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Abstract

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. 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. 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. 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.

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... Among the 16 included studies, there were 8 level IV studies, 12,13,16,19,24,40,47,59 all with prospective designs, 4 comparing outcomes between the involved and uninvolved limbs, 16,24,40,47 4 comparing outcomes over time, 13,19,47,59 1 reporting outcomes between males and females, 16 and 1 evaluating limb-loading postoperatively. 12 One study was a level III study, with the primary analysis comparing outcomes of males and females. ...
... Among the 16 included studies, there were 8 level IV studies, 12,13,16,19,24,40,47,59 all with prospective designs, 4 comparing outcomes between the involved and uninvolved limbs, 16,24,40,47 4 comparing outcomes over time, 13,19,47,59 1 reporting outcomes between males and females, 16 and 1 evaluating limb-loading postoperatively. 12 One study was a level III study, with the primary analysis comparing outcomes of males and females. ...
... 39 The remaining 7 studies were level I, 14,15,17,18,20,68,69 with 2 studies by the same group reporting outcomes following randomization into MF or ACI treatment groups 68,69 and 5 studies, 14,15,17,18,20 all from the same group, reporting outcomes following a randomization into 2 rehabilitation programs following ACI. Therefore, in this review, 10 of the 16 studies are from the same research group (5 case series 12,13,16,19,59 and 5 randomized controlled trials [RCTs] 14,15,17,18,20 of rehabilitation weight-bearing protocols), which could contribute to bias in the interpretation of the findings across the studies. The average  SD total modified Coleman Methodology Score was 68  11, with the highest score being 85 14 and the lowest score 52. ...
Article
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Study design: Systematic literature review. Objective: To systematically review the literature relative to muscle performance, knee joint biomechanics, and performance-based functional outcomes following articular cartilage repair and restoration surgical procedures in the knee. Background: Articular cartilage injuries are associated with functional limitations, poor quality of life, and the potential for long-term disability. This review systematically evaluates evidence related to muscle performance, joint biomechanics, and performance-based functional outcomes following articular cartilage procedures, and discusses their implications for rehabilitation. Methods: The online databases of PubMed (MEDLINE), CINAHL, SPORTDiscus, and Scopus were searched (inception to September 2013). Studies pertaining to muscle performance, knee joint biomechanics, and performance-based measures of function following articular cartilage procedure in the knee were included. Results: Sixteen articles met the specified inclusion criteria. Seven studies evaluated muscle performance, all showing persistent deficits in quadriceps femoris muscle strength for up to 7 years postprocedure. Quadriceps femoris strength deficits of greater than 20% were noted in 33% and 26% of individuals at 1 and 2 years following microfracture and autologous chondrocyte implantation (ACI), respectively. Two studies evaluated knee mechanics post-ACI, showing persistent deficits in knee kinematics and kinetics for up to 12 months postprocedure compared to uninjured individuals. Seven studies showed improved functional capacity (6-minute walk test) over time, and 3 studies showed persistent performance deficits during higher-level activities (single-leg hop test) for up to 6 years postprocedure. Five studies comparing weight-bearing protocols (accelerated versus traditional/current practice) following ACI found few differences between the groups in function and gait mechanics; however, persistent gait alterations were observed in both groups compared to uninjured individuals. Conclusion: Significant quadriceps femoris strength deficits, gait deviations, and functional deficits persist for 5 to 7 years following ACI and microfracture surgical procedures. Future research regarding rehabilitation interventions to help mitigate these deficits is warranted. Level of Evidence Prognosis, level 2a-.
... At three months, seven articles which used adapted MOCART scoring reported mean scores between 2.71 (± 0.16) and 3.11 (± 0.20) [8, 9, 11-13, 16, 25]. Ebert et al. reported in two different studies [10,12] that 71% and 60%, respectively, of patients had a good to excellent defect fill. Ebert et al. [14]. ...
... At two years, mean adapted MOCART scores varied between 3.18 (± 0.17) and 3.47 (± 0.18) [8,9,[11][12][13]25] and good to excellent rates varied between 83.9% and 100% [8,10,12,14]. The remaining articles used different scoring methods but nonetheless, results also improved compared to previous follow-ups [2,9,28]. ...
... In the first two years after surgery, hypertrophy rates varied between 6.4% and 26.1% (median 20%) [2,8,10,11,14,21,25] with one study [22] reporting no hypertrophic grafts at 24 months; however, this study only included 13 patients. At final follow-up, the rates varied as the hypertrophic grafts either remained unchanged or regressed [2,12,14,17,21]. ...
Article
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Purpose: The purpose of the present article was (1) to systematically review the current literature and (2) to collect data regarding the postoperative magnetic resonance imaging (MRI) appearance of third-generation autologous chondrocyte implantation (ACI) grafts and (3) to provide an overview of imaging findings at various postoperative time points. Methods: A systematic review of the literature in Medline (Pubmed) and Embase was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles which reported the post-operative MRI morphological outcomes following the use of third-generation ACI for treatment of knee cartilage lesions were included. All MRI results were allocated to six different time intervals: ≤ 3 months, > 3-6 months, > 6 months-1 year, > 1 year-2 years, > 2-5 years and > 5 years after surgery. Results: A total of 22 studies were included and the study populations ranged from 13 to 180 patients adding up to a total of 951 patients. Parameters such as defect fill, border integration, surface contour, graft morphology and integrity of the subchondral lamina all improve gradually with a peak two years following surgery suggesting complete graft maturation at this time point. After this peak, a statistically insignificant decline is noted for most of the parameters. Signal intensity was found to gradually shift from hyperintense to isointense in the first 36 months and to hypointense later on. Contrarily, subchondral bone edema is not only a postoperative feature of the procedure but also can reappear or persist up to ten years after surgery. As graft failures can appear after two years, consequently, the MRI composite score is also affected. Conclusion: Recurring patterns in postoperative MRI appearance were observed in certain parameters including defect filling, graft signal intensity and structure, border integration of the graft while parameters like subchondral bone tend to be unpredictable. Given the heterogenous findings in terms of clinical correlation, and relating that aspect to the patterns found in this review, an MRI is justified at three months, one year, two years and five years after surgery, unless the clinical symptomatology and individual patient needs dictate otherwise. Level of evidence: IV.
... Of these, 11 studies used the MOCART scoring system for their evaluation. Three studies used an MRI composite score composed of the same parameters [38,39,53]. Marlovits et al. [50] and Selmi et al. [51] reported integration outcomes using their own scoring systems. ...
... Ten studies reported the proportions of patients achieving each possible degree of integration [40,41,[43][44][45][46]48,50,52,53]. Of these, seven showed that most patients had achieved completed integration with the surrounding native cartilage at the time of final follow-up, ranging from 61-100% of patients [43][44][45][46]48,50,53]. Two studies investigating the same group of patients at different time points showed that a minority of patients achieved complete integration [40,41]. ...
... Ten studies reported the proportions of patients achieving each possible degree of integration [40,41,[43][44][45][46]48,50,52,53]. Of these, seven showed that most patients had achieved completed integration with the surrounding native cartilage at the time of final follow-up, ranging from 61-100% of patients [43][44][45][46]48,50,53]. Two studies investigating the same group of patients at different time points showed that a minority of patients achieved complete integration [40,41]. ...
Article
Full-text available
Focal chondral defects of the knee occur commonly in the young, active population due to trauma. Damage can insidiously spread and lead to osteoarthritis with significant functional and socioeconomic consequences. Implants consisting of autologous chondrocytes or mesenchymal stem cells (MSC) seeded onto scaffolds have been suggested as promising therapies to restore these defects. However, the degree of integration between the implant and native cartilage still requires optimization. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, CINAHL) to identify studies that used autologous chondrocyte implants (ACI) or MSC implant therapies to repair chondral defects of the tibiofemoral joint. Data on the integration of the implant-cartilage interface, as well as outcomes of clinical scoring systems, were extracted. Most eligible studies investigated the use of ACI only. Our meta-analysis showed that, across a total of 200 patients, 64% (95% CI (51%, 75%)) achieved complete integration with native cartilage. In addition, a pooled improvement in the mean MOCART integration score was observed during post-operative follow-up (standardized mean difference: 1.16; 95% CI (0.07, 2.24), p = 0.04). All studies showed an improvement in the clinical scores. The use of a collagen-based scaffold was associated with better integration and clinical outcomes. This review demonstrated that cell-seeded scaffolds can achieve good quality integration in most patients, which improves over time and is associated with clinical improvements. A greater number of studies comparing these techniques to traditional cartilage repair methods, with more inclusion of MSC-seeded scaffolds, should allow for a standardized approach to cartilage regeneration to develop.
... To minimize complications associated with open ACI, research has been focused on better options to deliver and ensure the permanence of chondrocytes at the repair site. [7][8][9] Matrix-seeded autologous chondrocyte implantation (MACI) and similar techniques address some of the potential limiting factors of ACI. By using an absorbable scaffold to allow cells to adhere and produce extracellular matrix, permanence of cells at the repair site could be obtained and complications related to the periosteal patch could be reduced. ...
... Good clinical results were found in 89% of the patients. Ebert et al. 8 showed efficacy and safety with an arthroscopic matrix-induced ACI technique using fibrin glue implant fixation to the subchondral bone. They showed improvement in clinical and MRI findings at the 24-month follow-up in 20 patients, with 1 failure seen by MRI. ...
... Although some authors use the intrinsic adherence of the scaffolds or fibrin glue to paste the scaffolds to subchondral bone, others rely on other types of fixation. 7,8,12,13,15 Herbort et al. 13 described bioabsorbable pins as a fixation method for cell-less scaffolds used for cartilage repair. In an in vitro model, they found that the biomechanical strength of pin fixation was superior to suturing to the adjacent cartilage and that the angle of pin insertion was critical to avoid damage to the tibial surface. ...
Article
Full-text available
The purpose of this study was to evaluate the clinical and sequential imaging follow-up results at a mean of 36 months after an arthroscopic technique for implantation of matrix-encapsulated autologous chondrocytes for the treatment of articular cartilage lesions on the femoral condyles. Ten patients underwent arthroscopic implantation of autologous chondrocytes seeded onto a bioabsorbable scaffold. The patients were evaluated clinically using a visual analog scale (VAS) for pain and International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores. Magnetic resonance imaging (MRI) T2-mapping and magnetic resonance observation of cartilage repair tissue (MOCART) evaluations were also performed. Second-look arthroscopic evaluation using the International Cartilage Repair Society (ICRS) grading classification was performed at 12 months. Compared with their preoperative values, at 36 months mean values ± standard deviation for the VAS scale for pain were 6.0 ± 1.5 to 0.3 ± 0.4. Improvement in clinical scores between preoperative values and 36-month follow-up values in subjective IKDC scores was 46.9 ± 18.5 to 77.2 ± 12.8; in Lysholm scores, it was 51.8 ± 25.1 to 87.9 ± 6.5, and in the Tegner activity scale it was 2.9 ± 1.7 to 5.9 ± 1.9. Mean T2 mapping and MOCART scores improved over time to 38.1 ± 4.4 ms and 72.5 ± 10, respectively. Mean ICRS score by second-look arthroscopy at 1 year was 10.4 ± 0.1. All clinical scores improved over time compared with the preoperative values. Clinical results are comparable with MRI T2 mapping and ICRS evaluations, suggesting that this arthroscopic technique for cell-based cartilage repair is efficacious and reproducible at a mean of 36 months of follow-up. Level IV, therapeutic case series.
