Article

Two-Year Outcomes of a Randomized Trial Investigating a 6-Week Return to Full Weightbearing After Matrix-Induced Autologous Chondrocyte Implantation

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Abstract

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

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... 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). ...
... There was no significant difference between the two groups at 24 months, nor at 5 years of follow-up. Ebert et al. later performed a trial comparing a 6-week return to full weightbearing with an 8-week return [54]. The groups did not show a statistically significant improvement in their respective integration scores over time, but the mean score of the 6-week group (3.29 ± 0.25) was significantly better compared to that of the 8-week group (2.79 ± 0.23) at 24 months post-operatively. ...
... 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. ...
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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.
... 7-020-06339 -0) contains supplementary material, which is available to authorized users. first stage, followed by culture of the chondrocytes, and finally seeding of the chondrocytes onto a membrane before reimplantation into the cartilage defect [8,33]. ...
... In terms of levels of evidence, five papers were level I (randomized control trials) [8,9,13,16,32], four were level II (cohort studies) [15,20,27,29] and 13 were level IV (case series) [1, 2, 10-12, 14, 17, 21-23, 25, 28, 30]. The papers were assessed using Coleman Methods Criteria [6] for randomized control trials (RCT) and Methodological Items for non-RCT studies (MINORS) [31]. ...
... The 22 articles of the present review included both prospective and retrospective studies comprised a total of 951 patients who underwent morphological MRI assessment at least one time during the observation period. The observation period in each study varied from a minimum of three [8] to a maximum of ten years [1,9] (Table 1). Five papers had only one follow-up and the others had at least two consecutive radiological assessments [1,20,22,23,30]. ...
Article
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Purpose: The purpose of the present article was (1) to systematically review the current literature and (2) to collect data regarding the postoperative magnetic resonance imaging (MRI) appearance of third-generation autologous chondrocyte implantation (ACI) grafts and (3) to provide an overview of imaging findings at various postoperative time points. Methods: A systematic review of the literature in Medline (Pubmed) and Embase was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles which reported the post-operative MRI morphological outcomes following the use of third-generation ACI for treatment of knee cartilage lesions were included. All MRI results were allocated to six different time intervals: ≤ 3 months, > 3-6 months, > 6 months-1 year, > 1 year-2 years, > 2-5 years and > 5 years after surgery. Results: A total of 22 studies were included and the study populations ranged from 13 to 180 patients adding up to a total of 951 patients. Parameters such as defect fill, border integration, surface contour, graft morphology and integrity of the subchondral lamina all improve gradually with a peak two years following surgery suggesting complete graft maturation at this time point. After this peak, a statistically insignificant decline is noted for most of the parameters. Signal intensity was found to gradually shift from hyperintense to isointense in the first 36 months and to hypointense later on. Contrarily, subchondral bone edema is not only a postoperative feature of the procedure but also can reappear or persist up to ten years after surgery. As graft failures can appear after two years, consequently, the MRI composite score is also affected. Conclusion: Recurring patterns in postoperative MRI appearance were observed in certain parameters including defect filling, graft signal intensity and structure, border integration of the graft while parameters like subchondral bone tend to be unpredictable. Given the heterogenous findings in terms of clinical correlation, and relating that aspect to the patterns found in this review, an MRI is justified at three months, one year, two years and five years after surgery, unless the clinical symptomatology and individual patient needs dictate otherwise. Level of evidence: IV.
... Each study [8][9][10][11][12]35,36 used a third-generation MACI product. This procedure is a 2-stage technique in which an arthroscopic approach is first used to harvest a sample of normal articular cartilage from a non-WB region of the knee. ...
... The graft is assessed for stability before the wound is closed. Two studies 8,12 performed the second stage of the MACI procedure either arthroscopically or through miniarthrotomy. In addition to the 2 different MACI techniques, there was also a variety of matrix scaffold types and manufacturers used (Table 1). ...
... Four studies 8,12,35,36 described a 6-week rehabilitation protocol consisting of an initial 2-week period of WB at 20%, followed by a progressive increase to full WB at 6 weeks postoperatively. Five studies [8][9][10][11][12] described an 8-week rehabilitation protocol consisting of a 2-week period of WB at 20%, with a progressive increase to full WB at 8 weeks postoperatively. Two studies 35,36 described a 10-week rehabilitation protocol consisting of toe-touch WB for 4 weeks, followed by partial WB at 20% between weeks 4 and 6, 50% WB between weeks 6 and 8, and full WB by 10 weeks postoperatively. ...
Article
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Background Proper rehabilitation after matrix-associated autologous chondrocyte implantation (MACI) is essential to restore a patient’s normal function without overloading the repair site. Purpose To evaluate the current literature to assess clinical outcomes of MACI in the knee based on postoperative rehabilitation protocols, namely, the time to return to full weightbearing (WB). Study Design Systematic review; Level of evidence, 1. Methods A systematic review was performed to locate studies of level 1 evidence comparing the outcomes of patients who underwent MACI with a 6-week, 8-week, or 10/11-week time period to return to full WB. Patient-reported outcomes assessed included the Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner activity scale, Short Form Health Survey–36 (SF-36), and visual analog scale (VAS) for pain frequency and severity. Results Seven studies met the inclusion criteria, including a total of 136 patients (138 lesions) who underwent MACI. Treatment failure had occurred in 0.0% of patients in the 6-week group, 7.5% in the 8-week group, and 8.3% in the 10/11-week group at a mean follow-up of 2.5 years (P = .46). KOOS, SF-36, and VAS scores in each group improved significantly from preoperatively to follow-up (P < .001). Conclusion Patients undergoing MACI in the knee can be expected to experience improvement in clinical outcomes with the rehabilitation protocols outlined in this work. No significant differences were seen in failure rates based on the time to return to full WB.
... 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. 9,23,25,34,38,39 Several studies have evaluated a variety of early postoperative weightbearing (WB) rehabilitation pathways, 11,14,17,28,48 with 5-year outcomes demonstrating no significant difference with faster WB pathways while also not jeopardizing the tissue repair site. 14,48 Longer term outcomes in these cohorts are required to ensure that early and faster loading regimens do not affect the longer term sustainability of tissue repair. ...
... However, no clinical or MRI-based differences were observed at longer term follow-up, as expected, between patients who followed either of the 2 WB rehabilitation pathways over the first 8 to 12 weeks after surgery. Prior studies, including the earlier reported outcomes of the current study, have evaluated the potential benefit of a faster return to full WB after surgery, 11,14,17,28,48 with 5-year outcomes not demonstrating any significant difference between protocols. However, it is also important to keep in mind that the postoperative loading pathway after ACI (and MACI) has traditionally been very conservative, creating anecdotal patient frustration, together with a further loss in muscle tone and lower limb strength. ...
... Of course, at the onset of the current study, an 8-week return to full WB was considered ''accelerated,'' although studies reporting 6-week protocols have since been reported with success. 11,17,48,49 We acknowledge some limitations in the present study. First, as previously mentioned, the study included patients aged 15 to 65 years and defect sizes that were \2 to 3 cm 2 , inclusion criteria that were reflective of how MACI was being used clinically at the time of study onset. ...
Article
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.
... In the current study, the overall satisfaction rate (81%) is comparable to prior reports though satisfaction scores varied by procedure. In particular, cartilage restoration patients had lower satisfaction scores at the time of rehabilitation completion; this may be related to a longer time interval of up to two years before knee symptoms are maximally improved, 24 , which is substantially longer than the active postoperative rehabilitation period. 24 Ardern et al report a satisfaction rating of 72% after primary ACL reconstruction. ...
... In particular, cartilage restoration patients had lower satisfaction scores at the time of rehabilitation completion; this may be related to a longer time interval of up to two years before knee symptoms are maximally improved, 24 , which is substantially longer than the active postoperative rehabilitation period. 24 Ardern et al report a satisfaction rating of 72% after primary ACL reconstruction. 3 Partial meniscectomy satisfaction has been reported around 83%. 4 Rue et al report cartilage repair/meniscus transplantation satisfaction rate of 71% 25 whereas Cole et al report 77.5% satisfaction after meniscus transplantation. ...
Article
We sought to determine whether individual coping strategies and optimism are associated with satisfaction after sports-related knee surgery at the time of rehabilitation completion and whether the association between coping strategies/optimism and satisfaction varies by surgical procedure or length of rehabilitation. A total of 104 recreational and competitive athletes who underwent knee surgery completed preoperative assessments for intrinsic optimism using the revised Life Orientation Test and coping strategies using the brief Coping Orientations to the Problem Experience inventory. Postoperative assessments at completion of rehabilitation (mean: 5.5-month follow-up.; maximum: 15 months) included satisfaction with surgery, return to prior level of sport, and International Knee Documentation Committee (IKDC-S) symptom scores. Eighty-one percent were satisfied after completion of rehabilitation with a 68% return to prior level of sport. Irrespective of surgical procedure or length of rehabilitation (p > 0.25, all comparisons), greater reliance on others for emotional support as a coping mechanism increased risk of dissatisfaction after surgery (per point: odds ratio [OR]: 1.75; confidence interval [CI]: 1.13–2.92; p = 0.01), whereas greater use of positive reframing as a coping mechanism was protective (per point: OR: 0.43; CI: 0.21–0.82; p = 0.009). Intrinsic optimism was not predictive of postoperative satisfaction (p = 0.71). Satisfied patients had mean 13.5 points higher IKDC-S scores at follow-up than unsatisfied patients (p = 0.001). Patients who returned to prior level of sport had significantly higher satisfaction scores than patients who had not. Irrespective of surgical procedure or length of rehabilitation, use of positive reframing and reliance on others for emotional support are positive and negative predictors, respectively, of satisfaction after sports-related knee surgery. Preoperative optimism is not predictive of postoperative satisfaction.
... The best postoperative rehabilitation protocols are those of 6 weeks, starting the first 2 weeks with a partial load of 20% of body weight, followed by a progressive increase to a full load at 6 weeks postoperatively [67][68][69][70][71][72][73]. ...
Chapter
The joint injury is a common disorder. Some techniques have been employed to repair the joint or regenerate the cartilage defects with different degrees of success. Four commonly performed techniques to preserve the joint included osteotomies, bone marrow stimulation, cartilage repair, and cartilage regeneration.
