Results Of Autologous Chondrocyte Implantation Research Articles

Comparative Outcomes of Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation with Patellar Realignment for Patellar Instability with Associated Cartilage Defects

PurposeThe purpose of this study was to determine clinical and functional outcomes in patients treated with autologous chondrocyte implantation (ACI) or osteochondral allograft (OCA) transplantation for chondral defects secondary to patellar instability with concomitant medial patellofemoral ligament (MPFL) reconstruction and tibial tubercle osteotomy (TTO) for patellar realignment. MethodsA retrospective review identified patients who underwent ACI or OCA transplantation with concomitant MPFL reconstruction and TTO . Patients were excluded if they did not have concomitant MPFL reconstruction and TTO, had the presence of other intra-articular pathologies, or failed to complete postoperative subjective outcome evaluations at a minimum of 2 years following surgery. Subjective outcome measures included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and Short Form Health Survey (SF-12) physical scores, collected a minimum of 2 years after surgery. Defect location, size, complications, and rate of subsequent surgery were determined. ResultsEighteen total patients were included in this study. The ACI cohort included 11 patients with 13 total defects that were treated with ACI. The OCA cohort included 7 patients with 10 total defects that were treated with OCA. This was due to a number of patients in either group having multiple cartilage defects. Twenty-three total chondral defects were compared to analyze clinical and functional outcomes following surgical correction (ACI: n=13, OCA: n=10). Five defects were noted on the femoral condyle and 18 on the patellar facets/central ridge. Defects were comparable between groups including, size measured during index-arthroscopy (ACI = 3.34 cm2, 95% CI [2.3 cm2 - 4.4 cm2] vs OCA = 4.03 cm2, 95% CI [3.1 cm2 - 5.0 cm2]; P=.351), Outerbridge classification (ACI = 54.8% grade 4 vs OCA = 60.0% grade 4; P=1.000), and AMADEUS score (ACI = 47.1 vs OCA = 58.6; P=.298). Postoperative outcomes were comparable including revision rate (ACI = 15.4% vs OCA = 10.0%; P=1.000) and 2-year IKDC scores (ACI = 74.2, 95% CI [65.2 - 83.2] vs OCA = 51.2, 95% CI [30.3 - 72.1]; P=.077). ACI did have significantly higher 2-year KOOS JR (85.1, 95% CI [76.9 - 93.3] vs 63.7, 95% CI [49.1 - 78.3]; P=.031) and SF-12 scores (54.1, 95% CI [52.0 - 56.2] vs 42.6, 95% CI [35.8 - 49.4]; P=.007) compared to OCA. ConclusionACI or OCA transplantation for chondral defects with concomitant MPFL reconstruction and TTO can be safely performed in an outpatient setting with functional and clinical outcomes being comparable. Level of EvidenceRetrospective Case Series Study (Level 3)

A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee

Background: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. Purpose: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. Results: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, −1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, −0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). Conclusion: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. Registration: International Standard Randomised Controlled Trial Number: 48911177

Effect of Platelet-Rich Plasma on Autologous Chondrocyte Implantation for Chondral Defects: Results Using an In Vivo Rabbit Model.

