Cartilage Repair Tissue Research Articles

Microfracture Versus a Porcine-Derived Collagen-Augmented Chondrogenesis Technique for Treating Knee Cartilage Defects: Results at Midterm Follow-up.

Damaged cartilage can be treated using the creation of microfractures (MFxs) or the porcine-derived collagen-augmented chondrogenesis technique (C-ACT). To provide the midterm results of a multicenter randomized controlled trial comparing MFx and C-ACT for knee cartilage defects. Randomized controlled trial; Level of evidence, 1. The study cohort comprised 36 patients with medial femoral condyle cartilage defects who were followed up for 6 years with clinical and magnetic resonance imaging data (n = 14 treated with MFx alone, n = 22 treated with C-ACT). Clinical outcomes were assessed preoperatively and at 1, 2, and 6 years postoperatively using a visual analog scale (VAS) for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the International Knee Documentation Committee (IKDC) subjective score. Magnetic resonance imaging scans were performed preoperatively and at 1 and 6 years postoperatively, and the repaired cartilage tissue was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score. The repaired tissue/reference cartilage ratio was quantified using T2 mapping. Adverse events during follow-up were also evaluated. In both groups, the VAS pain score improved and was maintained for 1, 2, and 6 years postoperatively compared with preoperatively (P < .05 for all). Although there were no significant differences between groups in the VAS pain, KOOS, or IKDC scores at any time point, the change in the IKDC-Activities of Daily Living subscore from preoperatively to 6 years postoperatively was better in the C-ACT group than the MFx group (P = .0423). At 6 years postoperatively, the MOCART assessment showed superior results regarding the surface of the repair tissue in the C-ACT group compared with the MFx group (P = .0288). There were no differences between the groups in the total MOCART score or other subscores. The study results suggest that C-ACT has similar effects to MFx in improving pain, joint function, and imaging findings and may be superior to MFx in improving daily life function and improving the quality of the surface of the cartilage tissue. ClinicalTrials.gov identifier: NCT02539030.

AMIC achieves sustained clinical improvement in isolated patellar cartilage defects over 5 years, correlating with MRI.

To evaluate 5-year postoperative clinical outcomes of autologous matrix-induced chondrogenesis (AMIC) for isolated ICRS grade 3-4 patellar cartilage defects and correlate outcomes with magnetic resonance imaging (MRI). The hypothesis was that AMIC would improve clinical symptoms and induce neocartilage formation, visible on MRI, making it a safe and effective option for repairing focal patellar cartilage defects. The cohort comprised 13 focal patellar lesions in 12 patients. Pain visual analogue scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala score, EuroQol-5D Health Survey questionnaire and MRI data were assessed preoperatively and at 2 and 5 years postoperatively. All MRI scans were evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue System. Descriptive statistics were calculated on all data. Inferential analysis comparing outcome scores before and after surgery employed the nonparametric Wilcoxon signed-rank test, with the nonparametric Friedman test used to detect differences across multiple test attempts. p < 0.05 was considered statistically significant. Twelve patients (23-52 years old) with patellofemoral chondral full-thickness defects (2-4 cm2) were treated. At a 5-year follow-up, eleven knees showed MRI improvement. Two were asymptomatic and nine showed clear clinical improvement. Only one knee showed no clinical improvement. MRI revealed a defect filling with newly formed cartilage characterized by a less compact and heterogeneous signal. Cartilage degradation or joint damage was observed in two knees, and bone formation within the plate was identified in four. AMIC significantly improved patients' VAS pain, KOOS, EuroQol-5D and Kujala scores compared to preoperative baseline for up to 5 years postoperatively. Satisfactory clinical outcomes and new cartilage formation, as observed by MRI, are achieved with AMIC at mid-term follow-up for ICRS grade 3-4 in small-to-medium-sized patellar defects in patients under 52 years of age, with improvements maintained for up to 5 years. Level III.

Osteochondral Autograft Transplantation for Symptomatic Full-thickness Patellar Cartilage Defects in Adolescents.

