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Background: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint., Purpose: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI., Study Design: Case series; Level of evidence, 4., Methods: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score., Results: All patient-reported outcome measures improved ( P < .0001) up to 2 years after surgery. Apart from the significant increase ( P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life ( P = .010) and Sport and Recreation ( P < .001), as well as a greater knee extensor strength LSI ( P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill ( P = .027), there were no other MRI-based differences ( P > .05)., Conclusion: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This research has received some funding from the National Health and Medical Research Council (ID254622 and ID1003452) and the Hollywood Private Hospital Research Foundation (RF31 and RF050). This research was approved by the Hollywood Private Hospital (HPH145) Human Research Ethics Committee. J.R.E. has received support for education and research support from Vericel. G.C.J. has shares in Orthocell. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: To investigate the mid-term outcomes of an accelerated return to full weight bearing (WB) after matrix-induced autologous chondrocyte implantation (MACI)., Methods: This randomized study allocated 35 patients (37 knees) to a 6 week (n = 18) or 8 week (n = 19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2 and minimum 5 years (range 5.5-7 years), using the KOOS, SF-36, visual analogue pain scale, 6-min walk test and active knee range of motion (ROM). Peak isokinetic knee extensor and flexor strength was assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) was undertaken to evaluate the repair tissue, and an MRI composite score was calculated., Results: While no group differences (n.s.) were observed, significant improvement was observed for all patient-reported outcome measures (p < 0.05), 6-min walk distance (p = 0.040), active knee flexion (p = 0.002) and extension (p < 0.0001) ROM, and the LSI for peak knee extensor strength (p < 0.0001). At final review, 87.5% (6 weeks) and 82.4% (8 weeks) of patients were satisfied overall. A non-significant decline (n.s.) was observed for the MRI composite score from 1-year post-surgery to final review, with no significant MRI-based differences (n.s.) between groups. At final review, two grafts (6-week n = 1, 8-week n = 1) demonstrated MRI-based graft failure, while an additional patient had progressed toward knee arthroplasty (8.1% failure rate at minimum 5 years)., Conclusions: The 6-week return to full WB after MACI provided comparable clinical and MRI-based outcomes beyond 5 years post-surgery, without jeopardizing the graft. This 6-week WB protocol is faster than those previously proposed and studied., Level of Evidence: II., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging midterm clinical outcomes, although published studies presenting longer-term clinical and radiological outcomes, across varied tibiofemoral and patellofemoral graft locations, are scarce., Purpose: To present the clinical and radiological outcomes a minimum of 10 years after surgery in a consecutive series of patients who underwent MACI in the tibiofemoral or patellofemoral knee joint. Secondly, to investigate any association between outcomes and patient characteristics, graft parameters, and injury and surgery history., Study Design: Case series; Level of evidence, 4., Methods: Overall, 87 patients (99 grafts: 57 medial femoral condyle, 24 lateral femoral condyle, 11 trochlea, 7 patella) were prospectively evaluated clinically and with magnetic resonance imaging (MRI) before surgery and at 2, 5, and minimum 10 years after MACI (mean, 13.1 years; range, 10.5-16 years). Patients were evaluated with a range of patient-reported outcome measures (PROMs), including the Knee injury and Osteoarthritis Outcome Score (KOOS) and patient satisfaction. The 6-minute walk test, active knee range of motion, and peak isokinetic knee extensor and flexor strength were assessed. Limb symmetry indices (LSIs) were calculated for strength measures. MRI was undertaken to evaluate the repair tissue, and an MRI composite score was calculated., Results: All PROMs significantly improved ( P < .05) over the pre- to postoperative period. Apart from KOOS Sport ( P = .018) and the LSI for peak isokinetic knee extensor strength ( P = .005), which significantly improved, no significant change ( P > .05) was observed from 2 years after surgery to final follow-up (range, 10.5-16 years) in all other PROMs, 6-minute walk distance, active knee range of motion, and the LSI for peak isokinetic knee flexor strength. At final follow-up, while the mean LSIs for peak isokinetic knee flexor and extensor strength were 96.9% and 95.7%, respectively, 74.7% of patients were satisfied with their ability to participate in sports, and 88.5% were satisfied overall. A nonsignificant decline was observed for tissue infill ( P = .211) and the MRI composite score ( P = .099) from 2 years to final review. At final MRI review, 9 grafts (9.1%) had failed. While no significant association ( P > .05) was observed between clinical or MRI-based outcomes and patient demographics (age, body weight, body mass index), defect size, or the duration of preoperative symptoms, the number of previous surgical procedures was significantly and negatively associated with KOOS Symptoms ( P = .015), KOOS Sport ( P = .011), and the degree of tissue infill ( P = .045)., Conclusion: MACI provided high levels of satisfaction and adequate graft survivorship as visualized on MRI at 10.5 to 16 years after surgery.

