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A Prospective Clinical and Radiological Evaluation at 5 Years After Arthroscopic Matrix-Induced Autologous Chondrocyte Implantation
Abstract
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.
... Any conflicts of interest declared in the studies included in this review were also reported. [32] Case series IV Fair Potential Ebert (2021) [14] Case series IV Fair None Ebert (2020) [22] RCT I Good Potential Ebert (2020) [16] RCT I Fair Potential Ebert (2019) [27] Case-control III Good Potential Ebert (2017) [25] Case series IV Good Potential Ebert (2015) [26] Case series IV Good None Gupton (2021) [33] Case report IV Fair Potential Igarashi (2020) [35] Case report IV Fair None Kreuz (2014) [30] Prospective cohort II Good Unknown Löken (2009) [40] Case series IV Fair None Lopez-Alcorocho (2018) [37] Case series IV Good None McNickle (2009) [34] Case series IV Good Potential Meyerkort (2014) [43] Case series IV Good None Müller (2015) [44] Prospective cohort II Good None Ridley (2017) [45] Case report IV Fair None Robertson (2006) [31] Case series IV Good Unknown Van Assche (2009) [29] RCT I Good Potential ...
... The authors confirmed that the 15 papers included 6 discreet patient cohorts, with some cohorts being included in multiple papers due to the different follow-up times. These groups were defined as: 1) Cohort with early experience of MACI [14,15], 2) Randomised controlled trials of postoperative rehabilitation (8 weeks vs 12 weeks) [16][17][18][19][20][21], 3) Randomised controlled trials of postoperative rehabilitation (6 weeks vs 8 weeks) [22][23][24], 4) Cohort with early experience of arthroscopically performed MACI [25], 5) Cohort that underwent patellofemoral MACI [26], and 6) Cohorts that underwent isokinetic knee strength assessments [27,28]. To prevent the analysis of duplicate cohorts, only one paper from each discreet patient cohort was included in this review. ...
... No conflict of interest was declared in nine studies (47.4%). Five studies declared a conflict of interest, where the conflicts appeared not to be relevant to the study in question (26.3%) [16,22,25,27,29]. Two studies did not disclose whether or not there was a conflict of interest (10.5%) [30,31]. ...
Purpose:
Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. This systematic review aimed to evaluate the biomechanical and functional outcomes of ACI.
Methods:
Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms 'Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI'. Inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. Means and standard deviations of all collected variables were calculated and presented in the review.
Prospero id:
CRD42021238768.
Results:
Nineteen articles including 20 ACI cohorts were included. In general, the average range of motion (ROM) improved with clinical (>5°) and statistical significance (p < 0.05) postoperatively: 130.5 ± 14.8° to 136.1 ± 10.2°. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up. No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test.
Conclusion:
Knee range of motion generally improved following ACI. Although, some studies reported that knee strengths remained significantly poorer than healthy controls, particularly >2-years postoperatively, implying that longer-term strength training may benefit patients.However, the volume of research and current level of evidence remain low, thus further research is required to better understand the impact of ACI on knee function and guide future rehabilitative protocols.
... After short-and long-term follow-up analysis (2-16 years) for different types of MACI implantations, most patients have good curative effects. 10,[109][110][111][112][113][114][115][116][117][118][119][120] The 5-year patient satisfaction after MACI can be as high as 90%. 114 Another study found that 121 MACI significantly improved the quality of life in children and adolescents (<20 years old) compared with adults. ...
... 10,[109][110][111][112][113][114][115][116][117][118][119][120] The 5-year patient satisfaction after MACI can be as high as 90%. 114 Another study found that 121 MACI significantly improved the quality of life in children and adolescents (<20 years old) compared with adults. Related studies 114,115 have shown that the 5-year survival rate of MACI implantations is *90%. ...
... 114 Another study found that 121 MACI significantly improved the quality of life in children and adolescents (<20 years old) compared with adults. Related studies 114,115 have shown that the 5-year survival rate of MACI implantations is *90%. Gille et al. 116 found that the 15-year survival rate for MACI was 79%, and most failures due to transplant complications were reported between 5 and 10 years. ...
Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.
... Of these, all included patients with defects of the medial and/or lateral femoral condyles (MFC, LFC). Four also included patients with trochlear defects [45][46][47][48], and two included defects of the tibial plateau [46,49]. One study treated patellar defects, but reporting of individual patient data allowed for inclusion [45]. ...
... A meta-analysis showed that, from a total of 200 patients, 64% (95% CI (51%, 75%)) of patients achieved complete integration at endpoint (Figure 2). Five studies (four RCTs and one case series) reported the MOCART integration score as a mean score using the following scoring system: 1 = poor integration, 2 = fair, 3 = good, 4 = excellent [38,39,42,49,54]. All showed an improvement in the mean integration score over time, although this was not always statistically significant (Table 2). ...
... All of these reported the degree of filling of the chondral defect. Seven studies reported that a majority of patients achieved complete defect filling by final follow-up [41,43,45,46,[51][52][53]. Four studies reporting mean MOCART scores demonstrated an improvement in the mean filling score over time [38,42,49,54]. Whether or not the surface of the repair was intact was also assessed by 13 studies. ...
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.
... conversely, aci is not recommended if deep subchondral bone involvement is present and joint space narrowing on weight-bearing radiographs is 50% or more; in patients who do not intend to respect the long postoperative rehabilitation protocol; in obese patients; in smokers and patients with inflammatory arthropathy; in concomitant meniscal deficits and ligament instability. 117,121,122 The first surgical stage is the cartilage harvest from the trochlea. after harvest, the chondrocytes are allowed to proliferate in vitro for five to nine weeks. in the second step, with a mini-arthrotomy the unstable cartilage is removed, subchondral bone cysts are addressed with bone-grafting (sandwich technique), the proliferated chondrocytes are applied to the defect and covered with a periosteal patch which is sutured circumferentially in place and sealed with fibrin glue to obtain a better seal of the grafted cells. ...
... the second phase begins with a second arthroscopy which involves the implantation of the scaffold. some authors 122,146,147 prefer to remove the lesion during this second phase and therefore at the moment of implantation to model the scaffold without any reactions during the waiting period of chondrocyte cultivation. The scaffold is fixed with an autologous fibrin glue mixed with thrombin allogeneic fibrinogen from commercially available fibrin glue. ...
... indeed, the matrix itself guarantees nourishment and adhesion to the chondrocytes; 148 • the technique does not require sutures or screws. therefore, it is simple and quick to carry out, and minimally invasive; 122,147 • the technique has adaptive properties in terms of shape and can be adapted to difficult surfaces such as the patellofemoral joint. ...
... First and second generations of the surgical technique required suturing of a periosteal [4] or collagen [32] cover to retain the cell-based solution within the chondral defect. However, third-generation techniques (matrixinduced ACI) seed the cells onto a collagen membrane, which is then glued to the subchondral bone, with encouraging mid-term outcomes demonstrated overall [3,5,13,14,18,19,24,37]. ...
... The inclusion/exclusion criteria for this prospective RCT have been previously defined [13,23]. Briefly, patients were indicated for MACI if they were 15-65 years of age and had undergone MACI to address full thickness femoral condylar defects in the knee. ...
... The MACI surgical technique(s) has been previously described. 13,23 Briefly, an initial arthroscopic cartilage biopsy was undertaken followed by isolation, culturing and seeding of cells onto a type I/III collagen membrane (ACI-Maix Matricel GmbH, Germany). In a second surgery, undertaken via a mini-open (6-week n = 7, 8-week n = 8) or arthroscopic (6-week n = 11, 8-week n = 11) approach, the scaffold was glued to the cleaned and prepared subchondral bone. ...
PurposeTo investigate the mid-term outcomes of an accelerated return to full weight bearing (WB) after matrix-induced autologous chondrocyte implantation (MACI).Methods
This randomized study allocated 35 patients (37 knees) to a 6 week (n = 18) or 8 week (n = 19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2 and minimum 5 years (range 5.5–7 years), using the KOOS, SF-36, visual analogue pain scale, 6-min walk test and active knee range of motion (ROM). Peak isokinetic knee extensor and flexor strength was assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) was undertaken to evaluate the repair tissue, and an MRI composite score was calculated.ResultsWhile no group differences (n.s.) were observed, significant improvement was observed for all patient-reported outcome measures (p < 0.05), 6-min walk distance (p = 0.040), active knee flexion (p = 0.002) and extension (p < 0.0001) ROM, and the LSI for peak knee extensor strength (p < 0.0001). At final review, 87.5% (6 weeks) and 82.4% (8 weeks) of patients were satisfied overall. A non-significant decline (n.s.) was observed for the MRI composite score from 1-year post-surgery to final review, with no significant MRI-based differences (n.s.) between groups. At final review, two grafts (6-week n = 1, 8-week n = 1) demonstrated MRI-based graft failure, while an additional patient had progressed toward knee arthroplasty (8.1% failure rate at minimum 5 years).Conclusions
The 6-week return to full WB after MACI provided comparable clinical and MRI-based outcomes beyond 5 years post-surgery, without jeopardizing the graft. This 6-week WB protocol is faster than those previously proposed and studied.Level of EvidenceII.
... 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]. ...
... 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]. ...
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.
... Overall, MACI has demonstrated encouraging midterm outcomes, with studies reporting good clinical scores and tissue regeneration sustained to 5 years after surgery. 4,7,13,14,18,21,27,48 However, limited information exists (and in relatively small patient cohorts) on its sustained benefit out to !10 years after surgery. 1,19 The importance of structured postoperative rehabilitation after MACI is also acknowledged widely for initial graft protection through progressive loading, facilitation of chondrocyte differentiation and tissue maturation, and the addressing of muscular and functional deficits aiming to return the patient to pain-free and normal physical function. ...
... While MACI has demonstrated encouraging midterm outcomes to 5 years after surgery, 4,7,13,14,18,21,27,48 very limited information exists on its sustained benefit to !10 years after surgery. 1,19 The most important findings from the current study were that MACI produced sustained clinical outcomes and high levels of patient satisfaction to 10 years, with a sound level of tissue sustainability as assessed on MRI over the 10-year period. ...
... The reasons for this are unknown, given that patients were clinically good at 5 years, providing no specific reason for why activity would be higher at the 10year postoperative period. Previous studies undertaken specifically in patients undergoing MACI have reported good clinical scores sustained to 5 years after surgery, 4,7,13,14,18,21,27,48 and it was encouraging to see these clinical outcomes of pain, symptoms, and function sustained longer term. While limited long-term (!10 years) evidence exists for MACI, Aldrian et al 1 reported 10-and 15-year clinical benefits, respectively, in patients undergoing MACI, although they were reported in smaller cohorts of 16 (n = 23 grafts) and 15 patients. ...
Background
Longer term outcomes after matrix-induced autologous chondrocyte implantation (MACI) are lacking, while early postoperative weightbearing (WB) management has traditionally been conservative.
Purpose
To investigate the longer term clinical and radiological outcomes after an 8-week (vs 12-week) WB protocol after MACI.
Study Design
Randomized controlled trial; Level of evidence, 1.
