Articular cartilage defects in 1,000 knee arthroscopies. An empirical study of the possible relation of treatment differences to quality scores in controlled randomized clinical trials. Increased Failure Rate of Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Techniques The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis Autologous Chondrocyte Implantation and Osteochondral Cylinder Transplantation in Cartilage Repair of the Knee Joint: A Prospective, Comparative Trial Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2-year follow-up The Role of Autologous Chondrocyte Implantation in the Patellofemoral Joint MR appearance of autologous chondrocyte implantation in the knee: correlation with the knee features and clinical outcome Treatment of Symptomatic Cartilage Defects of the Knee 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. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. Comparative Evaluation of Autologous Chondrocyte Implantation and Mosaicplasty: A Multicentered Randomized Clinical Trial [Osteochondral transplantation versus autogenous chondrocyte transplantation. A prospective comparative clinical study]. Autologous Chondrocyte Implantation for Focal Chondral Defects of the Knee Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures--initial experience. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial versus Microfracture
PURPOSE Focal chondral or osteochondral defects can be painful and disabling , have a poor capacity for repair , and may predispose patients for osteoarthritis . New surgical procedures that aim to reestablish hyaline cartilage have been introduced and the results seem promising . The purpose of this study is to provide reliable data on chondral and osteochondral defects in patients with symptomatic knees requiring arthroscopy  and to calculate the prevalence of patients who might benefit from cartilage repair surgery . TYPE OF STUDY Prospect i ve study . METHODS One thous and consecutive knee arthroscopies were included in this study . Immediately after each arthroscopy , the surgeon completed a question naire providing detailed information about the findings . Chondral and osteochondral lesions were classified in accordance with the system recommended by the International Cartilage Repair Society ( ICRS ) . RESULTS Chondral or osteochondral lesions ( of any type ) were found in 61 % of the patients . Focal chondral or osteochondral defects were found in 19 % of the patients . In these patients , 61 % related their current knee problem to a previous trauma , and a concomitant meniscal or anterior cruciate ligament injury was found in 42 % ( n = 81 ) and 26 % ( n = 50 ) , respectively . The mean chondral or osteochondral total defect area was 2.1 cm(2 ) ( range , 0.5 to 12 ; st and ard deviation [ SD ] , 1.5 ) . The main focal chondral or osteochondral defect was found on the medial femoral condyle in 58 % , patella in 11 % , lateral tibia in 11 % , lateral femoral condyle in 9 % , trochlea in 6 % , and medial tibia in 5 % . It has been suggested that cartilage repair surgery may be most suitable in patients younger than 40 to 50 years old . A single , well-defined ICRS grade III or IV defect with an area of at least 1 cm(2 ) in a patient younger than 40 , 45 , or 50 years accounted for 5.3 % , 6.1 % , and 7.1 % of all arthroscopies , respectively . CONCLUSIONS Our study supports the contention that articular cartilage defects are common . It has the advantages of a prospect i ve design and use of a new classification system recommended by the ICRS . This modern system focuses on objective ly measurable parameters of the lesion 's extent and not its surface appearance Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular  quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports Background Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects . Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation . Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate . Study Design Cohort study ; Level of evidence , 2 . Methods The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospect ively collected data . Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique . Outcomes were classified as complete failure if more than 25 % of a grafted defect area had to be removed in later procedures because of persistent symptoms . Results There were 522 defects in 321 patients ( 325 joints ) treated with autologous chondrocyte implantation .  On average , there were 1.7 lesions per patient . Of these joints , 111 had previously undergone surgery that penetrated the subchondral bone ; 214 joints had no prior treatment that affected the subchondral bone and served as controls . Within the marrow stimulation group , there were 29 ( 26 % ) failures , compared with 17 ( 8 % ) failures in the control group . Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of nontreated defects . The failure rates for drilling ( 28 % ) , abrasion arthroplasty ( 27 % ) , and microfracture ( 20 % ) were not significantly different , possibly because of the lower number of microfracture patients in this cohort ( 25 of 110 marrow-stimulation procedures ) . The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and therefore should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation BACKGROUND Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee . Despite the popularity of the technique , prospect i ve information about the clinical results after microfracture is still limited . The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique . METHODS Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique . Prospect i ve evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of vali date d outcome scores , subjective clinical rating , and cartilage-sensitive magnetic resonance imaging . RESULTS At the time of the latest follow-up , knee function was rated good to excellent for thirty-two patients ( 67 % ) , fair for twelve patients ( 25 % ) , and poor for four ( 8 % ) . Significant increases in the activities of daily living scores , International Knee Documentation Committee scores , and the physical component score of the Short Form-36 were demonstrated after microfracture ( p < 0.05 ) . A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component , with the worst results for patients with a body-mass index of > 30 kg/m(2 ) . Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months ( p < 0.05 ) . Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients ( 54 % ) , moderate fill in seven ( 29 % ) , and poor fill in four patients ( 17 % ) . The fill grade correlated with the knee function scores . All knees with good fill demonstrated improved knee function , whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months . CONCLUSIONS Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years . The best short-term results are observed with good fill grade , low body-mass index , and a short duration of preoperative symptoms . A high body-mass index adversely affects short-term outcome , and a poor fill grade is associated with limited short-term durability Osteoarthritis is a major contributor to functional impairment and reduced independence in older adults ( 1 - 4 ) . It is the leading cause of arthritis in the United States , affecting an estimated 21 million persons ( 5 ) , and has substantial economic impact ( 6 , 7 ) . History of an injury to a joint , particularly at the knee and hip , is associated with an increased risk for osteoarthritis in cross-sectional and casecontrol studies ( 8 - 11 ) . Such studies , however , may overestimate this relation because persons with symptomatic osteoarthritis may be more likely to recall a past injury or to interpret early symptoms of osteoarthritis as indicative of joint injury . A prospect i ve cohort study can address this weakness by determining exposure status before the outcome develops . To date , prospect i ve studies have examined the relation between history of joint injury and osteoarthritis in middle-aged persons and senior citizens ( 12 , 13 ) , but not in young adults . However , many athletic injuries occur in high school and college . In addition , joint trauma may be a more common cause of osteoarthritis than has been previously recognized ( 14 ) . We performed a prospect i ve cohort study of 1321 young adults to examine the risk for knee and hip osteoarthritis associated with joint injury during young adult life . Methods Study Participants The Johns Hopkins Precursors Study was design ed by the late Caroline Bedell Thomas , MD , to identify precursors of the aging process ( 15 ) . A total of 1337 medical students , members of the graduating classes of 1948 through 1964 at the Johns Hopkins University School of Medicine in Baltimore , Maryl and , enrolled in the study . The cohort was 91 % male and 97 % white ; the mean age was 22 years . At entry , participants underwent a st and ard history and examination , including  assessment of musculoskeletal disorders , history of trauma , level of physical activity , and measurement of weight and height . Body mass index was calculated as weight in kilograms divided by height in meters squared . In addition , participants were asked to categorize their level of physical training during the past month as none , little , moderate , or much , as described elsewhere ( 16 ) . Since graduation , participants have been followed prospect ively with annual self-administered question naires to detect incident disease and to up date risk factor status over time . At the time that baseline data were collected , it was not customary to obtain informed consent . After establishment of the Joint Committee on Clinical Investigation at Johns Hopkins , the follow-up protocol was review ed and approved . Assessment of Injury Injury was defined as a report of trauma to the knee or hip joint , including internal derangement and fracture . During the baseline assessment , knee and hip injuries that occurred before graduation from medical school and the year of their occurrence were recorded . Postgraduation injuries were assessed by annual morbidity question naires . During every 5-year follow-up period , at least 86 % of the living participants responded at least once to the question naires . Injuries were assigned diagnosis codes according to the International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) ( 17 ) . Diagnoses included torn meniscus ( code 836.2 ) ; torn knee ligament ( code 844.9 ) ; tibial fracture ( code 823.8 ) ; femoral fracture ( code 821.01 ) ; fibular fracture ( code 823.81 ) ; patellar fracture ( code 822 ) ; broken leg , site not otherwise specified ( code 827.0 ) ; knee injury , not otherwise specified ( code 959.7 ) ; gunshot wound ( code 891 ) ; hemarthrosis ( code 844.9 ) ; shin splints ( code 844.9 ) ; and hip dislocation ( code 836.5 ) . Incidence of Osteoarthritis The methods used to determine osteoarthritis incidence in this cohort have been described elsewhere ( 18 ) . Briefly , all participants were mailed annual morbidity question naires . Before 1985 , respondents were queried about the development of physical