... A power calculation was performed using G-Power for the primary outcome variable (MRI composite score), demonstrating that 38 patients were required in each group to reveal differences at the 5% significance level, with 90% power and employing an effect size of 0.76 based on previous research. 13 consent before study enrollment and preoperative clinical evaluation, and ethics approval was obtained from the Hollywood Private Hospital (HPH145). ...
Article
Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging clinical results in the treatment of knee chondral defects. However, earlier studies suggested that chondrocyte implantation in the patellofemoral (PF) joint was less effective than in the tibiofemoral (TF) joint. Purpose: To compare the radiological and clinical outcomes of those undergoing MACI to either the femoral condyles or PF joint. Study design: Cohort study; Level of evidence, 3. Methods: A total of 194 patients were included in this analysis, including 127 undergoing MACI to the medial (n = 94) and lateral (n = 33) femoral condyle, as well as 67 to the patella (n = 35) or trochlea (n = 32). All patients were evaluated clinically (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale, Short Form-36) before surgery and at 3, 12, and 24 months after surgery, while magnetic resonance imaging (MRI) was undertaken at 3, 12, and 24 months, with the MOCART (magnetic resonance observation of cartilage repair tissue) scoring system employed to evaluate the quality and quantity of repair tissue, as well as an MRI composite score. Patient satisfaction was evaluated. Results: No significant group differences ( P > .05) were seen in demographics, defect size, prior injury, or surgical history, while the majority of clinical scores were similar preoperatively. All clinical scores significantly improved over time ( P < .05), with a significant group effect observed for KOOS activities of daily living ( P = .008), quality of life ( P = .008), and sport ( P = .017), reflecting better postoperative scores in the TF group. While the PF group had significantly lower values at baseline for the KOOS activities of daily living and quality of life subscales, it actually displayed a similar net improvement over time compared with the TF group. At 24 months, 93.7% (n = 119) and 91.0% (n = 61) of patients were satisfied with the ability of MACI to relieve their knee pain, 74.0% (n = 94) and 65.7% (n = 44) with their ability to participate in sport, and 90.5% (n = 115) and 83.6% (n = 56) satisfied overall, in the TF and PF groups, respectively. MRI evaluation via the MOCART score revealed a significant time effect ( P < .05) for the MRI composite score and graft infill over the 24-month period. While subchondral lamina scored significantly better ( P = .002) in the TF group, subchondral bone scored significantly worse ( P < .001). At 24 months, the overall MRI composite score was classified as good/excellent in 98 TF patients (77%) and 54 PF patients (81%). Conclusion: MACI in the PF joint with concurrent correction of PF maltracking if required leads to similar clinical and radiological outcomes compared with MACI on the femoral condyles.
... Several randomized trials of delayed versus accelerated weight-bearing after MACI have been performed ( Table 3). A randomized trial of 6 week versus 8 week return to full weight bearing found no significant difference in failure rates or symptom improvement at 2 years (interim 12-month results reported in an earlier publication [19]); the study authors concluded accelerated weight bearing after MACI is safe [20]. Another trial of 6 week versus 10 week return to full weight bearing with 5 years follow-up after MACI similarly found no difference in symptom improvement between groups [21]. ...
... This is why frequent two-stage assisted walking without the injured lower limb touching the ground (foot in the air) is not recommended, unless necessary. The negative clinical consequences of underloading the crutches can be even more severe with certain injuries or types of surgery such as noncemented knee or hip prostheses, osteotomy [40,41], or autologous chondrocyte implantation [62]. In such cases, overloading the injured area can lead to further surgery, longer functional recovery times, or other side effects or sequelae, among other drawbacks [42]. ...
Article
Background Measuring weight bearing is an essential aspect of clinical care for lower limb injuries such as sprains or meniscopathy surgeries. This care often involves the use of forearm crutches for partial loads progressing to full loads. Therefore, feasible methods of load monitoring for daily clinical use are needed. Objective The main objective of this study was to design an innovative multifunctional desktop load-measuring software that complements GCH System 2.0–instrumented forearm crutches and monitors the applied loads, displaying real-time graphical and numerical information, and enabling the correction of inaccuracies through feedback technology during assisted gait. The secondary objective was to perform a preliminary implementation trial. Methods The software was designed for indoor use (clinics/laboratories). This software translates the crutch sensor signal in millivolts into force units, records and analyzes data (10-80 Hz), and provides real-time effective curves of the loads exerted on crutches. It covers numerous types of extrinsic feedback, including visual, acoustic (verbal/beeps), concurrent, terminal, and descriptive feedback, and includes a clinical and research use database. An observational descriptive pilot study was performed with 10 healthy subjects experienced in bilateral assisted gait. The Wilcoxon matched-pairs signed-rank test was used to evaluate the load accuracy evolution of each subject (ie, changes in the loads exerted on crutches for each support) among various walks, which was interpreted at the 95% confidence level. Results GCH Control Software was developed as a multifunctional desktop tool complementing GCH System 2.0–instrumented forearm crutches. The pilot implementation of the feedback mechanism observed 96/100 load errors at baseline (walk 0, no feedback) with 7/10 subjects exhibiting crutch overloading. Errors ranged from 61.09% to 203.98%, demonstrating heterogeneity. The double-bar feedback found 54/100 errors in walk 1, 28/100 in walk 2, and 14/100 in walk 3. The first walk with double-bar feedback (walk 1) began with errors similar to the baseline walk, generally followed by attempts at correction. The Wilcoxon matched-pairs signed-rank test used to evaluate each subject’s progress showed that all participants steadily improved the accuracy of the loads applied to the crutches. In particular, Subject 9 required extra feedback with two single-bar walks to focus on the total load. The participants also corrected the load balance between crutches and fluency errors. Three subjects made one error of load balance and one subject made six fluctuation errors during the three double-bar walks. The latter subject performed additional feedback with two balance-bar walks to focus on the load balance. Conclusions GCH Control Software proved to be useful for monitoring the loads exerted on forearm crutches, providing a variety of feedback for correcting load accuracy, load balance between crutches, and fluency. The findings of the complementary implementation were satisfactory, although clinical trials with larger samples are needed to assess the efficacy of the different feedback mechanisms and to select the best alternatives in each case.
... The best postoperative rehabilitation protocols are those of 6 weeks, starting the first 2 weeks with a partial load of 20% of body weight, followed by a progressive increase to a full load at 6 weeks postoperatively [67][68][69][70][71][72][73]. ...
Chapter
Full-text available
The joint injury is a common disorder. Some techniques have been employed to repair the joint or regenerate the cartilage defects with different degrees of success. Four commonly performed techniques to preserve the joint included osteotomies, bone marrow stimulation, cartilage repair, and cartilage regeneration.
... 28,34 Similar to ACL repair, accelerated rehabilitation after cartilage surgery may be safe and tends to suggest improved outcomes. [12][13][14][15][16][17]28 In direct comparisons of different weightbearing protocols after matrixinduced autologous chondrocyte implantation, accelerated weightbearing resulted in improvements in pain and function compared with traditional rehabilitation protocols, with no increased risk of graft delamination or failure. [13][14][15][16][17] Similarly, equivalent cartilage repair resulted from NWB and WBAT protocols after osteochondral autograft transfer during second-look knee arthroscopy. ...
Article
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Context: We present the current spectrum of postoperative management practices for patients receiving distal femur osteochondral allograft (OCA) transplants. Evidence acquisition: The Joint Restoration Foundation database was examined in cooperation with the Metrics of Osteochondral Allografts study group to identify 121 surgeons who had performed at least 1 OCA transplant in the past year; 63% of surgeons responded. Study design: Clinical survey. Level of evidence: Level 3. Results: Postoperative weightbearing restrictions ranged from immediate nonweightbearing with full weightbearing by 12 weeks to immediate weightbearing as tolerated. Most surgeons who performed fewer (<10) OCA transplants per year followed the most restrictive protocol, while surgeons who performed more (>20) OCA transplants per year followed the least restrictive protocol. One-third of surgeons with the most restrictive protocol were more likely to change their protocol to be less restrictive over time, while none of those with the least restrictive protocol changed their protocol over time. Fifty-five percent of surgeons permitted return to full activity at 26 weeks, while 27% of surgeons lifted restrictions at 16 weeks. Conclusion: Characterization of the spectrum of postoperative management practices after OCA transplantation provides a foundation for future investigations regarding patient outcomes and associated cost to establish best practice guidelines. Fundamentally, surgeons with more experience with this procedure tended to be more aggressive with their postoperative rehabilitation guidelines. Most commonly, rehabilitation provided for some degree of limited weightbearing; however, the spectrum also included immediate full weightbearing practices.
... The studies on ACI do, however, report longer wait times before resumption of full WB status. However, Ebert et al. 24 found in a randomized controlled trial that it was safe to resume full WB at 6 weeks compared with at 8 weeks. They used this as the literature standard and found no significant difference at 2-year follow-up. ...
Article
Objective The purpose of this study is to systematically review the literature and to evaluate the reported rehabilitation protocols, return-to-play guidelines, and subsequent rates of return to play following cartilage restoration procedures in the knee. Design MEDLINE, EMBASE, and the Cochrane Library were searched according to the PRISMA guidelines to find studies on cartilage restoration procedures in the knee, including (1) microfracture (Mfx), (2) osteochondral autograft transfer (AOT), (3) osteochondral allograft implantation (OCA), and (4) autologous chondrocyte implantation (ACI). Studies were included if they reported return-to-play data or rehabilitation protocols. Results Overall, 179 studies fit our inclusion criteria, with 48 on Mfx, 34 on AOT, 54 on OCA, and 51 on ACI. The rate of return to play was reported as high as 88.2% with AOT, and as low as 77.2% following OCA, with rates of return to play at the same/higher level as high as 79.3% with AOT, and as low as 57.3% following ACI. The average reported time of return to play was as low as 4.9 months with AOT, and as high as 11.6 months following ACI. Conclusions The majority of patients are able to return to play following cartilage restoration procedures in the knee, regardless of surgical procedure utilized. However, while the rate of return to play at the same level was similar to the overall rate of return following AOT, there was a large number of patients unable to return to the same level following Mfx, OCA, and ACI. Additionally, there is wide variety in the rehabilitation protocols, and scant literature on return-to-play protocols.
