Does the Choice of Acellular Scaffold and Augmentation With Bone Marrow Aspirate Concentrate Affect Short-term Outcomes in Cartilage Repair? A Systematic Review and Meta-analysis.

BACKGROUND: Matrix-induced chondrogenesis (MIC) is a promising treatment option for critical-size cartilage lesions of the knee; however, there exists substantial heterogeneity in the choice of acellular scaffold matrix for MIC cartilage repairs. HYPOTHESIS: The choice of acellular matrix will not affect patient outcomes after MIC cartilage repair procedures, and the addition of concentrated bone marrow aspirate (cBMA) will improve short-term patient outcomes regardless of matrix choice. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: Studies were stratified by matrix type: multilayered, single layered, and gel based. Continuous outcomes were analyzed with pairwise meta-analysis using the inverse variance model with random effects applied. Binary outcomes were analyzed as pooled proportions in a single-arm fashion; after which, reconstruction of relative risks (RRs) with confidence intervals was performed using the Katz logarithmic method. RESULTS: A total of 876 patients were included: 469 received multilayered bioscaffolds; 238, gel-based scaffolds; and 169, single-layered scaffolds. The mean age of patients was 36.2 years (95% CI, 33.9 to 38.4), while the mean lesion size was 3.91 cm2 (95% CI, 3.40 to 4.42). The weighted mean follow-up was 23.8 months (95% CI, 20.1 to 27.6). Multilayered bioscaffolds were most effective at improving visual analog scale scores (P = .03; weighted mean difference [WMD], -4.44 [95% CI, -4.83 to -4.06]; P < .001). There were significantly lower risks of incomplete defect filling for gel-based scaffolds when compared with multilayered scaffolds (RR, 0.78 [95% CI, 0.69 to 0.88]; P < .001) and single-layered scaffolds (RR, 0.58 [95% CI, 0.41 to 0.81]; P = .001). Augmentation with cBMA further improved clinical scores across all scaffolds, with significant improvements in Tegner score (P = .02), while decreasing incomplete defect filling rates as well. There was significantly greater improvement in visual analog scale scores (P = .01) for single-layered scaffolds with cBMA augmentation (WMD, -4.88 [95% CI, -5.38 to -4.37]; P < .001) as compared with single-layered scaffolds without cBMA augmentation (WMD, -4.08 [95% CI, -4.46 to -3.71]; P < .001). All significant improvements were below their respective minimum clinically important differences. CONCLUSION: While cartilage repair with acellular scaffolds provides significant improvements in pain and function for patients, there is insufficient clinical evidence to suggest which scaffold material is the most superior in influencing such improvements. The enhancement of cartilage repair procedures with cBMA may provide further functional improvements and improve defect filling; however, more long-term evidence is required to evaluate the effects.

Safety, Feasibility, and Radiographic Outcomes of the Anterior Meniscal Takedown Technique to Approach Chondral Defects on the Tibia and Posterior Femoral Condyle: A Matched Control Study.

OBJECTIVE: Takedown of the anterior meniscus to facilitate exposure of the cartilage defects located on the tibial plateau and/or posterior femoral condyle with subsequent reattachment is being performed clinically; however, clinical evidence is lacking to support the safety of this technique. The aim of this study was therefore to investigate whether meniscal extrusion develops after patients undergo meniscus takedown and transosseous refixation during autologous chondrocyte implantation (ACI). DESIGN: We analyzed data from 124 patients with a mean follow-up of 6.8 ± 2.5 years. Sixty-two patients who underwent (ACI) with anterior meniscus takedown and refixation by the senior surgeon (TM), were compared with a matched control group of patients who underwent ACI without meniscus takedown. Meniscal extrusion was investigated by measuring the absolute value and the relative percentage of extrusion (RPE) on 1.5-T magnetic resonance images (MRI) at final follow-up. The number of menisci with radial displacement greater or lesser than 3 mm was determined. In cases where a preoperative MRI was available, both pre- and postoperative meniscal extrusion was evaluated (n = 30) in those patients undergoing meniscal takedown. RESULTS: There was no significant difference in either absolute meniscus extrusion, RPE, or extrusion rate in patients with and without meniscus takedown. Among patients with meniscal takedown and both pre- and postoperative MRI scans, absolute meniscus extrusion, RPE, and extrusion rate showed no significant differences. CONCLUSION: Meniscal takedown and subsequent transosseous refixation is a safe and effective technique for exposure of the tibial plateau and posterior femoral condyle.