Methods
A randomized study design allocated 70 patients to an 8- (n = 34) or 12-week (n = 36) approach to full WB after MACI of the medial or lateral femoral condyle. Patients were evaluated preoperatively; at 3, 12, and 24 months after surgery; and at 5 and 10 years after surgery. At 10 years (range, 10.5-11.5 years), 60 patients (85.7%; 8 weeks: n = 29; 12 weeks: n = 31) were available for review. Clinical outcomes included patient-reported outcomes, maximal isokinetic knee extensor and flexor strength, and functional hop capacity. High-resolution magnetic resonance imaging (MRI) was undertaken to assess the quality and quantity of repair tissue per the MOCART (magnetic resonance observation of cartilage repair tissue) system. A combined MRI composite score was also evaluated.
Results
Clinical and MRI-based scores for the full cohort significantly improved ( P < .05) over the 10-year period. Apart from the Tegner activity score, which improved ( P = .041), as well as tissue structure ( P = .030), which deteriorated, there were no further statistically significant changes ( P > .05) from 5 to 10 years. There were no 10-year differences between the 2 WB rehabilitation groups. At 10 years, 81.5% and 82.8% of patients in the 8- and 12-week groups, respectively, demonstrated good-excellent tissue infill. Graft failure was observed on MRI at 10 years in 7 patients overall, which included 4 located on 10-year MRI (8 weeks: n = 1; 12 weeks: n = 3) and a further 3 patients (8 weeks: n = 1; 12 weeks: n = 2) not included in the current analysis who proceeded to total knee arthroplasty. At 10 years, 93.3% of patients were satisfied with MACI for relieving their pain, with 83.3% satisfied with their ability to participate in sport.
Conclusion
MACI provided high satisfaction levels and tissue durability beyond 10 years. The outcomes of this randomized trial demonstrate a safe 8-week WB rehabilitation protocol without jeopardizing longer term outcomes.
... Of the remaining examined cohort of 29 patients, 25 were male and 4 were female. Mean age was 39.8 AE 7.4 (range 25-53) years, and the average time to follow-up was 24.9 AE 1.1 (range [24][25][26][27] months. Of all chondral lesions treated, mean defect size was 4.5 AE 1.6 (range 2.3-8.0) ...
... It has been proposed that clinical outcome scores improve throughout the postoperative timeline, short follow-up time as a limitation of the study might account for this discrepancy and clinical scores of the present patients might even improve over the time. 14,26 Despite the significant improvement of all clinical scores from baseline to follow-up in the present study and the comparable values in line with previous studies, absolute values of VAS, Tegner score and IKDC reflect moderate subjective levels and MCID values were only reached in 48% to 69%, so that these results could hopefully even improve in the further course. ...
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.
... However, periosteal patch hypertrophy, high reoperation rates for debridement, bulky sutures, and cell leakage negatively contributed to the overall outcomes of the ACI procedure compared with more traditional OCA and bone marrow stimulation (BMS) techniques [76][77][78][79] . These issues prompted the development of a third-generation MACI technique 79,80 . The MACI technique differs from its predecessors in that it involves culturing the harvested chondrocytes for 3 to 4 weeks and directly seeding the cells into a type-I/III collagen scaffold matrix, which is subsequently fixated into the chondral defect with fibrin glue 74,75,[80][81][82][83] (Figs. 5 and 6). ...
... These issues prompted the development of a third-generation MACI technique 79,80 . The MACI technique differs from its predecessors in that it involves culturing the harvested chondrocytes for 3 to 4 weeks and directly seeding the cells into a type-I/III collagen scaffold matrix, which is subsequently fixated into the chondral defect with fibrin glue 74,75,[80][81][82][83] (Figs. 5 and 6). MACI used for focal cartilage defects of the patella. ...
»:
Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and rotation, and the physical and mental health of the individual patient.
»:
There are a multitude of options to address chondral pathologies of the knee that allow individualized treatment for the specific needs and demands of the patient.
»:
Osteochondral autograft transfer remains a durable and predictable graft option in smaller lesions (<2 cm2) in the young and active patient population.
»:
Both mid-term and long-term results for large chondral lesions (≥3 cm2) of the knee have demonstrated favorable results with the use of osteochondral allograft or matrix-associated chondrocyte implantation.
»:
Treatment options for small lesions (<2 cm2) include osteochondral autograft transfer and marrow stimulation and/or microfracture with biologic adjunct, while larger lesions (≥2 cm2) are typically treated with osteochondral allograft transplantation, particulated juvenile articular cartilage, or matrix-associated chondrocyte implantation.
»:
Emerging technologies, such as allograft scaffolds and cryopreserved allograft, are being explored for different graft sources to address complex knee chondral pathology; however, further study is needed.
... Encouraging midterm clinical and magnetic resonance imaging (MRI) outcomes have been observed after MACI. 5,6,10,11,17,35 However, only limited studies are available reporting outcomes for third-generation ACI techniques beyond 10 years, with these generally including smaller patient cohorts and/or lacking postoperative MRI ...
... Encouraging midterm clinical and MRI-based outcomes have been observed after MACI. 5,6,10,11,17,20,21,35 However, limited published information is available on outcomes beyond 10 years after third-generation ACI techniques, and those available include cohorts of only 16 to 30 patients. 1,18,26 A recent study did report 10-year outcomes in 60 patients after MACI, albeit isolated to patients undergoing MACI in the tibiofemoral joint, with no patellofemoral joint MACI grafts undertaken. ...
Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging midterm clinical outcomes, although published studies presenting longer-term clinical and radiological outcomes, across varied tibiofemoral and patellofemoral graft locations, are scarce.
Purpose: To present the clinical and radiological outcomes a minimum of 10 years after surgery in a consecutive series of patients who underwent MACI in the tibiofemoral or patellofemoral knee joint. Secondly, to investigate any association between outcomes and patient characteristics, graft parameters, and injury and surgery history.
Study design: Case series; Level of evidence, 4.
Methods: Overall, 87 patients (99 grafts: 57 medial femoral condyle, 24 lateral femoral condyle, 11 trochlea, 7 patella) were prospectively evaluated clinically and with magnetic resonance imaging (MRI) before surgery and at 2, 5, and minimum 10 years after MACI (mean, 13.1 years; range, 10.5-16 years). Patients were evaluated with a range of patient-reported outcome measures (PROMs), including the Knee injury and Osteoarthritis Outcome Score (KOOS) and patient satisfaction. The 6-minute walk test, active knee range of motion, and peak isokinetic knee extensor and flexor strength were assessed. Limb symmetry indices (LSIs) were calculated for strength measures. MRI was undertaken to evaluate the repair tissue, and an MRI composite score was calculated.
Results: All PROMs significantly improved (P < .05) over the pre- to postoperative period. Apart from KOOS Sport (P = .018) and the LSI for peak isokinetic knee extensor strength (P = .005), which significantly improved, no significant change (P > .05) was observed from 2 years after surgery to final follow-up (range, 10.5-16 years) in all other PROMs, 6-minute walk distance, active knee range of motion, and the LSI for peak isokinetic knee flexor strength. At final follow-up, while the mean LSIs for peak isokinetic knee flexor and extensor strength were 96.9% and 95.7%, respectively, 74.7% of patients were satisfied with their ability to participate in sports, and 88.5% were satisfied overall. A nonsignificant decline was observed for tissue infill (P = .211) and the MRI composite score (P = .099) from 2 years to final review. At final MRI review, 9 grafts (9.1%) had failed. While no significant association (P > .05) was observed between clinical or MRI-based outcomes and patient demographics (age, body weight, body mass index), defect size, or the duration of preoperative symptoms, the number of previous surgical procedures was significantly and negatively associated with KOOS Symptoms (P = .015), KOOS Sport (P = .011), and the degree of tissue infill (P = .045).
Conclusion: MACI provided high levels of satisfaction and adequate graft survivorship as visualized on MRI at 10.5 to 16 years after surgery.
... Importantly, clinical workflow parameters of allogeneic cytotherapies and cartilage tissue engineering products present significant potential advantages over ACI in its various generations (e.g., reduced operative burdens, no autologous biopsy harvest, no manufacturing-related delays) ( Figure 4). Therefore, building on the large available clinical hindsight in ACI (e.g., 5-year follow-up with quantitative endpoints/outcomes), appropriate efficacy targets may be specified for novel allogeneic orthopedic approaches [106][107][108][109][110][111][112][113][114]. However, as regards the preclinical efficacy evaluation of novel cell or gene-based orthopedic products, high methodological inhomogeneity has been documented and no consensus is currently available [70]. ...
Primary chondroprogenitors obtained from standardized cell sources (e.g., FE002 clinical grade cell sources) may be cultured in vitro and may be cytotherapeutically applied in allogeneic musculoskeletal regenerative medicine. Multicentric translational research on FE002 human primary chondroprogenitors under the Swiss progenitor cell transplantation program has notably validated their robustness and high versatility for therapeutic formulation in clinically compatible prototypes, as well as a good safety profile in diverse in vivo preclinical models. Therein, stringently controlled primary cell source establishment and extensive cell manufacturing optimization have technically confirmed the adequation of FE002 primary chondroprogenitors with standard industrial biotechnology workflows for consistent diploid cell biobanking under GMP. Laboratory characterization studies and extensive qualification work on FE002 progenitor cell sources have elucidated the key and critical attributes of the cellular materials of interest for potential and diversified human cytotherapeutic uses. Multiple formulation studies (i.e., hydrogel-based standardized transplants, polymeric-scaffold-based tissue engineering products) have shown the high versatility of FE002 primary chondroprogenitors, for the obtention of functional allogeneic cytotherapeutics. Multiple in vivo preclinical studies (e.g., rodent models, GLP goat model) have robustly documented the safety of FE002 primary chondroprogenitors following implantation. Clinically, FE002 primary chondroprogenitors may potentially be used in various forms for volumetric tissue replacement (e.g., treatment of large chondral/osteochondral defects of the knee) or for the local management of chondral affections and pathologies (i.e., injection use in mild to moderate osteoarthritis cases). Overall, standardized FE002 primary chondroprogenitors as investigated under the Swiss progenitor cell transplantation program were shown to constitute tangible contenders in novel human musculoskeletal regenerative medicine approaches, for versatile and safe allogeneic clinical cytotherapeutic management.
... Compared with many studies on ACI-P, ACI-C, and MACI, the incidence of repaired cartilage hypertrophy was high. 4,8,9,16,26,27,30 The exact reason why UCB-MSC implantation revealed a high incidence of repaired cartilage hypertrophy is not known yet. First, multiple 4-mm holes made on the subchondral bone might be a reason. ...
Background
There is a paucity of literature reporting clinical and magnetic resonance imaging (MRI) outcomes after allogeneic umbilical cord blood–derived mesenchymal stem cell (UCB-MSC) implantation for chondral defects of the knee.
Purpose
To report clinical and MRI outcomes after UCB-MSC implantation for chondral lesions of the knee.
Study Design
Case series; Level of evidence, 4.
Methods
Inclusion criteria were patients aged between 40 and 70 years with focal chondral lesions of grade 3 or 4 on the medial femoral condyle, defect sizes >4 cm ² , and intact ligaments. Exclusion criteria were patients who required realignment osteotomy or who had a meniscal deficiency, ligamentous instability, or a concomitant full-thickness chondral defect in the lateral or patellofemoral compartment. A mixture of human UCB-MSCs and sodium hyaluronate was implanted into the chondral defect through mini-arthrotomy. MRI at 1-year follow-up was performed to evaluate repaired cartilage hypertrophy. Repaired cartilage thickness was measured, and hypertrophy was classified as grade 1 (<125%), grade 2 (<150%), or grade 3 (<200%). Patient-reported outcomes (PROs; International Knee Documentation Committee, visual analog scale for pain, and Western Ontario and McMaster Universities Osteoarthritis Index) were evaluated preoperatively and at 1, 2, and 3 years postoperatively. Repaired cartilage hypertrophy was evaluated for a correlation with PRO scores.
