Autologous Chondrocyte Implantation Procedure Research Articles

Autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral autograft transplantation and osteochondral allograft improve knee function and pain with considerations for patient and cartilage defects characteristics: A systematic review and meta-analysis.

Previous studies have reported on the outcomes of autologous chondrocyte implantation (ACI) versus matrix-induced ACI (MACI) and microfracture. Specific clinical outcomes of ACI, MACI, osteochondral autograft transplantation (OAT) and osteochondral allograft (OCA) have not been well studied. The purpose of this systematic review and meta-analysis was to analyze the outcomes of these regenerative surgical techniques with an emphasis on comparing their effectiveness using the International Knee Documentation Committee (IKDC) subjective score, the Lysholm Knee Scoring Scale, the Tegner Activity Scale and the Visual Analogue Scale (VAS) score for the surgical treatment of tibiofemoral joint cartilage defects. An electronic search of MEDLINE, Embase and Cochrane Library was performed to identify studies that reported clinical outcomes for ACI, MACI, OAT and OCA procedures. The literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and only studies involving cartilage defects in the tibiofemoral joint were included. Outcomes were measured with the IKDC evaluation, Lysholm Knee Scoring Scale, Tegner Activity Scale and the VAS. Outcomes were compared to the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). The methodological quality of the included studies was analyzed by the Methodological Index for Nonrandomized Studies and the Jadad scale. Forty-seven studies were included representing a total of 1993 patients with a mean follow-up time of 57.2 ± 40.3 months (range: 4.0-160.0 months). The location of cartilage defects was reported in 46 studies, with a total of 1922 cartilage defects. There were 1277 medial femoral condyle cartilage defects, 488 lateral femoral condyle cartilage defects, 139 unspecified femoral condyle cartilage defects and 18 tibial plateau cartilage defects. All four procedures reported significant improvements in the Lysholm, IKDC, Tegner and VAS scores with no significant differences between them. The OAT technique surpassed the PASS threshold for the IKDC score while all four techniques surpassed the PASS threshold for Tegner and Lysholm scores. Additionally, all procedures met the MCID for each clinical outcome. This systematic review and meta-analysis indicate that ACI, MACI, OAT and OCA all result in significant improvements in knee function and pain for cartilage defects of the tibiofemoral joint. When selecting a procedure, patient and cartilage defect characteristics should be assessed to determine the best technique for each individual patient. Systematic review and meta-analysis. Level III.

Trends in knee cartilage repair procedures in the United States, 2010 to 2020

IntroductionSurgical intervention of knee articular cartilage injuries may prevent degeneration in symptomatic patients. ObjectiveThis study aims to analyze trends, demographics, and yearly incidence of four different knee cartilage repair procedures in the U.S. from 2010 to 2020. MethodsThe PearlDiver database was queried for patients who underwent knee microfracture, autologous chondrocyte implantation (ACI), osteochondral autograft transfer (OAT) and osteochondral allograft transplantation (OCA) procedures from 2010 to 2020. Student t and χ-square tests were used for statistical comparisons and analysis of data trends. Regression models and Compound Annual Growth Rates (CAGR) further assessed trends of each procedure. Results220,674 patients from 2010 to 2020 were included in this study. Microfracture incurred a 62.4% decrease in occurrence (P < 0.001). Incidence of OCA trended upwards (37.7%; P = 0.065) whilst OAT procedures significantly decline (53.9%; P < 0.001). ACI procedure numbers remained relatively stable (11.2% increase; P = 0.847). ConclusionsThe incidence of microfracture significantly decreased in the United States from 2010 to 2020. There was a positive trend in the incidence of OCA cases, whilst the number of OAT cases decreased significantly. The number of ACI cases performed per year did not change significantly over the study period with the exception of an increase from 2017-2019. Microfracture procedures were performed in an older patient population than the other cartilage procedures. Males were more likely to undergo the four cartilage preservation surgeries compared to females. Similar studies should be carried out in other large health databases to confirm the external validity of these trends across the United States.

Collagen and Alginate Hydrogels Support Chondrocytes Redifferentiation In Vitro without Supplementation of Exogenous Growth Factors.