This study aimed to review the clinical, radiographic, and magnetic resonance imaging (MRI) outcomes of osteochondral autograft transplantation applied to patellar cartilage lesions of patients under 18 years of age. Data from nine consecutive patients were retrospectively analyzed for indications, preoperative complications, and clinical-radiographic outcomes. Patients were clinically evaluated using the Pedi-IKDC and Lysholm scores. In addition, return to sports and knee pain were assessed. MRI evaluation included an analysis of osteochondral graft integration using the magnetic resonance observation of cartilage repair tissue 2.0 score and radiographic classification of osteoarthritis using the Kellgren-Lawrence system. Nine patients (9 knees, 6 males) with a mean age of 14 years (SD: 1.7, range; 11 to 17y) were analyzed. Lesions were located on the medial facet (N=5), lateral facet (N=3), and central ridge of the patella (N=1). One or 2 cylindrical osteochondral grafts were transplanted, with a median diameter of 9mm (range: 8 to 10mm). The average lesion size was 102.9mm2. At a mean follow-up of 45.1 months (range: 23 to 117mo), the mean Pedi-IKDC score was 89.2 (SD: 9.8), and the Lysholm score was 94.4 (SD: 4.8). Patients returned to sports in an average of 7.3 months (SD: 2, range: 6 to 12mo). MRI of 8 patients showed osteochondral graft integration with a mean magnetic resonance observation of cartilage repair tissue 2.0 score of 86.9 (SD: 7, range: 80 to 100). Six knees showed Kellgren-Lawrence grade 0 joint space on radiographs, and 3 showed grade 1. Eight patients were asymptomatic at the last follow-up, and 1 reported occasional mild pain with intense physical activity. One patient developed arthrofibrosis, requiring arthroscopic lysis of adhesions and manipulation. Osteochondral autograft transplantation is a safe and effective technique for treating symptomatic patellar full-thickness chondral lesions in adolescents. Long-term follow-up studies will determine whether the affected area maintains structural and functional integrity over time. Level IV-therapeutic study.

Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes

BackgroundThe phenomenon of intercellular mitochondrial transfer from mesenchymal stromal cells (MSCs) has shown promise for improving tissue healing after injury and has potential for treating degenerative diseases like osteoarthritis (OA). Recently MSC to chondrocyte mitochondrial transfer has been documented, but the mechanism of transfer is unknown. Full-length connexin 43 (Cx43, encoded by GJA1) and the truncated, internally translated isoform GJA1-20k have been implicated in mitochondrial transfer between highly oxidative cells, but have not been explored in orthopaedic tissues. Here, our goal was to investigate the role of Cx43 in MSC to chondrocyte mitochondrial transfer. In this study, we tested the hypotheses that (a) mitochondrial transfer from MSCs to chondrocytes is increased when chondrocytes are under oxidative stress and (b) MSC Cx43 expression mediates mitochondrial transfer to chondrocytes.MethodsOxidative stress was induced in immortalized human chondrocytes using tert-Butyl hydroperoxide (t-BHP) and cells were evaluated for mitochondrial membrane depolarization and reactive oxygen species (ROS) production. Human bone-marrow derived MSCs were transduced for mitochondrial fluorescence using lentiviral vectors. MSC Cx43 expression was knocked down using siRNA or overexpressed (GJA1 + and GJA1-20k+) using lentiviral transduction. Chondrocytes and MSCs were co-cultured for 24 h in direct contact or separated using transwells. Mitochondrial transfer was quantified using flow cytometry. Co-cultures were fixed and stained for actin and Cx43 to visualize cell-cell interactions during transfer.ResultsMitochondrial transfer was significantly higher in t-BHP-stressed chondrocytes. Contact co-cultures had significantly higher mitochondrial transfer compared to transwell co-cultures. Confocal images showed direct cell contacts between MSCs and chondrocytes where Cx43 staining was enriched at the terminal ends of actin cellular extensions containing mitochondria in MSCs. MSC Cx43 expression was associated with the magnitude of mitochondrial transfer to chondrocytes; knocking down Cx43 significantly decreased transfer while Cx43 overexpression significantly increased transfer. Interestingly, GJA1-20k expression was highly correlated with incidence of mitochondrial transfer from MSCs to chondrocytes.ConclusionsOverexpression of GJA1-20k in MSCs increases mitochondrial transfer to chondrocytes, highlighting GJA1-20k as a potential target for promoting mitochondrial transfer from MSCs as a regenerative therapy for cartilage tissue repair in OA.

The collagen-augmented chondrogenesis technique demonstrates superior cartilage repair compared to microfracture for cartilage defects of the knee joint, regardless of age.

