Properties Of Articular Cartilage Research Articles

Longitudinal in vivo cationic contrast-enhanced computed tomography classifies equine articular cartilage injury and repair.

Cationic contrast-enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE2 concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6- and 8-week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri-defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage.

A Traumatic Impact Immediately Changes the Mechanical Properties of Articular Cartilage.

To investigate whether and how a single traumatic impact changes the mechanical properties of talar articular cartilage. A marble was placed on the joint surface and a weight was dropped on both medial and lateral caprine talus to create a well-defined single focal impact. The mechanical properties of intact and impacted talar cartilage were measured with a micro-indenter. Elastic (storage) and viscous (loss) moduli were determined by oscillatory ramp and dynamic mechanical analysis protocols. We found significant differences between ankles and within the same ankle joint, with the medial talus having significantly higher storage- and loss moduli than the lateral talus. The storage- and loss moduli of intact articular cartilage increased with greater indentation depths. However, postimpact the storage- and loss moduli were significantly and consistently lower in all specimens indicating immediate posttraumatic damage. The deeper regions of talar cartilage were less affected by the impact than the more superficial regions. A single traumatic impact results in an immediate and significant decrease of storage- and loss moduli. Further research must focus on the development of non- or minimally invasive diagnostic tools to address the exact microdamage caused by the impact. We speculate that the traumatic impact damaged the collagen fibers that confine the water-binding proteoglycans and thereby decreasing the hydrostatic pressure of cartilage. As part of the treatment directly after a trauma, one could imagine a reduction or restriction of peak loads to prevent the progression of the cascade towards PTOA of the ankle joint.

Biomechanical properties of articular cartilage in different regions and sites of the knee joint: acquisition of osteochondral allografts

Osteochondral allograft (OCA) transplantation involves grafting of natural hyaline cartilage and supporting subchondral bone into the cartilage defect area to restore its biomechanical and tissue structure. However, differences in biomechanical properties and donor-host matching may impair the integration of articular cartilage (AC). This study analyzed the biomechanical properties of the AC in different regions of different sites of the knee joint and provided a novel approach to OCA transplantation. Intact stifle joints from skeletally mature pigs were collected from a local abattoir less than 8 h after slaughter. OCAs were collected from different regions of the joints. The patella and the tibial plateau were divided into medial and lateral regions, while the trochlea and femoral condyle were divided into six regions. The OCAs were analyzed and compared for Young’s modulus, the compressive modulus, and cartilage thickness. Young’s modulus, cartilage thickness, and compressive modulus of OCA were significantly different in different regions of the joints. A negative correlation was observed between Young's modulus and the proportion of the subchondral bone (r = − 0.4241, P < 0.0001). Cartilage thickness was positively correlated with Young’s modulus (r = 0.4473, P < 0.0001) and the compressive modulus (r = 0.3678, P < 0.0001). During OCA transplantation, OCAs should be transplanted in the same regions, or at the closest possible regions to maintain consistency of the biomechanical properties and cartilage thickness of the donor and recipient, to ensure smooth integration with the surrounding tissue. A 7 mm depth achieved a higher Young's modulus, and may represent the ideal length.

