traumatol Arthrosc 2002;10:154-159. 17. Petersen W, Zelle S, Zantop T. Arthroscopic implantation of a three dimensional scaffold for autologous chondrocyte transplantation. Arch Orthop Trauma Surg 2008;128:505-508. 18. Ronga M, Grassi FA, Bulgheroni P. Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee. Arthroscopy 2004;20:79-84. 19. Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 2003;85:58-69 (Suppl 2). 20. Noordin S, McEwen JA, Kragh CJ Jr, Eisen A, Masri BA. Surgical tourniquets in orthopaedics. J Bone Joint Surg Am 2009;91:2958-2967. 21. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T. Traditional vs accelerated approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes. Osteoarthritis Cartilage 2008;16:1131-1140. 22. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T. A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-Year clinical outcomes. Cartilage 2010;1:180-187. 23. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)— Development of a self-administered outcome measure. J Orthop Sports Phys Ther 1998;28:88-96. 24. Bartlett W, Gooding CR, Carrington RW, Briggs TW, Skinner JA, Bentley G. The role of the Short Form 36 Health Survey in autologous chondrocyte implantation. Knee 2005; 12:281-285. 25. Robertson WB, Fick D, Wood DJ, Linklater JM, Zheng MH, Ackland TR. MRI and clinical evaluation of collagen-covered autologous chondrocyte implantation (CACI) at two years. Knee 2007;14:117-127.
26. Marlovits S, Striessnig G, Resinger CT, et al. Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging. Eur J Radiol 2004;52:310-319. 27. Trattnig S, Pinker K, Krestan C, Plank C, Millington S, Marlovits S. Matrix-based autologous chondrocyte implantation for cartilage repair with Hyalograft C: Two-year follow-up by magnetic resonance imaging. Eur J Radiol 2006;57:9-15. 28. Laffargue P, Delalande JL, Maillet M, Vanhecke C, Decoulx J. Reconstruction of the anterior cruciate ligament: Arthrotomy versus arthroscopy. Rev Chir Orthop Reparatrice Appar Mot 1999;85:367-373 (in French). 29. Oretorp N, Gillquist J. Transcutaneous meniscectomy under arthroscopic control. Int Orthop 1979;3:19-25. 30. Zantop T, Petersen W. Arthroscopic implantation of a matrix to cover large chondral defect during microfracture. Arthroscopy 2009;25:1354-1360. 31. Hambly K, Bobic V, Wondrasch B, Van Assche D, Marlovits S. Autologous chondrocyte implantation postoperative care and rehabilitation: Science and practice. Am J Sports Med 2006;34:1-19. 32. Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S. Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol 2006;57:16-23. 33. Welsch GH, Mamisch TC, Zak L, et al. Evaluation of cartilage repair tissue after matrix-associated autologous chondrocyte transplantation using a hyaluronic-based or a collagen-based scaffold with morphological MOCART scoring and biochemical T2 mapping: Preliminary results. Am J Sports Med 2010; 38:934-942. 34. Wondrasch B, Zak L, Welsch GH, Marlovits S. Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle on radiographic and clinical outcome after 2 years: A prospective, randomized controlled pilot study. Am J Sports Med 2009;37: 88S-96S (Suppl 1). 35. Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH. Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg Br 2003;85:1060-1066. 36. King PJ, Bryant T, Minas T. Autologous chondrocyte implantation for chondral defects of the knee: Indications and technique. J Knee Surg 2002;15:177-184. 37. Minas T, Peterson L. Advanced techniques in autologous chondrocyte transplantation. Clin Sports Med 1999;18:13-44. 38. Ebert JR, Fallon M, Robertson WB, et al. Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI). Cartilage 2011;2:60-72. 39. Kurkijärvi JE, Nissi MJ, Kiviranta I, Jurvelin JS, Nieminen MT. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage: Topographical variation and relationships to mechanical properties. Magn Reson Med 2004;52:41-46. 40. Tiderius CJ, Tjörnstrand J, Akeson P, Södersten K, Dahlberg L, Leander P. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): Intra- and interobserver variability in standardized drawing of regions of interest. Acta Radiol 2004;45:628-634. 41. Trattnig S, Millington SA, Szomolanyi P, Marlovits S. MR imaging of osteochondral grafts and autologous chondrocyte implantation. Eur Radiol 2007;17:103-118. 42. Domayer SE, Welsch GH, Dorotka R, et al. MRI monitoring of cartilage repair in the knee: A review. Semin Musculoskelet Radiol 2008;12:302-317.
ARTHROSCOPIC MACI TABLE 2. Progression of Postoperative Weight Bearing, Knee ROM, and Exercise Rehabilitation After Arthroscopic MACI Time Line
Rehabilitation Guidelines
1-2 wk
WB status TF joint: ⬍20% BW PF joint: 20%-30% BW Ambulatory aids TF joint: 2 crutches used at all times PF joint: 2 crutches used at all times Knee ROM TF joint: passive and active ROM from 0°-30° PF joint: passive and active ROM from 0°-20° Knee bracing TF joint: 0°-30° PF joint: locked at full knee extension Treatment/rehabilitation: isometric contractions and circulation exercises, CPM, and cryotherapy WB status TF joint: 30% BW (wk 3) to 60% BW (wk 6) PF joint: 50% BW (wk 3) to 75% BW (wk 6) Ambulatory aids TF joint: 2 crutches used at all times PF joint: 1-2 crutches used at all times Knee ROM TF joint: active ROM from 0°-90° (wk 3) to 0°-125° (wk 6) PF joint: active ROM from 0°-60° (wk 3) to 0°-125° (wk 6) Knee bracing TF joint: 0°-45° (wk 3) to full knee flexion (wk 6) PF joint: 0°-30° (wk 3) to brace removal (wk 6) Treatment/rehabilitation: isometric/straight leg and passive/active knee flexion exercises, remedial massage, patella mobilization, CPM, cryotherapy, and hydrotherapy WB status TF joint: 60% BW (wk 6) to full WB as tolerated (wk 8) PF joint: Full WB Ambulatory aids TF joint: 1 crutch as required until full WB achieved PF joint: 1 crutch as required until full WB achieved Knee ROM TF joint: Full active ROM (wk 7) PF joint: Full active ROM (wk 7) Knee bracing TF joint: Full knee flexion PF joint: No brace Rehabilitation: introduction of proprioceptive/balance activities, cycling, walking, resistance, and CKC activities Rehabilitation: introduction of more demanding OKC (terminal leg extension) and CKC (inner range quadriceps and modified leg press), upright cycling, rowing ergometry, and elliptical trainers
3-6 wk
7-12 wk
3-6 mo
964.e1 TABLE 2.
Continued
Time Line
Rehabilitation Guidelines
6-9 mo
Rehabilitation: increase in difficulty of proprioceptive/balance and OKC and CKC exercises (i.e., step-ups/step-downs and squats) and introduction of controlled mini-trampoline jogging Rehabilitation: increase in difficulty of CKC exercises (i.e., lunge and squat activities on unstable surfaces), introduction of agility drills relevant to patient’s sport, and return to competitive activity after 12 mo
9-12 mo
Abbreviations: BW, body weight; CKC, closed kinetic chain; CPM, continuous passive motion; OKC, open kinetic chain; PF, patellofemoral; TF, tibiofemoral; WB, weight bearing.
964.e2 TABLE 3.
