Autologous Chondrocyte Implantation For Treatment Research Articles

AUTOLOGOUS CHONDROCYTE IMPLANTATION: MULTILEVEL MODELLING OF 20-YEAR LONGITUDINAL OUTCOME DATA

The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set.Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number.The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects.Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions.

Autologous chondrocyte implantation for treatment of articular cartilage defects in the knee and ankle of football (soccer) players

BackgroundAutologous chondrocyte implantation (ACI) continues to evolve into one of the most efficient and common techniques for repair of articular cartilage defects. Significant progress has been made within the last decade regarding its application in the context of professional sports, such as football. This article provides a current overview of the application of ACI in the context of amateur and professional football. MethodsClinical studies involving football players and other high-impact sports athletes treated with ACI were reviewed. The scientific and technical development of ACI was evaluated considering latest publications, and analyzed for treatment outcome parameters. ResultsFootball players reported good to excellent results after treatment with ACI or matrix-associated chondrocyte implantation (MACI). Activity scores and clinical knee and ankle scores were significantly improved after surgery. Great advances have been made in surgery specific rehabilitation algorithms, leading to shorter return to play times. New surgical techniques have been introduced, reducing the 2-stage design of ACI to only one surgical intervention, accelerating return to play time further while reducing morbidity. ConclusionSurgical repair of focal articular cartilage defects via ACI in football players often provides successful return-to-competition and produces long lasting regeneration tissue, enabling players to continue their career on the pre-injury level of play. The technique itself is constantly evolving, addressing initial shortcomings and making it more widespread available to the recreational and professional athlete.

Efficacy and safety of autologous chondrocyte implantation for osteochondral defects of the talus: a systematic review and meta-analysis.

Studies have reported various effects of autologous chondrocyte implantation (ACI) on osteochondral defects of the talus. Therefore, to assess the effectiveness of ACI for osteochondral defects of the talus, we used the meta-analytic approach. Electronic databases PubMed, Embase, and the Cochrane Library were systematically searched to identify eligible studies from their inception until November 2020. The random-effects model was used to calculate the incidence of success rate and American Orthopaedic Foot and Ankle Society (AOFAS) score for patients after ACI treatment. Subgroup analyses were also conducted based on age, technique, indication, size, and follow-up duration. For the final meta-analysis, we selected 23 case series studies with a total of 458 patients with osteochondral defects of the talus. Overall, after ACI for patients with osteochondral defects of the talus, we noted that the incidence of success rate was 89% (95% confidence interval (95% CI) 85%-92%; P < 0.001). Moreover, after ACI for patients with osteochondral defects of the talus, the AOFAS score was 86.33 (95% CI 83.33-89.33; P < 0.001). Subgroup analysis showed that the AOFAS score after ACI is significantly different when stratified by the mean age of the patients (P = 0.006). This study revealed that the use of ACI could provide a relatively high success rate and improve the AOFAS score for patients with osteochondral defects of the talus, which should be recommended in clinical practice.

Costal Chondrocyte–Derived Pellet-Type Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defect

Background: Because articular chondrocyte-based autologous chondrocyte implantations (ACIs) have restrictively restored articular cartilage defects, alternative cell sources as a new therapeutic option for cartilage repair have been introduced. Purpose: To assess whether implantation of a costal chondrocyte–derived pellet-type (CCP) ACI allows safe, functional, and structural restoration of full-thickness cartilage defects in the knee. Study Design: Case series; Level of evidence, 4. Methods: In this first-in-human study, 7 patients with symptomatic, full-thickness cartilage lesions were enrolled. The chondrocytes isolated from the patients’ costal cartilage were expanded, followed by 3-dimensional pellet culture to prepare the CCP-ACI. Implantation of the pellets was performed via minimal arthrotomy and secured with a fibrin sealant. Clinical scores, including the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scores, were estimated preoperatively and at 1, 2, and 5 years postoperatively. High-resolution magnetic resonance imaging was also performed to evaluate cartilage repair as well as to calculate the MOCART (magnetic resonance observation of cartilage repair tissue) score. Results: The costal chondrocytes of all patients formed homogeneous-sized pellets, which showed the characteristics of the hyaline cartilaginous tissue with lacunae-occupied chondrocytes surrounded by glycosaminoglycan and type II collagen-rich extracellular matrix. There were no treatment-related serious adverse events during the 5-year follow-up period. Significant improvements were seen in all clinical scores from preoperative baseline to the 5-year follow-up (IKDC subjective score, 34.67 to 75.86; Lysholm score, 34.00 to 85.33; Tegner activity score, 1.17 to 4.67; and MOCART score, 28.33 to 83.33). Two patients had complete defect filling on magnetic resonance imaging evaluation at 1 year. Moreover, at 5 years postoperatively, complete defect filling was observed in 4 patients, and hypertrophy or incomplete defect filling (50%-100%) was observed in 2 patients. Conclusion: The overall results of this clinical study suggest that CCP-ACI can emerge as a promising therapeutic option for articular cartilage repair with good clinical outcomes and structural regeneration and with stable results at midterm follow-up. Registration: NCT03517046 (ClinicalTrials.gov identifier)

