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Cartilage[JOURNAL]

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Sex and Age Affect Progression to Total Knee Arthroplasty After Cartilage Surgery: A UK Biobank Cohort Study.

Kuiper NJ, Hulme CH, Snow M … +3 more , Frisher M, Wright KT, Kuiper JH

Cartilage · 2026 Jun · PMID 42370515 · Full text

ObjectiveEvaluate the association of sex and age at surgery with time to total knee arthroplasty (TKA) following knee cartilage surgery in UK Biobank (UKB) participants.DesignParticipants with a history of knee cartilage... ObjectiveEvaluate the association of sex and age at surgery with time to total knee arthroplasty (TKA) following knee cartilage surgery in UK Biobank (UKB) participants.DesignParticipants with a history of knee cartilage surgery were classified into four surgical subgroups: cartilage repair, debridement, microfracture, and unicompartmental knee arthroplasty. Time from index surgery to primary TKA in each group was analysed using the Kaplan-Meier method and the sexes compared using log-rank tests. Cox proportional hazards regression evaluated associations between age at surgery, sex, and surgery type with risk of progression to TKA.ResultsThe study included 1,967 males and 1,741 females. Log‑rank testing demonstrated significant sex‑based differences in time to TKA following debridement ( = 0.002) and microfracture ( = 0.003), with shorter TKA‑free survival observed in females. Cox regression showed that female sex was associated with a higher hazard of progression to TKA compared with male sex (hazard ratio [HR] = 1.19,  = 0.021). Increasing age at surgery was associated with increased risk (HR = 1.05 per year, < 0.0001).ConclusionFemale sex and older age at surgery were associated with a higher risk of progression to TKA following cartilage surgery. Sex‑specific differences in time to TKA were most evident after debridement and microfracture. These findings describe associations observed within the constraints of available UKB data.

In Vitro Cytotoxicity and Inflammatory Response of Local Anaesthetics and Corticosteroids in Canine Fibroblast-Like Synoviocytes.

Sousa C, Lima A, Belas A … +1 more , Campos S

Cartilage · 2026 Jun · PMID 42330243 · Full text

ObjectiveThis study investigated the dose-dependent cytotoxicity and immunomodulatory effects of intra-articular local anaesthetics (lidocaine, mepivacaine, levobupivacaine) and corticosteroids (dexamethasone, methylpred... ObjectiveThis study investigated the dose-dependent cytotoxicity and immunomodulatory effects of intra-articular local anaesthetics (lidocaine, mepivacaine, levobupivacaine) and corticosteroids (dexamethasone, methylprednisolone, methylprednisolone acetate) on canine fibroblast-like synoviocytes (FLS) . We evaluated cell viability and the expression of IL-6 and MMP-9.MethodsCanine FLS were exposed to increasing concentrations of intra-articular agents. Cell viability was determined via MTT assays. Immunomodulatory effects were assessed via ELISA for IL-6 and gelatin zymography for MMP-9 activity after TNF-α stimulation with IC concentrations.ResultsAll agents exhibited dose-dependent cytotoxicity. Dexamethasone was most cytotoxic (IC ≈ 3.4×10 mg/mL) but selectively inhibited TNF-α-induced MMP-9 activity without affecting IL-6 or inducing cytotoxicity at its IC. Mepivacaine significantly inhibited MMP-9 activity by 40% at 1 mg/mL and uniquely induced IL-6 in unstimulated cells. Lidocaine, methylprednisolone, and methylprednisolone acetate suppressed TNF-α-induced IL-6 expression.ConclusionsCommonly used intra-articular agents induce dose-dependent cytotoxic effects on canine FLS at clinically relevant concentrations. This study provides the first evidence of species-specific responses for mepivacaine, levobupivacaine, and dexamethasone in canine FLS, highlighting mediator-specific and concentration-dependent effects crucial for optimizing intra-articular therapies in veterinary and translational medicine.

Exosomal LINC01106 From PRP-Treated ADSCs Alleviates Chondrocyte Inflammatory Injury by Sponging miR-34a-5p to Upregulate SIRT1 Expression.

