Autologous Chondrocyte Implantation Research Articles

Operative management of osteochondral lesions of the talus: 2024 recommendations of the working group 'clinical tissue regeneration' of the German Society of Orthopedics and Traumatology (DGOU).

The working group 'Clinical Tissue Regeneration' of the German Society of Orthopedics and Traumatology (DGOU) issues this paper with updating its guidelines. Literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLT) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available with a grade of recommendation. All group members rated the statements to identify possible gaps between literature and current clinical practice. Fixation of a vital bony fragment should be considered in large fragments. In children with open physis, retrograde drilling seems to work better than in adults, but even there, the revision rate reaches 50%. The literature supports debridement with bone marrow stimulation (BMS) in lesions smaller than 1.0 cm² without bony defect. The additional use of a scaffold can be recommended in lesions larger than 1.0 cm². For other scaffolds besides AMIC®/Chondro-Gide®, there is only limited evidence. Systematic reviews report good to excellent clinical results in 87% of the patients after osteochondral transplantation (OCT), but donor site morbidity is of concern, reaching 16.9%. There is no evidence of any additional benefit from autologous chondrocyte implantation (ACI). Minced cartilage lacks any supporting data. Metallic resurfacing of OLT can only be recommended as a second-line treatment. A medial malleolar osteotomy has a minor effect on the clinical outcome compared to the many other factors influencing the clinical result.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. Level III.

10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes

Background: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. Purpose: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. Study Design: Case series; Level of evidence, 4. Methods: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. Results: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). Conclusion: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Autologous Chondrocyte Implantation Is Not Better Than Arthroscopic Debridement for the Treatment of Symptomatic Cartilage Lesions of the Knee: Two-Year Results From a Randomized-Controlled Trial

PurposeTo compare the functional and patient reported outcome measures (PROMs) after autologous chondrocyte implantation (ACI) and arthroscopic debridement (AD) in symptomatic, isolated cartilage injuries larger than 2cm2 in patients aged 18–50 years. MethodsTwenty-eight patients were included and randomized to ACI (n=15) or AD (n=13), and followed for two years. The primary outcome was the change in the Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QoL) subscale. ResultsThe mean age at inclusion was 34.1 (standard deviation (SD) 8.5) years. There were 19 (68%) males. The mean size of the lesion was 4.2 (SD 1.7) cm2. There was a statistically significant and clinically meaningful improvement in PROMs from baseline to two years in both groups. The improvement from baseline to final follow-up for the primary endpoint (the KOOS QoL subscale) was larger for the AD group (39.8, SD 9.4) compared to the ACI group (23.8, SD 6.7), but this difference was not statistically significant (p=0.17). However, according to a mixed linear model there were statistically significantly higher scores in the AD group for several KOOS sub-scales at several time-points, including KOOS QoL, KOOS pain and KOOS sport and recreation at two years. ConclusionsThis study indicates that AD followed by supervised physiotherapy is equal to or better than ACI followed by supervised physiotherapy in patients with isolated cartilage lesions of the knee larger than 2 cm2. The improvement in DASH score from baseline to two years was clinically meaningful for both groups (23.8 points for ACI and 39.8 points AD), and larger for the AD group by 16 points.

A review of advanced hydrogels for cartilage tissue engineering.

With the increase in weight and age of the population, the consumption of tobacco, inappropriate foods, and the reduction of sports activities in recent years, bone and joint diseases such as osteoarthritis (OA) have become more common in the world. From the past until now, various treatment strategies (e.g., microfracture treatment, Autologous Chondrocyte Implantation (ACI), and Mosaicplasty) have been investigated and studied for the prevention and treatment of this disease. However, these methods face problems such as being invasive, not fully repairing the tissue, and damaging the surrounding tissues. Tissue engineering, including cartilage tissue engineering, is one of the minimally invasive, innovative, and effective methods for the treatment and regeneration of damaged cartilage, which has attracted the attention of scientists in the fields of medicine and biomaterials engineering in the past several years. Hydrogels of different types with diverse properties have become desirable candidates for engineering and treating cartilage tissue. They can cover most of the shortcomings of other treatment methods and cause the least secondary damage to the patient. Besides using hydrogels as an ideal strategy, new drug delivery and treatment methods, such as targeted drug delivery and treatment through mechanical signaling, have been studied as interesting strategies. In this study, we review and discuss various types of hydrogels, biomaterials used for hydrogel manufacturing, cartilage-targeting drug delivery, and mechanosignaling as modern strategies for cartilage treatment.

Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes.

Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure, such as matrix-induced autologous chondrocyte implantation. Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to (1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a three-dimensional (3D) culture; and (2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0 population doublings, 8 population doublings, and 16 population doublings (PD16) in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a 3D hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for PD16 and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded bovine chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.

Minimum 10-Year Outcomes of Matrix-Induced Autologous Chondrocyte Implantation in the Knee: A Systematic Review.

Matrix-induced autologous chondrocyte implantation (MACI) is an established cell-based therapy for the treatment of chondral defects of the knee. As long-term outcomes are now being reported in the literature, it is important to systematically review available evidence to better inform clinical practice. To report (1) subjective patient-reported outcomes (PROs) and (2) the rate of graft failure, reoperation, and progression to total knee arthroplasty (TKA) after undergoing MACI of the knee at a minimum 10-year follow-up. Systematic review; Level of evidence, 4. A comprehensive search of Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus from 2008 to September 15, 2022, was conducted in the English language. Study eligibility criteria included (1) full-text articles in the English language, (2) patients undergoing a MACI within the knee, (3) clinical outcomes reported, and (4) a minimum 10-year follow-up. In total, 168 patients (99 male, 69 female; mean age, 37 years [range, 15-63 years]; mean body mass index, 26.2 [range, 18.6-39.4]) representing 188 treated chondral defects at a minimum 10-year follow-up after MACI were included in this review. Significant and durable long-term improvements were observed across multiple PRO measures. Follow-up magnetic resonance imaging (MRI), when performed, also demonstrated satisfactory defect fill and an intact graft in the majority of patients. The all-cause reoperation rate was 9.0%, with an overall 7.4% rate of progression to TKA at 10 to 17 years of follow-up. At a minimum 10-year follow-up, patients undergoing MACI for knee chondral defects demonstrated significant and durable improvements in PROs, satisfactory defect fill on MRI-based assessment, and low rates of reoperation and TKA. These data support the use of MACI as a long-term treatment of focal cartilage defects of the knee.

Osteochondritis Dissecans Lesions of the Knee: Evidence-Based Treatment.

Osteochondritis dissecans (OCD) of the knee is a potentially disabling condition in adolescent and young adults, which is likely multifactorial in origin. In recent years, there have been notable improvements in identification and treatment. Clinical presentation varies based mostly on OCD lesion stability. Patients with stable lesions generally present with vague knee pain and altered gait while mechanical symptoms and effusion are more common with unstable lesions. Lesions most commonly occur on the lateral aspect of the medial femoral condyle in patients aged 10 to 20 years. Magnetic resonance imaging is vital to diagnose and predict clinical treatment, which is largely based on stability of the fragment. Conservative treatment of stable lesions in patients with open physis is recommended with protected weight-bearing and gradual progression of activities over the course of 3 to 6 months. Stable OCD lesions which failed a nonsurgical course can be treated with transarticular or retrograde drilling while unstable lesions usually require fixation, autologous chondrocyte implantation (ACI), osteochondral autograft transfer (OATS), or osteochondral allograft transplantation. This review highlights the most current understanding of knee OCD lesions and treatment options with the goal of optimizing outcomes in this difficult pathology.

Responsiveness of Patient-Reported Outcome Measures After Large Knee Articular Cartilage Transplantation: A Systematic Review and Meta-analysis

