Search

Healthy articular cartilage is characterized by extremely low friction and high compressive stiffness. This dual-functionality is tailored by its biphasic structure, whereby a fluid phase interacts with the extracellular matrix. Osteoarthritis (OA) causes structural changes, thereby altering the biomechanical and frictional properties. How the structural and functional properties of human cartilage are associated with OA remain unknown. To address this, we identified relationships between structural parameters, viscoelastic and frictional properties of degenerated human cartilage through correlation analyses. We found that cartilage friction was mainly influenced by its microscopic structure, while the viscoelastic properties were also related to the macroscopic structure. The viscoelastic and frictional properties displayed a weak correlation. These findings provide insights into the interplay between cartilage structure and its functional properties in OA, which might provide a basis for advancements in diagnosing and treating degenerated human cartilage. STATEMENT OF SIGNIFICANCE: Osteoarthritis causes changes in the cartilages biphasic structure, thereby affecting functionality by altered biomechanical and frictional properties. Currently a cartilage-preserving therapeutic option remains lacking, because the disease is not fully understood. In our correlation analyses, we investigated relationships between the structural, the viscoelastic and frictional properties of degenerated human cartilage. We found that cartilage friction was particularly dependent on the microscopic structure, while the viscoelastic properties also correlated with the macroscopic structure. The frictional properties displayed only a weak dependency with the viscoelastic properties. These new insights into the structure-function and inter-functional relationships may provide new options to advance the diagnosis and treatment of degenerated cartilage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests of personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fatigue failure in biological soft tissues plays a critical role in the etiology of chronic soft tissue injuries and diseases such as osteoarthritis (OA). Understanding failure mechanisms is hindered by the decades-long timescales over which damage takes place. Analyzing the factors contributing to fatigue failure requires the help of validated computational models developed for soft tissues. This study presents a framework for fatigue failure of fibrous biological tissues based on reaction kinetics, where the composition of intact and fatigued material regions can evolve via degradation and breakage over time, in response to energy-based fatigue and damage criteria. Using reactive constrained mixture theory, material region mass fractions are governed by the axiom of mass balance. Progression of fatigue is controlled by an energy-based reaction rate, with user-selected probability functions defining the damage propensity of intact and fatigued material regions. Verification of this reactive theory, which is implemented in the open-source FEBio finite element software, is provided in this study. Validation is also demonstrated against experimental data, showing that predicted damage can be linked to results from biochemical assays. The framework is also applied to study fatigue failure during frictional contact of cartilage. Simulating previous experiments suggests that frictional effects slightly increase fatigue progression, but the main driver is cyclic compressive contact loading. This study demonstrated the ability of theoretical models to complement and extend experimental findings, advancing our understanding of the time progression of fatigue in biological tissues., (Copyright © 2024 by ASME.)

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to conduct arthroscopic evaluation of cartilage electromechanical properties and establish their correlation with International Cartilage Repair Society (ICRS) grading scores., Methods: In 18 patients, quantitative parameter (QP) measurements were taken on the weight-bearing surface of the medial femoral condyle. Adjacently, the same site was graded using ICRS scores (0-4). Electromechanical QPs for ICRS grades 0 to 3 were obtained during arthroscopy, while complete grade 4 injuries were assessed using femur cartilage-bone blocks from knee arthroplasty. The QP values for ICRS grades 0 to 2 were compared with grades 3 and 4 using Welch t test. The corresponding QP values were assigned to ICRS grades 0 to 4 and compared using Welch ANOVA (analysis of variance). Pearson's coefficient evaluated QP-ICRS grade relationship., Results: Healthy grade 0 cartilage displayed a mean QP value of 10.5 (±2.8 SD, n = 4). The ICRS grade 1 and grade 2 injuries were associated with QP values of 12 (±0.7, n = 2) and 13.25 (±1.77, n = 2), respectively. The grade 3 defects had QP values of 20.43 (±4.84, n = 4), whereas complete grade 4 defects showed electromechanical values of 30.17 (±2.19, n = 6). Significant differences in QP values were observed between ICRS grades 0 to 2 (mean QP 11.56 ± 2.3, n = 8) and grades 3 and 4 (26.27 ± 6, n = 10; P < 0.0001). Pearson's correlation coefficient of 0.9 indicated a strong association between higher ICRS cartilage injury grades and elevated QP values ( P < 0.0001)., Conclusion: Arthroscopic electromechanical QP assessment robustly correlates with ICRS scores. The QP values for ICRS grades 0 to 2 are significantly lower, compared with grades 3 and 4., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Physics-based modeling methods have the potential to investigate the mechanical factors associated with knee osteoarthritis (OA) and predict the future radiographic condition of the joint. However, it remains unclear what level of detail is optimal in these methods to achieve accurate prediction results in cohort studies. In this work, we extended a template-based finite element (FE) method to include the lateral and medial compartments of the tibiofemoral joint and simulated the mechanical responses of 97 knees under three conditions of gait loading. Furthermore, the effects of variations in cartilage thickness and failure equation on predicted cartilage degeneration were investigated. Our results showed that using neural network-based estimations of peak knee loading provided classification performances of 0.70 (AUC, p < 0.05) in distinguishing between knees that developed severe OA or mild OA and knees that did not develop OA eight years after a healthy radiographic baseline. However, FE models incorporating subject-specific femoral and tibial cartilage thickness did not improve this classification performance, suggesting there exists an optimal point between personalized loading and geometry for discrimination purposes. In summary, we proposed a modeling framework that streamlines the rapid generation of individualized knee models achieving promising classification performance while avoiding motion capture and cartilage image segmentation., (© 2024. The Author(s).)

Purpose: High body mass index (BMI) is a strong predictor of posttraumatic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR). Altered gait mechanics are independently affected by BMI and ACLR, and influence OA risk. Yet, evidence directly assessing the impact of high BMI on gait or cartilage characteristics after ACLR are limited. Here, we evaluated if high BMI moderates associations between gait and trochlear cartilage structure in individuals with ACLR., Methods: Treadmill walking biomechanics were evaluated in 40 normal BMI and 24 high BMI participants with ACLR at self-selected speeds. Normalized and absolute peak and cumulative loads (i.e., impulse) were extracted for peak knee flexion and adduction moments (KFM, KAM) and vertical ground reaction force (GRF). Medial and lateral femoral cartilage thickness and medial/lateral thickness ratios were assessed via ultrasound., Results: Those with ACLR and high BMI walked with reduced normalized peak vertical GRFs, and greater absolute peak and cumulative loads compared with normal BMI individuals with ACLR. Those with ACLR and high BMI also exhibited thinner cartilage and greater medial/lateral ratios in ACLR limbs compared with contralateral limbs whereas normal BMI individuals with ACLR exhibited thicker ACLR limb cartilage. Lastly, greater peak KAM and KAM cumulative load were associated with thicker lateral cartilage and lesser medial/lateral thickness ratios, but only in the high BMI group., Conclusions: We observed those with high BMI after ACLR exhibited trochlear cartilage structural alterations not observed in normal BMI patients, whereas differential associations between loading outcomes and cartilage thickness in ACLR knees were observed between groups. Those with high BMI after ACLR may require different therapeutic strategies to optimize joint health in this subset of patients., (Copyright © 2024 by the American College of Sports Medicine.)

Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. Although structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate (SBP), and subchondral trabecular bone (STB) using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified SBP microstructure, plate-and-rod morphological properties of the STB using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while Osteoarthritis Research Society International score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the SBP, thickness and tissue mineral density were higher in moderate and severe OA regions. Tissue modulus of STB was lower in moderate OA regions despite a thicker and more mineralized SBP; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and STB properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Patellofemoral osteoarthritis (PFOA) is the result of degeneration and loss of articular cartilage of the patella and trochlea, and is a common cause of anterior knee pain. PFOA is triggered by insufficient adaptation to overload of the articular cartilage of the PF joint created by abnormal biomechanics. It is important to understand the pathophysiology and natural history to make the diagnosis and to plan treatment. Innate factors including malalignment, patellar instability, kinematic disorders, and acquired factors like trauma, obesity, and endocrine diseases have been found to be causes of PFOA. Genetic predisposition is also described as a contributing cause but without much scientific evidence. The diagnosis will be based on clinical manifestations, such as anterior knee pain aggravated by overloading activities, identification of risk factors, and exclusion of referred pain from other pathologies, followed by a systematic and structured physical examination. Imaging will be useful for assessing the presence of early osteoarthritis in the other compartments, for classification of the PFOA, and to identify features to establish an adequate treatment. This paper discusses varying management options for different causes of patellofemoral disease and explains the complexity of the PF joint and its often poorly understood biomechanics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore associations between hip muscle strength and cartilage defects (presence and severity) on magnetic resonance imaging (MRI) in young adults with hip/groin pain participating in sub-elite football., Design: Sub-elite football players with hip/groin pain (>6 months) completed assessments of isometric hip strength and functional task performance. Hip cartilage defects were assessed using the Scoring Hip Osteoarthritis with MRI tool. This exploratory, cross-sectional study used logistic and negative binomial models to assess the relationships between hip muscle strength or functional task performance and hip cartilage defects, controlling for body mass index, age, testing site and cam morphology, incorporating sex-specific interaction terms., Results: One hundred and eighty-two (37 women) sub-elite (soccer or Australian football) players with hip/groin pain (age 26 ± 7 years) were included. Greater hip extension strength was associated with higher cartilage total score (adjusted incidence rate ratio [aIRR] 1.01, 95%CI: 1.0 to 1.02, p = 0.013) and superolateral cartilage score (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI): 1.01 to 1.06, p < 0.01). In female sub-elite football players, greater hip external rotation strength was associated with lateral cartilage defects (aOR 1.61, 95%CI: 1.05 to 2.48, p = 0.03) and higher cartilage total score (aIRR 1.25, 95%CI: 1.01 to 1.66, p = 0.042). A one-repetition increase in one-leg rise performance was related to lower odds of superomedial cartilage defects (aOR 0.96, 95%CI: 0.94 to 0.99, p < 0.01)., Conclusions: Overall, there were few associations between peak isometric hip muscle strength and overall hip cartilage defects. It is possible that other factors may have relevance in sub-elite football players. Additional studies are needed to support or refute our findings that higher one leg rise performance was associated with reduced superomedial cartilage defect severity and greater hip extension strength was related to higher cartilage defect severity scores., Competing Interests: Competing interests The authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Articular cartilage exhibits site-specific biomechanical properties. However, no study has comprehensively characterized site-specific cartilage properties from the same knee joints at different stages of osteoarthritis (OA). Cylindrical osteochondral explants (n = 381) were harvested from donor-matched lateral and medial tibia, lateral and medial femur, patella, and trochlea of cadaveric knees (N = 17). Indentation test was used to measure the elastic and viscoelastic mechanical properties of the samples, and Osteoarthritis Research Society International (OARSI) grading system was used to categorize the samples into normal (OARSI 0-1), early OA (OARSI 2-3), and advanced OA (OARSI 4-5) groups. OA-related changes in cartilage mechanical properties were site-specific. In the lateral and medial tibia and trochlea sites, equilibrium, instantaneous and dynamic moduli were higher (p < 0.001) in normal tissue than in early and advanced OA tissue. In lateral and medial femur, equilibrium, instantaneous and dynamic moduli were smaller in advanced OA, but not in early OA, than in normal tissue. The phase difference (0.1-0.25 Hz) between stress and strain was significantly smaller (p < 0.05) in advanced OA than in normal tissue across all sites except medial tibia. Our results indicated that in contrast to femoral and patellar cartilage, equilibrium, instantaneous and dynamic moduli of the tibia and trochlear cartilage decreased in early OA. These may suggest that the tibia and trochlear cartilage degrades faster than the femoral and patellar cartilage. The information is relevant for developing site-specific computational models and engineered cartilage constructs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone., Competing Interests: The authors declare no conflict of interest.

Degeneration of articular cartilage is often triggered by a small tissue crack. As cartilage structure and composition change with age, the mechanics of cracked cartilage may depend on the tissue age, but this relationship is poorly understood. Here, we investigated cartilage mechanics and crack deformation in immature and mature cartilage exposed to a full-thickness tissue crack using indentation testing and histology, respectively. When a cut was introduced, tissue cracks opened wider in the mature cartilage compared to the immature cartilage. However, the opposite occurred upon mechanical indentation over the cracked region. Functionally, the immature-cracked cartilages stress-relaxed faster, experienced increased tissue strain, and had reduced instantaneous stiffness, compared to the mature-cracked cartilages. Taken together, mature cartilage appears to withstand surface cracks and maintains its mechanical properties better than immature cartilage and these superior properties can be explained by the structure of their collagen fibrous network., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Objective: To observe expression of CD38, a key modulator of nicotinamide dinucleotide (NAD+) metabolism in mice with knee osteoarthritis, and protective effect of CD38 inhibition during the osteoarthritis (OA) development., Method: The destabilization of the medial meniscus (DMM) model was performed in mice to mimic the process of OA. Immunofluorescence of CD38 was performed to evaluate its response during the OA process. Limb bud-derived mesenchymal cells were isolated for micromass culture. 100 nM or 1 μM CD38 inhibitor (78c) treatment for 14 days and CD38 sgRNA infection were then used to explore the effects of chondrogenic differentiation via Alcian blue staining. The expressions of chondrogenic markers were detected using RT-PCR and Western blot. To explore the protective effect of CD38 inhibitor on cartilage degradation during OA in vivo, a CD38 inhibitor was injected into the knee joint after DMM operations. Micro-CT analysis and Safranin O-fast green staining were used to evaluate subchondral bone micro-architecture changes and cartilage degeneration., Results: Compared to the control group, the CD38 expression in superficial cartilage was obviously increased in DMM group (P < 0.05). During the normal chondrogenic differentiation, the extracellular matrix formed and expression of Sox9, Col2, aggrecan increased apparently while CD38 expression decreased, which could be reversed with ablation of CD38 in limb bud-derived mesenchymal cells. Consistent with findings in vitro, CD38 blockage via CD38 inhibitor injection protected against osteosclerosis in medial subchondral bone and cartilage degeneration in DMM-induced experimental mice. Compared to the Sham group, DMM mice showed significantly increased values of BV and BV/TV in subchondral bone (P < 0.05) and Mankin score, which could be rescued by 78c treatment (P < 0.05). Also the CD38 inhibitor contributed to homeostasis of anabolism and catabolism by upregulating Sox9, Col2, aggrecan and downregulating Runx2, Col10 and Mmp13., Conclusion: This study primarily implicates CD38 as an important regulator of chondrogenic differentiation. Inhibition of CD38 demonstrated protection against cartilage degeneration, which suggests that CD38 could be a potential therapeutic target for OA., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Introduction: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology., Materials and Methods: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA., Results: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression., Conclusions: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA., (© 2021. The Japanese Society Bone and Mineral Research.)

