The American Journal of Sports Medicine

Background: Damaged articular cartilage has limited capacity for self-repair. Autologous chondrocyte implantation using a characterized cell therapy product results in significantly better early structural repair as compared with microfracture in patients with symptomatic joint surface defects of the femoral condyles of the knee.

Purpose: To evaluate clinical outcome at 36 months after characterized chondrocyte implantation (CCI) versus microfracture (MF).

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: Patients aged 18 to 50 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of the femoral condyles were randomized to CCI (n = 57) or MF (n = 61). Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS). Serial magnetic resonance imaging (MRI) scans were scored using the Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system and 9 additional items. Gene expression profile scores associated with ectopic cartilage formation were determined by RT-PCR.

Results: Baseline mean overall KOOS (±SE) was comparable between the CCI and MF groups (56.30 ± 1.91 vs 59.46 ± 1.98, respectively). Mean improvement (±SE) from baseline to 36 months in overall KOOS was greater in the CCI group than the MF group (21.25 ± 3.60 vs 15.83 ± 3.48, respectively), while in a mixed linear model analysis with time as a categorical variable, significant differences favoring CCI were shown in overall KOOS (P = .048) and the subdomains of Pain (P = .044) and QoL (P = .036). More CCI- than MF-treated patients were treatment responders (83% vs 62%, respectively). In patients with symptom onset of <2 years, the mean improvement (±SE) from baseline to 36 months in overall KOOS was greater with CCI than MF (24.98 ± 4.34 vs 16.50 ± 3.99, respectively) and even greater in patients with symptom onset of <3 years (26.08 ± 4.10 vs 17.09 ± 3.77, respectively). Characterized chondrocyte implantation patients with high (>2) versus low (<2) gene profile scores showed greater improvement from baseline in mean overall KOOS (±SE) at 36 months (28.91 ± 5.69 vs 18.18 ± 5.08, respectively). Subchondral bone reaction significantly worsened over time with MF compared with CCI (P < .05).

Conclusion: Characterized chondrocyte implantation for the treatment of articular cartilage defects of the femoral condyles of the knee results in significantly better clinical outcome at 36 months in a randomized trial compared with MF. Time to treatment and chondrocyte quality were shown to affect outcome.

Background: Autologous chondrocyte implantation is associated with a high rate of reoperation, mostly due to hypertrophy of the periosteal patch. European studies investigating the use of collagen membranes as a periosteal substitute report significant decreases in reoperation rates to less than 5%. This multicenter study investigates the off-label use of 1 collagen membrane as a periosteal substitute for autologous chondrocyte implantation.

Hypothesis: The use of a collagen membrane for autologous chondrocyte implantation will decrease reoperation rates for hypertrophy with comparable rates of failure.

Study Design: Cohort study; Level of evidence, 3.

Methods: A multicenter cohort of 300 patients treated with periosteal-covered autologous chondrocyte implantation was compared with a consecutive series of 101 patients who underwent collagen membrane–covered autologous chondrocyte implantation with the Bio-Gide membrane by the same group of surgeons. The 1-year hypertrophy-related reoperation rates and overall failure rates of autologous chondrocyte implantation were evaluated in both groups.

Results: Both groups were comparable for age (periosteal autologous chondrocyte implantation, 31.9 years; collagen autologous chondrocyte implantation, 32.4 years; P 5 .8) and average defect size (4.6 cm2 and 4.7 cm2, respectively; P 5 .7). The average number of defects (1.5 and 1.8; P 5 .001) and total defect area per knee (6.7 cm2 and 8.6 cm2; P 5 .003) were larger in the collagen membrane group. Within 1 year of surgery, 25.7% of patients treated with periosteal-covered autologous chondrocyte implantation required reoperation for hypertrophy and 2.3% were considered to have failed their treatment with autologous chon-drocyte implantation. In comparison, only 5% of patients required reoperation for hypertrophy after collagen membrane–covered autologous chondrocyte implantation, and 4% were considered treatment failures.

Conclusion: The use of a collagen membrane for autologous chondrocyte implantation decreased the reoperation rate for hypertrophy after autologous chondrocyte implantation from 25.7% to 5% (P < .0001). Overall 1-year failure rates were comparable between the groups (P 5 .2). Even though the use of a collagen membrane for autologous chondrocyte implantation constitutes an off-label indication, its application appears justified by the lower morbidity to patients and decreased cost to the health care system. A detailed discussion with the patient is required regarding the use of an off-label device.

