Composition Of Articular Cartilage Research Articles

Hydrogel-Enhanced Autologous Chondrocyte Implantation for Cartilage Regeneration-An Update on Preclinical Studies.

Autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI) have demonstrated improved clinical outcomes and reduced revision rates for treating osteochondral and chondral defects. However, their ability to achieve lasting, fully functional repair remains limited. To overcome these challenges, scaffold-enhanced ACI, particularly utilizing hydrogel-based biomaterials, has emerged as an innovative strategy. These biomaterials are intended to mimic the biological composition, structural organization, and biomechanical properties of native articular cartilage. This review aims to provide comprehensive and up-to-date information on advancements in hydrogel-enhanced ACI from the past decade. We begin with a brief introduction to cartilage biology, mechanisms of cartilage injury, and the evolution of surgical techniques, particularly looking at ACI. Subsequently, we review the diversity of hydrogel scaffolds currently undergoing development and evaluation in preclinical studies for articular cartilage regeneration, emphasizing chondrocyte-laden hydrogels applicable to ACI. Finally, we address the key challenges impeding effective clinical translation, with particular attention to issues surrounding fixation and integration, aiming to inform and guide the future progression of tissue engineering strategies.

(Chemical) Roles of HOCl in Rheumatic Diseases.

Chronic rheumatic diseases such as rheumatoid arthritis (RA) are characterized by a dysregulated immune response and persistent inflammation. The large number of neutrophilic granulocytes in the synovial fluid (SF) from RA patients leads to elevated enzyme activities, for example, from myeloperoxidase (MPO) and elastase. Hypochlorous acid (HOCl), as the most important MPO-derived product, is a strong reactive oxygen species (ROS) and known to be involved in the processes of cartilage destruction (particularly regarding the glycosaminoglycans). This review will discuss open questions about the contribution of HOCl in RA in order to improve the understanding of oxidative tissue damaging. First, the (chemical) composition of articular cartilage and SF and the mechanisms of cartilage degradation will be discussed. Afterwards, the products released by neutrophils during inflammation will be summarized and their effects towards the individual, most abundant cartilage compounds (collagen, proteoglycans) and selected cellular components (lipids, DNA) discussed. New developments about neutrophil extracellular traps (NETs) and the use of antioxidants as drugs will be outlined, too. Finally, we will try to estimate the effects induced by these different agents and their contributions in RA.

Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. Twenty patients with ACLR (time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self-selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = -0.99 and p = 0.004) during running. Our findings suggest that those who are between 6 and 24 months post-ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF.

Compositional MR imaging of cartilage and joint mechanics

MRI-based compositional measurements of cartilage have been developed to characterize the biochemical composition of articular cartilage and the menisci, allowing the assessment of cartilage quality before cartilage loss has occurred and changes are still potentially reversible. They have also been used to investigate the complex relationship between biomechanics and cartilage health. This review focuses on cartilage T1rho and T2 cartilage compositional measurements as these techniques have been most frequently used in studies involving joint biomechanics. Recent clinical and in vitro studies are covered, including those investigating the relationship of cartilage composition with physical activity, gait, muscle strength, and biomechanical loading of specimens. These studies clearly illustrate the impact of physical activity on cartilage, how gait alterations after anterior cruciate ligament reconstruction may lead to early degenerative disease, and the complex interplay between muscle strength, gait, and cartilage composition. In vitro work also demonstrates how indentation stiffness correlates with cartilage composition. The review further consolidates the important role of cartilage compositional imaging in understanding the biomechanics and pathophysiology of degenerative joint disease.

Biomechanical Threshold Values for Identifying Clinically Significant Knee-Related Symptoms Six Months Following Anterior Cruciate Ligament Reconstruction.

