Autologous Chondrocyte Implantation Research Articles

Operative Treatment of Nonprimary Osteochondral Lesions of the Talus: A Systematic Review.

Nonprimary osteochondral lesions of the talus (OLT) pose a significant challenge in orthopaedics, with no definitive consensus on optimal surgical treatment. To consolidate the most recent evidence on operative treatments for nonprimary OLT by assessing patient-reported outcomes (PROs), postoperative complications, and clinical failures. Systematic review; Level of evidence, 4. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and PRISMA in Exercise, Rehabilitation, Sport medicine and Sports science guidelines. Searches were conducted in PubMed, Embase, and Cochrane Library databases through June 2023. Eligible studies evaluated operative outcomes in skeletally mature patients with nonprimary OLT after failed previous surgeries. Primary outcomes included clinical and functional PROs. Secondary outcomes included postoperative complications and clinical failures. Quantitative analyses involved weighted means, mean differences, minimal clinically important differences, success rates (95% binomial proportion confidence interval), and a pre-to-postoperative meta-analysis. Out of 3992 identified records, 50 studies involving 806 ankles from 794 patients were included. All operative treatments significantly improved PROs (P < .05), except osteochondral allograft transplantation (OCA) for American Orthopaedic Foot and Ankle Society and pain (visual analog scale/numeric rating scale [VAS/NRS]) scores and HemiCAP for pain (VAS/NRS) scores. Autologous chondrocyte implantation (ACI) and osteochondral autologous transplantation (OAT) demonstrated the greatest PRO success rates, exceeding 80%. Postoperative complications occurred in 4% of cases, most frequently with HemiCAP. Clinical failures affected 22% of cases, particularly with autologous matrix-induced chondrogenesis, OAT, OCA, and HemiCAP. Our systematic review demonstrated that ACI and OAT are promising treatments for nonprimary OLT, with ACI showing fewer clinical failures than OAT. Conversely, OCA and HemiCAP exhibited lower effectiveness and higher clinical failure rates, suggesting a need for reassessment.

Hydrogel-Enhanced Autologous Chondrocyte Implantation for Cartilage Regeneration-An Update on Preclinical Studies.

Autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI) have demonstrated improved clinical outcomes and reduced revision rates for treating osteochondral and chondral defects. However, their ability to achieve lasting, fully functional repair remains limited. To overcome these challenges, scaffold-enhanced ACI, particularly utilizing hydrogel-based biomaterials, has emerged as an innovative strategy. These biomaterials are intended to mimic the biological composition, structural organization, and biomechanical properties of native articular cartilage. This review aims to provide comprehensive and up-to-date information on advancements in hydrogel-enhanced ACI from the past decade. We begin with a brief introduction to cartilage biology, mechanisms of cartilage injury, and the evolution of surgical techniques, particularly looking at ACI. Subsequently, we review the diversity of hydrogel scaffolds currently undergoing development and evaluation in preclinical studies for articular cartilage regeneration, emphasizing chondrocyte-laden hydrogels applicable to ACI. Finally, we address the key challenges impeding effective clinical translation, with particular attention to issues surrounding fixation and integration, aiming to inform and guide the future progression of tissue engineering strategies.

Undergoing cartilage procedures before total knee arthroplasty is not associated with worse postoperative functional outcomes, readmission rates or complication rates.

