First-generation Autologous Chondrocyte Implantation Research Articles

Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BackgroundThe purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. MethodsEleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2 ± 6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. ResultsThe AOFAS score improved significantly from the baseline value of 40.4 ± 19.8 to 82.7 ± 12.9 at the final follow-up (p < 0.0005). The NRS for pain improved significantly from 7.8 ± 0.7 at baseline to 4.8 ± 2.1 at the final follow-up (p < 0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1–3) and from a pre-injury value of 5 (range: 3–7) to 3 (range: 2–4) at the final follow-up (p < 0.0005). ConclusionsACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. Level of evidenceLevel IV

Autologous Chondrocyte Implantation (ACI) for Cartilage Defects of the Knee Using Novocart 3D and Novocart Inject

Ever since autologous chondrocyte implantation (ACI) has been introduced, there have been important advancements and progress leading to a more reliable and more standardized application of this technology. While first-generation ACI followed the principle of a cell-suspension being injected under an autologous periosteum patch, second and third generation of ACI are characterized by the use of biomaterials, either using a cell-suspension (2 nd generation) or a combination of cells and the biomaterial (3 rd generation). Due to easier handling and improved clinical outcome, 3 rd generation ACI has become the gold standard for the use of ACI at this time. The present chapter focuses on the Novocart® 3 rd generation ACI products. While Novocart® 3D uses a collagen membrane and therefore a implantable biomaterial, Novocart® Inject is a hydrogel-based ACI product which can be injected into the cartilage defects. Both products are currently under way for central European market authorization by the European Medicinal Agency (EMA), additionally a FDA-approval trial is under way for Novocart® 3D. Products characteristics, indication, surgical technique and clinical outcome are summarized in the present chapter.

Long-term Results of Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation: A Prospective Follow-up at 15 Years

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) procedures have been developed to overcome some of the limits of first-generation autologous chondrocyte implantation. However, while good autologous chondrocyte implantation results have been documented over time, data are scarce on the long-term MACT results. Purpose: To evaluate long-term clinical results of a large cohort of patients treated with hyaluronic acid–based MACT for articular cartilage defects of the knee. Study Design: Case series; Level of evidence, 4. Methods: A long-term evaluation of 113 patients was performed (91 men, 22 women; mean ± SD age, 29.0 ± 10.6 years) for 115 knees affected by chondral and osteochondral lesions of the femoral condyles and trochlea. Of these, 61 knees had undergone previous surgery, while other procedures were combined during the same operation in 48 knees. These patients were prospectively evaluated before surgery and at 2, 5, and 10 years after surgery, as well as at a final mean follow-up of 15 years (range, 12-18 years), with various clinical scores: International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner. Both surgical and clinical failures were documented. Results: The IKDC subjective score increased from the basal level of 39.9 ± 14.6 (mean ± SD) to 77.3 ± 20.5 (P < .0005) at 2 years; results remained stable up to the 15-year follow-up (76.9 ± 20.5). EQ-VAS and Tegner scores showed a statistically significant improvement up to 10 years, with a further significant improvement at the final follow-up. A failure rate of 15.0% was documented, which increased to 21.7% when clinical failures were also considered. A worse outcome was found for older age (P < .0005), female sex (P = .002), degenerative lesions (P < .0005), longer duration of symptoms (P = .005), and previous surgery (P < .0005). Conclusion: Arthroscopic MACT offered good and long-lasting results that were stable over time and resulted in a limited number of failures and reinterventions for up to 15 years of follow-up. Several factors were identified as having a prognostic value: a worse outcome could be expected in older patients, female patients, those affected by lesions with a degenerative cause, those having a longer duration of symptoms, and patients who underwent previous surgery.

Chondral and Osteochondritis Dissecans Lesions Treated by Autologous Chondrocytes Implantation: A Mid- to Long-Term Nonrandomized Comparison.