Focal cartilage defects are a prevalent knee problem affecting people of all ages. Articular cartilage (AC) possesses limited healing potential, and osteochondral defects can lead to pain and long-term complications such as osteoarthritis. Autologous chondrocyte implantation (ACI) has been a successful surgical approach for repairing osteochondral defects over the past two decades. However, a major drawback of ACI is the dedifferentiation of chondrocytes during their in vitro expansion. In this study, we isolated ovine chondrocytes and cultured them in a two-dimensional environment for ACI procedures. We hypothesized that 3D scaffolds would support the cells' redifferentiation without the need for growth factors so we encapsulated them into soft collagen and alginate (col/alg) hydrogels. Chondrocytes embedded into the hydrogels were viable and proliferated. After 7 days, they regained their original rounded morphology (aspect ratio 1.08) and started to aggregate. Gene expression studies showed an upregulation of COL2A1, FOXO3A, FOXO1, ACAN, and COL6A1 (37, 1.13, 22, 1123, and 1.08-fold change expression, respectively) as early as day one. At 21 days, chondrocytes had extensively colonized the hydrogel, forming large cell clusters. They started to replace the degrading scaffold by depositing collagen II and aggrecan, but with limited collagen type I deposition. This approach allows us to overcome the limitations of current approaches such as the dedifferentiation occurring in 2D in vitro expansion and the necrotic formation in spheroids. Further studies are warranted to assess long-term ECM deposition and integration with native cartilage. Though limitations exist, this study suggests a promising avenue for cartilage repair with col/alg hydrogel scaffolds.

Isokinetic Training After A Matrix-Induced Autologous Chondrocyte Implantation Procedure: A Case Study

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) is an effective surgical procedure to repair defective cartilage. CASE PRESENTATION: This case study examined the influence of an isokinetic training program on muscle strength, size, and vertical jump performance for a young female adult after a MACI procedure. The subject completed an isokinetic training program 3 days/week for 12 weeks. Weekly assessments included isometric and isokinetic assessments of thigh muscle strength and power, ultrasound assessments of quadriceps and hamstrings muscle size, and force plate assessments of bilateral and unilateral vertical jump performance. OUTCOME AND FOLLOW-UP: Thigh muscle size 15% to 23%. Thigh muscle strength increased from 19% to 105%, whereas power increased from 29% to 121%. Bilateral and unilateral vertical jump performance increased from 6% to 93%. DISCUSSION: This study demonstrates that a 12-week isokinetic training program appears effective for increasing muscle strength, size, and vertical jump performance within the year following a MACI procedure. JOSPT Cases 2023;3(3):150-157. Epub: 20 June 2023. doi:10.2519/josptcases.2023.11617

Poster 114: Viability and Expression of Chondrocytes Harvested During Arthroscopic Treatment of Femoroacetabular Impingement

Poster 114: Viability and Expression of Chondrocytes Harvested During Arthroscopic Treatment of Femoroacetabular Impingement

Poster 288: The Effect of Time Delay From Biopsy to Second-Stage Implantation on Return to Sport and Clinical Outcomes following Autologous Chondrocyte Implantation