... 17,[28][29][30] In 2012, we presented outcomes in a pilot series of patients who underwent a new arthroscopic technique for performing MACI to determine the early safety and efficacy of this procedure in treating articular cartilage defects in the knee. 9 This study presents an extension of this patient cohort, with a comprehensive clinical and radiological follow-up in patients up to 5 years after surgery. We hypothesized that a significant improvement in clinical and radiological outcomes after this arthroscopic MACI technique would exist throughout the postoperative timeline to 5 years after surgery, with high levels of patient satisfaction. ...
... Arthroscopic biopsy and subsequent implantation of the matrix have been previously described, 9 with this study presenting an extension of this cohort with midterm clinical and radiological follow-ups. Briefly, arthroscopic surgery was initially performed to harvest healthy articular cartilage from the nonweightbearing trochlear notch or the medial/lateral femoral condylar ridge for cell culturing. ...
... The distribution of these was the following: medial femoral condyle (n = 5), lateral femoral condyle (n = 1), and lateral tibial plateau (n = 1). One graft failure was previously 9 This patient had also failed MACI performed via open arthrotomy to the same defect location 6 years before this surgical procedure. In addition, 1 further failure was observed at 5 years after surgery in a patient who demonstrated good tissue infill at earlier postoperative time points (Figure 3). ...
Article
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.
... The IKDC score increased from a preoperative mean of 45.7 6 15.9 to 73. 6 (Table 3). ...
... Nevertheless, some conclusions can be drawn concerning the relative efficacy and safety profile of PJAC. Ebert et al 6 baseline scores were recorded in the current study. Rates of graft failure (5%) and hypertrophy (20%) were also similar. ...
Article
Background: Biological repair of cartilage lesions remains a significant clinical challenge because of the lack of natural regeneration and limited treatment options. Hypothesis: Treatment of articular cartilage lesions in the knee with particulated juvenile articular cartilage (PJAC) will result in an improvement in patient symptoms of pain and function and magnetic resonance imaging (MRI) findings at 2 years compared with baseline. Study design: Case series; Level of evidence, 4. Methods: Patients with symptomatic articular cartilage lesions on the femoral condyles or trochlear groove of the knee were identified for treatment with PJAC. There were 25 patients with a mean age of 37.0 ± 11.1 years and a mean lesion size of 2.7 ± 0.8 cm(2). All patients were assessed preoperatively (baseline) with a knee examination and surveys including the International Knee Documentation Committee (IKDC) subjective knee form, 100-mm visual analog scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS). Patients were followed at predetermined time points postoperatively through 2 years. Also, MRI was performed at baseline and at 3, 6, 12, and 24 months. At 2 years, patients were given the option of undergoing voluntary diagnostic arthroscopic surgery with cartilage biopsy to assess the histological appearance of the cartilage repair including safranin O staining for proteoglycans and immunostaining for type I and II collagen. Results: Clinical outcomes demonstrated statistically significant increases at 2 years after surgery compared with baseline, with improvements seen as early as 3 months. Over the 24-month follow-up period, the IKDC score increased from a mean of 45.7 to 73.6, KOOS-pain score from 64.1 to 83.7, KOOS-symptoms score from 64.6 to 81.4, KOOS-activities of daily living score from 73.8 to 91.5, KOOS-sports and recreation score from 44.6 to 68.3, and KOOS-quality of life score from 31.8 to 59.9. The MRI results suggested that T2-weighted scores were returning to a level approximating that of normal articular cartilage by 2 years. Histologically, the repair tissue in biopsy samples from 8 patients was composed of a mixture of hyaline and fibrocartilage; immunopositivity for type II collagen was generally higher than for type I collagen, and there appeared to be excellent integration of the transplanted tissue with the surrounding native articular cartilage. Other than elective biopsies, there were no reoperations, although 1 graft delamination was reported at 24 months. Conclusion: This study demonstrates a rapid, safe, and effective treatment for cartilage defects. For the patient population investigated, the clinical outcomes of the PJAC technique showed a significant improvement over baseline, with histologically favorable repair tissue 2 years postoperatively.
... MACI is a 2-stage surgery that involves isolating and culturing a patient's own chondrocytes in vitro and reimplanting them into the chondral defect. However, the 37 knees that underwent MACI as part this study underwent a combination of traditional miniopen [12][13][14][15] (7 in the AR group, 8 in the CR group) and arthroscopically performed 6,11 (11 in the AR group, 11 in the CR group) implantation techniques. Irrespective of the implantation method, an arthroscopic biopsy of healthy articular cartilage was initially performed, harvested from a non-WB area of the knee. ...
... At the time of second-stage implantation, the defect site was accessed and prepared via a medial or lateral parapatellar miniarthrotomy (for the miniopen technique) 13,14,16,18 or via a standard arthroscopy routine using anteromedial and anterolateral portals (for the arthroscopic technique). 5,11 Postoperative WB Protocols With respect to the 2 comparative WB gradients, a randomnumber generator via Microsoft Excel was used to allocate patients to an 8-week graduated return to full WB (CR group) based on the research of Ebert et al [12][13][14][15] or to a 6week return to full WB (AR group). As documented by Edwards et al, 18 allocation was concealed and only the study coordinator had access to the randomization list. ...
Article
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.
... Functionally, the 6-minute walk test 6,8,11,33,40 was employed postoperatively to assess the maximum comfortable distance that the patient could walk in a 6-minute period, as were maximal active knee flexion and extension range of motion. Isokinetic strength of the quadriceps and hamstrings muscle groups was assessed using an isokinetic dynamometer (Isosport International) at 12 and 24 months after surgery. ...
... 42 However, we acknowledge that other PRO scores-including the International Knee Documentation Committee subjective knee form, Cincinnati Knee Rating System, Lysholm score, and Tegner activity scale-have been used in other studies reporting on ACI in the patellofemoral joint. [17][18][19][20][21]29,30,36,48 Furthermore, we employed the 6-minute walk test as a basic measure of function, and while this test has been used in ACI patients, 6,8,11,33,40 to the best of our knowledge it has not been validated. ...
Article
Full-text available
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. To prospectively evaluate the clinical and radiologic outcome of MACI in the patellofemoral joint. Case series; Level of evidence, 4. 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. 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. 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).
... 12 This study did not examine the clinical outcomes of patients; a clinical review of 20 patients who underwent arthroscopic ACI at 24 months postoperatively showed acceptable results. 6 However, this is very early noncomparative data. A cohort of patients who underwent arthroscopic ACI was compared with a group that underwent second-stage surgery via arthrotomy. ...
Article
Background: Autologous chondrocyte implantation (ACI) is an effective method of repair of articular cartilage defects. It is a 2-stage operation, with the second stage most commonly performed via mini-arthrotomy. Arthroscopic ACI is gaining popularity, as it is less invasive and may accelerate early rehabilitation. However, handling and manipulation of the implant have been shown to cause chondrocyte cell death. Purpose: To assess the number and viability of cells delivered via an open versus arthroscopic approach in ACI surgery. Study design: Controlled laboratory study. Methods: Sixteen ACI surgeries were performed on young cadaveric knees by 2 experienced surgeons: 8 via mini-arthrotomy and 8 arthroscopically. Live and dead cells were stained and counted on implants after surgery. The cell number and viability were assessed using confocal laser scanning microscopy. Surgery was timed from knife to skin until the end of cycling the knee 10 times after implantation of the cell-membrane construct. Results: On receipt of cell membranes after transportation from the laboratory, ≥92% of the cells were viable. There were significantly more remaining cells (8.47E+07 arthroscopic vs 1.41E+08 open; P < .001) and 16 times more viable cells (3.62% arthroscopic vs 37.34% open; P < .001) on the implants when they were inserted via mini-open surgery compared with the arthroscopic technique. Open surgery was of a significantly shorter duration (6 vs 32 minutes; P < .001). Conclusion: In this study, there were significantly more viable cells on the implant when ACI was performed via mini-arthrotomy compared with an arthroscopic technique. Clinical relevance: The viability of cells delivered for ACI via an arthroscopic approach was 16 times less than via an open approach. The mini-arthrotomy approach is recommended until long-term clinical comparative data are available.
... [34][35][36][37] Arthroscopic Third-Generation ACI While chondrocyte-implantation techniques have, until recently, required an open arthrotomy, MACI now lends itself to an arthroscopic implantation technique. [38][39][40][41][42][43][44] This may decrease the associated comorbidity of arthrotomy, reducing such complications as adhesions, decreased postoperative range of movement, excessive pain, and impressive scarring. 45 Furthermore, this may also allow for accelerated postoperative weight-bearing rehabilitation and an earlier return to full physical function. ...
Article
Autologous Chondrocyte Implantation (ACI) has demonstrated good clinical success in the repair of articular cartilage defects in the knee. Post-operative rehabilitation following ACI is considered critical in returning the patient to an optimal level of function by attempting to create the appropriate mechanical environment for cartilage re-growth, and involves a progressive program that emphasizes full motion, progressive partial weight bearing (PWB) and controlled exercises. While evidence-based research is clearly lacking in all components of ACI rehabilitation, one important element in this treatment algorithm which has been subjected to some early scientific study is the gradual progression of the patient back to full weight bearing (WB) gait following surgery. With the continual advancement of ACI surgical techniques, along with clinical experience, improved knowledge of histology and of the maturation process of chondrocytes, proposed post-operative WB protocols have evolved to better reflect the nature of the specific ACI surgery. The purpose of this manuscript is to present the varied PWB programs that have been practiced alongside the evolving ACI surgical technique, the experimental basis for such protocols, the issues pertinent to the accurate prescription of WB and future directions for developing such methods in order to best return the patient to an optimal level of function after ACI.
