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The purpose was to examine (1) the effect of measurement position and sex on femoral cartilage outcomes, and (2) the association between gait biomechanics and cartilage outcomes. Fifty individuals participated (25 males and 25 females; age = 20.62 [1.80] y). Ultrasound measured femoral cartilage thickness and echo-intensity at 90°, 115°, and 140° of knee flexion. Gait outcomes included the external knee adduction and knee flexion moments. Cartilage outcomes were compared using 2 (sex) × 3 (position) repeated-measures analysis of variance. Gait and cartilage associations were assessed using stepwise regression. Medial cartilage was thicker when measured at 90° compared with 115° (P =.02) and 140° (P <.01), and 115° compared with 140°, (P <.01) in males but not in females. Cartilage was thicker at 90° compared with 140° across both sexes within all regions (P <.01). Males had thicker cartilage than females in all positions (P <.01). Echo-intensity was lower at 90° than 115° (P <.01) and 140° (P =.01) in the central and lower at 90° than at 115° (P <.01) and 140° (P =.03) in lateral regions. No association was found between gait and cartilage outcomes. Ultrasound imaging position effects cartilage features more in males compared with females. Imaging position and sex influence cartilage outcomes and should be considered in study designs and clinical evaluation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Realignment osteotomy performed concomitantly with cartilage restoration typically requires early restricted weightbearing and can add significant morbidity, potentially leading to an increased risk of early perioperative complications. The purpose of this study was to compare the 30-day complication rates after isolated cartilage restoration (ICR) versus concomitant cartilage restoration and osteotomy (CRO) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. DESIGN: NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing ICR (autologous chondrocyte implantation, osteochondral autograft transfer, or osteochondral allograft transplantation) and CRO (with concomitant high tibial osteotomy, distal femoral osteotomy, and/or tibial tubercle osteotomy). Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and respiratory status. RESULTS: A total of 773 ICR and 97 CRO surgical procedures were identified. Mean patient ages were 35.9 years for the ICR group and 31.2 years for the CRO group. Operative time was significantly longer in the CRO group (170.8 min) compared with the ICR group (97.8 min). Multivariate analysis demonstrated no significant differences in rates of PE, VTE, and all-cause readmission between the ICR and CRO groups. No events of wound disruption, SSI and reoperation were found in the CRO group, while the ICR group was characterized by low rates of wound disruption, reoperation, and SSI (

Background: While measuring meniscal extrusion quantitatively is an early risk factor for knee osteoarthritis (KOA), the biomechanics involved in this process are not well understood. This study aimed to investigate the effects of varying degrees of medial and lateral meniscal extrusion and their material softening on knee osteoarthritis progression. Methods: Finite element analysis (FEA) was utilized to simulate varying degrees of meniscal extrusion (1–5 mm) in 72 knee joint models, representing progressive meniscal degeneration and material softening due to injury. Changes in von Mises stress of the cartilage and menisci and the load distribution on the tibial plateau's meniscus and cartilage were studied under balanced standing posture in both healthy and injured knees, and statistical analysis was performed using Spearman correlation. Results: Compared to healthy knees, peak stress in medial compartment tissues increased by over 40% with 4 mm of medial meniscus extrusion, and in lateral compartment tissues with 2 mm of lateral meniscus extrusion. Meniscus extrusion reduced the contact load between the meniscus and femoral cartilage but increased it between the tibial and femoral cartilages, with a maximum increase up to fivefold. Spearman correlation analysis indicated that meniscal extrusion significantly affected peak stress and contact loads in the respective knee compartment (p < 0.001), with a lesser impact on the opposite compartment. Notably, medial meniscal extrusion also significantly increased peak stress in the lateral tibial cartilage (p < 0.05). Conclusions: The quantitative analysis revealed that meniscal extrusion significantly affected the biomechanics of soft tissues within the same compartment, with limited impact on the opposite side. Specifically, Medial extrusion beyond 4 mm significantly affected the biomechanics of the medial compartment, while lateral extrusion over 2 mm had a similar impact on the lateral compartment. Meniscal softening, without altering joint contact characteristics, primarily affected the biomechanics of the meniscus itself, with minimal impact on other soft tissues. [ABSTRACT FROM AUTHOR]

Diclofenac etalhyaluronate (DF‐HA) sustained diclofenac release with the effects of hyaluronic acid (HA), offering long‐term analgesia in osteoarthritis. In this study, the effects of DF‐HA on pain improvement and osteoarthritis were evaluated in a rat knee monoiodoacetate‐induced osteoarthritis model compared to HA. Eight rats per group had been injected with monoiodoacetate (2.0 mg) or saline in the right knee for 4 weeks and were injected with either DF‐HA (1.25 mg/kg; 0.5 mg), HA (0.5 mg), vehicle which was a substrate without DF‐HA (50 μL), or saline and followed for 4 weeks. Mechanical plantar skin sensitivity was assessed weekly using the von Frey assay. Osteoarthritis changes were monitored with Larsen scores via CT imaging at every 2 weeks. The articular cartilage was analyzed using OARSI scores through H&E, Safranin‐O staining at 8 weeks. The percentage of Iba‐1 positive microglia in the spinal dorsal horn and of FG + CGRP‐labeled cells among FG‐positive cells in the dorsal root ganglion were evaluated by immunohistochemical staining. TNF‐α and IL‐6 mRNA expression levels in the knee synovium were evaluated by PCR. The DF‐HA showed significantly improved pain hypersensitivity compared with the HA at 6–8 weeks. The percentage of Iba‐1‐positive microglia was significantly lower than that in the vehicle and the percentage of FG + CGRP/FG was significantly lower than that in the HA. OARSI scores did not differ among treatment groups, Larsen scores indicated lower in the DF‐HA than in the vehicle. DF‐HA was as effective as HA in joint protection and significantly improved inflammatory pain compared to HA. [ABSTRACT FROM AUTHOR]