Objectives: Expansion of chondral defect size and clinical outcomes in patients with cartilage lesions are thought to be modulated by several risk factors. Previous studies suggest that time delay until implantation may be a risk factor for an increase in the number and size of chondral lesions at the time of implantation. Reports on the effect of time delay on clinical outcomes, however, remain limited. Therefore, the purpose of this study was to evaluate the effect of time delay from cartilage biopsy to implantation on patient satisfaction, return to sport (RTS), and clinical outcomes following autologous chondrocyte implantation. Methods: A retrospective review was performed among patient who underwent autologous chondrocyte implantation (ACI) and matrix-associated autologous chondrocyte implantation (MACI) at a single institution between the years 2012 to 2020 with minimum 2-year clinical follow-up. Clinical outcomes were measured using the Visual Analog Scale (VAS) for pain and satisfaction and the Knee Injury and Osteoarthritis Outcome Score (KOOS; subscores: symptoms, pain, sport, and quality of life (QOL)). Time delay was calculated as the elapsed time between cartilage biopsy and implantation. Cartilage lesions were categorized based on the Outerbridge classification of chondral lesions. The number of high-grade lesions (Outerbridge grade 3 or 4) and size of lesions were analyzed at time of biopsy and implantation. T-tests or non-parametric tests and Chi-squared tests were used to analyze continuous variables and categorical variables, respectively. A one-way ANOVA was used to compare outcomes based on RTS status, using a post-hoc Tukey’s HSD test for multiple comparisons. Bivariate linear regression was used to determine the impact of the time interval from biopsy to implantation on the change in size of the largest high-grade lesion and RTS. Results: A total of 36 patients, mainly female (55.6%) aged 29.25 (± 9.49) with a mean follow-up of 6.51 ± 2.5 years were included in our analysis. Thirteen patients (36.1%) did not RTS. Of the 23 patients (63.9%) who returned to sport, 11 (30.6%) returned at their preoperative level or higher, and 12 (33.3%) returned at a lower level. VAS pain scores were significantly higher in patients who did not RTS vs those who did (42.85 vs. 9.35, p &lt;0.001). All KOOS subscores (Symptom: 56.54 vs. 81.96, Pain: 72.22 vs. 91.74, Sports: 40.38 vs. 79.3, QOL: 35.58 vs. 70.38, p &lt;0.001) were significantly lower in patients who did not RTS compared to those who returned. Increase in time delay from biopsy to implantation was associated with an increase in VAS pain score (OR [95% CI]; 1.42 [0.16 to 2.69], p=0.02) and inversely related to KOOS pain scores (OR [95% CI]; -1.01 [-1.83 to -0.01], p= 0.01. Furthermore, when comparing time from biopsy to implantation and expansion of the largest highgrade lesion, it was found that for every month increase in time, lesion surface area increased by 0.588 cm2; however, this correlation did not reach significance (p=0.09). The number of high-grade lesions at time of implantation were significantly higher in those that returned to sport at a lower level than those who did not return (1.67 vs. 1.23, p=0.02). The average surface area of the defect at biopsy and implantation were 3.13 cm2 and 4.38 cm2 respectively. The number of patients who had an increase in the number of high-grade lesions from biopsy to implantation was significantly higher in those who returned to sport at a lower level compared to those who did not return (4 vs. 1, p=0.05). Logistic regression demonstrated no significant relationship between time interval and rate of return to sport (p=3.59). No other associations were observed between time from biopsy to implantation and clinical outcomes. Conclusions: An increase in time delay from biopsy to graft implantation is associated with worse pain after surgery. Both the number of high-grade lesions at the time of implantation and an increase in time delay were not associated with lower rates of return to sport. Further studies are needed to evaluate the effects of time delay until implantation and its potential role as a risk factor for worse clinical outcomes in patients undergoing autologous chondrocyte implantation procedures. [Table: see text]

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.

Cell transplantation techniques for cartilage restoration

BackgroundFocal articular chondral lesions are a common finding among patients presenting with knee pain. If symptomatic and unresponsive to conservative treatment, cell transplantation techniques offer a unique solution to address larger defects by engineering chondrocytes to integrate within the subchondral bone of the lesion and regenerate cartilage. ObjectivesThe purpose of this article is to review the evaluation of, and clinical decision making for, patients being considered for cell transplantation and the available techniques an orthopaedic surgeon has at their disposal. MethodsA review of recent literature regarding cartilage defects in the knee and cell transplantation techniques was performed to provide strategies for evaluating and treating chondral defects with matrix-induced autologous chondrocyte implantation (MACI) or particulated juvenile allograft cartilage (PJAC) procedures. ResultsChondral defects in the knee can be treated with patients’ own chondrocytes embedded into a collagen membrane as a MACI procedure, or minced autologous donor cartilage that is then implanted onto a scaffold as a PJAC procedure. These cell transplantation techniques offer advantages compared to bone marrow stimulation or mosaicplasty, and have shown clinically significant improvements in outcome scores with low rates of complications. ConclusionCell transplantation techniques such as MACI and PJAC offer treatment options that can effectively address large full-thickness chondral defects in the tibiofemoral joint or patellofemoral joint that may respond poorly to bone marrow stimulation or mosaicplasty.