J. R. EBERT ET AL. Postoperative MRI Assessment of Grafts: Scoring of Parameters and Calculation of MRI Composite Score
Scoring Parameter Signal intensity
Graft infill
Border integration
Surface contour
Structure
Subchondral lamina
Subchondral bone
Effusion
Score
Description
Weighting Factor
1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 3.5 (very good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent)
Fluid signal/hyperintense diffuse Hyperintense basal layer ⬎50%/⬍50% Hypointense Isointense Subchondral bone exposed ⬍50% Height of adjacent cartilage ⬎50% Height of adjacent cartilage Hypertrophy Complete infill Incomplete border, visible defect Incomplete border, split visible Complete border, minor split Complete integration Ulceration, delamination, full thickness ⬍50% Surface fibrillation Focal changes only Smooth surface Heterogeneous, clefts Heterogeneous, no clefts ⬎50% Homogeneous ⬎75% Homogeneous No visible lamina ⬍25% Intact ⬎50% Intact Fully reconstituted Cysts, sclerosis, edema Edema ⬎1 cm from lamina Edema ⬍1 cm from lamina Intact no significant edema Severe Moderate Mild None
0.3
0.2
0.15
0.1
0.1
0.05
0.05
0.05
Purpose: To determine the safety and efficacy of a new arthroscopic technique for matrix-induced autologous chondrocyte implantation (MACI) for articular cartilage defects in the knee. Methods: We undertook a prospective evaluation of the first 20 patients treated with the MACI technique (including 14 defects on the femoral condyle and 6 on the tibial plateau), followed up for 24 months after surgery. A 12-week structured rehabilitation program was undertaken by all patients. Patients underwent clinical assessment (Knee Injury and Osteoarthritis Outcome Score, Short Form 36 Health Survey, visual analog pain scale, 6-minute walk test, knee range of motion) before surgery and at 3, 6, 12, and 24 months after surgery and underwent magnetic resonance imaging (MRI) assessment at 3, 12, and 24 months after surgery. MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score. Results: A significant improvement (P ⬍ .05) was shown throughout the postoperative time line for all Knee Injury and Osteoarthritis Outcome Score subscales, the physical component score of the Short Form 36 Health Survey, the frequency and severity of knee pain, and the 6-minute walk test. An improvement in pertinent morphologic parameters of graft repair was observed to 24 months, whereas a good to excellent graft infill score and MRI composite score were observed at 24 months after surgery in 90% and 70% of patients, respectively. Conclusions: We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period. Level of Evidence: Level IV, therapeutic case series.
M
atrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, showing good outcomes.1-6 It is a 2-stage
procedure involving an initial arthroscopic harvest of healthy cartilage, isolation and expansion of chondrocytes ex vivo, and subsequent reimplantation of the cells into the knee as a cell-scaffold construct. This
From the School of Sport Science, Exercise and Health (J.R.E., T.R.A.) and School of Surgery (J.R.E., D.J.W.), University of Western Australia, Crawley, Australia; Perth Radiological Clinic (M.F.), Subiaco, Australia; and Perth Orthopaedic and Sports Medicine Centre (G.C.J.), West Perth, Australia. The authors report the following potential conflict of interest or source of funding in relation to this article: Hollywood Private Hospital Research Foundation (RF31 and RF050), National Health and Medical Research Council (ID1003452), and Genzyme. Received December 16, 2010; accepted December 5, 2011. Note: To access the supplementary tables (Tables 2 and 3) accompanying this report, visit the [Month] issue of Arthroscopy at www.arthroscopyjournal.org. Address correspondence to Jay R. Ebert, B.Sc., Ph.D., School of Sport Science, Exercise and Health (M408), University of Western Australia, 35 Stirling Highway, Crawley, 6009, Australia. E-mail: [email protected] © 2012 by the Arthroscopy Association of North America 0749-8063/10752/$36.00 doi:10.1016/j.arthro.2011.12.022
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ARTHROSCOPIC MACI matrix can subsequently be cut to the exact size of the defect and fixed in place with fibrin glue, which has been shown to support migration and proliferation of human chondrocytes.7,8 One of the disadvantages of the MACI technique versus other osteoarticular transplantation systems (OATS) and microfracture techniques is that MACI requires a second surgery and an arthrotomy for implantation of the matrix.9-12 This arthrotomy may lead to a range of associated complications, such as arthrofibrosis, decreased range of movement, pain, and scarring.13 However, the MACI procedure lends itself to an arthroscopic implantation technique, decreasing the associated comorbidity of arthrotomy while allowing for faster postoperative rehabilitation because of reduced pain and muscular deficits.13 With the aforementioned proposed benefits of an arthroscopic procedure, several arthroscopic MACI techniques have already been described, with a variety of associated technical difficulties and results reported.13-18 The purpose of this study was to determine the safety and efficacy of a new arthroscopic MACI technique for treating articular cartilage defects in the knee. We hypothesized that this surgical technique would be safe and effective in the treatment of articular cartilage defects of the femoral condyles and tibial plateau. METHODS Patients A consecutive series of 20 patients, amenable to the arthroscopic technique, underwent arthroscopic MACI between June 2006 and September 2009. Initially, patients were identified as being suitable for MACI. This included being aged 15 to 65 years and deemed able to follow the structured postoperative rehabilitation program. Patients were excluded if they had a body mass index (BMI) greater than 35, had ligamentous instability, had undergone a prior extensive meniscectomy, had ongoing progressive inflammatory arthritis, or had varus/valgus lower limb malalignment (as indicated by a tibiofemoral anatomic angle ⬎3°). The orthopaedic specialist initially evaluated the patient for joint malalignment, and should further investigation have been warranted, long leg alignment radiographs (Maquet views) were obtained. Preoperatively, all patients had persistent pain associated with grade III or IV chondral lesions, assessed with the International Cartilage Repair Society chondral defect classification system.19 This was confirmed in all patients by preoperative magnetic reso-
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nance imaging (MRI) assessment and was later confirmed at the time of first-stage arthroscopic chondral biopsy. Preoperative MRI was used to approximately assess the location, size, and severity of the chondral defect, as well as any other soft-tissue damage incorporating the menisci or ligamentous structures. Once patients were identified as being suitable for MACI, on the basis of the aforementioned criteria, we would then consider whether they might be suitable for an arthroscopic approach. The arthroscopic approach was considered in all patients who had isolated lesions on the weight-bearing surface of either the femoral or tibial condyle (medial or lateral) unless their lesions were at the external periphery of the condyle, because these lesions might be problematic with the arthroscopic technique we are using because of the potential interference of the menisci with the inflatable portion of the indwelling catheter. The arthroscopic approach was likewise not considered for patients with patella, trochlea, or multiple lesions, because they were considered beyond the current capabilities of this technique. Therefore, over the recruitment period (June 2006 to September 2009), a total of 61 patients underwent MACI grafting (20 of whom underwent the arthroscopic technique). One of the advantages of planning and performing the arthroscopic technique is that it may be converted to a mini-open technique at any stage during the operation. Among all patients in whom we embarked on the arthroscopic technique (n ⫽ 20), none required conversion to an open technique during the course of the procedure. Among the 20 patients, the matrix was implanted in 11 medial femoral condyles, 3 lateral femoral condyles, 2 medial tibial plateaus, and 4 lateral tibial plateaus (Table 1). The mean defect size was 2.72 cm2 (range, 1.00 to 5.00 cm2) (Table 1). At the time of implantation, the mean age of patients was 34 years (range, 16 to 57 years) and mean BMI was 26.6 (range, 21.1 to 34.8) (Table 1). Of the 20 patients recruited into this prospective trial, 14 (70%) had been treated previously with 1 or more surgical procedures to address knee pain and/or symptoms, including arthroscopy with chondral debridement with or without the removal of a loose body (n ⫽ 10), partial meniscectomy (n ⫽ 6), anterior cruciate ligament reconstruction (n ⫽ 3), and MACI through an open arthrotomy 6 years previously that failed. Six patients had not undergone any prior surgery in the designated knee, apart from the arthroscopic biopsy. Patients provided written informed consent before study enrollment, and ethics approval was obtained from the University of Western Australia
954
J. R. EBERT ET AL. TABLE 1.
Descriptive Parameters for Patient Cohort That Underwent Arthroscopic MACI
Patient No.