Slower habitual walking speed and aberrant gait biomechanics are linked to clinically significant knee-related symptoms and articular cartilage composition changes linked to posttraumatic osteoarthritis (PTOA) following anterior cruciate ligament reconstruction (ACLR). To determine specific gait biomechanical variables that can accurately identify individuals with clinically significant knee-related symptoms post-ACLR, and the corresponding threshold values, sensitivity, specificity, and odds ratios for each biomechanical variable. Cross-sectional analysis. Laboratory. Seventy-one individuals (n=38 female; age=21±4 years; height=1.76±0.11 m; mass=75.38±13.79 kg) who were 6 months post-primary unilateral ACLR (6.2±0.4 months). 3D motion capture of 5 overground walking trials was used to calculate discrete gait biomechanical variables of interest during stance phase (1st and 2nd peak vertical ground reaction force [vGRF]; midstance minimum vGRF; peak internal knee abduction and extension moments; and peak knee flexion angle), along with habitual walking speed. Knee Injury and Osteoarthritis Outcome Scores (KOOS) was used to dichotomize patients as symptomatic (n=51) or asymptomatic (n=20) using the Englund et al. 2003 KOOS guidelines for defining clinically significant knee-related symptoms. Separate receiver operating characteristic (ROC) curves and respective areas under the curve (AUC) were used to evaluate the capability of each biomechanical variable of interest for identifying individuals with clinically significant knee-related symptoms. Habitual walking speed (AUC=0.66), vGRF at midstance (AUC=0.69), and 2nd peak vGRF (AUC=0.76), demonstrated low-to-moderate accuracy for identifying individuals with clinically significant knee-related symptoms. Individuals who exhibited habitual walking speeds ≤1.27 m/s, midstance vGRF ≥0.82 BW, and 2nd peak vGRF ≤1.11 BW, demonstrated 3.13, 6.36, and 9.57 times higher odds of experiencing clinically significant knee-related symptoms, respectively. Critical thresholds for gait variables may be utilized to identify individuals with increased odds of clinically significant knee-related symptoms and potential targets for future interventions.

Strategies to engineer articular cartilage with biomimetic zonal features: a review.

Articular cartilage (AC) is a highly specialized tissue with restricted ability for self-regeneration, given its avascular and acellular nature. Although a considerable number of surgical treatments is available for the repair, reconstruction, and regeneration of AC defects, most of them do not prioritize the development of engineered cartilage with zonal stratification derived from biomimetic biochemical, biomechanical and topographic cues. In the absence of these zonal elements, engineered cartilage will exhibit increased susceptibility to failure and will neither be able to withstand the mechanical loading to which AC is subjected nor will it integrate well with the surrounding tissue. In this regard, new breakthroughs in the development of hierarchical stratified engineered cartilage are highly sought after. Initially, this review provides a comprehensive analysis of the composition and zonal organization of AC, aiming to enhance our understanding of the significance of the structure of AC for its function. Next, we direct our attention towards the existing in vitro and in vivo studies that introduce zonal elements in engineered cartilage to elicit appropriate AC regeneration by employing tissue engineering strategies. Finally, the advantages, challenges, and future perspectives of these approaches are presented.

Designing a Synthetic 3D-Printed Knee Cartilage: FEA Model, Micro-Structure and Mechanical Characteristics

Articular cartilage morphology and composition are essential factors in joint biomechanics, and their alteration is a crucial aspect of osteoarthritis (OA), a prevalent disease that causes pain and functional loss. This research focuses on developing patient-specific synthetic cartilage using innovative Digital Anatomy polymers. The objectives include investigating the morphology, characterizing the mechanical properties, and replicating the architecture of natural cartilage. This approach offers potential alternatives to traditional manufacturing methods and reduces the need for expensive in vivo experiments. Finite Element Analysis (FEA) validates a novel patient-specific measurement setup. It provides insights into the role of morphology in the distribution of stress and strain within cartilage. CAD design is also utilized to create standardized fiber-reinforced samples that mimic the layered micro-architecture of natural cartilage, allowing for the study of their contribution to the overall mechanical properties. The results demonstrate that 3D-printed polymers can effectively replicate the elastic properties of cartilage. The proposed patient-specific simulator produces reliable results, which have been validated through FEM analysis. While the recreated microstructure closely resembles biological cartilage samples, the elastic properties are slightly underestimated. In conclusion, designing an in silico knee joint is a feasible approach that offers numerous advantages for further development. The Young’s modulus values of our synthetic cartilage modules range from 2.43 MPa to 7.24 MPa, within the range reported in the literature. Moreover, Young´s modulus at the micro level shows the differences between surface 1.74 MPa and internal substrate 1.83 MPa depending on the fiber orientation. Finally, our model proves to be mechanically and morphologically accurate at both the macro and micro levels.

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering.

Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

Hypotrochoidal scaffolds for cartilage regeneration

The main function of articular cartilage is to provide a low friction surface and protect the underlying subchondral bone. The extracellular matrix composition of articular cartilage mainly consists of glycosaminoglycans and collagen type II. Specifically, collagen type II fibers have an arch-like organization that can be mimicked with segments of a hypotrochoidal curve. In this study, a script was developed that allowed the fabrication of scaffolds with a hypotrochoidal design. This design was investigated and compared to a regular 0–90 woodpile design. The mechanical analyses revealed that the hypotrochoidal design had a lower component Young's modulus while the toughness and strain at yield were higher compared to the woodpile design. Fatigue tests showed that the hypotrochoidal design lost more energy per cycle due to the damping effect of the unique microarchitecture. In addition, data from cell culture under dynamic stimulation demonstrated that the collagen type II deposition was improved and collagen type X reduced in the hypotrochoidal design. Finally, Alcian blue staining revealed that the areas where the stress was higher during the stimulation produced more glycosaminoglycans. Our results highlight a new and simple scaffold design based on hypotrochoidal curves that could be used for cartilage tissue engineering.

Articular Cartilage-From Basic Science Structural Imaging to Non-Invasive Clinical Quantitative Molecular Functional Information for AI Classification and Prediction.

This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to image the structure and associated functions of articular cartilage but, instead, to devise methods for generating non-invasive, function-depicting images with quantitative information that is useful for detecting the early, pre-clinical stage of diseases such as primary or post-traumatic osteoarthritis (OA/PTOA). In this context, this review summarizes (a) the structure and function of articular cartilage as a molecular imaging target, (b) quantitative MRI for non-invasive assessment of articular cartilage composition, microstructure, and function with the current state of medical diagnostic imaging, (c), non-destructive imaging methods, (c) non-destructive quantitative articular cartilage live-imaging methods, (d) artificial intelligence (AI) classification of degeneration and prediction of OA progression, and (e) our contribution to this field, which is an AI-supported, non-destructive quantitative optical biopsy for early disease detection that operates on a digital tissue architectural fingerprint. Collectively, this review shows that articular cartilage imaging has undergone profound changes in the purpose and expectations for which cartilage imaging is used; the image is becoming an AI-usable biomarker with non-invasive quantitative functional information. This may aid in the development of translational diagnostic applications and preventive or early therapeutic interventions that are yet beyond our reach.

Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture.

Intra-articular fractures (IAF) result in significant and prolonged inflammation, increasing the chances of developing post-traumatic osteoarthritis (PTOA). Interleukin-one beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α) are key inflammatory factors shown to be involved in osteochondral degradation following IAF. As such, use of targeted biologics such as Infliximab (INX), a TNF-α inhibitor, and Anakinra (ANR), an interleukin-one (IL-1) receptor antagonist (IL1RA), may protect against PTOA by damping the inflammatory response to IAF and reducing osteochondral degradation. To test this hypothesis, IAFs were induced in the hindlimb knee joints of rats treated with INX at 10 mg/kg/day, ANR at 100 g/kg/day, or saline (vehicle control) by subcutaneous infusion for a period of two weeks and healing was evaluated at 8-weeks post injury. Serum and synovial fluid (SF) were analyzed for soluble factors. In-vivo microcomputed tomography (µCT) scans assessed bone mineral density and bone morphometry measurements. Cationic CA4+ agent assessed articular cartilage composition via ex vivo µCT. Scoring according to the Osteoarthritis Research Society International (OARSI) guidelines was performed on stained histologic tibia sections at the 56-day endpoint on a 0-6 scale. Systemically, ANR reduced many pro-inflammatory cytokines and reduced osteochondral degradation markers Cross Linked C-Telopeptide Of Type II (CTXII, p < 0.05) and tartrate-resistant acid phosphatase (TRAP, p < 0.05). ANR treatment resulted in increased chemokines; macrophage-chemotractant protein-1 (MCP-1), MPC-3, macrophage inhibitory protein 2 (MIP2) with a concomitant decrease in proinflammatory interleukin-17A (IL17A) at 14 days post-injury within the SF. Microcomputed tomography (µCT) at 56 days post-injury revealed ANR Treatment decreased epiphyseal degree of anisotropy (DA) (p < 0.05) relative to saline. No differences were found with OARSI scoring but contrast-enhanced µCT revealed a reduction in glycosaminoglycan content with ANR treatment. These findings suggest targeted cytokine inhibition, specifically IL-1 signaling, as a monotherapy has minimal utility for improving IAF healing outcomes but may have utility for promoting a more permissive inflammatory environment that would allow more potent disease modifying osteoarthritis drugs to mitigate the progression of PTOA after IAF.

