Autologous Chondrocyte Research Articles

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

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. To evaluate the effectiveness and safety of pMACI for large articular cartilage defects (≥4 cm2) in the knee joint using real-world data analysis. Case series; Level of evidence, 4. 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. 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. 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.

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.

Engineered autologous nasal cartilage for repair of nasal septal perforations - a case series.

This phase I clinical trial assessed the use of autologous nasal chondrocyte tissue-engineered cartilage (N-TEC) for functional repair of nasal septal perforations (NSP). The most widely used technique to treat NSP, namely interposition grafting with a polydioxanone (PDS) plate combined with a deep temporal fascia (DTF) graft, is still suboptimal towards patient satisfaction and revision rates. Patients (n=5, all female, age range: 23-54 years) had a 0.5-2.0cm diameter NSP. N-TEC was manufactured by expansion and 3D culture of autologous nasal septum chondrocytes into Chondro-Gide® collagen membranes. N-TEC was then shaped intraoperatively and enveloped in the harvested DTF before suturing it into the NSP. Safety (primary outcome) was assessed by the number of serious adverse reactions (SAR) until 12 months. Secondary outcomes included feasibility, assessed by surgical graft manipulation, and efficacy, assessed using subjective scoring (Nasal Obstruction Symptom Evaluation, NOSE, and Visual Analogue Scale, VAS, scores) and objective breathing function tests. Structural closure of NSP after 12 months was defined using endoscopy and computed tomography (CT) scans. NSP treatment by N-TEC implantation was safe and feasible, as no SAR and no challenge in graft manipulation was recorded for any of the patients. One year postoperative, subjective scoring improved in all patients, unless already optimal (average improvement of 23 and 28.6 points out of 100 respectively for NOSE and VAS scores). Objective respiratory function overall confirmed - with the exception of one case - the observations above (average improvement of 172 ml/s). NSP were closed and the mucosae completely healed in three patients. Autologous N-TEC is a valid treatment for NSP and warrants further clinical tests.

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.

Boosting chondrocyte bioactivity with ultra-sulfated glycopeptide supramolecular polymers

Although autologous chondrocyte transplantation can be effective in articular cartilage repair, negative side effects limit the utility of the treatment, such as long recovery times, poor engraftment or chondrogenic dedifferentiation, and cell leakage. Peptide-based supramolecular polymers have emerged as promising bioactive systems to promote tissue regeneration through cell signaling and dynamic behavior. We report here on the development of a series of glycopeptide amphiphile supramolecular nanofibers with chondrogenic bioactivity. These supramolecular polymers were found to have the ability to boost TGFβ-1 signaling by displaying galactosamine moieties with differing degrees of sulfation on their surfaces. We were also able to encapsulate chondrocytes with these nanostructures as single cells without affecting viability and proliferation. Among the monomers tested, assemblies of trisulfated glycopeptides led to elevated expression of chondrogenic markers relative to those with lower degrees of sulfation that mimic chondroitin sulfate repeating units. We hypothesize the enhanced bioactivity is rooted in specific interactions of the supramolecular assemblies with TGFβ-1 and its consequence on cell signaling, which may involve elevated levels of supramolecular motion as a result of high charge in trisulfated glycopeptide amphiphiles. Our findings suggest that supramolecular polymers formed by the ultra-sulfated glycopeptide amphiphiles could provide better outcomes in chondrocyte transplantation therapies for cartilage regeneration. Statement of significanceThis study prepares glycopeptide amphiphiles conjugated at their termini with chondroitin sulfate mimetic residues with varying degrees of sulfation that self-assemble into supramolecular nanofibers in aqueous solution. These supramolecular polymers encapsulate chondrocytes as single cells through intimate contact with cell surface structures, forming artificial matrix that can localize the growth factor TGFβ-1 in the intercellular environment. A high degree of sulfation on the glycopeptide amphiphile is found to be critical in elevating chondrogenic cellular responses that supersede the efficacy of natural chondroitin sulfate. This work demonstrates that supramolecular assembly of a unique molecular structure designed to mimic chondroitin sulfate successfully boosts chondrocyte bioactivity by single cell encapsulation, suggesting a new avenue implementing chondrocyte transplantation with supramolecular nanomaterials for cartilage regeneration.

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.

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.

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.

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/m2 (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.

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.

Analysis of Patients Who Undergo Index Arthroscopy With Biopsy but Not Implantation for Staged Chondrocyte Cell Transplantation.

Autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are 2-stage procedures requiring an index full-thickness cartilage biopsy. Only a portion of patients ultimately undergo second-stage ACI/MACI. To identify patients with articular cartilage defects who underwent arthroscopic debridement with biopsy for ACI/MACI and compare those who did with those who did not proceed with implantation within 2 years after biopsy. Additionally, the authors sought to identify why patients did not proceed with implantation. Case-control study; Level of evidence, 3. Patients who underwent arthroscopy and autologous chondrocyte biopsy from January 1, 2015, to December 31, 2019, and who had minimum 2-year follow-up data were grouped into those who proceeded with second-stage ACI/MACI (implant group; n = 97) and those who did not (biopsy group; n = 63). Demographic factors, cartilage defect characteristics, and preoperative International Knee Documentation Committee (IKDC) scores were analyzed. Patients in both groups were evaluated postoperatively using the IKDC, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) for pain, and patients who did not undergo implantation were asked for their reasoning. Body mass index (BMI) (P < .001) and Outerbridge grades at index arthroscopy (P = .047) were significantly higher for the implant group than the biopsy group. Both groups had significantly improved IKDC scores from their initial presentation to final follow-up (implant group: 46.4 ± 16.2 preoperative vs 69.6 ± 20.6 postoperative [P < .001]; biopsy group: 47.2 ± 15.9 preoperative vs 70.7 ± 19.1 postoperative [P < .001]); however, the level of improvement did not differ significantly between groups. Postoperative WOMAC, SANE, and VAS pain scores were also similar between groups. In the biopsy group, 23 patients (37%) cited symptom resolution or activity level improvement after initial arthroscopy as the reason for not proceeding with implantation. Patients who proceeded to the second stage of chondrocyte implantation via either ACI or MACI had higher-grade articular defects and higher BMI compared with those who underwent biopsy with concomitant debridement chondroplasty alone. Postoperative outcomes were similar between the groups.

Factors Influencing Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Implantation: Long-term Results at 10 Years

Background: Matrix-induced autologous chondrocyte implantation (MACI), the third-generation of the technique, is an established procedure for the treatment of focal cartilage defects in the knee. However, the literature lacks long-term results of MACI with good statistical power. Purpose: To determine long-term survival and patient-reported outcomes (PROs) in a representative cohort and to identify patient- and surgery-related parameters that may influence long-term clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 103 patients were clinically evaluated at the current follow-up of 8.1 years (range, 5-11.9 years). PRO measures (PROMs) included the Knee injury and Osteoarthritis Outcome Score (KOOS), EQ-5D, visual analog scale for pain, and Tegner Activity Scale. Magnetic resonance imaging results were evaluated by using the AMADEUS (area measurement and depth and underlying structures) and MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 knee score classification systems. Potential factors influencing PROs were first identified univariately and investigated in a multivariate regression model. Results: The defects had a mean size of 4.8 cm2 (range, 1.2-12 cm2) and were predominantly femorotibial (66%). The mean Kaplan-Meier survival rate of revision for any reason was 97.2% ± 1.6% at 10 years. In comparison to preoperative values, all PROMs were significantly improved at the current follow-up (P < .05). The MOCART 2.0 score peaked at 12 months (mean, 80.2 ± 15.3 months) and showed no significant change at 96 months (mean, 76.1 ± 19.5 months; P = .142). The linear multivariate regression model identified an association of body mass index (BMI), MOCART 2.0 score, and number of previous knee surgeries with KOOS (R2 = 0.41; f2 = 0.69). Further analysis of the individual determinants revealed an optimal BMI range of 20 to 29 for favorable PROs at 96 months. Significant correlations of MOCART subscores with the overall KOOS were found for graft surface and structure, bony reaction, and subchondral detectable changes. Only 30% of patients with2 previous surgeries and 20% of patients with 3 previous surgeries achieved a Patient Acceptable Symptom State (χ2 = 10.93; P = .012). Conclusion: The present study shows consistently good long-term clinical outcomes after MACI with a low revision rate and high patient satisfaction. BMI and number of previous knee surgeries may influence clinical outcomes and should be considered in patient selection and education. There is a correlation between graft structure, subchondral bone changes on magnetic resonance imaging, and long-term PROMs.

Comparable Outcomes Between Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation in the Setting of Patellar Realignment

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

Interleukin-4-Loaded Gelatin Methacryloyl Hydrogel Promotes Subcutaneous Chondrogenesis of Engineered Auricular Cartilage in a Rabbit Model.

Tissue engineering technology offers a promising solution for ear reconstruction; however, it faces the challenge of foreign body reaction and neocartilage malformation. This study investigates the impact of interleukin-4 (IL-4), an anti-inflammatory factor, on cartilage regeneration of hydrogel encapsulating autologous auricular chondrocytes in a rabbit subcutaneous environment. Initially, we assessed the influence of IL-4 on chondrocyte proliferation and determined the appropriate concentration using the CCK-8 test in vitro. Subsequently, we loaded IL-4 into gelatin methacryloyl (GelMA) hydrogel containing chondrocytes and measured its release profile through ELISA. The constructs were then implanted autologously into rabbits' subcutis, and after 3, 7, 14, and 28 days, cartilage matrix formation was evaluated by histological examinations, and gene expression levels were detected by qRT-PCR. Results demonstrated that IL-4 promotes chondrocyte proliferation in vitro, and maximum release from constructs occurred during the first week. In the rabbit subcutaneous implantation model, IL-4-loaded constructs (20 ng/mL) maintained a superior chondrocytic phenotype compared to controls with increased expression of anti-inflammatory factors. These findings highlight IL-4 as a potential strategy for promoting chondrogenesis in a subcutaneous environment and improving ear reconstruction.