... The MRI graft evaluation has been outlined previously. 13,15,18 First, MRI parameters (signal intensity, graft infill, border integration, surface contour, structure, subchondral lamina, subchondral bone, and effusion) were selected to best describe the shape and signal intensity of the repair tissue, each scored individually from 1 to 4 (1 = poor; 2 = fair; 3 = good; 4 = excellent) in comparison with the native cartilage. An additional score of 3.5 for graft infill was awarded for a fifth level (very good), corresponding with graft hypertrophy. ...
Article
Full-text available
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.
... There was no reason to stress the press-fit implant further, since the CPM mobilization already clearly outlined the criticalities of this fixation. Lesions were not large, but they are similar to those reported for large cartilage treatment databases 24,35 . Moreover, smaller lesions should in theory favor the shoulder protection of the graft: therefore, the highly significant results should make the positive effect of fibrin glue plausible also for bigger lesions. ...
Article
To evaluate stability and integrity of bi-layer and three-layer collagen-hydroxyapatite (C-HA) osteochondral scaffolds in a human cadaveric knee exposed to continuous passive motion (CPM) with and without loading and the role of added fibrin glue to improve the press-fit fixation of C-HA scaffolds. Osteochondral lesions (2.0 x 1.5 cm) were chiseled out on both condyles and trochlea in eight human cadaveric knees. A total of 24 bi-layer (5 mm, 4 in each condyle) or three-layer C-HA scaffolds (8 mm, 8 in the trochlea, 4 in each condyle) were first press-fit implanted and underwent testing with CPM, 90 cycles, 0° to 90°. The second set of 24 scaffolds was implanted in cleaned lesions with the addition of fibrin glue. Two knees with fibrin glue fixation were additionally exposed to 15 kg loading, with 30 cycles of CPM, 0° to 30°. Then, the knees were re-opened and the scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores. All but two scaffolds remained in the lesions site throughout CPM. Two implants failed: both were bi-layer osteochondral scaffolds, press-fit implanted at the LFC. A statistically significant difference was obtained between press-fit and fibrin glue implants with both Drobnic (2.9±0.7 vs 4.3±0.1, p<0.0005) and Bekkers (3.3±1.0 vs 5.0±0.1, p<0.0005) scores. Additional knee loading did not affect fibrin glue scaffold fixation or integrity. This cadaveric study showed fibrin glue notably improved bi-layer or three-layer C-HA scaffold press-fit fixation regardless of lesion location. It is therefore recommended that fibrin glue be used during surgery to improve early post-operative C-HA scaffold stability and integrity.
... Few studies have used PBAs to document the return of function after ACI. Most of those that have examined either very low-demand activity such as the 6-minutewalk test [23][24][25][26][27] or very high-demand activity via the singlelimb hop. 28 No known studies have examined the timeline for return to function after ACI using low-to moderatedemand PBAs that recreate the demands and stresses of common activities of daily living such as squatting, rising from sitting, or going up and down stairs, in addition to walking. ...
Article
Full-text available
It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year following ACI. To document the recovery of functional performance of activities of daily living following ACI. ACI Patients (n=48, 29 males, 35.1±8.0yrs). All patients completed functional tests (Weight Bearing Squat, Walk Across, Sit-to-Stand, Step Up/Over, and Forward Lunge) using the NeuroCom Long Forceplate(Clackamas, OR), and completed patient reported outcome measures (IKDC, Lysholm, WOMAC, and SF-36) preoperatively and 3, 6, and 12 months postoperatively. A covariance pattern model was used to compare performance and self-reported outcome across time and provide a time line for functional recovery following ACI. Participants demonstrated significant improvement in Walk Across stride length from baseline (42.0±8.9 % height) at 6 (46.8±8.1%) and 12 months (46.6±7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 months as compared to pre-surgery. Step Up/Over time was significantly slower at 3 months (1.67±0.69) compared to baseline (1.49±0.33s), 6 months (1.51±0.36s), and 12 months (1.40±0.26s). Step Up/Over, lift-up index was increased from baseline (41.0±11.3 %BW) at 3 (45.0±11.7%BW) 6 (47.0±11.3 %BW) and 12 months (47.3±11.6 %BW). Forward lunge time was decreased at 3 months (1.51±0.44s) compared to baseline (1.39±0.43s), 6 months (1.32±0.046s), and 12 months (1.27±0.056). Similarly, Forward Lunge impact force was decreased at 3 months (22.2±1.4 %BW) compared to baseline (25.4±1.5 %BW). The WOMAC demonstrated significant improvements at 3 months. All patient reported outcomes were improved from baseline at 6 and 12 months post-surgery. Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 months following ACI should be anticipated, and improvement in performance of tasks requiring weight bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or longer following surgery.
... A wide range of definitions has been reported. 19,71 Commonly used criteria are focused on the need for further surgery, such as: reimplantation with a cartilage implant to the same area 72,73 or subsequent procedure that violated the subchondral bone for the treatment of the same defect, delamination, or detachment, 37,41,52,66,74,75 or removal of the tissue-engineered cartilage y 76,77 Other definitions referred instead to symptoms and functional outcome: patient without improvement in clinical scores, 78 knee with severely abnormal scores, 79 patients evaluating themselves as a failure y 80 In general, when dealing with a clinical perspective in interpreting failures, clinical definitions can be further categorized into criteria based on absolute score values (objective or subjective), or on score improvement from baseline. The choice of failure definition is not a mere philosophical matter and may be critical in determining the failure rate. ...
Article
Long-term results of autologous chondrocyte implantation and matrix-assisted autologous chondrocyte transplantation in the knee are satisfying, but not enough attention has been paid to the evaluation of failures. Thus, a systematic review of the literature was performed, underlining a failure rate in the 58 included articles of 14.9% among 4294 patients, most of them occurring in the first 5 years after surgery, and with no difference between autologous chondrocyte implantation and matrix-assisted autologous chondrocyte transplantation. Failures are very heterogenously defined in the current literature. A widely accepted definition is needed, and a comprehensive definition taking into consideration the patient's perception of the outcome, not just the surgeon's or researcher's point of view, would be advisable. Finally, there is no agreement on the most appropriate treatment of failures, and further studies are needed to give better indications to properly manage patients failed after cartilage procedures. Level of evidence: Level IV.
... Marlovits et al [56] reported 2 failures from 21 patients treated with ACI after 5 years and with MRI evaluation it was observed that in 80% of patients,defects had totally healed and integrated with peripheral chondral tissue. Eber et al [57] reported successful results in 20 patients treated with arthroscopic surgical technique and MACI after 2 years. The follow-up MRI showed 90% defect healing and 70% integration. ...
Article
Full-text available
Treatment of articular cartilage injuries to the knee remains a considerable challenge today. Current procedures succeed in providing relief of symptoms, however damaged articular tissue is not replaced with new tissue of the same biomechanical properties and long-term durability as normal hyaline cartilage. Despite many arthroscopic procedures that often manage to achieve these goals, results are far from perfect and there is no agreement on which of these procedures are appropriate, particularly when full-thickness chondral defects are considered.Therefore, the search for biological solution in long-term functional healing and increasing the quality of wounded cartilage has been continuing. For achieving this goal and apply in wide defects, scaffolds are developed.The rationale of using a scaffold is to create an environment with biodegradable polymers for the in vitro growth of living cells and their subsequent implantation into the lesion area. Previously a few numbers of surgical treatment algorithm was described in reports, however none of them contained one-step or two -steps scaffolds. The ultimate aim of this article was to review various arthroscopic treatment options for different stage lesions and develop a new treatment algorithm which included the scaffolds.
... There is consensus in the literature that MACI represents a safe and effective regenerative technique in isolated cartilage defects larger than 3 cm 2 [4,14,35,40,43] but it has been difficult to correlate the clinical and macroscopic appearance of regenerative tissue closely with the histological outcomes [15]. Although their usefulness is limited by the small sample size of the subgroups studied, the results of the present study, which focuses on the functional status of a comparatively high number of patients, are in agreement with this consensus and add to the existing evidence [6,13,17,25]. ...
Article
Full-text available
Purpose Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated effectiveness in treating isolated cartilage defects of the knee but medium- and long-term evidence and information on the management of postoperative complications or partially successful cases are sparse. This study hypothesised that MACI is effective for up to 5 years and that patients with posttreatment problems may go on to obtain clinical benefit from other interventions. Methods A follow-on, prospective case series of patients recruited into a previous controlled, randomised, prospective study or newly enroled. Patients were followed up 6, 12, 24 and 60 months after surgery. Outcome measures were Tegner (activity levels) and Lysholm (pain, stability, gait, clinical symptoms) scores. Zone-specific subgroups were analysed 6, 12 and 24 months postoperatively. Results Sixty-five patients were treated with MACI. Median Tegner score improved from II to IV at 12 months; an improvement maintained to 60 months. Mean Lysholm score improved from 28.5 to 76.6 points (±19.8) at 24 months, settling back to 75.5 points after 5 years (p > 0.0001). No significant differences were identified in the zone-specific analysis. Posttreatment issues (N = 12/18.5 %) were resolved with microfracture, debridement, OATS or bone grafting. Conclusions MACI is safe and effective in the majority of patients. Patients in whom treatment is only partially successful can go on to obtain clinical benefit from other cartilage repair options. This study adds to the clinical evidence on the MACI procedure, offers insight into likely treatment outcomes, and highlights MACI’s usefulness as part of an armamentarium of surgical approaches to the treatment of isolated knee defects. Level of evidence Prospective case control study with no control group, Level III.
... The implantation procedure has been previously described. 9,10 Similar to the open technique, the cartilage lesion was initially prepared by removing all damaged cartilage down to, but without penetrating, the subchondral bone plate, while the edges of the defect were debrided to ensure a well-defined and contained defect bordered by healthy, native cartilage. However, instead of using the foil template for defect sizing, the resultant defect was then measured using the end of an arthroscopy probe in several planes to enable defect "mapping" (Figure 3), and subsequent measurements were used to size, shape, and cut the graft based on these measurements ( Figure 2). ...
