Jay R. Ebert

Clinical and Magnetic Resonance Imaging–Based Outcomes to 5 Years After Matrix-Induced Autologous Chondrocyte Implantation to Address Articular Cartilage Defects in the Knee

Background: The availability remains limited of midterm clinical and radiologic results into matrix-induced autologous chondrocyte implantation (MACI). Outcomes are required to validate the efficacy of MACI as a suitable surgical treatment option for articular cartilage defects in the knee. Hypothesis: A significant improvement in clinical and magnetic resonance imaging–based (MRI-based) outcomes after MACI will exist throughout the postoperative timeline to 5 years after surgery. Furthermore, patient demographics, cartilage defect parameters, and injury/surgery history will be associated with patient and graft outcome, whereas a significant correlation will exist between clinical and MRI-based outcomes at 5 years after surgery. Study Design: Case series; Level of evidence, 4. Methods: A prospective evaluation was undertaken to assess clinical and MRI-based outcomes to 5 years in 41 patients (53 grafts) after MACI to the knee. After MACI surgery and a 12-week structured rehabilitation program, patients underwent clinical assessments (Knee injury and Osteoarthritis Outcome Score, SF-36, 6-minute walk test, knee range of motion) and MRI assessments at 3, 12, and 24 months, as well as 5 years after surgery. The MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score. Results: A significant improvement (P < .05) was demonstrated for all Knee injury and Osteoarthritis Outcome Score and SF-36 subscales over the postoperative timeline, as well as the 6-minute walk test and active knee extension. A significant improvement (P < .0001) was observed for the MRI composite score, as well as several individual graft scoring parameters. At 5 years after surgery, 67% of MACI grafts demonstrated complete infill, whereas 89% demonstrated good to excellent filling of the chondral defect. Patient demographics, cartilage defect parameters, and injury/surgery history demonstrated no significant pertinent correlations with clinical or MRI-based outcomes at 5 years, and no significant correlations existed between clinical and MRI-based outcome measures. At 5 years after surgery, 98% of patients were satisfied with the ability of MACI surgery to relieve knee pain; 86%, with improvement in their ability to perform normal daily tasks; and 73%, with their ability to participate in sport 5 years after MACI. Conclusion: These results suggest that MACI provides a suitable midterm treatment option for articular cartilage defects in the knee. Long-term follow-up is essential to confirm whether the repair tissue has the durability required to maintain long-term patient quality of life.

A Randomized Trial Comparing Accelerated and Traditional Approaches to Postoperative Weightbearing Rehabilitation After Matrix-Induced Autologous Chondrocyte Implantation Findings at 5 Years

Background: While structured postoperative rehabilitation after matrix-induced autologous chondrocyte implantation (MACI) is considered critical, very little has been made available on how best to progressively increase weightbearing and exercise after surgery. Hypothesis: A significant improvement will exist in clinical and magnetic resonance imaging (MRI)–based scoring measures to 5 years after surgery. Furthermore, there will be no significant differences in outcomes in MACI patients at 5 years when comparing a traditional and an accelerated postoperative weightbearing regimen. Finally, patient demographics, cartilage defect parameters, and injury/surgery history will be associated with graft outcome. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Clinical and radiological outcomes were studied in 70 patients who underwent MACI to the medial or lateral femoral condyle, in conjunction with either an “accelerated” or a “traditional” approach to postoperative weightbearing rehabilitation. Under the accelerated protocol, patients reached full weightbearing at 8 weeks after surgery, compared with 11 weeks for the traditional group. Clinical measures (Knee Injury and Osteoarthritis Outcome Score [KOOS], Short-Form Health Survey [SF-36], visual analog scale [VAS], 6-minute walk test, and knee range of motion) were assessed before surgery and at 3, 6, 12, and 24 months and 5 years after surgery. High-resolution MRI was undertaken at 3, 12, and 24 months and 5 years after surgery and assessed 8 previously defined pertinent parameters of graft repair as well as a combined MRI composite score. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/surgery history was investigated. Results: Of the 70 patients recruited, 63 (31 accelerated, 32 traditional) underwent clinical follow-up at 5 years; 58 (29 accelerated, 29 traditional) also underwent radiological assessment. A significant time effect (P < .05) was demonstrated for all clinical and MRI-based scores over the 5-year period. While the VAS demonstrated significantly less frequent pain at 5 years in the accelerated group, there were no other significant differences between the 2 groups. Between 24 months and 5 years, a significant improvement (P < .05) in both groups was observed for the sport and recreation subscale of the KOOS as well as a significant decrease (P < .05) in active knee extension for the traditional group. There were no significant differences (P > .05) in the MRI-based scores between 24 months and 5 years after surgery. Patient age and defect size exhibited significant negative correlations (P < .05) with several MRI-based outcomes at 5 years, while there were no significant correlations (P > .05) between clinical and MRI-based outcomes. At 5 years after surgery, 94% and 95% were satisfied with the ability of MACI to relieve their knee pain and improve their ability to undertake daily activities, respectively. Conclusion: The outcomes of this randomized trial demonstrate a safe and effective accelerated rehabilitation protocol as well as a regimen that provides comparable, if not superior, clinical outcomes to patients throughout the postoperative timeline.