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose‐dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full‐length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose‐dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionThe aberrant H-type vessel formation was found to be intimately linked to subchondral bone remodeling during osteoarthritis (OA) development. Herein, we investigated the role and mechanism of osteoblast-secreted slit guidance ligand 3 (Slit3) in H-type vessel formation during OA progression.Slit3 protein levels in subchondral bone samples of OA patients were detected. The isolated osteoblasts were transfected with Slit3 overexpression or knockdown plasmids, and their conditioned medium was cultured with endothelial progenitor cells (EPCs). The migration, tube formation, VEGF, and H-type vessel marker protein CD31 and endomucin (EMCN) levels in EPCs were accessed. The interactions between Slit3 and roundabout (Robo) family members were validated by Co-IP assay. Besides, whether the Slit3/Robo signaling affects the transforming growth factor β1 (TGF-β1)/SMADs pathway was determined. Additionally, sh-Slit3 was injected into OA mice, followed by the detection of articular cartilage degradation, subchondral bone remodeling, and H-type vessel formation.Slit3 was upregulated in subchondral bone tissues of OA patients. Slit3 overexpression in osteoblasts intensified the migration and H-type vessel formation of EPCs, while Slit3 knockdown showed the opposite results. Slit3 overexpression enhanced Robo1 protein level. Robo1 knockdown abrogated Slit3-mediated migration and H-type vessel formation in EPCs. Slit3 activated the TGF-β1/SMADs pathway in EPCs, which might be associated with H-type vessel formation in EPCs. Additionally, Slit3 silencing restrained articular cartilage degradation, aberrant subchondral bone formation, and H-type vessel formation in OA mice.Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in the subchondral bone. [ABSTRACT FROM AUTHOR]

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect. Methods: PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein–protein interaction network analysis. Results: The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein–protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect. Conclusion: PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis (OA) is a prevalent clinical chronic degenerative condition characterized by the degeneration of articular cartilage. Currently, drug treatments for OA come with varying degrees of side effects, making the development of new therapeutic approaches for OA imperative. Mesenchymal stem cells (MSCs) are known to mitigate the progression of OA primarily through paracrine effects. The conditioned medium (CM) derived from MSCs encapsulates a variety of paracrine factors secreted by these cells. Methods: In this study, we investigated the effect of the CM of infrapatellar fat pad-derived MSCs (IPFSCs) on OA in vitro and in vivo, as well as and the potential underlying mechanisms. We established three experimental groups: the normal group, the OA group, and the CM intervention group. In vitro experiments, we used methods such as qPCR, Western blot, immunofluorescence, and flow cytometry to detect the impact of CM on OA chondrocytes. In vivo experiments, we evaluated the changes in the knee joints of OA rats after intra-articular injection of CM treatment. Results: The results showed that injection of CM into the knee joint inhibited OA development in a rat model induced by destabilization of the medial meniscus and anterior cruciate ligament transection. The CM increased the deposition of extracellular matrix-related components (type II collagen and Proteoglycan). The activation of PI3K/AKT/NF-κB signaling pathway was induced by IL-1β in chondrocytes, which was finally inhibited by CM-IPFSCs treatment. Conclusion: In summary, IPFSCs-CM may have therapeutic potential for OA. [ABSTRACT FROM AUTHOR]

Objectives Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis. Methods Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20 mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1β, and TNF-α were evaluated by ELISA. Results Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1β, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20 mg/kg. Conclusions Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allograft transplantation (OCAT) has become a standard-of-care treatment option for patients with large symptomatic articular defects. Recent advances in allograft science and OCAT protocols have been reported to result in consistently robust outcomes after OCAT in the knee. However, only short-term comparisons have been reported, and analyses are lacking for treatment failure risk factors that account for confounding variables. Hypothesis: Midterm functional graft survival rate would exceed 80% for all OCATs combined, with consideration of risk factors for lower survivorship including older patient age, higher body mass index (BMI), tibiofemoral bipolar OCAT, and nonadherence to prescribed postoperative rehabilitation protocols. Study Design: Case series; Level of evidence, 4. Methods: Patients with outcome data available at ≥5 years after primary OCAT using high chondrocyte–viability (HCV) osteochondral allografts were analyzed according to 2 clinically relevant definitions: (1) initial treatment failure, defined by revision or arthroplasty surgery performed for the primary OCAT at any time point during the study period; and (2) functional graft failure, defined by documented conversion to arthroplasty after primary or revision OCAT at any time point during the study period. Analyses were used to assess outcomes for each definition, separately for age group, sex, obesity status, tobacco use, type of OCAT surgery, osteotomy status, concurrent ligament surgery status, and adherence to postoperative protocols. Kaplan-Meier analyses were used to assess differences in survival rates, and Cox proportional hazards models were used to assess risk factors and multivariable relationships with survival. Patient-reported outcome measures for pain, function, mobility, and satisfaction were also analyzed. Results: Analysis included 137 primary knee OCATs performed in 134 patients with a mean follow-up of 66 months (59 female, 75 male; mean age, 37.8 years; mean BMI, 28.5). The midterm (5- to 8-year) functional graft survival rate for patients undergoing primary OCAT in the knee using HCV grafts was 82% for all cases combined, ranging from 69% for tibiofemoral bipolar HCV OCATs to 89% for patellofemoral bipolar, 94% for multisurface unipolar, and 97% for single-surface unipolar. Initial treatment failure rates (revision or arthroplasty after primary OCAT) and OCAT nonsurvival rates (arthroplasty after primary or revision OCAT) were greater for older patient age, concurrent ligament reconstruction, tibiofemoral bipolar OCAT, and nonadherence to the prescribed postoperative rehabilitation protocols. When adjusted for patients' age, BMI, and tobacco use status, different surgery types did not demonstrate an increased risk for failure, while concurrent ligament reconstruction and nonadherence did. Patients who experienced functional graft survival after primary OCAT reported significantly greater improvements in PROMIS Physical Function and Mobility (Patient-Reported Outcomes Measurement Information System), International Knee Documentation Committee questionnaire, and Single Assessment Numeric Evaluation scores such that they were significantly higher at final follow-up as compared with patients who required arthroplasty. Patient-reported improvements in pain, function, and mobility exceeded minimal clinically important differences for ≥5 years after primary OCAT. When asked if they were satisfied with primary OCAT surgery, 76.2% of patients were very satisfied or satisfied with their results, while 8.5% were neutral and 15.4% were unsatisfied or very unsatisfied. Conclusion: With use of HCV osteochondral allografts, midterm (5- to 8-year) functional graft survival rates for patients undergoing primary OCAT in the knee were notably higher than previously reported midterm rates for traditional OCATs. When adjusted for patient characteristics, risk factors for nonsurvival included concurrent ligament reconstruction for knee instability and nonadherence to the prescribed postoperative rehabilitation protocols. Patients who experienced functional graft survival for ≥5 years after primary OCAT reported statistically significant and clinically meaningful improvements in pain, function, and mobility. [ABSTRACT FROM AUTHOR]