DEVELOPMENT OF A DYNAMIC COIL-SHAPED SCAFFOLD FOR ARTICULAR CARTILAGE TISSUE ENGINEERING

Even minor lesions in articular cartilage (AC) can cause underlying bone damage creating an osteochondral (OC) defect. OC defects can cause pain, impaired mobility and can develop to osteoarthritis (OA). OA is a disease that affects nearly 10% of the population worldwide[1], and represents a significant economic burden to patients and society[2]. While significant progress has been made in this field, realising an efficacious therapeutic option for unresolved OA remains elusive and is considered one of the greatest challenges in the field of orthopaedic regenerative medicine[3]. Therefore, there is a societal need to develop new strategies for AC regeneration. In recent years there has been increased interest in the use of tissue-specific aligned porous freeze-dried extracellular matrix (ECM) scaffolds as an off-the-shelf approach for AC repair, as they allow for cell infiltration, provide biological cues to direct target-tissue repair and permit aligned tissue deposition, desired in AC repair[4]. However, most ECM-scaffolds lack the appropriate mechanical properties to withstand the loads passing through the joint[5]. One solution to this problem is to reinforce the ECM with a stiffer framework made of synthetic materials, such as polylactic acid (PLA)[6]. Such framework can be 3D printed to produce anatomically accurate implants[7], attractive in personalized medicine. However, typical 3D prints are static, their design is not optimized for soft-hard interfaces (OC interface), and they may not adapt to the cyclic loading passing through our joints, thus risking implant failure. To tackle this limitation, more compliant or dynamic designs can be printed, such as coil-shaped structures[8]. Thus, in this study we use finite element modelling to create different designs that mimic the mechanical properties of AC and prototype them in PLA, using polyvinyl alcohol as support. The optimal design will be combined with an ECM scaffold containing a tailored microarchitecture mimicking aspects of native AC.Acknowledgments: This project has received funding from the European Union's Horizon Europe research and innovation MSCA PF programme under grant agreement No. 101110000.

Effect of biaxial cyclic loading path on the mechanical and microstructure properties of articular cartilage

Cyclic loading stimulation has the potential to change both the mechanical properties and microstructure of cartilage, subsequently damaging the articular cartilage and contributing to joint osteoarthritis. This study focuses on investigating the behavior of knee articular cartilage under biaxial cyclic loading and analyzing the associated microstructural changes at the ultrastructural level. We studied the in-plane biaxial cyclic loading behavior of cartilage with a particular emphasis on understanding the effects of loading paths, taking into consideration the complex loading conditions encountered during daily activities. The experimental results reveal a clear influence of the constraints in the Y-direction (orthogonal direction) on the strain evolution in the X-direction. Furthermore, the variation in orthogonal stress corresponding to the loading path significantly impacts the biaxial mean strain of the test sample. To be specific, the uniaxial path, characterized by no constraints in the Y-direction, demonstrates the highest mean strain of 25.08 ± 0.88% in the X-direction, while the proportional path exhibits the lowest mean strain (10.77 ± 0.49%) in the X-direction due to the Y-direction's largest stress constraint. We explored the effects of stress amplitude and peak stress holding time on mean strain under a square path. Our observations indicate that the mean strain of cartilage increases with the higher stress amplitude or the longer peak stress holding time. Additionally, we analyzed the collagen fibril networks before and after biaxial cyclic loading to reveal the intrinsic deformation mechanism. The rearrangement of collagen fibril networks is closely associated with the stress state of cartilage, where higher stress levels lead to more severe fibril damage.

Determining the Relationship between Mechanical Properties and Quantitative Magnetic Resonance Imaging of Joint Soft Tissues Using Patient-Specific Templates.

To determine whether the mechanical properties of joint soft tissues such as cartilage can be calculated from quantitative magnetic resonance imaging (MRI) data, we investigated whether the mechanical properties of articular cartilage and meniscus scheduled to be resected during arthroplasty are correlated with the T2 relaxation time on quantitative MRI at the same location. Six patients who had undergone knee arthroplasty and seven who had undergone hip arthroplasty were examined. For the knee joint, the articular cartilage and lateral meniscus of the distal lateral condyle of the femur and proximal lateral tibia were examined, while for the hip joint, the articular cartilage above the femoral head was studied. We investigated the relationship between T2 relaxation time by quantitative MRI and stiffness using a hand-made compression tester at 235 locations. The patient-individualized template technique was used to align the two measurement sites. The results showed a negative correlation (from -0.30 to -0.35) in the less severely damaged articular cartilage and meniscus. This indicates that tissue mechanical properties can be calculated from T2 relaxation time, suggesting that quantitative MRI is useful in determining when to start loading after interventional surgery on cartilage tissue and in managing the health of elderly patients.