Background: Longer term outcomes after matrix-induced autologous chondrocyte implantation (MACI) are lacking, while early postoperative weightbearing (WB) management has traditionally been conservative., Purpose: To investigate the longer term clinical and radiological outcomes after an 8-week (vs 12-week) WB protocol after MACI., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: A randomized study design allocated 70 patients to an 8- (n = 34) or 12-week (n = 36) approach to full WB after MACI of the medial or lateral femoral condyle. Patients were evaluated preoperatively; at 3, 12, and 24 months after surgery; and at 5 and 10 years after surgery. At 10 years (range, 10.5-11.5 years), 60 patients (85.7%; 8 weeks: n = 29; 12 weeks: n = 31) were available for review. Clinical outcomes included patient-reported outcomes, maximal isokinetic knee extensor and flexor strength, and functional hop capacity. High-resolution magnetic resonance imaging (MRI) was undertaken to assess the quality and quantity of repair tissue per the MOCART (magnetic resonance observation of cartilage repair tissue) system. A combined MRI composite score was also evaluated., Results: Clinical and MRI-based scores for the full cohort significantly improved ( P < .05) over the 10-year period. Apart from the Tegner activity score, which improved ( P = .041), as well as tissue structure ( P = .030), which deteriorated, there were no further statistically significant changes ( P > .05) from 5 to 10 years. There were no 10-year differences between the 2 WB rehabilitation groups. At 10 years, 81.5% and 82.8% of patients in the 8- and 12-week groups, respectively, demonstrated good-excellent tissue infill. Graft failure was observed on MRI at 10 years in 7 patients overall, which included 4 located on 10-year MRI (8 weeks: n = 1; 12 weeks: n = 3) and a further 3 patients (8 weeks: n = 1; 12 weeks: n = 2) not included in the current analysis who proceeded to total knee arthroplasty. At 10 years, 93.3% of patients were satisfied with MACI for relieving their pain, with 83.3% satisfied with their ability to participate in sport., Conclusion: MACI provided high satisfaction levels and tissue durability beyond 10 years. The outcomes of this randomized trial demonstrate a safe 8-week WB rehabilitation protocol without jeopardizing longer term outcomes.