Recent progress on 3D-printed gelatin methacrylate-based biomaterials for articular cartilage repair

The structure and composition of articular cartilage is complex, and its self-healing ability is limited, and thus, it is difficult to achieve ideal healing once the articular cartilage is damaged. Recently, three-dimensional (3D) printing technology has provided a new possibility for the repair of articular cartilage. Engineered cartilage tissues can be fabricated by superimposing customized inks, considering different geometric structures and components of tissues. 3D printing can be effectively used to manufacture high-precision structures with complex geometry, solving the shortcomings of traditional scaffold fabrication techniques. Gelatin methacrylate (GelMA) is modified gelatin and is currently a widely used 3D printing ink due to its photocrosslinking properties. With good biocompatibility and tunable physical properties, it can provide a good scaffold platform for cell proliferation and growth factor release. Given that the role of 3D printing technology in cartilage repair has been widely reported, this article reviews the research progress of 3D-printed GelMA-based biomaterials in articular cartilage tissue engineering. We focus primarily on how 3D printing technology addresses the existing challenges inherent to the field of articular cartilage tissue engineering. We accentuate the modifications implemented in GelMA-based 3D printing scaffolds to optimize articular cartilage regeneration. Additionally, we provide a comprehensive summary of the utilization of GelMA-based biomaterials incorporating various cells, growth factors, or other tissue components and highlight how these adaptations, in conjunction with the benefits of 3D printing technology, facilitate improvements the articular cartilage repair.

Effect of glycosaminoglycans on the structure and composition of articular cartilage and bone of broilers

This study aimed to assess the influence of glycosaminoglycan (chondroitin and glucosamine sulfates) supplementation in the diet of broilers on the expression of matrix metallopeptidase 9 (MMP-9) and metallopeptidase inhibitor 2 (TIMP-2) genes, the synthesis of proteoglycans, collagen type II and chondrocytes, bone and cartilage macroscopy, bone mineral densitometry, bone breaking strength and mineral profile. A completely randomized design was carried out in a 3×3 factorial scheme (3 levels of chondroitin sulfate: 0.00, 0.05, and 0.10%; and 3 levels of glucosamine sulfate: 0.00, 0.15, and 0.30%), totaling 9 treatments. At 21 and 42 d of age, broilers were slaughtered, and tibias and femurs were collected for evaluation. There was an interaction (P < 0.05) of sulfates for the expression of MMP-9 and its inhibitor TIMP-2 in femur articular cartilage, as well as for the number of chondrocytes, collagen type II and proteoglycans in tibia articular cartilage, bone and cartilage macroscopy and mineral profile (P < 0.05), with better results obtained with the inclusion of chondroitin and/or glucosamine sulfates in the feed. In conclusion, chondroitin and glucosamine sulfates can be used in broiler diets in order to favor the development of the structure of the locomotor system (bones and joints), thus preventing locomotion problems.

Combining biomechanical stimulation and chronobiology: a novel approach for augmented chondrogenesis?

The unique structure and composition of articular cartilage is critical for its physiological function. However, this architecture may get disrupted by degeneration or trauma. Due to the low intrinsic regeneration properties of the tissue, the healing response is generally poor. Low-grade inflammation in patients with osteoarthritis advances cartilage degradation, resulting in pain, immobility, and reduced quality of life. Generating neocartilage using advanced tissue engineering approaches may address these limitations. The biocompatible microenvironment that is suitable for cartilage regeneration may not only rely on cells and scaffolds, but also on the spatial and temporal features of biomechanics. Cell-autonomous biological clocks that generate circadian rhythms in chondrocytes are generally accepted to be indispensable for normal cartilage homeostasis. While the molecular details of the circadian clockwork are increasingly well understood at the cellular level, the mechanisms that enable clock entrainment by biomechanical signals, which are highly relevant in cartilage, are still largely unknown. This narrative review outlines the role of the biomechanical microenvironment to advance cartilage tissue engineering via entraining the molecular circadian clockwork, and highlights how application of this concept may enhance the development and successful translation of biomechanically relevant tissue engineering interventions.

Composition, architecture and biomechanical properties of articular cartilage in differently loaded areas of the equine stifle.