A Janus hydrogel material with lubrication and underwater adhesion

Double-layer hydrogel materials combine excellent hydrophilicity, outstanding lubricating properties, high load-bearing modulus, and good biocompatibility, and are often used to achieve high load-bearing (high modulus) and low frictional (low modulus) properties of articular cartilage, but which also makes it difficult for them to form efficient, stable and long-term adhesion underwater. Herein, we constructed a kind of novel underwater Janus hydrogel patches with strong adhesion performance by robustly anchoring mussel-protein-inspired poly (dopamine methacrylamide-co-methoxyethyl acrylate) p(DMA-co-MEA) copolymer onto the surface of poly(acrylic acid-co- acrylamide) p(AAc-co-AAm) hydrogel with bilayer modulus structure analogous to articular cartilage. Due to the coupling of the top lubrication layer and the bottom load-bearing layer, the constructed Janus hydrogel patch not only has fatigue resistance and low friction but also high load-bearing [coefficient of friction (COF) ∼0.0076, 5 N; COF∼0.048, 30 N]. Moreover, the Janus hydrogel also exhibits excellent bonding strength underwater (bonding strength ∼41.6 kPa, Fe substrate). Our strategy for constructing a novel underwater Janus hydrogel patch will provide valuable guidance for the realization of interface bonding of soft material of bionic articular cartilage and promote the practical application of tissue engineering.

Early Degenerative Changes in a Spontaneous Osteoarthritis Model Assessed by Nanoindentation.

Understanding early mechanical changes in articular cartilage (AC) and subchondral bone (SB) is crucial for improved treatment of osteoarthritis (OA). The aim of this study was to develop a method for nanoindentation of fresh, unfixed osteochondral tissue to assess the early changes in the mechanical properties of AC and SB. Nanoindentation was performed throughout the depth of AC and SB in the proximal tibia of Dunkin Hartley guinea pigs at 2 months, 3 months, and 2 years of age. The contralateral tibias were either histologically graded for OA or analyzed using immunohistochemistry. The results showed an increase in the reduced modulus (Er) in the deep zone of AC during early-stage OA (6.0 ± 1.75 MPa) compared to values at 2 months (4.04 ± 1.25 MPa) (*** p < 0.001). In severe OA (2-year) specimens, there was a significant reduction in Er throughout the superficial and middle AC zones, which correlated to increased ADAMTS 4 and 5 staining, and proteoglycan loss in these regions. In the subchondral bone, a 35.0% reduction in stiffness was observed between 2-month and 3-month specimens (*** p < 0.001). The severe OA age group had significantly increased SB stiffness of 36.2% and 109.6% compared to 2-month and 3-month-old specimens respectively (*** p < 0.001). In conclusion, this study provides useful information about the changes in the mechanical properties of both AC and SB during both early- and late-stage OA and indicates that an initial reduction in stiffness of the SB and an increase in stiffness in the deep zone of AC may precede early-stage cartilage degeneration.

Biomechanical Impact of Phosphate Wasting on Articular Cartilage Using the Murine Hyp Model of X-linked hypophosphatemia.

Degenerative osteoarthritis (OA) is recognized as an early-onset comorbidity of X-linked hypophosphatemia (XLH), contributing to pain and stiffness and limiting range of motion and activities of daily living. Here, we extend prior findings describing biochemical and cellular changes of articular cartilage (AC) in the phosphate-wasting environment of XLH to determine the impact of these changes on the biomechanical properties of AC in compression and potential role in the etiology of OA. We hypothesize that despite increased proteoglycan biosynthesis, disruption of the mineralized zone of AC impacts the mechanical properties of cartilage that function to accommodate loads and that therapeutic restoration of this zone will improve the mechanical properties of AC. Data were compared between three groups: wild type (WT), Hyp, and Hyp mice treated with calcitriol and oral phosphate. EPIC microCT confirmed AC mineral deficits and responsiveness to therapy. MicroCT of the Hyp subchondral bone plate revealed that treatment improved trabecular bone volume (BV/TV) but remained significantly lower than WT mice in other trabecular microstructures (p < 0.05). Microindentation AC studies revealed that, compared with WT mice, the mean stiffness of tibial AC was significantly lower in untreated Hyp mice (2.65 ± 0.95 versus 0.87 ± 0.33 N/mm, p < 0.001) and improved with therapy (2.15 + 0.38 N/mm) to within WT values. Stress relaxation of AC under compressive loading displayed similar biphasic relaxation time constants (Taufast and Tauslow) between controls and Hyp mice, although Tauslow trended toward slowed relaxation times. In addition, Taufast and Tauslow times correlated with peak load in WT mice (r = 0.80; r = 0.78, respectively), whereas correlation coefficient values for Hyp mice (r = 0.46; r = 0.21) improved with treatment (r = 0.71; r = 0.56). These data provide rationale for therapies that both preserve AC stiffness and recovery from compression. The Hyp mouse also provides unique insight into determinants of structural stiffness and the viscoelastic properties of AC in the progression of OA. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Paper 08: In Vitro Effects of Triamcinolone and Methylprednisolone on the Viability and Mechanics of Native Articular Cartilage