Autologous chondrocyte implantation for treatment of focal articular cartilage defects of the humeral head

Autologous chondrocyte implantation (ACI) constitutes an established treatment option for cartilage defects of the knee joint. Experience in the shoulder, however, islimited, and the management of cartilage defects remains a challenge. The purpose of this study was to evaluate the results after ACI with 3-dimensionalspheroids of human autologous matrix-associated chondrocytes in the shoulder. Seven male patients (median age, 42.8 years [range, 18-55 years]) underwent ACI for symptomatic focal grade IV cartilage lesions of the humeral head by an open or arthroscopic approach. Clinical parameters (range of motion, visual analog scale score, Subjective Shoulder Value, Constant score, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score) and osteoarthritis grades were assessed. Arthroscopic re-evaluation was additionally performed in 5 patients. After a median follow-up period of 32 months (range, 22-58 months), the median Subjective Shoulder Value was 95% (range, 70%-100%)compared with 60% (range, 30%-60%) preoperatively, the visual analog scale score was 0 at rest and was a median of 0 (range, 0-2) during exercise, the median Constant score was 95 points (range, 80-100 points), and the median American Shoulder and Elbow Surgeons score was 97 points (range, 90-100 points). The median preoperative size of the cartilage lesion was 3 cm2 (range, 2.3-4.5 cm2). Arthroscopically, complete coverage of the cartilage defect was observed in 4 cases whereas a circumferential residual defect of 0.25 cm2 was found in 1 patient. Grade I osteoarthritis (Samilson and Prieto classification) was observed in 2 cases. One patient had postoperative adhesive capsulitis and required revision surgery. ACI using 3-dimensional spheroids of human autologous matrix-associated chondrocytes for treatment of grade IV articular cartilage lesions of the humeral head achieves satisfactory clinical results during a short- to mid-term follow-up period and leads to successful defect coverage with only minor radiologic degenerative changes. In this case series, ACI proved to constitute a viable treatment in the shoulder joint. However, in consideration of the 2-stage surgical design and the cost intensiveness of this procedure, the indication is restricted to young and active symptomatic patients in our practice.

Collagen-Covered Autologous Chondrocyte Implantation Versus Autologous Matrix-Induced Chondrogenesis: A Randomized Trial Comparing 2 Methods for Repair of Cartilage Defects of the Knee.

Background:Autologous matrix-induced chondrogenesis (AMIC) is a single-stage alternative to autologous chondrocyte implantation for treatment of localized cartilage defects of the knee. To our knowledge, no randomized controlled trial exists comparing the 2 methods.Purpose:To evaluate any difference in the outcome of AMIC as compared with collagen-covered autologous chondrocyte implantation (ACI-C).Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A prospective randomized controlled clinical trial was designed to assess any differences in the outcomes between ACI-C and AMIC for the treatment of ≥1 chondral or osteochondral defects of the distal femur and/or patella. The inclusion period was set to 3 years, and the aim was to include 80 patients (40 in each group). Patient inclusion was broad, with few exclusion criteria. The primary outcome was change in Knee injury and Osteoarthritis Outcome Score (KOOS) at 2 years as compared with baseline. The secondary outcomes were the number of failures in each group at 2 years and the change in KOOS subscale, Lysholm, and pain visual analog scale (VAS) scores at 2 years as compared with baseline. A 2-sample t test with a significance level of P < .05 was used to compare the change in score from baseline between groups.Results:A total of 41 patients over 3 years were included in the study: 21 in the ACI-C group and 20 in the AMIC group. All the patients had prior surgery to the index knee. At 2-year follow-up, the clinical scores for both groups improved significantly from baseline. No significant differences between groups were seen in the change from baseline for KOOS (AMIC, 18.1; ACI-C, 10.3), any of the KOOS subscales, the Lysholm score (AMIC, 19.7; ACI-C, 17.0), or the VAS pain score (AMIC, 30.6; ACI-C, 19.6). Two patients in the AMIC group had progressed to a total knee replacement by the 2-year follow-up as compared with none in the ACI-C group.Conclusion:At 2-year follow-up, no significant differences were found regarding outcomes between ACI-C and AMIC. Mid- and long-term results will be important.Registration:NCT01458782 (ClinicalTrials.gov identifier).