Background: Cartilage transplantation is commonly used to treat large (>4 cm2) articular cartilage defects of the knee. The 2 most common transplants are osteochondral allograft transplantation and autologous chondrocyte implantation. Several patient-reported outcome measures (PROMs) have been used to determine the efficacy of treatment, but it is unknown which measures are the most effective. Purpose: To report the multiple PROMs used after large knee articular cartilage transplantation surgery and to compare the responsiveness between them. Study Design: Meta-analysis; Level of evidence, 4. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of the PubMed/MEDLINE and Web of Science databases was performed. A total of 181 articles met inclusion criteria. Patient and study characteristics were extracted, including pre- and postoperative means for PROMs. From the articles that met inclusion criteria for responsiveness analysis (2+ PROMs reported, 1-year minimum follow-up, reported pre- and postoperative means and standard deviations; n = 131), the authors compared the responsiveness between PROM instruments using effect size and relative efficiency (RE) if a PROM could be compared with another in ≥10 articles. Results: A total of 10,015 patients (10,093 knees; mean age, 34.8 years; mean body mass index, 26.1) were included in this study. The mean follow-up time was 58.3 months (range, 1.5-247.2 months), imaging findings were reported in 80 articles (44.2%), patient satisfaction was reported in 39 articles (21.5%), and range of motion was reported in 10 articles (5.5%). There were 58 unique PROM instruments identified, with the most used being the International Knee Documentation Committee (IKDC) score (n = 118; 65.2%), followed by Knee injury and Osteoarthritis Outcome Score (KOOS) Pain (n = 58; 32.0%), KOOS Sport and Recreation (n = 58; 32.0%), KOOS Quality of Life (n = 57; 31.5%), KOOS Activities of Daily Living (n = 57; 31.5%), and KOOS Symptoms (n = 57; 31.5%). Overall, IKDC was found to have the greatest effect size (1.68) and the best responsiveness of the other PROMs, which include KOOS Pain (RE, 1.38), KOOS Symptoms (RE, 3.06), KOOS Activities of Daily Living (RE, 1.65), KOOS Sport and Recreation (RE, 1.44), Lysholm (RE, 1.76), and Tegner (RE, 1.56). Conclusion: The IKDC is the most responsive PROM after large knee articular cartilage transplantation surgery. The IKDC score is recommended for assessing outcomes after cartilage transplantation surgery.

Impact of Wiberg Patellar Type on Outcomes and Survival Following Cell-Based Cartilage Repair for Patellar Chondral Lesions at Midterm Follow-up.

Cell-based cartilage repair procedures of the patellofemoral joint have less reliable outcomes than those of the tibiofemoral joint. No previous studies have evaluated the influence of patellar shape on cell-based cartilage repair outcomes. Patellar dysplasia may predispose patients to worse outcomes after cell-based cartilage repair. The purpose of this study was to evaluate the relationship between Wiberg patellar type and outcomes after cell-based cartilage repair (autologous chondrocyte implantation or particulated juvenile allograft cartilage transplantation) for the treatment of patellar chondral lesions at a minimum 2-year follow-up. It was hypothesized that Wiberg classification of patellar shape would have no effect on patient-reported outcome measures (PROMs) or graft survival. Cohort study; Level of evidence, 3. Patients undergoing autologous chondrocyte implantation or particulated juvenile allograft cartilage transplantation for full-thickness patellar chondral defects between 2016 and 2020 were retrospectively reviewed after institutional review board approval. The change in PROMs, including International Knee Documentation Committee (IKDC), Kujala, and Veterans RAND 12-item Health Survey Mental and Physical scores, from pre- to postoperatively and the percentage of patients who achieved the minimal clinically important difference (MCID) for IKDC and Kujala scores were compared for the Wiberg type A versus Wiberg type B versus Wiberg type C groups. The log-rank test was used to evaluate for differences in survival between subgroups. A total of 59 patients (63 knees) were included, with a mean age of 33.3 ± 8.6 years, median body mass index of 26.0 (IQR, 21.8-30.2), and median follow-up time of 3.5 years (IQR, 2.6-4.2 years). In total, 26 (41%) patellae were Wiberg type A, 29 (46%) were Wiberg type B, and 8 (13%) were Wiberg type C. There were no differences between Wiberg type A versus Wiberg type B versus Wiberg type C groups with respect to change in PROMs from pre- to postoperatively or the percentage of patients who achieved the MCID for IKDC or Kujala scores (P > .05 for all). There were no differences in survival between groups (P = .45). Wiberg patellar type has no effect on patient-reported outcomes or graft survival at midterm follow-up. Patellar dysplasia should not be seen as a contraindication for cell-based cartilage repair procedures.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