Accuracy of partial weight bearing after autologous chondrocyte implantation

OBJECTIVE To determine whether patients can accurately replicate and retain weight-bearing restrictions in both stationary (static) and dynamic conditions after autologous chondrocyte implantation (ACI). DESIGN Case series. SETTING Rehabilitation clinic. PARTICIPANTS A consecutive sample of patients (N=48) who had undergone ACI to a medial or lateral femoral condylar defect in the knee. INTERVENTIONS Patients were trained to partially weight bear using bathroom scales and forearm crutches prior to assessment. MAIN OUTCOME MEASURES A force platform was used to measure peak vertical ground reaction forces in patients during static and dynamic conditions immediately after weight-bearing instruction and training, and again during gait 7 days after training. RESULTS Immediately after instruction and weight-bearing practice on a set of scales, patients exerted a mean of 15.8% body weight more than expected during walking for 20% weight-bearing trials, 8.3% more for the 40% trials, 11.9% more for the 60% trials, and 1.2% less for the prescribed 80% trials. Accuracy of weight-bearing replication improved across all weight-bearing levels when assessed 7 days later, when patients exerted a mean of 6.6% body weight more than expected during walking for 20% weight-bearing trials (9.2% body weight improvement), 4.2% more for the 40% trials (4.1% body weight improvement), 9.9% more for the 60% trials (2% body weight improvement), and 0.2% more for the 60% trials (1% body weight improvement). CONCLUSIONS Patients were unable to follow weight-bearing restrictions after instruction and practice on a set of scales, and patients were unable to replicate weight-bearing levels in both static and dynamic conditions.

Arthroscopic Matrix-Induced Autologous Chondrocyte Implantation: 2-Year Outcomes

PURPOSE To determine the safety and efficacy of a new arthroscopic technique for matrix-induced autologous chondrocyte implantation (MACI) for articular cartilage defects in the knee. METHODS We undertook a prospective evaluation of the first 20 patients treated with the MACI technique (including 14 defects on the femoral condyle and 6 on the tibial plateau), followed up for 24 months after surgery. A 12-week structured rehabilitation program was undertaken by all patients. Patients underwent clinical assessment (Knee Injury and Osteoarthritis Outcome Score, Short Form 36 Health Survey, visual analog pain scale, 6-minute walk test, knee range of motion) before surgery and at 3, 6, 12, and 24 months after surgery and underwent magnetic resonance imaging (MRI) assessment at 3, 12, and 24 months after surgery. MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score. RESULTS A significant improvement (P < .05) was shown throughout the postoperative time line for all Knee Injury and Osteoarthritis Outcome Score subscales, the physical component score of the Short Form 36 Health Survey, the frequency and severity of knee pain, and the 6-minute walk test. An improvement in pertinent morphologic parameters of graft repair was observed to 24 months, whereas a good to excellent graft infill score and MRI composite score were observed at 24 months after surgery in 90% and 70% of patients, respectively. CONCLUSIONS We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period.