Gender
Defect Location
Knee
Age (yr)
Weight (kg)
BMI
Defect Size (cm2)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean Range
F M F M M F M M F F M M M F M F M F F F
MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC LFC LFC LFC MTP MTP LTP LTP LTP LTP
R L R R R L R R L L R R L L R R L R L L
36 22 41 18 20 46 57 37 52 42 37 21 29 23 39 35 23 16 42 50 34 16-57
58.8 74.2 65.0 99.0 70.0 97.0 107.9 78.0 78.0 60.5 88.0 93.0 95.0 80.0 82.4 66.0 70.5 55.8 74.0 83.7 78.8 55.8-107.9
22.7 24.2 23.9 31.2 21.1 34.8 33.3 24.6 28.7 23.1 28.4 29.0 26.0 32.0 26.0 21.6 24.7 21.3 23.6 32.3 26.6 21.1-34.8
1.76 3.40 3.20 5.00 5.00 1.50 3.00 1.65 1.50 5.00 2.10 1.00 3.00 1.50 3.75 3.20 3.78 2.38 1.20 1.50 2.72 1.00-5.00
Prior Procedures DOS (yr) 1 1 1 0 0 0 1 0 1 1 0 4 4 0 3 1 2 2 0 0 1 0-4
17 6 15 2 2 1 1 5 1 4 1 8 9 2 1 10 11 6 5 5 6 1-17
Abbreviations: DOS, duration of symptoms; F, female; L, left; LFC, lateral femoral condyle; LTP, lateral tibial plateau; M, male; MFC, medial femoral condyle; MTP, medial tibial plateau; R, right.
and Hollywood Private Hospital Human Research Ethics Committees. Surgical Technique Surgery was performed by 2 orthopaedic surgeons, operating within the same hospital. Initially, an arthroscopic surgery was undertaken to harvest a fullthickness area of healthy articular cartilage (200 to 300 mg) from a non–weight-bearing area of the knee (the trochlear notch or the medial or lateral femoral condylar ridge). This was performed with the patient under general anesthesia with a thigh-high tourniquet.20 At this time, the site, geometry, and containment of the defect were further assessed, as was the integrity of the menisci and ligamentous structures. The suitability of the chondral defect for second-stage arthroscopic implantation was also further assessed at this time. The cartilage biopsy specimen was then sent to the laboratory (Genzyme, Perth, Australia), whereby chondrocytes were isolated from the cartilage tissue, cultured for approximately 4 to 8 weeks, and seeded onto a type I/III collagen membrane (ACI-Maix; Matricel GmbH, Herzogenrath, Germany) 3 days before second-stage reimplantation. At the time of second-stage graft implantation, standard arthroscopy with anteromedial and anterolateral
portals was performed by use of Ringer lactate solution to irrigate the joint. The cartilage defect was prepared by removing all damaged cartilage down to, but not through, the subchondral plate. The edges of the defect were debrided to ensure a well-defined and contained defect. The resultant defect was then “mapped” in several planes by use of the end of a graduated arthroscopy probe (Smith & Nephew, Memphis, TN) (Fig 1), and the membrane was initially oversized and cut based on these approximated measurements (Fig 2). After graft preparation, we converted to performing a “dry” arthroscopy of the knee by draining all irrigation fluid. An arthroscopic “sucker” was used to dry the defect bed, while an adrenaline-soaked patty was pressed onto the subchondral bone to further dry it and prevent any bleeding. The graft was introduced into the knee through a large-bore arthroscopic cannula, with an 8-mm inner diameter, with no valves (ConMed Linvatec, Largo, FL), and positioned within the defect by use of the probe (Fig 3). Care was taken to ensure that the membrane was oriented correctly. Dots were placed with a surgical marker on the different edges of the graft to assist with orientation within the knee (Fig 3). Graft size was reassessed to ensure an exact fit, and further graft trimming was performed if required. The large cannula facilitated multiple passes of the graft in and out of the
ARTHROSCOPIC MACI
FIGURE 1. The chondral defect was initially mapped in several planes arthroscopically for MACI graft shaping, by use of the graduated arthroscopic probe.
joint for fine-tuning without damaging it. Once we were satisfied with membrane fit and orientation, the graft was folded away from the defect to allow for the introduction of the fibrin glue through a 19-gauge needle (Becton and Dickinson, Franklin Lakes, NJ) through the most appropriate portal. An even spread of glue was achieved by use of the arthroscopic probe, and the graft was then replaced over the glue. Application of even pressure over the graft for 30 seconds is required to ensure uniform graft stability, before the fibrin glue becomes adherent. This was achieved with a Silastic Foley catheter (Cook Urological, Spencer, IN) (Fig 4). The end of the catheter was
FIGURE 2. After chondral defect measurement, the MACI graft was initially oversized and cut based on the approximated arthroscopic measurements.
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FIGURE 3. After initial sizing of the MACI graft, the membrane was introduced into the knee through a large-bore arthroscopic cannula and care was taken to ensure that it was placed and oriented correctly over the subchondral bed.
introduced into the knee through the most appropriate portal, while visualization was maintained through the opposite portal. Once centered over the graft, the balloon was then inflated with saline solution instilled into the end of the catheter outside of the knee, to distribute 30 seconds of even pressure over the area of the membrane. The transparent Silastic allows visualization of the graft underneath (Fig 4). After uniform membrane fixation, the knee was put through several cycles of knee flexion and extension under visualization to ensure graft stability. Any area
FIGURE 4. Once membrane sizing was satisfactory and an even spread of fibrin glue had been placed over the subchondral bed, even pressure over the graft was achieved by use of the balloon end of a Silastic Foley catheter (inset), inflated over the graft for 30 seconds.