More negative sagittal tibial tuberosity-trochlear groove distances are correlated with larger patellofemoral chondral lesion size.

The purpose of this study is to assess the association between sagittal tibial tuberosity-trochlear groove (sTT-TG) distance and patellofemoral chondral lesion size in patients undergoing cartilage restoration procedures. A retrospective cohort analysis of patients who underwent an osteochondral allograft transplantation or matrix-induced autologous chondrocyte implantation in the patellofemoral compartment, from 2010 to 2020, were included if they had patellofemoral high-grade lesions, magnetic resonance imaging (MRI) and minimum 2-year follow-up. The preoperative sTT-TG distance was measured independently on axial T2-weighted MRI sequences by two authors, each at least two weeks apart. Intraoperative lesion size was reported according to operative report measurements by the attending surgeon. An interclass correlation coefficient (ICC) was calculated to assess intra- and inter-rater reliability, and categorical data analysis and linear regression models were used to assess the relationship between sTT-TG and lesion size. A total of 80 patients (50 females) with a mean age of 31.5 ± 10.4 years, body mass index of 27.0 ± 5.9 kg/m2 and follow-up of 61.5 ± 21.4 months were included. A total of 107 lesions were present: 63 patients with unipolar (patella = 41, trochlea = 22) and 22 with bipolar lesions. The mean MRI defect size was 1.6 ± 1.0 cm2 and the mean intraoperative defect size was 3.8 ± 2.4cm2. Intra- (ICC: 0.99,0.98) and inter-rater reliability (ICC: 0.96) were excellent for both MRI defect size and sTT-TG measurements. The mean sTT-TG was -4.8 ± 4.9 mm and was significantly inversely related to MRI defect size (-0.45, p < 0.01), intraoperative patellar lesion size (-0.32, p = 0.01), total lesion area (-0.22, p = 0.04), but not trochlear lesion size (-0.09, p = 0.56). Multivariable regression demonstrated a more negative sTT-TG remained an independent variable correlated with larger MRI-measured patellofemoral defect sizes and intraoperative patellar lesions. A more negative sTT-TG was an independent variable correlated with larger patellofemoral lesions in patients undergoing patellofemoral cartilage restoration. Level III, Diagnostic.

Management of patellar and trochlear cartilage lesions with matrix-induced autologous chondrocyte implantation in conjunction with patellofemoral realignment procedures improves patient-reported outcomes and magnetic resonance image appearance

ObjectivesThe aim of this study is to evaluate the relationship between the achievement of clinically significant improvement in patient-reported outcome measures (PROMs) and the postoperative magnetic resonance image (MRI) appearance of matrix-associated chondrocyte implantation (MACI), in conjunction with patellofemoral realignment procedures, for the treatment of grade-IV chondral defects about the patellofemoral joint. MethodsA retrospective review of patients undergoing MACI for grade-IV chondral defects of the patella or trochlea by a single sports-medicine-fellowship-trained surgeon from 2017 to 2020 was performed. Concomitant realignment procedures, including tibial tubercle osteotomy and medial patellofemoral ligament reconstruction, were also performed as needed. Patients with preoperative and minimum 1-year postoperative PROMs and postoperative knee MRI were included. MRI scans were obtained at 6.3 (interquartile range: 5.8, 7.5) months postoperatively. A fellowship-trained musculoskeletal radiologist assigned a Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score (range: 0–100, with 100 equating to complete graft healing) to each MRI. Achievement of the minimal clinically important difference (MCID) for International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Score—Quality of Life, and Kujala scores were determined for each patient. Paired t-tests or Wilcoxon rank-sum tests were used to evaluate for an association between achievement of the MCID for each PROM and MOCART score. The average follow-up time and time from surgery to PROMs were 2.7 ​± ​1.5 years and 1.7 ​± ​0.66 years, respectively. ResultsThirty patients were included. There was a significant improvement in all PROMs from preoperative to postoperative (p ​< ​0.001). More than two-thirds of patients achieved the MCID for each PROM. Patients who achieved the MCID for IKDC had significantly higher MOCART scores (66.5 ​± ​16.2) than those who did not meet the MCID for IKDC (50.6 ​± ​23.6, p ​= ​0.043). ConclusionMACI for the treatment of patellofemoral chondral injuries is associated with clinically significant improvement in PROMs at short-term follow-up. Clinically significant improvements in IKDC scores are associated with a more mature MRI appearance of the autologous chondrocyte implantation graft on postoperative MRI, as indicated by higher MOCART scores. Level of evidenceIV—Case Series.