Patients undergoing total knee arthroplasty (TKA) with prior knee cartilage surgery have unclear outcomes in the literature. This study compared outcomes after TKA in patients with or without prior knee cartilage surgery, and we hypothesized there would be equivocal outcomes between groups. A retrospective matched case-control study was conducted on patients from our institution who underwent ipsilateral cartilage procedure(s) and TKA (cases) or TKA alone (controls) from 2000 to 2022. Cartilage procedures included Autologous Chondrocyte Implantation (ACI), Osteochondral Allograft (OCA) and Microfracture (MFx). Matching was performed in 1:3 (case:control) ratio for age, sex, body mass index, Charlson Comorbidity Index, pre-TKA Kellgren-Lawrence osteoarthritis grade and follow-up for knee injury and osteoarthritis outcome score for joint replacement (KOOS-JR). Mann-Whitney U and χ2 analyses were conducted, with significance being a p < 0.05. A priori power analysis required 29 patients per cohort to reach a clinically detectable difference of 11 for KOOS-JR. Forty-three cases (one ACI, eight OCA and 34 MFx) and 129 controls were included after matching, with no significant demographic differences. Cases underwent TKA after cartilage surgery at a mean of 4.6 years. No significant differences existed between cases and controls for the preoperative KOOS-JR (45.2 vs. 47.8; p = 0.353), postoperative KOOS-JR (69.8 vs. 69.9; p = 0.974) or Delta KOOS-JR (30.4 vs. 26.0; p = 0.387). No significant differences existed for 90-day readmission rates (4.7% vs. 2.3%; p = 0.600) or revision TKA rates (11.6% vs. 5.4%; p = 0.177). Patients with and without prior cartilage surgery experience similar functional outcomes, readmission rates and revision rates after TKA on the same knee. Patients who are candidates for TKA with a history of cartilage surgery may be counselled that their surgical history on that knee does not convey the risk of worse functional outcomes. Level III case-control study.

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

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

Patellar Dysplasia and Cell-Based Cartilage Repair Outcomes

Objectives We aimed to evaluate the relationship between Wiberg patella type and outcomes following cell-based cartilage repair (autologous chondrocyte implantation [ACI] or particulated juvenile allograft cartilage transplantation [PJAC]) for the treatment of patellar chondral lesions at minimum 2-year follow-up. We hypothesized that Wiberg classification of patella shape would have no impact on patient-reported outcome measures (PROMs) or graft survival. Methods Patients undergoing ACI or PJAC for full-thickness patellar chondral defects between 2016-2020 were retrospectively reviewed following Institutional Review Board approval. The change in PROMs, including International Knee Documentation Committee (IKDC), Kujala, Veterans Rand 12 (VR-12) Mental, and VR-12 Physical scores, from pre- to postoperative and the percentage of patients who achieved the MCID for IKDC and Kujala scores were compared for the Wiberg A versus Wiberg B versus Wiberg C groups. Log-rank test was used to evaluate for differences in survival between subgroups. Results Fifty-nine patients (63 knees) were included, with an average age of 33.3±8.6 years, median BMI of 26.0 kg/m2 (interquartile range:21.8–30.2 kg/m2), and median time to follow up of 3.5 years (interquartile range:2.6–4.2 years). Twenty-six patellae (41%) were Wiberg type A, 29 (46%) were Wiberg type B, and 8 (13%) were Wiberg type C. There were no differences between Wiberg A versus B versus C groups with respect to change in PROMs from pre- to postoperative or the percentage of patients who achieved the MCID for IKDC or Kujala scores (p&gt;0.05 for all). There were no differences in survival between groups (p=0.45). Conclusion Wiberg patella type has no impact on patient-reported outcomes or graft survival at midterm follow-up. Patella dysplasia should not be seen as a contraindication for cell-based cartilage repair procedures.

A Randomized Controlled Trial Comparing "Early" Versus "Late" Periosteal Patch Attachment to Knee Chondral Defects in Autologous Chondrocyte Implantation.