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

Background: Both high body mass index (BMI) and anterior cruciate ligament reconstruction (ACLR) independently influence knee osteoarthritis risk. Preliminary evidence shows the combination of these risk factors leads to poorer recovery and altered biomechanical outcomes after ACLR, but few studies have directly evaluated early changes in cartilage health between normal-BMI and high-BMI groups in this population. Purpose: To evaluate ultrasound-based measures of cartilage strain and compositional changes (via echo-intensity [EI]) in response to an incline walking stress test between normal-BMI and high-BMI individuals with ACLR. A secondary evaluation was conducted of associations between habitual walking biomechanics (ie, ground-reaction forces, sagittal knee kinetics and kinematics) and cartilage strain and EI outcomes. Study Design: Controlled laboratory study. Methods: Gait biomechanics and femoral trochlear ultrasound analyses were evaluated in 64 participants with ACLR who had normal BMI (BMI < 27.0; n = 40) and high BMI (BMI ≥ 27.0; n = 24). Ultrasound images were collected bilaterally before and after an incline treadmill walk, and medial and lateral trochlear strain and EI changes pre-post exercise were used to compare BMI groups and limbs. Gait outcomes included ground-reaction forces, peak sagittal plane knee moments, angles, and excursions and were used to determine associations with cartilage outcomes in the entire cohort. Results: High-BMI individuals with ACLR exhibited greater medial trochlear cartilage strain in the ACLR limb compared with normal-BMI individuals (approximately 6%; P <.01). In those with high BMI, the ACLR limb exhibited greater medial trochlear strain relative to non-ACLR limbs (approximately 4%; P <.05), but between-limb differences were not observed in the normal-BMI group (P >.05). Medial trochlear EI changes were greater bilaterally in those with high BMI compared with normal-BMI ACLR counterparts (approximately 10%; P <.01). Last, individuals who walked with greater peak knee flexion angles exhibited less medial cartilage strain (Δ R 2 = 0.06; P =.025). Conclusion: The data suggested that high BMI affects cartilage functional properties after ACLR, whereas smaller knee flexion angles were associated with larger medial cartilage strain. Clinical Relevance: High-BMI individuals with ACLR may represent a subset of patients exhibiting earlier declines in cartilage functional integrity in response to loading, necessitating additional or more targeted interventions to mitigate disease development. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by the progressive deterioration of articular cartilage and concomitant alterations in subchondral bone architecture. However, the precise mechanisms underlying the initiation and progression of OA remains poorly understood. In the present study, we explored whether the calcification in the articular cartilage occurred in the early stage of mouse OA model, generated by the surgery destabilization of the medial meniscus (DMM), via the intra‐articular injection of alizarin complexone due to its anionic nature for binding calcium‐containing crystals. Although we did not observe the calcification in the articular cartilage of early stage of DMM mice, we unexpectedly identified alizarin complexone had the diffusion capacity for detecting the permeability from the articular cartilage to subchondral bone. Our data showed that the diffusion of alizarin complexone from the articular cartilage to calcified cartilage was greater in the early stage of DMM mice than that in sham controls. Additionally, we observed enhanced penetration of alizarin complexone through the periosteum in DMM mice compared to sham mice. In summary, we developed a novel imaging method that offers a valuable tool for further exploration of biochemical communication underlying OA development. Our findings provided new evidence that increased molecular interactions between the articular cartilage and subchondral bone is involved in the pathogenesis of OA progression. [ABSTRACT FROM AUTHOR]

Objective OA is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA. Methods We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry and Alcian blue staining were performed. In vitro , immunofluorescence, quantitative real-time PCR (RT-qPCR), ELISA and western blot assays were performed. Results serpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioural responses and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1β and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation. Conclusions serpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA. [ABSTRACT FROM AUTHOR]

In this study, polycaprolactone (PCL) scaffolds have been employed as structural framework scaffolds for patellofemoral cartilage tissue regeneration. The biomechanical and biological properties of different scaffolds were investigated by varying alginate concentrations and the number of scaffold layers. Patellofemoral cartilage defects result in knee pain and reduced mobility, and they are usually treated with conventional methods, often with limited success. Generally, tissue-engineered PCL-alginate scaffolds fabricated by bioprinting technology show promise for enhanced cartilage regeneration due to the biocompatibility and mechanical stability of PCL. In addition, alginate is known for its cell encapsulation capabilities and for promoting cell viability. Biological and morphological assessments, utilizing water contact angle, cell adhesion tests, MTT assays, and scanning electron microscopy (SEM), informed the selection of the optimized scaffold. Comparative analyses between the initial optimal scaffolds with the same chemical composition also included flexural and compression tests and fracture surface observations using SEM. The controlled integration of PCL and alginate offers a hybrid approach, that assembles the mechanical strength of PCL and the bioactive properties of alginate for tissue reconstruction potential. This study aims to identify the most effective scaffold composition for patellofemoral articular cartilage tissue engineering, emphasizing cell viability, structural morphology, and mechanical integrity. The results showed that the optimum biomechanical and biological properties of scaffolds were obtained with a 10% alginate concentration in the monolayer of PCL structure. The findings contribute to regenerative medicine by advancing the understanding of functional tissue constructs, bringing us closer to addressing articular cartilage defects and related clinical challenges. [ABSTRACT FROM AUTHOR]