Chondrocyte Isolation from Loose Bodies-An Option for Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation.

Loose bodies (LBs) from patients with osteochondritis dissecans (OCD) are usually removed and discarded during surgical treatment of the defect. In this study, we address the question of whether these LBs contain sufficient viable and functional chondrocytes that could serve as a source for autologous chondrocyte implantation (ACI) and how the required prolonged in vitro expansion affects their phenotype. Chondrocytes were isolated from LBs of 18 patients and compared with control chondrocyte from non-weight-bearing joint regions (n = 7) and bone marrow mesenchymal stromal cells (BMSCs, n = 6) obtained during primary arthroplasty. No significant differences in the initial cell yield per isolation and the expression of the chondrocyte progenitor cell markers CD44 + /CD146+ were found between chondrocyte populations from LBs (LB-CH) and control patients (Ctrl-CH). During long-term expansion, LB-CH exhibited comparable viability and proliferation rates to control cells and no ultimate cell cycle arrest was observed within 12 passages respectively 15.3 ± 1.1 mean cumulative populations doublings (CPD). The chondrogenic differentiation potential was comparable between LB-CH and Ctrl-CH, but both groups showed a significantly higher ability to form a hyaline cartilage matrix in vitro than BMSC. Our data suggest that LBs are a promising cell source for obtaining qualitatively and quantitatively suitable chondrocytes for therapeutic applications, thereby circumventing donor site morbidity as a consequence of the biopsies required for the current ACI procedure.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years

BackgroundRecently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PurposeTo evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. MethodsThirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. ResultsThe mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36–84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8–41 months) after A-ACI. ConclusionThe present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36–84 months).

Loose Body Versus Trochlear Biopsy Matrix-Induced Autologous Chondrocyte Implantation (MACI) MOCART Scores and IKDC Reported Outcomes in Pediatric Patients.

Matrix-induced autologous chondrocyte implantation (MACI) has shown promising results in the treatment of osteochondral lesions of the knee. A recent study showed similar viability comparing chondrocytes harvested from the intercondylar notch compared to those harvested from osteochondral loose bodies. However, there is limited evidence assessing how these different biopsies perform clinically. The goal of this study was to compare both radiographic and patient-reported outcomes in patients with patellar and femoral osteochondral lesions treated with MACI using either a standard intercondylar notch biopsy or an osteochondral loose body biopsy. A retrospective study was performed on all pediatric autologous chondrocyte implantation procedures performed from 2014 to 2017 at a single institution. Patients were divided into 2 groups: one group had cartilage derived from a standard intercondylar notch biopsy (n=9) and the other group had cartilage derived from an osteochondral loose body found within the ipsilateral knee (n=10). At a minimum of 1-year postimplantation, magnetic resonance imagings of the operative knee were performed and the Magnetic Resonance Observation of Cartilage Repair Tissue Knee Score (MOCART 2.0) knee score was used to assess the integrity and quality of the cartilage repair tissue. Interclass correlation coefficients were calculated between the 2 groups. International Knee Documentation Committee (IKDC) outcome scores were determined at a minimum 2 years post-implantation. The interclass correlation coefficient between three independent examiners for the MOCART scoring was excellent at 0.94. With regards to the MOCART score, the loose body group had an insignificant 17-point lower median score at 63 [interquartile range (IQR): 58 to 89] compared to the intercondylar group at 80 (IQR: 65 to 90) ( P =0.15). There was no difference in IKDC scores with the loose body group having a median score of 82 (IQR: 65 to 95) and the intercondylar group having a median score of 84 (IQR: 53 to 99) ( P =0.90). These results demonstrate that osteochondral loose bodies can be used as viable harvest site in MACI procedures with no difference in functional and radiographic outcomes at 2 years postimplantation. This may limit both short and long-term donor site morbidity. Level III-retrospective comparative study.