Background: Osteochondral allografts are currently stored at 4°C for 2 to 6 weeks before implantation. At 4°C, chondrocyte viability, especially in the superficial zone, deteriorates starting at 2 weeks. Alternative storage conditions could maintain chondrocyte viability beyond 2 weeks, and thereby facilitate increased graft availability and enhanced graft quality.

Purpose: The objective of the study was to determine the effects of prolonged 37°C storage compared with traditional 4°C storage on chondrocyte viability and cartilage matrix content.

Study Design: Controlled laboratory study.

Methods: Osteochondral samples from humeral heads of adult goats were analyzed (i) fresh, or after storage in medium for (ii) 14 days at 4°C including 10% fetal bovine serum, (iii) 28 days at 4°C including 10% fetal bovine serum, (iv) 28 days at 37°C without fetal bovine serum, (v) 28 days at 37°C including 2% fetal bovine serum, or (vi) 28 days at 37°C including 10% fetal bovine serum. Portions of samples were analyzed by microscopy after LIVE/DEAD staining to determine chondrocyte viability and density, both en face (to visualize the articular surface) and vertically (overall and in superficial, middle, and deep zones). The remaining cartilage was analyzed for sulfated glycosaminoglycan and collagen.

Results: The 37°C storage maintained high chondrocyte viability compared with 4°C storage. Viability of samples after 28 days at 37°C was ˜80% at the cartilage surface en face, ˜65% in the superficial zone, and ˜70% in the middle zone, which was much higher than ˜45%, ˜20%, and ˜35%, respectively, in 4°C samples after 28 days, and slightly decreased from ˜100%, ˜85%, and ˜95%, respectively, in fresh controls. Cartilage thickness, glycosaminoglycan content, and collagen content were maintained for 37°C and 4°C samples compared with fresh controls.

Conclusion: The 37°C storage of osteochondral grafts supports long-term chondrocyte viability, especially at the vulnerable surface and superficial zone of cartilage.

Clinical Relevance: Storage of allografts at a physiologic temperature of 37°C may prolong storage duration, improve graft availability, and improve treatment outcomes.

Background: Reported results of autologous chondrocyte implantation for chondral lesions in the patellofemoral joint have been encouraging when combined with realignment procedures.

Purpose: The objective of this study was to examine the clinical results of a patient cohort undergoing autologous chondrocyte implantation of the patellofemoral joint and elucidate characteristics associated with successful implantation.

Study Design: Case series; Level of evidence, 4.

Methods: The cohort included 62 patients who underwent autologous chondrocyte implantation of the PF joint. The mean defect size was 4.2 cm2 (61.6). The average age was 31.8 years (range, 15.8-49.4), and the average follow-up was 4 years (range, 2-7). Outcomes were assessed via clinical assessment and established outcome scales, including the Lysholm, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Scale (KOOS; includes the 5 categories of Pain, Symptoms, Activities of Daily Living, Sport, and Quality of Life), Tegner, Cincinnati, and Short Form-12.

Results: Mean improvement in the preoperative to postoperative scores was significant for the Lysholm (37-63, P<.001), International Knee Documentation Committee (31-57, P<.001), KOOS Pain (48-71, P<.001), KOOS Symptoms (51-70, P <.001), KOOS Activities of Daily Living (60-80, P <.001), KOOS Sport (25-42, P <.001), KOOS Quality of Life (24-49, P <.001), Short Form-12 Physical (38-41, P<.05), Cincinnati (43-63, P <.005), and Tegner (4-6, P <.05), but not for the Short Form-12 Mental. There was no statistical difference between outcomes in patients with a history of a previous failed cartilage procedure compared with those patients without a prior cartilage procedure (P > 05). Patients undergoing anteromedialization tended toward better outcomes than those without realignment. Forty-four percent of patients needed a subsequent procedure. There were 4 clinical failures (7.7%), which were defined as progression to arthroplasty or conversion to osteochondral allograft transplantation.

Conclusion: Autologous chondrocyte implantation is a viable treatment option for chondral defects of the patellofemoral joint. Combined autologous chondrocyte implantation with anteromedialization improves outcomes more than autologous chondrocyte implantation alone. Patients with failed prior cartilage procedures can also expect sustained and clinically meaningful improvement.

Background: Characterized chondrocyte implantation results in superior structural repair compared with microfracture, but may be associated with a slower recovery of physical activity levels due to the arthrotomy.