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inadequately fixed had fibrin glue reapplied before closure of the portals. The arthroscopy portals were then closed in standard fashion without drainage. Postoperative Rehabilitation After hospital discharge, patients underwent a coordinated outpatient rehabilitation program of progressive exercise and graduated weight bearing over a period of 12 weeks, and further education and advice were provided up to the 12-month time point (Table 2, online only, available at www.arthroscopyjournal.org).21,22 Clinical Assessment Three subjective questionnaires were used to evaluate patient outcome before surgery and at 3, 6, 12, and 24 months after surgery: (1) the Knee Injury and Osteoarthritis Outcome Score (KOOS)23 to assess knee pain, symptoms, activities of daily living (ADLs), sports and recreation, and knee-related quality of life; (2) the Short Form 36 Health Survey (SF-36), which evaluated the general health of the patient, producing a mental component score and a physical component score24; and (3) a visual analog scale (VAS) that assessed the frequency and severity of knee pain on a scale from 0 to 10. Two functional tests were used by an independent therapist to evaluate functional status preoperatively and at 3, 6, 12, and 24 months after surgery: (1) the 6-minute walk test21,25 to assess the maximum comfortable distance the patient could walk in a 6-minute period and (2) assessment of maximal active knee flexion and extension range of motion (ROM), by use of a plastic goniometer. Defect size was calculated based on the dimensions of the chondral graft at the time of second-stage implantation, whereas the number of prior cartilage repair procedures and the duration of symptoms were obtained through a thorough patient history. MRI Assessment High-resolution MRI was conducted at 3, 12, and 24 months after surgery with a Siemens Symphony 1.5-T scanner (Siemens, Erlangen, Germany). Standardized proton density and T2-weighted fat-saturated images were obtained in the coronal and sagittal planes (slice thickness, 3 mm; field of view, 14 to 15 cm; 512 matrix in at least 1 axis for proton density images with minimum 256 matrix in 1 axis for T2weighted images). Additional axial proton density fatsaturated images were also obtained (slice thickness, 3 to 4 mm; field of view, 14 to 15 cm; minimum 224 matrix in at least 1 axis).
MRI evaluation used in this study assessed 8 pertinent parameters of graft repair (Table 3, online only, available at www.arthroscopyjournal.org) that have been previously outlined.26 Some modification was required to allow for discrepancies in MRI equipment and sequence protocols. MRI parameters (signal intensity, graft infill, border integration, surface contour, structure, subchondral lamina, subchondral bone, and effusion) were selected to best describe the morphology and signal intensity of the repair tissue. These parameters were scored individually from 1 to 4 (1, poor; 2, fair; 3, good; and 4, excellent) in comparison with the adjacent native cartilage. For the scoring parameter “graft infill,” an additional score of 3.5 was awarded for a fifth level (very good) corresponding with “graft hypertrophy,” as indicated by previous work.26,27 An MRI composite score was also calculated by multiplying each individual score by a weighting factor25 and adding the scores together. This composite score was, therefore, also scored from 1 to 4 (1, poor; 2, fair; 3, good; and 4, excellent). MRI evaluation was performed by an independent, experienced musculoskeletal radiologist, blinded to the clinical details and clinical outcome assessment. Data and Statistical Analysis A 1-way repeated-measures analysis of variance was used to investigate the progression of clinical (subjective and functional) outcomes over time. The number and percentage of grafts evaluated as good or excellent within each of the 8 pertinent parameters of graft repair, as well as the MRI composite score, at 3, 12, and 24 months after surgery were calculated and presented in table format. With regard to the MRI scoring system, intraobserver reliability assessment by use of the Spearman rank order () correlation was undertaken for the 8 pertinent MRI scores, as well as the MRI composite score, by use of 20 randomly selected images filtered through a second time to the radiologist. Statistical analysis was performed with SPSS software (version 17.0; SPSS, Chicago, IL), and statistical significance was determined at P ⬍ .05. RESULTS Clinical Assessment There was a significant improvement (P ⬍ .05) throughout the preoperative and postoperative time line for all 5 subscales of the KOOS, the physical component score subscale of the SF-36, the frequency and severity of knee pain as assessed by the VAS, and
ARTHROSCOPIC MACI TABLE 4.
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Summary of Analysis of Variance Results for Clinical Outcomes Throughout Preoperative and Postoperative Time Line
Variable KOOS Pain Symptoms ADLs Sports QOL SF-36 PCS MCS VAS Frequency Severity 6-min walk test (m) ROM (°) Knee flexion Knee extension
Before Surgery
3 mo
6 mo
12 mo
24 mo
P Value
58.06 (5.57) 59.46 (4.38) 73.24 (4.85) 27.88 (5.13) 24.86 (3.86)
76.17 (3.07) 83.93 (2.57) 85.76 (1.99) 24.87 (6.78) 42.54 (5.54)
80.92 (2.75) 87.5 (1.94) 87.69 (2.39) 32.37 (7.01) 48.03 (5.37)
80.07 (3.24) 85.3 (2.15) 89.67 (2.68) 51.05 (6.53) 51.97 (4.81)
86.81 (2.04) 85.94 (2.43) 94.61 (1.21) 67.19 (5.38) 56.25 (6.02)
⬍.0001 ⬍.0001 .008 ⬍.0001 ⬍.0001
38.51 (2.52) 49.79 (1.79)
39.43 (2.81) 53.2 (2.17)
43.84 (1.86) 55.47 (1.67)
47.21 (1.87) 53.66 (1.89)
49.98 (1.64) 55.19 (1.09)
.001 .194
6.53 (0.70) 5.48 (0.55) 501.6 (15.3)
3.68 (0.63) 3.26 (0.48) 570.6 (17.0)
2.66 (0.55) 2.24 (0.48) 599.5 (12.3)
2.45 (0.48) 2.21 (0.35) 592.2 (17.2)
2.56 (0.63) 1.94 (0.28) 587.1 (13.6)
.001 ⬍.0001 ⬍.0001
141.4 (1.5) ⫺1.3 (0.5)
141.2 (1.2) ⫺1.3 (0.4)
141.1 (1.8) ⫺1.2 (0.4)
141.3 (1.1) ⫺1.1 (0.4)
.614 .126
139.5 (1.8) ⫺0.25 (0.3)
NOTE. Data are shown as mean (SE). Abbreviations: ADLs, activities of daily living; KOOS, Knee Injury and Osteoarthritis Outcome Score; MCS, mental component score; PCS, physical component score; QOL, quality of life; ROM, range of motion; VAS, visual analog scale.
the 6-minute walk test (Table 4). Post hoc dependent t tests indicated that the improvement in knee pain, symptoms, and ADLs occurred predominantly in the first 3 months after surgery and was then maintained to 24 months. No significant improvement (P ⬎ .05) was observed for knee flexion and extension ROM or for the mental component score subscale of the SF-36 (Table 4) over the preoperative and postoperative period. MRI Assessment Intraobserver reliability for the defined MRI scoring method was evaluated by having the single radiologist score a repeat series of 20 MRI scans. This evaluation
indicated a significant correlation (P ⬍ .01) between radiologic scores within each of the 8 pertinent MRI scoring variables (signal intensity, ⫽ 1.00; graft infill, ⫽ 0.949; border integration, ⫽ 0.982; surface contour, ⫽ 1.00; structure, ⫽ 0.840; subchondral lamina, ⫽ 1.00; subchondral bone, ⫽ 0.920; and effusion, ⫽ 0.993), as well as the MRI composite score ( ⫽ 0.811), for the 20 randomly selected image pairs. At 3 months after surgery, 60% of grafts (n ⫽ 12) showed good to excellent filling of the chondral defect (Table 5) whereas signal intensity was described as good to excellent in only 5% (n ⫽ 1). Good to excellent scores were observed in 65% of grafts (n ⫽ 13)
TABLE 5. Number of Grafts at 3, 12, and 24 Months After Surgery Rated as Good to Excellent or Poor to Fair for MRI Composite Score and Each of 8 Individual MRI Parameters in Comparison With Adjacent Native Cartilage Postoperative Time Point 3 mo
12 mo
24 mo
Rating Good to excellent Poor to fair Good to excellent Poor to fair Good to excellent Poor to fair
Signal Border Surface Subchondral Subchondral Graft Infill Intensity Integration Contour Structure Lamina Bone
Effusion
MRI Composite Score
12 (60%)
1 (5%)
12 (60%) 11 (55%) 13 (65%)
17 (85%)
14 (70%)
20 (100%) 14 (70%)
8 (40%) 17 (85%)
19 (95%) 13 (65%)
8 (40%) 9 (45%) 7 (35%) 14 (70%) 13 (65%) 15 (75%)
3 (15%) 20 (100%)
6 (30%) 13 (65%)
0 (0%) 6 (30%) 20 (100%) 16 (80%)
3 (15%) 18 (90%)
7 (35%) 15 (75%)
7 (35%) 7 (35%) 5 (25%) 14 (70%) 13 (65%) 15 (75%)
0 (0%) 20 (100%)
7 (35%) 11 (55%)
0 (0%) 18 (90%)
4 (20%) 14 (70%)
2 (10%)
5 (25%)
0 (0%)
9 (45%)
2 (10%)
6 (30%)
6 (30%)
7 (35%)
5 (25%)
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J. R. EBERT ET AL. TABLE 6.