Traditional autologous chondrocyte implantation (ACI) involves arthroscopically harvesting a cartilage biopsy (stage 1), followed by arthrotomy 3 to 4 weeks later to apply a periosteal patch and implant culture-expanded chondrocytes underneath (stage 2). This study aimed to determine if patch application during stage 1 rather than stage 2 improved clinical outcome. A randomized controlled trial was conducted from 1998 to 2001. Patients were randomized to receive either traditional ACI (control/late) or ACI with "early" patch during stage 1 (intervention/early). Clinical outcome (Lysholm score) was assessed pre-operatively and annually post-operatively. Seventy-seven patients were recruited, with 40 patients randomized to the early and 37 to the late patch group. The overall mean pre-operative Lysholm score was 51.8 (range 11-89) and significantly improved by 11.1 points (95% confidence interval [CI] = 4.8 to 17.4) at mean 12.7 years (range 1.5-23.7) follow-up. Latest mean Lysholm scores for the early and late groups were 68.4 (95% CI = 19 to 100) versus 56.7 (95% CI = 18 to 98). Adjusted for covariate imbalances, no evidence was found for a difference between the groups (mean difference = 8.5, 95% CI = -5.2 to 22.2, P = 0.22). Twenty-year survival until any re-operation or arthroplasty was 59.6%/82.1% for the early and 56.8%/69.5% for the late group, with no evidence for a difference. ACI is an effective durable treatment for cartilage defects, with high levels of patient satisfaction and low failure rates. No evidence was found that applying the periosteal patch at the time of chondrocyte harvest improved long-term Lysholm scores or survival until any re-operation or arthroplasty.

A Sendai virus-based expression system directs efficient induction of chondrocytes by transcription factor-mediated reprogramming.

Cartilage rarely heals spontaneously once damaged. Osteoarthritis (OA) is the most common degenerative joint disease among the elderly; however, effective treatment for OA is currently lacking. Autologous chondrocyte implantation (ACI), an innovative regenerative technology involving the implantation of healthy chondrocytes, may restore damaged lesions. Chondrocytes for ACI may potentially be induced from differentiated somatic cells using retrovirus (RV)-mediated transduction of three reprogramming factors (SOX9, KLF4, and c-MYC). However, the efficiency of the current induction system needs to be improved and the safety issues arising from the genomic integration of the vector DNA have to be addressed. To solve these problems, we used an RNA vector, termed the replication-defective and persistent Sendai virus vector (SeVdp), to express reprogramming factors for chondrocyte induction. Our results showed that the SeVdp-based vector induced chondrocytes more efficiently than the RV vector, probably because of robust and rapid expression of the transgenes, without any apparent integration of the SeVdp vector. The induced chondrocytes formed cartilage-like tissues when injected subcutaneously into mice. Thus, the SeVdp-based system for inducing chondrocytes may act as a foundation for developing safer and more effective treatments for damaged cartilage.

An Adhesive Hydrogel Technology for Enhanced Cartilage Repair: A Preliminary Proof of Concept.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels' adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

Effectiveness and Safety of Matrix-Associated Autologous Chondrocyte Implantation for the Treatment of Articular Cartilage Defects: A Real-World Data Analysis in Japan

Background: The effectiveness and safety of matrix-associated autologous chondrocyte implantation with an autologous periosteal flap (pMACI) remain unclear. The Japanese Ministry of Health, Labor, and Welfare requires postmarketing surveillance of all patients undergoing pMACI using the tissue-engineered product JACC. Purpose: To evaluate the effectiveness and safety of pMACI for large articular cartilage defects (≥4 cm2) in the knee joint using real-world data analysis. Study Design: Case series; Level of evidence, 4. Methods: Data were collected from patients who underwent pMACI between 2012 and 2019, with 2 years of follow-up. The primary outcomes were the Lysholm knee score and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months. Adverse events were assessed by physical examination, magnetic resonance imaging, and/or arthroscopy. Results: Overall, 232 knees in 225 patients who presented with trauma (198 knees) or osteochondritis dissecans (34 knees) in the medial (132 knees) and lateral (44 knees) femoral condyle, patella (25 knees), trochlea (86 knees), and tibial plateau (4 knees) were included. The mean age of the patients was 40.9 ± 15.0 years, with mean cartilage defects of 5.6 ± 2.4 cm2 in size. Concomitant surgeries, such as osteotomy (50 knees), ligament reconstruction (27 knees), meniscal procedures (28 knees), osteochondral autograft transplantation (24 knees), and microfracture (14 knees), were performed in 113 (48.7%) knees. The minimal clinically important difference in the Lysholm knee score and KOOS Symptoms subscale was achieved in 79.7% and 63.5% of patients, respectively, and the Patient Acceptable Symptom State was achieved in 90.1% and 73.7%, respectively. Substantial clinical benefit was achieved in the KOOS Sports/Recreation and Quality of Life subscales at 39.6% and 37.8%, respectively. Knees that underwent concomitant microfracture had significantly worse KOOS values than the remainder of the cohort. Complications, including effusion (16.8%), graft delamination (14.7%), knee contracture (9.1%), graft hypertrophy (8.2%), and ossification (3.4%), were observed in 86 (37.1%) knees. Osteochondritis dissecans was significantly associated with graft hypertrophy and ossification, whereas concomitant surgery was significantly associated with delamination and contracture. Treatment failure required additional cartilage procedures in 11 (4.7%) knees. Conclusion: Treatment of large cartilage defects (≥4 cm2) with pMACI resulted in improved outcome scores in approximately 75% of patients. However, complications occurred in one-third of patients, and 4.7% required reoperation.