Hypotheses: Our hypotheses were that (1) microfracture results in increased activity levels over 2 years after surgery compared with characterized chondrocyte implantation, (2) patients with high preinjury activity levels have a better functional outcome, and (3) high levels of low-load activities after surgery improve functional outcome.

Study Design: Cohort study; Level of evidence, 2.

Methods: Sixty-seven patients with local cartilage defects (mean size, 2.4 cm2; standard deviation, 1.5 cm2) of the femoral condyle underwent characterized chondrocyte implantation (n = 33) or microfracture (n = 34), followed by an identical rehabilitation protocol. Activity levels (assessed using the Activity Rating Scale) and functional outcome were determined at baseline, and 1 and 2 years after surgery. Functional outcome was based on the pooled symmetry index (derived from isokinetic knee extension strength and 3 one-legged hop tests). Patients’ participation in low-load activities during the first 3 months after surgery was assessed using rehabilitation data. Mixed linear model analyses and Wilcoxon rank sum tests were used.

Results: Activity levels in patients treated with characterized chondrocyte implantation and microfracture were comparable at 1 and 2 years after surgery. Preinjury activity levels showed no relationship to functional outcome. Lack of postoperative low-load activities resulted in a significantly worse functional outcome (mean pooled symmetry index 78.2%) compared with high levels of postoperative surgery low-load activities (mean pooled symmetry index 92.4%).

Conclusion: Despite differences between the characterized chondrocyte implantation and microfracture procedures, patients’ activity levels were comparable at 2 years after surgery. Lack of low-load activities after surgery adversely affected functional outcome.

Background: A focal cartilage lesion has limited capacity to heal, and the repair modalities used at present are still unable to provide a universal solution. Pure cartilage graft implantation appears to be a simple option, but it has not been applied widely as cartilage will not reattach easily to the subchondral bone.

Hypothesis: We used a multiple-incision technique (processed chondrograft) to increase cartilage graft surface. We hypothesized that pure cartilage graft with augmented osteochondral fusion capacity may be used for cartilage repair and we compared this method with other repair techniques.

Study Design: Controlled laboratory study.

Methods: Full-thickness focal cartilage defects were created on the medial femoral condyle of 9-month-old pigs; defects were repaired using various methods including bone marrow stimulation, autologous chondrocyte implantation, and processed chon-drograft. After the repair, at weeks 6 and 24, macroscopic and histologic evaluation was carried out.

Results: Compared with other methods, processed chondrograft was found to besimilarly effective incartilage repair. Defects without repair and defects treated with bone marrow stimulation appeared slightly irregular with fibrocartilage filling. Autologous chondrocyte implantationproducedhyalinelikecartilage, althoughitscellularorganizationwasdistinguishablefromthesurroundingarticularcartilage. Processed chondrograft demonstrated good osteochondral integration, and the resulting tissue appeared to be hyaline cartilage.

Conclusion: The applied cartilage surface processing method allows acceptable osteochondral integration, and the repair tissue appears to have good macroscopic and histologic characteristics.

Clinical Relevance: If further studies confirm its efficacy, this technique could be considered for human application in the future.

Background: Cartilage therapy for focal articular lesions has been implemented for more than a decade, and it is becoming increasingly available. What is still lacking, however, is analysis of patient characteristics to help improve outcome or select patients for specific treatment.

Purpose: To analyze the prognostic value of patient age and defect size, age, and location on clinical outcome 3 years after cartilage therapy.

Study Design: Cohort study; Level of evidence, 3.

Methods: Fifty-five patients (age, 35 ± 9 years) were randomly selected from a prospective database. Each had a traumatic knee injury, each was treated for a focal cartilage lesion, and each was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) 3 years after surgery. Patient characteristics (ie, patient age and defect size, age, and location) were tested for valid inclusion in the regression model. Multiple linear regression was used to determine which variables influenced clinical improvement. Binary KOOS scores were generated on the basis of age-matched healthy patients and assessed in a logistic regression analysis.

Results: Normality tests confirmed normal distribution for each variable (P < .05). Defect size did not influence clinical improvement (P > .05). Clinical outcome regarding the treatment of medial defects was better than that of the lateral defects (10.38-25.26 points for the different KOOS subscales; P < .05). The KOOS improvement from baseline was better for patients <30 years compared with patients >30 years (7.31-29.24 points for the different KOOS subscales; P <.05). Patients with defects <24 months were more likely to report the age-matched healthy reference KOOS (odds ratio, 1.8-4.0; P <.05).