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint.

BACKGROUND: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. PURPOSE: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. STUDY DESIGN: Consensus statement. METHODS: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. RESULTS: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. CONCLUSION: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors.

Survival Analysis of Revision Autologous Chondrocyte Implantation for Failed ACI.

BACKGROUND: Autologous chondrocyte implantation (ACI) provides a successful outcome for treating articular cartilage lesions. However, there have been very few reports on the clinical outcomes of revision ACI for failed ACI. PURPOSE: To evaluate clinical outcomes in patients who underwent revision ACI of the knee for failure of an initial ACI and to determine the factors affecting the survival rate. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A review of a prospectively collected data set was performed from patients who underwent revision ACI of the knee for failure of an initial ACI between 1995 and 2014 by a single surgeon. The authors evaluated 53 patients (53 knees; mean age, 38 years) over a mean 11.2-year follow-up (range, 2-20). A total of 62 cartilage lesions were treated for failed graft lesions after an initial ACI, and 31 new cartilage lesions were treated at revision ACI, as there was progression of disease. Overall, 93 cartilage lesions (mean, 1.8 lesions per knee) with a total surface area of 7.4 cm2 (range, 2.5-18 cm2) per knee were treated at revision ACI. Survival analysis was performed with the Kaplan-Meier method, with ACI graft failure or conversion to a prosthetic arthroplasty as the endpoint. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and 36-Item Short Form Health Survey were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were evaluated with Kellgren-Lawrence grades. RESULTS: Survival rates were 71% and 53% at 5 and 10 years, respectively. Survival subanalysis revealed a trend that patients without previous cartilage repair procedures before an initial ACI had better survival rates than those with such procedures (81% vs 62% at 5 years, 64% vs 42% at 10 years, P = .0958). Patients with retained grafts showed significant improvement in pain and function, with a high level of satisfaction. At a mean 5.1 years postoperatively, 18 of 27 successful knees were radiographically assessed with no significant osteoarthritis progression. Outcomes for 26 patients were considered failures (mean, 4.9 years postoperatively), in which 15 patients had prosthetic arthroplasty (mean, 4.6 years) and the other 11 patients had revision cartilage repair (mean, 5.4 years) and thus could maintain their native knees. CONCLUSION: Results of revision ACI for patients who failed ACI showed acceptable clinical outcomes. Revision ACI may be an option for young patients after failed initial ACI, particularly patients without previous cartilage repair procedures and those who desire to maintain their native knees.

Autologous Chondrocyte Implantation "Segmental-Sandwich" Technique for Deep Osteochondral Defects in the Knee: Clinical Outcomes and Correlation With Magnetic Resonance Imaging Findings.

BACKGROUND: Symptomatic osteochondral defects are difficult to manage, especially in patients with deep (>8-10 mm) empty defects. The restoration of articular congruence is crucial to avoid the progression to osteoarthritis (OA). PURPOSE: To describe the autologous chondrocyte implantation (ACI) "segmental-sandwich" technique for restoration of the osteochondral unit and to evaluate midterm outcomes in patients treated with this procedure. Correlations between magnetic resonance imaging (MRI) and radiographic findings with outcomes were assessed. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Outcomes were evaluated for a consecutive cohort of 15 patients with symptomatic deep (>8 mm) osteochondral lesions who underwent autologous bone grafting plus the ACI segmental-sandwich technique performed by a single surgeon between 2003 and 2011. Patients with a minimum 2-year follow-up were included. All patients completed validated clinical outcome scales and a patient satisfaction survey. The Kellgren-Lawrence (K-L) grade was assessed for the progression to OA. The repair site was evaluated with the MOCART (magnetic resonance observation of cartilage repair tissue) score. Filling and tissue characteristics of the bone defect were analyzed with MRI. RESULTS: All patients (mean age at surgery, 31.0 ± 9.1 years) were available for follow-up (mean follow-up, 7.8 ± 3.0 years; range, 2-15 years). The mean chondral lesion size was 6.0 ± 3.5 cm2 (range, 1.5-13.5 cm2), with a mean bone defect area of 1.7 cm2 (27%-40% of overall surface area treated by ACI) and depth of 1.0 cm. All patients had successful clinical outcomes, and all functional scores improved significantly (P < .05). Patients reported a very high satisfaction rate (93%). The K-L grade demonstrated no significant progression to OA over a mean follow-up of 4.7 years. For 12 patients with MRI results available, the mean MOCART score at a mean of 3.3 years was 64.2 ± 19.9, with complete or near-complete (≥75% of defect volume) chondral defect filling (83%) and complete integration to adjacent cartilage (83%). Bone defects were completely filled in 83% of patients. CONCLUSION: The ACI segmental-sandwich technique provides significant functional improvements at midterm follow-up and excellent survival rates. This unique treatment allows for the resurfacing of cartilage defects and the repair of underlying segmental bone lesions.