Background:Articular cartilage repair remains challenging despite the availability of techniques, including autologous chondrocyte implantation (ACI) for repairing large cartilage defects. Platelet-rich plasma (PRP) therapy, a novel therapy focused on chondrocyte regeneration, needs to be investigated regarding its potential to improve the outcomes of ACI.Purpose:To examine the effect of PRP therapy on the outcomes of cartilage repair using the ACI procedure in a rabbit model of knee joint cartilage damage.Study Design:Controlled laboratory study.Methods:A total of 30 knees in 15 Japanese White rabbits (joint cartilage damage model) were divided into nontreatment (n = 7), PRP (n = 8), ACI (n = 7), and combined ACI and PRP (n = 8) groups. At 4 weeks and 12 weeks postoperatively, histological and visual examination of the surgical site was performed, and the regenerated cartilage and calcified bone areas were measured by imaging the specimens.Results:Pretransplantation evaluation in the cultured cartilage showed the histological properties of hyaline cartilage. At 4 weeks postoperatively, the regenerated cartilage area at the surgical site showed a larger safranin O–positive area in the ACI group (2.73 ± 4.46 mm2) than in the combined ACI and PRP group (1.71 ± 2.04 mm2). Calcified bone formation in the ACI group was relatively lower than that in the other groups. Cartilage repair failure occurred in all groups at 12 weeks postoperatively.Conclusion:The authors found no positive effects of PRP on the outcomes of ACI in a rabbit model. There was a smaller safranin O–positive region with the addition of PRP to ACI compared with ACI alone. In the subchondral bone, bone formation might have been promoted by PRP.Clinical Relevance:Administering PRP at the time of ACI may not have a positive effect and may have deleterious effects on cartilage engraftment and regeneration.

Is There an Association Between Authors' Conflicts of Interest and Outcomes in Clinical Studies Involving Autologous Chondrocyte Implantation?

Background:Autologous chondrocyte implantation (ACI) is an increasingly popular technique for the treatment of articular cartilage defects. Because several companies have financial interests in ACI, it is important to consider possible conflicts of interest when evaluating studies reporting outcomes of ACI.Purpose:To determine whether there is an association between authors’ financial conflicts of interest and the outcomes of ACI studies.Study Design:Cross-sectional study.Methods:A search of PubMed and MEDLINE databases for “autologous chondrocyte implantation” was performed. Clinical studies published after 2012 through May 15, 2019, and in English were included. Studies were determined to have financial conflicts of interest if any contributing author had relevant conflicts, either self-reported in the published study’s disclosures section or reported online in the American Academy of Orthopaedic Surgeons Disclosure database or the Centers for Medicare & Medicaid Services Open Payments database. The outcomes of each study were rated as favorable, equivocal, or unfavorable based on predefined criteria and then tested for association with conflicts of interest through use of the Fisher exact test.Results:A total of 79 studies met the inclusion criteria. Nearly all studies were of level 3 or 4 evidence. Conflicts of interest were established in 51.90% of studies (n = 41). Conflicts that were not self-reported by the authors were discovered in 18% of studies. The level of evidence was not associated with conflict of interest. No statistically significant difference was found in the rate of favorable outcomes between studies with conflicts (92.68%) and those with no conflicts (81.58%) (P = .126). Publications by US authors were more likely to have financial conflicts of interest (P = .003).Conclusion:Favorable results were reported in a majority of studies involving ACI. No statistical association was found between the frequency of favorable outcomes and the presence of financial conflicts of interest, country of authorship, or level of evidence. There was a trend toward more favorable outcomes in studies with conflicts of interest. Additionally, nearly 20% of publications had possible conflicts found online that were not self-reported. It is critical for orthopaedic surgeons to judiciously evaluate published studies and consider financial conflicts of interest before performing ACI techniques on patients.

Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation Render Comparable Outcomes in the Setting of Failed Marrow Stimulation