The Treatment of Adult Osteochondritis Dissecans with Autologous Cartilage Implantation: A Systematic Review.

We sought to evaluate the effectiveness of autologous chondrocyte implantation (ACI) for the treatment of adult osteochondritis dissecans (OCD) lesions according to patient-reported outcomes, complication rates, and failure rates. A search of MEDLINE, Scopus, and Cochrane Library was performed to identify clinical studies (levels I-IV) reporting outcomes after ACI treatment for OCD in adult knees. Our inclusion criteria included the following: (1) published between January 2000 and April 2017, (2) stable and unstable OCD lesions of the knee, (3) use of ACI in at least one group, (4) subjects ≥18 years old or skeletally mature, (5) inclusion of at least one patient-reported clinical outcome measure, and (6) written in English. A total of nine studies (179 patients), mean age of 27.6 years (range: 18-49 years), were included. There were 227 OCD lesions with an average size of 4.1 cm2 (range: 1.2-9.4 cm2). The average follow-up was 61.3 months (range: 6.5-120 months). In general, there was significant improvement in symptoms, but better results occurred among active male patients with smaller lesions as well as younger patients. Statistically significant improvement in patient-reported outcomes was reported in all studies. There were 23 complications reported (15.6%), including 12 failures (8.2%). Significant improvement in clinical outcome measures demonstrates clinical efficacy of autologous cartilage therapies for the treatment of OCD in adult patients. Better outcomes are often observed with males, active patients, smaller lesion sizes, and younger age at the time of surgery.

Sustained Results in Long-Term Follow-Up of Autologous Chondrocyte Implantation (ACI) for Distal Femur Juvenile Osteochondritis Dissecans (JOCD).

Introduction Concern regarding ability of autologous chondrocyte implantation (ACI) to correct for the bone and cartilage pathology of knee juvenile osteochondritis dissecans (JOCD) exists. The purpose of this study was to determine long-term, patient-based outcomes of ACI treatment of JOCD in young patients. Authors hypothesized long-term outcomes are comparable to reported mid-term outcomes. Methods A single institution, longitudinal cohort study design combining medical record review and outcome surveys was used. Inclusion criteria included isolated JOCD diagnosis, failed primary healing of operatively treated JOCD, ACI surgery > 5 years ago, and ≤20 years of age at time of ACI. Results 10/26 eligible patients (38.5%) participated (M: F = 5:5, age at ACI: 18.3 ± 2.5 y, current age: 30.8 ± 5.1 y, and current BMI: 24.6 ± 2.1). Follow-up was 12.0 ± 4.5 y. Lesion size at ACI was 9.1 ± 1.9 cm2. Femoral condyle location was medial = 6 and lateral = 4. All required treatment at some point for knee symptoms after ACI. During the past one year, four patients required treatment. Patient reported outcome scores at 12 years following ACI were IKDC score: 73.0 ± 3.6, KOOS scores including pain [88.7 ± 2.3], symptoms [78.2 ± 4.6], activity of daily living [94.7 ± 1.9], function, sports, and recreational activities [73.0 ± 5.3], and quality of life [57.5 ± 5.8], and Modified Cincinnati Knee Rating score was 77.9 ± 4.1. A moderate to good relationship was found between KOOS symptoms and BMI and lesion size. Function, sports, and recreational activities of the KOOS were greater in participants who had ≤1 lesion prior to ACI procedures (p = 0.044). Conclusion This study of ACI treatment of knee JOCD patients confirms sustained, long-term results. Number of lesions prior to ACI procedure influenced status of function, sports, and recreational activities.