Zhang X, Liu W, Ren J … +2 more , Yu Y, Xu Z

Cartilage · 2026 Jun · PMID 42303604 · Full text

ObjectiveOsteoarthritis (OA) is characterized by progressive cartilage degeneration driven by inflammation-induced chondrocyte injury, while effective disease-modifying therapies are still lacking. Exosome-based cell-fre... ObjectiveOsteoarthritis (OA) is characterized by progressive cartilage degeneration driven by inflammation-induced chondrocyte injury, while effective disease-modifying therapies are still lacking. Exosome-based cell-free approaches are emerging as promising alternatives, but their key molecular mediators remain incompletely defined.DesignAdipose-derived stem cells (ADSCs) were pretreated with platelet-rich plasma (PRP) to enhance exosomal function. Isolated exosomes were characterized, and LINC01106 expression was modulated by overexpression or knockdown. Interleukin (IL)-1β-stimulated chondrocytes were used to assess apoptosis, inflammatory cytokine secretion, oxidative stress, and extracellular matrix degradation. The LINC01106/miR-34a-5p/SIRT1 axis was examined using luciferase reporter assays, quantitative real-time polymerase chain reaction (PCR), Western blotting, and immunofluorescence.ResultsPRP pretreatment markedly increased LINC01106 enrichment in ADSC-derived exosomes. LINC01106-rich exosomes significantly reduced chondrocyte apoptosis, suppressed tumor necrosis factor-α (TNF-α) and IL-6 secretion, alleviated oxidative stress, and attenuated matrix metalloproteinase (MMP)-mediated matrix degradation under IL-1β stimulation. Mechanistically, LINC01106 acted as a competing endogenous RNA that sequestered miR-34a-5p, thereby restoring SIRT1 expression. Rescue experiments demonstrated that miR-34a-5p overexpression or SIRT1 silencing abolished these protective effects. In addition, LINC01106-enriched exosomes inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway activation in a SIRT1-dependent manner.ConclusionPRP-stimulated ADSC-derived exosomes confer potent chondroprotective effects through the LINC01106/miR-34a-5p/SIRT1 pathway, highlighting a promising cell-free therapeutic strategy for OA.

Comparative Assessment of Cartilage Quality in Human Induced Chondrocytes (hiCHOs) and Primary Articular Chondrocytes (hACs) Following Fibronectin-Based Selection.

Mazzini G, Tuerlings M, van der Stap V … +4 more , Boone I, Mahdad R, Ramos YFM, Meulenbelt I

Cartilage · 2026 Jun · PMID 42257373 · Full text

BackgroundCell-based cartilage repair is limited by loss of chondrogenic potential during expansion. Fibronectin (FN)-based selection may enrich progenitor-like cells with better matrix-forming ability, but its long-ter... BackgroundCell-based cartilage repair is limited by loss of chondrogenic potential during expansion. Fibronectin (FN)-based selection may enrich progenitor-like cells with better matrix-forming ability, but its long-term effect on ECM production by hiPSC-derived chondroprogenitors (hiCPCs), their derived chondrocytes (hiCHOs), and primary articular chondrocytes (hACs) from lesioned or preserved areas remains unclear.MethodsWe here compared cartilage ECM formation by hiCPCs/hiCHO's and hACs, with or without FN selection, over extended passaging using 3D organoids. Histology and quantitative image analysis were performed to assess tissue quality across passages.ResultsChondrogenicity in hiCPCs transiently improved early-stage ECM production upon FN-based selection, but accelerated loss of chondrogenicity was seen in later passages. This was evidenced by diminished matrix staining and structural degradation from passage 4 onward. In contrast, hACs from both preserved and lesioned cartilage maintained stable matrix-forming ability across passages, independent of FN-based selection.ConclusionFN-based selection does not preserve long-term chondrogenicity in hiCHOs and may even impair it during extended culture. In contrast, primary cell sources, regardless of cartilage integrity, demonstrate greater and robust chondrogenic capacity without requiring progenitor enrichment. These findings highlight the intrinsic ability of hACs and question the utility of FN-based selection in cartilage tissue engineering.

Return to Work after Surgical Treatment of Osteochondral Defects of the Talus: A Systematic Review and Meta-Analysis.

Emanuel KS, van Beelen S, Dahmen J … +4 more , Hollander JJ, Stufkens SAS, Kuijer PPFM, Kerkhoffs GMMJ

Cartilage · 2026 Jun · PMID 42240238 · Full text

IntroductionReturn to work (RTW) is a key goal for patients treated for osteochondral lesions of the talus (OLT).AimThe primary objective of this review is to determine the RTW after surgical treatment of an OLT.MethodsA... IntroductionReturn to work (RTW) is a key goal for patients treated for osteochondral lesions of the talus (OLT).AimThe primary objective of this review is to determine the RTW after surgical treatment of an OLT.MethodsAfter preregistration, MEDLINE (PubMed), Embase and Cochrane Library were screened by two authors. RTW time and rate were extracted, and pooled if sufficient data was available. Two authors assessed methodological quality using the MINORS criteria.ResultsA total of 18 studies were included for which 399 patients reported RTW rate and/or time. The overall methodological quality of the studies was poor. The RTW time ranged from 2 to 11 weeks post-operatively and varied across surgical techniques. The overall RTW rate was 93%, with arthroscopic procedures averaging 96%, and open procedures averaging 91% RTW.ConclusionAfter surgical treatment of OLTs, 93% of patients returned to work. Time to RTW ranged from 2 to 11 weeks, although reporting was heterogeneous and methodological quality was generally low. Future studies should include RTW as a core outcome and report work-related restrictions more consistently.

Hyperbaric Oxygen Therapy Improves Subchondral Perfusion and Cartilage Integrity in Established Osteoarthritis: A Pharmacokinetic DCE-MRI and T2* Quantification Study.