Utilization of Autologous Chondrocyte Implantation in the Knee Is Increasing While Reoperation Rates Are Decreasing Despite Increasing Preoperative Comorbidities

The primary purpose of this study was to assess the use of autologous chondrocyte implantation (ACI) procedures in the knee during last decade, and the secondary aims of the study were to determine reoperation rates after ACI and to identify associated risk factors. A retrospective cohort study from 2010-2020 was performed using the PearlDiver database. The database was queried for the Current Procedural Terminology (CPT) code for ACI performed in any knee location, including the patellofemoral and tibiofemoral joints. Reoperation was defined as interventional knee procedures or total knee arthroplasty after ACI. Reoperations were identified using CPT and International Classification of Diseases codes. Univariate and multivariate logistic regression were used to identify risk factors for reoperation. Significance was defined as P < .05. Among the 2010 patients included in this study, there were 90-day and overall reoperation rates of 2.24% and 30.4%, respectively, with an average follow up of 4.8 ± 3.3 years. The most common reoperations included chondroplasty, meniscectomy, and microfracture. There was an increased rate of ACI performed from 2017-2019 (5.53/100,000) compared to 2014-2016 (4.16/100,000; P < .001). ACI surgeries performed in2017-2019 were associated with decreased risk of reoperation within 2 years relative to 2014-2016 (odds ratio [OR]= 0.70; 95% confidence interval [CI], 0.52-0.94; P= .019). In the entire ACI cohort, older age (OR= 1.07; 95% CI, 1.05-1.09; P < .001) and tobacco use (OR= 2.13; 95% CI, 1.06-3.94; P= .022) were associated with increased risk of conversion to arthroplasty. Male sex was associated with decreased overall reoperation rates (OR= 0.73; 95% CI, 0.60-0.89; P= .002). There has been increasing use of ACI in the knee with decreased risk of reoperation since 2017 and the introduction of matrix-associated autologous chondrocyte implantation. Older age and tobacco use were predictors of increased risk of conversion to arthroplasty. Male sex was associated with decreased risk of reoperation. Level IV, retrospective cohort design; database study.

Autologous chondrocyte implantation for huge patellar cartilage defect

Autologous chondrocyte implantation (ACI) is associated with excellent long-term outcomes for isolated patellar chondral defects. A 24-year-old male with a history of road traffic accident 1 month back presented with locking of the knee. An MRI was done which revealed a full-thickness patellar cartilage defect measuring 1.5 × 2 cm with a loose body measuring the same size. Pre-operative planning and evaluation were done and the patient was posted for a two-stage ACI procedure. Staged post-operative rehabilitation protocol was followed. Annual outcome scale included the short form-36, modified Cincinnati activity score, and Knee Society Score and the patient reported excellent scores in all three outcomes scales at 2 years. Magnetic resonance imaging was done at 2 years for detailed analysis of the cartilage repair using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. The patient’s MOCART score demonstrated complete fill of the defect, integration to the border, no hypertrophy, and no effusion.

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.

Prior Bone Marrow Stimulation Surgery Influences Outcomes After Cell-Based Cartilage Restoration: A Systematic Review and Meta-analysis.

Background:Cell-based cartilage restoration with autologous chondrocyte implantation (ACI) is a safe and effective treatment for symptomatic cartilage lesions. Many patients undergoing ACI have a history of prior surgery, including bone marrow stimulation (BMS). There is mounting evidence that a history of prior BMS may impede healing of the ACI graft.Purpose/Hypothesis:The purpose of this study was to compare the failure rates of primary ACI with ACI after prior BMS. We hypothesized that ACI after BMS would have a significantly higher failure rate (defined as reoperation, conversion to arthroplasty, and/or imaging-based failure) compared with primary ACI.Study Design:Systematic review; Level of evidence, 4.Methods:A literature search was performed by use of PubMed and Embase databases for relevant articles published through October 2, 2020, to identify studies evaluating outcomes and failures rates of ACI after prior BMS in the knee.Results:Included were 11 studies comprising 1479 ACI procedures. The mean age at surgery ranged from 18.3 to 39.1 years, and the mean follow-up ranged from 3 to 20.6 years. All studies reported failure rates. The overall failure rate was significantly higher in the patients who underwent ACI after BMS, at 26.4% compared with 14.8% in the ACI group (P < .001). Meta-analysis demonstrated an increased risk of failure in patients with a history of prior BMS (log odds ratio = –0.90 [95% confidence interval, –1.38 to –0.42]).Conclusion:This systematic review demonstrated that failure rates were significantly higher for patients treated with ACI after BMS relative to patients undergoing ACI without prior BMS. This finding has important implications when considering the use of BMS for defects that are amenable to cell-based restoration and when determining treatment options after failed BMS.Registration:PROSPERO (CRD42020180387).