A Comparison of the Responsiveness of 4 Commonly Used Patient-Reported Outcome Instruments at 5 Years After Matrix-Induced Autologous Chondrocyte Implantation

Background: Patient-reported outcome (PRO) instruments are employed to assess outcomes after matrix-induced autologous chondrocyte implantation (MACI), although the PRO most responsive to change after surgery remains unknown. Purpose: To compare the responsiveness of 4 commonly used PRO instruments at 5 years after MACI. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The Knee Injury and Osteoarthritis Outcome Score (KOOS), the Lysholm score, the Tegner activity scale, and the 36-item Short Form Health Survey (SF-36) were administered to 104 patients before and at 5 years after MACI knee surgery. The Self-administered Patient Satisfaction Scale was employed at 5 years to investigate each patient’s overall level of satisfaction as well as satisfaction with relieving pain and improving the ability to perform daily activities, partake in recreational activities, and participate in sport. The effect size (ES) and standardized response mean (SRM) were used to compare PRO responsiveness. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the extent to which PRO changes were associated with satisfaction. The minimal clinically important difference (MCID) according to the criterion of patient satisfaction was identified as the PRO instrument change score maximizing classification accuracy. Results: The most responsive PRO measures were the KOOS sport/recreation (ES, 1.63; SRM, 1.43) and quality of life (QOL) (ES, 1.37; SRM, 1.18) subscales. The least responsive were the SF-36 mental component summary (MCS) (ES, 0.38; SRM, 0.40) and the Tegner activity scale (ES, 0.91; SRM, 0.59). Of the 104 patients, 54 (51.9%) reported being “very satisfied,” 38 (36.5%) “somewhat satisfied,” 8 (7.7%) “somewhat dissatisfied,” and 4 (3.9%) “very dissatisfied.” A ROC curve analysis was performed using “very satisfied” as the responder criterion. The strongest association was between the change in KOOS sport/recreation with satisfaction in improving the ability to perform recreational activities (area under the curve, 0.756; 95% confidence interval, 0.663-0.849), and the change score maximizing prediction accuracy (MCID) was 40 (sensitivity, 69%; specificity, 76%). Conclusion: The KOOS sport/recreation and QOL subscales were the most responsive PRO measures and were most predictive of satisfaction. This information will provide a guide as to the improvements required in pertinent PRO measures to produce a satisfied patient, while allowing researchers to better structure trials in these patients using the most relevant PRO instruments.

Clinical Rehabilitation Guidelines for Matrix-Induced Autologous Chondrocyte Implantation on the Tibiofemoral Joint

SYNOPSIS Autologous chondrocyte implantation (ACI) has become an established technique for the repair of full-thickness chondral defects in the knee. Matrix-induced ACI (MACI) is the third and current generation of this surgical technique, and, while postoperative rehabilitation following MACI aims to restore normal function in each patient as quickly as possible by facilitating a healing response without overloading the repair site, current published guidelines appear conservative, varied, potentially outdated, and often based on earlier ACI surgical techniques. This article reviews the existing evidence-based literature pertaining to cell loading and postoperative rehabilitation following generations of ACI. Based on this information, in combination with the technical benefits provided by third-generation MACI in comparison to its surgical predecessors, we present a rehabilitation protocol for patients undergoing MACI in the tibiofemoral joint that has now been implemented for several years by our institution in patients with MACI, with good clinical outcomes.