Huang GS, Chiang SW, Chen CC … +7 more , Peng YJ, Hsu YJ, Huang KL, Chou YC, Lin MH, Liu YC, Wang CY

Cartilage · 2026 Jun · PMID 42233693 · Full text

ObjectiveThis study investigated whether hyperbaric oxygen (HBO) therapy, initiated after disease establishment, exerts disease-modifying effects in a rat model of anterior cruciate ligament transection (ACLT)-induced po... ObjectiveThis study investigated whether hyperbaric oxygen (HBO) therapy, initiated after disease establishment, exerts disease-modifying effects in a rat model of anterior cruciate ligament transection (ACLT)-induced post-traumatic osteoarthritis (PTOA).DesignThirty-six Sprague-Dawley rats underwent ACLT surgery. HBO therapy commenced at Week 11 (established OA phase) and continued for 6 weeks. Outcomes were assessed using Von Frey testing, multimodal 7T MRI (T2* quantification and pharmacokinetic DCE-MRI), and histopathology.ResultsBy Week 10, ACLT induced significant mechanical allodynia, T2* prolongation, and SCB perfusion abnormalities ( increase; , decrease). Following HBO intervention, the ACLT+HBO group exhibited a marked recovery in mechanical withdrawal threshold and significantly lower T2* values compared to the ACLT-only group ( < 0.01). DCE-MRI demonstrated that HBO restored clearance kinetics (, ) and suppressed pathological blood volume (), effectively remediating subchondral venous congestion. Histologically, HBO reduced OARSI scores and suppressed α-SMA-positive vascular invasion across the tidemark. These findings suggest that HBO therapy may alleviate PTOA by suppressing catabolic activity and normalizing pathological subchondral angiogenesis.ConclusionsHBO therapy, initiated post-pathogenesis, effectively attenuates nociception and preserves cartilage integrity by restoring subchondral microcirculatory homeostasis. These findings establish HBO as a potent, non-invasive disease-modifying strategy for PTOA.

Proteomics Analysis Reveals Serum Biomarkers Reflecting Joint Pain and Physical Limitations in Knee Osteoarthritis Before and After Joint Replacement Surgery.

Mustonen AM, Tampio J, Huttunen KM … +9 more , Julkunen P, Säisänen L, Karttunen L, Reijonen J, Esrafilian A, Kuningas T, Kumar A, Kröger H, Nieminen P

Cartilage · 2026 May · PMID 42217239 · Full text

ObjectiveOsteoarthritis (OA) is an age-related musculoskeletal disorder lacking effective disease-modifying therapies and early diagnostic biomarkers. This study aimed to identify serum proteins that could indicate the o... ObjectiveOsteoarthritis (OA) is an age-related musculoskeletal disorder lacking effective disease-modifying therapies and early diagnostic biomarkers. This study aimed to identify serum proteins that could indicate the occurrence of knee OA (KOA) and correlate with patients' pain and functional impairment.Design/MethodsFasting serum samples were collected from controls (n = 8) and patients with end-stage KOA at baseline (n = 8) and 12 months after total knee arthroplasty (n = 8). Proteomics analysis was conducted with liquid chromatography-mass spectrometry, followed by univariate and multivariate statistics and pathway analyses by MetaboAnalyst and STRING. Partial correlations were calculated with R, adjusted for sex, age, and body mass index, using a linear regression model.Results151 proteins were upregulated and 5 proteins downregulated in baseline KOA compared to control. These proteins were linked to the complement system, immune response, coagulation, inflammatory response, calcium homeostasis, and extracellular matrix remodeling. Of these, complement factor I showed strong biomarker potential. Several proteins emerged as statistically significant predictors of cartilage loss, pain sensitivity, physical function, and corticospinal excitability. Systemic alterations persisted 12 months after surgery.ConclusionSerum proteins may serve as biomarkers of KOA, reflecting disease-related immune, inflammatory, and tissue-remodeling processes that persist after joint replacement.

Distinct Responses of Estrogen Receptor α and β in Chondrocytes Under Excessive Mechanical Stress.

Takesue S, Hirose N, Yanoshita M … +6 more , Nishiyama S, Tsuboi E, Kubo N, Kita D, Asakawa Y, Tanimoto K

Cartilage · 2026 May · PMID 42171354 · Full text

IntroductionOsteoarthritis (OA) is more common in women, suggesting a link to estrogen. Estrogen supports cartilage homeostasis and metabolism via two receptors: ERα and ERβ. Mechanical stress is the primary cause of OA... IntroductionOsteoarthritis (OA) is more common in women, suggesting a link to estrogen. Estrogen supports cartilage homeostasis and metabolism via two receptors: ERα and ERβ. Mechanical stress is the primary cause of OA and affects cellular functions, including receptor activity. The link between excessive mechanical stress and ERs in cartilage is poorly understood. This study examined ER expression changes in chondrocytes under mechanical stress and the role of estrogen in cartilage degradation and ER regulation.MethodsATDC5 chondrocytes were treated with 17β-estradiol (E2; 1.0 × 10⁻⁷M) and subjected to cyclic tensile strain using the Flexcell Tension Plus FX-2000. Total RNA and proteins were extracted, and IL-1β and MMP-13 expression were analyzed using RT-PCR and western blotting. RT-PCR was used to examine the expression of ERα and ERβ.ResultsThe CTS group had significantly downregulated ERα expression at all time points and upregulated ERβ expression after 3 and 6 hours compared with controls. In the E2+CTS group, IL-1β and MMP-13 expression were suppressed after 3 and 6 hours, coinciding with significant upregulation of ERβ compared with the CTS group.ConclusionsEstrogen exerts a chondroprotective effect under excessive mechanical stress, suggesting that ERβ mediates this effect.