... The gold standard cell therapy for cartilage restoration at this time remains autologous chondrocyte implantation (ACI), wherein autologous chondrocytes are harvested, culture-expanded in vitro, and then subsequently re-implanted into the cartilage defect in a two-stage procedure [6,7]. However, ACI has practical limitations including the need for autologous harvest and indications limited to unifocal, pre-arthritic defects [8]. ...
Article
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Purpose of review: To review the current basic science and clinical literature on mesenchymal stem cell (MSC) therapy for articular cartilage defects and osteoarthritis of the knee. Recent findings: MSCs derived from bone marrow, adipose, and umbilical tissue have the capacity for self-renewal and differentiation into the chondrocyte lineage. In theory, MSC therapy may help restore cartilage focally or diffusely where nascent regenerative potential in the intra-articular environment is limited. Over the last several years, in vitro and animal studies have elucidated the use of MSCs in isolation as injectables, in combination with biological delivery media and scaffolding, and as surgical adjuvants for cartilage regeneration and treatment of knee degenerative conditions. More recently, clinical and translational literature has grown more convincing from early descriptive case series to randomized controlled trials showing promise in efficacy and safety. Studies describing MSC for knee cartilage regeneration applications are numerous and varied in quality. Future research directions should include work on elucidating optimal cell concentration and dosing, as well as standardization in methodology and reporting in prospective trials. Backed by promise from in vitro and animal studies, preliminary clinical evidence on MSC therapy shows promise as a nonoperative therapeutic option or an adjuvant to existing surgical cartilage restoration techniques. While higher quality evidence to support MSC therapy has emerged over the last several years, further refinement of methodology will be necessary to support its routine clinical use.
... 6 Other randomized controlled trials showed a comparable 5-year failure rate of 14% for characterized chondrocyte implantation (ACI) and 2.5% to 10% for matrix-induced ACI at 5 and 10 years, respectively. 13,14,30 Radiographic signs of osteoarthritis were found after ACI in 8% to 30% of patients. 16,30 Graft failure characteristics, including subchondral bone status, were not provided for these clinical trials. ...
Article
Background: Long-term clinical evaluation of patient outcomes can steer treatment choices and further research for cartilage repair. Using mesenchymal stromal cells (MSCs) as signaling cells instead of stem cells is a novel approach in the field. Purpose: To report the 5-year follow-up of safety, clinical efficacy, and durability after treatment of symptomatic cartilage defects in the knee with allogenic MSCs mixed with recycled autologous chondrons in first-in-human study of 1-stage cartilage repair. Study design: Case series; Level of evidence, 4. Methods: This study is an investigator-driven study aiming at the feasibility and safety of this innovative cartilage repair procedure. Between 2013 and 2014, a total of 35 patients (mean ± SD age, 36 ± 8 years) were treated with a 1-stage cartilage repair procedure called IMPACT (Instant MSC Product Accompanying Autologous Chondron Transplantation) for a symptomatic cartilage defect on the femoral condyle or trochlear groove. Subsequent follow-up after initial publication was performed annually using online patient-reported outcome measures with a mean follow-up of 61 months (range, 56-71 months). Patient-reported outcome measures included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain, and EuroQol-5 Dimensions. All clinical data and serious adverse events, including additional treatment received after IMPACT, were recorded. A failure of IMPACT was defined as a chondral defect of at least 20% of the index lesion with a need for a reintervention including a surgical procedure or an intra-articular injection. Results: Using allogenic MSCs, no signs of a foreign body response or serious adverse reactions were recorded after 5 years. The majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline to 60 months: overall, 57.9 ± 16.3 to 78.9 ± 17.7 (P < .001); Pain, 62.3 ± 18.9 to 79.9 ± 20.0 (P = .03); Function, 61.6 ± 16.5 to 79.4 ± 17.3 (P = .01); Activities of Daily Living, 69.0 ± 19.0 to 89.9 ± 14.9 (P < .001); Sports and Recreation, 32.3 ± 22.6 to 57.5 ± 30.0 (P = .02); and Quality of Life, 25.9 ± 12.9 to 55.8 ± 26.8 (P < .001). The visual analog scale score for pain improved significantly from baseline (45.3 ± 23.6) to 60 months (15.4 ± 13.4) (P < .001). Five cases required reintervention. Conclusion: This is the first study showing the midterm safety and efficacy of the proof of concept that allogenic MSCs augment 1-stage articular cartilage repair. The absence of serious adverse events and the clinical outcome support the longevity of this unique concept. These data support MSC-augmented chondron transplantation (IMPACT) as a safe 1-stage surgical solution that is considerably more cost-effective and a logistically advantageous alternative to conventional 2-stage cell-based therapy for articular chondral defects in the knee.
Article
Objective Though multiple high-level comparative studies have been performed for matrix-assisted autologous chondrocyte transplantation (MACT), quantitative reviews synthesizing best-available clinical evidence on the topic are lacking. Design A meta-analysis was performed of prospective randomized or nonrandomized comparative studies utilizing MACT. A total of 13 studies reporting 13 prospective trials (9 randomized, 5 nonrandomized) were included (658 total study participants at weighted mean 3.1 years follow-up, range 1-7.5 years). Results Reporting and methodological quality was moderate according to mean Coleman (59.4 SD 7.6), Delphi (3.0 SD 2.1), and MINORS (Methodological Index For Non-Randomized Studies) scores (20.2 SD 1.6). There was no evidence of small study or reporting bias. Effect sizes were not correlated with reporting quality, financial conflict of interest, sample size, year of publication, or length of follow-up ( P > 0.05). Compared to microfracture, MACT had greater improvement in International Knee Documentation Committee (IKDC)-subjective and Knee Injury and Osteoarthritis Outcome Pain Subscale Score (KOOS)-pain scores in randomized studies ( P < 0.05). Accelerated weight-bearing protocols (6 or 8 weeks) resulted in greater improvements in IKDC-subjective and KOOS-pain scores than standard protocols (8 or 11 weeks) for MACT in randomized studies ( P < 0.05) with insufficient nonrandomized studies for pooled analysis. Conclusions Compared to microfracture, MACT has no increased risk of clinical failure and superior improvement in patient-reported outcome scores. Compared to MACT with standardized postoperative weight-bearing protocols, accelerated weight-bearing protocols have no increased risk of clinical failure and show superior improvement in patient-reported outcome scores. There is limited evidence regarding MACT compared to first-generation autologous chondrocyte implantation, mosaicplasty, and mesenchymal stem cell therapy without compelling differences in outcomes.
Article
Background: Multiple cartilage repair techniques are available for chondral defects in the knee. Optimal treatment is controversial. Purpose: To evaluate change from baseline in the 5 Knee injury and Osteoarthritis Outcome Score (KOOS) subscales among different cartilage repair techniques of the knee. Study design: Systematic review and meta-analysis; Level of evidence, 1A. Methods: Medline and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for randomized controlled trials with minimum 1 year follow-up reporting change from baseline KOOS (delta KOOS) subscale values. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. A meta-analysis was performed on the following surgery types: microfracture (Mfx); augmented microfracture techniques (Mfx+Augment); and culture-based therapies, including autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI). A random-effects metaregression model was used. Results: A total of 14 randomized trials with a total of 775 patients were included. The KOOS Sport and Recreation (Sport) and KOOS Quality of Life (QOL) were the 2 most responsive subscales after operative intervention. Outcomes from Mfx and Mfx+Augment were not different in any of the 5 KOOS subscales (minimum P > .3). The mean delta KOOS Sport after ACI/MACI was 9.9 points greater than after Mfx (P = .021) and 11.7 points greater than after Mfx+Augment (P = .027). Longer follow-up time correlated with greater delta KOOS Sport (P = .028). Larger body mass index led to greater delta KOOS QOL (P = .045). Larger cartilage defect size correlated with greater delta KOOS Pain and KOOS Activities of Daily Living scores (P = .023 and P = .002, respectively). Conclusion: The KOOS Sport and QOL were the most responsive subscales after cartilage restoration surgery of the knee. Culture-based therapies (ACI/MACI) led to clinically relevant improvements in the KOOS Sport score compared with marrow stimulation and may be a more appropriate treatment in younger and more active individuals. There were no benefits to Mfx+Augment over Mfx alone in any of the KOOS subscales.
Article
Retraction: ‘GABARAP promotes bone marrow mesenchymal stem cells‐based the osteoarthritis cartilage regeneration through the inhibition of PI3K/AKT/mTOR signaling pathway’, by Zhengyuan Wu, Huiping Lu, Jun Yao, Xiaohan Zhang, Yimei Huang, Shiting Ma, Kai Zou, Yan Wei, Zhengyi Yang, Jia Li, Jinmin Zhao, J Cell Physiol. 2019; 21014‐21026: The above article, published online on 24 April 2019 in Wiley Online Library (https://doi.org/10.1002/jcp.28705), has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. The authors confirmed that the original figures are flawed and were not able to provide original raw data. Accordingly, the conclusions of this article are considered invalid. All the authors agree with the retraction.
