Mechanical Properties Of Articular Cartilage Research Articles

Biphasic ECM assembled graphene oxide-collagen/nHap composites mimicking articular microenvironment for in situ osteochondral defect repair

Both bone and cartilage microenvironments play a crucial role in the regeneration of osteochondral defects caused by osteoarthritis (OA). A major challenge is how to simulate gradient changing mechanical properties and inducing abilities of regenerative microenvironments on the integrated scaffold to achieve simultaneous regeneration. In this work, a concept of biphasic ECM assembled graphene oxide-collagen (GO-COL)/ Nano-hydroxyapatite (nHap) composite is proposed. GO-COL/nHap bilayer scaffold with gradient concentration was formed by crosslinking and freeze-drying in stages to mimic the gradient distribution of mechanical properties of articular cartilage and bone. Then we prepared chondrogenic/osteogenic ECM membranes (CgECM/OgECM) with chondrocytes from rat knee respectively, and assembled them onto corresponding layers. The morphology, physical properties, biocompatibility, and osteochondrogenic capability of the scaffold were evaluated in vitro and in vivo. Mechanically, gene expression and protein level assessments showed greater osteochondrogenic activity in the biphasic ECM scaffold group compared to the GO-COL bilayer scaffold group. In vivo studies using a rat knee osteochondral defect model further confirmed the superior repair effect of the biphasic ECM-scaffold group compared to the blank group. Taken together, the proposed ECM assembled GO-COL/nHap strategy open a window to realize different microenvironment mimicking in a whole scaffold, making it a potential off-the-shelf method for osteochondral tissue engineering.

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.

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.

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.

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.

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.

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.

Zonally Stratified Decalcified Bone Scaffold with Different Stiffness Modified by Fibrinogen for Osteochondral Regeneration of Knee Joint Defect.

Articular cartilage is generally known to be a complex tissue with multiple layers. Each layer has different composition, structure, and mechanical properties, making regeneration after knee joint defects a troubling clinical problem. A novel integrated stratified decalcified bone matrix (SDBM) scaffold with different stiffness to mimic the mechanical properties of articular cartilage is presented herein. This SDBM scaffold was modified using fibrinogen (Fg) (Fg + SDBM) to enhance its vascularization ability and improve its repair efficiency for osteochondral defects of knee joints. A Fg + SDBM scaffold with different elastic modulus in each layer (high-stiffness DBM (HDBM) layer, 174.208 ± 44.330 MPa (Fg + HDBM); medium-stiffness DBM (MDBM) layer, 21.214 ± 6.922 MPa (Fg + MDBM); and low-stiffness DBM (LDBM) layer, 0.678 ± 0.269 MPa (Fg + LDBM)) was constructed by controlling the stratified decalcification time with layered embedding paraffin (0, 3, and 5 days). The low- and medium-stiffness layers of the Fg + SDBM scaffold remarkably promoted the cartilage differentiation of bone marrow mesenchymal stem cells in vitro. Subcutaneous transplantation and rabbit knee joint osteochondral defect repair experiments revealed that the low- and medium-stiffness layers of the Fg + SDBM scaffold exhibited wonderful cartilage capacity, whereas the high-stiffness layer of Fg + SDBM scaffold exhibited good osteogenesis ability. Furthermore, this scaffold could promote blood vessel formation in subchondral bone area. This study presents a feasible strategy for osteochondral regeneration of defective knee joints, which is of great clinical value for tissue repair.

Mechanical properties of cracked articular cartilage under uniaxial creep and cyclic tensile loading

Cracks may change the mechanical properties of articular cartilage, and further lead to early osteoarthritis. The study aimed to probe the mechanical properties of cracked cartilage under uniaxial tensile loading. The fracture process of cracked cartilage can be divided into two stages, namely crack-tip blunting stage and crack growth stage. The creep strain of cracked cartilage increases rapidly and then slowly with time, and it is well predicted by the nonlinear viscoelastic creep model. Compared with intact cartilage, cracked cartilage shows larger creep strain. During cyclic loading, the mean strain, degree of necking and crack-tip blunting of cracked cartilage increase with the increase of peak stress, while they decrease with the increase of loading frequency. The crack-tip morphology shows that cyclic loading has induced irreversible deformation in cartilage with a large number of collagen fibrils yielding, and further damaged the collagen fibril network of cartilage. However, no obvious crack growth is observed under the testing conditions.