Conclusion: This study illustrates the influence of patient age and defect location and age on clinical outcome 3 years after treatment of a focal cartilage lesion in patients with a traumatic knee injury.

Background: Arthroscopic microfracture is frequently used to repair osteochondral lesions of the talus. However, despite the popularity of this technique, no study has been conducted on cartilage repair after microfracture by second-look arthroscopy.

Purpose: The purpose of the present study was to evaluate cartilage repair in osteochondral lesions of the talus by second-look arthroscopy and to compare arthroscopic findings with clinical outcomes 12 months postoperatively.

Study Design: Case series; Level of evidence, 4.

Methods: Second-look arthroscopies were performed in 20 ankles of 19 patients at 12 months postoperatively. Arthroscopic findings were classified using the Ferkel and Cheng staging system, and cartilage repair was assessed using the International Cartilage Repair System (ICRS). Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale.

Results: According to the Ferkel and Cheng staging at second-look arthroscopy, 7 of the 20 ankles (35%) showed incomplete healing (stage D). In terms of ICRS overall repair grades, 8 ankles (40%) were abnormal (grade III). Mean AOFAS scores for Ferkel and Cheng stages A to C (n 5 13) and stage D (n 5 7) were 88.5 and 82.0 points, and those for ICRS repair grades I and II (n 5 12) and grade III (n 5 8) were 88.7 and 82.5, respectively. Good correlations were found between AOFAS scores and Ferkel and Cheng stages and ICRS grades. Overall, 90% of ankles achieved an excellent or good AOFAS score of over 80 points.

Conclusion: Second-look arthroscopic findings at 12 months postoperatively after microfracture for osteochondral lesions of the talus revealed that 40% of lesions were incompletely healed. Nevertheless, the majority of patients achieved a good clinical outcome. Furthermore, postoperative clinical scores were found to be correlated with ICRS repair grades.

Background: Current autologous chondrocyte implantation (ACI) techniques require 2 surgical procedures: 1 for cell harvest and 1 for reimplantation of cultured cells. A 1-step procedure is more desirable.

Purpose: A 1-step surgical procedure using autologous cartilage fragments on a polydioxanone scaffold, or CAIS (cartilage autograft implantation system), in a clinically relevant defect (15-mm diameter) within equine femoral trochlea was compared with a 2-step ACI technique as well as with empty defects and defects with polydioxanone foam scaffolds alone.

Study Design: Controlled laboratory study.

Methods: Ten skeletally mature horses were used. Articular cartilage from the lateral trochlea of the femur was harvested arthro-scopically (n 5 5), and chondrocytes were cultured on small intestinal submucosa to produce ACI constructs. The CAIS procedure had cartilage harvested during defect creation to prepare minced cartilage on polydioxanone-reinforced foam. The ACI and CAIS constructs were placed in defects using polydioxanone/polyglycolic acid staples. Defects were examined arthroscopically at 4, 8, and 12 months and with gross, histological, and immunohistochemical examination at 12 months.

Results: Arthroscopic, histologic, and immunohistochemistry results show superiority of both implantation techniques (ACI and CAIS) compared with empty defects and defects with polydioxanone foam alone, with CAIS having the highest score.

Conclusion: This is the first demonstration of long-term healing with strenuous exercise using ACI and CAIS in a critically sized defect.

Clinical Relevance: Given these results with the CAIS procedure, testing in human patients is the next logical step (a phase 1 human clinical study has proceeded from this work).

Background: Tissue engineering has become available for cartilage repair in clinical practice.

Hypothesis: The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autolo-gous chondrocytes provides stable improvement of clinical outcome up to 7 years.

Study Design: Case series; Level of evidence, 4.

Methods: Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 6 12 years, the mean defect size was 4.4 6 1.9 cm2, and the mean body mass index was 24.5 6 3.8 kg/m2. Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests.

Results: A highly significant increase (P<001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P <.001).

Conclusion: Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor.

Background: If chondrocytes from the superficial, middle, and deep zones of articular cartilage could maintain or regain their characteristic properties during in vitro culture, it would be feasible to create constructs comprising these distinctive zones.

Hypothesis: Zone-specific characteristics of zonal cell populations will disappear during 2-dimensional expansion but will reappear after 3-dimensional redifferentiation, independent of the culture technique used (alginate beads versus pellet culture).

Study Design: Controlled laboratory study.