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

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

Comparison of the Effects of Microfracture, Soft Callus Implantation, and Matrix-Supported Chondrocyte Implantation in an Experimental Osteochondral Defect Model in Rats

Background: The treatment of cartilage defects remains challenging due to the avascular nature of cartilage. Aim: This study investigates the therapeutic effect of soft callus in osteochondral defects and explores the ability of multipotent and pluripotent cells within the callus to form fibrous or hyaline cartilage in the defective area. Methods: Twenty-one rats were divided into three equal groups: Group 1 received only microfracture (MF), group 2 received microfracture with autologous chondrocyte implantation (MF+ACI), and group 3 received microfracture with soft callus implantation (MF+SCI). All rats underwent diaphyseal fracture in their left tibias, which was stabilized with a Kirshner wire. One week later, osteochondral defects were created in the right knees of all rats. For group 1, microfracture alone was applied to initiate healing in the defects. In group 2, heterologous chondrocytes, previously harvested from the lateral condyle of a rat’s left femur and cultivated in a laboratory environment, were implanted into the microfracture site. In group 3, soft callus tissue obtained from the left tibial fracture was compressed and implanted into the defective area. All groups were sacrificed at the 6th week, and the healing status of the osteochondral defect areas was histopathologically evaluated. Results: Macroscopic examination at the end of the study revealed comparable ICRS-1 scores for MF+ACI (group 2) (11.28 ± 1.25) and MF+SCI (group 3) (11.14 ± 0.37), while MF alone (group 1) (4.28 ± 1.25) showed significantly lower results. Microscopic examination yielded similar outcomes. Regarding histological scores, ICRS-2 scores for MF (group 1) (35.30 ± 1.13), MF+ACI (group 2) (47.09 ± 1.63), and MF+SCI (group 3) (43.97 ± 1.49) were statistically significantly lower. Conclusion: Defects treated with soft callus implantation demonstrated comparable outcomes to the widely used and gold-standard autologous chondrocyte implantation. When compared to microfracture alone, better macroscopic and microscopic results were achieved with soft callus implantation.

Autologous platelet-rich plasma and fibrin-augmented minced cartilage implantation in chondral lesions of the knee leads to good clinical and radiological outcomes after more than 12 months: A retrospective cohort study of 71 patients.