Results
Enrolled were 85 patients with a mean age of 56.8 ± 6.1 years and a mean chondral defect size of 6.7 ± 2.0 cm ² . At follow-up, a significant improvement in all PRO scores was seen compared with preoperatively ( P < .001 for all). MRI at 1-year follow-up demonstrated that 28 patients had grade 1 repaired cartilage hypertrophy, 41 patients had grade 2, and 16 patients had grade 3. MRI performed in 11 patients at 2 years after surgery indicated no difference in repaired cartilage hypertrophy between the 1- and 2-year time points. The grade of repaired cartilage hypertrophy did not correlate with PRO scores.
Conclusion
Clinical outcomes improved significantly at short-term follow-up after UCB-MSC implantation. Although all patients showed repaired cartilage hypertrophy, it did not correlate with clinical outcomes.
... There is increasing interest in treating articular cartilage and subchondral bone defects and osteoarthritis with autologous chondrocyte implants (ACI), matrix autologous chondrocyte implants (MACI) 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 knee joints [15][16][17][18][19]. In addition, MSCs mobilized to joints www.videleaf.com ...
... The responder rates at 6 years were 53% and 77% for MFx and M-ACI, respectively. 42 Long-term maintenance of significant improvements at up to 5 years and for more than 5 and 10 years after M-ACI/ ACI has been reported in several clinical studies 17,40,[43][44][45][46][47][48][49][50][51][52][53][54][55] and reviews. 28,56 While MFx is still considered a treatment option for smaller defects (<2-2.5 cm 2 ), there is evidence from several clinical studies, systematic reviews, and metaanalyses that even with smaller and medium defect sizes, MFx loses its clinical efficacy over time. ...
Objective:
The objective of this study was to evaluate the best available mid- to long-term evidence of surgical procedures for the treatment of localized full-thickness cartilage defects of the knee.
Design:
Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of Level 1 randomized clinical trials (RCTs), meta-analyses of RCTs and systematic reviews with a minimum follow-up of 5 years. Data extracted included patient demographics, defect characteristics, clinical and radiological outcomes, as well as treatment failures.
Results:
Six RCTs and 3 Level 1 systematic reviews were included. Two RCTs compared microfracture (MFx) to periosteum-covered autologous chondrocyte implantation (ACI-P), 1 to matrix-associated ACI (M-ACI) and 2 to osteochondral autograft transplantation (OAT). One study compared OAT to collagen membrane covered ACI (ACI-C). The 3 Level 1 systematic reviews/meta-analyses assessed the outcome of MFx, OAT, and various ACI methods in RCTs. OAT showed significantly better outcomes compared with MFx. In the 2 RCTs comparing ACI-P and MFx, no significant differences in clinical outcomes were seen, whereas significantly better outcomes were reported for M-ACI versus MFx in 1 study including patients with larger defects (5 cm2), and for ACI-C versus OAT in terms of Cincinnati Score. Higher failure rates were reported for MFx compared with OAT and for OAT compared with ACI-C, while no significant differences in failure rates were observed for ACI-P compared to MFx.
Conclusion:
Restorative cartilage procedures (ACI-C or M-ACI and OAT) are associated with better long-term clinical outcomes including lower complication and failure rates when compared with reparative techniques (MFx). Among the restorative procedures, OAT seems to be inferior to ACI especially in larger defects after longer follow-up periods.
Level of evidence:
Level I: Systematic review of Level I studies.
... [18,[23][24][25] Diğer taraftan son denemeler hızlandırılmış geri dönüşün güvenliğini göstermiştir. [26,27] Tıbbi ürünler için yasal gereklilikler ülkeye göre farklılık gösterir. Bazı ülkelerdeki yasal süreçler ACI/MACI''nın kullanılabilirliğini ve bu yöntemlerle ilgili araştırmaları sınırlayabilir. ...
... Yet, overall clinical and MR morphological outcome was good to excellent at the 2-year follow-up, and in line with previous studies, there was a significant improvement of clinical and radiologic scores over time. 36,37 However, a high overall prevalence of subchondral BMEL was found during follow-up and persisting BMEL was present in 56.3% of our cohort 24 months after surgery. Several studies have described large numbers of patients with BMEL after cartilage repair surgery, with a prevalence of up to 47% at 12 months follow-up, and 61.5% and 73.1% at mid-term (22-36 months) and long-term (96-194) months' follow-up, respectively. ...
Objective
The aim of this study was to longitudinally determine the prognostic value of early postoperative quantitative 3T-MRI (magnetic resonance imaging) parameters of subchondral bone marrow for 2-year clinical and MRI outcome after matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) at the knee.
Design
Consecutive subjects who received MACI with ABG for treatment of focal osteochondral defects received MRI follow-up 3, 6, 12, and 24 months postoperatively. Quantitative MRI included bone marrow edema-like lesion (BMEL) volume measurements and single-voxel magnetic resonance spectroscopy (MRS; n = 9) of the subchondral bone marrow. At 2-year follow-up, morphological MRI outcome included MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. Clinical outcomes were assessed using Lysholm scores.
Results
Among a total of 18 subjects (mean age: 28.7 ± 8.4 years, n = 14 males) with defects at the medial or lateral ( n = 15 and n = 3, respectively) condyle, mean BMEL volume decreased from 4.9 cm ³ at 3 months to 2.0 cm ³ at 2-year follow-up ( P = 0.040). MRS-based bone marrow water T2 showed a decrease from 20.7 ms at 1-year follow-up to 16.8 ms at 2-year follow-up ( P = 0.040). Higher BMEL volume at 6 months correlated with lower 2-year Lysholm (R = −0.616, P = 0.015) and MOCART 2.0 scores (R = −0.567, P = 0.027). Larger early postoperative BMEL volumes at 3 months (R = −0.850, P = 0.007) and 6 months (R = −0.811, P = 0.008) correlated with lower MRS-based unsaturated lipid fractions at 2-year follow-up. Furthermore, patients with early postoperative bony defects showed worse MOCART 2.0 ( P = 0.044) and Lysholm scores ( P = 0.017) after 24 months.
Conclusion
Low subchondral BMEL volume and optimal restoration of the subchondral bone at early postoperative time points predict better 2-year clinical and MRI outcomes after MACI with ABG.
... [3] Another study also found that five years after ACI, patients experienced significant pain relief and improved ability to perform daily activities, with 80 percent of patients able to perform more activities than before surgery. [150] Furthermore, ACI utilizes its own chondrocytes to minimize possible immunological problems and infection risks, as well as chondrocyte supply problems. [151] However, ACI often requires two surgeries and a lengthier recovery period for patients, limiting its practical use. ...
The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. To date, complete regeneration of hyaline cartilage exhibiting mechanical properties remains an elusive goal, despite the many available technologies. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, thereby resulting in fibrocartilage with poor mechanical qualities. All these factors suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage repair, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, this calls for elucidation of the immune microenvironment of cartilage repair after injury. This review provides a brief overview of: (1) the pathogenesis of cartilage injury; (2) immune cells in cartilage injury and repair; (3) effects of inflammatory cytokines on cartilage repair; (4) clinical strategies for treating cartilage defects; and (5) strategies for targeted immunoregulation in cartilage repair.
Statement of Significance
: Immune response is increasingly considered the key factor affecting cartilage repair. It has both negative and positive regulatory effects on the process of regeneration and repair. Proinflammatory factors are secreted in large numbers, and necrotic cartilage is removed. During the repair period, immune cells can secrete anti-inflammatory factors and chondrogenic cytokines, which can inhibit inflammation and promote cartilage repair. However, inflammatory factors persist, which accelerate the degradation of the cartilage matrix. Furthermore, in an inflammatory microenvironment, MSCs undergo abnormal differentiation, and chondrocytes begin to transform or dedifferentiate into fibroblast-like cells, forming fibrocartilage with poor mechanical properties. Consequently, cartilage regeneration requires multi-dimensional regulation of the joint inflammatory microenvironment in space and time to make it conducive to cartilage regeneration.
... For cartilage repair with a defect of less than 2cm 2 , autografts and allografts achieved a high satisfaction rate of long-term graft survival [6][7][8]. Currently, cell-based cartilage repair techniques are quite attractive for cartilage repair with a defect larger than 3-4cm 2 , especially for matrix induced autologous chondrocyte implantation (MACI), It has been reported that knee patients who underwent MACI surgery experienced significant pain reduction 5 years after surgery [9,10]. Although there are many methods for cartilage repair, the uncertainty of their efficacy and their disadvantages are still obvious. ...
Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair.
Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects.
Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery.
Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair.
Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors.
Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.
... Although the current study demonstrated that MACI has limited short-term efficacy, it still had a promising clinical effect with many cartilage-like tissues filling the lesion, which was also reported in several previous studies. In a prospective clinical following 31 patients for 5 years after MACI, Ebert et al. (2017b) also reported favorable clinical outcomes. That is, all grafts were preserved on follow-up MRI, except for two graft failure cases due to complications. ...
Background: Articular cartilage is a complex structure that allows for low frictional gliding and effective shock absorption. Various sports injuries and inflammatory conditions can lead to lesions in the articular cartilage, which has limited regenerative potential. Type I collagen combined with autologous chondrocytes in a three-dimensional culture were used to induce the regeneration of single-layer autologous expanded chondrocytes without chondrogenic differentiation.
Purpose: To assess the clinical, radiological, and histological changes following collagen-based autologous chondrocyte transplantation (MACT) for chondral knee lesions.
Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral lesions (mean size lesion was 2.41 ± 0.43 cm ² , range: 2.0–3.4 cm ² ) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. knee injury and osteoarthritis outcome score (KOOS) was assessed before the procedure, and periodic clinical follow-up was conducted every 3 months for a maximum of 12 months following the procedure and at 1-year intervals thereafter. Magnetic resonance imaging (MRI) T2 mapping of repaired cartilage was also used for the quantitative analysis of regeneration. In one patient, second-look arthroscopy was performed to assess cartilage regeneration characteristics, and a portion of regenerated cartilage was harvested for histological evaluation 12 months after implantation.
Results: At pre-operation and at three, six, 12, and 24 months after the operation, KOOS pain, symptoms, daily life activities, sports and recreation, as well as the quality of life were significantly improved between every two time points. Hematoxylin and eosin (HE) staining indicated that the newly formed cartilage was comprised of naive chondrocytes. Safranin O-fast (S-O) green staining of the regenerated tissue revealed fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry (IHC) analysis indicated that collagen type II was uniformly distributed at the deep zone of articular cartilage and type I collagen mainly depositing in the superficial cartilage layer. The T2 values for repaired tissue gradually decreased, eventually approaching near-average values.