Costal Chondrocyte–Derived Pellet-Type Autologous Chondrocyte Implantation Versus Microfracture for the Treatment of Articular Cartilage Defects: A 5-Year Follow-up of a Prospective Randomized Trial

Background: Costal chondrocyte–derived pellet-type autologous chondrocyte implantation (CCP-ACI) has been introduced as a new therapeutic option for the treatment of articular cartilage defects. We had previously conducted a randomized controlled trial comparing CCP-ACI versus microfracture at 1 year postoperatively. Purpose: To compare the efficacy and safety of CCP-ACI versus microfracture for the treatment of articular cartilage defects of the knee at 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: This study describes the mean 5-year follow-up of a previously published prospective clinical trial. The previous prospective trial compared the results of CCP-ACI versus microfracture until 1 year of follow-up. Of the 30 patients who were included in the previous study, 25 were followed up for 5 years. Patients were evaluated based on clinical outcome scores (Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score [KOOS], and visual analog scale for pain), magnetic resonance imaging findings, and rates of treatment failure at last follow-up. Results: The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in the CCP-ACI group was significantly higher than that in the microfracture group at 5 years (62.3 vs 26.7, respectively; P < .0001). The Lysholm score and KOOS score in the CCP-ACI group were significantly higher than those in the microfracture group at 5 years (84.5 vs 64.9, respectively, and 390.9 vs 303.0, respectively; P = .023 and P = .017, respectively). There was 1 case of treatment failure that occurred in the microfracture group. Conclusion: The present randomized controlled trial indicated that the results of both procedures clinically and statistically significantly improved at 1 and 5 years’ follow-up in treating cartilage defects, but the results of CCP-ACI were superior to those of microfracture. Magnetic resonance imaging conducted at 1 year and 5 years after CCP-ACI revealed statistically significant superior structural integration with native cartilage tissue compared with microfracture. Registration: NCT03545269 (ClinicalTrials.gov)

All-Arthroscopic Matrix-Associated Autologous Chondrocyte Implantation for a Trochlear Defect

Matrix-associated autologous chondrocyte implantation (MACI) is a 2-step technique designed to treat symptomatic full-thickness articular cartilage defects of the knee. In this technique article, MACI (autologous cultured chondrocytes on porcine collagen membrane) is used to treat a femoral trochlear defect of the knee. Treating a defect with this technique leads to improved clinical outcomes by restoring the native chondral surface architecture and biomechanics of the knee. In addition, it has the potential to prevent or delay further progressive degeneration of the joint. It is a 2-stage procedure consisting of an initial arthroscopic cartilage biopsy, followed by 4 to 6 weeks of in vitro chondrocyte expansion and, finally, re-implantation. We recommend performing the MACI procedure arthroscopically for the second stage to treat a femoral trochlear defect. During the second surgical procedure, we examine and prepare the recipient site, followed by graft introduction in an all-arthroscopic manner via dry scoping, secured by a thin layer of fibrin glue.

Treatment of cartilage defects in the patellofemoral joint with matrix-associated autologous chondrocyte implantation effectively improves pain, function, and radiological outcomes after 5-7 years.

The aim of the present study was to evaluate midterm outcomes 5-7years after matrix-associated autologous chondrocyte implantation (MACI) in the patellofemoral joint. Twenty-six patients who had undergone MACI using the Novocart® 3D scaffold were prospectively evaluated. Clinical outcomes were determined by measuring the 36-Item Short-Form Health Survey (SF-36) and International Knee Documentation Committee (IKDC) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) values preoperatively and 3, 6, and 12months, and a mean of 6years postoperatively. At the final follow-up, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was evaluated. Twenty-two patients with 23 focal cartilage defects (19 patella and four trochlea) were available for the final follow-up. The mean defect size was 4.0 ± 1.9 cm2 (range 2.4-9.4 cm2). All clinical outcome scores improved significantly until 5-7 years after MACI (SF-36 score, 61.2 ± 19.6 to 83.2 ± 11.6; P = 0.001; IKDC score, 47.5 ± 20.6 to 74.7 ± 15.5; P < 0.001; and WOMAC, 29.8 ± 15.7 to 8.2 ± 10.3; P < 0.001). The mean MOCART score was 76.0 ± 11.0 at the final follow-up. Nineteen of the 22 patients (86.4%) were satisfied with the outcomes after 5-7 years and responded that they would undergo the procedure again. MACI in the patellofemoral joint demonstrated good midterm clinical results with a significant reduction in pain, improvement in function, and high patient satisfaction. These clinical findings are supported by radiological evidence from MOCART scores. IV-case series.