Article
Background Osteochondral (OC) repair presents a significant challenge to clinicians. However, whether the use of acellular spongy poly(lactic-co-glycolic acid) (PLGA) scaffolding plus treadmill exercise as a rehabilitation program regenerates OC defects in a large-animal model has yet to be determined. Hypothesis PLGA scaffolding plus treadmill exercise may offer improved OC repair for both high and low weightbearing regions in a minipig model. Study Design Controlled laboratory study. Methods A total of 9 mature minipigs (18 knees) were randomly divided into the treadmill exercise (TRE) group or sedentary (SED) group. All pigs received critically sized OC defects in a higher weightbearing region of the medial condyle and a lower weightbearing region of the trochlear groove. In each minipig, a PLGA scaffold was placed in the defect of the right knee (PLGA subgroup), and the defect of the left knee was untreated (empty defect [ED] subgroup). The TRE group performed exercises in 3 phases: warm-up, 3 km/h for 5 minutes; main exercise, 4 km/h for 20 minutes; and cool-down, 3 km/h for 5 minutes. The total duration was about 30 minutes whenever possible. The SED group was allowed free cage activity. Results At 6 months, the TRE-PLGA group showed the highest gross morphology scores and regenerated a smooth articular surface covered with new hyaline-like tissue, while the defects of the other groups remained and contained nontransparent tissue. Histologically, the TRE-PLGA group also revealed sound OC integration, chondrocyte-like cells embedded in lacunae, abundant glycosaminoglycans, a sound collagen structure, and modest inflammatory cells with an inflammatory response (ie, tumor necrosis factor–α, interleukin-6). In addition, in the medial condyle region, the TRE-PLGA group (31.80 ± 3.03) had the highest total histological scores (TRE-ED: 20.20 ± 5.76; SED-PLGA: 10.25 ± 6.24; SED-ED: 11.75 ± 6.50; P = .004). In the trochlear groove region, the TRE-PLGA group (30.20 ± 6.42) displayed significantly higher total histological scores (TRE-ED: 19.60 ± 7.00; SED-PLGA: 10.00 ± 5.42; SED-ED: 11.25 ± 5.25; P = .006). In contrast, the SED-PLGA and SED-ED groups revealed an irregular surface with abrasion, fibrotic tissue with an empty void and inflammatory cells, disorganized collagen fibers, and less glycosaminoglycan deposition. Micro–computed tomography analysis revealed that the TRE-PLGA group had integrated OC interfaces with continued remodeling in the subchondral bone. Furthermore, comparing the 2 defect regions, no statistically significant differences in cartilage regeneration were detected, indicating the suitability of this regenerative approach for both high and low weightbearing regions. Conclusion Implanting an acellular PLGA scaffold plus treadmill exercise promoted articular cartilage regeneration for both high and low weightbearing regions in minipigs. Clinical Relevance This study suggests the use of a cell-free porous PLGA scaffold and treadmill exercise rehabilitation as an alternative therapeutic strategy for OC repair in a large-animal knee joint model. This combined effect may pave the way for biomaterials and exercise regimens in the application of OC repair.
Article
Objective: To summarize the research progress of rehabilitation after autologous chondrocyte implantation (ACI). Methods: The literature related to basic science and clinical practice about rehabilitation after ACI in recent years was searched, selected, and analyzed. Results: Based on the included literature, the progress of the graft maturation consists of proliferation phase (0-6 weeks), transition phase (6-12 weeks), remodeling phase (12-26 weeks), and maturation phase (26 weeks-2 years). To achieve early protection, stimulate the maturation, and promote the graft-bone integrity, rehabilitation protocol ought to be based on the biomechanical properties at different phases. Weight-bearing program, range of motion (ROM), and options or facilities of exercise are importance when considering a rehabilitation program. Conclusion: It has been proved that the patients need a program with an increasingly progressive weight-bearing and ROM in principles of rehabilitation after ACI. Specific facilities can be taken at a certain phase. Evidences extracted in the present work are rather low and the high-quality and controlled trials still need to improve the rehabilitation protocol.
Chapter
“When can I get back to sports?” One of the first questions an athlete asks after sustaining an articular cartilage injury of the knee. The answer to this question can be challenging as return-to-sport (RTS) is affected by multiple factors. Cartilage repair procedures such as microfracture, chondrocyte implantation, and osteochondral autograft and allograft have reported high percentages of athletes with good outcomes scores and the ability to return to sports. However, beside return to sports, the level of return as well as continued sports participation after return has to be considered when evaluating what technique to recommend for an athlete. Using available scientific data and an individualized approach that includes athlete-specific factors such as age, lesion characteristics, associated injuries, type of sports, and level of competition can help to optimize the long-term outcome in the athletic population. This chapter presents the growing body of literature focusing on the rate of returning athletes back to their sports after articular cartilage repair in the knee and discusses the relevant variations in surgical techniques and rehabilitation for each procedure.
Article
Purpose Anterior cruciate ligament (ACL) rupture commonly occurs in conjunction with articular cartilage injury. However, there is no consensus on the most appropriate rehabilitation which should be carried out for ACL reconstruction (ACLR) and the surgical management of articular cartilage lesions of the knee. The purpose of this study was to systematically review the literature to investigate the recommended rehabilitation protocol for patients undergoing ACLR with concomitant articular cartilage injury with a view to develop guidelines on the most appropriate treatment. Methods Two reviewers independently searched five database for randomised controlled trials (RCTs), non-randomised comparative and retrospective cohort studies (CS) describing the management of concomitant ACL rupture and articular cartilage injury and the postoperative rehabilitation regimen. Risk of bias was performed using a modified Downs & Black’s checklist. The primary outcome was specific rehabilitation protocols including weight-bearing status, immobilisation, continuous passive motion (CPM), and return to play criteria. Secondary outcomes included patient-reported outcomes. A best evidence synthesis was performed. Results The review yielded six studies which reported on rehabilitation techniques. All studies were of low methodological quality. There was considerable variability in not only the chondral lesion reported but also the treatment techniques utilised and especially the rehabilitation regimes. No consensus was found on weight-bearing status, postoperative immobilisation, the use of CPM, or return to play criteria. Given the quality of the papers, there was no evidence to recommend any specific rehabilitation regime in the postoperative management of concomitant ACLR and articular cartilage lesions. Conclusion This systematic review revealed that despite how common concomitant ACL rupture and articular cartilage injury is, there is no evidence to support one, most appropriate rehabilitation protocol. From a clinical perspective, decisions on postoperative rehabilitation for patients undergoing ACLR and treatment of articular cartilage lesions should be made on a case-by-case basis with criteria-based progression until more robust evidence becomes available. A list of specific rehabilitation protocols based on the cartilage restoration technique is provided. Level of evidence IV.
Article
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.
Article
Objective Large articular cartilage defects are a challenge to regenerative surgery. Biomaterial scaffolds might provide valuable support for restoration of articulating surface. The performance of a composite biomaterial scaffold was evaluated in a large porcine cartilage defect. Design Cartilage repair capacity of a biomaterial combining recombinant human type III collagen (rhCo) and poly-(l/d)-lactide (PLA) was tested in a porcine model. A full-thickness chondral defect covering the majority of the weightbearing area was inflicted to the medial femoral condyle of the right knee. Spontaneous cartilage repair and nonoperated healthy animals served as controls. The animals were sacrificed after a 4-month follow-up. The repair tissue was evaluated with the International Cartilage Repair Society (ICRS) macroscopic score, ICRS II histological score, and with micro-computed tomography. Additionally, histopathological evaluation of lymph nodes and synovial samples were done for toxicological analyses. Results The lateral half of the cartilage defect in the operated groups showed better filling than the medial half. The mean overall macroscopic score for the rhCo-PLA, spontaneous, and nonoperated groups were 5.96 ± 0.33, 4.63 ± 0.42, and 10.98 ± 0.35, respectively. The overall histological appearance of the specimens was predominantly hyaline cartilage in 3 of 9 samples of the rhCo-PLA group, 2 of 8 of the spontaneous group, and 9 of 9 of the nonoperated group. Conclusions The use of rhCo-PLA scaffold did not differ from spontaneous healing. The repair was affected by the spatial properties within the defect, as the lateral part of the defect showed better repair than the medial part, probably due to different weightbearing conditions.
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Background: Long-term effects of different weightbearing (WB) modalities after matrix-associated autologous chondrocyte implantation (MACI) on changes in knee articular cartilage and clinical outcomes are needed to establish more evidence-based recommendations for postoperative rehabilitation. Hypothesis: There will be no differences between accelerated WB compared with delayed WB regarding knee articular cartilage or patient self-reported knee function or activity level 5 years after MACI. Furthermore, significant correlations between magnetic resonance imaging (MRI)-based outcomes and patient-reported outcome measures 5 years postoperatively will exist. Study design: Randomized controlled trial; Level of evidence, 1. Methods: After MACI, 31 patients (23 male, 8 female) were randomly assigned to the accelerated WB group (AWB group) or to the delayed WB group (DWB group). With the exception of time and increase to full WB, both groups underwent the same rehabilitation program. The AWB group was allowed full WB after 6 weeks and the DWB group after 10 weeks. Assessments were performed 3 months, 2 years, and 5 years postoperatively, but this long-term follow-up study only included changes from 2 to 5 years postoperatively. The magnetic resonance observation of cartilage repair tissue (MOCART) score (primary outcome), the MRI-based variables of bone edema and effusion, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Tegner scale were included. In addition, the association between MRI-based outcomes and the KOOS at 5 years postoperatively was investigated. Results: There was a significant decrease in the MOCART score and a significant increase in bone edema 2 and 5 years postoperatively but no significant group differences. The only significant correlation between the MRI-based variables and the KOOS was found for bone edema and the KOOS subscale of pain (r=-0.435, P<.05) at 5-year follow-up. Conclusion: There were no significant differences in the MRI-based or clinical outcomes between the AWB group and DWB group 5 years after MACI. While the clinical outcomes remained stable, a decline of the MRI-based findings was observed between 2 and 5 years postoperatively. Furthermore, a significant association between bone edema and pain was found. No occurrence of unintended effects was observed.
Article
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To determine the safety and efficacy of "accelerated" postoperative load-bearing rehabilitation following matrix-induced autologous chondrocyte implantation (MACI). A randomized controlled study design was used to investigate clinical outcomes in 70 patients following MACI, in conjunction with either accelerated or traditional approaches to postoperative weight-bearing (WB) rehabilitation. Both interventions sought to protect the implant for an initial period and then incrementally increase WB. Under the accelerated protocol, patients reached full WB at 8 weeks postsurgery, compared to 11 weeks for the traditional group. Clinical outcomes were assessed presurgery and at 3, 6, 12, and 24 months postsurgery. A significant effect (P < 0.017) for time existed for all clinical measures, demonstrating improvement up to 24 months in both groups. A significant interaction effect (P < 0.017) existed for pain severity and the 6-minute walk test, with accelerated group patients reporting significantly less severe pain and demonstrating superior 6-minute walk distance over the period. Although there was a significant group effect (P < 0.017) for maximal active knee extension range in favor of the accelerated regime, no further significant differences existed. There was no incidence of graft delamination up to 24 months that resulted directly from the 3-month postoperative rehabilitation program. The accelerated load-bearing approach that reduced the length of time spent ambulating on crutches produced comparable if not superior clinical outcomes up to 24 months postsurgery in the accelerated rehabilitation group, without compromising graft integrity. This accelerated regime is safe and effective and demonstrates a faster return to normal function postsurgery.