Post-traumatic osteoarthritis (PTOA) of the knee is often attributed to anterior cruciate ligament (ACL) and meniscus injury. The development of PTOA, however, does not seem to depend on whether or not the damaged ACL is reconstructed. There has been a need to develop animal models to study the mechanisms of PTOA following reconstruction of a traumatized knee. Eighteen rabbits underwent closed-joint trauma to produce ACL rupture and meniscus damage. Then, for the first time, the traumatized knee was surgically repaired in this animal model. Upon euthanasia at 1-, 3- or 6-month post-trauma, joint stability, cartilage morphology and mechanical properties, as well as histology of the cartilage and subchondral bone were evaluated. Trauma-induced knee injury involved 72% mid-substance ACL rupture, 28% partial ACL tear and 56% concurrent medial meniscal damage. ACL reconstruction effectively restored joint stability by reducing joint laxity to a level similar to that in the contralateral intact knee. Compared to their contralateral controls, reconstructed limbs showed osteoarthritic changes to the cartilage and subchondral bone as early as 1-month post-trauma. The degeneration progressed over time up to 6-month. Overall, the medial compartments had more tissue damage than their corresponding lateral counterparts. Damage patterns to the ACL, the frequency of observed concurrent meniscal injury, and reductions in cartilage integrity and health were consistent with clinical observations of human patients who undergo ACL injury and reconstruction. Thus, we believe the combined closed-joint injury and surgical repair lapine model of PTOA, being first-ever and clinically relevant, shows promise to evaluate well-targeted therapeutics and other interventions for this chronic disease., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

This study aimed to investigate the relationship between the micro structural properties of the subchondral trabecular bone (STB) and the macro mechanical properties of the articular cartilage (AC) in patients with osteoporotic (OP) and osteopenic (OPE) fractures. Sixteen femoral head samples (OP;OPE, n = 8 each) were obtained from female patients who underwent hip hemiarthroplasty. STB and AC specimens were harvested from those heads. Bone specimens were scanned using µ-CT to determine the micro structural properties. In-situ nondestructive compressive tests were performed for the cartilages to obtain elastic properties. The finite element technique was implemented on STB models created from µ-CT data to compute apparent elastic modulus. In addition, dynamic cyclic destructive tests were performed on STB and AC specimens to assess failure cycles. The results demonstrated that STB specimens in OPE group have more interconnected structure and higher cyclic dynamic strength than those in OP group. Furthermore, bone mineral density, failure cycle, and trabecular number of STB were positively correlated with the cartilage failure cycle, which indicates that STB alteration may affect the macroscopic mechanical properties of AC. The findings suggest that STB loss correlates with a decrease in cartilage strength and that improving of bone quality may prevent cartilage weakness., (© 2021. Biomedical Engineering Society.)

Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair. Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects. Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery. Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair. Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors. Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) ( n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice ( n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM ( p =0.002 and p <0.0001, respectively) and loaded (both p <0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development., Competing Interests: The research leading to these results has received technical support from 3Dmagination Ltd, Didcot, UK. KM is co-founder and director of 3Dmagination Ltd in Oxfordshire, UK, a company which provides training and consultancy in 3D and 4D imaging. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Samvelyan, Madi, Törnqvist, Javaheri and Staines.)

Aim: To compare and assess T 1rho values of the femorotibial cartilage compartments and subregional menisci in patients with hyperuricaemia at 3 T., Materials and Methods: Thirty-two patients were enrolled in the study and were subdivided into two subgroups: 15 healthy controls (three women, 12 men; mean age = 45.3 ± 10.9 years, age range 25-72 years) and 17 patients with asymptomatic hyperuricaemia (two women, 15 men; mean age = 44.4 ± 12.7 years, age range 26-77 years). All patients were evaluated using 3 T magnetic resonance imaging (MRI) using an eight-channel phased-array knee coil (transmit-receive). Wilcoxon's rank sum test and analysis of covariance (ANCOVA) were conducted to determine whether there were any statistically significant differences in the T 1rho values of the femorotibial cartilage compartments and subregional menisci between the two subgroups., Results: Lateral tibial cartilage (45.8 ± 2.9 ms) in the healthy subgroup had significantly lower (p<0.05) T 1rho values than those of all subcompartments of the femorotibial cartilage in the hyperuricaemia subgroup. The lateral femoral cartilage (LF) in hyperuricaemia (54.6 ± 3.9 ms) subgroup had significantly higher (p<0.05) T 1rho values than those of all subcompartments of the femorotibial cartilage except the LF in the healthy subgroup. Significantly higher (p<0.05) T 1rho values existed in the LF of the healthy (54.6 ± 4.7 ms) subgroup in comparison with those of all subcompartments of femorotibial cartilage except the LF in hyperuricaemia subgroup., Conclusions: T 1rho values in certain compartments of the femorotibial cartilage in patients with hyperuricaemia are elevated compared to those in healthy patients presumably due to reduced proteoglycan content, to which particular attention should be paid when diagnosing and treating the patients with hyperuricaemia in a clinical setting., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) degrades articular cartilage and weakens its function. Modern fibril-reinforced poroelastic (FRPE) computational models can distinguish the mechanical properties of main cartilage constituents, namely collagen, proteoglycans, and fluid, thus, they can precisely characterize the complex mechanical behavior of the tissue. However, these properties are not known for human femoral condyle cartilage. Therefore, we aimed to characterize them from human subjects undergoing knee replacement and from deceased donors without known OA. Multi-step stress-relaxation measurements coupled with sample-specific finite element analyses were conducted to obtain the FRPE material properties. Samples were graded using OARSI scoring to determine the severity of histopathological cartilage degradation. The results suggest that alterations in the FRPE properties are not evident in the moderate stages of cartilage degradation (OARSI 2-3) as compared with normal tissue (OARSI 0-1). Drastic deterioration of the FRPE properties was observed in severely degraded cartilage (OARSI 4). We also found that the FRPE properties of femoral condyle cartilage related to the collagen network (initial fibril-network modulus) and proteoglycan matrix (non-fibrillar matrix modulus) were greater compared to tibial and patellar cartilage in OA. These findings may inform cartilage tissue-engineering efforts and help to improve the accuracy of cartilage representations in computational knee joint models., (© 2021. The Author(s).)