The aim of this study was to compare the clinical outcome of cartilage repair with autologous chondrocyte implantation (ACI) in patients with osteochondritis dissecans (OCD) lesions and full-thickness cartilage lesions. This study included a cohort of 115 consecutive patients with a cartilage lesion of the knee treated with ACI. Of the patients, 35 had an OCD lesion and 80 a full-thickness cartilage lesion. During a follow-up period from 2 to 13 years all treatment failures were identified. The failure rate between OCD lesions and full-thickness cartilage lesions was compared with Kaplan-Meier analysis. Patient-reported outcome was evaluated 2 years postoperatively with the Lysholm score. During the follow-up 21 out of 115 patients encountered a treatment failure. The failure rate for full-thickness cartilage lesions was 19.1% and for OCD lesions 43.3% over the 10-year follow-up. Patient-reported outcome improved from baseline to 2 years postoperatively. The improvement from baseline was statistically significant, and the Lysholm score improved more than the minimal clinically important difference. The patient-reported outcome showed no difference between lesion types at 2 years. In the presented retrospective study, the failure rate of first-generation ACI was higher in OCD lesions than in large full-thickness cartilage lesions, suggesting that OCD lesions may associate with properties that affect the durability of repair tissue. Future prospective studies are needed to tell us how to best repair OCD lesions with biological tissue engineering.

Failures, Reoperations, and Improvement in Knee Symptoms Following Matrix-Assisted Autologous Chondrocyte Transplantation: A Meta-Analysis of Prospective Comparative Trials.

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. 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). 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. 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.

Equivalent 10-Year Outcomes After Implantation of Autologous Bone Marrow–Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation for Chondral Defects of the Knee

Background: The use of bone marrow–derived mesenchymal stem cells (BMSCs) in cartilage repair procedures circumvents some of the limitations of autologous chondrocyte implantation (ACI), but long-term outcomes for this newer procedure are lacking. The authors previously reported comparable outcomes for the 2 procedures at 2-year follow-up. Purpose/Hypothesis: The purpose was to compare the long-term clinical outcomes of ACI versus BMSCs. It was hypothesized that there would be no significant difference between the groups in terms of patient-reported outcome scores and safety outcomes at 10-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Seventy-two patients who underwent either ACI or BMSC implantation—matched in terms of age and lesion site— were followed up to a median of at least 10 years. Patients were assessed with the 36-item Short Form Health Survey (SF-36), the International Knee Documentation Committee knee evaluation form, the Lysholm Knee Score, and the Tegner Activity Scale. In addition, information was obtained regarding any additional surgical procedures as well as safety data, with particular attention to infection and tumor formation. Results: There was an improvement in all patient-reported outcomes scores apart from the Mental Component Summary of the SF-36 after cartilage repair surgery. There was no significant difference in any of the patient-reported outcomes between cohorts at any time point. Six and 5 patients in the ACI and BMSC groups, respectively, underwent subsequent surgical procedures, including 1 total knee replacement in the BMSC group. None of the patients in either group developed any deep infection or tumor within the follow-up period. Conclusion: BMSC implantation used for the treatment of chondral defects of the knee appears to result in equivalent clinical outcomes to first-generation ACI at up to 10 years, with no apparent increased tumor formation risk.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint

Background: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). Purpose: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients’ level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. Results: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. Conclusion: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