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To assess the safety and efficacy of accelerated compared with traditional postoperative weightbearing (WB) rehabilitation following matrix-induced autologous chondrocyte implantation (MACI) of the knee, using MRI. A randomized controlled study design was used to assess MRI-based outcomes of MACI grafts in 70 patients (45 men, 25 women) who underwent MACI to the medial or lateral femoral condyle, in combination with either traditional or accelerated approaches to postoperative WB rehabilitation. High-resolution MRI was undertaken and assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score at 3, 12, and 24 months postsurgery. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/surgery history was investigated. Both groups significantly improved (P < 0.05) in the MRI composite score and pertinent descriptors of graft repair throughout the postoperative period until 24 months postsurgery. There were no differences (P > 0.05) observed between the 2 groups. Patient age, body mass index, chondral defect size, and duration of preoperative symptoms were significantly correlated (P < 0.05) with several MRI-based outcomes at 24 months, whereas there were no significant pertinent correlations (P > 0.05) observed between clinical and MRI-based outcomes. The accelerated WB approach was not detrimental to graft development at any stage throughout the postoperative assessment timeline from baseline to 24 months postsurgery and may potentially accelerate patient return to normal function, while reducing postoperative muscle loss, intra-articular adhesions, and associated gait abnormalities.
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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.
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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.
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Articular cartilage injury is observed with increasing frequency in both elite and amateur athletes and results from the significant acute and chronic joint stress associated with impact sports. Left untreated, articular cartilage defects can lead to chronic joint degeneration and athletic and functional disability. Treatment of articular cartilage defects in the athletic population presents a therapeutic challenge due to the high mechanical demands of athletic activity. Several articular cartilage repair techniques have been shown to successfully restore articular cartilage surfaces and allow athletes to return to high-impact sports. Postoperative rehabilitation is a critical component of the treatment process for athletic articular cartilage injury and should take into consideration the biology of the cartilage repair technique, cartilage defect characteristics, and each athlete's sport-specific demands to optimize functional outcome. Systematic, stepwise rehabilitation with criteria-based progression is recommended for an individualized rehabilitation of each athlete not only to achieve initial return to sport at the preinjury level but also to continue sports participation and reduce risk for reinjury or joint degeneration under the high mechanical demands of athletic activity.
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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.
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Autologous chondrocyte implantation for treatment of isolated cartilage defects of the knee has become well established. Although various publications report technical modifications, clinical results, and cell-related issues, little is known about appropriate and optimal rehabilitation after autologous chondrocyte implantation. This article reviews the literature on rehabilitation after autologous chondrocyte implantation and presents a rehabilitation protocol that has been developed considering the best available evidence and has been successfully used for several years in a large number of patients who underwent autologous chondrocyte implantation for cartilage defects of the knee.
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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.
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Despite improvement in treatment for articular cartilage lesions, prolonged recovery still precludes early return to competitive sports. The challenge of postoperative rehabilitation is to optimize return to preinjury activities without jeopardizing the graft. Intensive rehabilitation after second-generation arthroscopic autologous cartilage implantation (Hyalograft C) facilitates graft maturation and safely allows for early return to competition without jeopardizing clinical outcome at longer follow-up. Cohort study; Level of evidence, 3. The outcome of 31 competitive male athletes with International Cartilage Repair Society grade III-IV cartilaginous lesions of the medial or lateral femoral condyle or trochlea were evaluated at 1-, 2-, and 5-year follow-up. The athletic cohort was compared with a similar control cohort of 34 nonathletic patients who were treated with autologous chondrocyte implantation. The athletic cohort followed a 4-phase intensive rehabilitation protocol. Eleven of the patients in this cohort were also treated with an isokinetic exercise program and on-field rehabilitation. The patients in the control cohort completed only phase 1 of rehabilitation. When comparing the 2 groups, a greater improvement in the group of athletes was achieved at 5-year follow-up (P = .037) in the self-assessment of quality of life and International Knee Documentation Committee subjective evaluation at 12 months and at 5 years of follow-up (P = .001 and P = .002, respectively). When analyzing the return to sports activity, 80.6% of the athletes returned to their previous activity level in 12.4 +/- 1.6 months; athletes treated with the on-field rehabilitation and isokinetic exercise program had faster recovery and an even earlier return to competition (10.6 +/- 2.0 months). For optimal results, autologous chondrocyte implantation rehabilitation should not only follow but also facilitate the process of graft maturation. Intensive rehabilitation may safely allow a faster return to competition and also influence positively the clinical outcome at medium-term follow-up.
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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
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Patellofemoral lesions represent a very troublesome condition to treat for orthopaedic surgeons; however, second-generation autologous chondrocyte implantation (ACI) seems to offer an interesting treatment option with satisfactory results at short-term follow-up. Hyaluronan-based scaffold seeded with autologous chondrocytes is a viable treatment for the damaged articular surface of the patellofemoral joint. Case series; Level of evidence, 4. Among a group of 38 patients treated for full-thickness patellofemoral chondral lesions with second-generation ACI, we investigated 34 who were available for final follow-up at 5 years. These 34 had chondral lesions with a mean size of 4.45 cm(2). Twenty-one lesions were located on the patella, 9 on the trochlea, and 4 patients had multiple lesions: 3 had patellar and trochlear lesions, and 1 had patellar and lateral femoral condyle lesions. Twenty-six lesions (76.47%) were classified as International Cartilage Repair Society (ICRS) grade IV A or B, 5 lesions (14.70%) were grade IIIC, and 3 (8.82%) were lesions secondary to osteochondritis dissecans (OCD). Results were evaluated using the International Knee Documentation Committee (IKDC) 2000 subjective and objective scores, EuroQol (EQ) visual analog scale (VAS), and Tegner scores at 2 and 5 years. Eight patients had second-look arthroscopy and biopsies. All the scores used demonstrated a statistically significant improvement (P < .0005) at 2 and 5 years' follow-up. Objective preoperative data improved from 8 of 34 (23.52%) normal or nearly normal knees to 32 of 34 (94.12%) at 2 years and 31 of 34 (91.17%) at 5 years after transplantation. Mean subjective scores improved from 46.09 points preoperatively to 77.06 points 2 years after implantation and 70.39 at 5 years. The Tegner score improved from 2.56 to 4.94 and 4.68, and the EQ VAS improved from 56.76 to 81.47 and 78.23 at 2 and 5 years' follow-up, respectively. A significant decline of IKDC subjective and Tegner scores was found in patients with multiple and patellar lesions from 2 to 5 years' follow-up. Second-look arthroscopies in 8 cases revealed the repaired surface to be nearly normal with biopsy samples characterized as hyaline-like in appearance. Hyaluronan-based scaffold seeded with autologous chondrocytes can be a viable treatment for patellofemoral chondral lesions.
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This study focuses on the effect of static and dynamic mechanical compression on the biosynthetic activity of chondrocytes cultured within agarose gel. Chondrocyte/agarose disks (3 mm diameter) were placed between impermeable platens and subjected to uniaxial unconfined compression at various times in culture (2-43 days). [35S]sulfate and [3H]proline radiolabel incorporation were used as measures of proteoglycan and protein synthesis, respectively. Graded levels of static compression (up to 50%) produced little or no change in biosynthesis at very early times, but resulted in significant decreases in synthesis with increasing compression amplitude at later times in culture; the latter observation was qualitatively similar to that seen in intact cartilage explants. Dynamic compression of approximately 3% dynamic strain amplitude (approximately equal to 30 microns displacement amplitude) at 0.01-1.0 Hz, superimposed on a static offset compression, stimulated radiolabel incorporation by an amount that increased with time in culture prior to loading as more matrix was deposited around and near the cells. This stimulation was also similar to that observed in cartilage explants. The presence of greater matrix content at later times in culture also created differences in biosynthetic response at the center versus near the periphery of the 3 mm chondrocyte/agarose disks. The fact that chondrocyte response to static compression was significantly affected by the presence or absence of matrix, as were the physical properties of the disks, suggested that cell-matrix interactions (e.g. mechanical and/or receptor mediated) and extracellular physicochemical effects (increased [Na+], reduced pH) may be more important than matrix-independent cell deformation and transport limitations in determining the biosynthetic response to static compression. For dynamic compression, fluid flow, streaming potentials, and cell-matrix interactions appeared to be more significant as stimuli than the small increase in fluid pressure, altered molecular transport, and matrix-independent cell deformation. The qualitative similarity in the biosynthetic response to mechanical compression of chondrocytes cultured in agarose gel and chondrocytes in intact cartilage further indicates that gel culture preserves certain physiological features of chondrocyte behavior and can be used to investigate chondrocyte response to physical and chemical stimuli in a controlled manner.
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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.
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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.
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As part of a program of research aimed at determining the role of mechanical forces in connective tissue differentiation, we have developed a model for investigating the effects of dynamic compressive loading on chondrocyte differentiation in vitro. In the current study, we examined the influence of cyclic compressive loading of chick limb bud mesenchymal cells to a constant peak stress of 9.25 kPa during each of the first 3 days in culture. Cells embedded in agarose gel were subjected to uniaxial, cyclic compression at 0.03, 0.15, or 0.33 Hz for 2 h. In addition, load durations of 12, 54, or 120 min were evaluated while holding frequency constant at 0.33 Hz. For a 2 h duration, there was no response to loading at 0.03 Hz. A significant increase in chondrocyte differentiation was associated with loading at 0.15 Hz, and an even greater increase with loading at 0.33 Hz. Holding frequency constant at 0.33 Hz, a loading duration of 12 min elicited no response, whereas chondrocyte differentiation was enhanced by loading for either 54 or 120 min. Although not statistically significant from the 120 min response, average cartilage nodule density and glycosaminoglycan synthesis rate were highest in the 54 min duration group. This result suggests that cells may be sensitive to the level of cumulative (nonrecoverable) compressive strain, as well as to the dynamic strain history. © 2001 Biomedical Engineering Society. PAC01: 8717-d, 8719Rr
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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.
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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.