Objectives: The chondrotoxic effects of methylprednisolone acetate (MP) and triamcinolone acetonide (TA) have been well described. Prior studies have demonstrated a dose-dependent chondrotoxic effect of intra articular (IA) steroids starting at 7 mg for MP and 18 mg for TA. However, the effects of these steroids on the mechanical properties of articular cartilage are largely unknown. The purpose of this study was to investigate the in vitro effects of a single one-hour MP or TA exposure on the viability, mechanics, and biochemical content of native articular cartilage explants. Methods: Articular cartilage explants (n=6 per group) were harvested from the femoral condyle of the bovine stifle. Explants were exposed to chondrogenic medium containing a clinical dose of MP or TA for one hour, followed by fresh medium wash and exchange. Explants in the negative control group underwent the same treatment with chondrogenic medium alone. At t=24 hours post-treatment, samples were assessed for viability (live/dead), mechanical properties (creep indentation and Instron tensile testing), biochemical (collagen and glycosaminoglycan) content, and pyridinoline cross linking via mass spectrometry. Results: Mean cell viability was significantly decreased in native explants exposed to MP (35.5%) compared to control (49.8%, p &lt; 0.001) and TA (45.7%, p = 0.003) (Figure 1). There was significant weakening of mechanical properties of steroid-treated native explants when compared to control (Figure 2), with decreases in aggregate modulus (646.3 kPa vs 312.8 kPa [MP] and 257.0 kPa [TA), p &lt; 0.001), shear modulus (370.1 kPa vs 191.2 kPa [MP] and 157.4 kPa [TA], p &lt; 0.001), and ultimate tensile strength (UTS) (9.650 MPa vs 5.648 MPa [MP], p = 0.021 and 6.065 MPa [TA], p = 0.040). The Young’s modulus in TA-exposed native cartilage (7.924 MPa) was significantly lower than MP (12.35 MPa, p = 0.026) exposed explants but not significantly different compared to control (11.97 MPa, p =0.072). No significant differences in collagen and glycosaminoglycan content were found in the steroid-treated groups (Figure 3). Pyridinoline cross linking was significantly decreased in explants exposed to TA compared to control (p = 0.027). Conclusions: The results of this in vitro study suggest that a single clinical dose of MP is chondrotoxic and that a single clinical dose of MP or TA can lead to substantial early decreases in both the tensile and compressive properties of native articular cartilage. The shear modulus of steroid-exposed explants in this study dropped 48-57% compared to healthy control. In human knee cartilage, drops in shear modulus of this magnitude have been correlated with the progression from healthy knee cartilage to ICRS grade 1-2 osteoarthritis. Furthermore, decreases in Young’s modulus by 25-50% have been correlated with the same degree of osteoarthritis, and the Young’s modulus of steroid exposed cartilage dropped an average of 34% in this study. Although there were no detectable changes to the extracellular matrix composition or structure, a single one-hour steroid exposure was enough to cause chondrotoxicity and altered mechanics to native explants 24 hours after exposure, which raises the concern for risk of mechanical failure of the cartilage tissue. Clinicians should be judicious regarding use of intra-articular steroids, particularly in patients with intact healthy articular cartilage.

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.

In Vitro Analysis of Human Cartilage Infiltrated by Hydrogels and Hydrogel-Encapsulated Chondrocytes.