Conclusion: The present study demonstrated that type I collagen-based MACT is a clinically effective treatment for improving functionality and pain levels. Histological evidence confirmed hyaline cartilage induction and showed that repaired cartilage tended to emerge from the deep to the superficial layer. The quantitative MRI T2 mapping test indicated that there still was a difference between the transplanted cartilage and the surrounding hyaline cartilage. Taken together, the current method represents an efficient approach for the restoration of knee cartilage lesions.
... 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. ...
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.
... 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. ...
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.
... 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. ...
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.
... Our study showed good clinical e cacy with a large number of cartilage-like tissues lling the lesion, and this had also been evaluated in several studies. In a prospective clinical following 31 patients with MACI for 5 years, Ebert JR et al. [17] found good clinical outcomes, and all grafts were preserved on follow-up MRI except for two graft failure cases due to the complications. Moreover, Barié et al. ...
Purpose: To investigate the clinical, radiological, and histological results of type I collagen-based matrix-assisted autologous chondrocyte transplantation (MACT) in the treatment of chondral lesions of the knee.
Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral defects (mean size defect was 2.41±0.43 cm², range 2.0 to 3.4 cm²) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. KOOS was assessed preoperatively, with periodic clinical follow-up performed preoperatively and then every 3 months for up to 12 months postoperative period, and thereafter at 1-year intervals. During this follow-up, serial magnetic resonance imaging T2 mapping of repair cartilage was used to reflect the quantitative analysis quality of the regenerative cartilage. In one patient, second-look arthroscopy was performed at 12 months after implantation to assess the characteristics of cartilage regeneration.
Results: Compared with preoperation, the score of the pain, symptoms, activities of daily living, sports and recreation, and quality of life showed statistically significant improvement with a significant difference at 3, 6, 12, and 24 months after operation(P<0.05). The difference in KOOS subscales scores between every two-time point was statistically significant (P<0.001). HE stains showed the newly formed cartilage was naive chondrocytes. Safranin O-fast green stain manifested in the regenerated tissue comprising predominantly fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry analysis showed that the expression of collagen type II was more clearly and evenly distributed than collagen type I.
Conclusion: Type I collagen-based MACT was a clinically effective treatment for functional and pain level improvement, and this method presented histologic evidence of inducing hyaline‐like cartilage in cartilage lesions by biopsy in one case. The quantitative MRI T2-mapping test showed that there was a difference between the transplanted cartilage and the surrounding hyaline cartilage.
... Graft hypertrophy is one of the most common complications that affect the prognosis of cartilage repair following the clinical treatment. In cases of periosteal autologous chondrocyte implantations (PACI) treating cartilage defects, incidence of graft hypertrophy varies from 9% to 40% (Harris et al., 2011), and it reduced by replacing the periosteal membrane with collagen membrane (MACI ® ) or three-dimensional collagen matrix (Novocart ® ) (Bartlett et al., 2005;Ebert, Fallon, Wood, & Janes, 2017;Niethammer et al., 2014). Nevertheless, symptomatic graft hypertrophy primarily threatens the effect of cartilage defects repairing after acute trauma and osteochondritis dissecans (Genovese et al., 2011;Niethammer et al., 2014;Wylie, Hartley, Kapron, Aoki, & Maak, 2016). ...
Since chondrocyte hypertrophy greatly limits the efficiency of cartilage defects repairing via cartilage tissue engineering (CTE), it is critical to develop a functional CTE scaffold able to inhibit chondrocyte hypertrophy during this period of cartilage regeneration. In this study, we tested the applicability of using decellularized sturgeon cartilage ECM (dSCECM) scaffold to cease chondrocyte hypertrophy during cartilage damage repair. The dSCECM scaffolds with interconnected porous structure and pore size of 114.1 ± 20.9 μm were successfully prepared with freeze-dry method. Chondrocytes displayed a round shape and aggregated to form cellular spheroids within dSCECM scaffolds, which is similar to their chondrocytic phenotype within cartilage in vivo. Higher transcriptional level of chondrogenic related genes and integrin related genes was observed in chondrocytes incubated with dSCECM scaffolds instead of type I collagen (COL I) scaffolds, which were used as the control due to their widely usage in CTE and clinic applications. Furthermore, it confirmed that, compared with COL I scaffolds, dSCECM scaffolds significantly reduced the transcription of chondrocyte hypertrophy related genes in chondrocytes following the hypertrophic induction treatment. To test the ability of dSCECM scaffold to inhibit chondrocytes hypertrophy in vivo, chondrocytes with dSCECM scaffolds and COL I scaffolds were cultured with hypertrophic media and were implanted into nude mice respectively. Following 4 weeks implantation, interestingly, only the specimens derived from COL I scaffolds displayed consequences of chondrocyte hypertrophy like calcification deposition, demonstrating that chondrocyte hypertrophy is ceased by the dSCECM scaffold following hypertrophic induction. It suggests that the dSCECM scaffold can be potentially applied in clinical treating cartilage defects via the CTE approach to avoid the risk of chondrocyte hypertrophy.
... ACI/ MACI has been shown to have excellent short-term, midterm, and long-term clinical outcomes. 32,82 The shape of the patella and trochlea are more highly variable than the shape of the femoral condyles and tibial plateaus, which complicates morphology matching, particularly with the involvement of the central trochlear groove and median patellar ridge. For these reasons, ACI/MACI are the most common cartilage restoration procedure performed in the PF joint. ...
Objective
To create a treatment algorithm for focal grade 3 or 4 cartilage defects of the knee using both classic and novel cartilage restoration techniques.
Design
A comprehensive review of the literature was performed highlighting classic as well as novel cartilage restoration techniques supported by clinical and/or basic science research and currently being employed by orthopedic surgeons.
Results
There is a high level of evidence to support the treatment of small to medium size lesions (<2-4 cm ² ) without subchondral bone involvement with traditional techniques such as marrow stimulation, osteochondral autograft transplant (OAT), or osteochondral allograft transplant (OCA). Newer techniques such as autologous matrix-induced chondrogenesis and bone marrow aspirate concentrate implantation have also been shown to be effective in select studies. If subchondral bone loss is present OAT or OCA should be performed. For large lesions (>4 cm ² ), OCA or matrix autologous chondrocyte implantation (MACI) may be performed. OCA is preferred over MACI in the setting of subchondral bone involvement while cell-based modalities such as MACI or particulated juvenile allograft cartilage are preferred in the patellofemoral joint.
Conclusions
Numerous techniques exist for the orthopedic surgeon treating focal cartilage defects of the knee. Treatment strategies should be based on lesion size, lesion location, subchondral bone involvement, and the level of evidence supporting each technique in the literature.
... 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]. ...
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.
... 8 Studies of MACI for patellofemoral osteochondral lesions have shown comparable results to those in the tibiofemoral location when appropriate concomitant procedures are performed. 13 Filardo et al. 14 reported differences in outcomes between trochlear and patellar lesions when treated by MACI. Moreover, some studies have shown better results with MACI than with ACI for the patellofemoral joint. ...
In the past 30 years, bone marrow stimulation techniques such as microfracture (MF) have become a popular method to treat symptomatic focal articular cartilage lesions. Nonetheless, recent studies have not shown good long-term clinical outcomes, and MF has produced alterations in the subchondral bone architecture with degenerative changes. Autologous chondrocyte implantation (ACI) has shown good results at 20 years. Second- and third-generation ACI has shown superiority to MF and fewer complications than first-generation ACI. Each treatment option has its advantages and disadvantages. Recent research has shown that better filling of cartilage tissue occurs in patients treated with MF and collagen augmentation than in those treated with MF alone. Research from our clinic has shown that Hyaff scaffold combined with bone marrow aspirate concentrate in a 1-step technique yielded good results in patients with 10 years’ follow-up. We believe that high-quality randomized controlled trials are necessary to directly compare all cartilage restoration procedures.
Focal articular chondral lesions are a common finding among patients presenting with knee pain. If symptomatic and unresponsive to conservative treatment, cell transplantation techniques offer a unique solution to address larger defects by engineering chondrocytes to integrate within the subchondral bone of the lesion and regenerate cartilage. The chondrocytes used for these transplantations may come in the form of patients’ own chondrocytes imbedded into a collagen membrane as a matrix-induced autologous chondrocyte implantation (MACI) procedure, or minced autologous donor cartilage that is then implanted onto a scaffold as a particulated
juvenile allograft cartilage (PJAC) procedure. These cell transplantation techniques offer advantages compared to bone marrow stimulation or mosaicplasty. Both MACI and PJAC have shown clinically significant improvements in outcome scores and low rates of complications.
In this review, we discuss the histories and evolution of the MACI and PJAC techniques used today. We summarize the indications, contraindications, surgical techniques, and available outcomes for cell transplantation in the setting of chondral defects in the knee.
Purpose
Different surgical techniques to manage cartilage defects are available, including microfracture (MFx), autologous chondrocyte implantation (ACI), osteoarticular auto- or allograft transplantation (OAT), autologous matrix-induced chondrogenesis (AMIC). This study investigated the patient-related prognostic factors on the clinical outcomes of surgically treated knee and ankle cartilage defects.
Methods
This study followed the PRISMA statement. In May 2022, the following databases were accessed: PubMed, Google Scholar, Embase, and Scopus. All the studies investigating the outcomes of surgical management for knee and/or talus chondral defects were accessed. Only studies performing mesenchymal stem cells transplantation, OAT, MFx, ACI, and AMIC were considered. A multiple linear model regression analysis through the Pearson Product–Moment Correlation Coefficient was used.
Results
Data from 184 articles (8905 procedures) were retrieved. Female sex showed a positive moderate association with visual analogue scale at last follow-up (P = 0.02). Patient age had a negative association with the American Orthopaedic Foot and Ankle Score (P = 0.04) and Lysholm Knee Scoring Scale (P = 0.03). BMI was strongly associated with graft hypertrophy (P = 0.01). Greater values of VAS at baseline negatively correlate with lower values of Tegner Activity Scale at last follow-up (P < 0.0001).
Conclusion
The clinical outcomes were mostly related to the patients’ performance status prior surgery. A greater BMI was associated with greater rate of hypertrophy. Female sex and older age evidenced fair influence, while symptom duration prior to the surgical intervention and cartilage defect size evidenced no association with the surgical outcome. Lesion size and symptom duration did not evidence any association with the surgical outcome.
Introduction: It is unclear whether the type of membrane used for matrix-assisted autologous chondrocyte implantation (mACI) influences results. A systematic review was conducted to investigate the midterm results of the three most common types of membrane fixation for mACI. Methods: This systematic review was conducted according to the 2020 PRISMA checklist. PubMed, Google Scholar, Embase, and Scopus online databases were accessed in August 2022. All the prospective clinical trials reporting outcomes of mACI in the knee were considered. Studies that describe the modality of membrane fixation (glued, glued, and sutured, no fixation) used for mACI were eligible. Studies that conducted a minimum of 12 months of follow-up were considered. The outcomes of interest were the Tegner Activity Scale and International Knee Documentation Committee (IKDC) score. The rate of failure and revisions were also collected. Results: Data from 26 studies (1539 procedures; 554 of 1539 (36%) were women) were retrieved. The mean follow-up was 42.6 (12 to 84) months. No difference between the groups was found in terms of mean duration of symptoms, age, BMI, gender, and defect size (P > 0.1). No difference was found in terms of the Tegner score (P = 0.3). When no fixation was used, a statistically significant higher IKDC compared to the other groups (P = 0.02) was evidenced. No difference was found in the rate of failure (P = 0.1). The no-fixation group evidenced a statistically significant lower rate of revisions (P = 0.02). Conclusions: No membrane fixation for mACI in the knee scored better than the fastening techniques at the midterm follow-up.