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study.

The optimal treatment approach for the complex pathology of meniscal insufficiency and coexisting full-thickness cartilage defects remains unclear. The purpose of this study was to evaluate the viability, safety, and efficacy of this combined surgical approach at medium-term follow-up. This is a single-centre longitudinal study with blinded outcome assessment. All consecutive patients treated with combined all-arthroscopic meniscal allograft transplantation (MAT) with bone bridge fixation and ACI using chondrospheres at our institution between 2001 and 2021 were eligible for inclusion. Twenty patients with an average follow-up of 72.6 ± 34.4 months were included in the statistical analysis. Clinical outcomes were assessed pre- and postoperatively using the IKDC Subjective Knee Form, Lysholm Score, Tegner Activity Scale, KOOS, and Visual Analog Scale (VAS) for patient satisfaction. Failure and reoperation rates were assessed, and cartilage regeneration tissue was evaluated on postoperative MRI. IKDC scores significantly improved from 52.1 ± 16.9 to 68.5 ± 16.3 (p = 0.003). Lysholm scores improved from 61.5 ± 21.7 to 78.5 ± 12.9 (p = 0.004). Tegner scores improved from 3.5 (1-4) to 4.0 (2-6) (p = 0.014). KOOS scores improved significantly across all subcategories, except 'symptoms', where improvements did not reach statistical significance. VAS for overall patient satisfaction showed improvements but did not reach statistical significance. The combined procedure was successful in 17 patients (85%). Eight patients had to undergo reoperation (40%), comprising mostly small, arthroscopic procedures. Seven reoperations were directly attributable to meniscal allograft transplantation (46.7%). Postoperative Magnetic Resonance Observation of Cartilage Repair Tissue scores were 68.9 ± 16.8 (n = 14). Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI. Level III.

MACI Sandwich Technique With Autologous Bone Graft

Background: Osteochondral lesions of the knee are difficult to manage. Such lesions can be effectively treated with the matrix-induced autologous chondrocyte implantation (MACI) “sandwich” technique using autologous chondrocytes on porcine collagen membrane in conjuction with autologous cancellous bone grafting (ABG). Few studies have examined this technique to restore the osteochondral unit. Indications: The MACI “Sandwich” procedure is indicated when osteochondral lesions are larger than 2 cm2 in size and deeper than 8 to 10 mm, with symptoms consistent with the location of the lesion. Technique Description: The chondral defect is radically debrided back to healthy bone and cartilage tissue. The base of the bony cavity is drilled to enhance the vascular supply and promote healing. Next, the bony cavity is prepared to slightly undermine the subchondral bone surface around the articular margins, with the depth of the cavity wider than the opening, similar to a dental amalgam. The autologous cancellous bone is subsequently morselized and impacted up to the level of the native subchondral bone plate. The first MACI membrane with the cells facing up is placed directly onto the bone graft site and compressed with a neural patty. The neural patty is removed, and the second MACI membrane is then placed with the cells facing down. The edges are then micro-sutured to ensure stability. Results: The “sandwich” technique has superior survival rates compared with autologous bone grafting alone, with patients reporting decreased pain, improved function, and high satisfaction scores over a mid-term to long-term follow-up. Discussion/Conclusion: The MACI “sandwich” technique is an effective surgical intervention to restore the osteochondral unit and preserve the patient's native knee joint. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Application of human platelet lysate in chondrocyte expansion promotes chondrogenic phenotype and slows senescence progression via BMP–TAK1–p38 pathway