Contralateral Knee Alignment Parameters Have Limited Influence on Coronal Alignment Progression Compared With Ipsilateral Parameters in Patients With Knee Osteoarthritis.

Kang KS, Choi BS, Han HS … +3 more , Chang CB, Chung K, Ro DH

Cartilage · 2026 May · PMID 42168800 · Full text

ObjectiveTo compare alignment parameters in bilateral lower extremities and evaluate the effect of contralateral limb on hip-knee-ankle angle (HKAA) longitudinally.MethodsNative bilateral lower extremities of 3,045 Korea... ObjectiveTo compare alignment parameters in bilateral lower extremities and evaluate the effect of contralateral limb on hip-knee-ankle angle (HKAA) longitudinally.MethodsNative bilateral lower extremities of 3,045 Korean patients with long-leg radiographs were followed for progression of knee osteoarthritis. Concordance rates of Functional Knee Phenotypes (FKPs) and Coronal Plane Alignment of the Knee (CPAK), the proportion of patients with identical bilateral subtypes, were assessed. Varus, neutral, and valgus alignments were defined as baseline HKAA ≤177°, 177°< HKAA <183°, and HKAA ≥183°, respectively. Multivariable linear regressions for follow-up HKAA were conducted.ResultsConcordance rates for FKPs and CPAK were 41.6% (95% confidence interval: 39.9-43.4%) and 53.5% (51.7-55.2%), respectively, at baseline and 35.5% (33.8-37.2%) and 55.4% (53.7-57.2%) at a mean 4.0-year follow-up. Contralateral parameters, Kellgren-Lawrence grade ( = 0.005) in bilateral varus group, medial proximal tibial angle (MPTA) ( = 0.046) in ipsilateral varus-contralateral neutral group, MPTA, and mechanical lateral distal femoral angle in bilateral neutral ( < 0.001; = 0.012, respectively) and valgus ( = 0.003; = 0.004) groups, were associated with follow-up HKAA. However, their standardized β values were smaller than ipsilateral values.ConclusionConcordance rates of FKPs and CPAK between bilateral limbs were 41.6% and 53.5% at baseline, respectively. Contralateral parameters have limited influence on coronal alignment progression compared with ipsilateral parameters.

Subchondral Knee Injections: A Comprehensive Systematic Review of Current Clinical Outcomes, Safety, and Arthroplasty Delay.

Abu Salem Y, Franceschi C, Conte P … +4 more , Anzillotti G, D'Arrigo D, Di Matteo B, Kon E

Cartilage · 2026 May · PMID 42142000 · Full text

IntroductionOsteoarthritis is considered a whole-joint disease involving subchondral bone. Intraosseous therapies such as calcium phosphate (CaP), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs) offer joint... IntroductionOsteoarthritis is considered a whole-joint disease involving subchondral bone. Intraosseous therapies such as calcium phosphate (CaP), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs) offer joint-preserving options for knee osteoarthritis (OA).PurposeTo critically appraise and update the clinical evidence on intraosseous injections for knee osteoarthritis, focusing on safety, functional outcomes, need for retreatment, and conversion rates to total knee arthroplasty (TKA).MethodsA systematic review of PubMed, Embase, and Cochrane was conducted following PRISMA guidelines and PROSPERO registration (CRD420251104989). Clinical studies reporting outcomes of intraosseous injections with CaP, PRP, or MSCs for knee osteoarthritis with ≥5 patients and ≥6 months of follow-up were included. Methodological quality was assessed using the modified Coleman Methodology Score and Cochrane Risk of Bias 2.0 tool.ResultsTwenty-four studies involving 1,109 patients (mean age, 55 years; mean follow-up, 38 months) met inclusion criteria: 10 on CaP, 6 on PRP, and 8 on MSCs. Five were randomized controlled trials (RCTs). Most studies reported significant improvements in pain and function. CaP injection outcomes were variable, with TKA conversion rates ranging from 1.3% to 45%. PRP and MSCs studies showed favorable safety profiles and lower conversion rates. Long-term MSCs data indicated sustained relief and delayed TKA over up to 15 years. However, overall study quality was modest, with only one RCT rated as low risk of bias.ConclusionIntraosseous injections may improve symptoms and delay arthroplasty in selected patients with knee OA, with MSCs showing the most favorable long-term results. PRP appears to be a safe option whereas CaP outcomes are more variable. Standardized protocols and high-quality RCTs with long-term follow-up are needed to optimize patient selection and treatment efficacy.