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging clinical results in the treatment of knee chondral defects. However, earlier studies suggested that chondrocyte implantation in the patellofemoral (PF) joint was less effective than in the tibiofemoral (TF) joint., Purpose: To compare the radiological and clinical outcomes of those undergoing MACI to either the femoral condyles or PF joint., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 194 patients were included in this analysis, including 127 undergoing MACI to the medial (n = 94) and lateral (n = 33) femoral condyle, as well as 67 to the patella (n = 35) or trochlea (n = 32). All patients were evaluated clinically (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale, Short Form-36) before surgery and at 3, 12, and 24 months after surgery, while magnetic resonance imaging (MRI) was undertaken at 3, 12, and 24 months, with the MOCART (magnetic resonance observation of cartilage repair tissue) scoring system employed to evaluate the quality and quantity of repair tissue, as well as an MRI composite score. Patient satisfaction was evaluated., Results: No significant group differences ( P > .05) were seen in demographics, defect size, prior injury, or surgical history, while the majority of clinical scores were similar preoperatively. All clinical scores significantly improved over time ( P < .05), with a significant group effect observed for KOOS activities of daily living ( P = .008), quality of life ( P = .008), and sport ( P = .017), reflecting better postoperative scores in the TF group. While the PF group had significantly lower values at baseline for the KOOS activities of daily living and quality of life subscales, it actually displayed a similar net improvement over time compared with the TF group. At 24 months, 93.7% (n = 119) and 91.0% (n = 61) of patients were satisfied with the ability of MACI to relieve their knee pain, 74.0% (n = 94) and 65.7% (n = 44) with their ability to participate in sport, and 90.5% (n = 115) and 83.6% (n = 56) satisfied overall, in the TF and PF groups, respectively. MRI evaluation via the MOCART score revealed a significant time effect ( P < .05) for the MRI composite score and graft infill over the 24-month period. While subchondral lamina scored significantly better ( P = .002) in the TF group, subchondral bone scored significantly worse ( P < .001). At 24 months, the overall MRI composite score was classified as good/excellent in 98 TF patients (77%) and 54 PF patients (81%)., Conclusion: MACI in the PF joint with concurrent correction of PF maltracking if required leads to similar clinical and radiological outcomes compared with MACI on the femoral condyles.

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in treating patients with knee cartilage defects. Postoperatively, the time required to attain full weightbearing (WB) remains conservative., Hypothesis: We hypothesized that patients would have no significant clinical or radiological differences or graft complications after an 8-week or 6-week return to full WB after MACI., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: A total of 37 knees (n = 35 patients) were randomly allocated to either an 8-week return to full WB that we considered current best practice based on the existing literature (CR group; n = 19 knees) or an accelerated 6-week WB approach (AR group; n = 18 knees). Patients were evaluated preoperatively and at 1, 2, 3, 6, 12, and 24 months after surgery, using the Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Health Survey, visual analog pain scale, 6-minute walk test, and active knee range of motion. Isokinetic dynamometry was used to assess peak knee extension and flexion strength and limb symmetry indices (LSIs) between the operated and nonoperated limbs. Magnetic resonance imaging (MRI) was undertaken to evaluate the quality and quantity of repair tissue as well as to calculate an MRI composite score., Results: Significant improvements ( P < .05) were observed in all subjective scores, active knee flexion and extension, 6-minute capacity, peak knee extensor torque in the operated limb, and knee extensor LSI, although no group differences existed. Although knee flexor LSIs were above 100% for both groups at 12 and 24 months after surgery, LSIs for knee extensor torque at 24 months were 93.7% and 87.5% for the AR and CR groups, respectively. The MRI composite score and pertinent graft parameters significantly improved over time ( P < .05), with some superior in the AR group at 24 months. All patients in the AR group (100%) demonstrated good to excellent infill at 24 months, compared with 83% of patients in the CR group. Two cases of graft failure were observed, both in the CR group. At 24 months, 83% of patients in the CR group and 88% in the AR group were satisfied with the results of their MACI surgery., Conclusion: Patients in the AR group who reduced the length of time spent ambulating on crutches produced comparable outcomes up to 24 months, without compromising graft integrity.