Injectable autologous chondrocyte implantation in acetabular cartilage defects: 2-year minimum clinical and MRI results.

Early results using injectable autologous chondrocyte implantation (ACI) for the treatment of full thickness acetabular cartilage defects have been promising. However, so far there is no information on radiological results after injectable ACI using spheroids. The purpose of this sturdy was to (1) investigate the quality of tissue repair on MRI and (2) investigate the correlation between the MRI results and clinical results at a minimum follow-up of 24months after third generation ACI in full thickness acetabular cartilage defects. It was hypothesized that ACI shows good MRI results in patients with large full thickness acetabular cartilage defects 24months after surgery. It was also hypothesized that there is a correlation between postoperative clinical and MRI morphological results at a minimum follow-up of 24months. Retrospective case series. Patients with ACI for full thickness acetabular cartilage defects > 2 cm2 were evaluated by preoperative and postoperative clinical scoring tools including the modified Harris Hip Score (mHHS), the International Hip Outcome Tool (iHOT-33), and the Subjective Hip Value (SHV) as well as a high resolution indirect arthro-MRI 24months after surgery utilizing an identical imaging protocol for all patients. The magnetic resonance observation of cartilage repair tissue (MOCART) scoring system was used to classify the repair tissue on MRI. Demographic patient data was evaluated for influencing factors for pre- and postoperative clinical as well as radiological results. Thirty six consecutive patients (5 women/31 men, average age 32.9years) had undergone two stage ACI procedure. The average size of the cartilage defect was 5.0 (2-6) cm2. The average follow-up was 29.9 (24-42) months. Four patients were not available for the final follow-up (follow-up rate 89%). The postoperative average MOCART score was 82.2 (± 14.2). MOCART score showed medium correlation of the item defect fill and the postoperative mHHS (r = 0.384, p = 0.043). There was no correlation of the other items or the total score with postoperative results. The patients showed significant improvement in the outcome measurements between preoperative and postoperative in the mHHS, the iHOT-33, and the SHV. Despite the large acetabular cartilage defects included in this study, ACI showed good MRI results with complete defect fill in 87.5% after a minimum 24-month follow-up. Statistically significant correlation of MRI and clinical results could only be seen with the item defect fill. Further research with longer follow-up is needed to evaluate the long-term results of ACI in acetabular cartilage defects.

Porcine-Derived Collagen-Augmented Chondrogenesis Technique for Treating Knee Cartilage Defects.