Synovial Fluid Proteomic Biomarkers in Knee Osteoarthritis: A Systematic Review and Gene Ontology Analysis.

Parrotta EI, Benedetto GL, Cuda G … +6 more , Covello R, Longo UG, Carnevale A, Galasso O, Gasparini G, Mercurio M

Cartilage · 2026 May · PMID 42129958 · Full text

BackgroundOsteoarthritis (OA) of the knee is a degenerative disorder characterized by cartilage degradation, synovial inflammation, and structural remodeling. Synovial fluid (SF) biomarkers may improve diagnosis, staging... BackgroundOsteoarthritis (OA) of the knee is a degenerative disorder characterized by cartilage degradation, synovial inflammation, and structural remodeling. Synovial fluid (SF) biomarkers may improve diagnosis, staging, and patient stratification.MethodsFollowing PRISMA guidelines, a systematic search of PubMed and Scopus (2015-2025) was conducted. Human studies analyzing SF with proteomic techniques (LC-MS/MS, SWATH-MS, ELISA) were included. Extracted data were classified by OA stage, sample type, proteomic platform, and identified biomarkers. Functional enrichment was performed with ShinyGO, and protein-protein interaction (PPI) analysis with STRING (v12.0).ResultsSeven studies met the inclusion criteria. Reported biomarkers included Cathepsin G (CTSG), angiotensinogen (AGT), periostin (POSTN), haptoglobin (HP), complement components, and matrix-related proteins such as ADAMTS4 and LYVE-1, which are involved in extracellular matrix remodeling, inflammation, and joint tissue homeostasis. Functional annotation revealed enrichment in glycosaminoglycan binding, complement cascades, and redox pathways. PPI analysis identified central nodes including COL1A1, ACAN, COMP, and POSTN, together with matrix-degrading enzymes such as MMP1, MMP3, and MMP13, highlighting tightly connected extracellular matrix remodeling processes in OA.ConclusionThis review highlights reproducible SF biomarkers with diagnostic and prognostic potential in knee OA. Integrated proteomic and network analysis reinforces the multifactorial nature of OA and suggests key molecular targets. Translationally, a consistent biomarker signature could support early detection, more precise staging, and personalized management, enabling biomarker-guided diagnostics, targeted therapies, and the integration of precision medicine into OA care.

Synovial Biomarker Modulation and Clinical Response to Umbilical Cord-Derived MSC Treatment in Knee Osteoarthritis: A Case Series Study.

Švajger U, Kolar M, Pompe B … +2 more , Kobold A, Drobnič M

Cartilage · 2026 Apr · PMID 42060495 · Full text

ObjectiveUmbilical cord-derived mesenchymal stromal cells (UC-MSCs) are a promising treatment for knee osteoarthritis (KOA). This study aimed to (1) characterize early synovial fluid biomarker changes after intra-articul... ObjectiveUmbilical cord-derived mesenchymal stromal cells (UC-MSCs) are a promising treatment for knee osteoarthritis (KOA). This study aimed to (1) characterize early synovial fluid biomarker changes after intra-articular UC-MSCs therapy in advanced KOA and (2) explore their relationship with short-term clinical outcomes.MethodsIn this prospective, single-arm case series, 15 patients with advanced KOA (Kellgren-Lawrence III-IV) scheduled for total knee arthroplasty received a single intra-articular injection of 20 × 10 allogeneic UC-MSCs. Synovial fluid was aspirated at baseline and approximately 6 weeks post-injection. A panel of 29 soluble biomarkers related to inflammation, matrix remodeling, immune signaling, angiogenesis, and metabolism was quantified using multiplex immunoassays. Clinical status was evaluated with Patient-Reported Outcome Measures (PROMs) before and at a mean of 48 ± 18 days after the injection. Paired differences were analyzed using the Wilcoxon signed-rank tests.ResultsSignificant post-treatment differences were observed in biomarkers associated with extracellular matrix turnover (Matrix Metalloproteinase [MMP]-1, MMP-3, MMP-7, Cartilage Oligomeric Matrix Protein [COMP]), vascular remodeling (Vascular Endothelial Growth Factor [VEGF], Vascular Cell Adhesion Molecule [VCAM]-1), immune modulation (interleukin [IL]-8), and metabolic or structural regulation (Leptin, dickkopf [Dkk]-1). Most PROMs demonstrated significant improvements. These findings describe molecular changes in synovial fluid observed after intra-articular UC-MSC administration.ConclusionsIn this prospective single-arm cohort, intra-articular UC-MSC administration was feasible and well tolerated, and we observed pre-post changes in synovial fluid biomarkers and patient-reported outcomes. These findings do not establish causality and warrant confirmation in controlled studies. The study was registered at Clinicaltrials.gov: Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis, NCT06078059, https://clinicaltrials.gov/study/NCT06078059?intr=NCT06078059.

Automated Objective Scoring of Osteoarthritis Severity in Mouse Medial Tibial Cartilage Using Deep Learning.