A 20-Year Follow-up After First-Generation Autologous Chondrocyte Implantation

Background: Treating articular cartilage defects is a demanding problem. Although several studies have reported durable and improved clinical outcomes after autologous chondrocyte implantation (ACI) over a long-term period, there is no report with over 20 years’ follow-up. Purpose: To evaluate clinical outcomes after first-generation ACI for the treatment of knees with disabling, large single and multiple cartilage defects for which patients wished to avoid prosthetic arthroplasty, with a minimum of 20 years’ follow-up. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed prospectively collected data from 23 patients (24 knees; mean age, 35.4 years [range, 13-52 years]) undergoing ACI for the treatment of symptomatic, full-thickness articular cartilage lesions. A mean of 2.1 lesions per knee were treated over a mean total surface area of 11.8 cm2 (range, 2.4-30.5 cm2) per knee. Kaplan-Meier survival analysis and functional outcome scores, including the modified Cincinnati Knee Rating System, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form–36 (SF-36), were used. Patients also self-reported an improvement in pain with a visual analog scale and a satisfaction survey. Results: The 20-year survival rate was 63% (95% CI, 40%-78%). The evaluation of the 15 knees with retained grafts demonstrated that all clinical scores except the WOMAC subscore for stiffness and SF-36 mental component summary score improved significantly and were sustained to 20 years postoperatively. Ninety-three percent of these patients rated knee-specific outcomes as good or excellent. The outcomes for 9 of 24 knees were considered failures, including 5 undergoing revision ACI and 4 being converted to arthroplasty at a mean of 1.7 and 5.9 years, respectively. Only 1 of 5 knees that underwent revision ACI was converted to arthroplasty at 1.9 years after the index surgery, and the other 4 patients were able to maintain their biological knee. Overall, 20 years later, 79% of patients maintained their native knee, for which they initially sought treatment, and were satisfied when evaluated. Conclusion: First-generation ACI provided satisfactory survival rates and significant clinical improvements over a 20-year follow-up, which offers an important standard for comparison with newer-generation ACI technologies of the future.

A Cost-Effectiveness Analysis of Surgical Treatment Modalities for Chondral Lesions of the Knee: Microfracture, Osteochondral Autograft Transplantation, and Autologous Chondrocyte Implantation.

Background:Numerous surgical options exist to treat chondral lesions in the knee, including microfracture (MFx), osteochondral autograft transplantation (OAT), first-generation autologous chondrocyte implantation (ACI-1), and next-generation ACI (ACI-2).Purpose:To compare the cost-effectiveness of MFx, OAT, and ACI-1. The secondary purpose of this study was to compare the functional outcomes of MFx, OAT, ACI-1, and ACI-2.Study Design:Systematic review; Level of evidence, 2.Methods:Two independent reviewers conducted an online literature search of 2 databases for level 1 and 2 studies using the Lysholm, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), and/or Hospital for Special Surgery (HSS) Knee Score. A weighted mean difference in pre- to postoperative functional outcome score was calculated for each treatment. The mean per-patient costs associated with MFx, OAT, and ACI-1 were determined from a recent publication based on review of a national private insurance database. The cost for each procedure was then divided by the weighted mean difference in functional outcome score to give the cost-per-point change in outcome score.Results:A total of 12 studies (6 level 1, 6 level 2) met the inclusion criteria for the functional outcome analysis, including 730 knees (MFx, n = 300; OAT, n = 90; ACI-1, n = 68; ACI-2, n = 272). The mean follow-up was not significantly different between groups (MFx, 29.4 months; OAT, 38.3 months; ACI-1, 19.0 months; ACI-2, 26.7 months). The mean increase in functional outcome score was 23 for MFx, 19 for OAT, 20 for ACI-1, and 35 for ACI-2. The change in functional outcome score was significantly greater for ACI-2 when compared with all other treatments (P < .0001). The cost-per-point change in functional outcome score was $200.59 for MFx, $313.84 for OAT, and $536.59 for ACI-1.Conclusion:MFx, OAT, ACI-1, and ACI-2 are effective surgical procedures for the treatment of cartilage defects in the knee. All 4 treatments led to an increase in functional outcome scores postoperatively with a short-term follow-up. ACI-2 had a statistically greater improvement in functional outcome scores as compared with the other 3 procedures. MFx was found to be the most cost-effective treatment option and ACI-1 the least cost-effective.

Long-term clinical results and MRI changes after autologous chondrocyte implantation in the knee of young and active middle aged patients.