The treatment of cartilage lesions remains a challenge. Matrix-associated autologous chondrocyte implantation has evolved to become the gold standard procedure. However, this two-step procedure has crucial disadvantages, and the one-step minced cartilage procedure has gained attention. This retrospective study aimed to evaluate the clinical and radiological outcome of an all-autologous minced cartilage technique in cartilage lesions at the knee joint. In this retrospective cohort study, 71 patients (38.6 years ± 12.0, 39,4% female) with a magnetic resonance imaging (MRI) confirmed grade III-IV cartilage defect at the medial femur condyle (n = 20), lateral femur condyle (n = 2), lateral tibia plateau (n = 1), retropatellar (n = 28) and at the trochlea (n = 20) were included. All patients were treated with an all-autologous minced cartilage procedure (AutoCart™). Clinical knee function was evaluated by the Tegner score, visual analogue scale, the subjective and objective evaluation form of the International Knee Documentation Committee and the Knee Injury and Osteoarthritis Outcome Score (KOOS). MRI analyses were performed by magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 knee score. Follow-up examination was 13.7 ± 4.2 (12-24) months postoperative. All clinical scores significantly improved after surgical intervention (p < 0.0001), especially the subgroup sports and recreation of KOOS showed clear changes from baseline in the follow-up examination. In the postoperative MRI evaluation, 39 of 71 patients showed a complete fill of the cartilage defect without subchondral changes in 78% of the patients in the MOCART 2.0 score in the follow-up analysis. None of the patients showed adverse effects, which are linked to the minced cartilage procedure during the time of follow-up. An all-autologous minced cartilage technique for chondral lesions at the knee joint seems to be an effective and safe treatment method with good clinical and radiological short-term results. Level IV.

Commercial Insurance Coverage Criteria for Autologous Chondrocyte Implantation Poorly Reflect Current Research.

The aim of this study is to both quantify and qualify the way insurance companies justify their coverage policies for autologous chondrocyte implantation (ACI) and determine whether these policies align with recent research on the subject. The top 11 national commercial health insurance payers for ACI were identified. Coverage policy documents were recovered for 8 payers. These documents were examined, and the type of reference and the level of evidence (LOE) were recorded for each applicable reference. Specific coverage criteria for each individual payer were then extracted and assessed for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. This study found that the majority of cited references were primary journal articles (86, 58.1%) and that only 30 (20.2%) references were level I or level II evidence. This study also found significant homogeneity among payer coverage criteria. Cited sources inconsistently mentioned specific payer coverage criteria. In addition, payer criteria tended to be poorly supported by current evidence on ACI. This study demonstrates that commercial insurance payers' coverage policies for ACI poorly cite references, cite a majority of references with low LOE, and cite references which infrequently mention their specific coverage criteria. In addition, payer coverage policies have a high degree of homogeneity and many of their specific criteria are poorly supported by current research on ACI.

The transepicondylar distance is a reliable and easily measured parameter for estimating femoral cartilage surface area using MRI.

Different cartilage repair techniques are widely used to regenerate cartilage, such as autologous chondrocyte implantation (ACI), osteochondral autograft transfer, microfracturing and minced cartilage. Defect size is a key parameter for selecting the best procedure to repair cartilage. However, the defect's size is not related to the patient's total cartilage surface. This is because assessing the femoral cartilage surface area is time-consuming and therefore unsuitable in the daily clinical routine. It has been proposed that the femur's total cartilage area correlates positively with the transepicondylar distance (TEA). The knees of 40 subjects were analysed. Their average age was 30.1 ± 8.6 years. Twenty-four female and 16 male subjects were examined. Their mean body height was 176.2 ± 8.8 cm. MRI scans were performed via 3-Tesla MRI. These data were postprocessed and quantified using the browser-based, customizable SATORI platform (Fraunhofer MEVIS). This software computed the femoral cartilage surface area (FeCA), the patella cartilage surface area (PCA), the TEA and the patella length. Body height reveals a good correlation (r = 0.722, p < 0.001) with the distal femur's cartilage area surface. However, regression analysis shows only moderate dependence (R2: 0.514). A very good correlation (r = 0.830, p < 0.001) was observed between the TEA distance and the total cartilage surface area of the distal femur. The regression analysis yields a good value (R2: 0.684). The cranio-caudal length of the patella was chosen as a suitably measurable two-dimensional parameter for correlation analysis with the patella's total cartilage surface area. Those results yield a poor correlation (r = 0.577, p < 0.001) between the two parameters, and regression analysis reveals a low value (R2: 0.384). The TEA is a reliable parameter for estimating the femur's cartilage area using MRI. A simple determination of this parameter allows the estimation of the femur's total cartilage area as well as the surface-corrected defect size (SCDS) in daily routine. Level II.