Background: Marrow stimulation techniques (MSTs) such as subchondral drilling and microfracture are often chosen as first-line treatment options for symptomatic cartilage defects of the knee. When an MST fails, many cartilage restoration techniques are employed, including autologous chondrocyte implantation (ACI) and osteochondral allograft (OCA). However, a few series in the literature suggest that ACI after a failed MST results in inferior outcomes as compared with primary ACI. Purpose/Hypothesis: The purpose of this study was (1) to evaluate the clinical outcomes of ACI and OCA after a failed MST (secondary ACI and OCA) and compare them with the outcomes of primary ACI and OCA and (2) to compare clinical outcomes of secondary ACI and secondary OCA for refractory lesions involving the femoral condyle. The hypotheses were as follows: (1) secondary ACI will render inferior functional outcomes and an increased clinical failure rate as compared with primary ACI, (2) secondary OCA will render comparable results to primary OCA, and (3) secondary OCA will render superior outcomes to secondary ACI. Study Design: Cohort study; Level of evidence, 3. Methods: Patients were retrospectively identified who underwent ACI and OCA for symptomatic chondral lesions of the knee refractory to a previous MST. Age-, sex-, and body mass index–matched groups of patients undergoing primary ACI and OCA were used as controls. Postoperative data were prospectively collected using several subjective scoring systems (Tegner, Lysholm, International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, 12-Item Short Form Health Survey). Groups were compared with regard to patient-reported outcomes, subjective satisfaction, clinical failure rate, and reoperation. Student t tests were used for continuous data, and chi-square tests were performed for categorical data. Results: A total of 359 patients were examined: 92 patients undergoing secondary ACI, 100 primary ACI, 88 secondary OCA, and 79 primary OCA. The mean patient age was 30.3 years (range, 14.9-49.9 years) at the time of ACI and 35.4 (range, 15-54.5) at the time of OCA. There was no difference between the primary and secondary groups with regard to postoperative functional scores, subjective satisfaction, reoperation rate, and clinical failure rate. Conclusion: ACI and OCA are both viable treatment options for chondral defects of the knee, even in the setting of a failed MST. Secondary ACI renders functional outcomes, subjective satisfaction, and reoperation and failure rates comparable with primary ACI and secondary OCA.

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.

Short-term clinical results of autologous chondrocyte implantation (JACC) 2 years after surgery

Short-term clinical results of autologous chondrocyte implantation (JACC) 2 years after surgery

Modelling and predicting the long-term clinical outcome of autologous chondrocyte implantation

Modelling and predicting the long-term clinical outcome of autologous chondrocyte implantation

Treatment of Failed Articular Cartilage Reconstructive Procedures of the Knee: A Systematic Review.

Background:Symptomatic articular cartilage lesions of the knee are common and are being treated surgically with increasing frequency. While many studies have reported outcomes following a variety of cartilage restoration procedures, few have investigated outcomes of revision surgery after a failed attempt at cartilage repair or reconstruction.Purpose:To investigate outcomes of revision cartilage restoration procedures for symptomatic articular cartilage lesions of the knee following a previously failed cartilage reconstructive procedure.Study Design:Systematic review; Level of evidence, 4.Methods:A literature search was performed by use of the PubMed, EMBASE, and MEDLINE/Ovid databases for relevant articles published between 1975 and 2017 that evaluated patients undergoing revision cartilage restoration procedure(s) and reported outcomes using validated outcome measures. For studies meeting inclusion criteria, relevant information was extracted.Results:Ten studies met the inclusion criteria. Lesions most commonly occurred in the medial femoral condyle (MFC) (52.8%), with marrow stimulation techniques (MST) the index procedure most frequently performed (70.7%). Three studies demonstrated inferior outcomes of autologous chondrocyte implantation (ACI) following a previous failed cartilage procedure compared with primary ACI. One study comparing osteochondral allograft (OCA) transplant following failed microfracture (MFX) with primary OCA transplant demonstrated similar clinical outcomes and graft survival at midterm follow-up. No studies reported outcomes following osteochondral autograft transfer (OAT) or newer techniques.Conclusion:This systematic review of the literature reporting outcomes following revision articular cartilage restoration procedures (most commonly involving the MFC) demonstrated a high proportion of patients who underwent prior MST. Evidence is sufficient to suggest that caution should be taken in performing ACI in the setting of prior MST, likely secondary to subchondral bone compromise. OCA appears to be a good revision treatment option even if the subchondral bone has been violated from prior surgery or fracture.