Background: While midterm outcomes after matrix-induced autologous chondrocyte implantation (MACI) are encouraging, the procedure permits an arthroscopic approach that may reduce the morbidity of arthrotomy and permit accelerated rehabilitation., Hypothesis: A significant improvement in clinical and radiological outcomes after arthroscopic MACI will exist through to 5 years after surgery., Study Design: Case series; Level of evidence, 4., Methods: We prospectively evaluated the first 31 patients (15 male, 16 female) who underwent MACI via arthroscopic surgery to address symptomatic tibiofemoral chondral lesions. MACI was followed by a structured rehabilitation program in all patients. Clinical scores were administered preoperatively and at 3 and 6 months as well as 1, 2, and 5 years after surgery. These included the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm knee scale (LKS), Tegner activity scale (TAS), visual analog scale for pain, Short Form-36 Health Survey (SF-36), active knee motion, and 6-minute walk test. Isokinetic dynamometry was used to assess peak knee extension and flexion strength and limb symmetry indices (LSIs) between the operated and nonoperated limbs. High-resolution magnetic resonance imaging (MRI) was performed at 3 months and at 1, 2, and 5 years postoperatively to evaluate graft repair as well as calculate the MRI composite score., Results: There was a significant improvement ( P < .05) in all KOOS subscale scores, LKS and TAS scores, the SF-36 physical component score, pain frequency and severity, active knee flexion and extension, and 6-minute walk distance. Isokinetic knee extension strength significantly improved, and all knee extension and flexion LSIs were above 90% (apart from peak knee extension strength at 1 year). At 5 years, 93% of patients were satisfied with MACI to relieve their pain, 90% were satisfied with improving their ability to undertake daily activities, and 80% were satisfied with the improvement in participating in sport. Graft infill ( P = .033) and the MRI composite score ( P = .028) significantly improved over time, with 90% of patients demonstrating good to excellent tissue infill at 5 years. There were 2 graft failures at 5 years after surgery., Conclusion: The arthroscopically performed MACI technique demonstrated good clinical and radiological outcomes up to 5 years, with high levels of patient satisfaction.

Background: Microfracture and the autologous matrix-induced chondrogenesis (AMIC) technique are popular for the treatment of articular cartilage defects. However, breaching of the subchondral bone plate could compromise the subchondral bone structure., Hypothesis: Microfracture and AMIC will cause deleterious effects on the subchondral bone structure., Study Design: Controlled laboratory study., Methods: A total of 36 sheep received an 8-mm-diameter cartilage defect in the left medial femoral condyle. Control animals (n = 12) received no further treatment, and the rest received 5 microfracture holes either with a type I/III collagen scaffold implanted (n = 12; AMIC group) or without the collagen scaffold (n = 12; microfracture group). Macroscopic infill of defects, histology, and histomorphometry of the subchondral bone were performed at 13 and 26 weeks postoperatively, and micro-computed tomography (CT) was also performed at 26 weeks postoperatively., Results: Microfracture and AMIC resulted in subchondral bone cyst formation in 5 of 12 (42%) and 11 of 12 (92%) specimens at 13 and 26 weeks, respectively. Subchondral bone changes induced by microfracture and AMIC were characterized by an increased percentage of bone volume, increased trabecular thickness, and a decreased trabecular separation, and extended beyond the area below the defect. High numbers of osteoclasts were observed at the cyst periphery, and all cysts communicated with the microfracture holes. Cartilage repair tissue was of poor quality and quantity at both time points and rarely reached the tidemark at 13 weeks., Conclusion: Microfracture technique caused bone cyst formation and induced severe pathology of the subchondral bone in a sheep model., Clinical Relevance: The potential of microfracture technique to induce subchondral bone pathology should be considered., (© 2016 The Author(s).)