PurposeTo investigate whether the quality of cartilage repair tissue is associated with patellofemoral osteoarthritis (PFOA) at a three year follow-up after matrix-induced autologous chondrocyte implantation (MACI).Methods
This retrospective study included 32 patients who underwent MACI between October 2014 and May 2018 at our institute. The Lysholm score and Visual Analog Scale (VAS) score were assessed. The magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and T2* relaxation time of repair tissue were used to evaluate cartilage repair tissue quality. A modified MRI Osteoarthritis Knee Score (mMOAKS) was used to evaluate PFOA.ResultsCompared with pre-operative scores, the final Lysholm score (50.71 ± 2.22 vs 89.70 ± 1.18; t = 15.5, P < 0.0001) and VAS score (4.67 ± 0.47 vs 0.92 ± 0.64; t = 22.62, P < 0.0001) were improved at 3 years after MACI. At the three year follow-up, the mean MOCART 2.0 score was 61.56 ± 18.11, and the T2* relaxation time of the repair tissue was significantly lower than that in the healthy control region (24.11 ± 6.38 vs 34.39 ± 1.33, t = − 8.635, P < 0.0001). The mean mMOAKS score was 9.16 ± 4.51. On univariate analysis, the MOCART 2.0 score and T2* relaxation time were negatively associated with the mMOAKS score.ConclusionMACI can lead to significant pain relief and restoration of knee joint function, and good quality cartilage repair tissue was a protective factor against PFOA at the three year follow-up.
Long-term clinical repair of articular cartilage remains elusive despite advances in cartilage tissue engineering. Only one cartilage repair therapy classified as a “cellular and gene therapy product” has obtained Food and Drug Administration (FDA) approval within the past decade although more than 200 large animal cartilage repair studies were published. Here, we identify the challenges impeding translation of strategies and technologies for cell-based cartilage repair, such as the disconnect between university funding and regulatory requirements. Understanding the barriers to translation and developing solutions to address them will be critical for advancing cell therapy products for cartilage repair to clinical use.
Precise knowledge of the size and location of hyaline cartilage defects is essential for the development of robotic tools for cartilage repair surgery in the knee. The German Cartilage Registry indicates that about 45% of the defects are at the medial femoral condyle and nearly 30% at the patella. Our literature analysis confirms that the femur, especially the medial side, is the most frequent location for cartilage defects in the knee but that defects in the retropatellar region are common as well. Surgery methods to treat cartilage defects can be differentiated by the type of surgical approach. Most defects are eligible for minimal-invasive arthroscopic treatment. Accordingly developed instruments should reach the femoral and retropatellar region. Regarding cartilage defect size a range from 0.02 cm\(^2\) to 50 cm\(^2\) was reported in literature.KeywordsCartilage replacement surgeryRobotic knee surgeryChondral defect knee
Articular cartilage damage is a common cause of disability in the knee. Damage to the articular cartilage represents a spectrum of disease ranging from isolated chondral defects to diffuse cartilage loss to osteoarthritis. Establishing a correct diagnosis and correctly characterizing the lesion are critical in determining a treatment plan. Operative treatment is typically considered if nonoperative treatment measures fail. Operative interventions include debridement, marrow-stimulating techniques, cartilage restoration procedures (such as ACI), and cartilage replacement (osteochondral autograft or allograft). The type of cartilage procedure chosen depends on many factors including the size of the lesion, condition of the underlying bone, location of the lesion, prior procedures performed, and demands of the patient. Advanced imaging with magnetic resonance imaging (MRI) should be done to evaluate the articular cartilage and subchondral bone and to assess for concomitant meniscus and ligamentous injuries or deficiencies. However, the accuracy of MRI in predicting the size of the lesion has been questioned and has been found to underestimate the size of the lesion. Diagnostic arthroscopy and staged procedures can be very useful. This chapter utilizes a case-based format to demonstrate the correlation between MRI and arthroscopy for articular cartilage lesions of the knee. Diagnosis and management of each patient are discussed for each of the seven cases.KeywordsCartilageChondralMRIMagnetic resonance imagingCorrelationKneeArthroscopy
Background/objective
The purpose of this study was to report the outcomes of a clinical trial conducted in Japan to assess the safety and effectiveness of third-generation autologous chondrocyte implantation (ACI) using IK-01 (CaReS™), which does not require flap coverage, in the treatment of patients with focal cartilage injury of the knee.
Methods
This was an open label, exploratory clinical trial. Patients were enrolled between June 2012 and September 2016. The primary endpoint of the study was the International Knee Documentation Committee (IKDC) score at 52 weeks after implantation. The IKDC, Lysholm, and visual analog scale (VAS) scores were evaluated at the time of screening and at 4, 12, 24, 36, and 52 weeks after implantation. Improvements from the baseline scores were evaluated using the equation “(postoperative score) − (preoperative score).” Magnetic resonance imaging (MRI) was performed at 2, 12, 24, and 52 weeks after implantation, and MRI measurements were evaluated using T1 rho and T2 mapping.
Results
Nine patients were enrolled in this study and were examined for safety. Product quality did not satisfy the specification in one patient, and bacterial joint infection occurred in one patient. As a result, seven patients were included in the outcome analyses. The mean IKDC score significantly improved from 36.4 preoperatively to 74.1% at 52 weeks after implantation (p < 0.0001). The mean Lysholm and VAS scores also significantly improved from 39.6 to 57.4 to 89.6 and 22.9, respectively, after surgery. In the MRI evaluation, the T1 rho and T2 values of the implanted area were similar to those of the surrounding cartilage at 52 weeks after implantation.
Conclusions
Third generation ACI (IK-01) can be an effective treatment option for focal cartilage defects of the knee; however, surgeons must pay careful attention to the risk of postoperative joint infection.
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.
Case:
A 21-year-old male division I collegiate athlete presented for right knee pain, effusion, and mechanical symptoms. The patient was found to have 2.4 × 2-cm medial patellar facet, 1 × 0.8-cm central trochlea, and 2.5 × 3-cm lateral femoral condyle articular cartilage defects on arthroscopy. The patient was treated with a matrix-induced autologous chondrocyte implantation (MACI) procedure for all 3 lesions. At 9 months postoperatively, the patient returned to full American football activities and remains asymptomatic 16 months postoperatively.
Conclusion:
Multiple lesions and lesions involving the patellofemoral joint can be treated with a MACI procedure with short-term promising results in high-demand athletes.
The purpose of this study was to evaluate clinical and magnetic resonance imaging (MRI) outcomes in patients who underwent cryopreserved viable osteochondral allograft (CVOCA) implantation for focal cartilage defects in the knee at a minimum of 2-years postoperatively. This is a retrospective follow-up study of twelve patients who underwent CVOCA implantation from 2013 to 2015 by a single surgeon for a International Cartilage Repair Society (ICRS) grade 3 or 4 chondral defect. Patient-reported outcome (PRO) measurements and MRI were obtained 2-years postoperatively. Collected PRO measures included: International Knee Documentation Committee (IKDC) form; Visual Analog Scale (VAS) pain score; Veterans RAND 12-Item Health Survey (VR-12); Knee Injury and Osteoarthritis Outcome Score (KOOS); and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Patients completed a standard return to work and sports/recreation survey. A blinded, fellowship-trained musculoskeletal radiologist independently evaluated each MRI to determine the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Mean follow-up was 2.1 years (2.0–2.3). There were 6 women and 6 men with a mean age of 46.2 ± 11.9 years. Mean PRO scores were: IKDC 72.6 ± 17.4; VAS 2.9 ± 2.8; WOMAC 84.2 ± 15.1; KOOS- Pain 83.8 ± 18.5, Symptoms 77.6 ± 16.0, ADL 88.0 ± 16.9, Sports/Rec 67.7 ± 33.3, QOL 54.8 ± 24.2; and VR-12 PCS 45.0 ± 8.5 and MCS 51.1 ± 9.5. The mean MOCART score was 59.5 ± 12.9. To our knowledge, this is the largest study to report clinical and MRI outcomes of CVOCA implantation in the knee. With positive functional outcomes and lack of failures at 2-year follow-up, CVOCA is a promising treatment option for focal chondral defects in the knee.
Study design
Retrospective case series, Level of evidence 4.
Despite the recent decrease in high tempo combat operations, threats to the medical readiness of Service Members remain a persistent issue. In fact, recent research efforts have demonstrated that musculoskeletal disease nonbattle injury represents perhaps the most immediate threat to the medical readiness of Service Members over the past several years. Innovations in a number of therapeutic options, particularly orthobiologics, have shown substantial promise in accelerating recovery and returning tactical athletes to full, unrestricted duties. Posttraumatic osteoarthritis remains a vexing topic but at the same time an intersectional opportunity for a multidisciplinary approach to better understand its pathogenesis, limit its prevalence, and mitigate the functional consequences of its sequalae. The expansion of a clinical infrastructure capable of the prospective collection of Service Members' functional outcomes across military treatment facilities promises to sharpen clinicians' understanding of both the impact of novel treatments for common injuries and the success of efforts to prevent recurrence (Military Orthopaedics Tracking Injury Network, Bethesda, MD). However, policy makers and stakeholders will increasingly find themselves in an environment of increasingly limited resources, which will necessitate creative strategies to maintain the lethality of a fit, fighting force.
Full thickness chondral defects can be debilitating for athletes. Due to the low potential for intrinsic healing of articular cartilage, surgical intervention is often considered when patients continue to experience functionally limiting symptoms despite an adequate trial of nonoperative management. Matrix-induced autologous chondrocyte implantation (MACI) is a 2-stage procedure used to treat chondral lesions with minimal subchondral bone involvement. MACI has significant advantages over previous generations of autologous chondrocyte implantation (ACI), including a simplified surgical technique and accelerated postoperative rehabilitation protocol. MACI has been shown to result in good clinical outcomes, with several studies showing high success rates. Additionally, MACI has a low rate of complications specific to the procedure.
Large, focal articular cartilage defects of the knee (> 4 cm2) can be a source of significant morbidity and often require surgical intervention. Patient- and lesion-specific factors must be identified when evaluating a patient with an articular cartilage defect. In the management of large cartilage defects, the two classically utilized cartilage restoration procedures are osteochondral allograft (OCA) transplantation and cell therapy, or autologous chondrocyte implantation (ACI). Alternative techniques that are available or currently in clinical trials include a hyaluronan-based scaffold plus bone marrow aspirate concentrate, a third-generation autologous chondrocyte implant, and an aragonite-based scaffold. In this review, we will focus on OCA and ACI as the mainstay in management of large chondral and osteochondral defects of the knee. We will discuss the techniques and associated clinical outcomes for each, while including a brief mention of alternative treatments. Overall, cartilage restoration techniques have yielded favorable clinical outcomes and can be successfully employed to treat these challenging large focal lesions.
Background
Quantitative magnetic resonance (MR) imaging techniques are established for evaluation of cartilage composition and trabecular bone microstructure at the knee. It remains unclear whether quantitative MR parameters predict the midterm morphological outcome after matrix-associated chondrocyte implantation (MACI) with autologous bone grafting (ABG).