Purpose: In symptomatic mid‐sized focal chondral defects, autologous matrix‐induced chondrogenesis (AMIC) and minced cartilage implantation (MCI) offer two versatile treatment options. This study aimed to conduct a matched‐patient analysis of patient‐reported outcome measures to compare these two surgical treatment methods for focal chondral defects. Methods: At the first centre, patients underwent a single‐stage procedure in which autologous cartilage was hand‐minced, implanted into the defect and fixed with fibrin glue. At the second centre, patients underwent AMIC, which was fixed in place with fibrin glue. All patients were seen 2–4 years postoperatively. Postoperative outcomes were assessed using the visual analogue scale for pain (VAS), the Lysholm score and the five domains of the knee osteoarthritis outcome score (KOOS). Patients from each surgical centre were matched by age, sex, defect size and defect localisation. Results: In total, 48 patients from two surgical centres (24 from each site) were matched for sex, age (MCI 30.3 ± 14.9 years vs. AMIC 30.8 ± 13.7 years) and defect size (MCI 2.49 ± 1.5 cm2 vs. AMIC 2.65 ± 1.1 cm2). Significantly better scores in the AMIC cohort were noted for VAS (p = 0.004), Lysholm (p = 0.043) and the KOOS subscales for pain (p = 0.016) and quality of life (p = 0.036). There was a significantly greater proportion of positive responders for Lysholm in the AMIC group (92%) compared with the MCI group (64%). Conclusions: The AMIC procedure delivers superior patient outcomes compared with hand‐minced autologous cartilage implantation. These are mid‐term outcomes, with follow‐up between 2 and 4 years. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and characterise articular cartilage degeneration in patients with osteonecrosis of the femoral head (ONFH) using T2 mapping magnetic resonance imaging. Methods: We reviewed 35 patients with ONFH (20 males and 15 females, mean age: 45.7 ± 12.9 years) without obvious cartilage abnormalities on plain magnetic resonance imaging (ONFH group) and 25 healthy volunteers (9 males and 16 females, mean age: 42.9 ± 5.8 years) (control group). All patients underwent T2 mapping magnetic resonance imaging after ONFH onset. The region of interest was defined as the weight-bearing portion of the articular cartilage in the femoral head and acetabulum in the coronal view. Results: The T2 values of the articular cartilage of the acetabulum and femoral head, including necrotic and normal regions, were significantly higher in the ONFH group than those in the control group. These T2 values of the acetabulum and femoral head in Stages 3A and 2 were significantly higher in the ONFH group than those in the control group. Conclusions: The articular cartilage of the acetabulum and femoral head can deteriorate after the onset of ONFH, which may affect the natural history of ONFH and ONFH treatment. Our findings suggest the need for early intervention in joint preservation surgery. [ABSTRACT FROM AUTHOR]

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no‐go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8‐weeks post‐surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC‐microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight‐bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself. [ABSTRACT FROM AUTHOR]

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post‐anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty‐five patients (54% female, 26.4 ± 11.8 days post‐injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury. [ABSTRACT FROM AUTHOR]

Intra‐articular corticosteroid injections, such as triamcinolone acetonide (TA), are commonly used by clinicians to manage joint synovial inflammation. However, due to conflicting evidence in literature, there is a fear among clinicians that the injections may be harmful to otherwise healthy cartilage in young patients. The purpose of this study was to evaluate the effects of TA on young, healthy chondrocytes. Articular cartilage samples were harvested from bovine knee joints (1–2 months old). In both healthy and inflammatory (interleukin‐1β) challenged cartilage, samples were treated with TA at doses ranging from 1 nM to 200 μM. Following a short‐ (2 days) or long‐term (10–14 days) treatment, chondrocyte viability, proliferation, and extracellular matrix (ECM) synthesis and degradation were evaluated with a click chemistry‐based technique. Chondrocyte viability, proliferation, and anabolic activity were all minimally affected by short‐term and long‐term TA treatment. After both acute and sustained inflammatory challenges, TA reduced the catabolic activities in cartilage, reducing nascent glycosaminoglycan loss and maintaining cartilage mechanical properties. Overall, at physiologically relevant doses, TA had minimal negative impact on chondrocytes when maintained within their native ECM. Clinical significance: The findings provide new insight for current clinical practices concerning the use of TA in intra‐articular injections, especially in young patients, and established a foundation for future investigations into the impact of corticosteroids on joint homeostasis. [ABSTRACT FROM AUTHOR]

Background: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. Objective: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). Methods: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin‐1β (rrIL‐1β) and SDC4 small interfering RNA (si‐SDC4). Anti‐SDC4 ectodomain‐specific antibodies or IgG were intra‐articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4‐cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col‐II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. Results: SDC4 expression was evidently increased in MIA‐model animals compared to control groups. rrIL‐1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col‐II. These effects were reversed by si‐SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col‐II and ACAN, and a decrease in SDC4, MMP13 and cleaved‐CASP3‐positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. Conclusions: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Early diagnosis of post‐traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high‐resolution imaging to investigate early‐stage deterioration in articular cartilage and the subchondral bone plate from a sub‐critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2‐ and 14‐week post‐impact surgery, cartilage‐bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (μCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post‐impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post‐impact, only minor, non‐significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2‐week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries. [ABSTRACT FROM AUTHOR]