Osteoarthritis (OA) is a degenerative joint disease causing loss of articular cartilage and structural damage in all joint tissues. Given the limited regenerative capacity of articular cartilage, methods to support the native structural properties of articular cartilage are highly anticipated. The aim of this study was to infiltrate zwitterionic monomer solutions into human OA-cartilage explants to replace lost proteoglycans. The study included polymerization and deposition of methacryloyloxyethyl-phosphorylcholine- and a novel sulfobetaine-methacrylate-based monomer solution within ex vivo human OA-cartilage explants and the encapsulation of isolated chondrocytes within hydrogels and the corresponding effects on chondrocyte viability. The results demonstrated that zwitterionic cartilage-hydrogel networks are formed by infiltration. In general, cytotoxic effects of the monomer solutions were observed, as was a time-dependent infiltration behavior into the tissue accompanied by increasing cell death and penetration depth. The successful deposition of zwitterionic hydrogels within OA cartilage identifies the infiltration method as a potential future therapeutic option for the repair/replacement of OA-cartilage extracellular suprastructure. Due to the toxic effects of the monomer solutions, the focus should be on sealing the OA-cartilage surface, instead of complete infiltration. An alternative treatment option for focal cartilage defects could be the usage of monomer solutions, especially the novel generated sulfobetaine-methacrylate-based monomer solution, as bionic for cell-based 3D bioprintable hydrogels.

Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics.

Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the biomechanical properties of the extracellular matrix essential for its function. Collagen plays a very important role in maintaining the mechanical properties of articular cartilage and the stability of the ECM. Noteworthily, many pathogenic factors in the course of osteoarthritis and rheumatoid arthritis, such as mechanical injury, inflammation, and senescence, are involved in the irreversible degradation of collagen, leading to the progressive destruction of cartilage. The degradation of collagen can generate new biochemical markers with the ability to monitor disease progression and facilitate drug development. In addition, collagen can also be used as a biomaterial with excellent properties such as low immunogenicity, biodegradability, biocompatibility, and hydrophilicity. This review not only provides a systematic description of collagen and analyzes the structural characteristics of articular cartilage and the mechanisms of cartilage damage in disease states but also provides a detailed characterization of the biomarkers of collagen production and the role of collagen in cartilage repair, providing ideas and techniques for clinical diagnosis and treatment.

Full Regional Creep Displacement Map of Articular Cartilage Based on Nanoindentation Array.

The elucidation of the mechanisms underlying articular cartilage lesions poses a formidable challenge in the field of cartilage repair. Despite significant strides in cartilage mechanics research, the region-dependent creep properties of articular cartilage remain elusive. In this study, we employ depth-sensing indentation tests to experimentally determine the creep properties of four distinct regions of articular cartilage, thereby unveiling a region-dependent full map of creep parameters. The measured creep displacement-time response curves indicate that the creep properties of the articular cartilage exhibit a clear regional correlation. Accordingly, the full regional creep map of articular cartilage is experimentally constructed for the first time. The correlation between the microstructures and the creep properties of cartilage in different regions is revealed. A three-parameter model is established to describe the creep velocity-displacement response of cartilage. Raman spectra reveal that the proteoglycan content is positively correlated with creep properties. The Raman shift directly indicates diverse residual stresses in different microregions. The obtained data facilitate a deep understanding of the potential creep dependent damage mechanism of cartilage and the further development of artificial cartilage materials.

Characterizing site-specific mechanical properties of knee cartilage with indentation-relaxation maps and machine learning

Knee cartilage experiences site-specific focal lesion and degeneration, which is likely associated with tissue inhomogeneity and nonuniform mechanical stimuli in the joint, for which a complete picture remains to be depicted. The present study aimed to develop a methodology to quantify knee cartilage inhomogeneity using porcine knee specimens. Automated indentation-relaxation and needle probing were performed on fully intact cartilage to obtain data that essentially represent continuous distributions of cartilage properties in the knee. Machine learning was then introduced to approximate the tissue inhomogeneity with several regions via clusters of indentation locations, and finite element modeling was used to obtain poromechanical properties for each region using indentation-relaxation and thickness data. Significant region dependence was established from the full time-dependent mechanical response. Seventeen regions, or clusters, were found to best approximate the site-specific poromechanical properties of articular cartilage for femoral groove, lateral and medial condyles and tibial plateaus, after up to eight clusters were tested for each of the five cartilage sections. The region partitions recommended, and tissue properties acquired would facilitate implementation of tissue inhomogeneity in future applications, e.g., contact modeling of the knee joint. The results obtained from 14 porcine knees revealed interesting region differences, for example, the two condyles have the same effective stiffness when responding to slowly applied mechanical loadings but substantially lower stiffness in the medial condyle when responding to fast loadings. This mechanical behavior may be associated with the fact that medial femoral cartilage is more prone to focal lesions than the lateral one.