Purpose
To assess longitudinal changes and associations of the biochemical composition of cartilage repair tissue, the subchondral bone architecture, and morphological knee joint abnormalities on 3-T MR imaging after MACI with ABG at the knee.
Study Design
Case series; Level of evidence, 4.
Methods
Knees of 18 patients (28.7 ± 8.4 years [mean ± SD]; 5 women) were examined preoperatively and 3, 6, 12, and 24 months after MACI and ABG using 3-T MR imaging. Cartilage composition was assessed using T 2 relaxation time measurements. Subchondral bone microstructure was quantified using a 3-dimensional phase-cycled balanced steady-state free precision sequence. Trabecular bone parameters were calculated using a dual threshold algorithm (apparent bone fraction, apparent trabecular number, and apparent trabecular separation). Morphological abnormalities were assessed using the MOCART (magnetic resonace observation of cartilage repair tissue) score, the WORMS (Whole-Organ Magnetic Resonance Imaging Score), and the CROAKS (Cartilage Repair Osteoarthritis Knee Score). Clinical symptoms were assessed using the Tegner activity and Lysholm knee scores. Statistical analyses were performed by using multiple linear regression analysis.
Results
Total WORMS ( P = .02) and MOCART ( P = .001) scores significantly improved over 24 months after MACI. Clinical symptoms were significantly associated with the presence of bone marrow edema pattern abnormalities 24 months after surgery ( P = .035). Overall there was a good to excellent radiological outcome found after 24 months (MOCART score, 88.8 ± 10.1). Cartilage repair T 2 values significantly decreased between 12 and 24 months after MACI ( P = .009). Lower global T 2 values after 3 months were significantly associated with better MOCART scores after 24 months ( P = .04). Moreover, trabecular bone parameters after 3 months were significantly associated with the total WORMS after 24 months (apparent bone fraction, P = .048; apparent trabecular number, P = .013; apparent trabecular separation, P = .013).
Conclusion
After MACI with ABG, early postoperative quantitative assessment of biochemical composition of cartilage and microstructure of subchondral bone may predict the outcome after 24 months. The perioperative global joint cartilage matrix quality is essential for proper proliferation of the repair tissue, reflected by MOCART scores. The subchondral bone quality of the ABG site is essential for proper maturation of the cartilage repair tissue, reflected by cartilage T 2 values.
BACKGROUND
There is still lack of consensus about the best treatment of chondral defects of the knee. We conducted a systematic PRISMA review to evaluate clinical outcomes of Autologous Chondrocyte Implantation (ACI) and Mesenchymal Stem Cell (MSC) injections for the treatment of focal chondral defects of the knee.
METHODS
A systematic review of literature was performed according to the PRISMA guidelines. All the articles reporting data on ACI and MSC treatments for chondral defects of the knee were considered for inclusion. The main databases were accessed: PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar. The statistical analysis was performed using the Review Manager Software.
RESULTS
In the p-ACI group (987 knees), the Cincinnati Score improved by 18.94% (p=0.1), VAS by 38% (p=0.01), Tegner score by 19.11% (p=0.03), Lysholm score by 22.40% (p=0.01), IKCD by 27.36% (p=0.003). In the c-ACI group (444 knees), the Cincinnati Score improved by 23.80% (p=0.08), KOOS by 23.48% (p=0.03), VAS by 33.2% (p=0.005), IKDC by 33.30% (p=0.005). In the m-ACI group (599 knees), the Cincinnati Score improved by 26.80% (p=0.08), KOOS by 31.59% (p=0.1), VAS by 30.43% (p=0.4), Tegner score by 23.1% (p=0.002), Lysholm score by 31.14% (p=0.004), IKCD by 30.57% (p<0.001). In the MSCs group (291 knees), the KOOS improved by 29.7% (p=0.003), VAS by 41.89% (p<0.001), Tegner score by 25.81% (p=0.003), Lysholm score by 36.96% (p<0.001), IKCD by 30.57% (p=0.001).
CONCLUSIONS
Both ACI and MSC therapies can be considered as a concrete solution to treat focal chondral defects of the knee.
Una significativa cantidad de adultos jóvenes activos sufre lesiones condrales focales. Estas lesiones, si no se tratan, pueden pro- gresar hacia la artrosis, que es una de las principales enfermedades musculoesqueléticas debilitantes y de gran carga económica que afectan a toda sociedad. Pese a los tratamientos quirúrgicos disponibles para la reparación de defectos condrales focales sintomáticos que mejoran la calidad de vida a mediano plazo, hay un mayor riesgo de progresión hacia la artrosis prematura. Los tratamientos biológicos (células madre, bioingeniería tisular) han avanzado a grandes pasos en los últimos años. La bioingeniería es un área que ha progresado en la regeneración de cartílago articular y que potencialmente podría progresar en el terreno de tratamientos articulares, promoviendo la regeneración y evitando la degeneración. Las células madre y los hidrogeles pueden proveer un tejido símil biológico de comportamiento dinámico-funcional equivalente que induce la regeneración tisular al ser degradado y reemplazado gradualmente. El abordaje consiste en colocar un hidrogel precursor o un biomaterial tridimensional impreso dentro del defecto condral por ocupar para inducir la regeneración. Esta revisión se focaliza en el uso actual y futuro de hidrogeles y bioimpresión tridimensional para la regeneración de cartílago articular en el tratamiento de lesiones condrales foca- les y proporciona datos preliminares de dos estudios piloto en animales.
Cell therapy combined with biomaterial scaffolds is used to treat cartilage defects. We hypothesized that chondrogenic differentiation bone marrow-derived mesenchymal stem cells (BM-MSCs) in three-dimensional biomaterial scaffolds would initiate cartilaginous matrix deposition and prepare the construct for cartilage regeneration in situ. The chondrogenic capability of human BM-MSCs was first verified in a pellet culture. The BM-MSCs were then either seeded onto a composite scaffold rhCo-PLA combining polylactide and collagen type II (C2) or type III (C3), or commercial collagen type I/III membrane (CG). The BM-MSCs were either cultured in a proliferation medium or chondrogenic culture medium. Adult human chondrocytes (ACs) served as controls. After 3, 14, and 28 days, the constructs were analyzed with quantitative polymerase chain reaction and confocal microscopy and sulfated glycosaminoglycans (GAGs) were measured. The differentiated BM-MSCs entered a hypertrophic state by Day 14 of culture. The ACs showed dedifferentiation with no expression of chondrogenic genes and low amount of GAG. The CG membrane induced the highest expression levels of hypertrophic genes. The two different collagen types in composite scaffolds yielded similar results. Regardless of the biomaterial scaffold, culturing BM-MSCs in chondrogenic differentiation medium resulted in chondrocyte hypertrophy. Thus, caution for cell fate is required when designing cell-biomaterial constructs for cartilage regeneration.
Focal chondral defects are common in the patellofemoral joint, particularly in young and active patients, and can significantly impair quality of life. The pathomechanism of cartilage lesions in the patellofemoral joint are multifactorial and can be divided into chronic repetitive microtrauma due to patellar maltracking and acute macrotrauma such as patellar dislocation. Numerous risk factors for patellar instability have been reported including trochlear dysplasia, patella alta, chronic lateral patellar static position, excessive lateral position of the tibial tuberosity, excessive internal rotation of femur/external rotation of tibia, and patholaxity of the medial patellofemoral ligament. Patients with patellofemoral chondral lesions typically present with anterior knee pain that is exacerbated by activity, patellar instability, and/or loss of motion. This is often accompanied by effusion, soft tissue swelling, giving way, crepitance, and loose body sensation. If conservative treatment fails, various surgical treatment options are available ranging from palliative (chondroplasty), over reparative (marrow stimulation techniques) to restorative (autologous chondrocyte implantation and particulated juvenile allograft cartilage), and reconstructive procedures (osteochondral transplantation). A thorough physical and imaging evaluation of the patient is crucial to detect concomitant pathologies and to eventually allow planning a comprehensive individual treatment approach for each patient that addresses both the chondral lesion and any associated pathology. Also, setting realistic expectations and elucidating patient's goals are important parts of a successful treatment. Following these principles, favorable outcomes and high satisfaction rates can be achieved after cartilage restoration in the PFJ.
A significant number of young active adults are affected by focal chondral lesions. These lesions, if left untreated, will progress to osteoarthritis (OA). OA is one of the main debilitating musculoskeletal diseases and leads to a high economic and social burden.
Despite surgical cartilage repair for focal chondral lesions, which improve patient-reported outcomes at short- and mid-term, there is a risk of early OA progression. Biological treatments (i.e., stem-cell therapy, bioengineering) have made great progress in the last years. Tissue engineering is an evolving field for articular cartilage repair which could potentially be used for the treatment of focal chondral lesions, promoting regeneration and preventing joint surface degeneration. Stem cells and hydrogels may provide a functional, dynamic and biologically equivalent tissue that promotes tissue regeneration while being gradually degraded and replaced. The standard approach to tissue engineering consists in delivering cells within a hydrogel or a three-dimensional printed biomaterial scaffold into the chondral lesion to induce regeneration. This review focuses on the current and future use of
hydrogels and tissue scaffold bioprinting for the treatment of focal chondral lesions, and provides preliminary data from two pilot animal studies.
This paper aims to review the current evidence for autologous chondrocyte implantation (ACI) generations relative to other treatment modalities, different cell delivery methods and different cell source application.
Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.
Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.
At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.
II.
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.
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.
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.
This study assessed the sensitivity of four different types of one-legged hop tests. The goal was to deter mine alterations in lower limb function in ACL deficient knees. Regression analyses were conducted between limb symmetry as measured by the hop tests and muscle strength, symptoms, and self-assessed func tion.
In 67 patients, 50% had abnormal limb symmetry scores on a single hop test. When the results of two hop tests were calculated, the percent of abnormal scores increased to 62%. The percentage of normal scores indicated that these hop tests had a low sensi tivity rate. However, the high specificity and low false- positive rates allow the tests to be used to confirm suspected defects in lower limb function. Statistical trends were noted between abnormal limb symmetry on the hop tests and low velocity quadriceps isokinetic test results.
While structured postoperative rehabilitation after matrix-induced autologous chondrocyte implantation (MACI) is considered critical, very little has been made available on how best to progressively increase weightbearing and exercise after surgery.
A significant improvement will exist in clinical and magnetic resonance imaging (MRI)-based scoring measures to 5 years after surgery. Furthermore, there will be no significant differences in outcomes in MACI patients at 5 years when comparing a traditional and an accelerated postoperative weightbearing regimen. Finally, patient demographics, cartilage defect parameters, and injury/surgery history will be associated with graft outcome.
Randomized controlled trial; level of evidence, 1.
Clinical and radiological outcomes were studied in 70 patients who underwent MACI to the medial or lateral femoral condyle, in conjunction with either an "accelerated" or a "traditional" approach to postoperative weightbearing rehabilitation. Under the accelerated protocol, patients reached full weightbearing at 8 weeks after surgery, compared with 11 weeks for the traditional group. Clinical measures (knee injury and osteoarthritis outcome score [KOOS], short-form health survey [SF-36], visual analog scale [VAS], 6-minute walk test, and knee range of motion) were assessed before surgery and at 3, 6, 12, and 24 months and 5 years after surgery. High-resolution MRI was undertaken at 3, 12, and 24 months and 5 years after surgery and assessed 8 previously defined pertinent parameters of graft repair as well as a combined MRI composite score. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/surgery history was investigated.