Hydrogel, as one of potential soft materials for articular cartilage, has encountered pressing obstacles, such as insufficient mechanical properties, poor lubrication, and easy to wear. To tackle these, we propose a strong yet slippery polyvinyl alcohol/chitosan (PVA/CS) hydrogel with dual-physically crosslinked networks by harnessing freeze-thawing, salting-out, annealing, and rehydration. High mechanical properties of PVA/CS hydrogel can be readily regulated by adjusting proportion of PVA/CS and annealing temperature. The optimized hydrogel exhibits high mechanical properties with tensile strength of ∼ 19 MPa at strain of 550%, compression strength of ∼ 11 MPa at small strain of 39%, and outstanding toughness and antifatigue owing to the robust physical interactions, including hydrogen bonds, crystallization, and ionic coordination. Moreover, the equilibrium hydrogel shows low friction coefficient of ∼ 0.05 against Al2O3 ball under the condition of 30 N, 1 Hz, with water as the tribological medium, which is close to the lubrication performance of native cartilage. And meanwhile, the proposed cartilage-like slippery hydrogel displays stable long-term lubrication performance for 1 × 105 reciprocating cycles without destructive wear and structure damage. It is therefore believed that the biocompatible cartilage-like slippery hydrogel opens innovative scenarios for developing cartilage-mimicking water-lubricated coating and biomedical implants with satisfactory load-bearing and lubrication performance. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential for accelerating continuous‐wave (CW) T1ρ dispersion measurement with compressed sensing approach via studying the effect that the data reduction has on the ability to detect differences between intact and degenerated articular cartilage with different spin‐lock amplitudes and to assess quantitative bias due to acceleration. Methods: Osteochondral plugs (n = 27, 4 mm diameter) from femur (n = 14) and tibia (n = 13) regions from human cadaver knee joints were obtained from commercial biobank (Science Care, USA) under Ethical permission 134/2015. MRI of specimens was performed at 9.4T with magnetization prepared radial balanced SSFP (bSSFP) readout sequence, and the CWT1ρ relaxation time maps were computed from the measured data. The relaxation time maps were evaluated in the cartilage zones for different acceleration factors. For reference, Osteoarthritis Research Society International (OARSI) grading and biomechanical measurements were performed and correlated with the MRI findings. Results: Four‐fold acceleration of CWT1ρ dispersion measurement by compressed sensing approach was feasible without meaningful loss in the sensitivity to osteoarthritic (OA) changes within the articular cartilage. Differences were significant between intact and OA groups in the superficial and transitional zones, and CWT1ρ correlated moderately with the reference measurements (0.3 < r < 0.7). Conclusion: CWT1ρ was able to differentiate between intact and OA cartilage even with four‐fold acceleration. This indicates that acceleration of CWT1ρ dispersion measurement by compressed sensing approach is feasible with negligible loss in the sensitivity to osteoarthritic changes in articular cartilage. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common joint disorder affecting about 7% of the global population, primarily characterized by the gradual loss of articular cartilage. This degeneration results from local inflammation, matrix depletion, and direct cartilage damage. A critical element in this process is the activation of the stimulator of the interferon genes (STING) pathway. Emerging evidence highlights its potential as a therapeutic target, with natural products showing promise as inhibitors. Our study centers on Acacetin, a basic unit of polyketides known for its anti-inflammatory properties. Prior research has highlighted its potential interaction with STING based on the structure. Thus, this study aimed to assess the effectiveness of Acacetin as a STING inhibitor and its protective role against OA. In vitro experiments showed that Acacetin pretreatment not only mitigated interleukin-1β (IL-1β)-induced cytotoxicity but also decreased the inflammatory response and degeneration in chondrocytes stimulated IL-1β. In vivo studies revealed that Acacetin administration significantly reduced articular cartilage destruction, abnormal bone remodeling, and osteophyte formation in a model of OA induced by destabilization of the medial meniscus (DMM). Mechanistically, Acacetin was found to interact directly with STING, and inhibit IL-1β-induced activation of STING, along with the subsequent phosphorylation of the TBK1/NF-κB pathway in chondrocytes. In conclusion, our findings establish Acacetin as an effective inhibitor of STING that protects chondrocytes from IL-1β-induced damage and slows the progression of OA in mice. [ABSTRACT FROM AUTHOR]

Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded ex vivo model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28 days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of ex vivo models and challenges of working with bioreactors that must be overcome to increase their utility. This ex vivo model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible in vivo. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence To compare the load distributed to the medial tibial articular cartilage after refixation of posterior medial meniscus root tears between the suture anchor and transtibial pullout techniques in posterior medial meniscus root tears.Twelve Thiel's embalmed human cadaveric knees are used and divided into three groups (four knees in each group): (1) intact meniscus (IM), (2) fixation with suture anchor technique (SA) and (3) fixation with transtibial pullout technique (TP). Each group applies an axial compression load up to 1500 N by Instron E 10000 at two knee flexion angles (0° and 60°). A Tekscan 4000 pressure sensor is used to record the contact pressure and the contact area for each testing condition.The contact pressure and the contact area between the three conditions are not significantly different at 0° and 60° knee flexion angles. The peak contact pressure and contact area are 3734.8 ± 2642.2 kPa, 288.2 ± 115.0 mm2, 4510 ± 2930.5 kPa, 204.4 ± 36.8 mm2 and 5328.8 ± 2607.7 kPa, 219.2 ± 84.7 mm2 in IM, SA and TP, respectively.Both suture anchor and transtibial pullout refixation of PMMRT can restore contact pressure and contact area similar to the intact meniscus. This finding suggests that either technique can be reliably used in clinical practice to preserve joint function and potentially reduce the risk of osteoarthritis progression following posterior medial meniscus root tear repairs.Level III. [ABSTRACT FROM AUTHOR]