Article
Full-text available
Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of chondral defects in the knee. MACI has traditionally required an open arthrotomy, though now lends itself to an arthroscopic technique, which may decrease the associated co-morbidity of arthrotomy, potentially allowing for faster rehabilitation. To compare post-operative outcomes between arthroscopic and open-arthrotomy techniques of MACI and present a case for faster recovery and accelerated rehabilitation following surgery. Retrospective Cohort Study. Private functional rehabilitation facility. 78 patients (41 arthroscopic, 37 open) treated with MACI for full-thickness cartilage defects to the femoral condyles. According to surgeon preference, patients recruited over the same time period underwent MACI performed arthroscopically or via a conventional open arthrotomy. Both surgical groups were subjected to an identical rehabilitation protocol. Patient-reported (KOOS, SF-36 and VAS) and functional (six minute walk test, three-repetition straight leg raise test) outcomes were compared pre-surgery and at 3, 6 and 12 months post-surgery. Active knee range of motion (ROM) was additionally assessed at 4 and 8 weeks post-surgery. MRI evaluation was assessed using magnetic resonance observation of cartilage repair tissue (MOCART) scores at 3 and 12 months. The length of hospital stay was evaluated, while post-surgery complications were documented. Significant improvements (p<0.05) for both groups were observed over the 12-month period for patient-reported and functional outcomes; however, the arthroscopic cohort performed significantly better (p<0.05) in active knee flexion and extension ROM, and the three-repetition straight leg raise test. No differences were observed in MOCART scores between the two groups at 12 months. Patients who received arthroscopic implantation required a significantly reduced (p<0.001) hospital stay, and experienced less post-operative complications. Arthroscopic MACI in combination with 'best practice' rehabilitation has shown encouraging early results, with good clinical outcomes to 12 months, reduced length of patient hospitalization and reduced risk of post-surgery complications. This may have important implications on post-operative rehabilitation and a faster return to full function.
... Marcacci et al. made tremendous contribution, not only to arthroscopic secondgeneration autologous chondrocyte implantation using a hyaluronan-based implant [15] but also to arthroscopic osteochondral grafting [16], and meniscus transplantation [17]. Following generations of chondrocyte implantation or cartilage regeneration in a broader sense using membranes such as the ChondroGide® [18][19][20], or particulated cartilage such as CAIS or DeNovo NT are basically designed to allow for arthroscopic purposes [21]. ...
Article
Full-text available
Introduction: We present the first retrospective study that compares two various autologous matrix-induced chondrogenesis (AMIC) surgical interventions to repair grade III-IV cartilage defects in the knee. Patients who underwent minimally invasive (arthroscopy) or open (mini-arthrotomy) AMIC were followed up to 2 years to investigate if minimally invasive AMIC is superior to open procedures. Materials and methods: Overall n = 50 patients with focal and contained grade III-IV articular cartilage defects in the knee joint were followed in a consecutive cohort study. 20 patients were treated arthroscopically (female 7, male 13; age: mean 38.2 years, range 18-70 years; BMI: mean 27.0, range 18.7-34.7; defect size: mean 3.1 cm2, range 1.0-6.0 cm2), and 30 patients via mini-arthrotomy (female 13, male 17; age: mean 34.4 years, range 14-53 years, BMI: mean 23.9, range 18.4-28.7; defect size: mean 3.4 cm2, range 1.5-12.0 cm2). The primary defect localization was the medial femoral condyle. Results: AMIC led to a significant improvement of VAS pain, KOOS and Lysholm scoring for up to 2 years compared to pre-op. Outcome analysis revealed no significant differences between the two different surgical approaches. Conclusions: Our results suggest that mini-open AMIC is equivalent to the arthroscopic procedure. The anticipatory hypothesis that minimally invasive approaches bring greater patient benefit per se could not be confirmed. Therefore, we recommend to perform AMIC where indicated and suggest that the surgeon's personal skills profile guide the choice of surgical approach. Level of evidence: III.
... The MRI graft evaluation has been outlined previously. 13,15,18 First, MRI parameters (signal intensity, graft infill, border integration, surface contour, structure, subchondral lamina, subchondral bone, and effusion) were selected to best describe the shape and signal intensity of the repair tissue, each scored individually from 1 to 4 (1 = poor; 2 = fair; 3 = good; 4 = excellent) in comparison with the native cartilage. An additional score of 3.5 for graft infill was awarded for a fifth level (very good), corresponding with graft hypertrophy. ...
Article
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.
... Furthermore, surgical techniques for cartilage repair and ACI continue to evolve, making it difficult for long-term evidence-based research to be developed and implemented. For example, the evolution of the general ACI technique to third-generation MACI, and then to arthroscopic MACI implantation techniques, 1,14,23,43,80,93,94,123 has reduced the surgical morbidity associated with an open arthrotomy and may allow for accelerated rehabilitation. Edwards et al 34 have recently presented encouraging clinical results up to 12 months postsurgery, including a reduced length of patient hospitalization and reduced risk of postsurgery complications, following arthroscopic MACI. ...
Article
Full-text available
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.
... Research that supports the efficacy of valgus unloading braces has been undertaken in patients with medial compartment osteoarthritis and varus malalignment. In addition, recent research suggests autologous chondrocyte implantation to address chondral defects on the lateral compartment of the tibiofemoral joint makes up 25% to 35% of all tibiofemoral grafts [13, 15, 16]. There is currently no empirical research demonstrating the biomechanical efficacy of varus bracing to unload the lateral compartment of the knee in a healthy or pathological population. ...
Article
Full-text available
Unloading knee braces often are used after tibiofemoral articular cartilage repair. However, the experimental basis for their use in patients with normal tibiofemoral alignment such as those undergoing cartilage repair is lacking. The purpose of this study was to investigate the effect of varus and valgus adjustments to one commercially available unloader knee brace on tibiofemoral joint loading and knee muscle activation in populations with normal knee alignment. The gait of 20 healthy participants (mean age 28.3 years; body mass index 22.9 kg/m(2)) was analyzed with varus and valgus knee brace conditions and without a brace. Spatiotemporal variables were calculated as were knee adduction moments and muscle activation during stance. A directed cocontraction ratio was also calculated to investigate the relative change in the activation of muscles with medial (versus lateral) moment arms about the knee. Group differences were investigated using analysis of variance. The numbers available would have provided 85% power to detect a 0.05 increase or decrease in the knee adduction moment (Nm/kg*m) in the braced condition compared with the no brace condition. With the numbers available, there were no differences between the braced and nonbraced conditions in kinetic or muscle activity parameters. Both varus (directed cocontraction ratio 0.29, SD 0.21, effect size 0.95, p = 0.315) and valgus (directed cocontraction ratio 0.28, SD 0.24, effect size 0.93, p = 0.315) bracing conditions increased the relative activation of muscles with lateral moment arms compared with no brace (directed cocontraction ratio 0.49, SD 0.21). Results revealed inconsistencies in knee kinetics and muscle activation strategies after varus and valgus bracing conditions. Although in this pilot study the results were not statistically significant, the magnitudes of the observed effect sizes were moderate to large and represent suitable pilot data for future work. Varus bracing increased knee adduction moments as expected; however, they produced a more laterally directed muscular activation profile. Valgus bracing produced a more laterally directed muscular activation profile; however, it increased knee adduction moments. When evaluating changes in knee kinetics and muscle activation together, this study demonstrated conflicting outcomes and questions the efficacy for the use of unloader bracing for people with normally aligned knees such as those after articular cartilage repair.
... Accordingly, the treatment of progressive lesions along with large cartilage loss is one of the most significant unmet needs. Previous studies, in general, agree on the safety and efficacy of autologous chondrocyte implantations (ACI) in isolated cartilage defects larger than 4 cm 2 (5)(6)(7)(8). ...
Article
Full-text available
Objective: The aim of this study was compare the clinical success of treatments for avascular necrosis and osteochondritis dissecans in cases who underwent matrix autologous chondrocyte implantations, and evaluate cartilage thickness on the clinical outcomes after implantation. Methods: A total of 37 patients (29 men, and 8 women; mean age: 23.8 years (16-38)) were treated prospectively with a two-stage matrix autologous chondrocyte implantation (avascular necrosis, n=21; osteochondritis dissecans, n=18). Clinical improvements and follows-up were assessed based on the patients' International Cartilage Repair Society (ICRS) scores with simultaneous cartilage thickness measurement using short-TI inversion recovery magnetic resonance imaging. The patients were divided into four subgroups based on their clinical scores, as group D <65 points, Group C 65-83 points, Group B 84-90 and Group A ≥90. Results: The mean ICRS score was 28.33±7.14 in the preoperative period in the avascular necrosis group, which increased to 70.88±12.61 at 60 months; while the mean ICRS score increased from 29.75±7.15 preoperatively to 87.58±12.83 at 60 months in the osteochondritis dissecans group. A statistically significant difference in the ICRS scores was noted between the two groups, and also between the ICRS scores and cartilage thicknesses of the subgroups (p<0.05). Conclusion: Our study results revealed that greater clinical improvement was achieved in patients with osteochondritis dissecans undergoing matrix autologous chondrocyte implantation than in those with avascular necrosis. In addition, cartilage thickness greater than 3.7 mm following an autologous chondrocyte transplantation showed excellent clinical improvement. Level of evidence: Level III, Therapeutic Study.
... There is increasing interest in treating articular cartilage and subchondral bone defects and osteoarthritis with autologous chondrocyte implants (ACIs), matrix autologous chondrocyte implants (MACIs), and bone marrow-derived mesenchymal cell implants or injections [8][9][10][11][12][13][14]. ACI and MACI procedures have been shown to produce durable long-term outcomes in the treatment of partial and full-thickness articular cartilage defects in tibiofemoral joints [15][16][17][18][19]. In addition, mesenchymal stem cells mobilized to joints from the peripheral blood or placed on implantation matrices have the potential to repair cartilage by differentiating into chondrocytes [20]. ...
Article
Full-text available
This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.
... This permits an allarthroscopic second-stage implantation, albeit we have previously reported the arthroscopic use of MACI in the tibiofemoral knee joint with good short-and mid-term outcomes. 10,11 I also note that despite the allarthroscopic second-stage implantation, a very conservative 6-week period of nonweight-bearing was advocated for treated tibiofemoral lesions, despite studies reporting safety and efficacy in a progressive period of weight-bearing (culminating in full weight bearing at 6-8 weeks) after tibiofemoral MACI. 2,12,13 Not to say that the author team had not been diligent in collecting the outcomes presented, although the vast array of retrospective studies continually published, often undertaken as an afterthought and/or for clinical interest, are limited in sound methodology and, therefore, often outcomes of robust interest. ...
Article
A growing number of knee cartilage repair studies continue to be published, employing both traditional and also novel and emerging surgical methods. Marrow stimulation, osteochondral transplantation, and autologous chondrocyte implantation via varied surgical techniques and delivery methods exist, as well as isolated, or concomitant, realignment procedures. However, while some value exists in small clinical cohorts (prospective and retrospective), we still lack high-quality comparative studies that better direct us toward the ideal cartilage repair treatment, specific to each individual patient situation including chondral defect (size, location, shape, etc.), the local environment (early degenerative knee changes, concomitant pathology), the surrounding environment (including individual physical conditioning and lower-limb alignment), and of course the patient’s tolerance to the pathology and individual physical demands. How do we sort this out? High-quality, and hopefully prospective and randomized, clinical trials are required.