Objective: The relationship between in vivo knee load predictions and longitudinal cartilage changes has not been investigated. We undertook this study to develop an equation to predict the medial tibiofemoral contact force (MCF) peak during walking in persons with instrumented knee implants, and to apply this equation to determine the relationship between the predicted MCF peak and cartilage loss in patients with knee osteoarthritis (OA)., Methods: In adults with knee OA (39 women, 8 men; mean ± SD age 61.1 ± 6.8 years), baseline biomechanical gait analyses were performed, and annualized change in medial tibial cartilage volume (mm 3 /year) over 2.5 years was determined using magnetic resonance imaging. In a separate sample of patients with force-measuring tibial prostheses (3 women, 6 men; mean ± SD age 70.3 ± 5.2 years), gait data plus in vivo knee loads were used to develop an equation to predict the MCF peak using machine learning. This equation was then applied to the knee OA group, and the relationship between the predicted MCF peak and annualized cartilage volume change was determined., Results: The MCF peak was best predicted using gait speed, the knee adduction moment peak, and the vertical knee reaction force peak (root mean square error 132.88N; R 2 = 0.81, P < 0.001). In participants with knee OA, the predicted MCF peak was related to cartilage volume change (R 2 = 0.35, β = -0.119, P < 0.001)., Conclusion: Machine learning was used to develop a novel equation for predicting the MCF peak from external biomechanical parameters. The predicted MCF peak was positively related to medial tibial cartilage volume loss in patients with knee OA., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The circadian clock is a specialized cell signalling pathway present in all cells. Loss of clock function leads to tissue degeneration and premature ageing in animal models demonstrating the fundamental importance of clocks for cell, tissue and organism health. There is now considerable evidence that the chondrocyte circadian clock is altered in OA. The purpose of this review is to summarize current knowledge regarding the nature of the change in the chondrocyte clock in OA and the implications of this change for disease development. Expression of the core clock component, BMAL1, has consistently been shown to be lower in OA chondrocytes. This may contribute to changes in chondrocyte differentiation and extracellular matrix turnover in disease. Circadian clocks are highly responsive to environmental factors. Mechanical loading, diet, inflammation and oxidative insult can all influence clock function. These factors may contribute to causing the change in the chondrocyte clock in OA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Articular chondroprogenitors are a promising contender for cartilage repair due to their inherent nature which stands primed for chondrogenesis and minimal hypertrophic preponderance. Platelet rich plasma (PRP) has been extensively used for treating cartilage defects and osteoarthritis (OA), due to its chondro-inductive properties and abundant pool of growth factors. The aim of this study was to assess the efficacy of chondroprogenitors injected with PRP versus PRP alone in the healing of experimentally created early OA and osteochondral defects (OCD) in a rabbit model., Methods: Adult New Zealand White male rabbits were used for cell and PRP isolation. Chondroprogenitors were isolated by fibronectin adhesion assay, labelled with iron oxide, characterized for surface markers, differential potential and expanded. PRP was isolated by double spin centrifugation using a TriCell kit. Study groups included (a) Monosodium iodoacetate induced early OA and (b) critical OCD. Following intervention (test arm: PRP+ chondroprogenitors and control arm: PRP), assessment was performed at 6- and 12-weeks which included histopathological examination and scoring (OARSI and Modified Wakitani score), immunohistochemistry analysis (Collagen type II and X) and synovial fluid S100A12 levels., Results and Conclusion: Comparable, evident healing was noticed in both test and control arms when the OA group samples were assessed at both time points. In the OCD group, PRP alone exhibited significantly better results than the test arm, although repair was notable in both interventions. Further evaluation of chondroprogenitors is required to assess their role as a standalone therapy and in combination with PRP to further cartilage regeneration., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: This study aimed 1) to determine whether talar cartilage deformation measured via ultrasonography (US) after standing and hopping loading protocols differs between chronic ankle instability (CAI) patients and healthy controls and 2) to determine whether the US measurement of cartilage deformation reflects viscoelasticity between standing and hopping protocols., Methods: A total of 30 CAI and 30 controls participated. After a 60-min off-loading period, US images of the talar cartilage were acquired before and after static (2-min single-leg standing) and dynamic (60 single-leg forward hops) loading conditions. We calculated cartilage deformation by assessing the change in average thickness (mm) for overall, medial, and lateral talar cartilage. The independent variables include time (Pre60 and postloading), condition (standing and dynamic loading), and group (CAI and control). A three-way mixed-model repeated-measures ANCOVA and appropriate post hoc tests were used to compare cartilage deformation between the groups after static and dynamic loading., Results: After the static loading condition, those with CAI had greater talar cartilage deformation compared with healthy individuals for overall (-10.87% vs -6.84%, P = 0.032) and medial (-12.98% vs -5.80%, P = 0.006) talar cartilage. Similarly, the CAI group had greater deformation relative to the control group for overall (-8.59% vs -3.46%, P = 0.038) and medial (-8.51% vs -3.31%, P = 0.043) talar cartilage after the dynamic loading condition. In the combined cohort, cartilage deformation was greater after static loading compared with dynamic in overall (-8.85% vs -6.03%, P = 0.003), medial (-9.38% vs -5.91%, P = 0.043), and lateral (-7.90% vs -5.65%, P = 0.009) cartilage., Conclusion: US is capable of detecting differences in cartilage deformation between those with CAI and uninjured controls after standardized physiologic loads. Across both groups, our results demonstrate that static loading results in greater cartilage deformation compared with dynamic loading., (Copyright © 2021 by the American College of Sports Medicine.)

Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated arthritic changes in the medial knee compartment that bears the highest loads across the knee after actual and simulated spaceflight, and recovery with subsequent full weight-bearing. Cartilage and meniscal degradation in mice were measured via microCT, histology, and proteomics and/or biochemically after: (1) ~ 35 days on the International Space Station (ISS); (2) 13-days aboard the Space Shuttle Atlantis; or (3) 30 days of HLU, followed by a 49-day weight-bearing readaptation with/without exercise. Cartilage degradation post-ISS and HLU occurred at similar spatial locations, the tibial-femoral cartilage-cartilage contact point, with meniscal volume decline. Cartilage and meniscal glycosaminoglycan content were decreased in unloaded mice, with elevated catabolic enzymes (e.g., matrix metalloproteinases), and elevated oxidative stress and catabolic molecular pathway responses in menisci. After the 13-day Shuttle flight, meniscal degradation was observed. During readaptation, recovery of cartilage volume and thickness occurred with exercise. Reduced weight-bearing from either spaceflight or HLU induced an arthritic phenotype in cartilage and menisci, and exercise promoted recovery.

Articular cartilage heals poorly but experiences mechanically induced damage across a broad range of loading rates and matrix integrity. Because loading rates and matrix integrity affect cartilage mechanical responses due to poroviscoelastic relaxation mechanisms, their effects on cartilage failure are important for assessing and preventing failure. This paper investigated rate- and integrity-dependent crack nucleation in cartilage from pre- to post-relaxation timescales. Rate-dependent crack nucleation and relaxation responses were obtained as a function of matrix integrity through microindentation. Total work for crack nucleation increased with decreased matrix integrity, and with decreased loading rates. Critical energy release rate of intact cartilage was estimated as 2.39 ± 1.39 to 2.48 ± 1.26 kJ m -2 in a pre-relaxation timescale. These findings showed that crack nucleation is delayed when cartilage can accommodate localized loading through poroviscoelastic relaxation mechanisms before fracture at a given loading rate and integrity state.