Clinical comprehensive of microfracture, autologous chondrocyte implantation, and periosteum-covered iliac bone grafting for Hepple stage IV-V lesions.

Chronic ankle pain significantly impairs daily activities and athletic performance with osteochondral lesions of the talus (OLT) in Hepple stages IV and V, which are often causative factors. This study aimed to assess the efficacy and safety of autologous osteochondral transplantation (AOT) for the treatment of these conditions. This retrospective study was conducted from May 2020 to May 2023 at Cangzhou Traditional Chinese and Western Medicine Combined Hospital, including patients with a diagnosis of Hepple stage IV or V OLT confirmed by magnetic resonance imaging (MRI) and arthroscopy. Surgical interventions involved arthroscopic debridement, followed by AOT or limited arthrotomy based on the location and size of the lesion. Preoperative and postoperative evaluations used the Visual Analog Scale, American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale, MRI-Based Cartilage Repair Tissue Scoring, and the International Knee Documentation Committee Knee Evaluation Form. Statistical analysis was conducted using paired-sample t tests to compare the preoperative and postoperative data. Twenty patients were included, revealing significant postoperative improvements in Visual Analog Scale, American Orthopedic Foot and Ankle Society, and MRI-based cartilage repair tissue scores (P < .05). The radiographic findings suggested effective cartilage regeneration. No adverse effects were observed in the donor knee sites, as confirmed by the stable pre- and postoperative International Knee Documentation Committee Knee Evaluation Form scores. Recovery of physical abilities was achieved on average within 7.3 weeks for daily activities and 13.4 weeks for sports activities. AOT effectively treats Hepple stage IV-V OLT, improves ankle function, promotes cartilage regrowth, and allows quick resumption of daily and athletic activities without compromising donor-site integrity.

Cell‐preserving scheme for mechanobiological research on dedifferentiation of chondrocytes

AbstractIn the present work, we introduce a scheme for efficient mechanobiological research on the dedifferentiation of chondrocytes (CHs) using a deep neural network (DNN) model that does not require sacrificing the cells and thus, saving resources. Cells are a part of active biological systems subjected to physical stimuli such as mechanical loading. Such loading affects cellular processes including proliferation, differentiation, and the interplay with the surrounding environment. CHs are mechanosensitive cells that produce and maintain the cartilaginous matrix that allows cartilage to bear and distribute mechanical loads in joints; their role in cartilage regeneration and treatment of osteoarthritis (OA) has been the focus of research projects. Nevertheless, it remains an open challenge to fully understand the effect of mechanical stimuli on CHs. One of the unresolved mechanobiological behaviors of CHs is dedifferentiation. Dedifferentiation of CHs is the phenomenon where isolated CHs alter their phenotype when cultured in a 2D in vitro environment over passages. While intact, cobblestone‐shaped CHs mainly produce collagen II, dedifferentiated CHs with elongated shapes produce fibroblastic collagen I. This limits the scalability of a promising treatment for OA, called ‘autologous chondrocyte implantation (ACI)’. To overcome this limit, research is being carried out to understand the dedifferentiation mechanism in detail. This proposed scheme is composed of three parts: (i) the cell‐seeded specimens are loaded in a bioreactor system, (ii) an optical microscope is used to obtain the phase‐contrast images of living cells, and (iii) the images are analyzed using a DNN. This scheme provides an efficient tool to analyze the ratio of intact to dedifferentiated CHs while preserving cells on our way to elucidate the effects of mechanical loading on the dedifferentiation of CHs.

Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair

BackgroundArticular cartilage degeneration can result from injury, age, or arthritis, causing significant joint pain and disability without surgical intervention. Currently, the only FDA cell-based therapy for articular cartilage injury is Autologous Chondrocyte Implantation (ACI); however, this procedure is costly, time-intensive, and requires multiple treatments. Mesenchymal stromal cells (MSCs) are an attractive alternative autologous therapy due to their availability and ability to robustly differentiate into chondrocytes for transplantation with good safety profiles. However, treatment outcomes are variable due to donor-to-donor variability as well as intrapopulation heterogeneity and unstandardized MSC manufacturing protocols. Process improvements that reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential during expansion culture are needed to realize the full potential of MSC therapy.MethodsIn this study, we investigated the potential of MSC metabolic modulation during expansion to enhance their chondrogenic commitment by varying the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid in culture media. We tested the effect of metabolic modulation in short-term (one passage) and long-term (up to seven passages). We measured metabolic state, cell size, population doubling time, and senescence and employed novel tools including micro-magnetic resonance relaxometry (µMRR) relaxation time (T2) to characterize the effects of AA on improved MSC expansion and chondrogenic potential.ResultsOur data show that the addition of 1 mM L-ascorbic acid-2-phosphate (AA) to cultures for one passage during MSC expansion prior to initiation of differentiation improves chondrogenic differentiation. We further demonstrate that AA treatment reduced the proportion of senescent cells and cell heterogeneity also allowing for long-term expansion that led to a > 300-fold increase in yield of MSCs with enhanced chondrogenic potential compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS and higher µMRR T2 values, identifying critical quality attributes that could be implemented in MSC manufacturing for articular cartilage repair.ConclusionsOur results suggest an improved MSC manufacturing process that can enhance chondrogenic potential by targeting MSC metabolism and integrating process analytic tools during expansion.

Long-Term Outcomes of Arthroscopically Verified Focal Cartilage Lesions in the Knee: A 19-Year Multicenter Follow-up with Patient-Reported Outcomes.

Focal cartilage lesions (FCLs) are frequently found during knee arthroscopies and may impair quality of life (QoL) significantly. Several treatment options with good short-term results are available, but the natural history without any treatment is largely unknown. The aim of this study was to evaluate patient-reported outcome measures (PROMs), the need for subsequent cartilage surgery, and the risk of treatment failure 20 years after diagnosis of an FCL in the knee. Patients undergoing any knee arthroscopy for an FCL between 1999 and 2012 in 6 major Norwegian hospitals were identified. Inclusion criteria were an arthroscopically classified FCL in the knee, patient age of ≥18 years at surgery, and any preoperative PROM. Exclusion criteria were lesions representing knee osteoarthritis or "kissing lesions" at surgery. Demographic data, later knee surgery, and PROMs were collected by questionnaire. Regression models were used to adjust for and evaluate the factors impacting the long-term PROMs and risk factors for treatment failure (defined as knee arthroplasty, osteotomy, or a Knee injury and Osteoarthritis Outcome Score-Quality of Life [KOOS QoL] subscore of <50). Of the 553 eligible patients, 322 evaluated patients (328 knees) were included and analyzed. The mean follow-up was 19.1 years, and the mean age at index FCL surgery was 36.8 years (95% confidence interval [CI], 35.6 to 38.0 years). The patients without knee arthroplasty or osteotomy had significantly better mean PROMs (pain, Lysholm, and KOOS) at the time of final follow-up than preoperatively. At the time of follow-up, 17.7% of the knees had undergone subsequent cartilage surgery. Nearly 50% of the patients had treatment failure, and the main risk factors were a body mass index of ≥25 kg/m 2 (odds ratio [OR] for overweight patients, 2.0 [95% CI, 1.1 to 3.6]), >1 FCL (OR, 1.9 [CI, 1.1 to 3.3]), a full-thickness lesion (OR, 2.5 [95% CI, 1.3 to 5.0]), and a lower level of education (OR, 1.8 [95% Cl, 1.1 to 2.8]). Autologous chondrocyte implantation (ACI) was associated with significantly higher KOOS QoL, by 17.5 (95% CI, 3.2 to 31.7) points, and a lower risk of treatment failure compared with no cartilage treatment, microfracture, or mosaicplasty. After a mean follow-up of 19 years, patients with an FCL who did not require a subsequent knee arthroplasty had significantly higher PROM scores than preoperatively. Nonsurgical treatment of FCLs had results equal to those of the surgical FCL treatments except for ACI, which was associated with a better KOOS and lower risk of treatment failure. Full-thickness lesions, >1 FCL, a lower level of education, and a greater BMI were the main risk factors associated with poorer results. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Bone marrow edema-like signal after cartilage repair does not affect outcomes in a five-year follow-up.