... Thus, it is unclear whether the quicker recovery seen at 12-month follow-up related to the approach or the different membrane. Two studies by Ebert et al. [27,28] performed a similar full-arthroscopic procedure: after shaving and debridement, the defect was mapped in several planes using a graduated arthroscopy probe. ...
Article
Full-text available
Background Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. Methods This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). Results Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12–60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size ( P > 0.1). No difference was found in terms of Tegner Score ( P = 0.3), Lysholm Score ( P = 0.2), and International Knee Documentation Committee (IKDC) Score ( P = 0.1). No difference was found in the rate of failures ( P = 0.2) and revisions ( P = 0.06). Conclusion Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. Level of evidence II, systematic review of prospective studies.
... 25 Most of the procedures in which a collagenic membrane was implanted used a mini-arthrotomy, and in only two studies was a full arthroscopic approach employed. 34,36 After implantation into the focal articular cartilage defect, the membrane is commonly secured though fibrin glue or suture. 54,55 Whether sutured performed better than fibrin glue is controversial, and no consensus has been reached. ...
Article
Introduction: Chondral defects of the knee are common and their management is challenging. Source of data: Current scientific literature published in PubMed, Google scholar, Embase and Scopus. Areas of agreement: Membrane-induced autologous chondrocyte implantation (mACI) has been used to manage chondral defects of the knee. Areas of controversy: Hyaluronic acid membrane provides better outcomes than a collagenic membrane for mACI in the knee at midterm follow-up is controversial. Growing points: To investigate whether hyaluronic acid membrane may provide comparable clinical outcomes than collagenic membranes for mACI in focal defects of the knee. Areas timely for developing research: Hyaluronic acid membrane yields a lower rate of failures and revision surgeries for mACI in the management of focal articular cartilage defects of the knee compared with collagenic scaffolds at midterm follow-up. No difference was found in patient reported outcome measures (PROMs). Further comparative studies are required to validate these results in a clinical setting.
... [12][13][14] After its introduction, membrane-induced autologous chondrocyte implantation (mACI) has been broadly performed. 11,15,16 In 2005, Behrens 17 first described an enhanced microfractures technique, which quickly evolved into the autologous matrix-induced chondrogenesis (AMIC) procedure. Given its simplicity, AMIC quickly gained the favour of surgeons and patients. ...
Article
Full-text available
Introduction Chondral defects of the knee are common and their treatment is challenging. Source of data PubMed, Google scholar, Embase and Scopus databases. Areas of agreement Both autologous matrix-induced chondrogenesis (AMIC) and membrane-induced autologous chondrocyte implantation (mACI) have been used to manage chondral defects of the knee. Areas of controversy It is debated whether AMIC and mACI provide equivalent outcomes for the management of chondral defects in the knee at midterm follow-up. Despite the large number of clinical studies, the optimal treatment is still controversial. Growing points To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up. Areas timely for developing research AMIC may provide better outcomes than mACI for chondral defects of the knee. Further studies are required to verify these results in a clinical setting.
Chapter
Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique to treat articular cartilage defects in the knee. Traditionally, the chondral graft is harvested arthroscopically and the implant is implanted via an open or mini-open technique. An arthroscopic implantation technique carries with it the potential for reduced pain, improved rehabilitation, and reduced arthrofibrosis. This particular technique involves a standard arthroscopic biopsy followed by cell culture and seeding on to a collagen membrane. The implantation procedure is performed 6-8 weeks later. A standard arthroscopy is performed and the defect is debrided to stable vertical walls using curettes and arthroscopic shavers. The knee is subsequently emptied of all fluid and the rest of the procedure is performed as a dry arthroscopy. The defect is sized using a graduated probe. If required, a template may be cut out of the supplied membrane. A wide-bore valveless cannula inserted through the working portal allows the repeated atraumatic passage of the prepared membrane. The probe is used to position the graft and check for size. A definitive graft is then cut and placed in the knee. Fibrin glue is applied to the base of the defect, the membrane is positioned, and an embolectomy or indwelling catheter balloon is inflated to apply even pressure to the graft whilst the glue sets. A validated, accelerated rehabilitation program is recommended, with full weight bearing at 8 weeks postprocedure. Early results have shown this to be a safe, reliable, and reproducible procedure at 24-month follow-up.
Article
Autologous chondrocyte implantation (ACI) is a tissue-engineered surgical technique initially developed for articular cartilage repair of isolated chondral lesions of the knee. Third generation techniques (ACI3) are now available that deliver autologous cultured chondrocytes into the defect using cell scaffolds. The successful outcomes of these techniques have some dependency on the pre and post-surgical patient rehabilitation. To determine if the standard of reporting for rehabilitation has improved in ACI3 studies; previous reviews in this field recommended describing the detail of this rehabilitation and patient compliance as integral elements. A computerized search was performed in March 2013. Criteria for inclusion were any studies that evaluated or described the process of ACI3 in the knee and subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used to rate the standard of reporting of rehabilitation and surgical procedures; review articles were also evaluated for quality using the Strength of Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence intervals and Mann-Whitney U statistics were calculated. An improvement in mean CMS was seen compared to previous reviews but rehabilitation reporting scores were lower than their surgical equivalent; significant association was seen between those studies with rehabilitator involvement and high scores in the individual CMS rehabilitation element. Predominant SORT scores of 2A indicated medium strength of recommendation. The CMS provides a general overview of methodological quality but a more specialised tool to report on the quantitative and qualitative aspects of the rehabilitation process would assist in raising the standards. It is recommended that rehabilitation therapists are included as key members of research teams and are involved in the design, implementation and reporting of future studies.
Article
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.
Article
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The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.
Article
Articular cartilage injuries of the knee are frequently observed in athletes. This may be related to the increased sport participation seen in recreational athletes, and to the increased number of training sessions and games played annually by professional athletes. These injuries limit the ability to play and in some instances can have career ending potential. In this article the authors present an overview of the currently available techniques for cartilage repair, focusing on studies reporting the outcomes of the treatment of knee cartilage lesions in athletes. Several surgical techniques are nowadays available with the aim of restoring function, allowing a return to sports at pre-injury level, while retarding the progression of isolated cartilage injuries toward osteoarthritis (OA). It has been shown that most of these techniques lead to improved and durable clinical outcomes, but there is still no gold standard treatment. Despite the paucity of randomized clinical trials, there is evidence that osteochondral autograft and articular cartilage injuries ensure a higher rate of return to the preinjury sport level. On the other hand, microfracture and osteochondral autograft allow a faster return to sport. Interestingly, while the results of osteochondral autograft tend to improve over 1 to 3 years, the outcomes of microfracture tend to deteriorate over time. The authors also identified several factors affecting the outcomes. Age, preoperative level of sport participation, duration of symptoms before surgery, location and size of the defects, and previous surgery are factors able to influence the functional scores and the rate of return to sports.
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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.
Article
Dissecting osteochondritis of the knee joint, Koenigs disease is a disease of the knee joint that result in articular surface and osteoarthritis congruence. The disease incidence reaches 15% in the pathological knee joint structure in children. The comparative effectiveness of various treatment methods for children with Koenigs disease, from conservative therapy to orthobiological technologies, is a topical subject of discussion among specialists. The effectiveness of modern treatment methods for children with Koenigs disease has been evaluated and is the leading trend in the use of biotechnology for further experimental and clinical studies. The literature search was conducted in the electronic databases of PubMed, Web of Science, Scopus, MEDLINE, eLibrary, RSCI, and Cyberleninka, whereas 2300 references were analyzed, 283 articles were viewed, and 90 publications on orthopedics and biotechnology were selected for the review. Indications for conservative treatment in children with Koenigs disease are currently limited to stages III of the process. Surgical methods occupy a dominant position when pain relief and pathological focus regeneration stimulation are necessary. However, the long-term results of therapy indicate the replacement of the necrosis zone with coarse fibrous connective tissue, which is significantly inferior to hyaline cartilage in terms of biomechanical characteristics, which determines a high risk of developing osteoarthritis. The actively developing direction of orthobiology allows the use of a patients tissues to activate the processes of reparative regeneration with the relief of clinical manifestations and favorable immediate results. The focus of attention of researchers has shifted to the plane of orthobiological technologies following the established trends in regenerative medicine development, which provide a high proportion of favorable immediate interventional results. However, the limited number of publications and the lack of long-term results of therapy do not meet the criteria for demonstrative effectiveness of technologies.
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Context Autologous chondrocyte implantation (ACI) is a tissue-engineered surgical technique initially developed for articular cartilage repair of isolated chondral lesions of the knee. Third-generation techniques (ACI3) are now available that deliver autologous cultured chondrocytes into the defect using cell scaffolds. The successful outcomes of these techniques have some dependency on presurgical and postsurgical patient rehabilitation. Objectives To determine if the standard of reporting for rehabilitation has improved in ACI3 studies; previous reviews in this field recommended describing the detail of this rehabilitation and patient compliance as integral elements. Evidence Acquisition A computerized search was performed in March 2013. Criteria for inclusion were any studies that evaluated or described the process of ACI3 in the knee and subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used to rate the standard of reporting of rehabilitation and surgical procedures; review articles were also evaluated for quality using the Strength of Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence intervals, and Mann-Whitney U statistics were calculated. Evidence Synthesis An improvement in mean CMS was seen compared with previous reviews, but rehabilitation reporting scores were lower than their surgical equivalent; significant association was seen between studies with rehabilitator involvement and high scores in the individual CMS rehabilitation element. Predominant SORT scores of 2A indicated medium strength of recommendation. Conclusions The CMS provides a general overview of methodological quality, but a more specialized tool to report on the quantitative and qualitative aspects of the rehabilitation process would help raise the standards. It is recommended that rehabilitation therapists be included as key members of research teams and be involved in the design, implementation, and reporting of future studies.
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Purpose: While midterm results of matrix-assisted autologous chondrocyte transplantation (MACT) are now available, less attention has been paid to the evaluation of failures of this surgical approach. Aim of this study was to analyse how "failures" are generally defined in cartilage surgery, in order to understand how the survival rate may change according to different definitions of failure. Methods: A systematic review on MACT in the knee was conducted to report failure rates as well as different failure definitions in the available literature. Afterwards, we analysed the survival curve at 8.5-year follow-up of a survey of 193 patients treated with MACT. Using different definitions to identify failures, we compared how the survival rate changed according to the different definitions of failure. Results: The systematic review on 93 papers showed that the average failure rate reported on 3,289 patients was 5.2 % at a mean 34 months of follow-up. However, 41 studies (44.1 %) did not even consider this aspect, and failures were variously defined, thus generating confusing data that make a meta-analysis or a study comparison meaningless. The failure analysis of the MACT survey showed that the survival curve changed significantly depending on the definition applied; in fact, the failure rate ranged from 3.6 to 33.7 %. According to a critical literature and survey analysis, we proposed a combined surgical- and improvement-based definition which led to a failure rate of 25.9 % at midterm/long-term follow-up. Conclusion: Nowadays, failure definitions of cartilage treatments differ in scientific articles, thus generating confusion and heterogeneous data even when applied to the same cohort of patients. While the literature analysis shows a low number of failures, this study demonstrated that if properly addressed with a comprehensive definition, the real failure rate of cartilage surgical procedures in the knee is higher than previously reported. Recognizing failures would give a better understanding and a more realistic prognosis to patients and physicians seeking treatment for cartilage lesions. LEVEL OF EVIDENCE: IV.