Aim: Osteoarthritis (OA) is the most common chronic joint disorder, resulting from the breakdown of joint cartilage. It occurs in the knees, hands, and hips, leading to pain, stiffness, inflammation, and swelling., Methods: In this study, 100 hand and knee OA patients, meeting the American College of Rheumatology criteria were included in the case group, and 100 healthy individuals were allocated to the control group. Blood samples were collected from the participants. After DNA extraction, genotyping was carried out for GDF5 rs143383 C/T polymorphism by allele-specific polymerase chain reaction (ASPCR) and for D-repeat alleles of asporin (ASPN) by conventional PCR assay., Results: The results showed that the frequency of the D14 allele of ASPN was significantly higher than other alleles in the case group (P = .0001). Also, the frequency of the D14 allele among women was significantly higher than in men (P = .004). Moreover, the frequency of the TT allele in GDF5 rs143383 C/T polymorphism was significantly higher than the CC and CT alleles in the case group, compared with the control group (P = .001). A significant difference was found between the TT allele and other alleles in female and male patients compared with the control group (P = .02)., Conclusions: The D14 allele of the ASPN gene and TT allele of the GDF5 gene (rs143383 + 104T/C) are associated with hand and knee OA in the Kurdish population, indicating that these alleles could be risk factors for OA, at least in our populations., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a validated technique for evaluating cartilage health in developmental dysplasia of the hip (DDH), which can be a helpful prognosticator for the response to surgical treatments. dGEMRIC requires intravenous injection of gadolinium contrast, however, which adds time, expense, and possible adverse reactions to the imaging procedure. Newer MRI cartilage mapping techniques such as T1 rho (ρ) and T2* have been performed in the hip without the need for any contrast, although it is unknown whether they are equivalent to dGEMRIC., Question/purpose: In this study, our purpose was to determine the correlation between the relaxation values of three cartilage mapping techniques, dGEMRIC, T1ρ, and T2*, in patients with DDH., Methods: Fifteen patients with DDH (three male, 12 female; mean age 29 ± 9 years) scheduled for periacetabular osteotomy underwent preoperative dGEMRIC, T1ρ, and T2* MRI at 3T with quantitative cartilage mapping. The outcomes of dGEMRIC, T1ρ, and T2* mapping were calculated for three regions of interest (ROI) to analyze the weightbearing cartilage of the hip: global ROI, anterior and posterior ROI, and further subdivided into medial, intermediate, and lateral to generate six smaller ROIs. The correlation between the respective relaxation time values was evaluated using the Spearman correlation coefficient (rS) for each ROI, categorized as negligible, weak, moderate, strong, or very strong. The relaxation values within the subdivided ROIs were compared for each of the three cartilage mapping techniques using the Kruskal-Wallis test., Results: There was a moderate correlation of T1ρ and T2* relaxation values with dGEMRIC relaxation values. For the global ROI, there was a moderate correlation between dGEMRIC and T2* (moderate; rS = 0.63; p = 0.01). For the anterior ROI, a moderate or strong correlation was found between dGEMRIC and both T1ρ and T2*: dGEMRIC and T1ρ (strong; rS = -0.71; p = 0.003) and dGEMRIC and T2* (moderate; rS = 0.69; p = 0.004). There were no correlations for the posterior ROI. The mean dGEMRIC, T1ρ, and T2* relaxation values were not different between the anterior and posterior ROIs nor between the subdivided six ROIs., Conclusion: Quantitative T1ρ and T2* cartilage mapping demonstrated a moderate correlation with dGEMRIC, anteriorly and globally, respectively. However, the clinical relevance of such a correlation remains unclear. Further research investigating the correlation of these two noncontrast techniques with clinical function and outcome scores is needed before broad implementation in the preoperative investigation of DDH., Level of Evidence: Level II, diagnostic study., Competing Interests: One of the authors certifies that he (PEB) has received funding, during the study period, in an amount of USD 10,000 to USD 100,000 from Zimmer Biomet. Each remaining author certifies that neither he, nor any member of his immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 by the Association of Bone and Joint Surgeons.)

Posterior cruciate ligament (PCL) injuries commonly occur in association with participation in sporting or recreational activities or due to a direct trauma. Cartilage and meniscal lesions are prevalent in PCL-injured knees with increasing likelihood and severity based on extent and duration of trauma to the knee. As such, comprehensive diagnostics should be performed to ascertain all related pathology, and patients should be thoroughly educated regarding treatment options, likely sequelae including posttraumatic osteoarthritis, and associated outcomes. Treatments should address the joint as an organ, ensuring stability, alignment, and functional tissue restoration are optimized by the most efficient and effective means possible. Compliance with patient- and procedure-specific postoperative management protocols is critical for optimizing successful outcomes for these complex cases. The objectives of this review article are to highlight the likelihood and importance of osteochondral and meniscal pathology in the PCL-injured knee, and to provide the best current evidence regarding comprehensive evaluation and management for PCL-injured knees with cartilage and/or meniscal comorbidities., Competing Interests: J.P.S. reports grants and personal fees from Arthrex, Inc., grants from DePuy Synthes, other from Journal of Knee Surgery, grants from National Institutes of Health (NIAMS & NICHD), personal fees and other from Thieme, grants from U.S. Department of Defense, other from AO Foundation, other from American Orthopaedic Association, other from AO North America, grants from Coulter Foundation, other from Mid-America Orthopaedic Association, personal fees from Orthopedic Designs North America, personal fees from Smith & Nephew, outside the submitted work. J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from AthleteIQ, grants from ConforMIS, personal fees from CONMED Linvatec, grants from Coulter Foundation, grants from DePuy Synthes, grants and personal fees from Eli Lilly, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Foundation, grants from National Institutes of Health (NIAMS and NICHD), grants from Purina, grants from Sites Medical, personal fees and other from Thieme, grants from TissueGen Inc, personal fees from Trupanion, grants from U.S. Department of Defense, grants from Zimmer-Biomet, outside the submitted work., (Thieme. All rights reserved.)

Objective: To address the need for early knee osteoarthritis (OA) markers by testing if longitudinal cartilage thickness changes are associated with specific biomechanical and biological measures acquired at a baseline test in asymptomatic aging subjects., Design: Thirty-eight asymptomatic subjects over age 45 years were studied at baseline and at an average of 7-9 year follow-up. Gait mechanics and knee MRI were measured at baseline and MRI was obtained at follow-up to assess cartilage thickness changes. A subset of the subjects (n = 12) also had serum cartilage oligomeric matrix protein measured at baseline in response to a mechanical stimulus (30-min walk) (mCOMP). Baseline measures, including the knee extension (KEM), flexion (KFM), adduction (KAM) moments and mCOMP, were tested for associations with cartilage thickness changes in specific regions of the knee., Results: Cartilage change in the full medial femoral condyle (p = 0.005) and external medial femoral region (p = 0.041) was negatively associated with larger early stance peak KEM. Similarly, cartilage change in the full medial femoral region (p = 0.009) and medial femoral external region (p = 0.043) was negatively associated with larger first peak KAM, while cartilage change in the anterior medial tibia was positively associated with larger first peak KAM (p = 0.003). Cartilage change in the anterior medial tibia was also significantly associated (p = 0.011) with mCOMP levels 5.5-h post-activity (percentage of pre-activity levels)., Conclusions: Interactions found between gait, mechanically-stimulated serum biomarkers, and cartilage thickness in an at-risk aging asymptomatic population suggest the opportunity for early detection of OA with new approaches that bridge across disciplines and scales., Competing Interests: Declaration of competing interest There are no conflicts of interest for any of the authors., (Copyright © 2021. Published by Elsevier Ltd.)