Bone marrow edema-like signal (BMELS) after cartilage repair is common, but its clinical significance remains uncertain. This study aimed to investigate the clinical and structural significance of BMELS following microfracturing (MFX) and matrix-induced autologous chondrocyte implantation (MACI). In this multicenter study, MRI examinations were performed over a period of 5 years after cartilage repair surgery (MFX n = 17; MACI n = 28) in 45 patients. Morphological assessments, including the MOCART 2.0 (magnetic resonance observation of cartilage repair tissue), quantitative imaging biomarkers (QIB) with T2 mapping of the repair tissue, and, specifically, assessment of the presence and size of BMELS, were conducted along with patient-reported outcome measures, such as the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC). BMELS structural and clinical assessments were obtained after 3 months, 12 months, and 60 months. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank test, Shapiro-Wilk test, and simulation-based power analysis. BMELS were a common finding 60 months after cartilage repair. The size of BMELS differed significantly only between MACI and MFX patients after 3 months, with larger BMELS occurring in the MFX group. There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores. BMELS frequently appeared after cartilage repair procedures. We could show that the postoperative size and change in the size of BMELS after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties of the treated area after 60 months. Question What is the clinical significance of bone marrow edema-like signal (BMELS) appearance after matrix-induced autologous chondrocyte implantation (MACI) or microfracture (MFX)? Finding There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores. Clinical relevance BMELS frequently appeared after cartilage repair, the appearance or the size dynamic after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties after 60 months.

Secondary matrix-associated autologous chondrocyte implantation after failed cartilage repair shows superior results when combined with autologous bone grafting: Findings from the German Cartilage Registry (KnorpelRegister DGOU).

The aim of this study was to evaluate whether additive autologous bone grafting (ABG) improves clinical outcome and survival in revision matrix-associated autologous chondrocyte implantation (M-ACI) after failed cartilage repair (CR). A retrospective, registry-based, matched-pair analysis was performed to compare patient-reported outcomes and survival in secondary M-ACI with or without additional bone grafting for focal full-thickness cartilage defects of the knee and to compare it with those in primary M-ACI. Patients were matched for age, sex, body mass index, defect size and localization, and number of previous CRs. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was assessed over a follow-up period of 36 months. The patient acceptable symptomatic state, the clinical response rate and the survival of the subgroups were determined. A total of 818 patients were matched. Revision M-ACI (n = 238) with concomitant bone grafting was associated with significantly higher PRO as measured by KOOS (80.8 ± 16.8 vs. 72.0 ± 17.5, p = 0.032) and higher CRR (81.4% vs. 52.0%, p = 0.018) at 36 months compared to patients with revision M-ACI alone. KOOS and KOOS improvement in these patients did not differ from those who underwent primary M-ACI (p = n.s.). The combination of M-ACI and ABG resulted in a significantly higher KOOS at 36 months than M-ACI alone, regardless of whether bone marrow stimulation (89.6 ± 12.5 vs. 68.1 ± 17.9, p = 0.003) or ACI (82.6 ± 17.0 vs. 72.8 ± 16.0, p = 0.021) was performed before. Additional bone grafting results in equivalent survival rates at 7 years in secondary compared to primary M-ACI (83% vs. 84%, p = n.s.). Regardless of the type of previous CR, additional bone grafting in secondary M-ACI improves the clinical outcome, response rate and survival at 36 months compared to M-ACI alone. Secondary M-ACI with ABG had comparable clinical response and survival rates to primary M-ACI. Therefore, subchondral bone should be treated even in cases of mild bone involvement in revision M-ACI. Level III.