The Absence of Detectable ADAMTS-4 (Aggrecanase-1) Activity in Synovial Fluid Is a Predictive Indicator of Autologous Chondrocyte Implantation Success

Background: Autologous chondrocyte implantation (ACI) is used worldwide in the treatment of cartilage defects in the knee. Several demographic and injury-specific risk factors have been identified that can affect the success of ACI treatment. However, the discovery of predictive biomarkers in this field has thus far been overlooked. Purpose: To identify potential biomarkers in synovial fluid and plasma that can be used in the preoperative setting to help optimize patient selection for cell-based cartilage repair strategies. Study Design: Controlled laboratory study. Methods: Fifty-four ACI-treated patients were included. Cartilage oligomeric matrix protein (COMP), hyaluronan, soluble CD14 levels, and aggrecanase-1 (ADAMTS-4) activity in synovial fluid and COMP and hyaluronan in plasma were measured. Baseline and postoperative functional outcomes were determined using the patient-reported Lysholm score. To find predictors of postoperative function, linear and logistic regression analyses were performed. The dependent variables were the baseline and postoperative Lysholm score; the independent variables were patient age and body mass index, defect location, defect area, having a bone-on-bone defect, type of defect patch (periosteum or collagen), requirement of an extra procedure, and baseline biomarker levels. Results: The mean baseline Lysholm score was 47.4 ± 17.0, which improved to 64.6 ± 21.7 postoperatively. The activity of ADAMTS-4 in synovial fluid was identified as an independent predictor of the postoperative Lysholm score. Indeed, simply the presence or absence of ADAMTS-4 activity in synovial fluid appeared to be the most important predictive factor. As determined by contingency analysis, when ADAMTS-4 activity was detectable, the odds of being a responder were 3 times smaller than when ADAMTS-4 activity was not detectable. Other predictive factors were the baseline Lysholm score, age at ACI, and defect patch type used. Conclusion: The absence of ADAMTS-4 activity in the synovial fluid of joints with cartilage defects may be used in conjunction with known demographic risk factors in the development of an ACI treatment algorithm to help inform the preclinical decision.

Matrix-induced autologous chondrocyte implantation for treatment of femoral trochlea cartilage injury

To determine the short-term effectiveness of matrix-induced autologous chondrocyte implantation (MACI) for femoral trochlea cartilage injury. A retrospective analysis was performed on the clinical data of 10 patients with femoral trochlea cartilage injury treated with MACI between June 2012 and October 2014. There were 6 males and 4 females, aged from 15 to 48 years (mean, 33 years). The left knee was involved in 3 cases and the right knee in 7 cases. Nine patients had a history of trauma, and 1 case suffered from osteochondritis dissecans. Combined injuries included meniscus injury in 1 case, anterior cruciate ligament injury in 3 cases, and lateral collateral ligament tear in 2 cases. The mean lesion depth was 2.80 mm (range, 2-7 mm), with the mean defect size of 84.85 mm 2 (range, 28.26-153.86 mm 2). The mean duration of definite diagnosis was 14 days (range, 5 days to 3 months). By using arthroscopic biopsy, 200-300 mg healthy articular cartilage at non weight-bearing area of the knee femoral trochlea was collected as a source of seed cells, which were isolated and cultured to prepare MACI membrane. The adhesion activity, growth rate, and mechanical properties of the chondrocytes on the Bio-gide collagen scaffold were evaluated. In addition, the stretch rate, tensile strength, and suture strength of scaffold were tested. MACI membrane was implanted after 2 weeks to 6 months. The visual analogou scale (VAS), Lysholm score, and Tegner movement level score at preoperation and last follow-up were used to assess the function. The MACI membrane was successfully prepared, and the human chondrocytes adhered and grew well on the Bio-gide collagen scaffold. Mechanical test showed that MACI membrane had the stretch rate of 65.27%, the tensile strength of 26.81 MPa, and the suture strength of 6.49 N, indicating good mechanical properties. MACI membrane was successfully implanted. The mean operation time was 58.5 minutes (range, 43-99 minutes), and the mean hospitalization time was 7 days (range, 6-15 days). All incisions healed well. Ten cases were followed up 9 to 16 months (mean, 12 months). Four cases underwent iliac bone graft surgery. The mean healing time was 14 weeks (range, 12-16 weeks). No complications of osteochondrolysis, knee pain, nerve and vascular injury, deep vein thrombosis, and knee adhesion occurred during follow-up. The VAS score, Lysholm score, and Tegner score at last follow-up were significantly improved when compared with preoperative scores ( t=12.060, P=0.000; t=-9.200, P=0.000; t=-14.000, P=0.000). MACI for femoral trochlea cartilage injury has good short-term effectiveness, with less injury and fast function recovery.