Porcine-derived C-ACT is initiated by creating a mixture of atelocollagen, thrombin, and fibrinogen. First, thrombin is mixed with atelocollagen and placed in one arm of an assembled Y-shaped syringe, and fibrinogen is placed in the other arm. The articular cartilage defect site is confirmed in a routine arthroscopic procedure. The articular margin is debrided, and the calcified lesion is cleanly removed. Then, microfractures are created. After creating a more extended incision at the anteromedial portal, the microfracture site is prepared by removing moisture. The prepared atelocollagen mixture is applied to the defect site as a single layer, although a second layer can be formed 1 to 2 minutes later. After 5 minutes, the stability is verified by range of motion of the knee.Indications for this procedure include (1) cartilage defects in the knee, including knee osteoarthritis and knee traumatic arthritis; (2) knee osteoarthritis with a Kellgren-Lawrence grade of 3 or less; (3) hip-knee-ankle malalignment of <5° or a deformity that is able to be surgically corrected; and (4) knee stability, or instability that is able to be surgically corrected.Contraindications for this procedure include (1) patient or family history of autoimmune disease, (2) history of anaphylactic reaction, (3) history of hypersensitivity to an implant, (4) history of allergy to porcine or bovine protein, and (5) inflammatory arthritis such as rheumatoid and gouty arthritis.C-ACT is a procedure for cartilage repair, and the effects of this procedure can be limited in cases with a deep subchondral bone defect; however, there is no limit to the size of the cartilage defect in terms of patient selection for C-ACT. There are several alternatives to C-ACT, ranging from the simple microfracture technique to autologous chondrocyte implantation5, matrix-induced autologous chondrocyte implantation6, autologous matrix-induced chondrogenesis7, osteochondral autograft transplantation8, and stem cell therapy. There are various ways to recover from an articular cartilage defect, but C-ACT does not require a 2-stage technique, as is necessary with both autologous chondrocyte implantation procedures. Therefore, C-ACT has the advantages of ease of operation and being a single-stage procedure3,9. C-ACT can be classified as an upgraded version of microfracture, which is the most common treatment method for articular cartilage defects. With the microfracture technique, repaired cartilage is limited to fibrous cartilage and does not include hyaline cartilage3,4. However, a recent study reported that C-ACT exhibited a superior quality of repaired cartilage compared with microfracture3,4. Previous studies have reported favorable results with the use of C-ACT3,4. Kim et al.4 compared atelocollagen augmentation with microfracture alone in patients undergoing medial opening wedge high tibial osteotomy for the treatment of medial compartment osteoarthritis. Although there was no clinical difference between the 2 groups, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and the International Cartilage Repair Society II score were superior in the atelocollagen augmentation group. In addition, the microfracture group formed fibrous-like cartilage compared with the hyaline-like cartilage created in the atelocollagen augmentation group. A recent multicenter randomized study compared the use of C-ACT and microfracture and found that C-ACT exhibited significantly better results in several MOCART subscores and quantitative T2 mapping, indicating a histologically superior form of repaired cartilage compared with microfracture3. According to recent research, microfracture is superior to autologous chondrocyte implantation in terms of cost-effectiveness10. Similar results appear to be applicable to C-ACT. C-ACT requires an additional $1,300 for material costs; however, C-ACT showed better cartilage regeneration on magnetic resonance imagining and histology3,4, and higher rate of patients meeting the 20%-improvement rate in visual analogue scale pain scores at 24 months postoperatively compared with microfracture3. Long-term studies will be needed to assess whether histological superiority of C-ACT is reflected in meaningful improvements to clinical outcomes. Debride all of the damaged cartilage to subchondral bone and remove the calcified layer without interfering with tissue repairTake special care when creating the atelocollagen mixture to ensure that it is accurately manufacturedDry the defect site with use of suction or gauze to aid in atelocollagen adhesion when applying atelocollagen.

LOOSE BODY VERSUS TROCHLEAR BIOPSY MATRIX-INDUCED AUTOLOGOUS CHONDROCYTE IMPLANTATION (MACI) MOCART SCORES AND IKDC REPORTED OUTCOMES IN PEDIATRIC PATIENTS

Background:Third generation autologous chondrocyte implantation (ACI) has traditionally used biopsies from non-weightbearing sites within the knee for culture and growth. Given the potential risk of functional deficits from this procedure, other donor sites are being investigated. A recent study showed no difference in the viability of the MACI implant using biopsies from the standard intercondylar region compared to biopsies from the osteochondral loose body. However, clinical outcomes using these two different donor sites remains unknown. The purpose of this study was to asses differences in clinical outcomes as measured by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) and International Knee Documentation Committee (IKDC) scores at a minimum of 2 years post-implantation in patients who underwent a MACI procedure in the knee using cartilage grown from either the intercondylar notch or the osteochondral loose bodies.Methods:A retrospective study was performed on all ACI procedures from 2014 to 2017 at a single institution. Patients were split into two groups: one group having their cartilage derived from a standard intercondylar biopsy while the other group had their cartilage derived from osteochondral loose bodies. At a minimum 1-year post-implantation, MRIs of the implantation site were performed and three individual orthopaedic surgeons used the MOCART 2.0 knee score to assess the cartilage. Interclass correlation coefficients (ICC) were calculated between the 2 groups. IKDC scores were determined at a minimum 2 years after implantation. Differences between outcomes were compared using a Wilcoxon rank-sum test.Results:The intraclass coefficient between examiners for the MOCART scoring was excellent at 0.94. With regards to the MOCART score, the loose body group had a statistically insignificant 15-point lower median score at 65 (IQR 61-83) compared to the intercondylar group at 80 (IQR 60-89) (p=0.46). With regards to the IKDC, the loose body group had a statistically insignificant 1-point higher median score at 85 (IQR 69-96) compared to the intercondylar group at 84 (IQR 53-99) (p=0.79).Conclusions:This study demonstrates no difference in MOCART and patient reported outcomes in patients who had MACI from cartilage derived from either a standard intercondylar biopsy or an osteochondral loose body. Surgeons should be aware that using cartilage derived from osteochondral loose bodies is a viable option for MACI as it eliminates donor site morbidity and has comparable MOCART and functional outcomes at 2 years post-implantation compared to the standard intercondylar biopsy.Level of evidence:Level III