Article
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.
Chapter
The restoration of damaged articular cartilage remains one of the biggest challenges in modern clinical orthopaedics. There is no pharmacological treatment that promotes the repair of cartilage, and non-operative treatment inevitably leads to the development of premature osteoarthritis. Current treatment modalities include microfracture, transplantation of osteochondral grafts and autologous chondrocyte implantation (ACI), each having its own benefits and shortcomings. New biological approaches to cartilage repair that are based on the use of cells and molecules that promote chondrogenesis and/or inhibit cartilage breakdown offer a promising alternative to current treatment options. Chondrogenesis is a precisely orchestrated process which involves many growth factors and signaling molecules, and by modifying the local cellular environment, it is possible to enhance formation of more natural cartilage tissue within the defect. These bioactive molecules are difficult to administer effectively. For those that are proteins or RNA molecules, gene transfer has emerged as an attractive option for their sustained synthesis at the site of repair. To accomplish this task, two main strategies have been explored. The direct or in vivo approach delivers exogenous DNA directly into the joint. In this case synovial lining cells are the main site of gene transfer; depending on the vector, cells around or within the defect may also be genetically modified. During indirect or ex vivo delivery, cells are recovered, genetically manipulated outside the body, and then returned to the defect. Delivery of the genetic material to the living cell can be accomplished by use of either viral or non-viral vectors. While viral vectors are much more effective, they raise several safety concerns. Numerous preclinical animal studies have confirmed the effectiveness of these approaches in joints, and several phase I and II clinical gene therapy studies in the local treatment of arthritis provide reason for cautious optimism. This chapter will provide insight into the field of gene therapy in cartilage repair, and its potential for safe and effective clinical translation.
Article
Biological repair of focal chondral defects represents a significant clinical challenge as cartilage lacks intrinsic healing ability. Although it can be difficult to measure the objective success of cartilage repair techniques, the primary objective is symptom relief leading to less pain and improved function for the patient. Likely, the most important key to success is proper clinical indications. Second to this, the type of cartilage treatment utilized should be based on lesion location, size, depth, and other patient factors. One such treatment is DeNovo Natural Tissue. This method relies on the ability of juvenile chondrocytes to migrate from cartilage explants after being secured in a cartilage defect. Although approximately 8700 cases have been performed since 2007, long-term clinical outcomes are not yet available. However, basic science and early clinical data are promising.
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Osteoarthritis (OA) of the shoulder is a chronic, progressive, and multifactorial disease characterized by degenerative and inflammatory processes affecting the glenohumeral joint. The incidence of primary OA has been reported as approximately 5 % of patients with shoulder complaints. Although OA in the shoulder is less common than OA of the knee or hip, OA can cause severe pain and dysfunction of the shoulder. Pathologic changes in shoulder OA involve the progressive breakdown of the articular cartilage within the glenohumeral joint starting with narrowing of the joint space and fibrillation of the surface, followed by osteochondral lesions, osteophyte formations, labrum degradation, capsular tightness, and inflammation. As OA may also affect supporting structures such as muscles, tendons, and ligaments, shoulder joint degeneration can also be linked to secondary causes such as rotator cuff tendon tears, shoulder instability especially in young patients, and trauma.
Chapter
Autologous chondrocyte implantation (ACI) has been used clinically since 1987. Most reports on ACI are on the first- and second-generation ACI with cells in suspension under a sutured membrane and performed with open surgery. Today's third-generation ACI with cells seeded and grown in or on matrices prior to implantation opens up for transarthroscopic implantations. Transarthroscopic surgery reduces the morbidity for the patients and also fastens up the rehab process. In this chapter, some of the techniques for transarthroscopic delivery are presented as examples, and the clinical results published so far up to date are discussed. © Springer-Verlag Berlin Heidelberg 2012, 2015, All Rights Reserved.
Article
Purpose: To identify the most appropriate implantation strategy for a novel chondral scaffold in a model simulating the early post-operative phase, in order to optimize the implant procedure and reduce the risk of early failure. Methods: Eight human cadaveric limbs were strapped to a continuous passive motion device and exposed to extension-flexion cycles (0°-90°). Chondral lesions (1.8 cm diameter) were prepared on condyles, patella and trochlea for the implant of a bi-layer collagen-hydroxyapatite scaffold. The first set-up compared four fixation techniques: press-fit (PF) vs. fibrin glue (FG) vs. pins vs. sutures; the second compared circular and square implants; the third investigated stability in a weight-bearing simulation. The scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores. Results: FG presented higher total Drobnic and Bekkers scores compared to PF (both p = 0.002), pins (p = 0.013 and 0.001) and sutures (p = 0.001 and < 0.0005). Pins offered better total Drobnic and Bekkers scores than PF in the anterior femoral condyles (p = 0.007 and 0.065), similar to FG. The comparison of round and square implants applied by FG showed worst results for square lesions (Drobnic score p = 0.049, Bekkers score p = 0.037). Finally, load caused worst overall results (Drobnic p = 0.018). Conclusions: FG improves the fixation of this collagen-HA scaffold regardless of lesion location, improving implant stability while preserving its integrity. Pins represent a suitable option only for lesions of the anterior condyles. Square scaffolds present weak corners, therefore, round implants should be preferred. Finally, partial weight-bearing simulation significantly affected the scaffold. These findings may be useful to improve surgical technique and post-operative management of patients, to optimize the outcome of chondral scaffold implantation.
Chapter
Matrix-induced autologous chondrocyte implantation (MACI) is an established technique to treat articular cartilage defects in the knee. Traditionally, the chondral graft is harvested arthroscopically and then implanted via an open or mini-open technique. However, an arthroscopic implantation technique carries with it the potential for reduced pain, improved rehabilitation, and reduced arthrofibrosis. The arthroscopic implantation first involves a standard arthroscopic biopsy followed by cell culture and seeding onto a collagen membrane. The implantation procedure itself is performed 6–8 weeks later. A standard arthroscopy is performed and the defect is debrided to stable vertical walls using curettes and arthroscopic shavers. All irrigation fluid is subsequently evacuated such that the rest of the procedure is performed as a dry arthroscopy. The defect is sized using a graduated probe. If required, a template may be cut out of the supplied membrane. A wide-bore valveless cannula, inserted through the working portal, permits the repeated atraumatic passage of the prepared membrane. The probe is used to position the graft and check for size. A definitive graft is then cut and placed in the knee. Fibrin glue is applied to the base of the defect, the membrane is positioned, and an embolectomy or indwelling catheter balloon is inflated to apply even pressure to the graft while the glue sets. A validated, accelerated rehabilitation program is recommended, with full weight-bearing at 8-week post-procedure. Results using this technique have shown this to be a safe, reliable, and reproducible procedure with good clinical and radiological outcomes at the 5-year follow-up.
Article
Objective: Successful clinical outcomes following cartilage restoration procedures are highly dependent on addressing concomitant pathology. The purpose of this study was to document methods for evaluating concomitant procedures of the knee when performed with articular cartilage restoration techniques, and to review their reported findings in high-impact clinical orthopedic studies. We hypothesized that there are substantial inconsistencies in reporting clinical outcomes associated with concomitant procedures relative to outcomes related to isolated cartilage repair. Design: A total of 133 clinical studies on articular cartilage repair of the knee were identified from 6 high-impact orthopedic journals between 2011 and 2017. Studies were included if they were primary research articles reporting clinical outcomes data following surgical treatment of articular cartilage lesions with a minimum sample size of 5 patients. Studies were excluded if they were review articles, meta-analyses, and articles reporting only nonclinical outcomes (e.g., imaging, histology). A full-text review was then used to evaluate details regarding study methodology and reporting on the following variables: primary cartilage repair procedure, and the utilization of concomitant procedures to address additional patient comorbidities, including malalignment, meniscus pathology, and ligamentous instability. Each study was additionally reviewed to document variation in clinical outcomes reporting in patients that had these comorbidities addressed at the time of surgery. Results: All studies reported on the type of primary cartilage repair procedure, with autologous chondrocyte implantation (ACI) noted in 43% of studies, microfracture (MF) reported in 16.5%, osteochondral allograft (OCA) in 15%, and osteochondral autograft transplant (OAT) in 8.2%. Regarding concomitant pathology, anterior cruciate ligament (ACL) reconstruction (24.8%) and meniscus repair (23.3%) were the most commonly addressed patient comorbidities. A total of 56 studies (42.1%) excluded patients with malalignment, meniscus injury, and ligamentous instability. For studies that addressed concomitant pathology, 72.7% reported clinical outcomes separately from the cohort treated with only cartilage repair. A total of 16.5% of studies neither excluded nor addressed concomitant pathologies. There was a significant amount of variation in the patient reported outcome scores used among the studies, with the majority of studies reporting International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcomes Score (KOOS) in 47.2% and 43.6% of articles, respectively. Conclusions: In this study on knee cartilage restoration, recognition and management of concomitant pathology is inadequately reported in approximately 28% of studies. Only 30% of articles reported adequate treatment of concomitant ailments while scoring their outcomes using one of a potential 18 different scoring systems. These findings highlight the need for more standardized methods to be applied in future research with regard to inclusion, exclusion, and scoring concomitant pathologies with regard to treatment of cartilage defects in the knee.