BackgroundAutologous chondrocyte implantation (ACI) represents a valid surgical option for symptomatic full-thickness chondral lesions of the knee. Here we report long-term clinical and MRI results of first-generation ACI.Materials and methodsFifteen patients (mean age 21.3 years) underwent first-generation ACI for symptomatic chondral defects of the knee between 1997 and 2001. The mean size of the lesions was 5.08 cm2 (range 2–9 cm2). Patients were evaluated using the International Knee Documentation Committee (IKDC) Knee Examination Form, the Tegner Activity Scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). High-resolution MRI was used to analyze the repair tissue with nine variables (the MOCART scoring system).ResultsThe mean follow-up period was 148 months (range 125–177 months). ACI resulted in substantial improvements in all clinical outcome parameters, even as much as 12 years after implantation. A significant decrease in the MOCART score was recorded at final measurement. Reoperation was required in 2 patients; failure was caused by partial detachment of the graft in both cases.ConclusionAutologous chondrocyte implantation is an effective and durable solution for the treatment of large, full-thickness cartilage and osteochondral lesions, even in young and active middle-aged patients. High-resolution MRI is a useful and noninvasive method for evaluating the repaired tissue.Level of evidenceIV.

Autologous Chondrocyte Implantation With Collagen Membrane

The first-generation autologous chondrocyte implantation (ACI-P) described by Peterson and colleagues used a periosteal patch to form a watertight cover over the articular cartilage defect, under which the autologous chondrocyte suspension was injected. Although good to excellent outcomes were often seen in >80% of patients and the durability of the repair documented up to 20 years, the procedure was noted to have a high rate of subsequent surgical procedures, most often for arthroscopic debridement of periosteal hypertrophy or incomplete incorporation. Consequently, the surgical technique advanced to use a porcine-derived bilayer of type I/III collagen with a porous layer that favors cell attachment and a smooth, compact layer that is cell occlusive. In use of the collagen membrane ACI, prospective studies have shown no diminution in clinical results and a marked reduction in subsequent surgeries from graft hypertrophy to <3%. Use of the collage membrane for ACI-C in the United States is currently an off-label use of an FDA-approved membrane, which should be discussed with the patient before surgery.

Clinical Profiling in Cartilage Regeneration

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) was developed to overcome the limitations of first-generation autologous chondrocyte implantation. Although short-term/midterm results are now available for a small series of patients, the literature still lacks studies on large cohorts of patients evaluated at midterm/long-term follow-up. Purpose: Not all patients can have the same benefit from this procedure. The aim of this study is to analyze a large cohort of patients treated with hyaluronan-based MACT to perform clinical profiling and to highlight the patient- and lesion-specific aspects that play a key role in determining the prognosis. Study Design: Case series; Level of evidence, 4. Methods: A total of 142 patients were treated for lesions involving the femoral condyles and trochleae; 133 knees were followed up yearly for 7 years. The average size of the defects was 2.3 ± 1.0 cm2. The origin was traumatic in 44 cases and degenerative in 57 cases, and 32 knees were affected by osteochondritis dissecans (OCD). The clinical outcome was analyzed using the International Knee Documentation Committee (IKDC), EuroQol visual analog scale, and Tegner scores. The influence of the following factors was analyzed: sex, age, body mass index, site, lesion origin, lesion size, previous or combined surgery, and symptom duration. Results: A marked improvement in all scores was found: the IKDC subjective score increased from the basal level of 39.6 ± 14.4 to 71.9 ± 19.8 (P < .0005) at 12 months; a further improvement was observed at 24 months (77.0 ± 20.5; P < .0005). The results were stable over time up to the 7-year evaluation (77.4 ± 22.1). The failure rate was 10.7%. Better results were seen in the trochleae, and among femoral condyles, the following factors were found to influence the clinical outcome positively: traumatic and OCD origin, male sex, short symptom duration (for traumatic lesions), small lesion size (for OCD), young age, and no previous surgery. Conclusion: Treatment with MACT provides good and stable clinical results. Injury origin, sex, symptom duration, lesion size, lesion site, age, and previous surgery might determine the final outcome and can be used as a sort of clinical profiling to guide the surgeon in the choice of this procedure and in giving realistic expectations to patients requiring cartilage treatment.