Factors Predictive of Outcome 5 Years After Matrix-Induced Autologous Chondrocyte Implantation in the Tibiofemoral Joint

Background: Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee. However, little is known about what variables most contribute to postoperative clinical and graft outcomes as well as overall patient satisfaction with the surgery. Purpose: To estimate the improvement in clinical and radiological outcomes and investigate the independent contribution of pertinent preoperative and postoperative patient, chondral defect, injury/surgery history, and rehabilitation factors to clinical and radiological outcomes, as well as patient satisfaction, 5 years after MACI. Study Design: Cohort study; Level of evidence, 3. Methods: This study was undertaken in 104 patients of an eligible 115 patients who were recruited with complete clinical and radiological follow-up at 5 years after MACI to the femoral or tibial condyles. After a review of the literature, a range of preoperative and postoperative variables that had demonstrated an association with postoperative clinical and graft outcomes was selected for investigation. These included age, sex, and body mass index; preoperative 36-item Short Form Health Survey (SF-36) mental component score (MCS) and physical component score (PCS); chondral defect size and location; duration of symptoms and prior surgeries; and postoperative time to full weightbearing gait. The sport and recreation (sport/rec) and knee-related quality of life (QOL) subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) were used as the patient-reported clinical evaluation tools at 5 years, while high-resolution magnetic resonance imaging (MRI) was used to evaluate graft assessment. An MRI composite score was calculated based on the magnetic resonance observation of cartilage repair tissue score. A patient satisfaction questionnaire was completed by all patients at 5 years. Regression analysis was used to investigate the contribution of these pertinent variables to 5-year postoperative clinical, radiological, and patient satisfaction outcomes. Results: Preoperative MCS and PCS and duration of symptoms contributed significantly to the KOOS sport/rec score at 5 years, while no variables, apart from the baseline KOOS QOL score, contributed significantly to the KOOS QOL score at 5 years. Preoperative MCS, duration of symptoms, and graft size were statistically significant predictors of the MRI score at 5 years after surgery. An 8-week postoperative return to full weightbearing (vs 12 weeks) was the only variable significantly associated with an improved level of patient satisfaction at 5 years. Conclusion: This study outlined factors such as preoperative SF-36 scores, duration of knee symptoms, graft size, and postoperative course of weightbearing rehabilitation as pertinent variables involved in 5-year clinical and radiological outcomes and overall satisfaction. This information may allow orthopaedic surgeons to better screen their patients as good candidates for MACI, while allowing treating therapists to better individualize their preoperative preparatory and postoperative rehabilitation regimens for a best possible outcome.

A Prospective, Randomized Comparison of Traditional and Accelerated Approaches to Postoperative Rehabilitation following Autologous Chondrocyte Implantation 2-Year Clinical Outcomes

Objective: To determine the safety and efficacy of “accelerated” postoperative load-bearing rehabilitation following matrix-induced autologous chondrocyte implantation (MACI). Design: A randomized controlled study design was used to investigate clinical outcomes in 70 patients following MACI, in conjunction with either accelerated or traditional approaches to postoperative weight-bearing (WB) rehabilitation. Both interventions sought to protect the implant for an initial period and then incrementally increase WB. Under the accelerated protocol, patients reached full WB at 8 weeks postsurgery, compared to 11 weeks for the traditional group. Clinical outcomes were assessed presurgery and at 3, 6, 12, and 24 months postsurgery. Results: A significant effect ( P < 0.017) for time existed for all clinical measures, demonstrating improvement up to 24 months in both groups. A significant interaction effect (P < 0.017) existed for pain severity and the 6-minute walk test, with accelerated group patients reporting significantly less severe pain and demonstrating superior 6-minute walk distance over the period. Although there was a significant group effect (P < 0.017) for maximal active knee extension range in favor of the accelerated regime, no further significant differences existed. There was no incidence of graft delamination up to 24 months that resulted directly from the 3-month postoperative rehabilitation program. Conclusion: The accelerated load-bearing approach that reduced the length of time spent ambulating on crutches produced comparable if not superior clinical outcomes up to 24 months postsurgery in the accelerated rehabilitation group, without compromising graft integrity. This accelerated regime is safe and effective and demonstrates a faster return to normal function postsurgery.