This study investigated whether age affects clinical outcomes and cartilage repair quality in patients who underwent collagen-augmented chondrogenesis. The study included patients who underwent either the collagen-augmented chondrogenesis technique or microfracture for cartilage defects of the knee joint of International Cartilage Repair Society grade 3 or 4. Patients were categorised according to an age threshold of 50 years and the treatment method, whether collagen-augmented chondrogenesis technique or microfracture. Group 1 comprised 31 patients aged 50 years or older who received the collagen-augmented chondrogenesis technique, Group 2 consisted of 32 patients under the age of 50 years who received the collagen-augmented chondrogenesis technique and Group 3 included 243 patients aged 50 years or older who received microfracture. Clinical outcomes were assessed using the walking visual analogue scale (VAS) for pain and the Western Ontario McMaster University Osteoarthritis Index scale score (WOMAC) two years after surgery. For patients with magnetic resonance imaging results 1 year postoperatively (Group 1: 30 patients; Group 2: 31 patients; and Group 3: 31 patients), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) assessment was used to evaluate repaired cartilage lesions. There were no significant differences in the VAS and WOMAC scores between the three groups 2 years after surgery (all n.s.). The MOCART score in patients who underwent MRI at 1 year postoperatively showed significant differences in the degree of defect repair, integration with the border zone, surface of the repaired tissue, adhesion and total score among the three groups (all p < 0.05). Post hoc analysis revealed no difference in the total MOCART scores between Groups 1 and 2. However, Groups 1 and 2 had significantly higher MOCART scores than Group 3 1 year after surgery (all p < 0.05). The collagen-augmented chondrogenesis technique group showed improved quality of cartilage repair compared to the microfracture group, regardless of patient age. Compared with simple microfracture treatment, there were no differences in clinical outcomes between the patient groups, related to age. Level Ⅲ.

Does scaffold enhancement show significant superiority over microfracture alone for treating knee chondral defects? A systematic review and meta-analysis of randomised clinical trials.

Chondral and osteochondral lesions in the knee are common conditions that significantly impair individuals' well-being and can lead to osteoarthritis, imposing substantial burdens on healthcare systems. The limited natural healing capacity of articular cartilage necessitates innovative treatment strategies. Microfracture (MF) is a widely used technique for knee chondral defects, but its long-term efficacy is often inadequate. Although recent randomised controlled trials have compared microfractures with scaffold-enhanced therapies, a comprehensive systematic review and meta-analysis are lacking. An extensive literature search was conducted in PubMed and EMBASE databases following PRISMA guidelines. Inclusion criteria focused on randomised controlled trials (RCTs) comparing microfractures alone to matrix-induced chondrogenesis for knee chondral defects with at least a 12-month follow-up. Ten randomised controlled trials conducted between 2013 and 2024, enroling 378 patients, were included. The meta-analysis showed no significant superiority of scaffolds over MF (p > 0.05) in International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, Visual Analog Scale, and Magnetic Resonance Observation of Cartilage Repair Tissue scores at 12 and 24 months. However, individual studies suggested the potential benefits of scaffolds, especially in long-term outcomes. Clinical improvements from MF typically decline after 2-3 years, underscoring the need for long-term follow-up in future research. Our meta-analysis shows no significant difference between MF and MF with scaffold in treating knee cartilage defects, though some long-term RCTs demonstrate statistically significant differences. The absence of a universally accepted algorithm for analysing knee chondral defects limits this study. Establishing reliable guidelines and standardised study protocols is essential to improve long-term patient outcomes and the quality of future papers. Level I.

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.

Microfracture for medium size to large knee chondral defects has limited long-term efficacy: A systematic review.