Background: Graft hypertrophy is a common occurrence after periosteal, collagen-covered and matrix-induced autologous chondrocyte implantation (MACI)., Purpose/hypothesis: The purpose of this study was to investigate the incidence, development, and degree of graft hypertrophy at 24 months after MACI. The hypothesis was that graft hypertrophy would not be associated with clinical outcome at 24 months., Study Design: Case series, Level of evidence, 4., Methods: This study was undertaken in 180 consecutive patients (113 male, 67 female) after MACI in the knee. All patients were assessed clinically using the Knee injury and Osteoarthritis Outcome Score (KOOS) and underwent magnetic resonance imaging (MRI) at 3, 12, and 24 months after surgery. The incidence of hypertrophy relevant to anatomic graft site was investigated, as was the progressive change in hypertrophic studies postoperatively. The degree of tissue overgrowth in hypertrophic cases was investigated, as was its association with patient clinical outcome at 24 months after surgery., Results: Of the 180 patients, 50 demonstrated a hypertrophic graft at 1 or more postoperative time points. This included 9 grafts (5.0%) at 3 months and 32 grafts (18.7%) at 12 months. At 24 months, 47 grafts (26.1%)-43 (32.1%) tibiofemoral and 4 (8.7%) patellofemoral-were hypertrophic. Patients with hypertrophic grafts at 24 months (n = 47) were younger (P = .051), they had a lower body mass index (BMI; P = .069), and significantly fewer of them had patellofemoral grafts (P = .007) compared with patients who had grafts with full (100%) tissue infill (n = 61). There were no significant differences in any of the KOOS subscales between patients with graft hypertrophy or full (100%) tissue infill at 24 months after surgery, while the severity of graft hypertrophy was not associated with KOOS subscales at 24 months., Conclusion: Hypertrophic grafts after MACI were common and continued to develop through to 24 months after surgery. Hypertrophic growth was associated with being younger and having a lower BMI, was more common on the femoral condyles, and overall was not associated with clinical outcome at 24 months after surgery. However, further research with longer term follow-up is required to evaluate the effect of persistent hypertrophy on graft stability and to assess the use of early surgical intervention to prevent such failure., (© 2015 The Author(s).)

Background: While matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee chondral defects, there remains little available research specifically investigating its use in the patellofemoral joint., Purpose: To prospectively evaluate the clinical and radiologic outcome of MACI in the patellofemoral joint., Study Design: Case series; Level of evidence, 4., Methods: In 47 consecutive patients undergoing patellofemoral MACI, clinical (Knee injury and Osteoarthritis Outcome Score, 36-Item Short Form Health Survey, visual analog scale for pain, 6-minute walk test, knee range of motion, and strength assessment) and magnetic resonance imaging (MRI) assessments were undertaken before and 3, 12, and 24 months after surgery. The MRI was performed to assess graft infill and determine an overall MRI composite score. Results were analyzed according to (1) the patient sample overall and (2) after stratification into 4 subgroups per implant location (patella or trochlea) as well as whether or not adjunct tibial tubercle transfer for patellofemoral malalignment was required., Results: The overall patient sample, as well as each of the 4 procedural subgroups, demonstrated clinically and statistically significant (P < .05) improvements over time for all clinical scores. Graft infill and the MRI composite score also demonstrated statistically significant (P < .05) improvements over time, with no evidence of a main effect for procedure group or interaction between procedure group and time. At 24 months after surgery, 40.4% (n = 19) of patients exhibited complete graft infill comparable with the adjacent native cartilage, with a further 6.4% (n = 3) demonstrating a hypertrophic graft. A further 31.9% (n = 15) of patients exhibited 50% to 100% tissue infill, and 17% (n = 8) demonstrated <50% tissue infill. Two patients (4.3%) demonstrated graft failure. At 24 months after surgery, 85% (n = 40) of patients were satisfied with the results of their MACI surgery., Conclusion: These results demonstrate that MACI provides improved clinical and radiologic outcomes to 24 months in patients undergoing treatment specifically for articular cartilage defects on the patella or trochlea, with and without concurrent realignment of the extensor mechanism if required., (© 2015 The Author(s).)