T 2 orientation anisotropy mapping of articular cartilage using qMRI

Objective. To provide orientation-independent MR parameters potentially sensitive to articular cartilage degeneration by measuring isotropic and anisotropic components of T 2 relaxation, as well as 3D fiber orientation angle and anisotropy via multi-orientation MR scans. Approach. Seven bovine osteochondral plugs were scanned with a high angular resolution of thirty-seven orientations spanning 180° at 9.4 T. The obtained data was fitted to the magic angle model of anisotropic T 2 relaxation to produce pixel-wise maps of the parameters of interest. Quantitative Polarized Light Microscopy (qPLM) was used as a reference method for the anisotropy and fiber orientation. Main results. The number of scanned orientations was found to be sufficient for estimating both fiber orientation and anisotropy maps. The relaxation anisotropy maps demonstrated a high correspondence with qPLM reference measurements of the collagen anisotropy of the samples. The scans also enabled calculating orientation-independent T 2 maps. Little spatial variation was observed in the isotropic component of T 2 while the anisotropic component was much faster in the deep radial zone of cartilage. The estimated fiber orientation spanned the expected 0°–90° in samples that had a sufficiently thick superficial layer. The orientation-independent magnetic resonance imaging (MRI) measures can potentially reflect the true properties of articular cartilage more precisely and robustly. Significance. The methods presented in this study will likely improve the specificity of cartilage qMRI by allowing the assessment of the physical properties such as orientation and anisotropy of collagen fibers in articular cartilage.

Recent Progress in Hydrogel-Based Synthetic Cartilage: Focus on Lubrication and Load-Bearing Capacities

Articular cartilage (AC), which covers the ends of bones in joints, particularly the knee joints, provides a robust interface to maintain frictionless movement during daily life due to its remarkable lubricating and load-bearing capacities. However, osteoarthritis (OA), characterized by the progressive degradation of AC, compromises the properties of AC and thus leads to frayed and rough interfaces between the bones, which subsequently accelerates the progression of OA. Hydrogels, composed of highly hydrated and interconnected polymer chains, are potential candidates for AC replacement due to their physical and chemical properties being similar to those of AC. In this review, we summarize the recent progress of hydrogel-based synthetic cartilage, or cartilage-like hydrogels, with a particular focus on their lubrication and load-bearing properties. The different formulations, current limitations, and challenges of such hydrogels are also discussed. Moreover, we discuss the future directions of hydrogel-based synthetic cartilage to repair and even regenerate the damaged AC.

Perspective in Achieving Stratified Articular Cartilage Repair Using Zonal Chondrocytes.