Second Generation Autologous Chondrocyte Implantation in the Patella: Improved Pain Relief and Functional Outcomes among U.S. Army Servicemembers

Objectives:To evaluate the functional outcomes of autologous chondrocyte implantation (ACI) for high-grade patellofemoral chondral defects in a predominately young, high-demand military demographic.Methods:We conducted a retrospective review of all United States military and Tricare beneficiaries undergoing ACI for Outerbridge grade III or IV patellofemoral chondral defects at a two high-volume military medical centers between 2007 and 2014. Second generation surgical technique was performed using autologous cultured chondrocytes (Vericel, Inc; Boston, MA) secured with a type I/III collagen bilayer membrane. Inclusion criteria required minimum two-year surveillance, although patients with knee-related medical discharge were also included to limit non-responder bias. Exclusion criteria were applied to individuals with predominately condylar involvement, periosteal patch coverage, and/or procedure miscoding Demographic information, surgical characteristics, and clinical outcomes were extracted from the electronic medical record. Averages were calculated with standard deviations (SD). Univariate analysis was used to determine significant independent predictors of surgical failure, which was defined as revision chondral procedure or conversion to arthroplasty. Relative risk was quantified with use of odds ratios (OR) with 95% confidence intervals (95% CI).Results:A total 57 patients with 58 knees were identified at average 2.13 year follow-up within the military health care system. The median age was 33.8 years (range, 20.3 to 49.9). Males comprised 77% of patients (n=44), and 93% (n=53) were active duty military status. Mean patient body mass index (BMI) was 30.3 kg/m2, tobacco use was documented in at least 19.3% (n=11), and only one patient had failed prior marrow stimulation procedure. The average lesion size for ACI was 502 mm2 (SD 318; range, 121-1600 mm2) and most defects were based on patella (91.3%). The average tibial tubercle-trochlear groove (TT-TG) distance was 13.9 mm (SD 3.5), and nearly all knees underwent concomitant anteromedializing or offloading tibial tubercle osteotomy (n=56; 97%). Additionally, only three patients required proximal realignment procedure. Only 1 patient (1.7%) required revision chondral procedure, and there were no cases of graft site hypertrophy or conversion to knee arthroplasty. With a “high” or “severe” average patient-reported pain level (86%), the average postoperative visual analog scale (VAS) was 2.3 (SD 2.2; median, 2) at final follow-up. At an average of 1.9 years postoperatively, 14 patients (24.6%) underwent medical discharge due to reported persistent, rate-limiting knee pain, although the average patient-reported VAS was 3 (SD 2.3; range, 0 to 6). No demographic or surgical variables were significantly associated with subsequent adverse clinical outcome (p>0.05).Conclusion:For patellofemoral chondral defects without failed primary procedure, second generation ACI can successful decrease patient-reported anterior knee pain among highly-active and athletic subsets. Approximately 75% of patients resumed modified military duty or preoperative level of function at short-term follow-up, and only 2% underwent revision. Knee related medical discharge occurred in nearly a quarter of patients, but did not preclude significant pain relief or return to lower demand activities.

Failure of Autologous Chondrocyte Implantation.

Level IV.

DNA Methylation Profiling in Chondrocyte Dedifferentiation In Vitro

DNA methylation has emerged as a crucial regulator of chondrocyte dedifferentiation, which severely compromises the outcome of autologous chondrocyte implantation (ACI) treatment for cartilage defects. However, the full-scale DNA methylation profiling in chondrocyte dedifferentiation remains to be determined. Here, we performed a genome-wide DNA methylation profiling of dedifferentiated chondrocytes in monolayer culture and chondrocytes treated with DNA methylation inhibitor 5-azacytidine (5-AzaC). This research revealed that the general methylation level of CpG was increased while the COL-1A1 promoter methylation level was decreased during the chondrocyte dedifferentiation. 5-AzaC could reduce general methylation levels and reverse the chondrocyte dedifferentiation. Surprisingly, the DNA methylation level of COL-1A1 promoter was increased after 5-AzaC treatment. The COL-1A1 expression level was increased while that of SOX-9 was decreased during the chondrocyte dedifferentiation. 5-AzaC treatment up-regulated the SOX-9 expression while down-regulated the COL-1A1 promoter activity and gene expression. Taken together, these results suggested that differential regulation of the DNA methylation level of cartilage-specific genes might contribute to the chondrocyte dedifferentiation. Thus, the epigenetic manipulation of these genes could be a potential strategy to counteract the chondrocyte dedifferentiation accompanying in vitro propagation. J. Cell. Physiol. 232: 1708-1716, 2017. © 2016 Wiley Periodicals, Inc.