and musculoskeletal disorders . Since 1985 , follow-up morbidity question naires have contained the specific question , Have you ever had arthritis ? and have asked those who respond affirmatively to provide the type of arthritis , year of onset , and treatment received . An event of osteoarthritis was defined as the self-report of osteoarthritis or degenerative arthritis in response to the question naire . The incidence date was determined by the reported year of osteoarthritis onset . Two rheumatologists review ed each report of osteoarthritis , assigned ICD-9-CM codes ( 17 ) to the most specific arthritis site reported by the respondent , and excluded inflammatory arthritides . For this analysis , only osteoarthritis at the knee ( code 715.96 ) and hip ( code 715.95 ) were included as outcomes . In 1995 , all surviving participants who had previously reported osteoarthritis were mailed a more detailed question naire . They were asked , Have you had pain in or around the knee , including back of the knee , on most days for at least 1 month ? and Have you had pain in or around either hip joint , including the buttock , groin , and side of upper thigh , on most days for at least 1 month ? These symptom-related questions were used to screen for knee and hip osteoarthritis , respectively , in the National Health and Nutrition Examination Survey ( NHANES ) ( 19 ) . Respondents were also asked whether they had undergone  radiographic evaluation of their knees and hips  and whether radiography revealed osteophytes , joint space narrowing , subchondral cysts , or bony sclerosis ( the radiographic hallmarks of osteoarthritis ) ( 20 ) . Statistical Analysis The association between baseline characteristics and injury status was assessed by using the Student t-test for continuous variables and the chi-square test for categorical variables . These data are presented both for the entire cohort and separately by sex . Injury was the independent variable in the survival analysis ; age was the time variable . Knee and hip osteoarthritis were examined as separate outcomes . The relation of a joint injury at baseline to the incidence of osteoarthritis was examined by using KaplanMeier analysis ( 21 ) . The log-rank statistic was used to test whether the cumulative incidence of osteoarthritis differed according to injury status at cohort entry ( 22 ) . In addition , Cox proportional-hazards analysis was used to estimate the independent risk for osteoarthritis associated with a joint injury . Cox models were constructed for injury status at cohort entry and over follow-up , modeled as a time-dependent covariate . We adjusted for age at graduation , sex , body mass index , and level of physical activity , each of which was determined at baseline , to evaluate for possible confounding . In this cohort , body mass index at enrollment was more predictive of future osteoarthritis than average or most recent body mass index during follow-up ( 18 ) . These analyses were performed for all reported events of knee and hip osteoarthritis and for cases confirmed by both characteristic symptoms and radiographic findings . Hazard ratios are reported as relative risks with 95 % CIs . Statistical significance was defined as an level equal to 0.05 using a two-tailed test . We conducted a sensitivity analysis to assess the potential effect of an omitted covariate on the association between joint injury and subsequent osteoarthritis . Role of the Funding Sources The funding sources did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the study for publication . Results At graduation from medical school , the average age of the 1216 men and 121 women in the cohort was 26 years . Our analysis is based on events reported through 30 November 1995 and represents a median follow-up of 36 years . Information at baseline or during follow-up was available for 1321 participants , who form the basis of our longitudinal analysis . At the end of follow-up in 1995 , the mean age of the cohort SD was 61.4 8.9 years . Overall , 141 participants had a joint injury ( knee alone [ n = 111 ] , hip alone [ n = 16 ] , or injuries at both sites [ n = 14 ] ) before or after graduation . Table 1 shows the baseline characteristics of the cohort according to injury status at the end of follow-up . Proportions of men and women with joint injury were similar ( P > 0.2 , chi-square test ) . Participants were generally lean , 49 % were physically active , and 54 % smoked cigarettes . Men who had a joint injury were heavier at baseline than men who were injury-free , but both groups of men were similar in age , level of physical activity , and smoking status . Women with injury were , on average , 2 years older at baseline than those without injury . Table 1 . Baseline Characteristics of 1321 Men and Women according to Joint Injury at Cohort Entry or during Follow-up At baseline , 47 men ( 3.9 % ) reported a knee injury and 12 men ( 1.0 % ) reported a hip injury . The mean age at which the injuries occurred was 16 years . Knee injuries included 10 tibial fractures , 3 fibular fractures , 4 femoral fractures , 2 patellar fractures , and 9 otherwise unspecified leg fractures . In addition , 8 men incurred trauma result ing in torn knee cartilage , 2 had torn knee ligaments , 2 had knee injuries result ing from gunshot wounds , 1 had traumatic hemarthrosis , 1 had joint dislocation , 1 had shin splints , and 4 had otherwise unspecified knee injuries . Of men with a knee injury , 4 reported that they were injured while playing football , 2 each reported that they