To evaluate clinical and radiographic outcomes, return to sport, failure rate, operations and complications in patients undergoing microfracture of the knee, including the femoral condyle, tibial plateau, patella and trochlea, at a mean 10-year or greater follow-up. A literature search was performed by querying SCOPUS, PubMed, Medline and the Cochrane Central Register for Controlled Trials from database inception through May 2023 according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were level I-IV human studies reporting on outcomes, reoperations and complications following microfracture of the knee at a mean 10-year or greater follow-up. Biomechanical and epidemiological studies, including patients undergoing concomitant realignment procedures, and studies with patients under 18 years old were excluded. Data regarding failure, as defined by each study, as well as reoperations were gathered. Study quality was assessed via the Methodological Index for Nonrandomized Studies criteria. Nine studies from 2003 to 2018, consisting of 727 patients (mean age 38.9 ± 8.1 years; range 25.8-47.6) undergoing microfracture for chondral defects in the knee were identified. Mean follow-up ranged from 10 to 17 years. Males composed 56.5% of patients, with a mean defect size ranging from 2.3 to 4.01 cm2. Based on radiographs at follow-up, osteoarthritis progression occurred in 40%-48% of patients. Magnetic Resonance Observation of Cartilage Repair Tissue scores were low. Patient-reported outcome measures showed significant improvement in postoperative scores at final follow-up. Return-to-sport rate ranged from 17.2% to 20%. Longitudinal analysis revealed declining clinical outcomes and return-to-sport rates from short- and mid- to long-term follow-up. There was high variability in failure definition and reoperations, with 2.9%-41% of patients requiring total knee arthroplasty. At a mean 10-year or greater follow-up, microfracture for chondral defects of the knee 2-4 cm2 in size demonstrated a high rate of osteoarthritis progression with poor healing of the chondral defect and low overall return-to-sport rates. Failure and reoperation rates ranged from 2.9% to 41%, with declining outcomes from short- and mid- to long-term follow-up. The advantages of microfracture relating to availability, complexity, and cost should be weighed against concerns about long-term success, particularly with medium-size and larger lesions. Level IV systematic review.

Research Progress on the SDF-1/CXCR4 Axis in Cartilage Injury

The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1), is a small pro-inflammatory chemokine that primarily binds to CXC receptor 4 (CXCR4; CD184), serving as a major regulatory factor for cell transport and adhesion. When SDF-1 binds to CXCR4, it triggers intracellular signaling through several pathways that initiate processes such as chemotaxis, cell survival, proliferation, calcium influx, and gene transcription. The SDF-1/CXCR4 axis plays a crucial role in the development of bone marrow stem cells and the process of tissue regeneration. Repairing cartilage tissue necessitates a sufficient number of chondrocytes, making bone marrow mesenchymal stem cells particularly suitable for this purpose. This signaling pathway is essential for cartilage injury repair. It promotes stem cell migration and localization, regulates cell proliferation and differentiation, and inhibits inflammatory responses. This article reviews the current research advancements related to the SDF-1/CXCR4 axis in cartilage tissue repair.

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.

Cartilage Repair: Promise of Adhesive Orthopedic Hydrogels.

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.

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.

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.

Angelica sinensis polysaccharide facilitates chondrogenic differentiation of adipose-derived stem cells via MDK-PI3K/AKT signaling cascade

ObjectAdipose-derived mesenchymal stem cells (ADSCs) have received significant attention in the field of cartilage tissue repair. Angelica sinensis polysaccharide (ASP) can enhance both the proliferation and differentiation of mesenchymal stem cells. Therefore, we intend to explore the effect of ASP on chondrogenic differentiation of ADSCs in vitro, and elucidate the underlying mechanisms. MethodADSCs were treated with different concentrations of ASP to determine the optimal concentration. The chondrogenic differentiation of ADSCs was evaluated using Alcian blue staining, qRT-PCR, western blot, and IF staining. Transcriptome sequencing was performed to identify the expression profiles of ADSCs before and after ASP treatment, followed by bioinformatic analyses including differential expression analysis, enrichment analysis, and construction of PPI networks to identify differentially expressed genes (DEGs) associated with ASP and chondrogenic differentiation. ResultSurface markers of isolated rat-derived ADSCs were identified by CD44+CD90+CD45-CD106-, and exhibited the capacity for lipogenic, osteogenic, and chondrogenic differentiation. With increasing concentration of ASP treatment, there was an upregulation in the activity and acidic mucosubstance of ADSCs. The levels of Aggrecan, COL2A1, and Sox9 showed an increase in ADSCs after 28 days of 80 µg/ml ASP treatment. Transcriptome sequencing revealed that ASP-associated DEGs regulate extracellular matrix synthesis, immune response, inflammatory response, and cell cycle, and are involved in the NF-κB, AGE-RAGE, and calcium pathways. Moreover, Edn1, Frzb, Mdk, Nog, and Sulf1 are hub genes in DEGs. Notably, ASP upregulated MDK levels in ADSCs, while knockdown of MDK mitigated ASP-induced elevations in acidic mucosubstance, chondrogenic differentiation-related markers (Aggrecan, COL2A1, and Sox9), and the activity of the PI3K/AKT pathway. ConclusionASP enhances the proliferation and chondrogenic differentiation of ADSCs by activating the MDK-mediated PI3K/AKT pathway.