Park KH, Kim YG, Lee G … +7 more , Kim SJ, Won Y, Huh YH, Kim TJ, Chun JS, Song HJ, Ryu JH

Cartilage · 2026 Apr · PMID 42028840 · Full text

ObjectiveThis study developed and optimized a deep learning model to automate OARSI-based histologic scoring of mouse medial tibial cartilage.DesignSafranin-O-stained cartilage images were obtained from mice with OA indu... ObjectiveThis study developed and optimized a deep learning model to automate OARSI-based histologic scoring of mouse medial tibial cartilage.DesignSafranin-O-stained cartilage images were obtained from mice with OA induced by medial meniscus instability. A total of 2,788 images from 1,000 knees of 520 mice were included for model development and evaluation. Each data set was evaluated using deep learning models with multiple selection criteria for the reference standard. For preprocessing, horizontal cartilage alignment was learned using a VGG16-based regression model, and the tibial cartilage region was detected using YOLO-v7. These learned weights were applied to generate a rotation- and crop-adjusted cartilage data set, which was used to evaluate three CNNs.ResultsInitial classification of 544 mice cartilage images showed low accuracy, leading to an expansion of the data set to 2,788 images. An algorithm was applied to align the images horizontally and crop only the joint region, thereby reducing misclassification of noncartilaginous regions. This approach significantly improved the accuracy of cartilage degradation scoring. Among the deep learning models evaluated, VGG16 showed the best performance, achieving an MAE of 0.33. The model also recorded a precision of 0.680 (95% CI: 0.668-0.693), recall of 0.645 (95% CI: 0.627-0.664), F1-score of 0.653 (95% CI: 0.636-0.671), and accuracy of 0.648 (95% CI: 0.631-0.665).ConclusionIn this study, the VGG16 model showed high concordance with expert assessments, suggesting the feasibility of automating OA grading from histological images in large-scale animal studies.

The Effect of Curcumin Treatment on Healing in a Rat Distal Femoral Osteochondral Defect Model.

Balcı EC, Alagöz E, Acar A … +5 more , Uslu M, Biçer O, Öztürk A, Başer E, Yaprak Bayrak B

Cartilage · 2026 Apr · PMID 42017929 · Full text

BackgroundArticular cartilage injuries often heal with fibrocartilage rather than native hyaline cartilage, resulting in inferior biomechanical properties and increased osteoarthritis risk. Curcumin has anti-inflammatory... BackgroundArticular cartilage injuries often heal with fibrocartilage rather than native hyaline cartilage, resulting in inferior biomechanical properties and increased osteoarthritis risk. Curcumin has anti-inflammatory and antioxidant properties that may support cartilage repair; however, clinical use is limited by poor bioavailability. Micellar formulations enhance systemic absorption.PurposeTo evaluate the effects of orally administered micellar curcumin on structural and molecular markers of osteochondral repair in a rat distal femoral defect model.MethodsThirty-two female Wistar rats were randomly allocated to 4 groups ( = 8 per group). Standardized 2-mm osteochondral defects were created in the distal femur. Animals received 250 mg/kg/day micellar curcumin or distilled water for 30 or 90 days. Macroscopic repair was assessed using the International Cartilage Repair Society (ICRS) scoring system. Histological evaluation followed ICRS guidelines and was performed in a blinded manner by 2 independent observers (intraclass correlation coefficient ICC = 0.89). Immunohistochemical analyses included SRY-box transcription factor 9 (SOX9), collagen type I (COL I), collagen type II (COL II), aggrecan, and matrix metalloproteinase-13 (MMP-13).ResultsCurcumin-treated groups demonstrated significantly higher macroscopic and histological scores than controls, particularly at 90 days. Increased expression of hyaline cartilage markers (SOX9, collagen II, aggrecan) and reduced collagen I expression were observed in treated groups. MMP-13 expression did not differ significantly between groups.ConclusionOral micellar curcumin enhanced structural and molecular parameters of osteochondral repair in this preclinical model. Further translational and clinical studies are required before therapeutic application.

The Use of Intra-Articular Hydrogel in Knee Osteoarthritis: A Systematic Review.

Tan AKS, Vengkat Samynathan C V, Dh MS … +5 more , Wei Yung A, Koh DTS, Soong J, Lee KH, Bin Abd Razak HR