were injured while playing basketball or participating in athletics , and 1 each reported that he was injured while horseback riding , bicycling , skiing , playing volleyball , wrestling , playing baseball , or playing tennis . Knee trauma also result ed from motor vehicle accidents ( n =3 ) and falls ( n = 2 ) . At baseline , 4 of the 121 women ( 3.3 % ) had a history of knee injuries and 1 ( 0.8 % ) had a history of hip injuries . Sixty-two men and 7 women developed knee osteoarthritis , and 27 men and 5 women developed hip osteoarthritis . The mean SD ages at onset of Background : Current methods used to restore the joint surface in patients with localized articular cartilage defects include transplantation of an autologous osteochondral cylinder and implantation of autologous chondrocytes . The purpose of this study was to evaluate the clinical and histological outcomes of these two techniques . Methods : We performed a prospect i ve clinical study to investigate the two-year outcomes in forty patients with an articular cartilage lesion of the femoral condyle who had been r and omly treated with either transplantation of an autologous osteochondral cylinder or implantation of autologous chondrocytes . Biopsy specimens from representative patients of both groups were evaluated with histological staining , immunohistochemistry , and scanning electron microscopy . Results : According to the postoperative Lysholm score , the recovery after autologous chondrocyte implantation was slower than that after osteochondral transplantation at six months ( p ⩽ 0.015 ) , twelve months ( p ⩽ 0.001 ) , and twenty-four months ( p ⩽ 0.012 ) . On the basis of the Meyers score and the Tegner activity score , the results were equally good with the two methods two years after treatment . Histomorphological evaluation of biopsy specimens within two years after autologous chondrocyte implantation demonstrated a complete , mechanically stable resurfacing of the defect in all patients . The tissue consisted mainly of fibrocartilage , while localized areas of hyaline-like regenerative cartilage could be detected close to the subchondral bone . Although a gap remained at the site of the transplantation in all five biopsy specimens examined as long as two years after osteochondral cylinder transplantation , histomorphological analysis and scanning electron microscopy revealed no differences between the osteochondral transplants and the surrounding original cartilage . Conclusions : Both treatments result ed in a decrease in symptoms . However , the improvement provided by the autologous chondrocyte implantation lagged behind that provided by the osteochondral cylinder transplantation . Histologically , the defects treated with autologous chondrocyte implantation were primarily filled with fibrocartilage , whereas the osteochondral cylinder transplants retained their hyaline character , although there was a persistent interface between the transplant and the surrounding original cartilage . Limitations of our study included the small number of patients , the relatively short ( two-year ) follow-up , and the absence of a control group . Level of Evidence : Therapeutic study , Level II-2 ( poor- quality r and omized controlled trial [ e.g. , < 80 % follow-up ] ) . See Instructions to Authors for a complete description of levels of evidence Autologous chondrocyte implantation ( ACI ) is used widely as a treatment for  symptomatic chondral and osteochondral defects of the knee . Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover ( ACI-C ) and matrix-induced autologous chondrocyte implantation ( MACI ) using a collagen bilayer seeded with chondrocytes . We have performed a prospect i ve , r and omised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients , of whom 44 received ACI-C and 47 MACI grafts .  Both treatments result ed in improvement of the clinical score after one year . The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group ( p = 0.32 ) . Arthroscopic assessment s performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2 % of ACI-C and 66.6 % of MACI grafts . Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9 % of the ACI-C and 36.4 % of the MACI grafts after one year . The rate of hypertrophy of the graft was 9 % ( 4 of 44 ) in the ACI-C group and 6 % ( 3 of 47 ) in the MACI group . The frequency of re-operation was 9 % in each group . We conclude that the clinical , arthroscopic and histological outcomes are comparable for both ACI-C and MACI . While MACI is technically attractive , further long-term studies are required before the technique is widely adopted Autologous chondrocyte implantation ( ACI ) and mosaicplasty are both cl aim ed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods . A total of 100 patients with a mean age of 31.3 years ( 16 to 49 ) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was r and omised to undergo either  ACI or mosaicplasty ; 58 patients had ACI and 42 mosaicplasty .  Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2 . The mean duration of symptoms was 7.2 years and the mean number of previous operations , excluding arthroscopy , was 1.5 . The mean follow-up was 19 months ( 12 to 26 ) . Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88 % had excellent or good results after ACI compared with 69 % after mosaicplasty . Arthroscopy at one year demonstrated excellent or good repairs in 82 % after ACI and in 34 % after mosaicplasty . All five patellar mosaicplasties failed . Our prospect i ve , r and omised , clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee . The results for ACI are comparable with those in other studies , but those for mosaicplasty suggest that its continued use is of dubious value The objective was to evaluate the functional performance over a 2-year period following autologous chondrocyte implantation ( ACI ) in an open knee procedure compared to microfracture . Objective functional outcome was studied as secondary analysis in a subgroup of patients , in a r and omized clinical trial , with concealed allocation and independent evaluators . Sixty-seven patients with local cartilage defect , with a mean size of 2.4 cm² ( SD 1.5 ) of the femoral condyle of the knee were included . Thirty-three patients underwent the microfracture and 34 the ACI procedure .  An identical rehabilitation protocol was implemented for both groups . Active knee flexion and extension range , anterior laxity , knee extension strength ( concentric at 60 ° /s ) and single leg hop performance ( single hop , crossover triple hop and 6 m timed hop test ) were evaluated pre-surgery and at 6 , 9,12 and 24 months post-surgery . We calculated the symmetry index for individual and four performance tests pooled . Mixed linear model analyses were used with confidence interval set at 95 % . The change over 2 years for the pooled performance-based tests was comparable between the two treatment arms . At 2 years , 70 % ( 38/54 ) of all patients returned to > 85 % symmetry in overall functional performance . A decrease in functional performance at 6 months following ACI result ed in slower recovery at 9 and 12 months compared to microfracture . Rehabilitation following both cartilage repair procedures is a lengthy process . At 2 years after surgery , ACI patients have similar overall functional outcome compared to microfracture patients In a prospect i ve study to determine the clinical effectiveness of autologous chondrocyte implantation , 45 patients reached a minimum followup of 2 years ( range , 2 - 7 years ; average , 46.4 months ) after treatment involving the patellofemoral articulation . There were 28 men ( 61 % ) and 17 women ( 39 % ) and the average age of the patients was 37.5 years ( range , 15 - 55 years ) . The treatment groups included ( I ) isolated patella , n = 8 ; ( II ) isolated trochlea , n = 9 ; ( III ) patella plus trochlea , n = 4 ; ( IV ) weightbearing condyle plus patella n = 2 ; ( V ) weightbearing condyle plus trochlea , n = 2 ; and ( VI ) weightbearing condyle plus patella plus trochlea n = 20 . The average surface area per patella ( n = 34 ) was 4.86 cm2 and per trochlea ( n = 34 ) it was 5.22 cm2 . The average resurfacing per knee ( n = 45 ) was 10.45 cm2 . We showed a postoperative improvement in quality of life as measured by the Short Form-36 ; Western Ontario and McMaster University Score , Knee Society Score , modified Cincinnati Score , and a patient satisfaction survey . There were eight failures ( 18 % ) as a result of a patella or trochlea failure . Seventy-one percent of patients rated their outcomes as good or excellent , 22 % rated outcome as fair , and 7 % rated outcome as poor . Level of Evidence : Therapeutic Study , Level II-1 ( prospect i ve cohort study ) . See the Guidelines for Authors for a complete description of levels of evidence Objective To relate the magnetic resonance imaging ( MRI ) appearance of autologous chondrocyte implantation ( ACI )  in the knee in the 1st postoperative year with other knee features on MRI and with clinical outcome . Design and methods Forty-nine examinations were performed in 49 patients at 1 year after ACI in the knee . Forty-one preoperative magnetic resonance ( MR ) examinations were also available . The grafts were assessed for smoothness , thickness in comparison with that of adjacent cartilage , signal intensity , integration to underlying bone and adjacent cartilage , and congruity of subchondral bone . Presence of overgrowth and bone marrow appearance beneath the graft were also assessed . Presence of osteophyte formation , further cartilage defects , appearance of the cruciate ligaments and the menisci were also recorded . An overall graft score was constructed , using the graft appearances . This was correlated with the knee features and the Lysholm score , a clinical self- assessment score . The data were analysed by a Kruskal – Wallis H test followed by a Mann – Whitney U test with Bonferroni correction as post-hoc test . Results Of 49 grafts , 32 ( 65 % ) demonstrated complete defect filling 1 year postoperatively . General overgrowth was seen in eight grafts ( 16 % ) , and partial overgrowth in 13 grafts ( 26 % ) . Bone marrow change underneath the graft was seen ; oedema was seen in 23 grafts ( 47 % ) , cysts in six grafts ( 12 % ) and sclerosis in two grafts ( 4 % ) . Mean graft score was 8.7 ( of maximal 12 ) ( 95 % CI 8.0–9.5 ) . Knees without osteophyte formation or additional other cartilage defects ( other than the graft site ) had a significantly higher graft score than knees with multiple osteophytes ( P=0.0057 ) or multiple further cartilage defects ( P=0.014 ) . At 1 year follow-up improvement in the clinical scores was not significantly different for any subgroup . Knees with a graft score of 8 points or greater had a better improvement of the clinical score than those of 7 points or fewer . Conclusions At 1 year follow-up after ACI , higher graft scores are associated with an overall better preserved knee joint . ACI improves the clinical outcome , but there is no statistically significant correlation of graft score and clinical outcome 