Long-term Outcomes of Autologous Chondrocyte Implantation in Adolescent Patients

Background: Treating symptomatic articular cartilage lesions is challenging, especially in adolescent patients, because of longer life expectancies and higher levels of functional activity. For this population, long-term outcomes after autologous chondrocyte implantation (ACI) remain to be determined. Purpose: To evaluate long-term outcomes in adolescents after ACI using survival analyses, validated outcome questionnaires, and standard radiographs. Study Design: Case series; Level of evidence, 4. Methods: We performed a review of prospectively collected data from patients who underwent ACI between 1996 and 2013. We evaluated 27 patients aged <18 years old (29 knees; mean age, 15.9 years) who were treated by a single surgeon for symptomatic, full-thickness articular cartilage lesions over a mean 9.6-year follow-up (median, 13 years; range, 2-19 years). A mean of 1.5 lesions per knee were treated over a mean total surface area of 6.2 cm2 (range, 2.0-23.4 cm2) per knee. Survival analysis was performed using the Kaplan-Meier method, with graft failure as the end point. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and Short Form 36 scores were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were evaluated using Kellgren-Lawrence grades. Results: Both 5- and 10-year survival rates were 89%. All clinical scores improved significantly postoperatively. A total of 96% of patients rated knee function as better after surgery, and all patients indicated that they would undergo the same surgery again. Approximately 90% rated knee-specific outcomes as good or excellent and were satisfied with the procedure. At last follow-up, 12 of 26 successful knees were radiographically assessed (mean, 5.6 years postoperatively), with no significant osteoarthritis progression. Three knees were considered failures, which were managed by autologous bone grafting or osteochondral autologous transplantation. Twenty knees required subsequent surgical procedures. These were primarily associated with periosteum and were arthroscopically performed. Conclusion: ACI resulted in satisfactory survival rates and significant improvements in function, pain, and mental health for adolescent patients over a long-term follow-up. ACI was associated with very high satisfaction postoperatively, despite the subsequent procedure rate being relatively high primarily because of the use of periosteum. If periosteum is used, this rate should be a consideration when discussing ACI with patients and their parents.

Development of a Tool to Predict Outcome of Autologous Chondrocyte Implantation

ObjectiveThe study had 2 objectives: first, to evaluate the success of autologous chondrocyte implantation (ACI) in terms of incidence of surgical re-intervention, including arthroplasty, and investigate predictors of successful treatment outcome. The second objective was to derive a tool predicting a patient’s arthroplasty risk following ACI.DesignIn this Level II, prognostic study, 170 ACI-treated patients (110 males [aged 36.8 ± 9.4 years]; 60 females [aged 38.1 ± 10.2 years]) completed a questionnaire about further surgery on their knee treated with ACI 10.9 ± 3.5 years previously. Factors commonly assessed preoperatively (age, gender, defect location and number, previous surgery at this site, and the preoperative Lysholm score) were used as independent factors in regression analyses.ResultsAt final follow-up (maximum of 19 years post-ACI), 40 patients (23.5%) had undergone surgical re-intervention following ACI. Twenty-six patients (15.3%) underwent arthroplasty, more commonly females (25%) than males (10%; P = 0.001). Cox regression analyses identified 4 factors associated with re-intervention: age at ACI, multiple operations before ACI, patellar defects, and lower pretreatment Lysholm scores (Nagelkerke’s R2 = 0.20). Six predictive items associated with risk of arthroplasty following ACI (Nagelkerke’s R2 = 0.34) were used to develop the Oswestry Risk of Knee Arthroplasty index with internal cross-validation.ConclusionIn a single-center study, we have identified 6 factors (age, gender, location and number of defects, number of previous operations, and Lysholm score before ACI) that appear to influence the likelihood of ACI patients progressing to arthroplasty. We have used this information to propose a formula or “tool” that could aid treatment decisions and improve patient selection for ACI.