Severe Bone Marrow Edema Among Patients Who Underwent Prior Marrow Stimulation Technique Is a Significant Predictor of Graft Failure After Autologous Chondrocyte Implantation.

BACKGROUND: Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). PURPOSE: To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). RESULTS: In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI (P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups (P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. CONCLUSION: After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.

Open Meniscal Allograft Transplantation With Transosseous Suture Fixation of the Meniscal Body Significantly Decreases Meniscal Extrusion Rate Compared With Arthroscopic Technique.

PURPOSE: To assess and compare meniscal extrusion rates after lateral "bridge-in-slot" meniscal allograft transplantation (MAT) with arthroscopic versus open insertion. METHODS: In this review of prospectively collected data, we analyzed data from patients who underwent arthroscopic or open lateral MAT. Patients who underwent concomitant distal femoral osteotomy, for whom 1-year postoperative magnetic resonance imaging was unavailable, or who underwent open lateral MAT without the use of transosseous sutures were excluded. Meniscal extrusion in the included patients was assessed by 2 independent examiners by measuring the absolute value and the relative percentage of extrusion on 1.5-T magnetic resonance images at 1-year follow-up. The number of MATs with radial displacement larger or smaller than 3 mm was determined. RESULTS: A total of 20 patients met the inclusion criteria, of whom 10 underwent arthroscopic and 10 underwent open lateral MAT. No statistically significant differences were found in baseline demographic data. Absolute meniscal extrusion was similar between the groups (P = .091). A significantly larger relative percentage of extrusion (arthroscopic MAT, 31 ± 27 mm; open MAT, 10 ± 29 mm; 95% confidence interval, -0.4 to -0.02 mm; P = .03) and a significantly higher extrusion rate were found in patients treated with arthroscopic MAT than in those treated with open MAT (>3 mm in 5 patients [50%] with arthroscopic MAT and 0 patients with open MAT, P = .01). CONCLUSIONS: This study identified similar absolute extrusion and significantly lower postoperative lateral meniscal extrusion rates after open MAT compared with arthroscopic MAT. Transosseous fixation of the meniscal body appears protective against meniscal extrusion after MAT. LEVEL OF EVIDENCE: Level III, case-control study.

Effects of hydrostatic pressure and deviatoric stress on human articular chondrocytes for designing neo-cartilage construct.

Autologous chondrocyte implantation is a promising therapy for the treatment of the articular cartilage defects. Recently, we have developed a three-dimensional chondrocyte construct manufactured with a collagen gel/sponge scaffold and cyclic hydrostatic pressure. However, the roles of various mechanical stresses, specifically hydrostatic pressure and deviatoric stress, as well as poststress loading, were unclear on metabolic function in chondrocytes. We hypothesized that hydrostatic pressure and deviatoric stresses each alter individual metabolic characteristics of chondrocytes. We embedded human articular chondrocytes within an agarose hydrogel and applied hydrostatic pressure and/or deviatoric stress individually or simultaneously for 4 days. Subsequently, we kept the cell constructs without stress for an additional 3 days. With hydrostatic pressure and/or deviatoric stress, more cells proliferated significantly than no stress (p < .05) and more cells proliferated near the inner side of the construct than the outer (p < .05). Cartilage specific aggrecan core protein and collagen type II were upregulated significantly after off-loading hydrostatic pressure alone at Day 7 (p < .05). On the other hand, these molecules were upregulated significantly immediately after deviatoric stress alone and combined with hydrostatic pressure at Day 4 (p < .05). Tissue inhibitor of metalloproteinase-2 was upregulated significantly after off-loading hydrostatic pressure alone and combined deviatoric stress at Day 7 (p < .05). Metalloproteinnase-13 was upregulated significantly with deviatoric stress at Day 4 (p < .05) and combined with hydrostatic pressure at Day 4. These results suggest that metabolic functions are regulated by the combination of hydrostatic pressure and deviatoric stress and by the timing of stress loading.