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 R and omized 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 r and omized 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 r and omized trial compared with MF . Time to treatment and chondrocyte quality were shown to affect outcome PURPOSE The purpose of this study was to compare the outcomes of mosaic-type osteochondral autologous transplantation ( OAT ) and microfracture ( MF ) procedures for the treatment of the articular cartilage defects of the knee joint in young active athletes . TYPE OF STUDY Prospect i ve r and omized clinical study . METHODS Between 1998 and 2002 , a total of 60 athletes with a mean age of 24.3 years ( range , 15 to 40 years ) and with a symptomatic lesion of the articular cartilage in the knee were r and omized to undergo either an OAT or an MF procedure . Only those athletes playing in competitive sports at regional or national levels were included in the study . Fifty-seven athletes ( 95 % ) were available for a follow-up . There were 28 athletes in the OAT group and 29 athletes in the MF group . The mean duration of symptoms was 21.32 + /- 5.57 months and the mean follow-up was 37.1 months ( range , 36 to 38 months ) , and none of the athletes had prior surgical interventions to the affected knee . Patients were evaluated using modified Hospital for Special Surgery ( HSS ) and International Cartilage Repair Society ( ICRS ) scores , radiograph , magnetic resonance imaging ( MRI ) , and clinical assessment . An independent observer performed a follow-up examination after 6 , 12 , 24 , and 36 months . At 12.4 months postoperatively , arthroscopy with biopsy for histologic evaluation was carried out . A radiologist and a pathologist , both of whom were blinded to each patient 's treatment , did the radiologic and histologic evaluations . RESULTS After 37.1 months , both groups had significant clinical improvement ( P < .05 ) . According to the modified HSS and ICRS scores , functional and objective assessment showed that 96 % had excellent or good results after OAT compared with 52 % for the MF procedure ( P < .001 ) . At 12 , 24 , and 36 months after surgery , the HSS and ICRS showed statistically significantly better results in the OAT group ( P = .03 ; P = .006 ; P = .006 ) . Younger athletes did better in both groups . No serious complications were reported . There was 1 failure in the OAT group and 9 in the MF group . The ICRS Cartilage Repair Assessment for macroscopic evaluation during arthroscopy at 12.4 months showed excellent or good repairs in 84 % after OAT and in 57 % after MF . Biopsy specimens were obtained from 58 % of the patients and histologic evaluation of repair showed better scores ( according to ICRS ) for the OAT group ( P < .05 ) . MRI evaluation showed excellent or good repairs in 94 % after OAT compared with 49 % after MF . Twenty-six ( 93 % ) OAT patients and 15 ( 52 % ) MF patients returned to sports activities at the preinjury level at an average of 6.5 months ( range , 4 to 8 months ) . Others showed a decline in sports activity level . CONCLUSIONS At an average of 37.1 months ( range , 36 to 38 months ) follow-up , our prospect i ve , r and omized , clinical study in young active athletes under the age of 40 has shown significant superiority of OAT over MF for the repair of articular cartilage defects in the knee . We found that only 52 % of MF athletes could return to sports at the preinjury level . Limitations of our study included a small number of athletes and a relatively short ( 3-year ) follow-up . A long-term follow-up is needed to assess the durability of articular cartilage repair using these methods in young active athletes . LEVEL OF EVIDENCE Level I , Therapeutic study , r and omized controlled trial , significant difference ( a ) BACKGROUND The optimal treatment for cartilage lesions has not yet been established . The objective of this r and omized trial was to compare autologous chondrocyte implantation with microfracture . This paper represents an up date , with presentation of the clinical results at five years . METHODS Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study . Forty patients were treated with autologous chondrocyte implantation , and forty were treated with microfracture .  We used the International Cartilage Repair Society , Lysholm , Short Form-36 , and Tegner forms to collect clinical data , and radiographs were evaluated with use of the Kellgren and Lawrence grading system . RESULTS At two and five years , both groups had significant clinical improvement compared with the preoperative status . At the five-year follow-up interval , there were nine failures ( 23 % ) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the  microfracture  treatment at two years . Younger patients did better in both groups . We did not find a correlation between histological quality and clinical outcome . However , none of the patients with the best- quality cartilage ( predominantly hyaline ) at the two-year mark had a later failure . One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years . CONCLUSIONS Both methods provided satisfactory results in 77 % of the patients at five years . There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome . One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery . Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis Objective : To compare the respective performance and effectiveness of autologous chondrocyte implantation ( ACI ) and mosaicplasty at resurfacing local full-thickness chondral defects of the knee . Design : R and omized clinical trial . Setting : Multicenter trial at orthopedic clinics and university hospitals conducted from 1997 to 2000 . Patients : A population of patients selected according to eligibility criteria of age , traumatic origin of the defect , its localization , size , and gravity , and above all , no previous surgical treatment of the lesion . Forty-seven patients were r and omly assigned to ACI or mosaicplasty  and subjected to arthroscopic debridement of the lesion at the time of enrollment . They were called for surgery 6 months after the initial debridement . Main Outcome : Improved knee functionality as assessed by repeated clinical evaluation based on the International Knee Documentation Committee Scale and the Lysholm Knee Scoring Scale . Results : Fourteen patients ( 31.8 % ) experienced substantial improvement following the initial debridement and , being clinical ly cured , received no further treatment . Seven patients ( 15.9 % ) were lost to follow-up . Among the 23 patients ( 52.3 % ) who could effectively be evaluated , a complete recovery ( ie , Lysholm Knee Scoring Scale score , 90 - 100 ) was observed upon clinical examination in 88 % of the mosaicplasty-treated patients and in 68 % of the ACI-treated ones ( P = 0.093 ) . Conclusions : Although the low power of our study prevents definitive conclusions , ACI and mosaicplasty are cartilage repair techniques that are clinical ly equivalent and similar in performance . The high percentage of spontaneous improvement ( ⅓ of the patients ) observed after simple debridement calls into question the need for prompt surgical treatment of patients with lesions similar to those included in this clinical trial . Moreover , this finding warrants further investigation , ideally through r and omized clinical trials in which patients subjected to debridement alone are compared with patients undergoing reconstructive surgery INTRODUCTION The treatment of full-thickness cartilage defects still represents a problem that has not yet been solved satisfactorily . Current methods used to cover defects in the knee joint are osteochondral cylinder transplantation ( OCT ) and autologous chondrocyte transplantation ( ACT ) . METHODS With a prospect i ve clinical investigation , at the time being with 2-year results , we have examined ACT in comparison to OCT in 20 patients with regard to clinical and histomorphological ( histology , immunohistochemistry , RES ) outcome . RESULTS We found equally good results with both methods in Lysholm , Meyers and Tegner Activity Scores . Histomorphologic evaluation of biopsies obtained by arthroscopy after ACT showed a defect filling in all cases , mainly with fibrous cartilage , while localized areas of hyalinelike regenerative cartilage were documented near the base . We did not see any histomorphologically visible change in the transplants after OCT . CONCLUSION At the time we prefer OCT instead of ACT given the correct indication Autologous chondrocyte implantation has been used since March 1995 in a prospect i ve cohort evaluation . One hundred sixty-nine patients , 13 to 58 years , have been treated as of December 1999 . One hundred seven patients have greater than 12 months followup , and 56 have greater than 24 months followup . Overall 87 % of patients improved . Patient assessment instruments include the modified Cincinnati knee rating scale , Short Form-36 , Knee Society score , Western Ontario McMaster Universities Osteoarthritis Index score , and patient satisfaction survey . Treatment cases included the following categories : Simple ( N = 12 ) isolated femoral condyles ; Complex ( N = 86 ) nonarthritic knees with multiple defects on the femur , or isolated lesions to the patella or tibia ; and Salvage ( N = 71 ) knees with early arthritic changes . The areas treated were large : Simple , 4.3 cm 2 ( one defect ) ; Complex , 6.75 cm 2 ( 4.5 cm 2 per defect × 1.5 defects per case ) , and Salvage , 11.66 cm 2 ( 5.3 cm 2 per defect × 2.2 defects per case ) . Patients who had complex and salvage treatments ( N = 107 ) with greater than 1 year followup frequently had adjuvant treatments including valgus tibial ( N = 24 ) or tibial tubercle ( N = 15 ) osteotomies or ligament reconstruction ( N = 5 ) . At the 2-year followup , statistically significant functional improvements occurred in the patients in the Simple and Complex categories ( Cincinnati score ; Simple , baseline 3.57 , 24 months = 5.38 ; Complex , baseline 3.40 , 24 months = 6.06 ; ) . Patients in the Salvage category had statistically significant improvement in Short Form-36 quality of life scores ( Physical summary , 24 months ) and an increase in the Cincinnati rating scale when the patellofemoral joint was not involved . Patient satisfaction at 24 months for Simple , Complex , and Salvage categories was 60 % , 70 % , and 90 % , respectively . There were 22 failures in 169 patients treated ( 13 % ) , which was defined as no clinical improvement or graft failure PURPOSE To prospect ively compare cartilage T2 values after microfracture therapy ( MFX ) and matrix-associated autologous chondrocyte transplantation ( MACT ) repair procedures . MATERIAL S AND METHODS The study had institutional review board approval by the ethics committee of the Medical University of Vienna ; informed consent was obtained . Twenty patients who underwent MFX or MACT ( 10 in each group ) were enrolled . For comparability , patients of each group were matched by mean age ( MFX , 40.0 years + /- 15.4 [ st and ard deviation ] ; MACT , 41.0 