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To establish the reproducibility of a standardized region of interest (ROI) drawing procedure in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC). A large ROI in lateral and medial femoral weight-bearing cartilage was drawn in images of 12 healthy male volunteers by 6 investigators with different skills in MRI. The procedure was done twice, with a 1-week interval. Calculated T1-values were evaluated for intra- and interobserver variability. The mean interobserver variability for both compartments ranged between 1.3% and 2.3% for the 6 different investigators without correlation to their experience in MRI. Post-contrast intra-observer variability was low in both the lateral and the medial femoral cartilage, 2.6% and 1.5%, respectively. The larger variability in lateral than in medial cartilage was related to slightly longer and thinner ROIs. Intra-observer variability and interobserver variability are both low when a large standardized ROI is used in dGEMRIC. The experience of the investigator does not affect the variability, which further supports a clinical applicability of the method.
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Autologous chondrocyte implantation is an advanced, cell-based orthobiological technology used for the treatment of chondral defects of the knee. It has been in clinical use since 1987 and has been performed on 12 000 patients internationally; but despite having been in clinical use for more than 15 years, the evidence base for rehabilitation after autologous chondrocyte implantation is notably deficient. The authors review current clinical practice and present an overview of the principles behind autologous chondrocyte implantation rehabilitation practices. They examine the main rehabilitation components and discuss their practical applications within the overall treatment program, with the aim of facilitating the formulation of appropriate, individualized patient rehabilitation protocols for autologous chondrocyte implantation.
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Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.
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Postoperative rehabilitation programs following articular cartilage repair procedures will vary greatly among patients and need to be individualized based on the nature of the lesion, the unique characteristics of the patient, and the type and detail of each surgical procedure. These programs are based on knowledge of the basic science, anatomy, and biomechanics of articular cartilage as well as the biological course of healing following surgery. The goal is to restore full function in each patient as quickly as possible by facilitating a healing response without overloading the healing articular cartilage. The purpose of this paper is to overview the principles of rehabilitation following articular cartilage repair procedures. Furthermore, specific rehabilitation guidelines for debridement, abrasion chondroplasty, microfracture, osteochondral autograft transplantation, and autologous chondrocyte implantation will be presented based upon our current understanding of the biological healing response postoperatively.
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Background Knee reinjury after ACL reconstruction is common and increases the risk of osteoarthritis. There is sparse evidence to guide return to sport (RTS) decisions in this population. Objectives To assess the relationship between knee reinjury after ACL reconstruction and (1) return to level I sports, (2) timing of RTS and (3) knee function prior to return. Methods 106 patients who participated in pivoting sports participated in this prospective 2-year cohort study. Sports participation and knee reinjury were recorded monthly. Knee function was assessed with the Knee Outcome Survey—Activities of Daily Living Scale, global rating scale of function, and quadriceps strength and hop test symmetry. Pass RTS criteria were defined as scores >90 on all tests, failure as failing any. Results Patients who returned to level I sports had a 4.32 (p=0.048) times higher reinjury rate than those who did not. The reinjury rate was significantly reduced by 51% for each month RTS was delayed until 9 months after surgery, after which no further risk reduction was observed. 38.2% of those who failed RTS criteria suffered reinjuries versus 5.6% of those who passed (HR 0.16, p=0.075). More symmetrical quadriceps strength prior to return significantly reduced the knee reinjury rate. Conclusions Returning to level I sports after ACL reconstruction leads to a more than 4-fold increase in reinjury rates over 2 years. RTS 9 months or later after surgery and more symmetrical quadriceps strength prior to return substantially reduce the reinjury rate.
Article
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.
Article
Background: Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, although best patient outcomes appear limited by a lack of evidence-based knowledge on how to progressively increase postoperative weightbearing (WB) and rehabilitation exercises. Hypothesis: To determine the safety and efficacy of an accelerated WB regimen after MACI in the tibiofemoral joint. Study design: Randomized controlled trial; Level of evidence, 1. Methods: Clinical and radiological assessments were performed in 28 knees at 12 months after MACI to the medial or lateral femoral condyle. Both rehabilitation interventions sought to protect the implant for an initial period and then incrementally increase load bearing. Under the "accelerated" (AR) protocol, patients reached full WB at 6 weeks after surgery compared with 8 weeks for what was considered to be the current "best practice" (CR) WB regimen based on previous research. Assessments included the Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), visual analog scale, 6-minute walk test, and active knee range of motion (ROM). High-resolution magnetic resonance imaging (MRI) was used to describe the quality and quantity of repair tissue via the assessment of pertinent parameters of graft repair as well as an MRI composite score. Results: Patients in both groups demonstrated significant improvement (P < .05) in all clinical measures over the preoperative and postoperative timeline from before surgery to 12 months after surgery. The AR group reported significantly better (P < .05) SF-36 physical component scores at 8 weeks and significantly greater (P < .05) KOOS quality of life scores at 6 and 12 months postoperatively. Although no differences (P > .05) were observed between the 2 groups for active knee ROM, the AR group did achieve full active knee extension as early as 4 weeks compared with the CR group at 12 weeks. There was no difference (P > .05) in graft quality as assessed by MRI (MOCART composite score: AR, 3.34; CR, 3.04), with no patients suffering any adverse effects from the implant up to 12 months, regardless of the rehabilitation protocol employed. Conclusion: The AR approach that reduced the length of time spent ambulating on crutches resulted in improved general physical function and quality of life and an earlier attainment of full active knee extension when compared with the CR approach. There were no graft complications ascertained through MRI. This regimen appears safe and may potentially speed up the recovery of normal gait function. A larger patient cohort and follow-up are required to observe long-term graft outcomes.
Article
Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of full-thickness chondral defects in the knee. It is a 2-stage procedure involving an initial arthroscopic harvest of healthy cartilage, isolation and expansion of chondrocytes ex vivo, and subsequent reimplantation of cells into the chondral defect through an open arthrotomy. However, the MACI procedure lends itself to an arthroscopic implantation technique decreasing the associated comorbidity of arthrotomy, potentially allowing for faster postoperative rehabilitation. We present a simple surgical technique for the arthroscopic implantation of MACI grafts, reducing the associated operative morbidity and allowing for accelerated postoperative rehabilitation and return to full physical function.
Article
To determine the safety and efficacy of a new arthroscopic technique for matrix-induced autologous chondrocyte implantation (MACI) for articular cartilage defects in the knee. We undertook a prospective evaluation of the first 20 patients treated with the MACI technique (including 14 defects on the femoral condyle and 6 on the tibial plateau), followed up for 24 months after surgery. A 12-week structured rehabilitation program was undertaken by all patients. Patients underwent clinical assessment (Knee Injury and Osteoarthritis Outcome Score, Short Form 36 Health Survey, visual analog pain scale, 6-minute walk test, knee range of motion) before surgery and at 3, 6, 12, and 24 months after surgery and underwent magnetic resonance imaging (MRI) assessment at 3, 12, and 24 months after surgery. MRI evaluation assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score. A significant improvement (P < .05) was shown throughout the postoperative time line for all Knee Injury and Osteoarthritis Outcome Score subscales, the physical component score of the Short Form 36 Health Survey, the frequency and severity of knee pain, and the 6-minute walk test. An improvement in pertinent morphologic parameters of graft repair was observed to 24 months, whereas a good to excellent graft infill score and MRI composite score were observed at 24 months after surgery in 90% and 70% of patients, respectively. We report a comprehensive 24-month follow-up in the first 20 patients who underwent the arthroscopic MACI technique. This technique is a safe and efficacious procedure with improved clinical and radiologic outcomes over the 2-year period.
Article
To evaluate the clinical outcome of hyaluronan-based arthroscopic autologous chondrocyte transplantation at a minimum of 5 years of follow-up and to correlate it with the MRI evaluation parameters. Fifty consecutive patients were included in the study and evaluated clinically using the Cartilage Standard Evaluation Form as proposed by ICRS and the Tegner score. Forty lesions underwent MRI evaluation at a minimum 5-year follow-up. For the description and evaluation of the graft, we employed the MOCART-scoring system. A statistically significant improvement in all clinical scores was observed at 2 and over 5 years. The total MOCART score and the signal intensity (3D-GE-FS) of the repair tissue were statistically correlated to the IKDC subjective evaluation. Larger size of the treated cartilage lesions had a negative influence on the degree of defect repair and filling, the integration to the border zone and the subchondral lamina integrity, whereas more intensive sport activity had a positive influence on the signal intensity of the repair tissue, the repair tissue surface, and the clinical outcome. Our findings confirm the durability of the clinical results obtained with Hyalograft C and the usefulness of MRI as a non-invasive method for the evaluation of the repaired tissue and the outcome after second-generation autologous transplantation over time.
Article
To define magnetic resonance (MR) arthrography imaging findings of matrix-induced autologous chondrocyte implantation (MACI) grafts of the knee in order to describe implant behaviour and to compare findings with validated clinical scores 30 and 60 months after MACI implant. Thirteen patients were recruited (10 male, 3 female) with a total number of 15 chondral lesions. Each patient underwent an MACI procedure and MR arthrography 30 and 60 months after surgery. MR arthrography was performed using a dedicated coil with a 1.5-Tesla unit. The status of the chondral implant was evaluated with the modified MOCART scoring scale. The lining of the implant, the integration to the border zone, the surface and structure of the repaired tissue were assessed, and the presence of bone marrow oedema and effusion was evaluated. For clinical assessment, the Cincinnati score was used. At 60 months, the abnormality showed worsening in 1 out of 15 cases. Integration showed improvement in 3 out of 15 cases, and worsening in 3 out of 15 cases. Two surfaces of the implant showed further deterioration at 60 months, and 1 afflicted implant fully recovered after the same time interval. Implant contrast enhancement at 30 months was seen in 2 out of 15 cases, 1 of which recovered at 60 months. According to the MOCART score, 4 cases were rated 68.4 out of 75 at 30 months and 65 out of 75 at 60 months. The mean clinical score decreased from 8.6 out of 10 at 30 months to 8.1 out of 10 at 60 months. Magnetic resonance arthrography improved the evaluation of implants and facilitated the characterisation of MACI integration with contiguous tissues. The follow-up showed significant changes in MACI, even at 60 months, allowing for useful long-term MR evaluations.