Methods: Equine articular chondrocytes from the 3 zones were expanded in monolayer culture (8 donors) and subsequently redifferentiated in pellet and alginate bead cultures for up to 4 weeks. Glycosaminoglycans and DNA were quantified, along with immunohistochemical assessment of the expression of various zonal markers, including cartilage oligomeric protein (marking cells from the deeper zones) and clusterin (specifically expressed by superficial chondrocytes).

Results: Cell yield varied between zones, but proliferation rates did not show significant differences. Expression of all evaluated zonal markers was lost during expansion. Compared to the alginate bead cultures, pellet cultures showed a higher amount of glycosaminoglycans produced per DNA after redifferentiation. In contrast to cells in pellet cultures, cells in alginate beads regained zonal differences, as evidenced by zone-specific reappearance of cartilage oligomeric protein and clusterin, as well as significantly higher glycosaminoglycans production by cells from the deep zone compared to the superficial zone.

Conclusion: Chondrocytes isolated from the 3 zones of equine cartilage can restore their zone-specific matrix expression when cultured in alginate after in vitro expansion.

Clinical Relevance: Appreciation of the zonal differences can lead to important advances in cartilage tissue engineering. Findings support the use of hydrogels such as alginate for engineering zonal cartilage constructs.

Background: There is no consensus about the optimal time for weightbearing activities after matrix-associated autologous chon-drocyte implantation (MACI) of the femoral condyle.

Hypothesis: A comprehensive protocol after MACI on the femoral condyle with accelerated weightbearing leads to a better functional and radiographic outcome compared with the same comprehensive protocol with delayed weightbearing.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: Thirty-one patients (22 male, 9 female) after MACI on the femoral condyle were randomly assigned to the accelerated weightbearing group (group A) or the delayed weightbearing group (group B). Aside from increase and time of full weightbearing, both groups adhered to the same rehabilitation protocol and exercises. Patients were assessed preoperatively and at 4, 12, 24, 52, and 104 weeks after surgery. Clinical evaluation was performed by determining the subjective form of the International Knee Documentation Committee (IKDC), the Tegner activity scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiological outcome was evaluated by the MOCART score and the size and amount of bone marrow edema and effusion.

Results: In both groups, there were no differences with regard to the clinical outcome. For the radiological outcome, group A showed a higher prevalence of bone marrow edema after 6 months without correlation to the clinical outcome (P 5 .06-.1). However, after 104 weeks, there were no differences in the radiological outcome between group A and group B.

Conclusion: A rehabilitation protocol with accelerated weightbearing leads to good clinical and functional outcome after 2 years without jeopardizing the healing graft.

Background: Osteochondral lesions are frequently seen in athletes after ankle injuries. At this time, osteochondral autologous transplantation (OATS, mosaicplasty) is the only surgical treatment that replaces the entire osteochondral unit in symptomatic lesions.

Purpose: To evaluate the clinical and radiological midterm to long-term outcome of ankles treated with knee-to-ankle mosaicplasty.

Study Design: Case series; Level of evidence, 4.

Methods: Clinical evaluation consisted of patient satisfaction, pain evaluation (visual analog scale [VAS]), American Orthopaedic Foot and Ankle Society (AOFAS) ankle score, sports activity score, range of motion, the radiological evaluation of magnetic resonance imaging (MRI), and single photon emission computed tomography–computed tomography (SPECT-CT) analysis of both the ankle and the knee joint.

Results: Twelve of 21 patients (mean age, 43 years; male, 8; female, 4) were available for latest follow-up (mean, 72 months). At follow-up, patients reported a satisfaction rate of good to excellent in 92% (n 5 11) and poor in 8% (n 5 1). The average VAS pain score was 3.9 (preoperative, 5.9; P 5 .02), AOFAS ankle score significantly increased from 45.9 to 80.2 points (P< .0001), sports activity score remained significantly decreased with 1.25 (preinjury level, 2.3; P 5 .035), and ankle dorsiflexion was significantly reduced (P 5 .003). Knee pain was reported in 6 patients (50%). Radiologically, recurrent lesions were found in 10 of 10 cases (100%) and some degree of cartilage degeneration and discontinuity of the subchondral bone plate in 100%.

Conclusion: Indications for mosaicplasty with a plug transfer from the knee to the talus must be considered carefully, as at midterm, moderate outcome and considerable donor-site morbidity may be found.