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.

Role of Growth Factors in Nasal Cartilage Development and Molding: A Comprehensive Review.

This review aims to investigate the properties of growth factors concerning the morphogenesis and development of nasal cartilage, which is fundamentally important for facial form and appearance. Since cartilagelacks a blood supply, it is more difficult to regenerate, as cartilage tissue obtains sustenance by diffusion. Cytokines are signalling molecules that control chondrocyte metabolism and extracellular matrix formation, which is required for cartilage development, homeostasis, and healing. Some craniofacial illnesses alter the composition of the cartilage and the structural organization of growth factors, allowing for moulding. TGF-β (transforming growth factor-β) encourages chondrocyte differentiation, whereas IGF-1 (insulin-like growth factor-1) stimulates cartilage-forming collagen synthesis and chondrocyte multiplication. We used the scoping review approach to present current research on the role of growth factors in the creation and architecture of nasal cartilage. We generally observed this structure before conducting specific experiments to determine the impact of growth agents on the development of chondrocytes and cartilage. Prominent findings increase our understanding of how growth factors influence the extracellular matrix, cell activities and features, and cartilage growth rate; all are critical for cartilage tissue development and repair. Research into growth factors and their physiological interactions with cartilage may help improve treatment's functional and aesthetic outcomes and our understanding of the origins and consequences of nasal congenital anomalies. This study emphasizes the importance of expanding knowledge and experience, as well as the use of growth factors in clinical practice, to stimulate cartilage development.

Effect of Cellular Dosage of Bone Marrow Aspiration Concentrate on the Radiological Outcomes in Knee Osteoarthritis: A Phase I Dose-Escalation Study.

Knee osteoarthritis(KOA), a chronic degenerative disease, significantly impairs quality of life due to pain and mobility limitations. Traditional treatments focus on symptom management without addressing the underlying disease progression, leading to a growing interest in regenerative medicine approaches. Bone marrow aspirate concentrate (BMAC), rich in mesenchymal stem cells and growth factors, has shown potential for cartilage repair and symptom relief in KOA. Despite promising outcomes, the optimal BMAC dosage for knee OA treatment remains undetermined. This study aims to evaluate the radiological outcomes of varying BMAC dosages in knee OA treatment. This prospective controlled dose-escalation study involved 75 patients with early-stage knee OA, categorized into three groups based on BMAC dosage administered 10x106 cells (low-dose group), 50×106 cells (medium-dose group), or 100x106 cells (high-dose group). All the patients underwent a single intra-articular injection of BMAC and were monitored over a year. The primary outcomes include magnetic resonance observation of cartilage repair tissue (MOCART 2.0) score to assess the cartilage. We noted significant improvement in the overall MOCART score (p=0.027) and subchondral change sub-score (p=0.048) and defect filling sub-score (p=0.025) in the medium- and high-dose cohorts compared to the low-dose cohort at 1year follow-up. Although we noted positive correlation between the clinical and radiological outcome (r=0.43), we did not find any significant different in the clinical outcome between the treatment groups. BMAC for OA knee resulted in significant improvement in the radiological scores compared to the baseline. Medium and high doses of BMAC result in significantly higher radiological scores compared to low-dose BMAC at 1year. However, the radiological improvement did not translate into functional improvement, irrespective of the dosage administered at 1year. Further research is necessary on the long-term outcomes to understand and optimize the dosing strategy based on clinico-radiological results.

Clinical and Radiological Outcomes at ≥10-Year Follow-up After Matrix-induced Autologous Chondrocyte Implantation in the Patellofemoral Joint

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. Purpose: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. Study Design: Case series; Level of evidence, 4. Methods: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). Results: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. Conclusion: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.

Glucosamine sulfate-loaded nanofiber reinforced carboxymethyl chitosan sponge for articular cartilage restoration

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core–shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.

Favourable clinical outcomes and low revision rate after M-ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years.

The purpose of this study was to evaluate long-term survival, patient-reported outcomes (PROs)and radiographic results of matrix-associated autologous chondrocyte implantation (M-ACI) in adolescents with immature cartilage and compare them to adult controls. A retrospective matched-pair analysis was performed comparing the PRO after M-ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated. A total of 54 patients were matched. At a mean of 96 months (65-144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow-up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long-term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long-term follow-ups. M-ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M-ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients. Level III.