ISAKOS Upper Extremity Committee Shoulder Rotator Cuff Consensus, Plus Chondrocyte Implantation and ACL Systematic Reviews

ISAKOS Upper Extremity Committee Shoulder Rotator Cuff Consensus, Plus Chondrocyte Implantation and ACL Systematic Reviews

Long-term Outcomes After First-Generation Autologous Chondrocyte Implantation for Cartilage Defects of the Knee

Background: Autologous chondrocyte implantation (ACI) represents an established surgical therapy for large cartilage defects of the knee joint. Although various studies report satisfying midterm results, little is known about long-term outcomes. Purpose: To evaluate long-term clinical and magnetic resonance imaging (MRI) outcomes after ACI. Study Design: Case series; Level of evidence, 4. Methods: Between January 1997 and June 2001, a total of 86 patients were treated with ACI for isolated cartilage defects of the knee. The mean patient age at the time of surgery was 33.3 ± 10.2 years, and the mean defect size was 6.5 ± 4.0 cm2. Thirty-four defects were located on the medial femoral condyle and 13 on the lateral femoral condyle, while 6 patients were treated for cartilage defects of the trochlear groove and 17 for patellar lesions. At a mean follow-up of 10.9 ± 1.1 years, 70 patients (follow-up rate, 82%) treated for 82 full-thickness cartilage defects of the knee were available for an evaluation of knee function using standard instruments, while 59 of these patients were additionally evaluated by 1.5-T MRI to quantify the magnetic resonance observation of cartilage repair tissue (MOCART) score. Clinical function at follow-up was assessed by means of the Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Knee injury and Osteoarthritis Outcome Score (KOOS). Patient activity was assessed by the Tegner score. In addition, pain on a visual analog scale (VAS) and patient satisfaction were evaluated separately. Results: At follow-up, 77% reported being “satisfied” or “very satisfied.” The mean IKDC score at follow-up was 74.0 ± 17.3. The mean Lysholm score improved from 42.0 ± 22.5 before surgery to 71.0 ± 17.4 at follow-up (P < .01). The mean pain score on the VAS decreased from 7.2 ± 1.9 preoperatively to 2.1 ± 2.1 postoperatively. The mean MOCART score was 44.9 ± 23.6. Defect-associated bone marrow edema was found in 78% of the cases. Nevertheless, no correlation between the MOCART score and clinical outcome (IKDC score) could be found (Pearson coefficient, r = 0.173). Conclusion: First-generation ACI leads to satisfying clinical results in terms of patient satisfaction, reduction of pain, and improvement in knee function. Nevertheless, full restoration of knee function cannot be achieved. Although MRI reveals lesions in the majority of the cases and the overall MOCART score seems moderate, this could not be correlated with long-term clinical outcomes.

Evidence-Based Status of Second- and Third-Generation Autologous Chondrocyte Implantation Over First Generation: A Systematic Review of Level I and II Studies

The purpose of this study was to examine the Level I and II evidence for newer generations of autologous chondrocyte implantation (ACI) versus first-generation ACI and to establish whether the newer generations have overcome the limitations associated with first-generation ACI. A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that dealt with ACI were identified. Only Level I and II studies that compared newer generations against earlier generations were selected, whereas studies that compared ACI against other methods of cartilage repair were excluded. A total of 7 studies matched the selection criteria. Two studies compared periosteum-based autologous chondrocyte implantation (P-ACI) against collagen membrane-based autologous chondrocyte implantation (C-ACI), whereas one study each compared membrane-associated autologous chondrocyte implantation (MACI) against P-ACI and C-ACI. One study on C-ACI compared results related to age, whereas 2 studies evaluated postoperative rehabilitation after MACI. There was weak evidence showing that C-ACI is better than P-ACI and that MACI is comparable with both P-ACI and C-ACI. The weak evidence is because of studies with short durations of follow-up, small numbers of patients, medium-sized defects, and younger age groups. There is good evidence favoring an accelerated weight-bearing regimen after MACI. There is currently no evidence that supports scaffold-based ACI or arthroscopic implantation over first-generation ACI. The hypothesis is thus partly proved in favor of C-ACI/MACI against P-ACI with weak evidence, in favor of accelerated weight bearing after MACI with strong evidence, and not in favor of arthroscopic and scaffold-based implantations because of unavailable evidence. LEVELOF EVIDENCE: Level II, systematic review of Level I and II studies.