Outcomes of Autologous Chondrocyte Implantation in the Knee following Failed Microfracture

Objectives:Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects of the knee. For young patients who have failed microfracture, cartilage restoration techniques such as autologous chondrocyte implantation (ACI), OATS, and osteochondral allograft and are frequently employed. Nevertheless, there a few reports in the literature evaluating the results of ACI following failed microfracture and those available suggest inferior outcomes compared to primary ACI. This study was performed to evaluate the clinical outcomes of autologous chondrocyte implantation (ACI) following failed microfracture in the knee and compare these outcomes to those of primary ACI.Methods:Patients were identified who underwent autologous chondrocyte implantation for symptomatic chondral lesions of the knee refractory to previous microfracture. Postoperative data were collected using several subjective scoring systems (Noyes, Tegner, Lysholm, IKDC, KOOS, SF12). An age-matched cohort of 103 patients who underwent primary ACI of the knee was used as a control group. Statistics were performed in a paired manner using a Student’s t-test for ordinal data and chi-square test for categorical data.Results:Ninety-two patients met the inclusion criteria. The average patient age was 30.1 years (range, 14-49 years) at the time of ACI. The average duration from microfracture to ACI was 21.2 months (range, 1-88 months). ACI was performed in the tibiofemoral compartment in 42 patients, the patellofemoral compartments in 38 patients, and in both in 12 patients. The primary lesion treated with ACI involved the MFC in 38 patients, the trochlea in 25 patients, the patella in 19 patients, and the LFC in 10 patients. The lesions averaged 467mm3 in the trochlea, 445mm3 in the LFC, 265mm3 in the patella, and 295mm3 in the patella. Nineteen patients underwent concurrent ACI to multiple lesions. Thirty-one patients underwent concomitant patellar anteromedialization, 9 patients underwent meniscal allograft, and 6 underwent realignment ostetomies (5 HTO, 1 DFO). Follow-up was available on 84 of 92 patients (91%) at an average length of follow-up of 47 months (range, 24-102 months). The control group of patients was well matched with regard to age, gender, BMI, workers compensation status, and preoperative subjective scores. Failure, defined by need for further cartilage restoration or knee arthroplasty, occurred in 8 patients (3 osteochondral allograft, 3 TKA, 1 revision ACI, 1 Denovo NT). Seventeen additional patients underwent reoperation for intra-articular debridement. There was no difference between the failure rate (8.7% v. 2.9%, p=0.21) or reoperation rate (27.2% v. 27.2%, p=0.98) in the study and control groups. For the study group, significant improvements were witnessed postoperatively for all measured questionairre parameters. No significant differences were witnessed between the study and control groups (p>0.05) with regard to any of the postoperative subjective parameters (Figure).Conclusion:In patients with discrete articular cartilage lesions of the knee and history of failed microfracture, ACI may render favorable clinical outcomes comparable to primary ACI. While other series have demonstrated inferior results following previous microfracture, our series suggests that in appropriately selected patients ACI may be used successfully as a second line treatment following failed microfracture.

Acid ceramidase treatment enhances the outcome of autologous chondrocyte implantation in a rat osteochondral defect model

The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model. Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry. Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (∼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced. The results further demonstrate the positive effects of rhAC treatment on chondrocyte growth and phenotype in vitro, and reveal for the first time the in vivo effects of the treated cells on cartilage repair.