Background: Ideal treatment of osteochondral lesions of the talus is still controversial. Although good clinical and histologic results have been reported for the knee, long-term results have not been reported for autologous chondrocyte implantation in the ankle. Furthermore, magnetic resonance imaging T2 mapping is becoming an increasingly used method for noninvasive assessment of repair tissue in the knee, but no experience on the ankle has been reported.

Hypothesis: The 10-year clinical results of autologous chondrocyte implantation in the treatment of osteochondral lesions of the talus has clinical efficacy comparable with the long-term efficacy of autologous chondrocyte implantation in the knee. A secondary hypothesis is that magnetic resonance imaging T2 mapping may provide noninvasive assessment of the repaired tissue quality in the ankle.

Study Design: Case series; Level of evidence, 4.

Methods: Between 1997 and 1999, 10 patients (age 25.8 6 6.4 years) with an osteochondral lesion of the talus were treated with autologous chondrocyte implantation. The mean size of the lesions was 3.1 cm2 (range, 2.2-4.3 cm2). All patients were evaluated clinically (American Orthopaedic Foot and Ankle Society score), radiographically, and by magnetic resonance imaging preoperatively and at established intervals up to a mean follow-up of 119 6 6.5 months. At the final follow-up, magnetic resonance imaging was graded with the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system and T2-mapping evaluation in 6 cases.

Results: Before surgery, the mean American Orthopaedic Foot and Ankle Society score was 37.9 6 17.8 points, while at final follow-up it was 92.7 6 9.9 (P <.0005). Magnetic resonance imaging showed well-modeled restoration of the articular surface. The regenerated cartilage showed a mean T2-mapping value of 46 microseconds (range, 34-50), with no significant difference compared with that of healthy hyaline cartilage.

Conclusion: The results of autologous chondrocyte implantation in the ankle joint are comparable with those in the knee as demonstrated by the significant clinical improvement, hyaline cartilage repair, and the durability of the results. Integration of both T2 mapping and Magnetic Resonance Observation of Cartilage Repair scoring permitted adequate evaluation of the repair site in the ankle.

Background: There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis.

Purpose: The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections.

Study Design: Controlled laboratory study.

Methods: Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices.

Results: The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P <.05 for area; P<.01 for thickness). The average increase in area was 14.8% and the average increase in maximum thickness was 15.1%. The histologic results revealed an average increase in area of 27.4% (P <.05) and an average increase in maximum thickness of 33.0% (P 5 .06). Correlation analysis between the magnetic resonance imaging and histology data revealed that the area values were significantly correlated (P <.01), but the values for thickness obtained from magnetic resonance imaging were not significantly different from the histology sections (P > 1).

Conclusion: These results demonstrate that 7.0-T magnetic resonance imaging provides an alternative method to histology to evaluate early osteoarthritic changes in articular cartilage in a canine model by detecting increases in articular cartilage area.

Clinical Relevance: The noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo monitoring of osteoarthritis progression and intervention in animal models and humans for osteoarthritis.

Background: Determination of appropriate treatment options for adult osteochondritis dissecans is difficult, as most published papers on surgical osteochondritis dissecans treatment report outcomes in a population consisting of both adult and juvenile patients.

Purpose: This study examines the outcomes of surgical procedures in patients with adult osteochondritis dissecans.

Study Design: Case series; Level of evidence, 4.

Methods: The cohort included 46 adult patients (48 knees) with adult osteochondritis dissecans of the knee who had undergone surgical treatment (debridement, drilling, loose-body removal, arthroscopic reduction and internal fixation, microfracture, osteo-chondral allograft, or autologous chondrocyte implantation). The average patient age was 34 6 9.5 years (range, 20-49) and patients were followed for 4.0 6 1.8 years. The mean defect size was 4.5 6 2.7 cm2. Outcomes were assessed via clinical assessment and established outcome scales, including the Lysholm, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner, Cincinnati, and Short Form-12.

Results: Statistically significant improvement (P<05) was noted in all outcome scales, including Noyes, Tegner, Lysholm, IKDC, KOOS (subdivided into 5 categories including Pain, Symptoms, Activities of Daily Living, Sport, and Quality of Life), Short Form-12 Physical, and Short Form-12 Mental. Seven knees (14%) had clinical failure of the initial treatment and underwent a revision procedure at a mean follow-up of 14 months. Patients treated with arthroscopic reduction and internal fixation and loose-body removal demonstrated a statistically higher postoperative percentage score increase for the KOOS Sport (P 5 .008) and KOOS Quality of Life (P 5 .03) categories than those treated with an osteochondral allograft.