Osteoarthritis (OA) is one of the most common musculoskeletal degenerative. OA treatments are aiming to slow down disease progression; however, lack of cartilage regeneration efficacy. Autologous chondrocyte implantation (ACI) is a promising cartilage-regeneration strategy that uses human articular chondrocytes (HACs) as cellular materials. However, the unreadiness of HACs from prolonged expansion, cellular senescence, and chondrogenic dedifferentiation occurred during conventional expansion, thus, minimizing the clinical efficacy of ACI. We aimed to examine the effects of a human platelet lysate (HPL) as an alternative human-derived HAC medium supplement to overcome the limitations of conventional expansion, and to explain the mechanism underlying the effects of HPL. During passages 2–4 (P2-P4), HPL significantly increased HAC proliferation capacities and upregulated chondrogenic markers. Simultaneously, HPL significantly reduced HAC senescence compared with conventional condition. HACs treated with LDN193189 exhibited a reduction in proliferation capacity and chondrogenic marker expression, whereas the HAC senescence increased slightly. These findings indicated involvement of BMP-2 signaling transduction in the growth-assistive, anti-senescent, and chondrogenic-inductive properties of HPL, which demonstrated its beneficial effects for application as HAC medium supplement to overcome current expansion limitations. Finally, our findings support the roles of platelets in platelet-rich plasma as a promising treatment for patients with OA.

Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta‐analysis

AbstractPurposeBone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone.MethodsAn online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non‐randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random‐effects model was used to compare the bone marrow aspirate concentrate‐augmented group with the control group.ResultsOut of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non‐randomised studies checklist, was weak. A significantly better functional outcome measures (p &lt; 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non‐blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix‐induced autologous chondrocyte implantation with matrix‐induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix‐induced chondrogenesis plus peripheral blood concentrate vs. matrix‐associated stem cell transplantation bone marrow aspirate concentrate.ConclusionThere is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient‐ and researcher‐blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved.Level of evidenceLevel III.

Meniscal Allograft Transplantation Concomitant With Cartilage Repair for Symptomatic Lateral Meniscus-Deficient Knees With Over Two Years of Follow-up.

Background and objective The treatment for symptomatic meniscus-deficient knees with cartilage defects remains challenging on account of insufficient meniscal substitutes. One solution for this might involve combining meniscal allograft transplantation (MAT) and cartilage repair. In this study, we aimed to analyze the effectiveness and safety of MAT concomitant with cartilage repair for symptomatic lateral meniscus-deficient knees in a setting with limited availability of meniscal transplants in Japan. Methods Nine patientswho underwent MAT concomitant with osteochondral transplantation (five) and/or autologous chondrocyte implantations (seven) were followed up for at least two years (mean: 51.2 months, range: 24-84 months). Their demographic data and other characteristics were as follows - mean age: 51.7 years, range: 36-67 years; men/women: 4/5; cause: trauma/discoid meniscus: 8/1; cartilage defect size: mean: 6.7 cm2/knee, range: 1.0-11.3. The effectiveness and safety were evaluated clinically by using the Lysholm Knee Scoring Scale(LKSS) and Japanese Orthopaedic Association (JOA) knee score, physical examination, X-rays, and MRI preoperatively and at one, 12, and 24 months after the implantation. Differences between the variables were analyzed using the Friedman test and Scheffe's multiple comparisons. Results The median LKSS and JOA scores significantly improved from 70 points (range: 21-80) and 35 (25-45) preoperatively to 86.5 (65-98) and 87.5 (80-95) at 24 months after surgery, respectively (p<0.001, p=0.0013). The range of motion (ROM), femorotibial angle, and the lateral joint space showed no significant changes. However, lateral meniscal extrusions (LMEs) increased by 3.0 mm (range: 0-6.3 mm) at one month postoperatively and remained unchanged until two years postoperatively. Treatment failure occurred in one case, which was revised by total knee arthroplasty (TKA) at 18 months postoperatively. Additional surgeries were needed in some cases: lateral meniscal tear (three cases), contracture (two cases), and patellar instability (one case). However, neither infection nor allergic reaction was observed in the blood exams. Conclusions Although MAT concomitant with cartilage repair showed good clinical outcomes, half of the cases needed additional surgeries. Based on our findings, this technique should be adopted only in select cases and performed bya handful of highly experienced surgeons.

Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU)

PurposeThis study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation.MethodsPatients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation.ResultsA total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1–2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]).ConclusionFemale patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries.Level of evidenceLevel III.