Strategies for articular cartilage repair need to take into account topographical differences in tissue composition and architecture to achieve durable functional outcome. These have not yet been investigated in the equine stifle. To analyse the biochemical composition and architecture of three differently loaded areas of the equine stifle. We hypothesise that site differences correlate with the biomechanical characteristics of the cartilage. Ex vivo study. Thirty osteochondral plugs per location were harvested from the lateral trochlear ridge (LTR), the distal intertrochlear groove (DITG) and the medial femoral condyle (MFC). These underwent biochemical, biomechanical and structural analysis. A linear mixed model with location as a fixed factor and horse as a random factor was applied, followed by pair-wise comparisons of estimated means with false discovery rate correction, to test for differences between locations. Correlations between biochemical and biomechanical parameters were tested using Spearman's correlation coefficient. Glycosaminoglycan content was different between all sites (estimated mean [95% confidence interval (CI)] for LTR 75.4 [64.5, 88.2], for intercondylar notch (ICN) 37.3 [31.9, 43.6], for MFC 93.7 [80.1109.6] μg/mg dry weight), as were equilibrium modulus (LTR2.20 [1.96, 2.46], ICN0.48 [0.37, 0.6], MFC1.36 [1.17, 1.56] MPa), dynamic modulus (LTR7.33 [6.54, 8.17], ICN4.38 [3.77, 5.03], MFC5.62 [4.93, 6.36] MPa) and viscosity (LTR7.49 [6.76, 8.26], ICN16.99 [15.88, 18.14], MFC8.7 [7.91,9.5]°). The two weightbearing areas (LTR and MCF) and the non-weightbearing area (ICN) differed in collagen content (LTR 139 [127, 152], ICN176[162, 191], MFC 127[115, 139] μg/mg dry weight), parallelism index and angle of collagen fibres. The strongest correlations were between proteoglycan content and equilibrium modulus (r: 0.642; p: 0.001), dynamic modulus (r: 0.554; p < 0.001) and phase shift (r: -0.675; p < 0.001), and between collagen orientation angle and equilibrium modulus (r: -0.612; p < 0.001), dynamic modulus (r: -0.424; p < 0.001) and phase shift (r: 0.609; p < 0.001). Only a single sample per location was analysed. There were significant differences in cartilage biochemical composition, biomechanics and architecture between the three differently loaded sites. The biochemical and structural composition correlated with the mechanical characteristics. These differences need to be acknowledged by designing cartilage repair strategies.

MRI-based degeneration grades for lumbar facet joints do not correlate with cartilage mechanics.

Lumbar facet joint arthritis is characterized by degeneration of articular cartilage, loss of joint spacing, and increased boney spur formation. These signs of facet joint degeneration have been previously measured using destructive biochemical and mechanical analysis. Nondestructive clinical evaluation of the facet joint has also been performed using MRI scoring, which ranks the health of the facet joint using the Fujiwara scale. However, nondestructive clinical evaluation of facet joint arthritis using standard MRI scoring provides low resolution images which result in high interobserver variability. Therefore, to assess the accuracy of nondestructive MRI analysis with regard to the health of the facet joint, this study determined whether any correlations existed between lumbar facet joint articular cartilage mechanics, facet articular cartilage biochemical signatures, and Fujiwara scores. To accomplish this aim, human cadaveric lumbar spines were obtained and imaged using T1 MRI, then independently scored by three spine researchers. An osteochondral plug from each of the L2 thru L5 facet joints was obtained and loaded under unconfined compression. The experiments showed no trends between histological images and changes in the Fujiwara score. The mechanical properties of articular cartilage (thickness, Young's modulus, instantaneous modulus, and permeability) also had no correlations with the Fujiwara score. These results show that the current Fujiwara score cannot accurately describe the biomechanics or biochemical composition of facet joint articular cartilage.

Research progress of self-assembling peptide hydrogels in repairing cartilage defects

Due to the lack of blood vessels, nerves and lymphatic vessels, the capacity of articular cartilage to heal is extremely limited. Once damaged, it is urgent for articular cartilage to repair the injury. In recent years, there has been an increase in cartilage tissue engineering studies. Self-assembling peptide hydrogel as a kind of hydrogels composed of peptides and water is widely used in cartilage tissue engineering. Under noncovalent interactions such as electrostatic interaction, hydrophobic interaction, hydrogen bonding and pi-pi stacking force, peptides self-assemble into three-dimensional (3D) structures that mimic the natural extracellular matrix and allow cells to grow, proliferate and differentiate. Because SAPHs have excellent biocompatibility and biodegradability, variable mechanical properties, low immunogenicity, injectability, and the ability to load cells and bioactive substances, many researchers utilized them to promote the repair and regeneration of articular cartilage after damage. Therefore, the purpose of this review is to sum up the composition, injury characteristics, and treatments of articular cartilage, as well as the action of SAPHs in repairing articular cartilage damage.

Layered mechanical and electrical properties of porcine articular cartilage.

The complex structure and composition of articular cartilage make its performance show depth-dependent characteristics, but its related parameters are not complete at present. In this study, porcine articular cartilage was divided into three zones along the thickness direction, and the cartilage tissue in each zone was tested for electrical impedance, compression relaxation, and permeability to obtain their mechanical and electrical impedance parameters. The results showed that there were significant differences in mechanical and electrical properties of cartilage tissue in different zones in which resistivity, elastic modulus, relaxation time, and final relaxation rate increased gradually from superficial zone to deep zone along the direction of cartilage thickness while the permeability decreased gradually. Bioimpedance analysis can capture the phenomenon of very slight histological changes, which is expected to provide information for predicting cartilage degeneration, but the electrical impedance parameters of cartilage are still very lacking. These data are expected to provide reference for the treatment of clinical osteoarthritis and the research of cartilage repair materials.

Machine Learning Prediction of Collagen Fiber Orientation and Proteoglycan Content From Multiparametric Quantitative MRI in Articular Cartilage.

Machine learning models trained with multiparametric quantitative MRIs (qMRIs) have the potential to provide valuable information about the structural composition of articular cartilage. To study the performance and feasibility of machine learning models combined with qMRIs for noninvasive assessment of collagen fiber orientation and proteoglycan content. Retrospective, animal model. An open-source single slice MRI dataset obtained from 20 samples of 10 Shetland ponies (seven with surgically induced cartilage lesions followed by treatment and three healthy controls) yielded to 1600 data points, including 10% for test and 90% for train validation. A 9.4 T MRI scanner/qMRI sequences: T1 , T2 , adiabatic T1ρ and T2ρ , continuous-wave T1ρ and relaxation along a fictitious field (TRAFF ) maps. Five machine learning regression models were developed: random forest (RF), support vector regression (SVR), gradient boosting (GB), multilayer perceptron (MLP), and Gaussian process regression (GPR). A nested cross-validation was used for performance evaluation. For reference, proteoglycan content and collagen fiber orientation were determined by quantitative histology from digital densitometry (DD) and polarized light microscopy (PLM), respectively. Normality was tested using Shapiro-Wilk test, and association between predicted and measured values was evaluated using Spearman's Rho test. A P-value of 0.05 was considered as the limit of statistical significance. Four out of the five models (RF, GB, MLP, and GPR) yielded high accuracy (R2 =0.68-0.75 for PLM and 0.62-0.66 for DD), and strong significant correlations between the reference measurements and predicted cartilage matrix properties (Spearman's Rho=0.72-0.88 for PLM and 0.61-0.83 for DD). GPR algorithm had the highest accuracy (R2 =0.75 and 0.66) and lowest prediction-error (root mean squared [RMSE]=1.34 and 2.55) for PLM and DD, respectively. Multiparametric qMRIs in combination with regression models can determine cartilage compositional and structural features, with higher accuracy for collagen fiber orientation than proteoglycan content. 2 TECHNICAL EFFICACY: Stage 2.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage (AC) is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints. AC defects are common in the knees of young and physically active individuals. Because of the lack of suitable tissue-engineered artificial matrices, current therapies for AC defects, especially full-thickness AC defects and osteochondral interfaces, fail to replace or regenerate damaged cartilage adequately. With rapid research and development advancements in AC tissue engineering (ACTE), functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favorable biomechanical properties, water content, swelling ability, cytocompatibility, biodegradability, and lubricating behaviors. They can be rationally designed and conveniently tuned to simulate the extracellular matrix of cartilage. This article briefly introduces the composition, structure, and function of AC and its defects, followed by a comprehensive review of the exquisite (bio)design and (bio)fabrication of functionalized hydrogels for AC repair. Finally, we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.