Return to Active Duty After Autologous Chondrocyte Implantation for Knee Cartilage Defects in US Marines

Return to Active Duty After Autologous Chondrocyte Implantation for Knee Cartilage Defects in US Marines

Return to Sports Activity and Work After Autologous Chondrocyte Implantation of the Knee

Background: Autologous chondrocyte implantation (ACI) has been associated with satisfying results in everyday activities. Clinical results after ACI treatment of femorotibial lesions are superior in comparison with patellofemoral lesions. There is limited information regarding at which level recreational, amateur, and professional athletes can resume sports and physical activities as well as work after ACI and what parameters influence return to work and sports. Hypothesis: Return to sports activity and work is dependent on defect characteristics such as location and size. Study Design: Case series; Level of evidence, 4. Methods: A total of 130 patients with isolated full-thickness cartilage defects of the knee joint treated with ACI between June 2000 and October 2007 were retrospectively studied by an established questionnaire that assessed sports-specific questions such as frequency, duration, and intensity. Engagement in 32 different sports disciplines was evaluated. In addition, work-specific data were evaluated according to classifications established by the REFA Association. Results were evaluated depending on patient- and defect-specific parameters. Results: The mean ± SD patient age at ACI was 36.2 ± 9.2 years, with a mean defect size of 4.4 ± 1.7 cm2. Defects were located at the femorotibial compartment in 55.7% of cases, whereas lesions of the patellofemoral compartment were found in 44.3%. Mean duration of inability to work after ACI was 13.6 ± 11.0 weeks and did not appear to be influenced by patient age. Defect location and defect size did not appear to significantly influence return-to-work rates, but work intensity before surgery significantly influenced return-to-work rates and duration of absence from work. Workplace adaptations were necessary in only 9.2% of cases postoperatively. With regard to postoperative sports activity, 73.1% of patients were able to return to sports. Neither defect location nor size significantly influenced return to physical activity. Patients participated in a mean of 2.3 different sports during their lifetime. Both duration of exercise and number of sessions per week significantly decreased from before to after surgery. Detailed analysis of 32 different sporting activities revealed that high-impact as well as start-stop sports were generally abandoned in favor of endurance and low-intensity exercises. A lifetime level of competitiveness was maintained in 31.3% of cases, while return to elite sports at the time of the survey became highly unlikely (0.8%). Conclusion: The study results illustrate that treatment of articular cartilage defects of the knee joint leads to satisfactory results concerning everyday activities. With the exception of physical labor, no essential adaptations needed to be made at work. Regarding sports activity, return to low- and moderate-intensity levels appears realistic in the majority of cases, whereas the likelihood of returning to activities with high stress applied on the knee joint is low. Neither defect location nor size appears to significantly influence postoperative sports activity or return-to-work rates.

Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. IV.

Autologous Chondrocyte Implantation for Treatment of Osteochondral Lesions of the Talus

Autologous chondrocyte implantation (ACI) technology and techniques are a rapidly evolving field. There are currently 3 generations of chondrocyte implantation techniques for osteochondral defects. First-generation and some second-generation ACI techniques are in use in the United States, whereas third-generation chondrocyte implantation methods are in the early phases of human clinical trials. ACI is reserved for patients who have failed marrow stimulation. Caveats to this may be the larger osteochondral lesion of the talus (>1.5 cm2) or the presence of significant subchondral cyst (>8 mm), where ACI with “sandwich” bone grafting is more likely to restore the congruity of the articular surface and underlying bone. Complications specific to ACI in osteochondral lesion of the talus include periosteal hypertrophy, capsular adhesion or arthrofibrosis, painful hardware from osteotomy fixation, and lack of graft incorporation. Newer 1-stage techniques that eliminate the need for a second procedure are also promising and less invasive than first-generation procedures. Furthermore, new-generation cell-based therapies eliminate the need for a periosteal patch, and although third-generation techniques are only investigational, it may eliminate complications associated with scaffolds, such as integration, rate of degradation, and biocompatibility. Prospective randomized studies with long-term follow-up are needed to assess the efficacy of ACI in comparison with marrow stimulation.