Conclusion: Patients with adult osteochondritis dissecans of the knee, treated with surgical cartilage procedures, show durable function and symptomatic improvement at a mean 4.0 years of follow-up. Patients treated with arthroscopic reduction and internal fixation and loose-body removal demonstrated a greater improvement in outcome scores than those treated with osteochon-dral allograft.

Background: Autologous chondrocyte implantation is a cell therapeutic approach for the treatment of chondral and osteochon-dral defects in the knee joint. The authors previously reported on the histologic and radiologic outcome of autologous chondro-cyte implantation in the short- to midterm, which yields mixed results.

Purpose: The objective is to report on the clinical outcome of autologous chondrocyte implantation for the knee in the midterm to long term.

Study Design: Cohort study; Level of evidence, 3.

Methods: Eighty patients who had undergone autologous chondrocyte implantation of the knee with mid- to long-term follow-up were analyzed. The mean patient age was 34.6 years (standard deviation, 9.1 years), with 63 men and 17 women. Seventy-one patients presented with a focal chondral defect, with a median defect area of 4.1 cm2 and a maximum defect area of 20 cm2. The modified Lysholm score was used as a self-reporting clinical outcome measure to determine the following: (1) What is the typical pattern over time of clinical outcome after autologous chondrocyte implantation; and (2) Which patient-related predictors for the clinical outcome pattern can be used to improve patient selection for autologous chondrocyte implantation?

Results: The average follow-up time was 5 years (range, 2.7-9.3). Improvement in clinical outcome was found in 65 patients (81%), while 15 patients (19%) showed a decline in outcome. The median preoperative Lysholm score of 54 increased to a median of 78 points. The most rapid improvement in Lysholm score was over the 15-month period after operation, after which the Lysholm score remained constant for up to 9 years. The authors were unable to identify any patient-specific factors (ie, age, gender, defect size, defect location, number of previous operations, preoperative Lysholm score) that could predict the change in clinical outcome in the first 15 months.

Conclusion: Autologous chondrocyte implantation seems to provide a durable clinical outcome in those patients demonstrating success at 15 months after operation. Comparisons between other outcome measures of autologous chondrocyte implantation should be focused on the clinical status at 15 months after surgery. The patient-reported clinical outcome at 15 months is a major predictor of the mid- to long-term success of autologous chondrocyte implantation.

Background: Cartilage and subchondral bone have recently been considered an osteochondral unit. The treatment of osteo-chondral lesions is still challenging, but better subchondral bone repair may result in higher quality repaired cartilage.

Hypotheses: Alendronate accelerates bone formation in osteochondral defects and affects the quality of the repaired cartilage.

Study Design: Controlled laboratory study.

Methods: Osteochondral defects were made on the left trochleas of 50 rabbits, which were assigned to 1 of 3 groups: control, ALN (weekly subcutaneous injection of 0.14 mg/mL alendronate), and ALN-S (alendronate injection in the first 8 weeks only). They were evaluated at 4, 8, 24, and 52 weeks. Bone repair was evaluated with microcomputed tomography and histologic evaluation. Cartilage repair was evaluated with ultrasound and histologic analyses.

Results: At 4 weeks, the defects were filled, and cartilage-like repair tissue was observed in the ALN group, whereas the defects were incompletely filled in the control group. Alendronate treatment enhanced early bone formation and mineralization in the osteochondral defect for the first 8 weeks. The continuous injection of alendronate for 24 weeks resulted in delayed bone remodeling, but the rabbits in the ALN-S group showed good integrity of the subchondral bone plate, without delayed remodeling. At 52 weeks, the ALN-S group had a columnar arrangement of chondrocytes that had less fibrillation and looked superior to those in the ALN and control groups. Ultrasound analysis showed better quality of repaired cartilage of the ALN and ALN-S group than the control group.

Conclusion: Alendronate accelerated bone formation without inhibiting its mineralization but thereafter inhibited bone remodeling in an osteochondral defect. The withdrawal of alendronate at 8 weeks avoided the delayed remodeling and showed better sub-chondral bone repair. At 52 weeks, better subchondral bone repair resulted in better cartilage quality.

Clinical Relevance: Alendronate administered in the early period accelerates bone formation and improves the quality of the repaired cartilage.

Background: Several treatment options are available to repair articular cartilage lesions of the knee; however, evidence-based parameters for treatment selection are lacking.