BACKGROUND: The traditional view is that proximal fibular fractures do not require fixation. Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint, and its mechanism of action is worth studying. OBJECTIVE: To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS: Finite element method was used to conduct simulated biomechanical experiments. A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data, and four proximal fibular shapes were simulated (Model A: intact, Model B: 1 cm fracture below the fibular head, Model C: 1 cm tip defect fracture from the proximal end of the fibula to the distal end, and Model D: 2 cm bone defect from the proximal end of the fibula). A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION: (1) In Model A, the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment, while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment. The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle, and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle. (2) Compared to Model A, there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C. (3) Compared to Model A, the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage (14.9%), medial condyle of femoral cartilage (13.6%), and medial meniscus (6.6%). The maximum first principal stress increase amplitude was the medial meniscus (11.06%), the medial tibial cartilage (8.65%), and the medial condyle of the femoral cartilage (7.46%). The maximum equivalent stress increase amplitude of the ligament was as follows: popliteal arch ligament (33.2%)>anterior cruciate ligament (21.3%)>fibular collateral ligament (17%)>posterior cruciate ligament (14.3%)>anterior lateral collateral ligament (13.2%)>medial collateral ligament (10.1%). (4) Compared to Model A, the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage (19.5%), femoral cartilage medial condyle (17.9%), and medial meniscus (9.9%). The maximum first principal stress in sequence was the medial meniscus (14.04%), the medial tibial cartilage (13.03%), and the medial condyle of the femoral cartilage (11.37%). The increasing trend of maximum equivalent stress in ligaments was as follows: anterior cruciate ligament (25.2%)>posterior cruciate ligament (18.9%)>medial collateral ligament (18.5%)>anterior lateral collateral ligament (12.7%). (5) It is suggested that when the knee joint is extended, a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage, anterior cruciate ligament, and posterior lateral ligament complex. [ABSTRACT FROM AUTHOR]

Since the advent of 3D printing technology, a significant effort has been made to develop new 3D printable materials. Despite the recent progress in the field of 3D printing, the limited availability of photoactive resins has motivated continuous research endeavors to develop novel photoresins with multifunctional capabilities. Herein a biobased photoresin derived is reported from modified olive oil, designed for high‐resolution solvent‐free 4D printing with multifunctional capabilities. The physicochemical properties of the printed polymers are fine‐tuned using acrylic acid as a diluent cum comonomer. The mechanical properties of the printed polymers are similar to various soft tissues, such as ligaments, articular cartilage, and soft collagenous bone, showcasing its potential for soft tissue engineering applications. While the excellent temperature‐responsive shape memory 4D attributes coupled with exceptional antimicrobial properties toward gram‐negative and gram‐positive bacteria highlight the multifunctional nature of the printed polymers. Moreover, the printed polymers exhibited outstanding hemocompatibility and good cytocompatibility toward mouse fibroblast cells, suggesting their potential soft tissue engineering applications. In sum, the newly developed biobased resin can be employed to minimize the environmental impact of additive manufacturing while being competitive with existing fossil‐based photoresins, thereby meeting the growing demand for advanced photoresins with superior high‐resolution printing and smart properties for biomedical applications. [ABSTRACT FROM AUTHOR]

Background: There are defects in the existing classification of capitellar cartilage injury (CCI) concomitant with radial head fracture (RHF). This study aimed to introduce a comprehensive classification of CCI and to analyze its surgical guidance value. Methods: According to the affected site and severity, CCI was classified into four types: Type I - partial-thickness loss of articular cartilage, Type II - full-thickness loss of articular cartilage, Type III - full-thickness loss of articular cartilage with subchondral bone loss, Type IV - full-thickness loss of articular cartilage with thin cortex loss on the border of the capitellum; Different types suggest different surgical methods. Between January 2017 and January 2023, this comprehensive CCI classification was applied in 31 operated patients with CCI concomitant with RHF. The ranges of motion (ROM), Mayo Elbow Performance Index (MEPI) score, Hospital for Special Surgery (HSS) score and visual analog scale (VAS) for pain, were used to evaluate the functional recovery of the affected limb. Results: Mason Type I-IV RHF accounted for 6.45%, 38.71%, 48.39%, and 6.45%, respectively. Type I-IV CCI accounted for 12.90%, 35.48%, 45.16% and 6.45%, respectively. There was no relationship between the CCI and RHF types (p > 0.05). At the end of the follow-up period of 11–26 months with an average of 16 months, the elbow flexion and extension ROM recovered to (147.39 ± 9.84)°, forearm rotation ROM recovered to (168.74 ± 11.70)°, MEPI score recovered to (89.19 ± 4.17), HSS score recovered to (88.74 ± 4.62), VAS score recovered to (0.50 ± 0.57), indicating significant differences compared to preoperative measurements (p < 0.05). According to the MEPI and HSS scores, the excellent and good rate of functional recovery was 100%. Conclusion: Different types of CCI differ not only in pathology but also in treatment methods. Surgical strategy according to the comprehensive CCI classification introduced in this paper may lead to a satisfactory outcome. [ABSTRACT FROM AUTHOR]

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self‐healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one‐pot synthesis of dual cross‐linked zinc‐coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross‐linking by Zn2+ ions and simultaneous covalent cross‐linking through a covalent cross‐linker viz methylene bisacrylamide. Fourier‐transform infrared (FTIR), X‐ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self‐healing features. Moreover, the percentage of the equilibrium water content of zinc‐coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel‐Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross‐linked hydrogel, HGel‐Zn(NO3)2, with a combination of good mechanical properties, efficient self‐recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage. [ABSTRACT FROM AUTHOR]

Diseased conditions of articular cartilage such as osteoarthritis (OA) are accompanied by a change in the water concentration, together with a decrease in cartilage thickness. These parameters are important indicators of the normal joint functioning. Light scattering in a heterogeneous joint tissue is a complex process and it is important to supplement its study with understanding gained from modelling. In this work we employed Monte Carlo for analysis of the relationship between changes in cartilage parameters and calculated diffuse reflectance spectra. It has been shown that water absorption peak at 980 nm is determined by both water content and cartilage thickness, while changes in diffuse reflectance spectra at 1450 nm are mostly driven only by water content. Since independent assessment of these parameters is clinically relevant, several approaches for their determination were developed. A heuristic algorithm for cartilage thickness determination and its quality metrics (R 2 = 0.96) were obtained. Several regression models were developed using the amplitudes of diffuse reflectance spectra at different wavelengths and it was shown that the use of a wide range of wavelengths (850–1700 nm) allows to determine the cartilage water concentration and its thickness with the accuracy R 2 0.96 and 0.99 while measuring at different probe-detector distances. [ABSTRACT FROM AUTHOR]

Chondrocytes, the resident cells of articular cartilage, play a vital role in tissue maintenance and regeneration. Recent studies have highlighted chondrocyte senescence as a key contributor to cartilage dysfunction. In this study, we investigated the influence of substrate stiffness on chondrocyte senescence using polydimethylsiloxane (PDMS) substrates with varying stiffness ratios (1:5, 1:20, and 1:60). After culturing chondrocytes on these substrates, we found that softer substrates (1:60) significantly reduced chondrocyte senescence, as evidenced by a decrease in senescence‐associated β‐galactosidase (SA‐β‐gal) activity by 33% compared with stiffer substrates (1:5). Furthermore, quantitative real‐time polymerase chain reaction (PCR) analysis revealed that chondrocytes cultured on softer substrates exhibited lower expression levels of senescence‐related genes (e.g., p16INK4a) and matrix‐degrading enzymes (e.g., MMP13). These findings suggest that substrate stiffness plays a critical role in regulating chondrocyte senescence and could potentially inform the design of scaffolds for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Lack of insight into factors that determine purity and quality of human iPSC (hiPSC)-derived neo-cartilage precludes applications of this powerful technology toward regenerative solutions in the clinical setting. Here, we set out to generate methylome-wide landscapes of hiPSC-derived neo-cartilages from different tissues-of-origin and integrated transcriptome-wide data to identify dissimilarities in set points of methylation with associated transcription and the respective pathways in which these genes act. Methods: We applied in vitro chondrogenesis using hiPSCs generated from two different tissue sources: skin fibroblasts and articular cartilage. Upon differentiation toward chondrocytes, these are referred to as hFiCs and hCiC, respectively. Genome-wide DNA methylation and RNA sequencing datasets were generated of the hiPSC-derived neo-cartilages, and the epigenetically regulated transcriptome was compared to that of neo-cartilage deposited by human primary articular cartilage (hPAC). Results: Methylome-wide landscapes of neo-cartilages of hiPSCs reprogrammed from two different somatic tissues were 85% similar to that of hPACs. By integration of transcriptome-wide data, differences in transcriptionally active CpGs between hCiC relative to hPAC were prioritized. Among the CpG-gene pairs lower expressed in hCiCs relative to hPACs, we identified genes such as MGP, GDF5, and CHAD enriched in closely related pathways and involved in cartilage development that likely mark phenotypic differences in chondrocyte states. Vice versa, among the CpG-gene pairs higher expressed, we identified genes such as KIF1A or NKX2-2 enriched in neurogenic pathways and likely reflecting off target differentiation. Conclusions: We did not find significant variation between the neo-cartilages derived from hiPSCs of different tissue sources, suggesting that application of a robust differentiation protocol such as we applied here is more important as compared to the epigenetic memory of the cells of origin. Results of our study could be further exploited to improve quality, purity, and maturity of hiPSC-derived neo-cartilage matrix, ultimately to realize introduction of sustainable, hiPSC-derived neo-cartilage implantation into clinical practice. [ABSTRACT FROM AUTHOR]

A new concept of biomimetic lubricating nanosystem that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property is developed. High drug loading ratio of 99%, great friction reduction by 75% for more than 7200 times without failure, and effective up-regulation of cartilage anabolic genes and down-regulation of catabolic proteases and pain-related genes are achieved. Our work provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for synergistic therapy of osteoarthritis. [Display omitted] Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core–shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications. [ABSTRACT FROM AUTHOR]

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra‐articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra‐articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6‐month‐old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center‐edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real‐time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C‐KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a degenerative disease of synovial joints affecting all tissues, including articular cartilage and subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early‐, mid‐, and late‐stages of osteoarthritis progression. Tibia of MMT‐operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3‐weeks post‐surgery. With contrast‐enhanced micro‐CT technique, quantitative, 3‐dimensional analysis of the tibia showed that the articular cartilage thickened at 3‐ and 6‐weeks post‐surgery and decreased at 12‐weeks post‐surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6‐weeks post‐surgery and followed cartilage damage. Osteophytes were found as early as 3‐weeks post‐surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3‐weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6‐ and 12‐weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late‐stage will be important for eventual clinical translation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found an association between basal metabolic rate (BMR) and various malignant neoplasms, including bone tumors. BMR is also associated with bone mineral density, but the causality between BMR and benign neoplasms of bone and articular cartilage remains uncertain. Design: Single nucleotide polymorphisms (SNPs) associated with BMR (p < 5 × 10-8) were used as instrumental variables for Mendelian randomization analysis of neoplasm risk. The inverse variance weighted (IVW) method was the primary approach, with the weighted median and MR-Egger regression serving as supplements. Results: In this MR analysis, the IVW method supported a causal relationship between BMR and benign neoplasms of bone and articular cartilage (OR = 1.417; 95% CI, 1.039 to 1.930; p = 0.027). No evidence of heterogeneity or pleiotropy in the selected SNPs was found in our study. Thus, based on these results, we discovered a possible causal relationship between BMR and benign neoplasms of bone and articular cartilage. Conclusions: In this MR study, evidence suggested a genetic correlation between genetically predicted BMR and the risk of neoplasms in bone and articular cartilage. [ABSTRACT FROM AUTHOR]

Aims: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by pain and functional limitations. Current treatments offer symptomatic relief but do not address the underlying pathology. This study explores the role of the infrapatellar fat pad (IFP) in KOA and evaluates the efficacy of its partial arthroscopic excision. Methods: A retrospective review was conducted on 37 KOA patients who underwent partial IFP excision. Pain and function were assessed using the WOMAC and VAS scores, while MRI evaluations focused on cartilage health. Results: Significant postoperative improvements were observed in both pain and functional outcomes, with substantial reductions in WOMAC and VAS scores (P < 0.001). MRI findings demonstrated notable enhancements in cartilage integrity, reflected in significantly improved WORMS scores (P < 0.001). Conclusions: Partial excision of the IFP significantly reduces pain and improves function in KOA patients, while also promoting cartilage health. These findings support the IFP's role in KOA pathology and highlight the potential benefits of targeted surgical intervention. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence 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 [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. Methods: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. Results: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). Conclusions: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA. [ABSTRACT FROM AUTHOR]

Summary vSPACE is a web-based application presenting a spatial representation of scRNAseq data obtained from human articular cartilage by emulating the concept of spatial transcriptomics technology, but virtually. This virtual 2D plot presentation of human articular cartage cells generates several zonal distribution patterns, for one or multiple genes at a time, revealing patterns that scientists can appreciate as imputed spatial distribution patterns along the zonal axis. Availability and implementation vSPACE is implemented in Python Dash as a web-based toolbox designed for data visualization of zonal gene expression patterns in articular cartilage chondrocytes. This tool is freely accessible at: https://vspace.cse.uconn.edu/ The source code and extra materials for this service can be downloaded from: https://github.com/zhacheny/vSPACE [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis is a common chronic disease that affects quality of life and increases public health costs. Knee osteoarthritis is a frequent form, marked by joint degeneration, pain, stiffness, and functional restrictions. Factors such as age, genetics, joint injuries, obesity, and vitamin D deficiency can affect knee osteoarthritis progression. While the exact link between vitamin D and osteoarthritis is still being studied, recent research indicates that low vitamin D levels might influence the articular cartilage's structure and function, potentially accelerating osteoarthritis. This review aims to analyze the last decade of research on vitamin D's role in osteoarthritis. Methods: A systematic review of the literature was conducted in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Relevant studies from the last ten years were included to evaluate the association between vitamin D levels and knee osteoarthritis. The inclusion criteria were studies examining the role of vitamin D in cartilage health and osteoarthritis progression and the potential clinical implications for disease management. Results: This review identified a variety of studies exploring the connection between vitamin D and osteoarthritis, with mixed findings. Conclusions: The relationship between vitamin D and knee osteoarthritis remains inconclusive, highlighting the need for further research. An updated evaluation of the literature is crucial for osteoarthritis management strategies and to potentially include vitamin D supplementation in therapeutic protocols. [ABSTRACT FROM AUTHOR]

cutting-edge field of study to create biological substitutes to maintain, restore, or enhance cartilage function is articular cartilage (AC) tissue engineering. Employing this innovative approach, polymer composites that mimic the structure and function of real cartilage tissues are created by carefully mixing biomaterials of scaffolds, cells, and biochemical components. Naturally polymers have recently gained attention as biomaterials to fabricate scaffolds, for instance, chitosan. Despite its shortcomings such as poor mechanical strength and low stiffness, chitosan-based hydrogel scaffolds have been cross-linked with other synthetic polymers, namely hybrid scaffolds, for future perspective of AC tissue engineering. To mimic AC compartment design, additive manufacturing closely resembles native tissue, and its flexibility is possibly tailored. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA's pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within the articular joint. Crucial for cell-to-cell communication, extracellular vesicles (EVs) contribute to OA progression through the delivery of bioactive molecules in the inflammatory microenvironment. By repurposing this acellular means of signal transmission, therapeutic drugs may be administered to degenerated cartilage tissue in the hopes of encouraging regeneration. Positive outcomes are apparent in in vivo studies on this subject; however, for this therapy to prove itself in the clinical world, efforts towards standardizing the characterization, application, biological contents, and dosage are essential. [ABSTRACT FROM AUTHOR]

In articular cartilage, the pericellular matrix acting as a specialized mechanical microenvironment modulates environmental signals to chondrocytes through mechanotransduction. Matrix viscoelastic alterations during cartilage development and osteoarthritis (OA) degeneration play an important role in regulating chondrocyte fate and cartilage matrix homeostasis. In recent years, scientists are gradually realizing the importance of matrix viscoelasticity in regulating chondrocyte function and phenotype. Notably, this is an emerging field, and this review summarizes the existing literatures to the best of our knowledge. This review provides an overview of the viscoelastic properties of hydrogels and the role of matrix viscoelasticity in directing chondrocyte behavior. In this review, we elaborated the mechanotransuction mechanisms by which cells sense and respond to the viscoelastic environment and also discussed the underlying signaling pathways. Moreover, emerging insights into the role of matrix viscoelasticity in regulating chondrocyte function and cartilage formation shed light into designing cell‐instructive biomaterial. We also describe the potential use of viscoelastic biomaterials in cartilage tissue engineering and regenerative medicine. Future perspectives on mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses, and biomaterial design are highlighted. Finally, this review also highlights recent strategies utilizing viscoelastic hydrogels for designing cartilage‐on‐a‐chip. Summary: It is well known that viscoelasticity has been found to be a universal characteristic of living tissues, cells, and molecules.Matrix viscoelasticity, as a critical physical cues of cartilage matrix microenvironment, regulates collective chondrocyte fate and cartilage formation. But, how matrix viscoelasticity affects the chondrocyte behavior and function remains unclear.Growing evidence has demonstrated that matrix viscoelasticity regulates chondrocytes in some ways not anticipated from previous mechanisms of mechanotransduction, which was based on purely substrate stiffness.In this review, we introduce recent work elucidating the effect of matrix viscoelasticity on chondrocytes morphology, phenotype, function, inflammatory response, and signaling pathways.These findings have provided insights into viscoelasticity as a design parameter for cartilage tissue engineering, regenerative medicine, and cartilage‐on‐a‐chip, even shed light into the pathological mechanism of joint growth and degeneration. [ABSTRACT FROM AUTHOR]