Article
In cartilage repair, bioregenerative approaches using tissue engineering techniques have tried to achieve a close resemblance to hyaline cartilage, which might be visualized using advanced magnetic resonance imaging. To compare cartilage repair tissue at the femoral condyle noninvasively after matrix-associated autologous chondrocyte transplantation using Hyalograft C, a hyaluronic-based scaffold, to cartilage repair tissue after transplantation using CaReS, a collagen-based scaffold, with magnetic resonance imaging using morphologic scoring and T2 mapping. Cohort study; Level of evidence, 3. Twenty patients after matrix-associated autologous chondrocyte transplantation (Hyalograft C, n = 10; CaReS, n = 10) underwent 3-T magnetic resonance imaging 24 months after surgery. Groups were matched by age and defect size/localization. For clinical outcome, the Brittberg score was assessed. Morphologic analysis was applied using the magnetic resonance observation of cartilage repair tissue score, and global and zonal biochemical T2 mapping was performed to reflect biomechanical properties with regard to collagen matrix/content and hydration. The clinical outcome was comparable in each group. The magnetic resonance observation of cartilage repair tissue score showed slightly but not significantly (P= .210) better results in the CaReS group (76.5) compared to the Hyalograft C group (70.0), with significantly better (P= .004) constitution of the surface of the repair tissue in the CaReS group. Global T2 relaxation times (milliseconds) for healthy surrounding cartilage were comparable in both groups (Hyalograft C, 49.9; CaReS, 51.9; P= .398), whereas cartilage repair tissue showed significantly higher results in the CaReS group (Hyalograft C, 48.2; CaReS, 55.5; P= .011). Zonal evaluation showed no significant differences (P > or = .05). Most morphologic parameters provided comparable results for both repair tissues. However, differences in the surface and higher T2 values for the cartilage repair tissue that was based on a collagen scaffold (CaReS), compared to the hyaluronic-based scaffold, indicated differences in the composition of the repair tissue even 2 years postimplantation. In the follow-up of cartilage repair procedures using matrix-associated autologous chondrocyte transplantation, differences due to scaffolds have to be taken into account.
Article
Tissue engineering has become available for cartilage repair in clinical practice. The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autologous chondrocytes provides stable improvement of clinical outcome up to 7 years. Case series; Level of evidence, 4. Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 +/- 12 years, the mean defect size was 4.4 +/- 1.9 cm(2), and the mean body mass index was 24.5 +/- 3.8 kg/m(2). Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests. A highly significant increase (P <.001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P <.001). Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor.
Article
There is no consensus about the optimal time for weightbearing activities after matrix-associated autologous chondrocyte implantation (MACI) of the femoral condyle. A comprehensive protocol after MACI on the femoral condyle with accelerated weightbearing leads to a better functional and radiographic outcome compared with the same comprehensive protocol with delayed weightbearing. Randomized controlled trial; Level of evidence, 1. Thirty-one patients (22 male, 9 female) after MACI on the femoral condyle were randomly assigned to the accelerated weightbearing group (group A) or the delayed weightbearing group (group B). Aside from increase and time of full weightbearing, both groups adhered to the same rehabilitation protocol and exercises. Patients were assessed preoperatively and at 4, 12, 24, 52, and 104 weeks after surgery. Clinical evaluation was performed by determining the subjective form of the International Knee Documentation Committee (IKDC), the Tegner activity scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiological outcome was evaluated by the MOCART score and the size and amount of bone marrow edema and effusion. In both groups, there were no differences with regard to the clinical outcome. For the radiological outcome, group A showed a higher prevalence of bone marrow edema after 6 months without correlation to the clinical outcome (P = .06-.1). However, after 104 weeks, there were no differences in the radiological outcome between group A and group B. A rehabilitation protocol with accelerated weightbearing leads to good clinical and functional outcome after 2 years without jeopardizing the healing graft.
Article
To study muscle strength and functional performance in patients with anterior cruciate ligament (ACL) injury with or without surgical reconstruction 2 to 5 years after injury. Good muscle function is important in preventing early-onset osteoarthritis (OA), but the role of reconstructive surgery in restoring muscle function is unclear. Of 121 patients with ACL injury included in a randomized controlled trial on training and surgical reconstruction versus training only (the Knee, Anterior cruciate ligament, NON-surgical versus surgical treatment [KANON] study, ISRCTN: 84752559), 54 (mean age at followup 30 years, range 20-39, 28% women) were assessed a mean +/- SD of 3 +/- 0.9 years after injury with reliable, valid, and responsive test batteries for strength (knee extension, knee flexion, leg press) and hop performance (vertical jump, one-leg hop, side hop). The Limb Symmetry Index (LSI; injured leg divided by uninjured and multiplied by 100) value and absolute values were used for comparisons between groups (analysis of variance). An LSI >or=90% was considered normal. There were no differences between the surgical and nonsurgical treatment groups in muscle strength or functional performance. Between 44% and 89% of subjects had normal muscle function in the single tests, and between 44% and 56% had normal function in the test batteries. The lack of differences between patients treated with training and surgical reconstruction or training only indicates that reconstructive surgery is not a prerequisite for restoring muscle function. Abnormal muscle function, found in approximately one-third or more of the patients, may be a predictor of future knee OA.
Article
Various treatment options for deep cartilage defects are presently available. The efficacy of bone marrow stimulation with microfracture, of mosaicplasty and of various autologous chondrocyte implantation (ACI) techniques has been subject to numerous studies recently. Magnetic resonance imaging (MRI) has gained a major role in the assessment of cartilage repair. The introduction of high-field MRI to clinical routine makes high resolution and three-dimensional imaging readily available. New quantitative MRI techniques that directly visualize the molecular structure of cartilage may further advance our understanding of cartilage repair. The clinical evaluation of cartilage repair tissue is a complex issue, and MR imaging will become increasingly important both in research and in clinical routine. This article reviews the clinical aspects of microfracture, mosaicplasty, and ACI and reports the recent technical advances that have improved MRI of cartilage. Morphological evaluation methods are recommended for each of the respective techniques. Finally, an overview of T2 mapping and delayed gadolinium-enhanced MR imaging of cartilage in cartilage repair is provided.
Article
To determine whether patients can accurately replicate and retain weight-bearing restrictions in both stationary (static) and dynamic conditions after autologous chondrocyte implantation (ACI). Case series. Rehabilitation clinic. A consecutive sample of patients (N=48) who had undergone ACI to a medial or lateral femoral condylar defect in the knee. Patients were trained to partially weight bear using bathroom scales and forearm crutches prior to assessment. A force platform was used to measure peak vertical ground reaction forces in patients during static and dynamic conditions immediately after weight-bearing instruction and training, and again during gait 7 days after training. Immediately after instruction and weight-bearing practice on a set of scales, patients exerted a mean of 15.8% body weight more than expected during walking for 20% weight-bearing trials, 8.3% more for the 40% trials, 11.9% more for the 60% trials, and 1.2% less for the prescribed 80% trials. Accuracy of weight-bearing replication improved across all weight-bearing levels when assessed 7 days later, when patients exerted a mean of 6.6% body weight more than expected during walking for 20% weight-bearing trials (9.2% body weight improvement), 4.2% more for the 40% trials (4.1% body weight improvement), 9.9% more for the 60% trials (2% body weight improvement), and 0.2% more for the 60% trials (1% body weight improvement). Patients were unable to follow weight-bearing restrictions after instruction and practice on a set of scales, and patients were unable to replicate weight-bearing levels in both static and dynamic conditions.
Article
A canine knee model of disuse atrophy produced by nonrigid fixation (sling) was characterized in respect to variables of proteoglycan size distribution, as well as biomechanical properties versus controls. Using this model, we found, in addition to the accepted dogma attributing changes to reduced protein synthesis by chondrocytes, that there is elevation of proteases and depression of tissue inhibitor of metalloproteases (TIMP) in atrophic knee cartilage. The findings are suggestive of cartilage remodelling reminiscent of bone remodelling in disuse atrophy reported by others. Whether the abnormal changes of protease-TIMP balance in knee cartilage can be retarded prophylactically by concurrent treatment with pentosan polysulfate and insulin like growth factor 1 remains uncertain.
Article
Functional tests are used to determine functional limitations in patients with anterior cruciate ligament injuries. The reproducibility of 4 such functional tests was determined in 21 normal athletes. The athletes performed the four functional tests (figure 8, vertical jump, triple jump test and stairs hopple tests) twice, with an interval of mean 3.9 weeks (1-7 weeks). The reliability of the tests was determined from each tests' coefficient of variation (CV). The figure 8 test showed a significant difference between the 2 performances and the variation from test I to test II. The CV values ranged from 2.0% for the triple jump test to 7.7% for the vertical jump test. These findings do not support the reliability of the figure 8 test and the vertical jump test, but do support the reliability of the triple jump test and the stairs hopple test.
Article
It is essential to assess the functional status of patients with surgically reconstructed and rehabilitated anterior cruciate ligaments prior to discharge. This study established a testing paradigm for functional force production and absorption. Data were obtained from 100 healthy subjects for maximal hops, controlled leaps, and hopping and leaping symmetry. Only 10% of symptomatic patients met maximal hopping criteria, while 15% achieved controlled leaping norms. Ninety-five percent of these patients failed to reach both hopping and leaping symmetry norms. Asymptomatic patients were 63% successful in meeting hopping criteria, and 57% were successful in meeting leaping criteria. Hop symmetry and leap symmetry were achieved at rates of 70% and 60%, respectively. The performance of both groups fell significantly below that of normal subjects (p < .05). Data suggest that this protocol does accurately assess functional and dysfunctional knees, and that force absorption may be more critical than force production in the determination of functional capacity.
Article
Autologous chondrocyte transplantation (ACT) provides durable hyaline repair tissue in correctly selected patients; it is indicated for full thickness, weightbearing condyle injuries, and injuries to the trochlea of the femur. ACT results in reproducibly satisfactory results, with return to high level activities, including sports, in over 90% of these patients. Second look arthroscopies demonstrate macroscopic integrity of the grafts; and biopsies demonstrate hyaline cartilage repair, which is critical, as shown clinically, to giving durable results at two to nine years follow-up. Also discussed in this article is surgical technique which is especially important for complex reconstructions. As technical refinements and rehabilitation protocols improve, results for treating patellar and tibial injuries may improve; at this time, the response to treating bipolar focal chondral injuries is unknown and not recommended.