Autologous Chondrocyte Implantation for Bipolar Chondral Lesions in the Patellofemoral Compartment: Clinical Outcomes at a Mean 9 Years' Follow-up.

BACKGROUND: Treating bipolar chondral lesions in the patellofemoral (PF) compartment is a challenging problem. There are few reports available on the treatment of bipolar chondral lesions in the PF compartment. PURPOSE: To evaluate the clinical outcomes and graft survivorship after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the PF compartment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors evaluated 58 patients who had ACI by a single surgeon for the treatment of symptomatic bipolar chondral lesions in the PF compartment between November 1995 and June 2014. All 58 patients (60 knees; mean age, 36.6 years) were included with a minimum 2-year follow-up. The mean ± SD sizes of the patellar and trochlear lesions were 5.6 ± 2.7 cm2 and 4.2 ± 2.8 cm2, respectively. Forty-two patients had osteotomy, as they had PF lateral maltracking, patellar instability, or tibiofemoral malalignment. Patients were evaluated with the modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, the 36-Item Short Form Health Survey, and a patient satisfaction survey. Radiographs were evaluated with the Iwano classification. RESULTS: Overall, the survival rates were 83% and 79% at 5 and 10 years, respectively. Of the 49 (82%) knees with retained grafts, all functional scores significantly improved postoperatively with a very high satisfaction rate (88%) at a mean 8.8 ± 4.2 years after ACI (range, 2-16 years). At the most recent follow-up, 28 of 49 successful knees were radiographically assessed (mean, 4.9 years; range, 2-17 years), with no increase of the Iwano classification in 26 knees. Outcomes for 11 patients were considered failures at a mean 2.9 years. Forty-two knees (70%) required a mean 1.0 subsequent surgical procedure. The primary reasons for chondroplasty were hypertrophy of the ACI graft (17; periosteum in 14, collagen membrane in 3), delamination of the ACI graft (5; periosteum in 4, collagen membrane in 1), and new chondral lesions (3). The best survival rates were observed among patients who underwent ACI with concomitant tibial tubercle osteotomy (TTO) as the first procedure without previous failed TTO and/or marrow stimulation technique (91% at 5 and 10 years), while the worst survival rates were observed among patients who had previous marrow stimulation (43% at 5 and 10 years). CONCLUSION: Results demonstrated that ACI with concomitant osteotomy, when it is necessary for the treatment of bipolar/kissing lesions in the PF compartments, gives significant improvement in pain and function, with good survival rates at 5 and 10 years (83% and 79%, respectively). The high patient satisfaction rate is encouraging, and a high survival rate can be expected when ACI with a concomitant TTO is performed at the initial surgery for this difficult condition.

A high level of satisfaction after bicompartmental individualized knee arthroplasty with patient-specific implants and instruments.