First-Generation Autologous Chondrocyte Implantation in Patients With Cartilage Defects of the Knee: 7 to 14 Years' Clinical and Magnetic Resonance Imaging Follow-up Evaluation

The purpose of this study was to evaluate the overall long-term improvement of autologous chondrocyte implantation (ACI) treatment in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Furthermore, we aimed to assess the impact of independent variables on clinical outcomes and patient satisfaction. We evaluated 23 patients (mean age, 30.5 ± 8.2 years) with full-thickness chondral lesions of the distal femur who underwent first-generation ACI with periosteum between 1997 and 2004. The Lysholm score, Tegner activity score, subjective International Knee Documentation Committee score, numeric rating scale score, and Short Form 36 score were used for clinical assessment preoperatively, at 1 year postoperatively, and at 7 to 14 years (mean, 9.9 years) after surgery. MRI was performed to evaluate the cartilage preoperatively and at final follow-up, by use of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. ACI resulted in a substantial improvement in all clinical outcome parameters, even as much as 14 years after implantation, although a small deterioration was noticed between intermediate and final evaluations in some outcome parameters. Of the patients, 73.1% stated that they would undergo the operation again. Younger patients with a shorter duration of preoperative symptoms and smaller defect sizes benefited most. MRI findings confirmed complete defect filling in 52.3% of the patients at final follow-up. Our long-term results confirm that first-generation ACI is an effective treatment for large full-thickness chondral and osteochondral lesions of the knee joint. Younger patients with a shorter duration of preoperative symptoms and smaller defect size benefited most in our study. Level IV, therapeutic case series.

ACI and MACI

Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results. Autologous chondrocyte implantation (ACI) has been developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented at medium-long follow-up. Bioengineering technology further improved this regenerative treatment approach to include matrix-assisted ACI (MACI) techniques. These procedures have been introduced in the clinical practice one decade ago, showing similar results while at the same time overcoming most of the concerns related to the first-generation ACI. The use of scaffolds to create a cartilage-like tissue in a three-dimensional culture system allows for the optimization of the procedure from both the biological and surgical point of view. However, despite thousands of treated patients and many published studies suggesting good clinical results and durability of these procedures, the properties of healthy, normal articular cartilage are still unmatched by any available substitute. Both indications and results of these substitutes are still controversial. The role of many variables that may influence the final outcome still need to be clarified to further improve the potential benefits of these biological regenerative procedures.

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.

One-stage vs two-stage cartilage repair: a current review

correspondence: Ming-hao Zheng centre of Orthopaedic Research, school of surgery, University of Western Australia, 35 stirling highway, crawley WA 6009, Perth, Australia Tel +61 8 6488 2807 Fax +61 8 6488 1919 email minghao.zheng@uwa.edu.au Introduction: Articular cartilage has a poor capacity for regeneration if damaged. Various methods have been used to restore the articular surface, improve pain, function, and slow progression to osteoarthritis. Method: A PubMed review was performed on 18 March, 2010. Search terms included “autologous chondrocyte implantation (ACI)” and “microfracture” or “mosaicplasty”. The aim of this review was to determine if 1-stage or 2-stage procedures for cartilage repair produced different functional outcomes. Results: The main procedures currently used are ACI and microfracture. Both first-generation ACI and microfracture result in clinical and functional improvement with no significant differences. A significant increase in functional outcome has been observed in second-generation procedures such as Hyalograft C, matrix-induced ACI, and ChondroCelect compared with microfracture. ACI results in a higher percentage of patients with clinical improvement than mosaicplasty; however, these results may take longer to achieve. Conclusion: Clinical and functional improvements have been demonstrated with ACI, microfracture, mosaicplasty, and synthetic cartilage constructs. Heterogeneous products and lack of good-quality randomized-control trials make product comparison difficult. Future developments involve scaffolds, gene therapy, growth factors, and stem cells to create a single-stage procedure that results in hyaline articular cartilage.

Autologous Chondrocyte Implantation

The purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures. We conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures. Thirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique. Cartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.