Accelerated Weightbearing Rehabilitation After Matrix-Induced Autologous Chondrocyte Implantation in the Tibiofemoral Joint Early Clinical and Radiological Outcomes

Background: Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, although best patient outcomes appear limited by a lack of evidence-based knowledge on how to progressively increase postoperative weightbearing (WB) and rehabilitation exercises. Hypothesis: To determine the safety and efficacy of an accelerated WB regimen after MACI in the tibiofemoral joint. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Clinical and radiological assessments were performed in 28 knees at 12 months after MACI to the medial or lateral femoral condyle. Both rehabilitation interventions sought to protect the implant for an initial period and then incrementally increase load bearing. Under the “accelerated” (AR) protocol, patients reached full WB at 6 weeks after surgery compared with 8 weeks for what was considered to be the current “best practice” (CR) WB regimen based on previous research. Assessments included the Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), visual analog scale, 6-minute walk test, and active knee range of motion (ROM). High-resolution magnetic resonance imaging (MRI) was used to describe the quality and quantity of repair tissue via the assessment of pertinent parameters of graft repair as well as an MRI composite score. Results: Patients in both groups demonstrated significant improvement (P < .05) in all clinical measures over the preoperative and postoperative timeline from before surgery to 12 months after surgery. The AR group reported significantly better (P < .05) SF-36 physical component scores at 8 weeks and significantly greater (P < .05) KOOS quality of life scores at 6 and 12 months postoperatively. Although no differences (P > .05) were observed between the 2 groups for active knee ROM, the AR group did achieve full active knee extension as early as 4 weeks compared with the CR group at 12 weeks. There was no difference (P > .05) in graft quality as assessed by MRI (MOCART composite score: AR, 3.34; CR, 3.04), with no patients suffering any adverse effects from the implant up to 12 months, regardless of the rehabilitation protocol employed. Conclusion: The AR approach that reduced the length of time spent ambulating on crutches resulted in improved general physical function and quality of life and an earlier attainment of full active knee extension when compared with the CR approach. There were no graft complications ascertained through MRI. This regimen appears safe and may potentially speed up the recovery of normal gait function. A larger patient cohort and follow-up are required to observe long-term graft outcomes.

Isokinetic knee extensor strength deficit following matrix-induced autologous chondrocyte implantation

BACKGROUND Autologous chondrocyte implantation has become an established technique for addressing knee cartilage defects. Despite reported improvement in pain and regeneration of hyaline-like repair tissue, little has been reported on the recovery of knee strength. METHODS Knee strength assessment was undertaken in 60 patients at 5 years following autologous chondrocyte implantation. Using an isokinetic dynamometer, and during isokinetic knee extension and flexion angular velocities of 60°, 90° and 120°/s, the peak torque, torque at 45° of knee flexion and hamstrings/quadriceps ratio was obtained, in both the operated and non-operated limbs. Pain at the time of assessment was obtained. Independent sample t-tests were used to assess differences in the operated and non-operated sides. FINDINGS There were no significant differences (p>0.05) between the operated and non-operated legs in the peak knee flexor torque or knee flexor torque at a knee flexion angle of 45°, at all angular velocities (60°, 90° and 120°/s). While the peak knee extensor torque was less in the operated leg at all angular velocities, these differences were not significant (p>0.05). However, a significantly reduced (p<0.05) knee extensor torque at a knee flexion angle of 45°, was observed at all speeds. INTERPRETATION While patients had recovered their knee flexor strength, they still demonstrated a reduced knee extensor strength profile at 5 years. This demonstrates that the early supervised rehabilitation phase following autologous chondrocyte implantation is not sufficient to restore long-term knee strength, and ongoing patient advice and rehabilitation is required extending beyond this early period. It is unknown how this prolonged reduction in strength may affect long-term graft outcome.