Biomechanics of the Femoral Head Cartilage and Subchondral Trabecular Bone in Osteoporotic and Osteopenic Fractures

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.

Indentation method accounting for thickness effect of viscoelastic layer

AbstractIndentation tests have been widely used to evaluate the mechanical properties of industrial and biological materials in many studies. In this study, we obtained an analytical solution for the axisymmetric contact problem for a viscoelastic layer bonded to a rigid substrate and indented by a flat‐ended cylindrical punch using the elastic–viscoelastic correspondence principle. The analytical solution was obtained from a method using an infinite system of simultaneous equations instead of a conventional method using the second kind of Fredholm equation. Relaxation indentation tests were conducted for silicon rubber, polyurethane gel (a soft material used for elastography), and articular cartilage from a bovine femoral head. The articular cartilage was tested as obtained and then tested again after treatment by collagenase. The viscoelastic models in this study were a three‐element model (standard linear solid model) and a five‐element model (generalized Maxwell model), and the viscoelastic parameters for the models were determined by fitting the analytical solution to results for applied load as it varied over time during relaxation indentation tests. The results suggested that the five‐element model was more appropriate than the three‐element model for reproducing the relaxation indentation behavior of silicon rubber, polyurethane gel, and articular cartilage. Furthermore, the viscoelastic parameters for treated articular cartilage clearly decreased compared with those for unaltered articular cartilage. These results suggest that the method for evaluating the time‐dependent mechanical properties of articular cartilage based on analytical solutions of relaxation indentation tests could be a useful tool for evaluating the state of degenerated cartilage.

Assessment of Native Human Articular Cartilage: A Biomechanical Protocol.

Recapitulating the mechanical properties of articular cartilage (AC) is vital to facilitate the clinical translation of cartilage tissue engineering. Prior to evaluation of tissue-engineered constructs, it is fundamental to investigate the biomechanical properties of native AC under sudden, prolonged, and cyclic loads in a practical manner. However, previous studies have typically reported only the response of native AC to one or other of these loading regimes. We therefore developed a streamlined testing protocol to characterize the elastic and viscoelastic properties of human knee AC, generating values for several important parameters from the same sample. Human AC was harvested from macroscopically normal regions of distal femoral condyles of patients (n = 3) undergoing total knee arthroplasty. Indentation and unconfined compression tests were conducted under physiological conditions (temperature 37 °C and pH 7.4) and testing parameters (strain rates and loading frequency) to assess elastic and viscoelastic parameters. The biomechanical properties obtained were as follows: Poisson ratio (0.4 ± 0.1), instantaneous modulus (52.14 ± 9.47 MPa) at a loading rate of 1 mm/s, Young's modulus (1.03 ± 0.48 MPa), equilibrium modulus (7.48 ± 4.42 MPa), compressive modulus (10.60 ± 3.62 MPa), dynamic modulus (7.71 ± 4.62 MPa) at 1 Hz and loss factor (0.11 ± 0.02). The measurements fell within the range of reported values for human knee AC biomechanics. To the authors' knowledge this study is the first to report such a range of biomechanical properties for human distal femoral AC. This protocol may facilitate the assessment of tissue-engineered composites for their functionality and biomechanical similarity to native AC prior to clinical trials.

Assessment of mechanical properties of articular cartilage with quantitative three-dimensional ultrashort echo time (UTE) cones magnetic resonance imaging