Cartilage · 2026 Apr · PMID 42015482 · Full text

BackgroundKnee osteoarthritis (KOA) is a prevalent cause of disability. Current intra-articular injections (hyaluronic acid [HA] and corticosteroids) fall short in maintaining long-term effects and repeated usage may res... BackgroundKnee osteoarthritis (KOA) is a prevalent cause of disability. Current intra-articular injections (hyaluronic acid [HA] and corticosteroids) fall short in maintaining long-term effects and repeated usage may result in deleterious effects on the knee. The development of hydrogels offers a potentially safe and longer-lasting alternative.PurposeTo assess current literature and analyse the clinical outcomes of intra-articular hydrogel in patients with KOA.MethodsA systematic search on 4 databases was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta‑Analyses. Quantitative findings were complemented by narrative synthesis. Study quality was assessed using the Cochrane Risk of Bias (RoB) 2.0 tool and Methodological Index for Non-Randomized Studies guidelines.ResultsTwelve studies comprising 1,413 patients were included. Most reported improvements in clinical outcomes above the minimal clinically important difference. Average follow-up was 11 months. Quality assessment revealed high risk of bias for randomized controlled trials (RCTs) ( = 4) and low to moderate risk of bias non-randomized studies ( = 8).ConclusionIntra-articular hydrogel injections for KOA represent an area of ongoing investigation. Current literature is heterogeneous and limited by methodological shortcomings. Adequately powered RCTs with standardized outcome reporting are needed to clarify their role in routine clinical practice.Level of evidence:Level II.

Serial Changes in Graft Diameter Following Anterior Cruciate Ligament Reconstruction Using Allograft.

You JS, Lee SS, Lee DH

Cartilage · 2026 Apr · PMID 42011883 · Full text

BackgroundTo evaluate the serial changes in graft diameter during the 2 years following anterior cruciate ligament (ACL) reconstruction using serial magnetic resonance imaging (MRI).MethodsThis study involved 38 patients... BackgroundTo evaluate the serial changes in graft diameter during the 2 years following anterior cruciate ligament (ACL) reconstruction using serial magnetic resonance imaging (MRI).MethodsThis study involved 38 patients (38 knees) who underwent arthroscopic ACL reconstruction and had MRI immediately after surgery, at 1 year, and at 2 years. Graft diameter was measured at the distal, middle, and proximal levels of the intra-articular length, selecting the sagittal MRI slice that optimally showed the graft at each level. Correlation analysis was performed to identify the relationship between the difference of each graft diameter and demographic data and postoperative assessment results.Results analysis over time showed substantial thickening from the immediate postoperative to the 1-year scan (distal, +3.098 mm; middle, +3.284 mm; proximal, +3.074 mm; all < 0.001), a modest but significant reduction from 1 to 2 years (distal, -0.749 mm; middle, -0.699 mm; proximal, -0.574 mm; all < 0.001), and persistent enlargement at 2 years compared with those at baseline (distal, +2.348 mm; middle, +2.586 mm; proximal, +2.499 mm; all < 0.001). Regarding the correlation analyses, the graft diameter measurements at the proximal, middle, and distal sites across the 3 different time points were not significantly correlated with the postoperative results.ConclusionThe graft diameter demonstrated a unimodal peak at 1 year postoperatively, followed by a gradual decrease until 2 years; however, it remained thicker at 2 years than immediately after surgery. These changes were not correlated with postoperative patients' reported outcomes and stability.

Bone Marrow Aspirate Concentrate on Hyaluronic Acid Scaffold Combined With Intraarticular Platelet-Rich Plasma for Full-Thickness Knee Cartilage Lesions: Clinical and Biological Outcomes in 165 Patients.

Lind M, Nielsen TG, Christensen BB … +1 more , Sørensen OG

Cartilage · 2026 Mar · PMID 41824355 · Full text

ObjectiveThis study aimed to evaluate the clinical and biological outcomes of a one-step regenerative treatment using bone marrow aspirate concentrate (BMAC) on a hyaluronic acid scaffold combined with intraarticular pla... ObjectiveThis study aimed to evaluate the clinical and biological outcomes of a one-step regenerative treatment using bone marrow aspirate concentrate (BMAC) on a hyaluronic acid scaffold combined with intraarticular platelet-rich plasma (PRP) for treatment of full-thickness cartilage lesions in the knee.Design/MethodsA total of 165 patients (mean age 26.4 years) with full thickness cartilage defects were included in the study. In a single-step procedure, bone marrow was aspirated from the iliac crest and centrifuged to obtain BMAC concentrate. PRP was prepared from whole blood. The BMAC concentrate was seeded onto a hyaluronic acid scaffold and implanted into the debrided cartilage defect and PRP was added intraarticularly. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a semiquantitative grading scale (Excellent, Good, Fair) at one-year follow-up. All patients underwent MRI preoperatively and at one year follow-up, with cartilage repair evaluated using the MOCART-2.0 scoring system.ResultsSignificant improvements were observed in all KOOS subscales at one year. Semiquantitative grading revealed excellent outcomes in 50% of patients, good in 28%, and poor in 22%. MRI analysis showed an average MOCART-2.0 score of 71, with 36% of patients achieving excellent cartilage repair (MOCART 2.0 >80).ConclusionThe combined use of BMAC on a hyaluronic acid scaffold and intraarticular PRP resulted in improved subjective clinical outcomes and demonstrated favourable biological cartilage healing responses at one year postoperatively. This one-step cartilage repair technique appears to be a clinically valid option for treatment of full-thickness cartilage lesions in the knee.

Protective Effects of Spirulina Supplementation on Chondrocytes Under Moderate Acute Dynamic Compression.