PURPOSE: Customized Individually Made (CIM) Bicompartmental Knee Arthroplasty (BKA) implants and three-dimensional printed customized instruments are available to fit to each patient's unique anatomy, medial or lateral with patellofemoral. This study aimed to evaluate the clinical outcomes after CIM-BKA. METHODS: Fifty-five patients [59 knees; average age, 51 years; standard deviation (SD), 6.8; range 37-65 years] who underwent CIM-BKA were evaluated over an average of 3.8-year follow-up (SD 1.6; range 1-6 years). Forty-one knees underwent BKA combined medial and patellofemoral replacement (BKA-MP) and 18 knees underwent BKA combined lateral with patellofemoral replacement (BKA-LP). Survival rates, the modified Cincinnati Knee Rating Scale, WOMAC, VAS, SF-36, a satisfaction survey, and radiographic evaluation were used to evaluate outcomes. RESULTS: Overall, survival rates were 98% and 92% at 2 and 5 years, respectively. Of 56 knees (95%) that did not fail, all patient-reported functional scores significantly improved post-operatively (P < 0.01), regardless of the previous surgeries, with a high level of satisfaction (51/56 knees, 91%). Radiographically, all the femoral components fit perfectly and 56 knees (95%) of the tibial components fit with less than 2 mm of undercoverage or overhang. Three knees (5%) required the conversion to TKA and 17 knees (29%) required subsequent surgical procedures, of which multiply operated knees had higher rate than virgin knee [14/40 (35%) vs. 3/16 (19%)]. CONCLUSION: CIM-BKA allowed precise fit of the components and provided a significant improvement post-operatively with a high level of satisfaction over short- to mid-term follow-up. This novel CIM-BKA is resurfacing, and does not require 10-mm faceted cuts, being only 3-mm-thick, which preserves bone stock for the future. It may be a promising option for relatively young active patients with bicompartmental osteoarthritis with a longer term follow-up being necessary. LEVEL OF EVIDENCE: IV.

Autologous Chondrocyte Implantation for Bipolar Chondral Lesions in the Tibiofemoral Compartment.

BACKGROUND: Treating bipolar chondral lesions in the tibiofemoral (TF) compartment with cartilage repair procedures is challenging, and a suitable treatment remains unclear. PURPOSE: To evaluate clinical outcomes after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the TF compartment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We evaluated 57 patients who underwent ACI for the treatment of symptomatic bipolar chondral lesions in the TF compartment by a single surgeon between October 1995 and June 2014. One patient did not return for follow-up. Thus, 56 patients (58 knees) were included with a minimum of 2 years' follow-up. A mean of 3.1 lesions per knee were treated, representing a mean total surface area of 16.1 cm2 (range, 3.2-44.5 cm2) per knee. Bipolar lesions were present in the medial compartment (32 knees) and in the lateral compartment (26 knees). Patients were evaluated with the modified Cincinnati Knee Rating Scale, visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form-36. Patients also answered questions regarding self-rated knee function and satisfaction with the procedure. Standard radiographs were evaluated with the Kellgren-Lawrence grading system. RESULTS: The survival rate was 80% at 5 years and 76% at 10 years. A significantly better survival rate was found in patients with the use of a collagen membrane than periosteum (97% vs 61% at 5 years, respectively; P = .0014). Of 46 knees with retained grafts, all functional scores significantly improved postoperatively, with a very high satisfaction rate (91%) at a mean of 8.3 ± 5.1 years (range, 2-20 years) after ACI. At last follow-up, 24 of 46 successful knees were radiographically assessed (mean, 5.5 ± 4.0 years [range, 2.0-18.7 years]) and showed no significant osteoarthritis progression ( P = .3173). Outcomes for 12 patients were considered as failures at a mean of 4.1 years. Of these, 9 patients were converted to partial or total knee arthroplasty at a mean of 4.4 years. Two patients underwent revision ACI at 5 and 17 months. The other 1 patient did not require revision surgery. CONCLUSION: Our study showed that ACI for the treatment of bipolar chondral lesions in the TF compartment provided successful clinical outcomes in patients with retained grafts and possibly prevented or delayed osteoarthritis progression at midterm to long-term follow-up. A collagen membrane is more encouraging than periosteum for bipolar lesions in the TF compartment. While addressing the predisposing factors affecting cartilage repair, ACI could be an adequate salvage procedure for bipolar chondral lesions in the TF compartment for the relatively young arthritic patient who wishes to avoid arthroplasty.

Optimization of Extracellular Matrix Synthesis and Accumulation by Human Articular Chondrocytes in 3-Dimensional Construct with Repetitive Hydrostatic Pressure.

Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

Autologous Chondrocyte Implantation "Sandwich" Technique Compared With Autologous Bone Grafting for Deep Osteochondral Lesions in the Knee.