Articular cartilage injury is the most common type of damage seen in clinical orthopedic practice. The matrix-induced autologous chondrocyte implant (MACI) was developed to repair articular cartilage with an advance on the autologous chondrocyte implant procedure. This study aimed to evaluate whether MACI is a safe and efficacious cartilage repair treatment for patients with knee cartilage lesions. The primary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS) domains and magnetic resonance imaging (MRI) results, compared between baseline and postoperative months 3, 6, 12, and 24. A total of 15 patients (20 knees), with an average age of 33.9 years, had a mean defect size of 4.01 cm(2). By 6-month follow-up, KOOS results demonstrated significant improvements in symptoms and knee-related quality of life. MRI showed significant improvements in four individual graft scoring parameters at 24 months postoperatively. At 24 months, 90% of MACI grafts had filled completely and 10% had good-to-excellent filling of the chondral defect. Most (95%) of the MACI grafts were isointense and 5% were slightly hyperintense. Histologic evaluation at 15 and 24 months showed predominantly hyaline cartilage in newly generated tissue. There were no postoperative complications in any patients and no adverse events related to the MACI operation. This 2-year study has confirmed that MACI is safe and effective with the advantages of a simple technique and significant clinical improvements. Further functional and mechanistic studies with longer follow-up are needed to validate the efficacy and safety of MACI in patients with articular cartilage injuries.

Background: Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of knee chondral defects. While a number of factors may affect the clinical outcome, little is known about the influence of subchondral bone abnormalities at the time of surgery on pain and graft outcomes after MACI., Purpose: To investigate the association between subchondral bone marrow edema within 3 months before MACI surgery on preoperative and postoperative reported pain and symptoms as well as postoperative graft outcomes., Study Design: Cohort study; Level of evidence, 3., Methods: This retrospective study was undertaken in 56 patients undergoing MACI with clinical and radiological assessments before surgery and at 3, 12, 24, and 60 months after surgery. Patients were assessed using the Pain and Symptoms subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS). High-resolution magnetic resonance imaging (MRI) was used to evaluate the severity of preoperative subchondral bone marrow edema, while graft infill and an MRI composite graft score were evaluated after surgery via the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Linear regression utilizing generalized estimating equations was used to investigate the association between preoperative subchondral bone marrow edema scores and preoperative and postoperative KOOS subscores as well as postoperative MRI-based scores of graft repair., Results: The degree of preoperative subchondral bone marrow edema was not significantly associated with postoperative outcomes, whereby there was no evidence of a difference between edema subgroups over all time points for the KOOS-Pain subscore (P = .644), KOOS-Symptoms subscore (P = .475), or MRI composite score (P = .685) after adjustment for potential confounders of age, body mass index, defect size, and defect location., Conclusion: No association was demonstrated between the severity of preoperative subchondral bone marrow edema with postoperative patient-reported knee pain or symptoms or postoperative graft repair assessed via MRI., (© 2014 The Author(s).)

Background: Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of knee chondral defects, although the correlation between clinical and radiological outcomes after surgery is poorly understood., Purpose: To determine the correlation between clinical and radiological outcomes throughout the postoperative timeline to 5 years after MACI., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: This retrospective study was undertaken in 83 patients (53 male, 30 female) with complete clinical and radiological follow-up at 1, 2, and 5 years after MACI. The mean age of patients was 38.9 years (range, 13-62 years), with a mean body mass index (BMI) of 26.6 kg/m(2) (range, 16.8-34.8 kg/m(2)), mean defect size of 3.3 cm(2) (range, 1-9 cm(2)), and mean preoperative duration of symptoms of 9.2 years (range, 1-46 years). Patients indicated for MACI in this follow-up were 13 to 65 years of age, although they were excluded if they had a BMI >35 kg/m(2), had undergone prior extensive meniscectomy, or had ongoing progressive inflammatory arthritis. Patients were assessed clinically using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Magnetic resonance imaging (MRI) was used to evaluate the graft using a 1.5-T or 3-T clinical scanner; the MRI assessment included 8 parameters of graft repair (infill, signal intensity, border integration, surface contour, structure, subchondral lamina, subchondral bone, and effusion) based on the magnetic resonance observation of cartilage repair tissue (MOCART) score as well as an MRI composite score. The degree of an association between the MRI parameters and the KOOS subscales at each postoperative time point was assessed with the Spearman correlation coefficient (SCC), and significance was determined at P < .05. Ethics approval was obtained from the appropriate hospital and university Human Research Ethics Committees, and informed consent was gathered from all patients., Results: The only MRI parameter displaying consistent evidence of an association with the KOOS subscales was effusion, with a pattern of increasing strength of correlations over time and statistically significant associations at 5 years with KOOS-Pain (SCC, 0.25; P = .020), KOOS-Activities of Daily Living (SCC, 0.26; P = .018), and KOOS-Sport (SCC, 0.32; P = .003). Apart from a significant correlation between subchondral lamina and KOOS-Sport at 1 year (SCC, 0.27; P = .016), no further significant findings were observed., Conclusion: Apart from some consistent evidence of an association between the KOOS and effusion, this analysis demonstrated a limited correlative capacity between clinical and radiological outcomes up to 5 years after surgery., (© 2014 The Author(s).)