Golestani N, Rafieian S, Waldman SD … +2 more , Zila L, Pearson W

Cartilage · 2026 Mar · PMID 41802934 · Full text

ObjectiveTo determine the influence of Spirulina supplementation on the response of bovine chondrocytes to mechanical compression with respect to extracellular matrix dynamics (proteoglycan and collagen) and inflammation... ObjectiveTo determine the influence of Spirulina supplementation on the response of bovine chondrocytes to mechanical compression with respect to extracellular matrix dynamics (proteoglycan and collagen) and inflammation [nitric oxide (NO)].MethodsBovine chondrocytes were embedded in agarose constructs and cultured for 14 days in basal media or media supplemented with Spirulina (30 or 90 µg/mL). Constructs were exposed to 10% dynamic compression. DNA content, NO levels, proteoglycan content and release, and collagen synthesis were measured to assess extracellular matrix (ECM) responses.ResultsDNA content did not differ among groups. Spirulina supplementation increased NO levels in constructs and media, with the highest effect observed at 90 µg/mL. Proteoglycan content decreased in Spirulina-treated constructs and declined further after compression, while proteoglycan release increased across all groups. Collagen synthesis and content were elevated by Spirulina, particularly at 90 µg/mL, and further increased following dynamic compression.ConclusionsSpirulina supplementation, particularly at higher concentrations, enhances ECM turnover and increases NO production in chondrocytes under mechanical loading, indicating potential modulation of matrix dynamics that may be beneficial. However, these results are derived from an model and may not fully represent physiological conditions.

What are the Chances of MACI Approval in the United States? A Deep Dive into the Insurance Authorization Data.

Cavendish PA, Milliron EM, Peterson CJ … +4 more , Sherman SL, Jones DG, Strauss EJ, Flanigan DC

Cartilage · 2026 Mar · PMID 41802932 · Full text

ObjectiveTo describe recent trends in US MACI (autologous cultured chondrocytes on porcine collagen membrane) insurance approval rates, including the impact of defect location and the number of defects.DesignMyCartilageC... ObjectiveTo describe recent trends in US MACI (autologous cultured chondrocytes on porcine collagen membrane) insurance approval rates, including the impact of defect location and the number of defects.DesignMyCartilageCare case management team provides insurance prior authorization support for potential MACI patients through Vericel Corporation, the manufacturer of MACI. Data from insurance claims from 2021 to 2022 were assessed for non-military patients aged 17 to 55 years. Insurance outcomes were summarized, with approval defined as pre-authorization or pre-determination for the MACI procedure being secured prior to the initiation of treatment or cases where an estimate of coverage was provided prior to the initiation of treatment, respectively.ResultsA total of 5,158 cases were identified. In total, 87.7% of MACI cases were approved on initial submission, 9.4% were approved on appeal, 2.4% were not appealed, and 0.5% were denied after appeal. A total of 51.4% of cases included a patella defect, with similar rates of approval: 87.4% approved on initial submission, 9.6% approved on appeal, 2.5% not appealed, 0.5% denied after appeal. 29.9% contained more than one defect which were approved at similar rates: 87.1% approved on initial submission, 10.2% approved on appeal, 2.3% not appealed, and 0.5% denied after appeal.ConclusionsMACI claims in the knee cartilage repair treatment algorithm are broadly supported by US third-party payers, with nearly 88% of all knee cartilage patients obtaining insurance approval on their initial submission and 97% of patients obtaining approval in total following appeal of initially denied claims. This is consistent across all groups including patella, non-patella, single, and multiple-defect cases.

Critical Size Defect in Adult Articular Cartilage: A Preclinical Study.

Hunziker EB, Shintani N, Keel MJB

Cartilage · 2026 Feb · PMID 41747715 · Full text

ObjectiveLesions of adult articular cartilage occur due to trauma or disease, such as osteoarthritis. If they do not penetrate the subchondral bone, they are called partial-thickness defects (PTDs), which are believed no... ObjectiveLesions of adult articular cartilage occur due to trauma or disease, such as osteoarthritis. If they do not penetrate the subchondral bone, they are called partial-thickness defects (PTDs), which are believed not to heal. However, some reports indicate that minor PTDs can be repaired. We hypothesize that a critical-size PTD exists below which spontaneous healing occurs.Design/MethodsIn an adult pig model, we created PTDs of minimal width (a scalpel cut) and systematically increased their width up to 0.5 mm. Defect analyses were conducted at 1 and 3 months post-surgery using light microscopy and histomorphometry.ResultsNone of the defects healed by repair cartilage; therefore, all PTDs are of a critical size. Surprisingly, a critical defect-size range was identified where significant mesenchymal tissue (MT) formation occurs, specifically in defects measuring 50-100 μm in width. The presence of this MT was limited to a 1-month time window. Furthermore, physiological joint loading during the postsurgical phase was associated with substantial structural tissue deformation, often leading to an overlapping of the side walls of the smallest defects. This results in a pseudo-covering of the defect void, which may thus be invisible when observed from above.ConclusionsThe main novel finding of this study is that there is no critical width below which PTDs undergo repair.
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