Articular cartilage is composed of superficial, medial, and deep zones, which endow the tissue with biphasic mechanical properties to withstand shearing force and compressional loading. The tissue has very limited self-healing capacity once it is damaged due to its avascular nature. To prevent the early onset of osteoarthritis, surgical intervention is often needed to repair the injured cartilage. Current noncell-based and cell-based treatments focus on the regeneration of homogeneous cartilage to achieve bulk compressional properties without recapitulating the zonal matrix and mechanical properties, and often oversight in aiding cartilage integration between host and repair cartilage. It is hypothesized that achieving zonal architecture in articular cartilage tissue repair could improve the structural and mechanical integrity and thus the life span of the regenerated tissue. Engineering stratified cartilage constructs using zonal chondrocytes have been hypothesized to improve the functionality and life span of the regenerated tissues. However, stratified articular cartilage repair has yet to be realized to date due to the lack of an efficient zonal chondrocyte isolation method and an expansion platform that would allow both cell propagation and phenotype maintenance. Various attempts and challenges in achieving stratified articular cartilage repair in a clinical setting are evaluated. In this review, different perspectives on achieving stratified articular cartilage repair using zonal chondrocytes are described. The effectiveness of different zonal chondrocyte isolation and zonal chondrocyte phenotype maintenance methodologies during expansion are compared, with the focus on recent advancements in zonal chondrocyte isolation and expansion that could present a possible strategy to overcome the limitation of applying zonal chondrocytes to facilitate zonal architecture development in articular cartilage regeneration. Impact Statement The zonal properties of articular cartilage contribute to the biphasic mechanical properties of the tissues. Recapitulation of the zonal architecture in regenerated articular cartilage has been hypothesized to improve the mechanical integrity and life span of the regenerated tissue. This review provides a comprehensive discussion on the current state of research relevant to achieving stratified articular cartilage repair using zonal chondrocytes from different perspectives. This review further elaborates on a zonal chondrocyte production pipeline that can potentially overcome the current clinical challenges and future work needed to realize stratified zonal chondrocyte implantation in a clinical setting.

Morphological and mechanical alterations in articular cartilage and subchondral bone during spontaneous hip osteoarthritis in guinea pigs.

Objectives: This study aimed to investigate the morphological and mechanical changes in articular cartilage and subchondral bone during spontaneous hip osteoarthritis in guinea pigs. Materials and methods: Hip joints of guinea pigs were investigated at 1, 3, 6, and 9 months of age (hereafter denoted as 1M, 3M, 6M, and 9M, respectively; n = 7 in each group). Morphological and mechanical alterations during spontaneous hip osteoarthritis in guinea pigs were investigated. The alterations included the micromechanical properties of articular cartilage (stiffness and creep deformation), microstructure of the subchondral bone (bone mineral density, bone volume fraction, trabecular thickness, trabecular number, and trabecular separation), micromorphology of the articular cartilage, and surface nanostructure (grain size and roughness) of the articular cartilage and subchondral bone. Results: Micromechanical properties of articular cartilage in 1M showed the lowest stiffness and highest creep deformation with no significant differences in stiffness or creep deformation amongst 3M, 6M, and 9M. Articular cartilage thickness decreased with age. The earliest degeneration of articular cartilage occurred at 6 months of age, characterised by surface unevenness and evident chondrocytes reduction in micromorphology, as well as increased grain size and decreased roughness in nanostructure. No degeneration at micro- or nanostructure of subchondral bone was observed before 9 months. Conclusion: Morphological degeneration of cartilage occurred before degeneration of mechanical properties. Meanwhile, degeneration of cartilage occurred before degeneration of subchondral bone during hip osteoarthritis. The current study provided novel insights into the structural and micromechanical interaction of hip osteoarthritis, which can serve as a theoretical basis for understanding the formation and progression of osteoarthritis.

Recent Advances in "Functional Engineering of Articular Cartilage Zones by Polymeric Biomaterials Mediated with Physical, Mechanical, and Biological/Chemical Cues".

Articular cartilage (AC) plays an unquestionable role in joint movements but unfortunately the healing capacity is restricted due to its avascular and acellular nature. While cartilage tissue engineering has been lifesaving, it is very challenging to remodel the complex cartilage composition and architecture with gradient physio-mechanical properties vital to proper tissue functions. To address these issues, a better understanding of the intrinsic AC properties and how cells respond to stimuli from the external microenvironment must be better understood. This is essential in order to take one step closer to producing functional cartilaginous constructs for clinical use. Recently, biopolymers have aroused much attention due to their versatility, processability, and flexibility because the properties can be tailored to match the requirements of AC. This review highlights polymeric scaffolds developed in the past decade for reconstruction of zonal AC layers including the superficial zone, middle zone, and deep zone by means of exogenous stimuli such as physical, mechanical, and biological/chemical signals. The mimicked properties are reviewed in terms of the biochemical composition and organization, cell fate (morphology, orientation, and differentiation), as well as mechanical properties and finally, the challenges and potential ways to tackle them are discussed.