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T 1ρ and T 2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T 1ρ and T 2 relaxation times increased during the follow-up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof-of-concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects., (© 2020 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Cartilage degeneration has been reported to deteriorate osteoarthritis (OA), a prevalent joint disease caused by intrinsic and epigenetic factors. This study aimed to examine the molecular mechanism of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)/microRNA-138 (miR-138)/syndecan 1 (SDC1) and its epigenetic regulation in cartilage degeneration in OA. An OA cell model was induced by stimulating chondrocytes with interleukin (IL)-1β at a final concentration of 10 ng/mL, followed by alterations in EZH2 and miR-138 expression. Afterwards, cell apoptosis was analyzed using flow cytometry. The expression patterns of cartilage catabolism-related factors (MMP-13, ADAMTS-4, and ADAMTS-5) were determined using RT-qPCR and western blot analyses. The EZH2 and H3K27me3 enrichment at the miR-138 promoter region were determined using ChIP-qPCR. Finally, an OA mouse model was constructed to verify the function of EZH2 in vivo. EZH2 was expressed at high levels in OA models. EZH2 depletion ameliorated OA, as evidenced by reduced cell apoptosis in IL-1β-treated chondrocytes and decreased levels of cartilage catabolism-related factors. Moreover, EZH2 promoted histone methylation at the miR-138 promoter to suppress miR-138 expression, thereby upregulating the expression of SDC1, a target gene of miR-138. Changes in this pathway increased the expression of cartilage catabolism-related factors in vitro while promoting cartilage degeneration in vivo. Our data provided evidence that EZH2 inhibits miR-138 expression by promoting the histone methylation of its promoter, which induces cartilage degeneration in OA models by upregulating SDC1 expression, suggesting a novel mechanistic strategy for OA treatment.

Objective: To investigate the diffusion trajectory of a cationic contrast medium (CA4+) into equine articular cartilage, and to assess normal and degenerative equine articular cartilage using cationic contrast-enhanced computed tomography (CECT)., Design: In the first experiment (Exp1), equine osteochondral specimens were serially imaged with cationic CECT to establish the diffusion time constant and time to reach equilibrium in healthy articular cartilage. In a separate experiment (Exp2), articular cartilage defects were created on the femoral trochlea (defect joint) in a juvenile horse, while the opposite joint was a sham-operated control. After 7 weeks, osteochondral biopsies were collected throughout the articular surfaces of both joints. Biopsies were analyzed for cationic CECT attenuation, glycosaminoglycan (GAG) content, mechanical stiffness (E eq ), and histology. Imaging, biochemical and mechanical data were compared between defect and control joints., Results: Exp1: The mean diffusion time constant was longer for medial condyle cartilage (3.05 ± 0.1 hours) than lateral condyle cartilage (1.54 ± 0.3 hours, P = 0.04). Exp2: Cationic CECT attenuation was lower in the defect joint than the control joint ( P = 0.005) and also varied by anatomic location ( P = 0.045). Mean cationic CECT attenuation from the lateral trochlear ridge was lower in the defect joint than in the control joint (2223 ± 329 HU and 2667 ± 540 HU, respectively; P = 0.02). Cationic CECT attenuation was strongly correlated with both GAG (ρ = 0.79, P < 0.0001) and E eq (ρ = 0.61, P < 0.0001)., Conclusions: The equilibration time of CA4+ into equine articular cartilage is affected by tissue volume. Quantitative cationic CECT imaging reflects the biochemical, biomechanical and histological state of normal and degenerative equine articular cartilage.

Quantitative magnetic resonance (MR) relaxation parameters demonstrate varying sensitivity to the orientation of the ordered tissues in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in cadaveric human cartilage with varying degree of natural degeneration, and compared with biomechanical testing, histological scoring, and quantitative histology. Twelve patellar cartilage samples were imaged at 9.4 T MRI with multiple relaxation parameters, including T 1 , T 2 , CW - T 1ρ , and adiabatic T 1ρ , at three different orientations with respect to the main magnetic field. Anisotropy of the relaxation parameters was quantified, and the results were compared with the reference measurements and between samples of different histological Osteoarthritis Research Society International (OARSI) grades. T 2 and CW - T 1ρ at 400 Hz spin-lock demonstrated the clearest anisotropy patterns. Radial zone anisotropy for T 2 was significantly higher for samples with OARSI grade 2 than for grade 4. The proteoglycan content (measured as optical density) correlated with the radial zone MRI orientation anisotropy for T 2 (r = 0.818) and CW - T 1ρ with 400 Hz spin-lock (r = 0.650). Orientation anisotropy of MRI parameters altered with progressing cartilage degeneration. This is associated with differences in the integrity of the collagen fiber network, but it also seems to be related to the proteoglycan content of the cartilage. Samples with advanced OA had great variation in all biomechanical and histological properties and exhibited more variation in MRI orientation anisotropy than the less degenerated samples. Understanding the background of relaxation anisotropy on a molecular level would help to develop new MRI contrasts and improve the application of previously established quantitative relaxation contrasts., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating "ready-to-use" hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.

Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.

Purpose: The study wanted to investigate the benefit, durability and safety of autologous protein solution (APS) injection(s) in a middle-aged female-only cohort suffering predominantly from patellofemoral osteoarthritis., Methods: Fifty females (aged 50.4 ± 6.5) with mainly moderate-severe (86%) patellofemoral cartilage wear (PFCW) were treated with a unilateral intra-articular APS injection. The KOOS, NRS, Kujala, UCLA and EQ-5D were assessed at baseline and 1, 3, 6, and 12 months post-injection. Therapeutic response rate (TRR) was based on KOOS pain improvement > 10 points. Absolute improvement for, respectively, therapy responders and non-responders was determined. Second APS injection was administered if improvement was deemed insufficient by the patient after 3 months., Results: The TRR remained stable averaging to 53.7% at final follow-up with subjects improving overall from 40.3 ± 18.7 to 57.3 ± 24.8 points on KOOS pain (p = 0.0002) and from 48.4 ± 13.0 to 56.3 ± 18.1 points on Kujala (p = 0.0203) at 12 months. Significant improvement was observed for the other KOOS subscales and NRS at each follow-up. In absolute values, APS responders improved with 30.5 ± 11.4 points on KOOS pain at 12 months. In contrast, non-responders deteriorated with 5.9 ± 8.9 points relative to baseline. A second APS injection was administered in 28 subjects. Patients with definite synovitis improved more on KOOS symptoms (p = 0.017) and KOOS ADL (p = 0.037) at 12 months compared to non-synovitis subjects. Mild-moderate arthralgia (46%) and effusion (29%) were commonly observed during the first month post-injection., Conclusion: This study evidenced a 54% response rate at 12 months to a single or second APS injection in a middle-aged female population with advanced patellofemoral cartilage wear. Moderate temporary flares can be expected without affecting clinical outcomes. Second APS injection has low efficacy in initially poor responding patients after 3 months. Major synovitis on baseline MRI appeared to be a beneficial prognosticator for pain relief and functional improvement after APS., Level of Evidence: IV.

Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.