Conventional magnetic resonance imaging (MRI) is not capable of detecting signal from the deep cartilage due to its short transverse relaxation time (T2). Moreover, several quantitative MRI techniques are significantly influenced by the magic angle effect. The combinations of ultrashort echo time (UTE) MRI with magnetization transfer (UTE-MT) and Adiabatic T1ρ (UTE-AdiabT1ρ) imaging allow magic angle-insensitive assessments of all regions of articular cartilage. The purpose of this study was to investigate the correlations between quantitative three-dimensional UTE MRI biomarkers and mechanical properties of human tibiofemoral cartilage specimens. In total, 40 human tibiofemoral cartilage specimens were harvested from three male and four female donors (64 ± 18 years old). Cartilage samples were scanned using a series of quantitative 3D UTE Cones T2* (UTE-T2*), T1 (UTE-T1), UTE-AdiabT1ρ, and UTE-MT sequences in a standard knee coil on a clinical 3T scanner. UTE-MT data were acquired with a series of MT powers and frequency offsets to calculate magnetization transfer ratio (MTR), as well as macromolecular fraction (MMF) and macromolecular T2 (T2mm) through modeling. Cartilage stiffness and Hayes elastic modulus were measured using indentation tests. Correlations of 3D UTE Cones MRI measurements in the superficial layer, deep layer, and global regions of interest (ROIs) with mechanical properties were investigated. Cartilage mechanical properties demonstrated highest correlations with UTE measures of the superficial layer of cartilage. AdiabT1ρ, MTR, and MMF in superficial layer ROIs showed significant correlations with Hayes elastic modulus (p < 0.05, R = −0.54, 0.49, and 0.66, respectively). These UTE measures in global ROIs showed significant, though slightly lower, correlations with Hayes elastic modulus (p < 0.05, R = −0.37, 0.52, and 0.60, respectively). Correlations between other UTE MRI measurements (T2*, T1, and T2mm) and mechanical properties were non-significant. The 3D UTE-AdiabT1ρ and UTE-MT sequences were highlighted as promising surrogates for non-invasive assessment of cartilage mechanical properties. MMF from UTE-MT modeling showed the highest correlations with cartilage mechanics.

Reinforcing interpenetrating network hydrogels with 3D printed polymer networks to engineer cartilage mimetic composites

Engineering constructs that mimic the complex structure, composition and biomechanics of the articular cartilage represents a promising route to joint regeneration. Such tissue engineering strategies require the development of biomaterials that mimic the mechanical properties of articular cartilage whilst simultaneously providing an environment supportive of chondrogenesis. Here three-dimensional (3D) bioprinting is used to develop polycaprolactone (PCL) fibre networks to mechanically reinforce interpenetrating network (IPN) hydrogels consisting of alginate and gelatin methacryloyl (GelMA). Inspired by the significant tension-compression nonlinearity of the collagen network in articular cartilage, we printed reinforcing PCL networks with different ratios of tensile to compressive modulus. Synergistic increases in compressive modulus were observed when IPN hydrogels were reinforced with PCL networks that were relatively soft in compression and stiff in tension. The resulting composites possessed equilibrium and dynamic mechanical properties that matched or approached that of native articular cartilage. Finite Element (FE) modelling revealed that the reinforcement of IPN hydrogels with specific PCL networks limited radial expansion and increased the hydrostatic pressure generated within the IPN upon the application of compressive loading. Next, multiple-tool biofabrication techniques were used to 3D bioprint PCL reinforced IPN hydrogels laden with a co-culture of bone marrow-derived stromal cells (BMSCs) and chondrocytes (CCs). The bioprinted biomimetic composites were found to support robust chondrogenesis, with encapsulated cells producing hyaline-like cartilage that stained strongly for sGAG and type II collagen deposition, and negatively for type X collagen and calcium deposition. Taken together, these results demonstrate how 3D bioprinting can be used to engineer constructs that are both pro-chondrogenic and biomimetic of the mechanical properties of articular cartilage.

Injectable Microannealed Porous Scaffold for Articular Cartilage Regeneration.