MRI-Based Assessment at 24 Months After Surgery for Each of 20 Patients Who Underwent Arthroscopic MACI
MRI Mean MRI Composite Patient Defect Graft Signal Border Surface Subchondral Subchondral Composite Score by Defect No. Location Infill Intensity Integration Contour Structure Lamina Bone Effusion Score Location 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC MFC LFC LFC LFC MTP MTP LTP LTP LTP LTP
4 3.5 4 3.5 3.5 4 3 4 3.5 3 3.5 3 1 4 4 3.5 2 3 4 3
3 2 3 2 3 3 2 4 3 3 3 3 1 4 4 3 3 2 4 3
3 3 3 4 4 1 4 4 3 1 3 3 1 4 4 4 1 2 4 2
3 3 3 4 4 1 2 3 4 1 3 4 1 4 4 4 1 2 3 1
3 3 4 3 3 1 3 3 4 2 4 4 1 4 4 4 1 2 3 3
4 3 4 4 4 3 4 3 4 3 4 4 4 4 4 4 4 4 4 3
1 1 3 3 3 4 1 4 3 1 3 1 1 3 1 2 1 3 3 3
3 2 3 3 4 4 4 4 4 2 4 4 4 4 3 4 3 3 3 3
3.25 3.25 3.45 3.25 3.5 2.7 2.85 3.8 3.45 2.25 3.35 3.2 1.3 3.65 3.8 3.55 2.10 2.25 3.7 3.10
3.19
2.72
3.68 2.75
NOTE. Individual patient scores are shown for the MRI composite score and each of the 8 individual MRI parameters in comparison with the adjacent native cartilage, as well as a mean MRI composite score by defect location. Abbreviations: LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau.
for tissue structure, 60% (n ⫽ 12) for border integration, and 55% (n ⫽ 11) for the tissue surface contour. The subchondral lamina was rated as good to excellent in 85% of grafts (n ⫽ 17) at 3 months, whereas the subchondral bone was rated as good to excellent in 70% (n ⫽ 14). No evidence of moderate to severe knee joint effusion was shown at 3 months after surgery (Table 5). At 12 months after surgery, the percentage of grafts with good to excellent infill had increased to 85% (n ⫽ 17), with 55% (n ⫽ 11) showing complete infill (or graft hypertrophy) in comparison with the adjacent native cartilage. The percentage of grafts with good to excellent scores had also improved for signal intensity (65%, n ⫽ 13), border zone integration (70%, n ⫽ 14), surface contour (65%, n ⫽ 13), tissue structure (75%, n ⫽ 15), and subchondral lamina (100%, n ⫽ 20). Although there remained no evidence of moderate to severe knee joint effusion at 12 months, the percentage of grafts with good to excellent subchondral bone decreased marginally from 3 to 12 months (Table 5). At 24 months after surgery, the percentage of grafts with good to excellent infill had further increased to 90% (n ⫽ 18), with 65% (n ⫽ 13) showing complete infill (or graft hypertrophy). However, the percentage
of grafts with a good to excellent MRI composite score had fallen to 70% (n ⫽ 14), down from 80% (n ⫽ 16) at 12 months. Whereas signal intensity improved and border integration, surface contour, structure, and subchondral lamina were unchanged, the percentage of patients with good to excellent subchondral bone and effusion decreased (Table 5). When assessed by graft location, MACI to the medial tibial plateau provided the best mean MRI composite score (3.68, n ⫽ 2) at 24 months after surgery, followed by the medial femoral condyle (3.19, n ⫽ 11), lateral tibial plateau (2.75, n ⫽ 4), and lateral femoral condyle (2.72, n ⫽ 3) (Table 6). When assessed by defect size (⬎2 cm2 or ⬍2 cm2), 8 of 20 grafts (40%) were less than 2 cm2 and showed a mean MRI composite score at 24 months of 3.09 compared with 12 of 20 grafts (60%) greater than 2 cm2 showing an MRI composite score of 3.08. No significant difference (P ⬎ .05) was observed for tissue infill or the MRI composite score when we compared graft outcome dependent on defect size at 24 months after surgery. Figures 5 and 6 show the successful development of a postoperative MACI graft located on the medial femoral
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FIGURE 5. Proton density fast spin echo magnetic resonance images of MACI graft (between arrows) to medial femoral condyle. The images are from the same patient and are representative of (A) before surgery; (B) 3 months after surgery, with reduced thickness and a hyperintense signal compared with the adjacent native cartilage; (C) 12 months after surgery, with equivalent signal and thickness characteristics to the adjacent native cartilage, good border zone integration, and good surface contour; and (D) 24 months after surgery, with relatively unchanged graft characteristics from 12 months, though with a mild increase in underlying bony edema.
condyle and on the lateral tibial plateau, respectively, for 2 different patients, as assessed with MRI. Complications and Failures Graft hypertrophy was reported in 5% of patients (1 graft) at 3 months after surgery and 20% (4 grafts) at both 12 and 24 months after surgery (Fig 7). All hypertrophic grafts were located on the medial femoral condyle. There was 1 graft failure (5%), as indicated by MRI, on a lesion of the lateral femoral condyle (33%) (Fig 8). DISCUSSION MACI performed as an open procedure has shown good short-term and midterm clinical results in the
treatment of articular cartilage defects in the knee.1-6 However, MACI performed through an open arthrotomy presents with a range of associated potential complications, such as arthrofibrosis, decreased range of movement, pain, and scarring, whereas the advantage of an arthroscopic surgical technique over an open surgical technique has been previously shown for other knee procedures.28,29 MACI lends itself to an arthroscopic implantation technique, decreasing the associated comorbidity of arthrotomy, and although methods of arthroscopically performed MACI remain in their infancy, several have been described, with a variety of associated technical difficulties and results reported.13-18 Marcacci et al.16 described the first arthroscopic MACI technique, whereby cells were seeded onto a
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FIGURE 6. Proton density fast spin echo magnetic resonance images of MACI graft (between arrows) to lateral tibial plateau. The images are from the same patient and are representative of (A) before surgery; (B) 3 months after surgery, with reduced thickness and a hyperintense signal compared with the adjacent native cartilage; (C) 12 months after surgery, with equivalent signal and thickness characteristics to the adjacent native cartilage, good border zone integration, and good surface contour; and (D) 24 months after surgery, with relatively unchanged graft characteristics from 12 months, though with a mild increase in underlying bony edema.