Long-term Results of Autologous Chondrocyte Implantation in the Knee for Chronic Chondral and Osteochondral Defects

Background: Autologous chondrocyte implantation (ACI) has been shown to be effective in the midterm for the treatment of symptomatic articular cartilage lesions of the knee, but few long-term series have been published. The multioperated chronic articular cartilage defect remains a difficult condition to treat. Purpose: To examine the long-term clinical results of ACI for large chronic articular cartilage defects, many treated as salvage. Study Design: Case series; Level of evidence, 4. Methods: This is a prospective case series of 104 patients with a mean age of 30.2 years and a symptomatic lesion of the articular cartilage in the knee, who underwent ACI between 1998 and 2001. The mean duration of symptoms before surgery was 7.8 years. The mean number of previous surgical procedures on the cartilage defect, excluding arthroscopic debridement, was 1.3. The defects were large, with a mean size of 477.1 mm2 (range, 120-2500 mm2). The modified Cincinnati, Stanmore/Bentley, and visual analog scale for pain scoring systems were used to assess pain and functional outcomes at a minimum 10 years (mean, 10.4 years; range, 10-12 years). Results: Twenty-seven patients (26%) experienced graft failure at a mean of 5.7 years after ACI. Of the 73 patients who did not fail, 46 patients (63% of patients with a surviving graft) had an excellent result, 18 (25%) were good, 6 (8%) were fair, and 3 (4%) had a poor result. Of a total of 100 patients successfully followed up, 98 were satisfied with the ACI technique for their chronic knee pain and would undergo the procedure again. Conclusion: Autologous chondrocyte implantation can provide a long-term solution in more than 70% of young patients of a difficult-to-treat group with large chronic articular cartilage lesions, even in the salvage situation.

Autologous Chondrocyte Implantation and Anteromedialization for Isolated Patellar Articular Cartilage Lesions

Background: Isolated chondral lesions of the patella are particularly challenging to treat, and long-term studies of treated isolated patellar lesions are limited. Previous short-term studies have reported favorable outcomes of autologous chondrocyte implantation (ACI) of the patella and/or trochlea, with a trend toward improvement when anteromedialization (AMZ) of the tibial tubercle was performed with the procedure. Hypothesis: Autologous chondrocyte implantation with concomitant AMZ for symptomatic isolated patellar lesions provides functional and symptomatic improvement in patients at a minimum 5-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with failed primary treatment of isolated patellar full-thickness articular cartilage defects and patellofemoral malalignment who were treated with ACI and AMZ of the tibial tubercle at least 5 years prior were contacted for final postoperative outcome scores. Outcome scales including the International Knee Documentation Committee (IKDC), Lysholm, modified Cincinnati Knee Rating System, and 12-item Short Form Health Survey (SF-12) scores were assessed at baseline and final follow-up. Results: Of 27 eligible patients, 23 (25 knees) were available for assessment at a mean follow-up of 7.6 years (range, 5.1-11.4 years). Significant improvements from baseline to final follow-up were observed in the IKDC score (from 42.5 to 75.7; P < .0001), modified Cincinnati Knee Rating System score (from 3.0 to 7.0; P < .0001), Lysholm score (from 40.2 to 79.3; P < .0001), and SF-12 score (physical component score: from 41.2 to 47.6; P = .002; mental component score: from 48.1 to 60.7; P = .0001). Most patients (83%; 19/23) rated their surgery as good or excellent. The overall reoperation rate was 40% (10/25) largely because of periosteal hypertrophy (33%). One patient failed at 5.9 years postoperatively and underwent patellofemoral arthroplasty. Conclusion: Combined ACI and AMZ resulted in significant improvements in symptoms and function with a low incidence of adverse events in patients with isolated symptomatic patellar chondral defects after a mean follow-up of more than 7 years.