BACKGROUND: Treating symptomatic osteochondral defects is challenging, especially in young adults with deep (>8-10 mm) empty defects after osteochondritis dissecans (OCD) or collapsed condyles secondary to avascular necrosis (AVN). For this population, osteoarthritis (OA) is inevitable if articular congruence is not restored. PURPOSE: To describe the autologous chondrocyte implantation (ACI) "sandwich" technique with autologous bone grafting (ABG) and compare it with ABG alone for restoration of the osteochondral unit. The midterm to long-term outcomes in patients after the treatment for OCD and AVN will be reported and compared. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The outcomes for a consecutive cohort of 24 patients who underwent combined ABG with the ACI sandwich technique between 2001 and 2013 (ACI sandwich group) was compared with a historical control group of 17 consecutive patients who underwent ABG alone between 1995 and 2002 (ABG group) by a single surgeon for symptomatic deep (>8 mm) osteochondral lesions. Patients who were followed up with a minimum of 2 years were included in this study. The modified Cincinnati Knee Rating System, the Western Ontario and McMaster Universities Osteoarthritis Index, a visual analog scale (VAS), the Short Form-36, and a patient satisfaction survey were used to evaluate clinical outcomes. Survival analysis was performed using the Kaplan-Meier method, with no clinical improvement, graft failure, or conversion to prosthetic arthroplasty as the endpoint (failure). Kellgren-Lawrence (K-L) grading to assess OA progression was also performed. RESULTS: In the ABG group, 13 of 17 patients (76%) were available with a mean follow-up of 15.7 years postoperatively (range, 5-21 years). In the ACI sandwich group, all 24 patients were available with a mean follow-up of 7.8 years postoperatively (range, 2-15 years). No significant differences were observed between the groups in terms of age, sex, side of the operated knee, body mass index, lesion type, lesion size, lesion depth, lesion location, or the need for realignment osteotomy. Eight patients (62%) were considered failures in the ABG group, while 3 patients (13%) were considered failures in the ACI sandwich group. The survival rate was significantly better in the ACI sandwich group than the ABG group (87% vs 54% at 5 years, respectively; P = .0025). All functional scores in patients with retained grafts significantly improved in the ACI sandwich group, whereas only the VAS score showed significant improvement in the ABG group. The patient satisfaction survey showed a very high satisfaction rate in the ACI sandwich group, with over 90% of patients reporting their knees as good or excellent and being satisfied with the procedure. In the ACI sandwich group, K-L grading demonstrated no significant OA progression from preoperatively to a mean 5.1 years postoperatively. CONCLUSION: Our study showed that the ACI sandwich technique provided excellent and superior survival rates compared to ABG alone and significant improvements over midterm to long-term follow-up. This unique treatment offers native joint preservation for conditions that naturally will progress to OA and eventually require prosthetic arthroplasty.

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.

Intermediate- to Long-Term Results of Combined Anterior Cruciate Ligament Reconstruction and Autologous Chondrocyte Implantation.

BACKGROUND: Cartilage injury associated with anterior cruciate ligament (ACL) ruptures is common; however, relatively few reports exist on concurrent cartilage repair with ACL reconstruction. Autologous chondrocyte implantation (ACI) has been utilized successfully for treatment of moderate to large chondral defects. HYPOTHESIS: ACL insufficiency with relatively large chondral defects may be effectively managed with concurrent ACL reconstruction and ACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients undergoing concurrent ACL primary or revision reconstruction with ACI of single or multiple cartilage defects were prospectively evaluated for a minimum 2 years. Pre- and postoperative outcome measures included the modified Cincinnati Rating Scale (MCRS), Western Ontario and McMaster Universities Osteoarthritis Index, visual analog pain scales, and postsurgery satisfaction surveys. ACI graft failure or persistent pain without functional improvement were considered treatment failures. RESULTS: Twenty-six patients were included, with 13 primary and 13 revision ACL reconstructions performed. Mean defect total surface area was 8.4 cm2, with a mean follow-up of 95 months (range, 24-240 months). MCRS improved from 3.62 ± 1.42 to 5.54 ± 2.32, Western Ontario and McMaster Universities Osteoarthritis Index from 45.31 ± 17.27 to 26.54 ± 17.71, and visual analog pain scale from 6.19 ± 1.27 to 3.65 ± 1.77 (all Ps <.001). Eight patients were clinical failures, 69% of patients were improved at final follow-up, and 92% stated they would likely undergo the procedure again. No outcome correlation was found with regard to age, body mass index, sex, defect size/number, follow-up time, or primary versus revision ACL reconstruction. In subanalysis, revision ACL reconstructions had worse preoperative MCRS scores and greater defect surface areas. However, revision MCRS score improvements were greater, resulting in similar final functional scores when compared with primary reconstructions. CONCLUSION: Challenging cases of ACL tears with large chondral defects treated with concurrent ACL reconstruction and ACI can lead to moderately improved pain and function at long-term follow-up. Factors associated with clinical failure are not clear. When combined with ACI, patients undergoing revision ACL reconstructions have worse function preoperatively compared with those undergoing primary reconstructions but have similar final outcomes.