hyaluronic acid scaffold (Hyaff 11, Fidia Advanced Biopolymers Laboratories, Padova, Italy), with circular stamps of this construct placed over the prepared defect site using a circular corer. Satisfactory clinical results were later reported up to 48 months after surgery15 while reducing the associated morbidity of the open technique. However, it has been reported that an even distribution of pressure is required over the graft as the glue sets,14 and there has been no biomechanical testing to evaluate whether this technique provides adequate graft fixation at the time of implantation. Erggelet et al.13 described a transosseous 4-point fixation technique of graft fixation whereby the corners of the graft were secured by needles driven through the defect and fixed to the outer bone surface,
whereas Petersen et al.17 used 2 bioresorbable pins, driven through the graft to anchor it to the subchondral bone. More recently, Zantop and Petersen30 reported a similar technique for arthroscopic matrix-covered microfracture. Longer-term results in a larger patient cohort using these techniques are yet to be reported, although the method of applying an even distribution of pressure over the graft as the fibrin glue sets is not reported. Furthermore, these techniques appear to be technically demanding procedures, whereas with regard to MACI, associated adverse effects may include damage to the immediate area of graft penetration and bleeding, potentially interfering with the regeneration of repair tissue.17 Ronga et al.18 described an arthroscopic MACI technique whereby graft pressure was applied with an
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961
minor deterioration from before surgery to 3 months after surgery, although significant physical limitation is placed on patients over this early postoperative period.31 The KOOS subscales for sports and recreation and for quality of life continued to improve throughout the 24-month period, as indicated by post hoc testing. However, the KOOS subscales for pain,
FIGURE 7. Proton density fast spin echo magnetic resonance image of 1 of the 4 MACI grafts (between arrows) that showed graft hypertrophy at 24 months after surgery. All hypertrophic grafts were located on the medial femoral condyle.
arthroscopic probe in combination with a valgus knee stress. Although good clinical and radiologic outcomes were attained in this case report up to 12 months after surgery, application of even pressure over the graft while the fibrin glue set could not be enabled with the probe. Furthermore, this reported case involved treatment of a defect on the lateral tibial plateau, and this particular technique would prove difficult in treating lesions on the femoral condyles. Reported arthroscopic implantation techniques fail to show how an even distribution of pressure is provided over the graft as the fibrin sets, which is potentially important in adequate graft adherence.14 Furthermore, currently proposed techniques use needles13 or pins17 driven through the membrane for fixation, which may result in damage to the immediate area of graft penetration and bleeding. Our technique provides an even distribution of pressure through the inflation of the balloon end of a Silastic Foley catheter as the glue sets whereas no additional fixation is required, thereby avoiding bleeding, which may interfere with the regeneration of repair tissue.17 In this study a significant improvement was achieved in all subscales of the KOOS, VAS, and the physical component score subscale of the SF-36 over the 24month assessment period, indicated by a significant time effect for all subjective variables (Table 4). The sports and recreation subscale of the KOOS showed a
FIGURE 8. Proton density fast spin echo magnetic resonance images of failed MACI graft to lateral femoral condyle (between arrows), with full-thickness loss at (A) 3 months after surgery and (B) 12 months after surgery.
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J. R. EBERT ET AL.
symptoms, and ADLs improved predominantly in the first 3 months, with further minor improvement up to 24 months, showing a good early postoperative improvement. These 24-month KOOS and SF-36 outcomes are comparable, if not superior, to those previously reported for MACI performed through open arthrotomy at 12 and 24 months.22,32 A significant improvement over time was observed for the 6-minute walk test, with improvement up to 6 months, with a mild deterioration through 24 months, although the largest improvement was shown from before surgery to 3 months after surgery (Table 4). This is contrary to many studies that have shown a fall from before surgery to 3 months using both open matrix-induced22 and collagen-covered25 autologous chondrocyte implantation techniques. No significant improvement was observed in active knee flexion or extension ROM over the 24-month period (Table 4), although both full knee flexion and mild knee hyperextension were shown as early as 3 months and were maintained up to 24 months after surgery. Although the degree of knee effusion was not evaluated in this patient cohort, the reduced knee pain and swelling that may accompany the arthroscopic technique, as opposed to an open arthrotomy, could prove pivotal in the early recovery of knee function. Full active knee extension ROM is important in the return of a normal gait pattern, whereas the 6-minute walk test has been reported as a key component of many activities of normal daily living and a foundation for functional independence.25 When we grouped all chondral grafts irrespective of location, MRI-based evaluation at 3 months after surgery showed an immature graft, primarily with respect to tissue infill and signal intensity (Table 5). At 3 months, tissue infill above 50% of the adjacent native cartilage was observed in only 60% of grafts (n ⫽ 12), whereas 70% of grafts (n ⫽ 14) were given an overall MRI composite score rated as good or excellent based on the 8 pertinent parameters of graft repair. Several graft changes were observed in the 12- and 24-month MRI assessments. The percentage of grafts showing good to excellent tissue infill had increased to 85% (n ⫽ 17) at 12 months and 90% (n ⫽ 18) at 24 months, with 13 of these (65%) showing complete infill (or graft hypertrophy) in comparison with the adjacent native cartilage. Although detailed morphologic graft evaluation with MRI after arthroscopically performed MACI is limited, the degree of complete tissue infill presented in the literature after open MACI is varied. Welsch et al.33 showed complete infill in only 4 of 10 patients (40%) at 24 months, in comparison with
Genovese et al.,2 who reported 11 of 12 patients (92%) with complete tissue infill at 5 years, although both of these studies had smaller patient cohorts. Our 12month findings are, however, comparable to the outcomes of Kon et al.,4 who showed complete infill in 65% of patients at a minimum 5-year follow-up, after undergoing a different technique for arthroscopic MACI. At 24 months, 75% of grafts (n ⫽ 15) were isointense or hypointense compared with the adjacent healthy articular cartilage, whereas the percentage of grafts with good to excellent ratings for border integration (70%), surface contour (65%), and structure (75%) had increased. Good reconstitution of the subchondral lamina was observed in all cases, and although the percentage of grafts with a good or excellent MRI composite score had improved to 80% (n ⫽ 16) at 12 months, this fell to 70% (n ⫽ 14) at 24 months (Table 5). This coincided with a deterioration in scores for subchondral bone and effusion between the 3- and 24-month period. Both bone edema and joint effusion may be seen as signs of overloading and, subsequently, an inability of the regenerative tissue up until 12 to 24 months to appropriately transmit forces acting across the tissue,34 especially with the increasing patient activity level throughout this period. Although MRI evaluation as early as 12 months after surgery has been shown to be a reasonable time for assessing graft maturation,35 it should be noted that the repair tissue continues to develop and remodel up to 3 years after surgery.31,36,37 Therefore further improvements in tissue repair would be expected beyond this 24-month assessment of safety and efficacy. At 24 months after surgery, a mean MRI composite score of 3.68 (n ⫽ 2) was observed for MACI grafts located on the medial tibial plateau, with both grafts showing a good to excellent MRI composite score and tissue infill at or above the surface of the adjacent native cartilage (Table 6). For the other defect locations, mean MRI composite scores of 3.19 (medial femoral condyle, n ⫽ 11), 2.75 (lateral tibial plateau, n ⫽ 3), and 2.72 (lateral femoral condyle, n ⫽ 3) were recorded. Although an assessment of this surgical technique based on defect location should be considered with caution because of the low graft numbers, the lowest mean score recorded for the lateral femoral condyle was skewed with a single study graft failure. Among the 20 grafts that underwent MRI evaluation at 24 months after surgery, there was a 20% incidence of graft hypertrophy (n ⫽ 4). The incidence of graft overgrowth after MACI ranges from 13% to