Of the 70 patients recruited, 63 (31 accelerated, 32 traditional) underwent clinical follow-up at 5 years; 58 (29 accelerated, 29 traditional) also underwent radiological assessment. A significant time effect (P < .05) was demonstrated for all clinical and MRI-based scores over the 5-year period. While the VAS demonstrated significantly less frequent pain at 5 years in the accelerated group, there were no other significant differences between the 2 groups. Between 24 months and 5 years, a significant improvement (P < .05) in both groups was observed for the sport and recreation subscale of the KOOS as well as a significant decrease (P < .05) in active knee extension for the traditional group. There were no significant differences (P > .05) in the MRI-based scores between 24 months and 5 years after surgery. Patient age and defect size exhibited significant negative correlations (P < .05) with several MRI-based outcomes at 5 years, while there were no significant correlations (P > .05) between clinical and MRI-based outcomes. At 5 years after surgery, 94% and 95% were satisfied with the ability of MACI to relieve their knee pain and improve their ability to undertake daily activities, respectively.
The outcomes of this randomized trial demonstrate a safe and effective accelerated rehabilitation protocol as well as a regimen that provides comparable, if not superior, clinical outcomes to patients throughout the postoperative timeline.
Anterior cruciate ligament (ACL) reconstruction is commonly performed in athletes, with the goal of return to sports activities. Unfortunately, this operation may fail, and the rates of either reinjuring an ACL-reconstructed knee or sustaining an ACL rupture to the contralateral knee range from 3% to 49%. One problem that exists is a lack of information and consensus regarding the appropriate criteria for releasing patients to unrestricted sports activities postoperatively. The purpose of this study was to determine the published criteria used to allow athletes to return to unrestricted sports activities after ACL reconstruction.
A systematic search was performed to identify the factors investigators used to determine when return to athletics was allowed after primary ACL reconstruction. Inclusion criteria were English language, publication within the last 10 years, clinical trial, all adult patients, primary ACL reconstruction, original research investigation, and minimum 12 months' follow-up.
Of 716 studies identified, 264 met the inclusion criteria. Of these, 105 (40%) failed to provide any criteria for return to sports after ACL reconstruction. In 84 studies (32%) the amount of time postoperatively was the only criterion provided. In 40 studies (15%) the amount of time along with subjective criteria were given. Only 35 studies (13%) noted objective criteria required for return to athletics. These criteria included muscle strength or thigh circumference (28 studies), general knee examination (15 studies), single-leg hop tests (10 studies), Lachman rating (1 study), and validated questionnaires (1 study).
The results of this systematic review show noteworthy problems and a lack of objective assessment before release to unrestricted sports activities. General recommendations are made for quantification of muscle strength, stability, neuromuscular control, and function in patients who desire to return to athletics after ACL reconstruction, with acknowledgment of the need for continued research in this area.
Level IV, systematic review of Level I to IV studies.
The purpose of this article is to present recommendations for new muscle strength and hop performance criteria prior to a return to sports after anterior cruciate ligament (ACL) reconstruction.
A search was made of relevant literature relating to muscle function, self-reported questionnaires on symptoms, function and knee-related quality of life, as well as the rate of re-injury, the rate of return to sports and the development of osteoarthritis after ACL reconstruction. The literature was reviewed and discussed by the European Board of Sports Rehabilitation in order to reach consensus on criteria for muscle strength and hop performance prior to a return to sports.
The majority of athletes that sustain an (ACL) injury do not successfully return to their pre-injury sport, even though most athletes achieve what is considered to be acceptable muscle function. On self-reported questionnaires, the athletes report high ratings for fear of re-injury, low ratings for their knee function during sports and low ratings for their knee-related quality of life.
The conclusion is that the muscle function tests that are commonly used are not demanding enough or not sensitive enough to identify differences between injured and non-injured sides. Recommendations for new criteria are given for the sports medicine community to consider, before allowing an athlete to return to sports after an ACL reconstruction.
Soccer is a highly demanding sport for the knee joint, and chondral injuries can cause disabling symptoms that may jeopardize an athlete's career. Articular cartilage lesions are difficult to treat, and the increased mechanical stress produced by this sport makes their management even more complex.
To evaluate whether the regenerative cell-based approach allows these highly demanding athletes a better functional recovery compared with the bone marrow stimulation approach.
Cohort study; Level of evidence, 2.
Forty-one professional or semiprofessional male soccer players were treated from 2000 to 2006 and evaluated prospectively at 2 years and at a final 7.5-year mean follow-up (minimum, 4 years). Twenty-one patients were treated with arthroscopic second-generation autologous chondrocyte implantation (Hyalograft C) and 20 with the microfracture technique. The clinical outcome of all patients was analyzed using the cartilage standard International Cartilage Repair Society (ICRS) evaluation package. The sport activity level was evaluated with the Tegner score, and the recovery time was also recorded.
A significant improvement in all clinical scores from preoperative to final follow-up was found in both groups. The percentage of patients who returned to competition was similar: 80% in the microfracture group and 86% in the Hyalograft C group. Patients treated with microfracture needed a median of 8 months before playing their first official soccer game, whereas the Hyalograft C group required a median time of 12.5 months (P = .009). The International Knee Documentation Committee (IKDC) subjective score showed similar results at 2 years' follow-up but significantly better results in the Hyalograft C group at the final evaluation (P = .005). In fact, in the microfracture group, results decreased over time (from 86.8 ± 9.7 to 79.0 ± 11.6, P < .0005), whereas the Hyalograft C group presented a more durable outcome with stable results (90.5 ± 12.8 at 2 years and 91.0 ± 13.9 at the final follow-up).
Despite similar success in returning to competitive sport, microfracture allows a faster recovery but present a clinical deterioration over time, whereas arthroscopic second-generation autologous chondrocyte implantation delays the return of high-level male soccer players to competition but can offer more durable clinical results.
The availability remains limited of midterm clinical and radiologic results into matrix-induced autologous chondrocyte implantation (MACI). Outcomes are required to validate the efficacy of MACI as a suitable surgical treatment option for articular cartilage defects in the knee.
A significant improvement in clinical and magnetic resonance imaging-based (MRI-based) outcomes after MACI will exist throughout the postoperative timeline to 5 years after surgery. Furthermore, patient demographics, cartilage defect parameters, and injury/surgery history will be associated with patient and graft outcome, whereas a significant correlation will exist between clinical and MRI-based outcomes at 5 years after surgery.
Case series; Level of evidence, 4.
A prospective evaluation was undertaken to assess clinical and MRI-based outcomes to 5 years in 41 patients (53 grafts) after MACI to the knee. After MACI surgery and a 12-week structured rehabilitation program, patients underwent clinical assessments (Knee injury and Osteoarthritis Outcome Score, SF-36, 6-minute walk test, knee range of motion) and MRI assessments at 3, 12, and 24 months, as well as 5 years after surgery. The MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score.
A significant improvement (P < .05) was demonstrated for all Knee injury and Osteoarthritis Outcome Score and SF-36 subscales over the postoperative timeline, as well as the 6-minute walk test and active knee extension. A significant improvement (P < .0001) was observed for the MRI composite score, as well as several individual graft scoring parameters. At 5 years after surgery, 67% of MACI grafts demonstrated complete infill, whereas 89% demonstrated good to excellent filling of the chondral defect. Patient demographics, cartilage defect parameters, and injury/surgery history demonstrated no significant pertinent correlations with clinical or MRI-based outcomes at 5 years, and no significant correlations existed between clinical and MRI-based outcome measures. At 5 years after surgery, 98% of patients were satisfied with the ability of MACI surgery to relieve knee pain; 86%, with improvement in their ability to perform normal daily tasks; and 73%, with their ability to participate in sport 5 years after MACI.
These results suggest that MACI provides a suitable midterm treatment option for articular cartilage defects in the knee. Long-term follow-up is essential to confirm whether the repair tissue has the durability required to maintain long-term patient quality of life.
Damaged articular cartilage has limited capacity for self-repair. Autologous chondrocyte implantation using a characterized cell therapy product results in significantly better early structural repair as compared with microfracture in patients with symptomatic joint surface defects of the femoral condyles of the knee.
Purpose: To evaluate. clinical outcome at 36 months after characterized chondrocyte implantation (CCI) versus microfracture (MF).
Study Design: Randomized controlled trial; Level of evidence, 1.
Methods: Patients aged 18 to 50 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of the femoral condyles were randomized to CCI (n = 57) or MF (n = 61). Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS). Serial magnetic resonance imaging (MRI) scans were scored using the Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system and 9 additional items. Gene expression profile scores associated with ectopic cartilage formation were determined by RT-PCR.
Results: Baseline mean overall KOOS (+/- SE) was comparable between the CCI and MF groups (56.30 +/- 1.91 vs 59.46 +/- 1.98, respectively). Mean improvement (+/- SE) from baseline to 36 months in overall KOOS was greater in the CCI group than the MF group (21.25 +/- 3.60 vs 15.83 +/- 3.48, respectively), while in a mixed linear model analysis with time as a categorical variable, significant differences favoring CCI were shown in overall KOOS (P = .048) and the subdomains of Pain (P = .044) and QoL (P = .036). More CCI- than MF-treated patients were treatment responders (83% vs 62%, respectively). In patients with symptom onset of
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.
Many different methods of evaluating disability after knee ligament injury exist. Most of them differ in design. Some are based on only patients' symptoms. Other include patients' symptoms, activity grading, performance in a test, and clinical findings. The rating in these evaluating systems can be either numerical, as in a score, or binary, with yes/no answers. Comparison between a symptom-related score and a score of more complex design showed that the symptom-related score gave a more differentiated picture of the disability. It was also shown that the binary rating system gave less detailed information than a score and that differences in a binary rating can depend on at what level the symptoms are regarded as "significant." A new activity grading scale, where work and sport activities were graded numerically, was constructed as complement to the functional score. When evaluating knee ligament injuries, stability testing, functional knee score, performance test, and activity grading are all important. However, the relative importance varies during the course of treatment, and therefore they should not all be included in one and the same score.
There is broad consensus that good outcome measures are needed to distinguish interventions that are effective from those that are not. This task requires standardized, patient-centered measures that can be administered at a low cost. We developed a questionnaire to assess short- and long-term patient-relevant outcomes following knee injury, based on the WOMAC Osteoarthritis Index, a literature review, an expert panel, and a pilot study. The Knee injury and Osteoarthritis Outcome Score (KOOS) is self-administered and assesses five outcomes: pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life. In this clinical study, the KOOS proved reliable, responsive to surgery and physical therapy, and valid for patients undergoing anterior cruciate ligament reconstruction. The KOOS meets basic criteria of outcome measures and can be used to evaluate the course of knee injury and treatment outcome.