The purpose of this study is to assess the feasibility of a novel microporous annealed particle (MAP) scaffolding hydrogel to enable both articular cartilage and subchondral bone biointegration and chondrocyte regeneration in a rat knee osteochondral defect model. An injectable, microporous scaffold was engineered and modified to match the mechanical properties of articular cartilage. Two experimental groups were utilized-negative saline control and MAP gel treatment group. Saline and MAP gel were injected into osteochondral defects created in the knees of Sprague-Dawley rats. Photo-annealing of the MAP gel was performed. Qualitative histologic and immunohistochemical analysis was performed of the treated defects at 2, 4, and 8 weeks postsurgery. The injectable MAP gel successfully annealed and was sustained within the osteochondral defect at each timepoint. Treatment with MAP gel resulted in maintained size of the osteochondral defect with evidence of tissue ingrowth and increased glycosaminoglycan production, whereas the control defects presented with evidence of disorganized scar tissue. Additionally, there was no significant inflammatory response to the MAP gel noted on histology. We have demonstrated the successful delivery of an injectable, flowable MAP gel scaffold into a rat knee osteochondral defect with subsequent annealing and stable integration into the healing wound. The flowable nature of this scaffold allows for minimally invasive application, for example, via an arthroscopic approach for management of wrist arthritis. The MAP gel was noted to fill the osteochondral defect and maintain the defect dimensions and provide a continuous and smooth surface for cartilage regeneration, suggesting its ability to provide a stable scaffold for tissue ingrowth. Future chemical, mechanical, and biological gel modifications may improve objective evidence of cartilage regeneration.

Additive manufacturing of an elastic poly(ester)urethane for cartilage tissue engineering

Although a growing knowledge on the field of tissue engineering of articular cartilage exists, reconstruction or in-vitro growth of functional hyaline tissue still represents an unmet challenge. Despite the simplicity of the tissue in terms of cell population and absence of innervation and vascularization, the outstanding mechanical properties of articular cartilage, which are the result of the specificity of its extra cellular matrix (ECM), are difficult to mimic. Most importantly, controlling the differentiation state or phenotype of chondrocytes, which are responsible of the deposition of this specialized ECM, represents a milestone in the regeneration of native articular cartilage. In this study, we fabricated fused deposition modelled (FDM) scaffolds with different pore sizes and architectures from an elastic and biodegradable poly(ester)urethane (PEU) with mechanical properties that can be modulated by design, and that ranged the elasticity of articular cartilage. Cell culture in additive manufactured 3D scaffolds exceeded the chondrogenic potential of the gold-standard pellet culture. In-vitro cell culture studies demonstrated the intrinsic potential of elastic (PEU) to drive the re-differentiation of de-differentiated chondrocytes when cultured in-vitro, in differentiation or basal media, better than pellet cultures. The formation of neo-tissue was assessed as a high deposition of GAGs and fibrillar collagen II, and a high expression of typical chondrogenic markers. Moreover, the collagen II / collagen I ratio commonly used to evaluate the differentiation state of chondrocytes (ratio > 1 being chondrocytes and, ratio < 0 being de-differentiated chondrocytes) was higher than 5. Statement of significanceTissue engineering of articular cartilage requires material scaffolds capable of driving the deposition of a coherent and specific ECM representative of articular cartilage. Materials explored so far account for low mechanical properties (hydrogels), or are too stiff to mimic the elasticity of the native tissue (traditional polyesters). Here, we fabricated 3D fibrous scaffolds via FDM with a biodegradable poly(ester)urethane. The compressive Young`s modulus and elastic limit of the scaffolds can be tuned by designed, mimicking those of the native tissue. The designed scaffolds showed an intrinsic potential to drive the formation of a GAG and collagen II rich ECM, and to drive a stable chondrogenic cell phenotype.

Changes in viscoelastic properties of articular cartilage in early stage of osteoarthritis, as determined by optical coherence tomography-based strain rate tomography