years + /- 8.9 ) and postoperative interval ( MFX , 28.6 months + /- 5.2 ; MACT , 27.4 months + /- 13.1 ) . Magnetic resonance ( MR ) imaging was performed with a 3-T MR imager , and T2 maps were calculated from a multiecho spin-echo measurement . Global , as well as zonal , quantitative T2 values were calculated within the cartilage repair area and within cartilage sites determined to be morphologically normal articular cartilage . Additionally , with consideration of the zonal organization , global regions of interest were subdivided into deep and superficial areas . Differences between cartilage sites and groups were calculated by using a three-way analysis of variance . RESULTS Quantitative T2 assessment of normal native hyaline cartilage showed similar results for all patients and a significant trend of increasing T2 values from deep to superficial zones ( P < .05 ) . In cartilage repair areas after MFX , global mean T2 was significantly reduced ( P < .05 ) , whereas after MACT , mean T2 was not reduced ( P > or = .05 ) . For zonal variation , repair tissue after MFX showed no significant trend between different depths ( P > or = .05 ) , in contrast to repair tissue after MACT , in which a significant increase from deep to superficial zones ( P < .05 ) could be observed . CONCLUSION Quantitative T2 mapping seems to reflect differences in repair tissues formed after two surgical cartilage repair procedures . ( c ) RSNA , 2008 BACKGROUND New methods have been used , with promising results , to treat full-thickness cartilage defects . The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a r and omized trial . We are not aware of any previous r and omized studies comparing these methods . METHODS Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture  ( forty in each group ) . We used the International Cartilage Repair Society , Lysholm , Short Form-36 ( SF-36 ) , and Tegner forms to collect data . An independent observer performed a follow-up examination at twelve and twenty-four months . Two years postoperatively , arthroscopy with biopsy for  histological evaluation was carried out . The histological evaluation was done by a pathologist and a clinical scientist , both of whom were blinded to each patient 's treatment . RESULTS In general , there were small differences between the two treatment groups . At two years , both groups had significant clinical improvement . According to the SF-36 physical component score at two years postoperatively , the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group ( p = 0.004 ) . Younger and more active patients did better in both groups . There were two failures in the autologous chondrocyte implantation group and one in the microfracture group . No serious complications were reported . Biopsy specimens were obtained from 84 % of the patients , and histological evaluation of repair tissues showed no significant differences between the two groups . We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale . CONCLUSIONS Both methods had acceptable short-term clinical results . There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point . LEVEL OF EVIDENCE Therapeutic study , Level I-1a ( r and omized controlled trial [ significant difference ] ) . See Instructions to Authors for a complete description of levels of evidence Background As the natural healing capacity of damaged articular cartilage is poor , joint surface injuries are a prime target for regenerative medicine . Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo . Purpose To determine whether , in symptomatic cartilage defects of the femoral condyle , structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial . Patients aged 18 to 50 years were r and omized to characterized chondrocyte implantation  ( n = 57 ) or  microfracture  ( n = 61 ) . Structural repair was blindly assessed in biopsy specimens taken at 1 year using ( 1 ) computerized histomorphometry and ( 2 ) evaluation of overall histological components of structural repair . Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score . Adverse events were recorded throughout the study . Results Characterized chondrocyte implantation result ed in better structural repair , as assessed by histomorphometry ( P = .003 ) and overall histologic evaluation ( P = .012 ) . Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation . Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage . Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score ( 56.30 ± 13.61 and 59.53 ± 14.95 for microfracture and characterized chondrocyte implantation , respectively ) , which increased in both groups to 70.56 ± 12.39 and 72.63 ± 15.55 at 6 months , 73.26 ± 14.66 and 73.10 ± 16.01 at 12 months , and 74.73 ± 17.01 and 75.04 ± 14.50 at 18 months , respectively . Both techniques were generally well tolerated ; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture . Conclusion One year after treatment , characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture . Short-term clinical outcome was similar for both treatments . The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation . Long-term follow-up is needed to confirm these findings
OBJECTIVE The relative differences in effectiveness of subchondral stimulation , osteochondral grafts , and autologous chondrocyte implantation ( ACI ) are still unclear .
It is the objective of this study to systematic ally review the literature on ACI compared to other treatments by clinical outcome and the quality of the repair tissue , including an assessment of the validity of these findings .