Influence of Sex on the Outcome of Autologous Chondrocyte Implantation in Chondral Defects of the Knee

Background: Sex-specific outcomes have been reported in anterior cruciate ligament reconstruction as well as in osteoarthrosis progression, but there are currently no related published data on autologous chondrocyte implantation (ACI). The present prospective study was performed to investigate sex-dependent differences in the results after ACI. Hypothesis: The clinical and magnetic resonance imaging (MRI) results after ACI of the knee are influenced by the patient’s sex. Study Design: Cohort study; Level of evidence, 2. Methods: The midterm clinical and MRI results of a cell-based fibrin-polymer graft for the treatment of full-thickness cartilage defects were evaluated preoperatively and 6, 12, and 48 months after surgery in 52 patients (male:female ratio, 25:27; average age, 35.6 years). Depending on the sex and the location of the defects (femoral condyles, n = 32; patellofemoral compartment, n = 20), patients were assigned to 4 different groups. Baseline clinical scores were compared with follow-up data by paired Wilcoxon tests for the Lysholm score and the International Knee Documentation Committee (IKDC) scoring system. Sex-specific differences were evaluated with the Mann-Whitney U test. The MRI evaluation was performed with the Henderson score at final follow-up. Results: Clinical scores improved in all groups over the whole study period (P < .05). Compared with female patients, male patients achieved significantly better results in the Lysholm score at all time intervals and in the IKDC score at 6 and 12 months after surgery (P < .05). In a subgroup analysis, female patients with patellar defects had the worst results in both clinical scores. With the available number of patients, MRI evaluation at 48 months after surgery revealed no significant difference in defect fill between male and female patients (P > .05). The Pearson correlation coefficient between both clinical scores and the MRI parameters of defect fill and cartilage signal was significant (P < .05). Conclusion: Autologous chondrocyte implantation is a promising treatment option for full-thickness cartilage defects of male and female knee joints. Female patients with patellar defects have worse prognostic factors.

Autologous chondrocyte implantation for traumatic full-thickness cartilage defects of the knee in 14 patients: 6-year functional outcomes

Autologous chondrocyte implantation (ACI) was introduced in 1987 in Sweden by Brittberg and Peterson for the treatment of severe chondral defects of the knee. Here, our objective was to evaluate mid-term outcomes of ACI in young athletic patients with deep chondral defects of the knee after trauma. ACI is effective in filling full-thickness chondral defects of the knee. We prospectively monitored 14 patients, with International Cartilage Repair Society grade III or IV lesions, who underwent ACI between 2001 and 2006. Standard evaluation measurements were used. Mean age at surgery was 37.7 years (range, 30-45). A history of surgery on the same knee was noted in ten (67%) patients. The defect was on the medial femoral condyle in 11 patients, lateral femoral condyle in two patients, and both femoral condyles in one patient. Mean defect surface area after debridement was 2.1cm(2) (1-6.3). After a mean follow-up of six years, improvements were noted in 12 (86%) patients, with an International Knee Documentation Committee (IKDC) score increase from 40 (27.6-65.5) to 60.2 (35.6-89.6) (P=0.003) and a Brittberg-Perterson score decrease from 54.4 (11.8-98.2) to 32.9 (0-83.9) (P=0.02), between the preoperative assessment and last follow-up. The visual analogic scale pain score decreased from 66.3 (44-89) to 23.2 (0-77) (P=0.0006). In two (14%) patients, no improvements were detectable at last follow-up. The remaining 12 patients were satisfied and able to resume sporting activities, albeit at a less strenuous level. Two ACI-specific complications occurred, namely, periosteal hypertrophy treated with debridement in one patient and transplant delamination in another. Our findings are consistent with previous reports but cover a longer follow-up period. Although the outcomes are promising, longer follow-ups are needed to confirm the long-term effectiveness of ACI. IV, prospective therapeutic study.