Purpose: To identify parameters for valid treatment selection in the repair of articular cartilage lesions of the knee.

Study Design: Systematic review.

Methods: A systematic search was conducted in the databases EMBASE, MEDLINE, and the Cochrane collaboration. The retrieved articles were screened for relevance on title and abstract followed by a full-text study quality appraisal of the remaining articles. Eventually, a total of 4 randomized controlled trials were included.

Results: Lesion size, activity level, and age were the influencing parameters for the outcome of articular cartilage repair surgery. Lesions greater than 2.5 cm2 should be treated with sophisticated techniques, such as autologous chondrocyte implantation or osteochondral autologous transplantation, while microfracture is a good first-line treatment option for smaller (<2.5 cm2) lesions. Patients who are active show better results after autologous chondrocyte implantation or osteochondral autologous transplantation when compared with microfracture. Younger patients (<30 years) seem to benefit more from any form of cartilage repair surgery compared with those over 30 years of age.

Conclusion: Lesion size, activity level, and patient age are factors that should be considered in selecting treatment of articular cartilage lesions of the knee. In addition, these factors are a step toward evidence-based, instead of surgeon-preferred, treatment of articular cartilage lesions of the knee.

Background: The clinical application of the second-generation tissue-engineering approach for the treatment of cartilage lesions has been documented for different types of scaffolds, but systematic information on clinical efficacy and long-term results is not available.

Purpose: To analyze and assess the quality of clinical studies on different products in the emerging field of matrix-assisted auto-logous chondrocyte transplantation. The secondary purpose of this review was to improve the quality assessment of studies by modifying the Coleman methodology score (CMS).

Study Design: Systematic review.

Methods: For this review, a literature search was performed to identify all published and unpublished clinical studies of matrixassisted (second-generation) autologous chondrocyte transplantation using the following medical electronic databases: MED-LINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, and British National Library of Health, including the Cochrane Central Register of Controlled Trials (CENTRAL). The search period was January 1, 1995, to July 1, 2008. To better assess cartilage-related studies, a modification of the CMS was proposed.

Results: Eighteen studies were included in the analysis, reporting on 731 patients with an average follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized controlled studies, 3 were prospective comparative studies, 11 were prospective cohort studies or prospective case series, and 2 were retrospective case series. Original CMSs for these studies (55.1 6 1.6) were significantly higher than those of cartilage repair studies in general (43.5 6 1.6, P <.0001) reported in 2005. The statistical analysis indicated that the modified CMS showed higher correlations and lower variability of correlations among 3 reviewers.

Conclusion: The quality of the currently available data on second-generation autologous chondrocyte transplantation is still limited by study designs. The modified CMS has demonstrated better sensitivity and reproducibility with respect to the original score, so it can be recommended for cartilage clinical studies evaluation.

Background: Articular cartilage injury in the athlete's knee presents a difficult clinical challenge. Despite the importance of returning injured athletes to sports, information is limited on whether full sports participation can be successfully achieved after articular cartilage repair in the knee.

Hypothesis: Systematic analysis of athletic participation after articular cartilage repair will demonstrate the efficacy of joint surface restoration in high-demand patients and help to optimize outcomes in athletes with articular cartilage injury of the knee.

Study Design: Systematic review.

Methods: A comprehensive literature review of original studies was performed to provide information about athletic participation after articular cartilage repair. The athlete's ability to perform sports postoperatively was assessed by activity outcome scores, rate of return to sport, timing of the return, level of postoperative sports participation, and the continuation of athletic activity over time.

Results: Twenty studies describing 1363 patients were included in the review, with an average follow-up of 42 months. Return to sports was possible in 73% overall, with highest return rates after osteochondral autograft transplantation. Time to return to sports varied between 7 and 18 months, depending on the cartilage repair technique. Initial return to sports at the preinjury level was possible in 68% and did not significantly vary between surgical techniques. Continued sports participation at the preinjury level was possible in 65%, with the best durability after autologous chondrocyte transplantation. Several factors affected the ability to return to sport: athlete's age, preoperative duration of symptoms, level of play, lesion size, and repair tissue morphology.

Conclusion: Articular cartilage repair in the athletic population allows for a high rate of return to sports, often at the preinjury level. Return to sports participation is influenced by several independent factors. The findings provide pertinent information that is helpful for the clinical decision-making process and for the management of the athlete's postoperative expectations.