Intralesional Osteophyte Regrowth Following Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Technique.

Objective Bone marrow stimulation surgeries are frequent in the treatment of cartilage lesions. Autologous chondrocyte implantation (ACI) may be performed after failed microfracture surgery. Alterations to subchondral bone as intralesional osteophytes are commonly seen after previous microfracture and removed during ACI. There have been no reports on potential recurrence. Our purpose was to evaluate the incidence of intralesional osteophyte development in 2 cohorts: existing intralesional osteophytes and without intralesional osteophytes at the time of ACI. Study Design We identified 87 patients (157 lesions) with intralesional osteophytes among a cohort of 497 ACI patients. Osteophyte regrowth was analyzed on magnetic resonance imaging and categorized as small or large (less or more than 50% of the cartilage thickness). Twenty patients (24 defects) without intralesional osteophytes at the time of ACI acted as control. Results Osteophyte regrowth was observed in 39.5% of lesions (34.4% of small osteophytes and 5.1% of large osteophytes). In subgroup analyses, regrowth was observed in 45.8% of periosteal-covered defects and in 18.9% of collagen membrane-covered defects. Large osteophyte regrowth occurred in less than 5% in either group. Periosteal defects showed a significantly higher incidence for regrowth of small osteophytes. In the control group, intralesional osteophytes developed in 16.7% of the lesions. Conclusions Even though intralesional osteophytes may regrow after removal during ACI, most of them are small. Small osteophyte regrowth occurs almost twice in periosteum-covered ACI. Large osteophytes occur only in 5% of patients. Intralesional osteophyte formation is not significantly different in preexisting intralesional osteophytes and control groups.

Autologous Chondrocyte Implantation to Isolated Patella Cartilage Defects.

Background Autologous chondrocyte implantation (ACI) is a durable treatment for patients with chondral defects. This study presents the comprehensive evaluation of patients with patella defects treated with ACI at medium- to long-term follow-up. Methods Thirty consecutive patients with isolated chondral lesions of the patella were enrolled prospectively. Primary outcome measures were validated patient reported outcome measures and objective magnetic resonance imaging. Results Nineteen of 30 patients underwent tibial tubercle osteotomy (TTO) to correct lateral maltracking in combination with soft tissue balancing. The defect sizes were large, averaging 4.7 ± 2.1 cm2 (range 2.2-30.0 cm2). Pidoriano/Fulkerson classification revealed that 3 defects were type II (lateral), 9 were type III (medial), and 18 were type IV (central/panpatella). Age at the time of surgery was 32 ± 10 years. At follow-up of 2 to 14 years, knee function was rated good to excellent in 25 (83%) patients, fair in 4 (13%) patients, and poor in 1 (3%) patient. Three patients failed treatment after a mean of 75 months (6.25 years). All 3 failures were Workers Compensation (WC) cases. They were older than the non-WC patients, 42 ± 6 years compared with the non-WC 28 ± 9 years ( P = 0.0019). Significant increases in all clinical and health utility outcome scores were seen. Magnetic resonance imaging demonstrated that the fill grade, surface and integrity of the repair tissue correlated with clinical scores. Conclusion ACI to isolated patella defects results in significant functional improvement at a minimum of 24 months, with the results remaining durable at latest follow-up of 15 years. Level of evidence Level 4.

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.

Biological Knee Reconstruction With Concomitant Autologous Chondrocyte Implantation and Meniscal Allograft Transplantation: Mid- to Long-term Outcomes.