Background: Osteoarthritis (OA) is the most common joint disorder in the USA, and knee OA has the highest prevalence. Inflammation and decrease in vascularization are key factors in the degeneration of articular cartilage and the associated pain and decrease in function. To combat this process, the use of biologics including umbilical cord-derived Wharton's Jelly (UC-derived WJ) has grown. UC-derived WJ contains large quantities of regenerative factors, including growth factors (GFs), cytokines (CKs), hyaluronic acid (HA), and extracellular vesicles (EVs). The proposed study evaluates the safety and efficacy of intraarticular injection of UC-derived WJ for treatment of knee OA symptoms., Methods and Analysis: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular UC-derived WJ in patients suffering from grade II/III OA will be assessed. Twelve patients with grade II/III OA who meet the inclusion and exclusion criteria will be recruited for this study which will be conducted at up to two sites within the USA. The participants will be followed for 1 s. Participants will be assessed using the Numeric Pain Rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-item short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, satisfaction, function, and cartilage regeneration., Discussion: This prospective study will contribute to the limited amount of data on UC-derived WJ, particularly with regard to its safety and efficacy. The outcomes from this study will also lay the groundwork for a large placebo-controlled trial of intraarticular UC-derived WJ for symptomatic knee OA., Trial Registration: ClinicalTrials.gov NCT04719793 . Registered on 22 January 2021.

Objective: Clinical trials for osteoarthritis (OA), the leading cause of global disability, are unable to pinpoint the early, potentially reversible disease with clinical technology. Hence, disease-modifying drug candidates cannot be tested early in the disease. To overcome this obstacle, we asked whether early OA-pathology detection is possible with current clinical technology., Methods: We determined the relationship between two sensitive early OA markers, atomic force microscopy (AFM)-measured human articular cartilage (AC) surface stiffness, and location-matched superficial zone chondrocyte spatial organizations (SCSOs), asking whether a significant loss of surface stiffness can be detected in early OA SCSO stages. We then tested whether current clinical technology can visualize and accurately diagnose the SCSOs using an approved probe-based confocal laser-endomicroscope and a random forest (RF) model., Results: We demonstrated a correlation between AC surface stiffness and the SCSO (r rm  = -0.91; 95%CI: -0.97, -0.73), and an extensive loss of surface stiffness specifically in those ACs with early OA-typical SCSO (95%CIs: string SCSO: 269-173 kPa, double string SCSO: 77-46 kPa). This established the SCSO as a visualizable, functionally relevant surrogate marker of early OA AC surface pathology. Moreover, SCSO-based stiffness discrimination worked well in each patient's AC. We then demonstrated feasibility of visualizing the SCSO by clinical laser-endomicroscopy and, importantly, accurate SCSO diagnosis using RF., Conclusion: We present the proof-of-concept of early OA-pathology detection with available clinical technology, introducing a future-oriented, AI-supported, non-destructive quantitative optical biopsy for early disease detection. Operationalizing SCSO recognition, this approach allows testing for correlations between local tissue architectures with other experimental and clinical read-outs, but needs clinical validation and a larger sample size for defining diagnostic thresholds., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method., Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention., Results: Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups., Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions., Trial Registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901 .

Background: Evaluating of the articular cartilage status of the distal humeral epiphysis is difficult. Ultrasound imaging of the elbow is increasingly being used to confirm the integrity of the articular cartilage of minimally displaced lateral humeral condyle fractures in children with minimally displaced fractures. The aims of this study were to assess the correlations between ultrasound and arthrography findings for predicting the integrity of the cartilage hinge and to describe the utility of ultrasound in determining the need for pre-treatment., Methods: Thirty-nine patients with minimally displaced lateral humeral condyle fractures who underwent ultrasound and arthrography examinations before surgery from May 2018 to December 2019 were included in this study. Ultrasound and arthrography predictors of the cartilage hinge status were independently measured. The ultrasound and arthrography results were compared., Results: The mean displacement of the fractures was 3.1 mm (range, 2.0~5.0 mm). Arthrography showed incomplete fractures in 24 patients (61.5%) and complete fractures in 15 patients (38.5%). Ultrasound showed incomplete fractures in 25 patients (64.1%) and complete fractures in 14 patients (35.9%). The ultrasound and arthrography results of the integrity of the articular surface were consistent in 92.3% of the cases, including 23 that were predicted to have an intact articular surface and 13 that were predicted to have an incongruity articular surface. There was no correlation between the displacement and the fracture appearing complete on the ultrasound scan. The Pearson coefficient between ultrasound and arthrography for assessing the integrity of the articular surface was 0.837., Conclusions: Ultrasound and arthrography assessments of the integrity of the cartilage hinge status appear to be highly consistent. Ultrasound can be used as a complementary tool with arthrography to predict the integrity of the cartilage hinge status in children with minimally displaced lateral humeral condyle fractures., Level of Evidence: Prospective study; level II.