Article
Cartilaginous constructs have been grown in vitro with use of isolated cells, biodegradable polymer scaffolds, and bioreactors. In the present work, the relationships between the composition and mechanical properties of engineered cartilage constructs were studied by culturing bovine calf articular chondrocytes on fibrous polyglycolic acid scaffolds (5 mm in diameter, 2-mm thick, and 97% porous) in three different environments: static flasks, mixed flasks, and rotating vessels. After 6 weeks of cultivation, the composition, morphology, and mechanical function of the constructs in radially confined static and dynamic compression all depended on the conditions of in vitro cultivation. Static culture yielded small and fragile constructs, while turbulent flow in mixed flasks yielded constructs with fibrous outer capsules; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels were the largest, contained continuous cartilage-like extracellular matrices with the highest fractions of glycosaminoglycan and collagen, and had the best mechanical properties. The equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential correlated with the wet-weight fractions of glycosaminoglycan, collagen, and water. These findings suggest that the hydrodynamic conditions in tissue-culture bioreactors can modulate the composition, morphology, mechanical properties, and electromechanical function of engineered cartilage.
Article
The American Thoracic Society has issued guidelines for the 6-minute walk test (6MWT). The 6MWT is safer, easier to administer, better tolerated, and better reflects activities of daily living than other walk tests (such as the shuttle walk test). The primary measurement is 6-min walk distance (6MWD), but during the 6MWT data can also be collected about the patient's blood oxygen saturation and perception of dyspnea during exertion. When conducting the 6MWT do not walk with the patient and do not assist the patient in carrying or pulling his or her supplemental oxygen. The patient should walk alone, not with other patients. Do not use a treadmill on which the patient adjusts the speed and/or the slope. Do not use an oval or circular track. Use standardized phrases while speaking to the patient, because your encouragement and enthusiasm can make a difference of up to 30% in the 6MWD. Count the laps with a lap counter. If the 6MWD is low, thoroughly search for the cause(s) of the impairment. Better 6MWD reference equations will be published in the future, so be sure you are using the best available reference equations.
Article
The macromolecular structure and mechanical properties of articular cartilage are interrelated and known to vary topographically in the human knee joint. To investigate the potential of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness cartilage disks were prepared from six anatomical locations in nonarthritic human knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were determined with the use of unconfined compression tests, followed by quantitative MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible, statistically significant differences in moduli between the patella and the medial/lateral femoral condyles. Typically, femoral cartilage showed higher Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately reproduced the topographical variation in moduli. Additionally, T1, T2, and dGEMRIC revealed topographical differences that were not registered mechanically. The different MRI and mechanical parameters showed poor to excellent linear correlations, up to r = 0.87, at individual test sites. After all specimens were pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N = 77). The results suggest that quantitative MRI can indirectly provide information on the mechanical properties of human knee articular cartilage, as well as the site-dependent variations of these properties. Investigators should consider the topographical variation in MRI parameters when conducting quantitative MRI of cartilage in vivo.
Article
To evaluate articular cartilage repair tissue after biological cartilage repair, we propose a new technique of non-invasive, high-resolution magnetic resonance imaging (MRI) and define a new classification system. For the definition of pertinent variables the repair tissue of 45 patients treated with three different techniques for cartilage repair (microfracture, autologous osteochondral transplantation, and autologous chondrocyte transplantation) was analyzed 6 and 12 months after the procedure. High-resolution imaging was obtained with a surface phased array coil placed over the knee compartment of interest and adapted sequences were used on a 1 T MRI scanner. The analysis of the repair tissue included the definition and rating of nine pertinent variables: the degree of filling of the defect, the integration to the border zone, the description of the surface and structure, the signal intensity, the status of the subchondral lamina and subchondral bone, the appearance of adhesions and the presence of synovitis. High-resolution MRI, using a surface phased array coil and specific sequences, can be used on every standard 1 or 1.5 T MRI scanner according to the in-house standard protocols for knee imaging in patients who have had cartilage repair procedures without substantially prolonging the total imaging time. The new classification and grading system allows a subtle description and suitable assessment of the articular cartilage repair tissue.
Article
The purpose of this study was to examine the use of the Short Form 36 Health Survey (SF-36) in the preoperative assessment and postoperative review of patients undergoing autologous chondrocyte implantation (ACI) of the knee. We used the SF-36, a validated health related quality of life survey, and The Modified Cincinnati Knee score, a commonly used knee function scoring system, to evaluate 25 consecutive patients preoperatively and 1 year following surgery. Before surgery, patients scored lower for all aspects of general health and level of functioning compared to a normalised general population. We demonstrated significant increases of overall SF-36 scores following surgery, reflecting improvements to perceived general health. Most significant improvements were seen in the physical categories of "Physical Functioning" (44.8 to 56.2, p=0.014), "Role Physical"(35.0 to 52.2, p=0.044) and "Bodily Pain"(33.6 to 50.9, p=0.001). Higher preoperative SF-36 scores were found to correlate significantly with greater increases of Modified Cincinnati Knee scores. Postoperative knee function scores correlated well with physical categories of the SF-36. However, we found poor correlation between postoperative Modified Cincinnati Knee scores and SF-36 scores for vitality, social functioning and emotional domains. This suggests that knee function scores alone do not incorporate all the benefits to patient health following ACI surgery. We recommend using a knee function scoring system and the SF-36 for both the preoperative assessment and postoperative review of ACI patients.
Article
Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation with HyalograftC by a new grading system based on non-invasive high-resolution magnetic resonance imaging. In 23 patients, postoperative magnetic resonance imaging (MRI) was performed between 76 and 120 weeks. In nine of these patients, five MRI examinations were performed at 4, 12, 24, 52 and 104 weeks after HyalograftC implant. The repair tissue was described with separate variables: degree of defect repair in width and length, signal intensity of the repair tissue and status of the subchondral bone. For these variables a grading system with point scale evaluation was applied. High-resolution MRI provides a non-invasive tool for monitoring the development of cartilage repair tissue following HyalograftC technology, shows a good correlation with clinical outcome and may help to differentiate abnormal repair tissue from a normal maturation process.
Article
In an observational study, the validity and reliability of magnetic resonance imaging (MRI) for the assessment of autologous chondrocyte transplantation (ACT) in the knee joint was determined. Two years after implantation, high-resolution MRI was used to analyze the repair tissue with nine pertinent variables. A complete filling of the defect was found in 61.5%, and a complete integration of the border zone to the adjacent cartilage in 76.9%. An intact subchondral lamina was present in 84.6% and an intact subchondral bone was present in 61.5%. Isointense signal intensities of the repair tissue compared to the adjacent native cartilage were seen in 92.3%. To evaluate interobserver variability, a reliability analysis with the determination of the intraclass correlation coefficient (ICC) was calculated. An "almost perfect" agreement, with an ICC value >0.81, was calculated in 8 of 9 variables. The clinical outcome after 2 years showed the visual analog score (VAS) at 2.62 (S.D. +/-0.65). The values for the knee injury and osteoarthritis outcome score (KOOS) subgroups were 68.29 (+/-23.90) for pain, 62.09 (+/-14.62) for symptoms, 75.45 (+/-21.91) for ADL function, 52.69 (+/-28.77) for sport and 70.19 (+/-22.41) for knee-related quality of life. The clinical scores were correlated with the MRI variables. A statistically significant correlation was found for the variables "filling of the defect," "structure of the repair tissue," "changes in the subchondral bone," and "signal intensities of the repair issue". High resolution MRI and well-defined MRI variables are a reliable, reproducible and accurate tool for assessing cartilage repair tissue.
Article
Rehabilitation is a key element of successful treatment of cartilage defects with cell transplantation. The process of graft maturation takes approximately 18 months and cannot be accelerated, but requires carefully introduced steps leading to early recovery of joint function. Rehabilitation starts at 8 hours after surgery with the continuous passive motion (CPM) exercises and physiotherapy. For the first 6 weeks, patients continue with CPM in the range of 0 degrees to 45 degrees for femoral and tibial defects and 0 degrees to 30 degrees for patellofemoral joint reconstruction. Isometric muscle training and scar manual therapy are introduced. Patients are allowed to weight-bear as tolerated from the second week after surgery. After this initial phase, from 6 to 8 weeks after surgery, rehabilitation is accelerated with increased load-bearing and progressive range of motion to full flexion. Usually patients are able to walk without crutches in this time. Proprioceptive training is introduced with the advance of pain-free full range of motion and no discomfort with full weight-bearing. At 6 months after surgery, most patients recover joint function, making it possible for them to return to daily living activities. However, they need to continue with muscle, proprioceptive, and sports-specific rehabilitation exercises. The rehabilitation process is complicated, requiring close cooperation between the patient and surgeon-physiotherapist team to understand the symptoms and address them in a timely fashion.
Article
Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI) is a new operation procedure using a cell seeded collagen matrix for the treatment of localized full-thickness cartilage defects. A prospective clinical investigation was carried out in order to clarify whether this proves suitable and confirms objective and subjective clinical improvement over a period of up to 5 years after operation. Thirty-eight patients with localised cartilage defects were treated with MACT. Within the context of clinical follow-up, these patients were evaluated for up to 5 years after the intervention. Four different scores (Meyers score, Tegner-Lysholm activity score, Lysholm-Gillquist score, ICRS score) as well as the results of six arthroscopies and biopsies obtained from four patients formed the basis of this study. For 15 patients, 5 or more years had elapsed since the operation at the time this study was completed. It was possible to obtain results 5 years postoperatively from 11 (73.3%) of these 15 patients. Overall, we included 25 patients into the evaluation with a 2-year or longer postoperative period. Five years after transplantation 8 out of 11 patients rated the function of their knee as much better or better than before. Three of the four scores showed significant improvement compared to the preoperative value. One score, the Tegner-Lysholm score showed improvement, which, however, did not prove to be significant. The significantly improved results on three scores after 5 years suggest that MACT represents a suitable but cost-intensive alternative in the treatment of local cartilage defects in the knee.