Article
Background: Recent studies demonstrated a 5% increase in cartilage repair procedures annually in the United States. There is currently no consensus regarding a superior technique, nor has there been a comprehensive evaluation of postoperative clinical outcomes with respect to a minimal clinically important difference (MCID). Purpose: To determine the proportion of available cartilage repair studies that meet or exceed MCID values for clinical outcomes improvement over short-, mid-, and long-term follow-up. Study design: Systematic review and meta-analysis. Methods: A systematic review was performed via the Medline, Scopus, and Cochrane Library databases. Available studies were included that investigated clinical outcomes for microfracture (MFX), osteoarticular transfer system (OATS), osteochondral allograft transplantation, and autologous chondrocyte implantation/matrix-induced autologous chondrocyte implantation (ACI/MACI) for the treatment of symptomatic knee chondral defects. Cohorts were combined on the basis of surgical intervention by performing a meta-analysis that utilized inverse-variance weighting in a DerSimonian-Laird random effects model. Weighted mean improvements in International Knee Documentation Committee (IKDC), Lysholm, and visual analog scale for pain (VAS pain) scores were calculated from preoperative to short- (1-4 years), mid- (5-9 years), and long-term (≥10 years) postoperative follow-up. Mean values were compared with established MCID values per 2-tailed 1-sample Student t tests. Results: A total of 89 studies with 3894 unique patients were analyzed after full-text review. MFX met MCID values for all outcome scores at short- and midterm follow-up with the exception of VAS pain in the midterm. OATS met MCID values for all outcome scores at all available time points; however, long-term data were not available for VAS pain. Osteochondral allograft transplantation met MCID values for IKDC at short- and midterm follow-up and for Lysholm at short-term follow-up, although data were not available for other time points or for VAS pain. ACI/MACI met MCID values for all outcome scores (IKDC, Lysholm, and VAS pain) at all time points. Conclusion: In the age of informed consent, it is important to critically evaluate the clinical outcomes and durability of cartilage surgery with respect to well-established standards of clinical improvement. MFX failed to maintain VAS pain improvements above MCID thresholds with follow-up from 5 to 9 years. All cartilage repair procedures met MCID values at short- and midterm follow-up for IKDC and Lysholm scores; ACI/MACI and OATS additionally met MCID values in the long term, demonstrating extended maintenance of clinical benefits for patients undergoing these surgical interventions as compared with MFX.
Article
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Background Returning to a sound level of activity after matrix-induced autologous chondrocyte implantation (MACI) is important to patients. Evaluating the patient’s level of satisfaction with his or her sports and recreational ability is critical. Purpose To investigate (1) satisfaction with sports and recreational ability after MACI and (2) the role that knee strength plays in self-reported knee function and satisfaction. Study Design Case-control study; Level of evidence, 3. Methods Isokinetic knee strength was assessed in 97 patients at 1, 2, and 5 years after MACI to calculate hamstrings-quadriceps ratios and peak knee extensor and flexor torque limb symmetry indices (LSIs). The Sports and Recreation subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS Sports/Rec) was completed. A satisfaction scale was used to evaluate how satisfied the patients were with their ability to return to recreational activities and their ability to participate in sport. Associations between knee strength LSI, KOOS Sports/Rec, and satisfaction with recreational and sporting activities were assessed through use of multivariable linear and logistic regression, with adjustment for confounders. Mediation analysis was conducted to assess the extent to which self-reported knee function mediated associations between strength LSI and satisfaction. Results Satisfaction with the ability to return to recreational activities was achieved in 82.4%, 85.6%, and 85.9% of patients at 1, 2, and 5 years, respectively, and satisfaction with sports participation was achieved in 55.7%, 73.2%, and 68.5% of patients at 1, 2, and 5 years, respectively. Knee extension torque LSIs were associated with KOOS Sports/Rec after adjustment for confounders over 1, 2, and 5 years (5-year regression coefficient, 6.0 points; 95% CI, 1.4-10.7; P = .012). KOOS Sports/Rec was associated with the likelihood of being satisfied at all time points (recreation: 5-year adjusted odds ratio [OR], 2.26; 95% CI, 1.48-3.46; P < .001; and sports: 5-year adjusted OR, 1.98; 95% CI, 1.47-2.68; P < .001). In a multivariable mediation model, the knee extension torque LSI was associated with satisfaction directly (standardized coefficient, 0.16; 95% CI, 0.03-0.28; P = .017) and indirectly via KOOS Sports/Rec (standardized coefficient, 0.19; 95% CI, 0.01-0.38; P = .027), the latter representing 55% of the total association of knee extension torque LSI with satisfaction. Conclusion Knee extensor symmetry was associated with satisfaction in recreational and sporting ability, both directly and indirectly, via self-reported sports and recreation–related knee function. Restoring strength deficits after MACI is important for achieving optimal outcomes.
Article
Purpose Aim of this study was to evaluate subjective and objective clinical and MRI-based radiological outcomes after short-term follow-up in patients with focal full-size cartilage lesions of the knee joint treated with all-arthroscopic hydrogel-based autologous chondrocyte transplantation. Methods A retrospective study on patients with isolated focal cartilage defects of the knee joint who were treated with arthroscopically conducted MACT was performed. Clinical scores were assessed at baseline and final follow-up using the Tegner Score, visual analogue scale (VAS), the International Knee Documentation Committee (IKDC) and the five subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS). MRIs of the treated knee joints were evaluated with the updated MOCART2.0 scoring system at follow-up. Results Twenty-nine consecutive patients were included in the study. Mean time to follow-up was 24.9 ± 1.1 months. Average VAS decreased significantly from 6.5 ± 3.1 preoperatively to 2.3 ± 1.6 at follow-up (p<0.0001). Tegner score increased from 3.1 ± 1.3 to 4.3 ± 1.2 (p<0.0001) and the IKDC from 43.8 ± 21.9 to 64.9 ± 18.9 (p<0.0001). Also, all KOOS subscales displayed significant improvements. Patients showed similar improvements of nearly all clinical scores independent of the defect size. Average MOCART2.0 score was 70.0 ± 13.6 and 20 patients scored ≥ 70 points. All 8 patients with large defects (>5cm²) scored ≥ 75 points. Conclusions In this small study, injectable MACT therapy in the knee joint led to favourable clinical and radiological short term results with significant improvements in all clinical scores and MOCART2.0 scores confirming morphologic integrity of the transplanted chondrocytes. Therefore, this minimally invasive procedure represents a promising operative technique for cartilage regeneration, even for large-diameter lesions.
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Graft hypertrophy is a common occurrence after periosteal, collagen-covered and matrix-induced autologous chondrocyte implantation (MACI). 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. Case series, Level of evidence, 4. 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. 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. 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).
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To assess the safety and efficacy of accelerated compared with traditional postoperative weightbearing (WB) rehabilitation following matrix-induced autologous chondrocyte implantation (MACI) of the knee, using MRI. A randomized controlled study design was used to assess MRI-based outcomes of MACI grafts in 70 patients (45 men, 25 women) who underwent MACI to the medial or lateral femoral condyle, in combination with either traditional or accelerated approaches to postoperative WB rehabilitation. High-resolution MRI was undertaken and assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score at 3, 12, and 24 months postsurgery. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/surgery history was investigated. Both groups significantly improved (P < 0.05) in the MRI composite score and pertinent descriptors of graft repair throughout the postoperative period until 24 months postsurgery. There were no differences (P > 0.05) observed between the 2 groups. Patient age, body mass index, chondral defect size, and duration of preoperative symptoms were significantly correlated (P < 0.05) with several MRI-based outcomes at 24 months, whereas there were no significant pertinent correlations (P > 0.05) observed between clinical and MRI-based outcomes. The accelerated WB approach was not detrimental to graft development at any stage throughout the postoperative assessment timeline from baseline to 24 months postsurgery and may potentially accelerate patient return to normal function, while reducing postoperative muscle loss, intra-articular adhesions, and associated gait abnormalities.
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Patellofemoral lesions represent a very troublesome condition to treat for orthopaedic surgeons; however, second-generation autologous chondrocyte implantation (ACI) seems to offer an interesting treatment option with satisfactory results at short-term follow-up. Hyaluronan-based scaffold seeded with autologous chondrocytes is a viable treatment for the damaged articular surface of the patellofemoral joint. Case series; Level of evidence, 4. Among a group of 38 patients treated for full-thickness patellofemoral chondral lesions with second-generation ACI, we investigated 34 who were available for final follow-up at 5 years. These 34 had chondral lesions with a mean size of 4.45 cm(2). Twenty-one lesions were located on the patella, 9 on the trochlea, and 4 patients had multiple lesions: 3 had patellar and trochlear lesions, and 1 had patellar and lateral femoral condyle lesions. Twenty-six lesions (76.47%) were classified as International Cartilage Repair Society (ICRS) grade IV A or B, 5 lesions (14.70%) were grade IIIC, and 3 (8.82%) were lesions secondary to osteochondritis dissecans (OCD). Results were evaluated using the International Knee Documentation Committee (IKDC) 2000 subjective and objective scores, EuroQol (EQ) visual analog scale (VAS), and Tegner scores at 2 and 5 years. Eight patients had second-look arthroscopy and biopsies. All the scores used demonstrated a statistically significant improvement (P < .0005) at 2 and 5 years' follow-up. Objective preoperative data improved from 8 of 34 (23.52%) normal or nearly normal knees to 32 of 34 (94.12%) at 2 years and 31 of 34 (91.17%) at 5 years after transplantation. Mean subjective scores improved from 46.09 points preoperatively to 77.06 points 2 years after implantation and 70.39 at 5 years. The Tegner score improved from 2.56 to 4.94 and 4.68, and the EQ VAS improved from 56.76 to 81.47 and 78.23 at 2 and 5 years' follow-up, respectively. A significant decline of IKDC subjective and Tegner scores was found in patients with multiple and patellar lesions from 2 to 5 years' follow-up. Second-look arthroscopies in 8 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance. Hyaluronan-based scaffold seeded with autologous chondrocytes can be a viable treatment for patellofemoral chondral lesions.
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In order to determine the usefulness of MRI in assessing autologous chondrocyte implantation (ACI) the first 57 patients (81 chondral lesions) with a 12-month review were evaluated clinically and with specialised MRI at three and 12 months. Improvement 12 months after operation was found subjectively (37.6 to 51.9) and in knee function levels (from 85% International Cartilage Repair Society (ICRS) III/IV to 61% I/II). The International Knee Documentation Committee (IKDC) scores showed an initial deterioration at three months (56% IKDC A/B) but marked improvement at 12 months (88% A/B). The MRI at three months showed 82% of patients with at least 50% defect fill, 59% with a normal or nearly normal signal at repair sites, 71% with a mild or no effusion and 80% with a mild or no underlying bone-marrow oedema. These improved at 12 months to 93%, 93%, 94% and 91%, respectively. The overall MR score at 12 months suggested production of normal or nearly normal cartilage in 82%, corresponding to a subjective improvement in 81% of patients and 88% IKDC A/B scores. Second-look surgery and biopsies in 15 patients (22 lesions) showed a moderate correlation of MRI with visual scoring; 70% of biopsies showed hyaline and hyaline-like cartilage. Thus, MRI at 12 months is a reasonable non-invasive means of assessment of ACI.