Concomitant Osteotomy Reduces Risk of Reoperation Following Cartilage Restoration Procedures of the Knee: A Matched Cohort Analysis.

The objective of this study is to compare the (1) reoperation rates, (2) 30-day complication rates, and (3) cost differences between patients undergoing isolated autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA) procedures alone versus patients with concomitant osteotomy. Retrospective cohort study, level III. Patients who underwent knee ACI (Current Procedural Terminology [CPT] 27412) or OCA (CPT 27415) with minimum 2-year follow-up were queried from a national insurance database. Resulting cohorts of patients that underwent ACI and OCA were then divided into patients who underwent isolated cartilage restoration procedure and patients who underwent concomitant osteotomy (CPT 27457, 27450, 27418). Reoperation was defined by ipsilateral knee procedure after the index surgery. The 30-day postoperative complication rates were assessed using ICD-9-CM codes. The cost per patient was calculated. A total of 1,113 patients (402 ACI, 67 ACI + osteotomy, 552 OCA, 92 OCA + osteotomy) were included (mean follow-up of 39.0 months). Reoperation rate was significantly higher after isolated ACI or OCA compared to ACI or OCA plus concomitant osteotomy (ACI 68.7% vs. ACI + osteotomy 23.9%; OCA 34.8% vs. OCA + osteotomy 16.3%). Overall complication rates were similar between isolated ACI (3.0%) and ACI + osteotomy (4.5%) groups and OCA (2.5%) and OCA + osteotomy (3.3%) groups. Payments were significantly higher in the osteotomy groups at day of surgery and 9 months compared to isolated ACI or OCA, but costs were similar by 2 years postoperatively. Concomitant osteotomy at the time of index ACI or OCA procedure significantly reduces the risk of reoperation with a similar rate of complications and similar overall costs compared with isolated ACI or OCA.

Assessment of Cartilage Growth After Biopsy of Osteochondral Loose Bodies in Adolescent Knees for Use in Autologous Chondrocyte Implantation.

The goal of this study is to determine whether harvested cartilage from an osteochondral loose body maintains the same viability for implantation as cartilage harvested from the traditional locations within the adolescent knee for autologous chondrocyte implantation (ACI). A retrospective study was performed on all ACI procedures performed from 2014 to 2017 at a single institution. Biopsies were derived from 2 groups: osteochondral loose body verses the intercondylar notch. The viability, yield, identity, potency, and density were obtained from each sample in addition to basic demographics and concomitant injuries. A total of 12 patients with osteochondral loose bodies 14.6 (SD=2.9) and 20 patients 13.6 (SD=3.3) with intercondylar notch biopsies were evaluated for the study. In the microscopic and histologic comparison, there was no significant difference in viability: 94% in the loose bodies and 93% in the intercondylar notch groups, identity: 7.4 d5L versus 6.3 d5L, or yield. Minimum yield is presented as different units in Carticel (1.2×10 cells/vial) and matrix-induced ACI (>8500 relative fluorescent units) products; however, there was no difference between groups and all samples were above the acceptable limit. Minimum identity value is recorded as d5L> -2.00 and all samples were above this limit. In addition, no sample had signs of contamination or endotoxin in either group. These results demonstrate an alternative method for obtaining cartilage biopsies in ACI procedures that may limit short-term and long-term donor site morbidity. Level III.