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.

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.

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., (Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To determine the effectiveness of 'accelerated' compared to 'traditional' post-operative load bearing rehabilitation protocols following matrix-induced autologous chondrocyte implantation (MACI)., Method: A randomized controlled study design was used to investigate clinical, biomechanical and radiographic assessment at 3 months post-surgery in 62 patients following MACI to the medial or lateral femoral condyle. Both rehabilitation interventions sought to protect the implant for an initial period, then incrementally increase load bearing. Under the 'accelerated' protocol, patients reached full weight bearing at 8 weeks post-surgery, compared to 11 weeks for the 'traditional' group., Results: Patients in the 'accelerated' group achieved greater 6 min walk distances and daily activity levels as measured by accelerometry (P<0.05) compared to the 'traditional' group. Furthermore, the 'accelerated' group reported significantly better improvement in knee pain at 12 weeks as indicated by the Knee Injury and Osteoarthritis Outcome Score (P<0.05), and regardless of the rehabilitation protocol employed, no patient suffered any adverse effect to the implant as assessed by magnetic resonance imaging at 3 months. Comparison of each rehabilitation group with an unaffected control group revealed a significant difference in peak knee adduction and flexion moments for the traditional group (P<0.05). However, there was no difference for accelerated patients (P>0.05), which may demonstrate a faster return to knee loading patterns typically observed in unaffected subjects., Conclusion: The 'accelerated' load bearing approach that reduced the length of time spent ambulating on crutches resulted in reduced knee pain, improved function, no graft complications and may speed up the recovery of normal gait function. Patient follow-up to at least 24 months would be required to observe longer-term graft outcomes.

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.

Objective: Calcitonin (CT) has been recently shown to exhibit direct protective effects on articular cartilage against joint degenerative disease. It has been proposed that CT might act via the CT receptor (CTR) to activate the cyclic AMP (cAMP) pathway and protect type II collagen degradation. In this study, we investigated the existence of CTR in human articular cartilage and chondrocytes, and examined the potential pharmacological effects and transduction pathway of salmon CT (sCT) in human chondrocytes., Methods: Five human articular cartilage samples were examined for the expression of the CTR by polymerase chain reaction (PCR), immunostaining and Western blot analysis. cAMP levels in human chondrocyte stimulated with sCT were assessed by ELISA. The effect of sCT on the gene expression profiles, including aggrecan, type II collagen, MMP-1, MMP-3 and MMP-13, of human chondrocytes was also examined by relative quantitative Real-time PCR., Results: We failed to detect the CTR at both the transcriptional and protein levels in human chondrocytes and cartilage tissue by PCR, immunostaining and Western blotting. cAMP levels were significantly elevated in human chondrocytes by forskolin (100muM) to more than 10-fold (P<0.001), however, were not induced by sCT (10(-7)M, 10(-8)M, 10(-9)M). Real-time PCR analysis demonstrated that sCT slightly reduced the gene expression of MMPs, although this effect was not statistically significant., Conclusion: In contrary to previous reports, our data indicate that human cartilage and chondrocytes do not express CTR. Furthermore, sCT does not appear to have direct effects on human chondrocytes. We propose that the chondroprotective effect of CT observed in vivo may be indirect via its impact on subchondral bone resorptive activity of osteoclasts.