Factors Influencing the Outcome of Autologous Chondrocyte Implantation: A Systematic Review

Autologous chondrocyte implantation (ACI) is an effective method of treatment of chondral defects of the knee. ACI outcomes are influenced by patient-, knee-, and lesion-specific factors. We compiled subject-level data from current studies on ACI and quantitatively analyzed this data set for associations between patient-, knee-, and lesion-specific factors and the outcome of ACI surgery. A systematic review of studies investigating ACI treatment outcomes in the knee was performed. Only studies that published subject-level data were included. Data on patient and lesion characteristics, as well as clinical outcome scores, were collected. Thirteen studies (305 defects) were included in this review. These studies showed that ACI treatment improves clinical outcomes in different patient populations. However, subject-specific variables such as patient age, gender, body mass index, duration of preoperative symptoms, as well as defect size and location were not associated with International Knee Documentation Committee score or visual analog scale score changes (p > 0.05 for all). Covariate analysis showed that patient age was related to symptom duration prior to surgery (p = 0.009). ACI surgery has been shown to improve outcomes in patients with chondral lesions of the knee. Despite evidence in the literature showing that multiple patient-, knee-, and lesion-specific factors may influence treatment outcomes, our review shows that these factors, solely, do not affect outcomes. However, together, they may synergistically affect outcomes.

Outcomes of Autologous Chondrocyte Implantation in Study of the Treatment of Articular Repair (STAR) Patients With Osteochondritis Dissecans

Background: This is an analysis of the prospective Study of the Treatment of Articular Repair (STAR) to evaluate the effectiveness of autologous chondrocyte implantation (ACI) in a subset of adult patients with osteochondritis dissecans (OCD) knee lesions. Hypothesis: Autologous chondrocyte implantation can improve clinical outcomes in patients with at least 1 chronic OCD lesion of the knee who failed a previous non-ACI cartilage repair treatment. Study Design: Case series; Level of evidence, 4. Methods: Forty patients with at least one failed non-ACI treatment for an OCD knee lesion received ACI in a multicenter study. The modified Cincinnati Knee Rating System, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Short-Form 36 Health Survey (SF-36) were used to assess patient outcomes at baseline and periodically to 48 months. Treatment failures, serious adverse events, and subsequent surgical procedures were recorded. Results: Thirty-two (80%) patients completed the 48-month study. Autologous chondrocyte implantation treatment was successful in 85% of patients. Mean (± standard deviation) overall knee condition score (modified Cincinnati) was 3.1 ± 1.1 at baseline and 6.8 ± 2.0 at month 48. Clinically and statistically significant (P < .001) mean improvements from baseline to month 48 for the KOOS were as follows: 51.5 to 79.5 (pain), 54.8 to 77.9 (symptoms), 27.5 to 63.6 (sports and recreation ability), 63.5 to 86.7 (activities of daily living), and 21.9 to 59.6 (knee-related quality of life). The mean improvement (P < .001) in overall health assessed by the SF-36 was 35.4 to 45.5. Thirty-five percent (n = 14/40) of patients had a subsequent surgical procedure, most frequently debridement of the cartilage lesion. Treatment failure occurred in 6 of 32 (19%) patients. Conclusion: Patients with OCD of the knee had statistically significant pain reduction and functional improvement for up to 48 months after ACI, despite the complexity and severity of the osteochondral lesions.