Objective: Cartilage health is maintained in response to a range of mechanical stimuli including compressive, shear and tensile strains and associated alterations in osmolality. The osmotic-sensitive ion channel Transient Receptor Potential Vanilloid 4 (TRPV4) is required for mechanotransduction. Mechanical stimuli inhibit interleukin-1β (IL-1β) mediated inflammatory signalling, however the mechanism is unclear. This study aims to clarify the role of TRPV4 in this response., Design: TRPV4 activity was modulated glycogen synthase kinase (GSK205 antagonist or GSK1016790 A (GSK101) agonist) in articular chondrocytes and cartilage explants in the presence or absence of IL-1β, mechanical (10% cyclic tensile strain (CTS), 0.33 Hz, 24hrs) or osmotic loading (200mOsm, 24hrs). Nitric oxide (NO), prostaglandin E 2 (PGE 2 ) and sulphated glycosaminoglycan (sGAG) release and cartilage biomechanics were analysed. Alterations in post-translational tubulin modifications and primary cilia length regulation were examined., Results: In isolated chondrocytes, mechanical loading inhibited IL-1β mediated NO and PGE 2 release. This response was inhibited by GSK205. Similarly, osmotic loading was anti-inflammatory in cells and explants, this response was abrogated by TRPV4 inhibition. In explants, GSK101 inhibited IL-1β mediated NO release and prevented cartilage degradation and loss of mechanical properties. Upon activation, TRPV4 cilia localisation was increased resulting in histone deacetylase 6 (HDAC6)-dependent modulation of soluble tubulin and altered cilia length regulation., Conclusion: Mechanical, osmotic or pharmaceutical activation of TRPV4 regulates HDAC6-dependent modulation of ciliary tubulin and is anti-inflammatory. This study reveals for the first time, the potential of TRPV4 manipulation as a novel therapeutic mechanism to supress pro-inflammatory signalling and cartilage degradation., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to evaluate the extent to which individuals with knee articular cartilage defects (ACDs) have kinesiophobia and pain catastrophizing, and how these psychological factors relate to self-reported knee outcomes., Methods: Thirty-five individuals seeking surgical consultation for an ACD in the knee confirmed with 3.0T MRI and 18 controls without history of knee injury participated in the study. Kinesiophobia was measured with the Tampa Scale of Kinesiophobia (TSK), and scored using the modified 11-item (TSK-11) methods. Pain catastrophizing was measured with the Pain Catastrophizing Scale (PCS). Data were analyzed using descriptive statistics, independent t-tests, chi-squared tests and Spearman's correlation coefficients, as appropriate (α = 0.05)., Results: Participants with ACDs reported higher TSK-11 scores (median 27 [IQR 25-29]) and higher PCS scores (median 10 [IQR 4-18]) than controls (median TSK-11 16 [IQR 14-17], p < 0.001; median PCS 0 [IQR 0-9], p < 0.001). Within those with knee ACDs, higher TSK-11 scores were associated with worse knee pain, function on activities of daily living, sports/recreation, and knee-related quality of life scores (rho = -0.38 to -0.61). Higher pain catastrophizing was associated with worse function with activities of daily living and knee-related quality of life (rho = -0.37 to -0.40)., Conclusions: Kinesiophobia and pain catastrophizing in people with knee ACDs were higher than controls. Higher kinesiophobia and pain catastrophizing were associated with worse function and quality of life. Further study of the impact of these psychological factors on outcomes and prognosis in people with knee ACDs is warranted., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to compare the outcomes and cost economics of TKA without patella resurfacing in patients with and without patellar cartilage loss., Methods: Prospective case control study of 209 consecutive patients undergoing TKA without patella resurfacing. Patella cartilage status was documented intra-operatively: 108 patients had patella cartilage loss (mean age 70 ± 9.7, mean BMI 31 ± 6.2, 72 (67%) female) and 101 control patients did not (age 68 ± 9.2, BMI 31 ± 5.6, 52 (51%) female). The primary outcome measure was Oxford Knee Score (OKS) improvement at one year. Secondary outcomes included OKS, EQ-5D, anterior knee pain (AKP), Kujala scores and reoperation at 2-4 years. The cost to prevent secondary patella resurfacing was calculated., Results: There were more women in the patella cartilage loss group (67% Vs 51%, p = 0.037), but no other preoperative characteristics differed. There was no difference in OKS improvement between those with and without patella cartilage loss at 1 year (mean difference -1.03, -3.68 to 1.62 95%CI, p = 0.446) or 2-4 years (mean difference 1.52, -1.43 to 4.45 95%CI, p = 0.310). At 2-4 years there was no difference in AKP (14/87 with vs 17/80 without, p = 0.430) nor Kujala score (mean difference 2.66, -3.82 to 9.13 95%CI, p = 0.418). Routine patella resurfacing would have cost £58,311 to prevent one secondary resurfacing., Conclusion: There was no difference in OKS, anterior knee pain, reoperation or Kujala scores up to 2-4 years between patients with and without patellar cartilage loss following TKA without patella resurfacing. Resurfacing for this indication would not have been a cost effective intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The nonoperative practitioner managing individuals with cartilage defects should use a patient-centered, multifaceted approach that aims to individualize treatment to provide optimal benefit. These include addressing modifiable risk factors for disease progression and instituting interventions such as weight loss, nutrition, physical activity, and potentially regenerative medicine strategies. This review will focus on these nonoperative treatment strategies with a focus on when treatments are necessary, who will benefit from these approaches, why they are specifically appropriate, and, finally, how these treatments directly modify the structure of a patient's cartilage and resulting symptoms., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue. Importantly, articular cartilage pathology affects the health of the entire joint and therefore should not be considered or addressed in isolation. Treating articular cartilage lesions is challenging because left alone, the tissue is incapable of regeneration or highly functional and durable repair. Nonoperative treatments can alleviate symptoms associated with cartilage pathology but are not curative or lasting. Current surgical treatments range from stimulation of intrinsic repair to whole-surface and whole-joint restoration. Unfortunately, there is a relative paucity of prospective, randomized controlled, or well-designed cohort-based clinical trials with respect to cartilage repair and restoration surgeries, such that there is a gap in knowledge that must be addressed to determine optimal treatment strategies for this ubiquitous problem in orthopedic health care. This review article discusses the basic science rationale and principles that influence pathology, symptoms, treatment algorithms, and outcomes associated with articular cartilage defects in the knee., Competing Interests: J.P.S. reports grants and personal fees from Arthrex, Inc., grants from DePuy Synthes, other from Journal of Knee Surgery, grants from National Institutes of Health (NIAMS and NICHD), personal fees and other from Thieme, grants from U.S. Department of Defense, other from AO Foundation, other from American Orthopedic Association, other from AO North America, grants from Coulter Foundation, other from Mid-America Orthopedic Association, personal fees from Orthopedic Designs North America, personal fees from Smith and Nephew outside the submitted work. A.M.S. reports personal fees from Arthrex, Inc., personal fees from Musculoskeletal Transplant Foundation outside the submitted work. J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from AthleteIQ, grants from ConforMIS, personal fees from CONMED Linvatec, grants from Coulter Foundation, grants from DePuy Synthes, grants and personal fees from Eli Lilly, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Foundation, grants from National Institutes of Health (NIAMS & NICHD), grants from Purina, grants from Sites Medical, personal fees and other from Thieme, grants from TissueGen Inc, personal fees from Trupanion, grants from U.S. Department of Defense, grants from Zimmer-Biomet, outside the submitted work; In addition, Dr. Cook has a patent US Patent #10,039,277 with royalties paid from Musculoskeletal Transplant Foundation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Localized cartilage defects are related to joint pain and reduced function to the development of osteoarthritis. The mechanical properties of the implant for treatment do influence its longevity. Therefore, we aimed to evaluate the effect of material properties' variations of anatomically shaped focal knee implants in the knee joint using numerical finite element analysis., Methods: Computational simulations were performed for different cases including an intact knee, a knee with a focal cartilage defect, and a knee fitted with a focal articular prosthetic having three distinct mechanical properties: cobalt-chromium, pyrolytic carbon, and polyethylene. Femoral cartilage, tibial cartilage, and menisci contact pressures were evaluated under the load. In addition, bone stress was evaluated to investigate the stress shielding effect., Results: Compared with the intact model, the contact stress of the focal implant model was increased; on the femoral lateral cartilage by 14%, on medial and lateral tibial cartilages by nine percent and 10%, on medial and lateral menisci by 23% and 20%. In contrast, the focal implant model had no effect on the menisci but contact stress on the tibial cartilage increased compared with the intact model. The BioPoly model showed the lowest contact stress on femoral and tibial cartilages. Additionally, the cobalt-chromium model showed the lowest bone stress that improved the load-sharing effect., Conclusions: The results suggested that implant material properties are an important parameter in the design of a focal implant. The polyethylene model potentially restored the intact knee contact mechanics and it reduced the risk of physiological damage to the articular cartilage., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine performance and repair kinetics of the ChonDux hydrogel scaffold for treating focal articular cartilage defects in the knee over 24 months., Design: This assessor-blinded trial evaluates ChonDux hydrogel scaffold implantation in combination with microfracture in 18 patients across 6 sites. Male and female patients 18 to 65 years of age with full-thickness femoral condyle defects 2 to 4 cm 2 in area were enrolled. Eligible patients received ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI relaxation time and patient surveys via visual analogue scale (VAS) pain and International Knee Documentation Committee (IKDC) knee function scoring., Results: ChonDux maintained durable tissue restoration over 24 months with final defect percent fill of 94.2% ± 16.3% and no significant loss of fill volume at any time points. Tissues treated with ChonDux maintained T2 relaxation times similar to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased between 1 and 6 weeks, and IKDC knee function scores improved by approximately 30.1 with ChonDux over 24 months., Conclusion: ChonDux treatment is a safe adjunct to microfracture therapy and promotes stable restoration of full thickness articular cartilage defects for at least 24 months.