ARTHROSCOPIC MACI 25% across different postoperative time points.2,6,27,38 The 4 patients with hypertrophic grafts at 12 and 24 months were nonsymptomatic, although they will be closely monitored to ascertain whether symptoms relating to graft “overfill” emerge. There was 1 graft failure (5%) as indicated by MRI at 12 months after surgery, which was observed in a compliant 29-year-old man, with a preoperative BMI of 26.0 and no pre-existing conditions that would warrant study exclusion. Although the reason for this graft failure remains unknown, this patient had undergone failed MACI 6 years prior in the same location, which was performed with an open arthrotomy. Although literature supporting arthroscopic MACI still remains limited, Nehrer et al.5 presented a 2- to 7-year follow-up and reported that 3 of 42 patients (7%) had graft failure, whereas Kon et al.4 outlined graft reabsorption in 2 of 50 patients (5%) at a minimum 5-year follow-up. Although this is a short-term follow-up more focused around the early safety and efficacy of the described arthroscopic MACI technique, it has been reported that graft delamination generally presents within the first 6 months.37 At this stage, outcomes pertaining to graft failure are comparable to those reported. Our study hypothesis was partially supported, whereby our arthroscopically performed MACI surgical technique was shown to be both safe and effective in addressing articular cartilage defects on the femoral and tibial condyles. This was with the exception of 1 failure (5%) on the lateral femoral condyle (33%) in a patient who had undergone failed MACI 6 years earlier through an open procedure. However, this failure rate is comparable to that reported in the literature, and the 12- to 24-month clinical outcomes are at least comparable to those reported in the literature for MACI performed through open arthrotomy, at 24 months and beyond. A number of limitations existed within this study. First, it is a small prospective case series with no comparative cohort and with a relatively short follow-up (24 months). Although the repair tissue produced by MACI requires a longer developmental time line and, therefore, prospective follow-up, the primary aim of this study was to evaluate the early safety and efficacy of the arthroscopic technique. Second, this study presented graft outcomes over varied locations, including the medial and lateral femoral, as well as tibial, weight-bearing condyles. A more comprehensive evaluation of this technique specific to each location is not yet attainable with such a small patient cohort. Third, 40% of the grafts treated in this cohort (8 of 20) were less than 2 cm2 (Table 1) and, therefore, are considered amenable to
963
other cartilage repair methods such as OATS and microfracture. However, our preferred method of treatment is MACI to achieve a “hyaline-like” articular cartilage as opposed to the fibrocartilage that is generally the result of microfracture. We also held the view that the MACI procedure was superior to the OATS procedure in that there was virtually no risk of donor-site morbidity and the procedure was less invasive. Fourth, although the morphologic MRI scoring system used within this study has been used previously, new methods have emerged that may assess the biochemical characteristics of repair tissue.39-41 These new methods may be used in a longerterm follow-up to evaluate the “ultrastructure” of the repair tissue.42 Finally, no follow-up arthroscopy or histologic analysis has been undertaken in this case series, which may provide more information on repair tissue structure. However, postoperative arthroscopic biopsy provides ethical barriers, particularly when patients have a good early outcome and remain asymptomatic. CONCLUSIONS We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period. REFERENCES 1. Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/ MACI)—5-Year follow-up. Knee 2006;13:194-202. 2. Genovese E, Ronga M, Angeretti MG, et al. Matrix-induced autologous chondrocyte implantation of the knee: Mid-term and long-term follow-up by MR arthrography. Skeletal Radiol 2011;40:47-56. 3. Gobbi A, Kon E, Berruto M, et al. Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: Results at 5 years’ follow-up. Am J Sports Med 2009;37:1083-1092. 4. Kon E, Di Martino A, Filardo G, et al. Second-generation autologous chondrocyte transplantation: MRI findings and clinical correlations at a minimum 5-year follow-up. Eur J Radiol 2011;79:382-388. 5. Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R. Treatment of full-thickness chondral defects with hyalograft C in the knee: A prospective clinical case series with 2 to 7 years’ follow-up. Am J Sports Med 2009;37:81S-87S (Suppl 1). 6. Saris DB, Vanlauwe J, Victor J, et al. Treatment of symptomatic cartilage defects of the knee: Characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 2009;37:10S-19S (Suppl 1). 7. Gille J, Meisner U, Ehlers EM, Müller A, Russlies M, Behrens P. Migration pattern, morphology and viability of cells suspended in or sealed with fibrin glue: A histomorphologic study. Tissue Cell 2005;37:339-348.
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8. Kirilak Y, Pavlos NJ, Willers CR, et al. Fibrin sealant promotes migration and proliferation of human articular chondrocytes: Possible involvement of thrombin and proteaseactivated receptors. Int J Mol Med 2006;17:551-558. 9. Gudas R, Kalesinskas RJ, Kimtys V, et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 2005;21:1066-1075. 10. Hangody L, Vásárhelyi G, Hangody LR, et al. Autologous osteochondral grafting—Technique and long-term results. Injury 2008;39:S32-S39 (Suppl 1). 11. Reddy S, Pedowitz DI, Parekh SG, Sennett BJ, Okereke E. The morbidity associated with osteochondral harvest from asymptomatic knees for the treatment of osteochondral lesions of the talus. Am J Sports Med 2007;35:80-85. 12. Steadman JR, Rodkey WG, Briggs KK, Rodrigo JJ. The microfracture technic in the management of complete cartilage defects in the knee joint. Orthopade 1999;28:26-32 (in German). 13. Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of fullthickness cartilage defects of the knee joint. Arthroscopy 2003; 19:108-110. 14. Carey-Smith R, Ebert JR, Davies H, Garrett S, Wood DJ, Janes GC. Arthroscopic matrix-induced autologous chondrocyte implantation (MACI): A simple surgical technique. Tech Knee Surg 2010;9:170-175. 15. Marcacci M, Kon E, Zaffagnini S, et al. Arthroscopic second generation autologous chondrocyte implantation. Knee Surg Sports Traumatol Arthrosc 2007;15:610-619. 16. Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I. Arthroscopic autologous chondrocyte transplantation: Technical note. Knee Surg Sports Traumatol Arthrosc 2002;10:154-159. 17. Petersen W, Zelle S, Zantop T. Arthroscopic implantation of a three dimensional scaffold for autologous chondrocyte transplantation. Arch Orthop Trauma Surg 2008;128:505-508. 18. Ronga M, Grassi FA, Bulgheroni P. Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee. Arthroscopy 2004;20:79-84. 19. Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 2003;85:58-69 (Suppl 2). 20. Noordin S, McEwen JA, Kragh CJ Jr, Eisen A, Masri BA. Surgical tourniquets in orthopaedics. J Bone Joint Surg Am 2009;91:2958-2967. 21. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T. Traditional vs accelerated approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes. Osteoarthritis Cartilage 2008;16:1131-1140. 22. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T. A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-Year clinical outcomes. Cartilage 2010;1:180-187. 23. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)— Development of a self-administered outcome measure. J Orthop Sports Phys Ther 1998;28:88-96. 24. Bartlett W, Gooding CR, Carrington RW, Briggs TW, Skinner JA, Bentley G. The role of the Short Form 36 Health Survey in autologous chondrocyte implantation. Knee 2005; 12:281-285. 25. Robertson WB, Fick D, Wood DJ, Linklater JM, Zheng MH, Ackland TR. MRI and clinical evaluation of collagen-covered autologous chondrocyte implantation (CACI) at two years. Knee 2007;14:117-127.