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To establish the reproducibility of a standardized region of interest (ROI) drawing procedure in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC). A large ROI in lateral and medial femoral weight-bearing cartilage was drawn in images of 12 healthy male volunteers by 6 investigators with different skills in MRI. The procedure was done twice, with a 1-week interval. Calculated T1-values were evaluated for intra- and interobserver variability. The mean interobserver variability for both compartments ranged between 1.3% and 2.3% for the 6 different investigators without correlation to their experience in MRI. Post-contrast intra-observer variability was low in both the lateral and the medial femoral cartilage, 2.6% and 1.5%, respectively. The larger variability in lateral than in medial cartilage was related to slightly longer and thinner ROIs. Intra-observer variability and interobserver variability are both low when a large standardized ROI is used in dGEMRIC. The experience of the investigator does not affect the variability, which further supports a clinical applicability of the method.
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Autologous chondrocyte implantation is an advanced, cell-based orthobiological technology used for the treatment of chondral defects of the knee. It has been in clinical use since 1987 and has been performed on 12 000 patients internationally; but despite having been in clinical use for more than 15 years, the evidence base for rehabilitation after autologous chondrocyte implantation is notably deficient. The authors review current clinical practice and present an overview of the principles behind autologous chondrocyte implantation rehabilitation practices. They examine the main rehabilitation components and discuss their practical applications within the overall treatment program, with the aim of facilitating the formulation of appropriate, individualized patient rehabilitation protocols for autologous chondrocyte implantation.
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Fibrin sealant (FS), a biological adhesive material, has been recently recommended as an adjunct in autologous chondrocyte implantation (ACI). While FS has been shown to possess osteoinductive potential, little is known about its effects on chondrogenic cells. In this study, we assessed the bioactivity of FS (Tisseel) on the migration and proliferation of human articular chondrocytes in vitro. Using a co-culture assay to mimic matrix-induced ACI (MACI), chondrocytes were found to migrate from collagen membranes towards FS within 12 h of culture, with significant migratory activity evident by 24 h. In addition, 5-bromo-2'-deoxyuridine (BrdU) incorporation experiments revealed that thrombin, the active component of the tissue glue, stimulated chondrocyte proliferation, with maximal efficacy observed at 48 h post-stimulation (1-10 U/ml). In an effort to elucidate the molecular mechanisms underlying these thrombin-induced effects, we examined the expression and activation of protease-activated receptors (PARs), established thrombin receptors. Using a combination of RT-PCR and immunohistochemistry, all four PARs were detected in human chondrocytes, with PAR-1 being the major isoform expressed. Moreover, thrombin and a PAR-1, but not other PAR-isotype-specific peptide agonists, were found to induce rapid intracellular Ca2+ responses in human chondrocytes in calcium mobilization assays. Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes.
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Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.
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Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of full-thickness chondral defects in the knee. It is a 2-stage procedure involving an initial arthroscopic harvest of healthy cartilage, isolation and expansion of chondrocytes ex vivo, and subsequent reimplantation of cells into the chondral defect through an open arthrotomy. However, the MACI procedure lends itself to an arthroscopic implantation technique decreasing the associated comorbidity of arthrotomy, potentially allowing for faster postoperative rehabilitation. We present a simple surgical technique for the arthroscopic implantation of MACI grafts, reducing the associated operative morbidity and allowing for accelerated postoperative rehabilitation and return to full physical function.
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Full thickness defects of the articular cartilage rarely heal spontaneously. While some patients do not develop clinically significant problems from chondral defects, most eventually develop degenerative changes associated with the cartilage damage over time. Techniques to treat chondral defects include abrasion, drilling, tissue autografts, allografts, and cell transplantation. The senior author has developed a procedure referred to as the "microfracture". This technique enhances chondral resurfacing by providing a suitable environment for tissue regeneration and by taking advantage of the body's own healing potential. This technique has now been used in more than 1400 patients. Specially designed awls are used to make multiple perforations, or "microfractures" into the subchondral bone plate. The perforations are made as close together as necessary, but not so close that one breaks into another. Consequently, the microfracture holes are approximately three to four millimeters apart (or 3 to 4 holes per square centimeter). Importantly, the integrity of the subchondral bone plate is maintained. The released marrow elements form a "super clot" which provides an enriched environment for tissue regeneration. Follow up with long term results of more than 8 years have been positive and Very encouraging.
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To evaluate the clinical outcome of hyaluronan-based arthroscopic autologous chondrocyte transplantation at a minimum of 5 years of follow-up and to correlate it with the MRI evaluation parameters. Fifty consecutive patients were included in the study and evaluated clinically using the Cartilage Standard Evaluation Form as proposed by ICRS and the Tegner score. Forty lesions underwent MRI evaluation at a minimum 5-year follow-up. For the description and evaluation of the graft, we employed the MOCART-scoring system. A statistically significant improvement in all clinical scores was observed at 2 and over 5 years. The total MOCART score and the signal intensity (3D-GE-FS) of the repair tissue were statistically correlated to the IKDC subjective evaluation. Larger size of the treated cartilage lesions had a negative influence on the degree of defect repair and filling, the integration to the border zone and the subchondral lamina integrity, whereas more intensive sport activity had a positive influence on the signal intensity of the repair tissue, the repair tissue surface, and the clinical outcome. Our findings confirm the durability of the clinical results obtained with Hyalograft C and the usefulness of MRI as a non-invasive method for the evaluation of the repaired tissue and the outcome after second-generation autologous transplantation over time.
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To define magnetic resonance (MR) arthrography imaging findings of matrix-induced autologous chondrocyte implantation (MACI) grafts of the knee in order to describe implant behaviour and to compare findings with validated clinical scores 30 and 60 months after MACI implant. Thirteen patients were recruited (10 male, 3 female) with a total number of 15 chondral lesions. Each patient underwent an MACI procedure and MR arthrography 30 and 60 months after surgery. MR arthrography was performed using a dedicated coil with a 1.5-Tesla unit. The status of the chondral implant was evaluated with the modified MOCART scoring scale. The lining of the implant, the integration to the border zone, the surface and structure of the repaired tissue were assessed, and the presence of bone marrow oedema and effusion was evaluated. For clinical assessment, the Cincinnati score was used. At 60 months, the abnormality showed worsening in 1 out of 15 cases. Integration showed improvement in 3 out of 15 cases, and worsening in 3 out of 15 cases. Two surfaces of the implant showed further deterioration at 60 months, and 1 afflicted implant fully recovered after the same time interval. Implant contrast enhancement at 30 months was seen in 2 out of 15 cases, 1 of which recovered at 60 months. According to the MOCART score, 4 cases were rated 68.4 out of 75 at 30 months and 65 out of 75 at 60 months. The mean clinical score decreased from 8.6 out of 10 at 30 months to 8.1 out of 10 at 60 months. Magnetic resonance arthrography improved the evaluation of implants and facilitated the characterisation of MACI integration with contiguous tissues. The follow-up showed significant changes in MACI, even at 60 months, allowing for useful long-term MR evaluations.
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In cartilage repair, bioregenerative approaches using tissue engineering techniques have tried to achieve a close resemblance to hyaline cartilage, which might be visualized using advanced magnetic resonance imaging. To compare cartilage repair tissue at the femoral condyle noninvasively after matrix-associated autologous chondrocyte transplantation using Hyalograft C, a hyaluronic-based scaffold, to cartilage repair tissue after transplantation using CaReS, a collagen-based scaffold, with magnetic resonance imaging using morphologic scoring and T2 mapping. Cohort study; Level of evidence, 3. Twenty patients after matrix-associated autologous chondrocyte transplantation (Hyalograft C, n = 10; CaReS, n = 10) underwent 3-T magnetic resonance imaging 24 months after surgery. Groups were matched by age and defect size/localization. For clinical outcome, the Brittberg score was assessed. Morphologic analysis was applied using the magnetic resonance observation of cartilage repair tissue score, and global and zonal biochemical T2 mapping was performed to reflect biomechanical properties with regard to collagen matrix/content and hydration. The clinical outcome was comparable in each group. The magnetic resonance observation of cartilage repair tissue score showed slightly but not significantly (P= .210) better results in the CaReS group (76.5) compared to the Hyalograft C group (70.0), with significantly better (P= .004) constitution of the surface of the repair tissue in the CaReS group. Global T2 relaxation times (milliseconds) for healthy surrounding cartilage were comparable in both groups (Hyalograft C, 49.9; CaReS, 51.9; P= .398), whereas cartilage repair tissue showed significantly higher results in the CaReS group (Hyalograft C, 48.2; CaReS, 55.5; P= .011). Zonal evaluation showed no significant differences (P > or = .05). Most morphologic parameters provided comparable results for both repair tissues. However, differences in the surface and higher T2 values for the cartilage repair tissue that was based on a collagen scaffold (CaReS), compared to the hyaluronic-based scaffold, indicated differences in the composition of the repair tissue even 2 years postimplantation. In the follow-up of cartilage repair procedures using matrix-associated autologous chondrocyte transplantation, differences due to scaffolds have to be taken into account.
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Higher levels of tourniquet pressure and higher pressure gradients beneath tourniquet cuffs are associated with a higher risk of nerve-related injury. Measurement of limb occlusion pressure can help to minimize tourniquet pressure levels and pressure gradients for individual patients and individual surgical procedures. Selective use of pneumatic, wider, and contoured tourniquet cuffs reduces tourniquet pressure levels and the applied pressure gradients.
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Microfracturing techniques have been reported to be successful cartilage-restoring treatment options in defects of smaller sizes. The success may be limited by the size of the defect and the shoulder of the intact surrounding cartilage. We report a new technique using a 3-dimensional matrix to cover large cartilage defects during microfracture healing. In contrast to autologous chondrocyte implantation techniques, this technique is a 1-stage procedure. The defect cover consists of a resorbable polymer felt and sodium hyaluronan to induce hemostasis and to protect the underlying tissue. After conventional microfracture, the defect size is determined with an intra-articular measuring device, and the matrix is sized and introduced with an arthroscopic grasp. Depending on the size of the defect, the 3-dimensional matrix is fixed with 1 or 2 biodegradable pins perpendicular to the surface. The combination of the common microfracture technique with the implantation of the matrix leads to complete defect filling with cartilaginous repair tissue and therefore improves cartilage regeneration in the defect. We conclude that the introduced technique may be helpful in large cartilage defects combining the benefit of microfracturing and avoidance of the increased morbidity of matrix-associated autologous chondrocyte implantation.
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Tissue engineering has become available for cartilage repair in clinical practice. The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autologous chondrocytes provides stable improvement of clinical outcome up to 7 years. Case series; Level of evidence, 4. Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 +/- 12 years, the mean defect size was 4.4 +/- 1.9 cm(2), and the mean body mass index was 24.5 +/- 3.8 kg/m(2). Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests. A highly significant increase (P <.001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P <.001). Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor.