Search

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]

Purpose Case Presentation Results Conclusion To describe the first report of third eyelid cartilage eversion in an adult American Quarter Horse mare.A 22‐year‐old American Quarter Horse mare presented to the University of Missouri Veterinary Health Center Equine Hospital for a 2‐week history of a third eyelid cartilage abnormality of the left eye with no known recent trauma. Complete ophthalmic examination revealed third eyelid cartilage eversion of the left nictitans. The abnormal scrolled cartilage was surgically excised using a handheld cautery unit and submitted for histopathologic evaluation.Histopathologic findings displayed normal third eyelid cartilage, without evidence of neoplasia or inflammation. Mucosal hyperplasia and increased vascularity of the submucosa were observed. The horse healed well after electrocautery excision and normal third eyelid conformation was restored.To the authors' knowledge, this is the first report of an acquired, presumed spontaneous, third eyelid cartilage eversion in a horse. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a prevalent chronic health condition that is mostly associated with the degeneration of joint cartilage due to aging or abnormal mechanical stress in the joint. Intraarticularly injected nanoparticle‐based lubricants decrease the friction between damaged cartilage surfaces, thus preventing their further degradation; however, the effectiveness of currently used nanoparticle‐based lubricants is limited by their short retention time in the joint space. To address this challenge, cationically modified biosourced phytoglycogen nanolubricants are utilized, which electrostatically bind to the cartilage components. The conjugation of the nanoparticles with red‐emissive fluorescent carbon dots enables in vivo studies of their retention in the joint. The hytoglycogen nanoconjugates exhibit high colloidal stability in physiological conditions, provide a friction coefficient of 10−3–10−2 between the sliding surfaces under physiologically relevant pressures, strongly bind to the major cartilage surface components, and show significantly prolonged retention time in the joint in vivo, with a fourfold increase in half‐life in comparison with conventionally used hyaluronic acid injectant. These properties make these functionalized phytoglycogen nanoparticles a highly promising candidate for joint lubrication. [ABSTRACT FROM AUTHOR]

Objective: Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. Methods: This cross‐sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age‐, weight‐ and height‐matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann–Whitney nonparametric t‐test, and correlations between different meniscal states and adjacent cartilage were analyzed. Results: Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p < 0.05), and the site of injury was predominantly centered in the medial compartment (femur, p = 0.000; tibia, p = 0.000; anterior horn, p = 0.000). In the respective compartments, the posterior horn of the lateral meniscus showed a significant positive correlation with the mid‐cartilage of the femoral and tibial (r = 0.566, p = 0.035; r = 0.611, p = 0.02); and the posterior horn of the medial meniscus showed a significant positive correlation with the posterior tibial cartilage (r = 0.668, p = 0.018). Conclusion: During the acute phase of ACL rupture, the internal composition of the cartilage and meniscus undergoes significant changes, even if the morphology is intact. More importantly, the state of the meniscus significantly affects the internal composition of the adjacent cartilage. This is an early warning sign of OA, which should be closely monitored and carefully managed in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusion Foot‐related lameness is common in Standardbred and Thoroughbred racehorses. Magnetic resonance imaging (MRI) provides information on both the soft tissue and osseous structures of the distal extremity. The aim of this study was to determine whether abnormalities identified on distal limb MRI differed between these two racehorse populations.The records of Standardbred and Thoroughbred racehorse distal extremity MRI examinations conducted at Camden Equine Centre and Ballarat Veterinary Practice between 2013 and 2023 were retrieved. Horses were included if pain causing lameness had been localised to the foot using perineural or intra‐articular analgesia. MRI abnormalities of the structures within the distal extremity were recorded and comparisons made between the two groups.There was a significant difference in the rate of occurrence of certain MRI abnormalities between the Thoroughbred and Standardbred racehorse populations, including distal phalangeal fractures, proximal phalangeal short tau inversion recovery (STIR) hyperintensity (distal aspect), the presence and severity of ungular cartilage ossification, abnormalities of the navicular bone distal border synovial invaginations/vascular channels and navicular bone distal border fragments. The presence of distal extremity STIR hyperintensity and fractures was significantly higher in Standardbred compared to Thoroughbred racehorses when these findings were grouped and considered in combination.There were many similarities in the distal extremity MRI abnormalities identified in lame Australian Standardbred and Thoroughbred racehorses. However, distal phalangeal fractures, ungular cartilage ossification and distal extremity STIR hyperintensity were identified in significantly more in Standardbred than Thoroughbred racehorses. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate a non‐resorbable implant for the focal repair of chondral defects in eight adult horses with 12‐month follow‐up. The bi‐layered construct composed of a polycarbonate‐urethane‐urea biomaterial which was printed in 3D fashion onto a bone anchor was implanted into surgically created osteochondral defects into the femoropatellar joints of eight horses. The analysis of post‐mortem outcomes were compared to defects treated with microfracture in the same animal on the contralateral femoropatellar jointfemoropatellar joint. The overall macroscopic scoring after 12 months yielded higher scores in the OCI‐treated stifles compared to MF treatment (p = 0.09) with better quality and filling of the defect. Histology revealed good anchorage of repair tissue growing into the 3D structure of the implant and histopathology scoring for adjacent native cartilage showed no difference between groups. MRI and micro‐CT showed overall less sclerotic reactions in the surrounding bone in the implant group and no foreign body reaction was detected. Biomechanical analysis of the repair tissue revealed a significantly higher peak modulus (p < 0.05) in the implant group (0.74 ± 0.45) compared to the microfracture control group (0.15 ± 0.11). Dynamic loading yielded higher values for the repair tissue overgrowing the implant group (0.23 ± 0.17) compared to the microfracture control (0.06 ± 0.06) (p < 0.05). The bi‐layered osteochondral implant provided a safe implant for focal repair of full‐thickness osteochondral defects, as no adverse reaction was seen within the joints and the level of degeneration of adjacent cartilage to the repair site was not different compared to that seen in defects treated with microfracture after 12 months. [ABSTRACT FROM AUTHOR]

EphrinB2, a member of the Ephrin family, has been linked to several orthopaedic conditions. Nevertheless, the correlation between ephrinB2 and post‐traumatic arthritis (PTOA) remains unclear. Human PTOA cartilage from human and mouse knee joints was systematically analysed to investigate the relationship between EphrinB2 and PTOA using SO‐FG and toluidine blue staining, micro‐CT, histomorphometry, immunohistochemistry, immunofluorescence, lentiviral articular injection and in situ end labeling (TUNEL) assays. EphrinB2 expression was significantly downregulated in PTOA chondrocytes. Blocking EphrinB2 increased the breakdown of cartilage matrix in mice with PTOA via reducing the process of chondrocyte autophagy. The presence of severe cartilage damage was evident, as indicated by a considerable decrease in both cartilage thickness and area, accompanied by an increase in chondrocyte death. Altogether, EphrinB2 is required for the maintenance of cartilage homeostasis in post‐traumatic arthritis, and EphrinB2 ablation is associated with accelerated chondrocyte matrix degeneration, finally causing damage to the articular cartilage. [ABSTRACT FROM AUTHOR]

The repair and regeneration of cartilage is a challenge for scientists and clinical surgery. Achieving cell adhesion and regeneration, anti‐inflammatory, lubrication, targeted drug delivery and controlled release simultaneously in cartilage treatment are the goals of researchers. Polymer composites and hybrids have the potential to realize above functions in cartilage tissue engineering. This review refers to cartilage injuries, current clinical techniques, and their benefits and limitations, focusing on the most relevant and state of art of advanced polymers for cartilage tissue engineering. The frontier applications of multifunctional polymer composites and hybrids in cartilage tissue engineering are discussed in depth, including polymer scaffold, polymer bio‐lubricant, and zwitterionic polymer for drug delivery and sustained drug release. A summary of comprehensive properties of polymers such as processability, mechanical properties, biocompatibility, biodegradability, hydrophilicity, cytotoxicity, etc., and their mechanisms are analyzed. Furthermore, some key challenges and outstanding concerns on polymer‐based materials for cartilage tissue engineering are presented followed by future perspectives. Highlights: The state of art of advanced polymers for cartilage tissue engineering.The advanced bionic property and mechanism of polymer composites and hybrids.Polymers for scaffold, biolubricant, drug delivery, sustained drug release.Future perspectives on polymer composites, hybrids‐based cartilage materials. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that the damaged regions in osteoarthritis are accompanied by the accumulation of iron ions. Ferroptosis, as an iron‐dependent form of cell death, holds significant implications in osteoarthritis. Melatonin, a natural product with strong scavenging abilities against reactive oxygen species and lipid peroxidation, plays a crucial role in the treatment of osteoarthritis. This study aims to demonstrate the existence of ferroptosis in osteoarthritis and explore the specific mechanism of melatonin in suppressing ferroptosis and alleviating osteoarthritis. Our findings reveal that melatonin reverses inflammation‐induced oxidative stress and lipid peroxidation while promoting the expression of extracellular matrix components in chondrocytes, safeguarding the cells. Our research has revealed that NADPH oxidase 4 (NOX4) serves as a crucial molecule in the ferroptosis process of osteoarthritis. Specifically, NOX4 is located on mitochondria in chondrocytes, which can induce disorders in mitochondrial energy metabolism and dysfunction, thereby intensifying oxidative stress and lipid peroxidation. LC‐MS analysis further uncovered that GRP78 is a downstream binding protein of NOX4. NOX4 induces ferroptosis by weakening GRP78's protective effect on GPX4 and reducing its expression. Melatonin can inhibit the upregulation of NOX4 on mitochondria and mitigate mitochondrial dysfunction, effectively suppressing ferroptosis and alleviating osteoarthritis. This suggests that melatonin therapy represents a promising new approach for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Purpose: The anisotropy of R2 and R1ρ relaxation rates in articular cartilage contains information about the collagenous structure of the tissue. Here we determine and study the anisotropic and isotropic components of T2 and T1ρ relaxation parameters in articular cartilage with a clinical 3T MRI device. Furthermore, a visual representation of the topographical variation in anisotropy is given via anisotropy mapping. Methods: Eight bovine stifle joints were imaged at 22 orientations with respect to the main magnetic field using T2, continuous‐wave (CW) T1ρ, and adiabatic T1ρ mapping sequences. Relaxation rates were separated into isotropic and anisotropic relaxation components using a previously established relaxation anisotropy model. Pixel‐wise anisotropy values were determined from the relaxation‐time maps using Michelson contrast. Results: The relaxation rates obtained from the samples displayed notable variation depending on the sample orientation, magnetization preparation, and cartilage layer. R2 demonstrated significant anisotropy, whereas CW‐R1ρ (300 Hz) and CW‐R1ρ (500 Hz) displayed a low degree of anisotropy. Adiabatic R1ρ was largely isotropic. In the deep cartilage regions, relaxation rates were generally faster and more anisotropic than in the cartilage closer to the tissue surface. The isotropic relaxation rate components were found to have similar values regardless of measurement sequence. Conclusions: The fitted relaxation model for T2 and T1ρ demonstrated varying amounts anisotropy, depending on magnetization preparation, and studied the articular cartilage layer. Anisotropy mapping of full joints showed varying amounts of anisotropy depending on the quantitative MRI parameter and topographical location, and in the case of T2, showed systematic changes in anisotropy across cartilage depth. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate tibial cartilage thickness (TCT), T1ρ and T2 values within both loaded and baseline configurations in a cadaveric knee model using a 3D bone based tibial coordinate system. Ten intact cadaveric knees were mounted into an magnetic resonance imaging (MRI) compatible loading device. Morphologic and quantitative MRI (qMRI) images were acquired with the knee in a baseline configuration and after application of 50% body weight. The morphologic images were evaluated for cartilage degeneration using a modified Noyes scoring system. A 3D bone‐based tibial coordinate system was utilized to evaluate regional changes of tibial T1ρ, T2, and cartilage thickness values among regions covered and uncovered by the meniscus. Inter‐regional differences in medial and lateral MRI outcomes were found between loaded and baseline configurations. Cartilage regions covered by the meniscus demonstrated disparate qMRI and TCT results as compared to cartilage regions not covered by the meniscus. The regions covered by meniscus experienced a ~3.5%, ~0.5%, and ~5.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT, respectively, in both compartments while regions not covered by the meniscus experienced larger reductions of ~10%, ~2%, and ~10.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT (p < 0.05, lateral compartment only), respectively, in both compartments. T1ρ and T2 decreases following application of 50% body weight load were substantially larger in the tibial regions with modified Noyes grade 3 (n = 2) compared to either healthy regions (n = 85, p < 0.0.003) or regions with modified Noyes grade 2 (n = 13, p < 0.004). Interregional differences in MRI outcomes reflect variations in structure and function, and largely followed a pattern in cartilage regions that were covered or not covered by the meniscus. Results of the current study suggest that ΔT1ρ and ΔT2 values may be sensitive to superficial fissuring, more than baseline or loaded T1ρ or T2 values, or TCT alone, however future studies with additional specimens, with greater variability in OA grade distribution, may further emphasize the current findings. [ABSTRACT FROM AUTHOR]

Natural cartilage exhibits superior lubricity as well as an ultra‐long service lifetime, which is related to its surface hydration, load‐bearing, and deformation recovery feature. Until now, it is of great challenge to develop reliable cartilage lubricating materials or coatings with persistent robustness. Inspired by the unique biochemical structure and mechanics of natural cartilage, the study reports a novel cartilage‐hydrogel composed of top composite lubrication layer and bottom mechanical load‐bearing layer, by covalently manufacturing thick polyelectrolyte brush phase through sub‐surface of tough hydrogel matrix with multi‐level crystallization phase. Due to multiple network dissipation mechanisms of matrix, this hydrogel can achieve a high compression modulus of 11.8 MPa, a reversible creep recovery (creep strain: ≈2%), along with excellent anti‐swelling feature in physiological medium (v/v0 < 5%). Using low‐viscosity PBS as lubricant, this hydrogel demonstrates persistent lubricity (average COF: ≈0.027) under a high contact pressure of 2.06 MPa with encountering 100k reciprocating sliding cycles, negligible wear and a deformation recovery of collapse pit in testing area. The extraordinary lubrication performance of this hydrogel is comparable to but beyond the natural animal cartilage, and can be used as compliant coating for implantable articular material of UHMWPE to present, offering more robust lubricity than current commercial system. [ABSTRACT FROM AUTHOR]

Recent research on ferroptosis and cuproptosis has underscored the crucial role of trace element regulation in osteoarthritis (OA) treatment. However, research systematically addressing the alterations in nutrient elements in OA cartilage is lacking. This study is initiated using clinical specimens to quantify metal element concentrations in both damaged and intact cartilage to identify deficient trace elements within the inflammatory and senescent microenvironments of OA. Based on the preliminary findings of selenium (Se) and gallium (Ga) deficiencies in OA cartilage, tailored nanoparticles based on Se and Ga are designed and validated for their antioxidant ability. GaSex nanoparticles demonstrated significant efficacy in mitigating chondrocyte degeneration and extracellular matrix degradation induced by inflammatory factors and in alleviating cartilage abrasion, hyperalgesia, and abnormal gait in a destabilization of the medial meniscus (DMM) mouse model. Mechanistically, GaSex nanoparticles activated the Nrf2 pathway and competitively inhibited the ubiquitin‐mediated degradation of Gpx4, thus inhibiting ferroptosis. This study systematically designed GaSex nanoparticles based on the imbalance of trace elements within the OA knee joint microenvironment and demonstrated robust antioxidant capabilities and remarkable competitive properties for ubiquitin, thereby providing a novel therapeutic solution for OA treatment. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix.This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA).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.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.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]

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration. [ABSTRACT FROM AUTHOR]

Auricular chondritis of unknown cause was suspected in a 10‐year‐old male Bolognese dog with a five‐month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals. [ABSTRACT FROM AUTHOR]

Proteomics is a growing field that offers insights into various aspects of disease processes and therapy responses. Within the field of orthopedics, there are a variety of diseases that have a poor prognosis due to a lack of targeted curative therapy or disease modifying therapy. Other diseases have been difficult to manage in part due to lack of clinical biomarkers that offer meaningful insight into disease progression or severity. As an emerging technology, proteomics has been increasingly applied in studying bone biology and an assortment of orthopedics related diseases, such as osteoarthritis, osteosarcoma and bone tumors, osteoporosis, traumatic bone injury, spinal cord injury, hip and knee arthroplasty, and fragile healing. These efforts range from mechanistic studies for elucidating novel insights in tissue activity and metabolism to identification of candidate biomarkers for diagnosis, prognosis, and targeted treatment. The knowledge gained from these proteomic and functional studies has provided unique perspectives in studying orthopedic diseases. In this review, we seek to report on the current state of the proteomic study in the field of orthopedics, overview the advances in clinically applicable discoveries, and discuss the opportunities that may guide us for future research. [ABSTRACT FROM AUTHOR]

Pannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggests Panx3 plays contrasting roles in traumatic versus aging osteoarthritis (OA) and intervertebral disc degeneration (IDD). However, whether its deletion influences the response of joint tissue to forced use is unknown. The purpose of this study was to determine if Panx3 deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and Panx3 knockout (KO) mice were randomized to either a no‐exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage and IVD histopathology were evaluated by histology, while tibial secondary ossification centers were analyzed using microcomputed tomography (µCT). Both male and female Panx3 KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared with SED WT mice. Additionally, Panx3 KO mice developed reduced bone volume, and female PANX3 KO mice had lengthening of the lateral tubercle at the intercondylar eminence. In the lower lumbar spine, both male and female Panx3 KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deleting Panx3 and forced treadmill running induces OA and causes histopathological changes associated with the degeneration of the IVDs in mice. [ABSTRACT FROM AUTHOR]

Large osteochondral defects are a major challenge in orthopedics, for which osteochondral allograft (OCA) transplantation is nowadays considered as an option, especially in young patients. However, a major issue with OCA is the need for graft storage, which ensures adequate cartilage integrity over time. The aim of this study was to test how long a Ringer‐based storage solution can provide good graft quality after explantation and thus meet the requirements for OCA. For this purpose, human osteochondral allografts of the knee and ankle were analyzed. Live/Dead analysis was performed and glycosaminoglycan, as well as hydroxyproline content, were measured as crucial chondrocyte integrity factors. Furthermore, biomechanical tests focusing on stress relaxation and elastic compression modulus were performed. The critical value of 70% living chondrocytes, which corresponds to a number of 300 cells/mm², was reached after an average of 16 weeks of storage. In addition, a constant cell shrinkage was observed over time. The amount of glycosaminoglycan and hydroxyroline showed a slight and constant decrease over time, but no significant differences when compared from Day 0 to the values at Weeks 40–43. Biomechanical testing also revealed no significant differences at the different time points. Therefore, the results show that the Ringer‐based storage solution at 4°C is able to provide a chondrocyte survival of 70% until Week 16. This is comparable to previously published storage solutions. Therefore, the study contributes to the establishment of a Ringer‐based osteochondral allograft transplantation system for countries where medium‐based storage solution cannot be approved. [ABSTRACT FROM AUTHOR]

Established risk factors for osteoarthritis (OA) include obesity, joint injury, age, race, and genetics. However, the relationship between cigarette smoking and OA has yet to be established. In the present study, we have employed the use of cigarette smoke extract (CSE), the water‐soluble vapor phase of cigarette smoke, with porcine cartilage explants to investigate the effects of cigarette smoking on cartilage catabolism at the tissue level. Articular cartilage explants were first exposed to 2.5%, 5%, and 10% CSE to assess its effects on cartilage homeostasis. Following, the effects of CSE on OA‐like inflammation was observed by culturing explants with a combined treatment of IL‐1β and TNF‐α and 10% CSE (CSE + OA). Cartilage explants were assessed for changes in viability, biochemical composition, extracellular matrix (ECM) integrity, and equilibrium mechanical properties (aggregate modulus and hydraulic permeability). CSE alone leads to both a time‐ and dose‐dependent decrease in chondrocyte viability but does not significantly affect sGAG content, percent sGAG loss, or the ECM integrity of cartilage explants. When IL‐1β and TNF‐α were combined with 10% CSE, this led to a synergistic effect with more significant losses in viability, significantly more sGAG loss, and significantly higher production of ROS than OA‐like inflammation only. Cartilage explant equilibrium mechanical properties were unaffected. Within the timeframe of this study, CSE alone does not cause OA but when combined with OA‐like inflammation leads to worsened articular cartilage degeneration as measured by chondrocyte viability, sGAG loss, proteoglycan staining, and ROS production. [ABSTRACT FROM AUTHOR]

The ideal cell source for articular cartilage repair remains elusive. Using developmentally inspired differentiation protocols, we induced human pluripotent stem cells (hPSCs) toward articular chondrocytes capable of joint cartilage repair in rodent models, which were distinct from growth plate chondrocytes, fated to be replaced by bone in vivo. Working toward clinical translation, we demonstrated controlled differentiation into chondrocytes by comprehensive gene expression analysis at each step of the differentiation. Articular chondrocytes derived from hPSCs could be expanded several passages in vitro without losing chondrogenic potential. Furthermore, chondrocytes isolated from these articular cartilage tissues had the potential to serially regenerate new articular and growth plate cartilage tissues. Finally, the ability to cryopreserve articular chondrocytes with the desired phenotype is critical for clinical translation and here we report no loss in cell viability or regenerative potential following cryopreservation. These results support the immense potential of hPSC‐derived articular chondrocytes as a cell‐based therapy for cartilage repair. [ABSTRACT FROM AUTHOR]

Background: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long‐term relief. Therefore, we investigated a novel self‐assembling tissue‐engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. Objectives: Examine the maturation of dynamic self‐regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. Materials and Methods: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin‐O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300–500 μm diameter and 1.2–1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser‐ablated lesion (experimental) and an empty laser‐ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. Results: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin‐O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. Conclusion: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair. [ABSTRACT FROM AUTHOR]

Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction. [ABSTRACT FROM AUTHOR]

Background: Three‐dimensional MR fingerprinting (3D‐MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. Purpose: To assess the intra‐day and inter‐day repeatabilities of knee cartilage T1, T2, and T1ρ maps using a 3D‐MRF sequence for simultaneous measurement. Study Type: Prospective. Subjects: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. Field Strength/Sequence: 3 T/3D‐MRF, T1, T2, and T1ρ maps. Assessment: The acquisition of 3D‐MRF cartilage (simultaneous acquisition of T1, T2, and T1ρ maps) were acquired using a dictionary pattern‐matching approach. Conventional cartilage T1, T2, and T1ρ maps were acquired using variable flip angles and a modified 3D‐Turbo‐Flash sequence with different echo and spin‐lock times, respectively, and were fitted using mono‐exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. Statistical Tests: The mean and SD for cartilage T1, T2, and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra‐subject and inter‐subject repeatabilities were assessed using coefficient of variation (CV) and intra‐class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland–Altman analysis were performed to compare maps between the conventional and 3D‐MRF sequences. Results: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1, T2, and T1ρ, respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. Conclusion: The 3D‐MRF sequence had high intra‐subject and inter‐subject repeatabilities for simultaneously measuring knee cartilage T1, T2, and T1ρ with good agreement with conventional sequences. Evidence Level: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Intra‐articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively lubricate and bind to the surface of cartilage in vitro. However, its ability to localize to cartilage and alter the tribological properties of the tissue in a live articulating large animal joint is not known. The goal of this study was to quantify the distribution and extent of localization of pAAm in the equine metacarpophalangeal or metatarsophalangeal joint (fetlock joint), and determine whether preferential localization of pAAm influences the tribological properties of the tissue. An established planar fluorescence imaging technique was used to visualize and quantify the distribution of fluorescently labeled pAAm within the joint. While the pAAm hydrogel was present on all surfaces, it was not uniformly distributed, with more material present near the site of the injection. The lubricating ability of the cartilage in the joint was then assessed using a custom tribometer across two orders of magnitude of sliding speed in healthy synovial fluid. Cartilage regions with a greater coverage of pAAm, that is, higher fluorescent intensities, exhibited friction coefficients nearly 2‐fold lower than regions with lesser pAAm (Rrm = −0.59, p < 0.001). Collectively, the findings from this study indicate that intra‐articular viscosupplement injections are not evenly distributed inside a joint, and the tribological outcomes of these materials is strongly determined by the ability of the material to localize to the articulating surfaces in the joint. [ABSTRACT FROM AUTHOR]

Purpose: This work aims to unravel the intricacies of adiabatic rotating frame relaxometry in biological tissues. Theory and Methods: The classical formalisms of dipolar relaxation R1ρ$$ {R}_{1\rho } $$ and R2ρ$$ {R}_{2\rho } $$ were systematically analyzed for water molecules reorienting on "fast" and "slow" timescales. These two timescales are, respectively, responsible for the absence and presence of R1ρ$$ {R}_{1\rho } $$ dispersion. A time‐averaged R1ρ$$ {R}_{1\rho } $$ or R2ρ$$ {R}_{2\rho } $$ over an adiabatic pulse duration was recast into a sum of R1$$ {R}_1 $$ and R2$$ {R}_2 $$, but with different weightings. These weightings depend on the specific modulations of adiabatic pulse waveforms. In this context, stretched hyperbolic secant (HSn$$ HSn $$) pulses were characterized. Previously published HS1$$ HS1 $$R1ρ$$ {R}_{1\rho } $$, continuous‐wave (CW) R1ρ$$ {R}_{1\rho } $$, and R1$$ {R}_1 $$ measures from 12 agarose phantoms were used to validate the theoretical predictions. A similar validation was also performed on previously published HSn$$ HSn $$R1ρ$$ {R}_{1\rho } $$ (n$$ n $$=1, 4, 8) and HS1$$ HS1 $$R2ρ$$ {R}_{2\rho } $$ from bovine cartilage specimens. Results: Longitudinal relaxation weighting decreases for HSn$$ HSn $$ pulses as n$$ n $$ increases. Predicted CW R1ρcal$$ {R}_{1\rho}^{cal} $$ values from agarose phantoms align well with the measured CW R1ρexp$$ {R}_{1\rho}^{exp} $$ values, as indicated by a linear regression function: R1ρcal=1.04*R1ρexp−1.96$$ {R}_{1\rho}^{cal}={1.04}^{\ast }{R}_{1\rho}^{exp}-1.96 $$. The predicted adiabatic R1ρ$$ {R}_{1\rho } $$ and R2ρ$$ {R}_{2\rho } $$ from cartilage specimens are consistent with those previously measured, as quantified by: R1ρ,2ρcal=1.10*R1ρ,2ρexp−0.41$$ {R}_{1\rho, 2\rho}^{cal}={1.10}^{\ast }{R}_{1\rho, 2\rho}^{exp}-0.41 $$. Conclusion: This work has theoretically and experimentally demonstrated that adiabatic R1ρ$$ {R}_{1\rho } $$ and R2ρ$$ {R}_{2\rho } $$ can be recast into a sum of R1$$ {R}_1 $$ and R2$$ {R}_2 $$, with varying weightings. Therefore, any suggestions that adiabatic rotating frame relaxometry in biological tissues could provide more information than the standard R1$$ {R}_1 $$ and R2$$ {R}_2 $$ warrant closer scrutiny. [ABSTRACT FROM AUTHOR]

Purpose: To optimize Relaxation along a Fictitious Field (RAFF) pulses for rotating frame relaxometry with improved robustness in the presence of B0$$ {\mathrm{B}}_0 $$ and B1+$$ {\mathrm{B}}_1^{+} $$ field inhomogeneities. Methods: The resilience of RAFF pulses against B0$$ {\mathrm{B}}_0 $$ and B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneities was studied using Bloch simulations. A parameterized extension of the RAFF formulation was introduced and used to derive a generalized inhomogeneity‐resilient RAFF (girRAFF) pulse. RAFF and girRAFF preparation efficiency, defined as the ratio of the longitudinal magnetization before and after the preparation (Mz(Tp)/M0$$ {M}_z\left({T}_p\right)/{M}_0 $$), were simulated and validated in phantom experiments. TRAFF$$ {T}_{\mathrm{RAFF}} $$ and TgirRAFF$$ {T}_{\mathrm{girRAFF}} $$ parametric maps were acquired at 3T in phantom, the calf muscle, and the knee cartilage of healthy subjects. The relaxation time maps were analyzed for resilience against artificially induced field inhomogeneities and assessed in terms of in vivo reproducibility. Results: Optimized girRAFF preparations yielded improved preparation efficiency (0.95/0.91 simulations/phantom) with respect to RAFF (0.36/0.67 simulations/phantom). TgirRAFF$$ {T}_{\mathrm{girRAFF}} $$ preparations showed in phantom/calf 6.0/4.8 times higher resilience to B0$$ {\mathrm{B}}_0 $$ inhomogeneities than RAFF, and a 4.7/5.3 improved resilience to B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneities. In the knee cartilage, TgirRAFF$$ {T}_{\mathrm{girRAFF}} $$ (53 ±$$ \pm $$ 14 ms) was higher than TRAFF$$ {T}_{\mathrm{RAFF}} $$ (42 ±$$ \pm $$ 11 ms). Moreover, girRAFF preparations yielded 7.6/4.9 times improved reproducibility across B0$$ {\mathrm{B}}_0 $$/B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneity conditions, 1.9 times better reproducibility across subjects and 1.2 times across slices compared with RAFF. Dixon‐based fat suppression led to a further 15‐fold improvement in the robustness of girRAFF to inhomogeneities. Conclusions: RAFF pulses display residual sensitivity to off‐resonance and pronounced sensitivity to B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneities. Optimized girRAFF pulses provide increased robustness and may be an appealing alternative for applications where resilience against field inhomogeneities is required. [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 degenerative whole‐joint disease in which the synovium and joint cartilage become inflamed and damaged. The essential role of inflammation in the development of OA has been recognized recently. Accordingly, simultaneous regulation of local inflammation and tissue degeneration is proposed as a promising therapeutic strategy. Herein, multifunctional biomimetic apoptotic nanovesicles (Apo‐NVs) are constructed with plasma membrane derived from apoptotic T cells. The anti‐inflammatory microRNA‐124 is further encapsulated into Apo‐NVs in the hope of achieving an enhanced immunomodulatory effect. It is found that apoptotic nanovesicles, including Apo‐NVs and Apo‐NVs‐miR‐124, both efficiently promote the M2 repolarization of M1 macrophages and inhibit the degenerative phenotype of chondrocytes. Further in vivo studies show that Apo‐NVs and Apo‐NVs‐miR‐124 alleviate synovial inflammation and protect cartilage tissue from degeneration in OA mice. The study highlights the potential of Apo‐NVs in treating OA and other inflammation‐related diseases. [ABSTRACT FROM AUTHOR]

Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease‐modifying drugs or other regulatory signals. In this study, a simple yet effective cell‐free nanoenabled Col‐PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic‐co‐glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col‐PLA) matrix. The developed nanoenabled scaffold successfully decreases IL‐1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col‐PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators', namely the complement component C5/C5a, C‐reactive protein, IL‐1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air‐pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies. [ABSTRACT FROM AUTHOR]

3D printing of articular cartilage tissue faces challenges like replicating its complex structure, time‐consuming in vitro stem cell culture, and a lack of robust in situ regeneration methods for osteochondral defects (OC). In response, an innovative approach utilizing pre‐designed bioink modular units for one‐step printing and immediate implantation is proposed, circumventing the need for prior in vitro stem cell cultivation. The resulting printed scaffold not only accurately reproduces the three‐layer structure and material gradient of articular cartilage tissue but also attains impressive compressive strength (6.3 MPa) through the reinforcement of hydroxyapatite nanofibers and the establishment of chemical bonds with hydrogels. Moreover, the scaffold integrates stem cell capturing and homing layers on its bottom and top layers via chemical crosslinking aptamer and loading poly (lactic‐co‐glycolic acid) (PLGA) nanospheres encapsulated with stromal cell‐derived factor‐1α (SDF‐1α), respectively. This design enables the specific capture of bone marrow mesenchymal stem cells (BMSCs) in vivo through aptamer interaction, followed by their mobilization to home in on the hyaline cartilage layer via the chemotaxis of SDF‐1α concentration gradient. Within the scaffold's microenvironment, these BMSCs undergo differentiation into distinct cells for each layer, effectively contributing to the repair of OC defects in rabbits. [ABSTRACT FROM AUTHOR]

Recent studies have shed light on the important role of aging in the pathogenesis of joint degenerative diseases and the anti‐aging effect of alpha‐ketoglutarate (αKG). However, whether αKG has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. Here, we demonstrate that αKG administration improves condylar cartilage health of middle‐aged/aged mice, and ameliorates pathological changes in a rat model of partial discectomy (PDE) induced TMJOA. In vitro, αKG reverses IL‐1β‐induced/H2O2‐induced decrease of chondrogenic markers (Col2, Acan and Sox9), and inhibited IL‐1β‐induced/ H2O2‐induced elevation of cartilage catabolic markers (ADAMTS5 and MMP13) in condylar chondrocytes. In addition, αKG downregulates senescence‐associated (SA) hallmarks of aged chondrocytes, including the mRNA/protein level of SA genes (p16 and p53), markers of nuclear disorders (Lamin A/C) and SA‐β‐gal activities. Mechanically, αKG decreases the expressions of p‐IKK and p‐NF‐κB, protecting TMJ from inflammation and senescence‐related damage by regulating the NF‐κB signaling. Collectively, our findings illuminate that αKG can ameliorate age‐related TMJOA and PDE‐induced TMJOA, maintain the homeostasis of cartilage matrix, and exert anti‐aging effects in chondrocytes, with a promising therapeutic potential in TMJOA, especially age‐related TMJOA. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a common degenerative disease characterized by continuous detachment of lubrication factors from damaged cartilage matrix. This study proposes a paradigm that combines natural polyanionic polysaccharides (hyaluronic acid, HA) with dopamine (DA) to design a synovial lubrication factors‐recruiting biomimetic polyphenolized lubrication system. The biomimetic lubricants can use DA's polarity and hydrophilic groups as specific binding sites of type II collagen's polarity and hydrophilic groups to stably bind cartilage surface, and further utilize molecular specific interaction to recruit detached, joint endogenous or chondrocytes expressed synovial lubrication factors, continuously forming supramolecular lubrication complex onto cartilage matrix to induce joint lubrication. Simultaneously, the biolubricants can also utilize catechol groups to eliminate anionic free radicals and resist reactive oxygen species invasion in the early stages of joint lubrication failure. The prepared biolubricants exhibit low coefficient of friction (µ < 0.08), which is attributed to fluid and hydration lubrication provided by HA and DA side chains through fluid dynamic effect and interfacial hydration adsorption. Cell and animal experiments also demonstrate polyphenolic biolubricants have good biocompatibility and promote cartilage regeneration. Therefore, the developed synovial lubricants‐recruiting biomimetic polyphenolized biolubricants have potential for treating osteoarthritis, and also provide a theoretical basis for other biological tissues with lubrication problems. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Sturgeon cartilage type II collagen peptides (SHCPs) can self‐assemble and be used to prepare collagen peptide assemblies. Self‐assembled peptides have great potential for applications in the food industry. In the present study, self‐assembled peptides were prepared from sturgeon cartilage and then characterized.The SHCPs self‐assembled and formed collagen peptide assemblies. After response surface experiment optimization, the optimal enzyme digestion process comprised 43.1 °C, 3.37 h and 0.96% enzyme addition, and the peptide yield was 78.46%. Physicochemical analysis showed that the SHCPs were amphiphilic, with an average molecular weight of 1081 Da, and were rich in hydrophobic amino acids. Peptide sequence identification showed that the peptides of SHCPs with polar amino acids followed by hydrophobic amino acids could be self‐assembled through hydrogen bonding and hydrophobic interaction. Through turbidity experiments, Fourier transform infrared spectroscopy and scanning electron microscopy, we demonstrated that SHCPs can self‐assemble into reticular and tubular structures under specific conditions. Furthermore, both the SHCPs‐Ca and SHCPs‐Mg assemblies were stabilized within a pH range consistent with that of the human gastrointestinal tract.The present study provides a simple and safe method for preparing novel self‐assembled peptide materials from sturgeon by‐products, providing a scientific basis for the exploitation of sturgeon cartilage and potentially reducing resource wastage. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly‐2‐acrylamide‐2‐methylpropanesulfonic acid sodium salt‐grafted aminofullerene, is developed to restore the cartilage lubrication system using an “In‐Out” strategy. The “Out” aspect involves reducing friction through a combination of hydration lubrication and ball‐bearing lubrication. Simultaneously, the “In” aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Understanding how porous biomaterials interact with cells at their surface and how they either promote or inhibit cellular processes has presented several challenges. Additive manufacturing enables the fabrication of scaffolds with distinct compositions and designs for different tissue engineering applications. To evaluate the in vitro performance of multiple printed materials, biochemical assays can be limiting in providing valuable insight and key information to select the best tissue destination. Omics technologies like proteomics are crucial for studying important cellular events and gathering valuable information about cellular processes and mechanisms. However, only few studies focus on proteomics to decipher cell–material interactions and cell differentiation on additive manufactured scaffolds. Here, scaffolds were fabricated using three polymers (polycaprolactone (PCL), poly(ethylene oxide)–poly(butylene terephthalate) (PEOT/PBT), and polylactic acid (PLA)) through additive manufacturing. Their chondrogenic and osteogenic potential were characterized and compared using human bone marrow‐derived mesenchymal stem cells (hBMSCs) through proteomics analysis. The 3D scaffolds were all hydrophilic and displayed Young's moduli close to those of bone or cartilage for PLA and PCL and PEOT/PBT, respectively. Biochemical assays indicated that PEOT/PBT and PLA scaffolds have a greater chondrogenic potential by higher glycosaminoglycan (GAG) and collagen deposition compared to PCL. PLA and PEOT/PBT showed to be more effective in promoting bone formation, as evidenced by higher calcium deposits detected by alizarin red staining, and higher alkaline phosphatase (ALP), especially for PLA in osteogenic medium. Proteomics data revealed the most distinct separation between conditions in chondrogenic medium, which had the highest protein identification rates. Pathway analysis showed that PCL did not induce any differentiation‐related pathways when compared to PEOT/PBT and PLA in any of the tested media conditions. Analysis of PEOT/PBT proteins showed pathways involved in chondrogenesis in all three media and pathways related to hypertrophic phenotype progression in chondrogenic medium. These data suggests that PEOT/PBT is a valuable candidate for cartilage and osteochondral applications, able to drive hBMSCs differentiation without the need of growth factors. PLA was also a valuable candidate for cartilage and bone applications by upregulating both chondrogenic and osteogenic‐related proteins in maintenance and chondrogenic media. In osteogenic and maintenance media, the upregulation of angiogenic proteins makes PLA a better candidate for bone application where vascularization is key. [ABSTRACT FROM AUTHOR]

Posttraumatic ankle osteoarthritis (PTAO) causes severe ankle and adjacent joint morbidity. We aimed to compare the treatment efficacy of previously tried and still applied intra‐articular injections and oral methylsulfonylmethane (MSM) at functional and histopathological level in PTAO animal model. Thirty‐two adult female Sprague‐Dawley rats were divided into four groups (Group 1: Control, Group 2: 0.06 g/kg/day MSM, Group 3: 0.04 mg/µL methylprednisolone [MP], Group 4: 0.04 mg/µL hyaluronic acid [HA]). MSM was started orally between Day 0 to the end of 8 weeks. Intra‐articular injections were applied to the right ankles of the subjects after surgery. All subjects were killed after radiological evaluation at the 8th week. Subsequently, functional (range of motion) and histopathological evaluation was performed. Radiological evaluation showed better results of the MP (p < 0.001) and MSM (p < 0.001) groups than the control group. Severity of osteoarthritis (OA) in the MP group was significantly less than in the HA group (p = 0.032). When the total Osteoarthritis Research Society International score was compared, the severity of OA was higher in the KS and HA groups than in the control group (p < 0.001). No significant statistical difference was found in the histopathological comparison of MSM and control group (p = 0.466). There was no difference between the groups in range of motion measurement according to the contralateral ankle joint. The radiological progression of OA was slowed in the MSM and MP groups, but significant histopathological worsening was found in the MP and HA applied groups. We suggest that the treatment methods used in daily practice need to be reviewed. [ABSTRACT FROM AUTHOR]

Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro‐inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well‐established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000‐fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = −0.6 to −0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E2 (PGE2), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA. [ABSTRACT FROM AUTHOR]

Optical coherence elastography (OCE) demonstrated impressive abilities for diagnosing tissue types/states using differences in their biomechanics. Usually, OCE visualizes tissue deformation induced by some additional stimulus (e.g., contact compression or auxiliary elastic‐wave excitation). We propose a new variant of OCE with osmotically induced straining (OIS‐OCE) and demonstrate its application to assess various stages of proteoglycan content degradation in cartilage. The information‐bearing signatures in OIS‐OCE are the magnitude and rate of strains caused by the application of osmotically active solutions onto the sample surface. OCE examination of the induced strains does not require special tissue preparation, the osmotic stimulation is highly reproducible, and strains are observed in noncontact mode. Several minutes suffice to obtain a conclusion. These features are promising for intraoperative method usage when express assessment of tissue state is required during surgical operations. The "waterfall" images demonstrate the development of cumulative osmotic strains in control and degraded cartilage samples. [ABSTRACT FROM AUTHOR]

Background: The polyarticular nature of Osteoarthritis (OA) tends to manifest in multi‐joints. Associations between cartilage health in connected joints can help identify early degeneration and offer the potential for biomechanical intervention. Such associations between hip and knee cartilages remain understudied. Purpose: To investigate T1p associations between hip‐femoral and acetabular‐cartilage subregions with Intra‐limb and Inter‐limb patellar cartilage; whole and deep‐medial (DM), deep‐lateral (DL), superficial‐medial (SM), superficial‐lateral (SL) subregions. Study Type: Prospective. Subjects: Twenty‐eight subjects (age 55.1 ± 12.8 years, 15 females) with none‐to‐moderate hip‐OA while no radiographic knee‐OA. Field Strength/Sequence: 3‐T, bilateral hip, and knee: 3D‐proton‐density‐fat‐saturated (PDFS) Cube and Magnetization‐Prepared‐Angle‐Modulated‐Partitioned‐k‐Space‐Spoiled‐Gradient‐Echo‐Snapshots (MAPSS). Assessment: Ages of subjects were categorized into Group‐1 (≤40), Group‐2 (41–50), Group‐3 (51–60), Group‐4 (61–70), Group‐5 (71–80), and Group‐6 (≥81). Hip T1p maps, co‐registered to Cube, underwent an atlas‐based algorithm to quantify femoral and acetabular subregional (R2–R7) cartilage T1p. For knee Cube, a combination of V‐Net architectures was used to segment the patellar cartilage and subregions (DM, DL, SM, SL). T1p values were computed from co‐registered MAPSS. Statistical Tests: For Intra‐and‐Inter‐limb, 5 optimum predictors out of 13 (Hip subregional T1p, age group, gender) were selected by univariate linear‐regression, to predict outcome (patellar T1p). The top five predictors were stepwise added to six linear mixed‐effect (LME) models. In all LME models, we assume the data come from the same subject sharing the same random effect. The best‐performing models (LME‐modelbest) selected via ANOVA, were tested with DM, SM, SL, and DL subregional‐mean T1p. LME assumptions were verified (normality of residuals, random‐effects, and posterior‐predictive‐checks). Results: LME‐modelbest (Intra‐limb) had significant negative and positive fixed‐effects of femoral‐R5 and acetabular‐R2 T1p, respectively (conditional‐R2 = 0.581). LME‐modelbest (Inter‐limb) had significant positive fixed‐effects of femoral‐R3 T1p (conditional‐R2 = 0.26). Data Conclusion: Significant positive and negative T1p associations were identified between load‐bearing hip cartilage‐subregions vs. ipsilateral and contralateral patellar cartilages respectively. The effects were localized on medial subregions of Inter‐limb, in particular. Evidence Level: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background: In vivo cartilage deformation has been studied by static magnetic resonance imaging (MRI) with in situ loading, but knowledge about strain dynamics after load onset and release is scarce. Purpose: To measure the dynamics of patellofemoral cartilage deformation and recovery in response to in situ loading and unloading by using MRI with prospective motion correction. Study Type: Prospective. Subjects: Ten healthy male volunteers (age: [31.4 ± 3.2] years). Field Strength/Sequence: T1‐weighted RF‐spoiled 2D gradient‐echo sequence with a golden angle radial acquisition scheme, augmented with prospective motion correction, at 3 T. Assessment: In situ knee loading was realized with a flexion angle of approximately 40° using an MR‐compatible pneumatic loading device. The loading paradigm consisted of 2 minutes of unloaded baseline followed by a 5‐minute loading bout with 50% body weight and an unloading period of 38 minutes. The cartilage strain was assessed as the mean distance between patellar and femoral bone–cartilage interfaces as a percentage of the initial (pre‐load) distance. Statistical Tests: Wilcoxon signed‐rank tests (significance level: P < 0.05), Pearson correlation coefficient (r). Results: The cartilage compression and recovery behavior was characterized by a viscoelastic response. The elastic compression ([−12.5 ± 3.1]%) was significantly larger than the viscous compression ([−7.6 ± 1.5]%) and the elastic recovery ([10.5 ± 2.1]%) was significantly larger than the viscous recovery ([6.1 ± 1.8]%). There was a significant residual offset strain ([−3.6 ± 2.3]%) across the cohort. A significant negative correlation between elastic compression and elastic recovery was observed (r = −0.75). Data Conclusion: The in vivo cartilage compression and recovery time course in response to loading was successfully measured via dynamic MRI with prospective motion correction. The clinical relevance of the strain characteristics needs to be assessed in larger subject and patient cohorts. Level of Evidence: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the relationship between the joint line convergence angle (JLCA) and the severity of medial knee osteoarthritis (OA). We hypothesise that JLCA is the most associated factor with the severity of medial knee OA. Methods: This retrospective study included a total of 202 knees that underwent either high tibial osteotomy or medial meniscus repair/partial resection. Kellgren–Lawrence grade and hip–knee–ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA) and JLCA were assessed from preoperative radiographs. Medial meniscus extrusion (MME) was measured using preoperative magnetic resonance imaging. The International Cartilage Research Society (ICRS) grade on the medial femoral condyle and medial tibial plateau were also assessed. The relationships between JLCA and Kellgren–Lawrence grades and MME and ICRS grades were analysed using Spearman's correlation test and regression analysis. Results: The JLCA was correlated with the Kellgren–Lawrence grade (R = 0.765, p < 0.001), MME (R = 0.638, p < 0.001), ICRS grade on the MFC (R = 0.586, p < 0.001) and the MTP (R = 0.586, p < 0.001). Regression analysis showed that age (p = 0.002) and JLCA (p < 0.001) were associated with Kellgren–Lawrence grade. Furthermore, JLCA was related to ICRS grade on the MFC (p < 0.001) and MTP (p < 0.001). Conclusion: The JLCA, reflecting radiological severity, meniscus status, and cartilage lesion, was the most associated alignment parameter in the severity of medial knee OA. The JLCA may be beneficial for quantitative assessment of medial knee OA. Level of Evidence: Level III, retrospective cohort study. [ABSTRACT FROM AUTHOR]

Purpose: The correlation of cartilage thickness measured by three‐dimensional (3D) magnetic resonance imaging (MRI) and the medial meniscal coverage ratio (MMCR), which presented pathology of the medial meniscus extrusion (MME) in 3D MRI, has not yet been elucidated. The study's purpose was to retrospectively verify whether the average cartilage thickness calculated by the automatic MRI 3D analysis system for each subregion was correlated with MMCR. Methods: A total of 60 patients underwent medial meniscus repair or high tibial osteotomy to treat their medial knee osteoarthritis. Cartilage thickness and MMCR were automatically calculated using 3D MRI software. The MMCR was defined as the ratio of the area covered by the meniscus within the medial tibial cartilage area to the total medial tibial cartilage area. The association between MMCR and the average cartilage thickness at 15 subregions in the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using Spearman's rank correlation coefficient. Results: Kellgren–Lawrence grade exhibited a negative correlation with MMCR and a positive correlation with MME width. Cartilage thickness in the MTP had a moderately positive correlation with MMCR at four subregions and a weakly positive correlation at another subregion. Cartilage thickness in the MFC showed a moderately positive correlation with MMCR at five subregions and a weakly positive correlation at one subregion. Conclusions: Cartilage thickness calculated by automatic MRI 3D analysis system had a positive correlation with MMCR for all subregions of the anterior and middle subregions in the MFC and for five regions of nine subregions of the anterior and middle subregions in the MTP. Level of evidence: Level II, cross‐sectional study (diagnosis). [ABSTRACT FROM AUTHOR]

Purpose: When dealing with the health status of the knee articular surface, the entire osteochondral unit has gained increasing attention, and in particular the subchondral bone, which plays a key role in the integrity of the osteochondral unit. The aim of this article was to discuss the current evidence on the role of the subchondral bone. Methods: Experts from different geographical regions were involved in performing a review on highly discussed topics about the subchondral bone, ranging from its etiopathogenetic role in joint degeneration processes to its prognostic role in chondral and osteochondral defects, up to treatment strategies to address both the subchondral bone and the articular surface. Discussion: Subchondral bone has a central role both from an aetiologic point of view and as a diagnostic tool, and its status was found to be relevant also as a prognostic factor in the follow‐up of chondral treatment. Finally, the recognition of its importance in the natural history of these lesions led to consider subchondral bone as a treatment target, with the development of osteochondral scaffolds and procedures to specifically address osteochondral lesions. Conclusion: Subchondral bone plays a central role in articular surface lesions from different points of view. Several aspects still need to be understood, but a growing interest in subchondral bone is to be expected in the upcoming future towards the optimization of joint preservation strategies. Level of Evidence: Level V, expert opinion. [ABSTRACT FROM AUTHOR]

Purpose: Patellar cartilage lesions are a frequent and challenging finding in orthopaedic clinical practice. This study aimed to evaluate a chitosan‐based scaffold's mid‐term clinical and imaging results patients with patellar cartilage lesions. Methods: Thirteen patients (nine men, four women, 31.3 ± 12.7 years old) were clinically evaluated prospectively at baseline, 12, 24 and at a final minimum follow‐up of 60 months (80.2 ± 14.7) with International Knee Documentation Committee (IKDC) subjective, Knee Injury and Osteoarthritis Outcome Score and Tegner scores. A magnetic resonance analysis was performed at the last follow‐up using the Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) 2.0 score. Results: An overall significant clinical improvement in the scores was observed from baseline to all follow‐ups, with stable clinical results from 24 months to the mid‐term evaluation. The IKDC subjective score passed from 46.3 ± 20.0 at baseline to 70.1 ± 21.5 at the last follow‐up (p = 0.029). Symptoms' duration before surgery negatively correlated with the clinical improvement from baseline to the final follow‐up (p = 0.013) and sex influenced the improvement of activity level from the preoperative evaluation to the final follow‐up, with better results in men (p = 0.049). In line with the clinical findings, positive results were documented in terms of cartilage repair quality with a mean MOCART 2.0 score of 72.4 ± 12.5. Conclusions: Overall, the use of this chitosan‐based scaffold provided satisfactory results with a stable clinical improvement up to mid‐term follow‐up, which should be confirmed by further high‐level studies to be considered a suitable surgical option to treat patients affected by patellar cartilage lesions. Level of Evidence: Level IV, prospective case series. [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]

Obesity is a known risk factor for development of osteoarthritis (OA). Numerical tools like finite‐element (FE) models combined with degenerative algorithms have been developed to understand the interplay between OA and obesity. In this study, we aimed to predict knee cartilage degeneration in a cohort of obese adults to investigate the importance of patient‐specific information on degeneration predictions. We used a validated FE modeling approach and three different age‐dependent functions (step‐wise, exponential, and linear) to simulate cartilage degradation under overloading in the knee joint. Gait motion analysis and magnetic resonance imaging data from 115 obese individuals with knee OA were used for musculoskeletal and FE modeling. Cartilage degeneration predictions were contrasted with Kellgren–Lawrence (KL) and Boston–Leeds Osteoarthritis Knee Score (BLOKS) grades. The findings show that overall, the similarities between numerical predictions and clinical measures were better for the medial (average area under the curve (AUC) = 0.62) compared to the lateral compartment (average AUC = 0.52) of the knee. Classification results for KL grades, full patient‐specific models and patient‐specific geometry with generic gait data showed higher AUC values (AUC = 0.71 and AUC = 0.68, respectively) compared to generic geometry and patient‐specific gait (AUC = 0.48). For BLOKS grades, AUC values for both full patient‐specific models and for patient‐specific geometry with generic gait locomotion were higher (AUC  = 0.66 and AUC = 0.64, respectively) compared to when the generic geometry and patient‐specific gait were used (AUC = 0.53). In summary, our study highlights the importance of considering individual information in knee OA prediction. Nevertheless, our findings suggest that personalized gait play a smaller role in the OA prediction and classification capacity than personalized joint geometry. [ABSTRACT FROM AUTHOR]

The incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed. [ABSTRACT FROM AUTHOR]

Objective: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. Methods: OA progression was examined in wild‐type and Irf1−/− mice using histologic assessments and microcomputed tomography analysis of whole‐joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase‐accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ‐H2AX foci and senescence‐associated beta‐galactosidase activity. Results: Our genome‐wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon‐responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down‐regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post‐traumatic OA in mice. Conclusion: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development. [ABSTRACT FROM AUTHOR]

Objective: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. Methods: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three‐dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One‐Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi‐square tests. Results: ACLD knees with CLs had significantly greater posterior tibial translation (7.7–8.0mm, 12%–18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6–5.5mm, 0%–23% GC, p < 0.001; 5.8–8.0mm, 86%–100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). Conclusion: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior. [ABSTRACT FROM AUTHOR]