BACKGROUND: Treating articular cartilage defects and meniscal deficiency is challenging. Although some short- to mid-term follow-up studies report good clinical outcomes after concurrent autologous chondrocyte implantation (ACI) and meniscal allograft transplantation (MAT), longer follow-up is needed. PURPOSE: To evaluate mid- to long-term outcomes after combined ACI with MAT. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We performed a retrospective review of prospectively gathered data from patients who had undergone ACI with MAT between 1999 and 2013. A single surgeon treated 18 patients for symptomatic full-thickness chondral defects with meniscal deficiency. One patient was lost to follow-up. Thus, 17 patients (18 knees; mean age, 31.7 years) were evaluated over a mean 7.9-year follow-up (range, 2-16 years). A mean 1.8 lesions per knee were treated over a total surface area of 7.6 cm2 (range, 2.3-21 cm2) per knee. Seventeen lateral and 1 medial MATs were performed. Survival was analyzed using the Kaplan-Meier method. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and Short Form-36 were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were scored for Kellgren-Lawrence (K-L) grade. RESULTS: Both 5- and 10-year survival rates were 75%. Outcomes for 6 knees were considered failures. Of the 6 failures, 4 knees were converted to arthroplasty and the other 2 knees underwent biological revision surgery. Of the 12 successfully operated knees, all clinical measures significantly improved postoperatively. Ten patients representing 11 of the 12 knees rated outcomes for their knees as good or excellent, and 1 rated their outcome as fair. Eight patients representing 9 of the 12 knees were satisfied with the procedure. There was no significant osteoarthritis progression based on K-L grading from preoperatively to a mean 5.9 years after surgery. Seven of the 12 knees (58%) required subsequent surgical procedures (5 arthroscopic alone, 2 both arthroscopic and open). CONCLUSION: Combined ACI with MAT provided significant improvement in 65% of the operated knees over a mid- to long-term follow-up. This procedure can allow patients to retain their biological knees, delay or prevent rapid degeneration to osteoarthritis, and could be recognized as a bridge procedure before artificial knee replacement. However, careful discussion between the patient and surgeon is necessary before surgery to ensure realistic expectations.

Autologous Chondrocyte Implantation.

INTRODUCTION: Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage lesions of the knee joint provides successful and durable long-term outcomes. STEP 1 PREOPERATIVE PLANNING VIDEO 1: Obtain standing radiographs and magnetic resonance imaging (MRI) scans to identify all associated abnormalities (background factors). STEP 2 ARTHROSCOPIC ASSESSMENT AND CARTILAGE BIOPSY VIDEO 2: Evaluate the knee joint systematically and harvest cartilage tissue from the non-weight-bearing area. STEP 3 MAKE THE INCISION FOR THE ARTHROTOMY VIDEO 3: Use a medial or lateral parapatellar arthrotomy and expose the lesion adequately. STEP 4 PREPARE THE DEFECT VIDEO 4: Debride all fissured and unstable articular cartilage surrounding the full-thickness chondral injury down to healthy contained cartilage. STEP 5 ADDRESS ASSOCIATED ABNORMALITIES: Address associated abnormalities (predisposing background factors) to optimize recovery and a successful outcome. STEP 6 PREPARE AND FIX THE COLLAGEN MEMBRANES VIDEO 5: Orient the membrane patch with the rough surface to the subchondral bone and the smooth surface toward the articular surface; then sew it, tying the sutures knots on the membrane and not the cartilage, to tension it adequately throughout the entire defect. STEP 7 CHONDROCYTE IMPLANTATION VIDEO 6: Gently deliver the cells and fill the defect. STEP 8 POSTOPERATIVE CARE: (1) Initiate range-of-motion exercises to enhance chondrocyte regeneration and decrease the likelihood of intra-articular adhesion, (2) protect the graft from loading for 6 to 12 weeks after surgery to prevent graft overload and central degeneration or delamination of the graft, and (3) initiate isometric muscle exercises to regain muscle tone and prevent atrophy. RESULTS: ACI provided durable outcomes in 210 patients followed prospectively for 10 to 17 years after treatment with the first-generation ACI-periosteum technique6.