Autologous Chondrocyte Implantation for Treatment of Cartilage Defects of the Knee

Background: Autologous chondrocyte implantation (ACI) is a well-established treatment option for isolated cartilage defects of the knee joint, providing satisfying outcome. However, cases of treatment failure with the need for surgical reintervention are reported; typical patient’s individual and environmental risk factors have previously not been described. Hypothesis: The need for reintervention after ACI is associated with specific preoperative detectable individual risk factors. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 413 patients following ACI (first, second, and third generation) were filtered for those who required revision surgery during their follow-up time (2-11.8 years). Factors were analyzed that might have significant effects on increased revision rate. Using preoperatively collected data, all patients were grouped according to 12 standard prognostic factors. Apart from odds ratio and Pearson χ2 test, statistical analysis of risk factors was performed with multivariate binary logistic regression models and Cox regression, the method of choice for survival time data. Results: After a follow-up of 4.4 ± 0.9 years (limited to 5 years), a total of 88 patients (21.3%) had undergone surgical revision. The time to revision surgery was 1.8 ± 1.1 years. Four prognostic factors associated with a significantly higher risk for reintervention were detected: (1) female gender (Cox survival fit: P = .033), (2) previous surgeries of the affected joint (P = .002), (3) previous bone marrow stimulation (P = .041), and (4) periosteum patch–covered ACI (P = .028). An influence of patient age, body mass index (BMI), defect number, defect size, lesion origin, lesion location, parallel treatment, or smoking on the risk for reintervention could not be observed. Conclusion: The study identifies clear facts that significantly increase the risk of revision surgery. These facts can be easily obtained preoperatively and may be taken into consideration when indicating ACI.

Evolution and Current Role of Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defects in the Football (Soccer) Player.

Background:Autologous chondrocyte implantation (ACI) continues to technically evolve, but how the technical innovations affect the ability to participate in high-impact sports such as football is unknown.Methods:Clinical studies describing athletes treated with first-, second-, or third-generation ACI techniques were reviewed. The technical developments of ACI were evaluated, and the results in athletes and specifically football (soccer) players were analyzed.Results:Football players reported 72% good to excellent results with significant overall improvement of knee function and activity scores. Return to football was 83% in competitive players but lower in recreational players. Eighty percent of players returned to the same competitive level after ACI, and 87% to 100% maintained their ability to play sports at 5 years postoperatively. Return to sport was better for younger, competitive players with shorter intervals between injury and ACI. New developments of the surgical technique and postoperative rehabilitation were able to reduce the limitations associated with first-generation ACI including invasiveness, graft hypertrophy, and particularly long postoperative rehabilitation. This allowed for faster return to sports like football without compromising the ability for continued competition over time.Conclusion:Articular cartilage repair in football players often allows for successful return to this high-impact sport with excellent durability. The continued evolution of this technique has improved initial shortcomings with important implications for both the professional and recreational athlete.

Rehabilitation After Autologous Chondrocyte Implantation for Isolated Cartilage Defects of the Knee

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.

Autologous Chondrocyte Implantation for Treatment of Focal Cartilage Defects in Patients Age 40 Years and Older

Background Autologous chondrocyte implantation (ACI) is an accepted surgical treatment in patients with isolated cartilage defects of the knee. Age has been considered as a limiting factor and the technique has not been recommended in patients older than 40 to 50 years. Nevertheless, some more recent studies report satisfying clinical results in middle-aged patients. Hypothesis Analogous to the microfracture technique, age over 40 years is associated with inferior clinical outcome after ACI. Study Design Cohort study; Level of evidence, 2. Methods Thirty-seven patients with an average age of 47.8 years (group 1) were matched with 37 patients with an average age of 31 years (group 2). Both groups underwent ACI for treatment of isolated cartilage defects of the knee. All patients were enrolled prospectively and followed for a period of 24 months using International Knee Documentation Committee (IKDC), Lysholm scale, Cincinnati sports scale, and Tegner activity evaluation instruments. Results Statistical analysis revealed a significant increase in function after ACI in both groups as early as 6 months after surgery until the end of the study period. There was only a slight tendency for better clinical outcome in younger patients (IKDC at 24 months: group 1, 72.2 ± 15.8 [standard deviation]; group 2: 76.1 ± 14.1; P = .261; Lysholm at 24 months: group 1: 80.42 ± 15.37; group 2: 80.65 ± 12.01), no statistical significant differences were found between patients of group 1 and group 2 at any of the time points investigated. Conclusion In contrast to other cartilage repair techniques, patients 40 years and older do not have an inferior outcome up to 24 months after ACI for isolated cartilage defects when compared with younger patients.