The purpose of this study was to analyze the validity of the newly designed functional ability test (FAT) for the normal population and patients with deficiency of the anterior cruciate ligament (ACL). The FAT consists of four tests: the figure-of-eight hop, the up-down hop, the side hop, and the single hop. Sixty control subjects and 50 patients with unilateral ACL deficiency were tested. In the control group, the values measured were significantly different between males and females in all of the tests. On the other hand, when left/right difference values were compared, no significant difference was found between males and females in any of the tests. More than 95% of control group exhibited symmetrical function in each part of the FAT, whereas in the ACL-deficient group, the percentage of patients who showed abnormal symmetry was 68% in the figure-of-eight hop, 58% in the up-down hop, 44% in the side hop, and 42% in the single hop. The percentage of ACL-deficient patients with functional asymmetry in at least one of the four tests was 82%. The FAT was found to be useful in evaluating lower limb function in ACL-deficient patients.
OBJECTIVE: To compare postural stability, single-leg hop, and isokinetic strength measurements in subjects after anterior cruciate ligament (ACL) reconstruction with an age- and activity-matched control group. DESIGN AND SETTING: Subjects reported to a sports medicine/athletic training research laboratory for testing. Subjects reported for one testing session for a total test time of 1 hour. SUBJECTS: Twenty subjects with ACL reconstructions (ACLRs) and 20 age- and activity-matched controls were selected to participate in this study. An arthroscopically assisted central one-third bone-patellar tendon procedure was used to repair the ACLs. MEASUREMENTS: We measured concentric and eccentric peak torque (Nm) measurements of the knee extensors and flexors at 120 degrees and 240 degrees /second on an isokinetic dynamometer. Unilateral and bilateral dynamic postural stability was measured as a stability index in the anterior-posterior and medial-lateral planes with the Biodex Stability System. We tested single-leg hop for distance to measure objective function. RESULTS: We found no significant difference between the ACLR and control subjects for stability index or knee-flexion peak torque scores. On the single-leg hop for distance, the ACLR subjects hopped significantly shorter distances with the involved limb than the uninvolved limb. Furthermore, the ACLR subjects' single-leg hop distance was significantly less when the involved limb was compared with the control-group matched involved limb, and the ACLR subjects performed significantly better when the uninvolved limb was compared with the control-group matched uninvolved limb. The ACLR subjects produced significantly greater torque in the uninvolved leg than in the involved leg. In addition, the peak torque was significantly less for the involved limb in the ACLR group when compared with the matched involved limb of the control group. CONCLUSIONS: After ACLR (mean = 18 +/- 10 months), single-leg hop-for-distance scores and quadriceps strength were not within normal limits when compared with the contralateral limb. Our results suggest that bilateral and single-limb postural stability in the ACLR group was not significantly different than the control group at an average follow-up of 18 months after surgery.
The aim of this study was to investigate the ability of a new hop test to determine functional deficits after anterior cruciate ligament (ACL) reconstruction. The test consists of a pre-exhaustion exercise protocol combined with a single-leg hop. Nineteen male patients with ACL reconstruction (mean time after operation 11 months) who exhibited normal single-leg hop symmetry values (> or =90% compared with the non-involved extremity) were tested for one-repetition maximum (1 RM) strength of a knee-extension exercise. The patients then performed single-leg hops following a standardised pre-exhaustion exercise protocol, which consisted of unilateral weight machine knee-extensions until failure at 50% of 1 RM. Although no patients displayed abnormal hop symmetry when non-fatigued, 68% of the patients showed abnormal hop symmetry for the fatigued test condition. Sixty-three per cent exhibited 1 RM strength scores of below 90% of the non-involved leg. Eighty-four percent of the patients exhibited abnormal symmetry in at least one of the tests. Our findings indicate that patients are not fully rehabilitated 11 months after ACL reconstruction. It is concluded that the pre-exhaustion exercise protocol, combined with the single-leg hop test, improved testing sensitivity when evaluating lower-extremity function after ACL reconstruction. For a more comprehensive evaluation of lower-extremity function after ACL reconstruction, it is therefore suggested that functional testing should be performed both under non-fatigued and fatigued test conditions.
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.
Focal cartilage defects of the knee are a substantial cause of pain and disability in active patients. There has been an emergence of randomized controlled trials evaluating surgical techniques to manage such injuries, including marrow stimulation (MS), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OAT).
A meta-analysis was conducted to determine if any single technique provides superior clinical results at intermediate follow-up.
Systematic review and meta-analysis of randomized controlled trials.
The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched and supplemented with manual searches of PubMed and reference lists. Eligible studies consisted exclusively of randomized controlled trials comparing MS, ACI, or OAT techniques in patients with focal cartilage defects of the knee. The primary outcome of interest was function (Lysholm score, International Knee Documentation Committee score, Knee Osteoarthritis Outcome Score) and pain at 24 months postoperatively. A meta-analysis using standardized mean differences was performed to provide a pooled estimate of effect comparing treatments.
A total of 12 eligible randomized trials with a cumulative sample size of 765 patients (62% males) and a mean (±SD) lesion size of 3.9 ± 1.3 cm(2) were included in this review. There were 5 trials comparing ACI with MS, 3 comparing ACI with OAT, and 3 evaluating different generations of ACI. In a pooled analysis comparing ACI with MS, there was no difference in outcomes at 24-month follow-up for function (standardized mean difference, 0.47 [95% CI, -0.19 to 1.13]; P = .16) or pain (standardized mean difference, -0.13 [95% CI, -0.39 to 0.13]; P = .33). The comparisons of ACI to OAT or between different generations of ACI were not amenable to pooled analysis. Overall, 5 of the 6 trials concluded that there was no significant difference in functional outcomes between ACI and OAT or between generations of ACI.
There is no significant difference between MS, ACI, and OAT in improving function and pain at intermediate-term follow-up. Further randomized trials with long-term outcomes are warranted.
© 2015 The Author(s).
We performed a systematic review of the treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation to determine the differences in patient outcomes after these procedures.
We searched PubMed/Medline, Embase, and The Cochrane Library databases in the period from January 10 through January 20, 2013, and included 34 articles in our qualitative analysis.
All studies showed improvement in outcome scores in comparison with baseline values, regardless of the treatment modality. The heterogeneity of the results presented in the studies precluded a meta-analysis.
Microfracture appears to be effective in smaller lesions and is usually associated with a greater proportion of fibrocartilage production, which may have an effect on durability and eventual failure. Autologous chondrocyte implantation is an effective treatment that may result in a greater proportion of hyaline-like tissue at the repair site, which may in turn have a beneficial effect on durability and failure; it appears to be effective in larger lesions. Autologous chondrocyte implantation with periosteum has been shown to be associated with symptomatic cartilage hypertrophy more frequently than autologous chondrocyte implantation with collagen membrane. Matrix-associated autologous chondrocyte implantation is technically less challenging than the other techniques available, and in lesions greater than 4 cm(2), it has been shown to be more effective than microfracture.
Level IV, systematic review of Level I-IV studies.
Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Context:
Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of knee chondral defects. Despite the reported clinical improvement in knee pain and symptoms, little is known on the recovery of knee strength and its return to an appropriate level compared with the unaffected limb.
Objective:
To investigate the progression of isokinetic knee strength and limb symmetry after MACI.
Design:
Prospective cohort.
Setting:
Private functional rehabilitation facility.
Patients:
58 patients treated with MACI for full-thickness cartilage defects to the femoral condyles.
Intervention:
MACI and a standardized rehabilitation protocol.
Main outcome measures:
Preoperatively and at 1, 2, and 5 y postsurgery, patients underwent a 3-repetition-maximum straight-leg raise test, as well as assessment of isokinetic knee-flexor and -extensor torque and hamstring:quadriceps (H:Q) ratios. Correlation analysis investigated the association between strength and pain, demographics, defect, and surgery characteristics. Linear-regression analysis estimated differences in strength measures between the operated and nonoperated limbs, as well as Limb Symmetry Indexes (LSI) over time.
Results:
Peak knee-extension torque improved significantly over time for both limbs but was significantly lower on the operated limb preoperatively and at 1, 2, and 5 y. Mean LSIs of 77.0%, 83.0%, and 86.5% were observed at 1, 2, and 5 y, respectively, while 53.4-72.4% of patients demonstrated an LSI < or = 90% across the postoperative timeline. Peak knee-flexion torque was significantly lower on the operated limb preoperatively and at 1 year. H:Q ratios were significantly higher on the operated limb at all time points.
Conclusions:
While peak knee-flexion and hip-flexor strength were within normal limits, the majority of patients in this study still demonstrated an LSI for peak knee-extensor strength < or = 90%, even at 5 y. It is unknown how this prolonged knee-extensor deficit may affect long-term graft outcome and risk of reinjury after return to activity.
Purpose
Our purpose was to examine the Level I and II evidence for the use of osteochondral cylinder transfer technique (OCT) for cartilage repair.
Methods
A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that involved OCT were identified. Only Level I and II studies that compared OCT to other modalities of treatment such as microfracture (MF) and autologous chondrocyte implantation (ACI) were selected.
Results
A total of 8 studies matched the selection criteria with 2 Level I and 6 Level II studies. Four studies compared OCT with MF, 3 compared OCT with ACI, and one compared all 3 techniques. Of 3 studies, 4 came from a single center. Mean age of patients ranged from 24 to 33 years, and mean follow-up ranged from 9 to 124 months. The studies from the single center showed superior results from OCT over MF, especially in younger patients, with one study having long-term follow-up of 10 years. They also showed an earlier return to sports. The size of the lesions were small (average < 3 cm2). The 4 other independent studies did not show any difference between OCT and ACI, with one study showing inferior outcome in the OCT group. Magnetic resonance imaging (MRI) showed good osseous integration of the osteochondral plugs to the subchondral bone. Histologic examination showed that there was hyaline cartilage in the transplanted osteochondral plugs but no hyaline cartilage between the plugs.
Conclusions
From the studies of a single center, OCT had an advantage over MF in younger patients with small chondral lesions. Comparison of outcomes between OCT and ACI showed no significant difference in 2 studies and contrasting results in another 2 studies. There was insufficient evidence for long-term results for OCT.
Level of Evidence
Level II, systematic review of Level I and II studies.
The purpose of this study was to examine the Level I and II evidence for newer generations of autologous chondrocyte implantation (ACI) versus first-generation ACI and to establish whether the newer generations have overcome the limitations associated with first-generation ACI.
A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that dealt with ACI were identified. Only Level I and II studies that compared newer generations against earlier generations were selected, whereas studies that compared ACI against other methods of cartilage repair were excluded.
A total of 7 studies matched the selection criteria. Two studies compared periosteum-based autologous chondrocyte implantation (P-ACI) against collagen membrane-based autologous chondrocyte implantation (C-ACI), whereas one study each compared membrane-associated autologous chondrocyte implantation (MACI) against P-ACI and C-ACI. One study on C-ACI compared results related to age, whereas 2 studies evaluated postoperative rehabilitation after MACI. There was weak evidence showing that C-ACI is better than P-ACI and that MACI is comparable with both P-ACI and C-ACI. The weak evidence is because of studies with short durations of follow-up, small numbers of patients, medium-sized defects, and younger age groups. There is good evidence favoring an accelerated weight-bearing regimen after MACI. There is currently no evidence that supports scaffold-based ACI or arthroscopic implantation over first-generation ACI.
The hypothesis is thus partly proved in favor of C-ACI/MACI against P-ACI with weak evidence, in favor of accelerated weight bearing after MACI with strong evidence, and not in favor of arthroscopic and scaffold-based implantations because of unavailable evidence. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.