26. Marlovits S, Striessnig G, Resinger CT, et al. Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging. Eur J Radiol 2004;52:310-319. 27. Trattnig S, Pinker K, Krestan C, Plank C, Millington S, Marlovits S. Matrix-based autologous chondrocyte implantation for cartilage repair with Hyalograft C: Two-year follow-up by magnetic resonance imaging. Eur J Radiol 2006;57:9-15. 28. Laffargue P, Delalande JL, Maillet M, Vanhecke C, Decoulx J. Reconstruction of the anterior cruciate ligament: Arthrotomy versus arthroscopy. Rev Chir Orthop Reparatrice Appar Mot 1999;85:367-373 (in French). 29. Oretorp N, Gillquist J. Transcutaneous meniscectomy under arthroscopic control. Int Orthop 1979;3:19-25. 30. Zantop T, Petersen W. Arthroscopic implantation of a matrix to cover large chondral defect during microfracture. Arthroscopy 2009;25:1354-1360. 31. Hambly K, Bobic V, Wondrasch B, Van Assche D, Marlovits S. Autologous chondrocyte implantation postoperative care and rehabilitation: Science and practice. Am J Sports Med 2006;34:1-19. 32. Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S. Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol 2006;57:16-23. 33. Welsch GH, Mamisch TC, Zak L, et al. Evaluation of cartilage repair tissue after matrix-associated autologous chondrocyte transplantation using a hyaluronic-based or a collagen-based scaffold with morphological MOCART scoring and biochemical T2 mapping: Preliminary results. Am J Sports Med 2010; 38:934-942. 34. Wondrasch B, Zak L, Welsch GH, Marlovits S. Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle on radiographic and clinical outcome after 2 years: A prospective, randomized controlled pilot study. Am J Sports Med 2009;37: 88S-96S (Suppl 1). 35. Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH. Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg Br 2003;85:1060-1066. 36. King PJ, Bryant T, Minas T. Autologous chondrocyte implantation for chondral defects of the knee: Indications and technique. J Knee Surg 2002;15:177-184. 37. Minas T, Peterson L. Advanced techniques in autologous chondrocyte transplantation. Clin Sports Med 1999;18:13-44. 38. Ebert JR, Fallon M, Robertson WB, et al. Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI). Cartilage 2011;2:60-72. 39. Kurkijärvi JE, Nissi MJ, Kiviranta I, Jurvelin JS, Nieminen MT. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage: Topographical variation and relationships to mechanical properties. Magn Reson Med 2004;52:41-46. 40. Tiderius CJ, Tjörnstrand J, Akeson P, Södersten K, Dahlberg L, Leander P. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): Intra- and interobserver variability in standardized drawing of regions of interest. Acta Radiol 2004;45:628-634. 41. Trattnig S, Millington SA, Szomolanyi P, Marlovits S. MR imaging of osteochondral grafts and autologous chondrocyte implantation. Eur Radiol 2007;17:103-118. 42. Domayer SE, Welsch GH, Dorotka R, et al. MRI monitoring of cartilage repair in the knee: A review. Semin Musculoskelet Radiol 2008;12:302-317.
ARTHROSCOPIC MACI TABLE 2. Progression of Postoperative Weight Bearing, Knee ROM, and Exercise Rehabilitation After Arthroscopic MACI Time Line
Rehabilitation Guidelines
1-2 wk
WB status TF joint: ⬍20% BW PF joint: 20%-30% BW Ambulatory aids TF joint: 2 crutches used at all times PF joint: 2 crutches used at all times Knee ROM TF joint: passive and active ROM from 0°-30° PF joint: passive and active ROM from 0°-20° Knee bracing TF joint: 0°-30° PF joint: locked at full knee extension Treatment/rehabilitation: isometric contractions and circulation exercises, CPM, and cryotherapy WB status TF joint: 30% BW (wk 3) to 60% BW (wk 6) PF joint: 50% BW (wk 3) to 75% BW (wk 6) Ambulatory aids TF joint: 2 crutches used at all times PF joint: 1-2 crutches used at all times Knee ROM TF joint: active ROM from 0°-90° (wk 3) to 0°-125° (wk 6) PF joint: active ROM from 0°-60° (wk 3) to 0°-125° (wk 6) Knee bracing TF joint: 0°-45° (wk 3) to full knee flexion (wk 6) PF joint: 0°-30° (wk 3) to brace removal (wk 6) Treatment/rehabilitation: isometric/straight leg and passive/active knee flexion exercises, remedial massage, patella mobilization, CPM, cryotherapy, and hydrotherapy WB status TF joint: 60% BW (wk 6) to full WB as tolerated (wk 8) PF joint: Full WB Ambulatory aids TF joint: 1 crutch as required until full WB achieved PF joint: 1 crutch as required until full WB achieved Knee ROM TF joint: Full active ROM (wk 7) PF joint: Full active ROM (wk 7) Knee bracing TF joint: Full knee flexion PF joint: No brace Rehabilitation: introduction of proprioceptive/balance activities, cycling, walking, resistance, and CKC activities Rehabilitation: introduction of more demanding OKC (terminal leg extension) and CKC (inner range quadriceps and modified leg press), upright cycling, rowing ergometry, and elliptical trainers
3-6 wk
7-12 wk
3-6 mo
964.e1 TABLE 2.
Continued
Time Line
Rehabilitation Guidelines
6-9 mo
Rehabilitation: increase in difficulty of proprioceptive/balance and OKC and CKC exercises (i.e., step-ups/step-downs and squats) and introduction of controlled mini-trampoline jogging Rehabilitation: increase in difficulty of CKC exercises (i.e., lunge and squat activities on unstable surfaces), introduction of agility drills relevant to patient’s sport, and return to competitive activity after 12 mo
9-12 mo
Abbreviations: BW, body weight; CKC, closed kinetic chain; CPM, continuous passive motion; OKC, open kinetic chain; PF, patellofemoral; TF, tibiofemoral; WB, weight bearing.
964.e2 TABLE 3.
J. R. EBERT ET AL. Postoperative MRI Assessment of Grafts: Scoring of Parameters and Calculation of MRI Composite Score
Scoring Parameter Signal intensity
Graft infill
Border integration
Surface contour
Structure
Subchondral lamina
Subchondral bone
Effusion
Score
Description
Weighting Factor
1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 3.5 (very good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent) 1 (poor) 2 (fair) 3 (good) 4 (excellent)
Fluid signal/hyperintense diffuse Hyperintense basal layer ⬎50%/⬍50% Hypointense Isointense Subchondral bone exposed ⬍50% Height of adjacent cartilage ⬎50% Height of adjacent cartilage Hypertrophy Complete infill Incomplete border, visible defect Incomplete border, split visible Complete border, minor split Complete integration Ulceration, delamination, full thickness ⬍50% Surface fibrillation Focal changes only Smooth surface Heterogeneous, clefts Heterogeneous, no clefts ⬎50% Homogeneous ⬎75% Homogeneous No visible lamina ⬍25% Intact ⬎50% Intact Fully reconstituted Cysts, sclerosis, edema Edema ⬎1 cm from lamina Edema ⬍1 cm from lamina Intact no significant edema Severe Moderate Mild None
0.3
0.2
0.15
0.1
0.1
0.05
0.05
0.05