BackgroundBiomechanical changes in articular cartilage are associated with the onset of osteoarthritis. We developed an optical coherence tomography-based strain rate tomography method: stress relaxation optical coherence straingraphy (SR-OCSA). The purpose of this study was to establish an approach for measuring mechanical properties of articular cartilage using SR-OCSA, and to investigate the distribution of viscoelastic properties of articular cartilage in early osteoarthritis.MethodsAnterior cruciate ligament transection surgery was performed on the left knees of 8–9-month-old New Zealand white rabbits. SR-OCSA was used to visualize and measure the viscoelastic properties of articular cartilage via attenuation coefficient of strain rate (ACSR). Using the same conditions as in the SR-OCSA test, an indentation test was conducted, and relaxation time was measured to evaluate the relationship between ACSR and relaxation time.ResultsSR-OCSA could nondestructively detect and visualize changes in the distribution of viscoelastic properties of articular cartilage in early osteoarthritis. SR-OCSA captured significant increases in ACSR in cartilage at 2 weeks after surgery, when a histologically slight osteoarthritis sign was present. As cartilage degeneration progressed, ACSR increased, whereas relaxation time decreased in a time-dependent manner. Moreover, ACSR negatively correlated with relaxation time. In particular, ACSR was elevated around the tidemark and the elevation tended to move as cartilage degeneration progressed.ConclusionsSR-OCSA could tomographically and nondestructively detect and visualize changes in the distribution of viscoelastic properties of articular cartilage in early osteoarthritis. The mechanical properties around the tidemark were degraded as cartilage degeneration progressed. Thus, SR-OCSA provides important data needed to understand the biomechanics of early osteoarthritis.

Effects of radiopharmaceuticals on articular cartilage’s mechanical properties

Abstract As radiation science and technology advances, nuclear medicine applications are increasing worldwide which necessitate the understanding of biological implications of such practices. Ionizing radiation has been shown to cause degraded matrix and reduced proteoglycan synthesis in cartilage, and the late consequences of which may include degenerative arthritis or arthropathy. Although degenerative effects of the ionizing radiation on cartilage tissue have been demonstrated, the effects on the mechanical properties of articular cartilage are largely unknown. The radiopharmaceuticals, technetium-99m and technetium-99m sestamibi, were utilized on bovine articular cartilage to investigate these effects. We used two different mechanical tests to determine the mechanical properties of articular cartilage. Dynamic and static mechanical tests were applied to calculate compressive modulus for articular cartilage. We observed clearly higher control modulus values than that of experimental groups which account for lesser stiffness in the exposed cartilage. In conclusion, compressive moduli of bovine articular cartilage were found to decrease after radiopharmaceutical exposure, after both instantaneous and equilibrium mechanical experiments.

Dual fluoroscopic evaluation of human tibiofemoral joint kinematics during a prolonged standing: A pilot study

A complete knowledge of tibiofemoral joint kinematics is essential for understanding the function of the healthy and pathological joint. The objective of the present study was to establish a dual fluoroscopic measurement protocol and a data processing approach for the creep response of the knee joint in order to further evaluate the mechanical properties of articular cartilage and meniscus in vivo. A computational approach was developed for the determination of 3D translations and rotations of the joints of young participants with no history of injury using dual fluoroscopic images of loaded joints and joint geometry reconstructed from magnetic resonance imaging of the unloaded joints. High-resolution X-ray images were obtained for the distal femur and proximal tibia during 10-min standing when approximately ¾ body weight was slowly applied to the right leg and then kept constant for the rest duration of the test. Anatomic coordinate systems were established for the 3D models of distal femur and proximal tibia. Translations and rotations of the joint as functions of time were then evaluated using the X-ray images and these coordinate systems with the JointTrack software. The displacements in the proximal-distal direction obtained from two participants were consistent, showing a substantial increase in the initial phase when joint loading increased from nil to ¾ body weight and a continued small increase over time while the joint loading remained constant. The maximum anterior-posterior translations during 10-min standing were approximately 4 mm for both participants, although one showed better stability than the other. In conclusion, a creep loading protocol of the knee joint can be reasonably established for in vivo conditions and evaluated with the image-based computational approach.

A compression system for studying depth-dependent mechanical properties of articular cartilage under dynamic loading conditions

The biological activities of chondrocytes are influenced by the mechanical characteristics of their environment. The overall real-time mechanical response of cartilage has been investigated earlier. However, the instantaneous local mechano-biology of cartilage has not been investigated in detail under dynamic loading conditions. In order to address this gap in the literature, we designed a compression testing device and implemented a dual photon microscopy technique with the goal of measuring local mechanical and biological responses of articular cartilage under dynamic loading conditions. The details of the compression system and results of a pilot study are presented here. A 15% ramp compression at a rate of 0.003/s with a subsequent stress relaxation phase was applied to the cartilage explant samples. The extra cellular matrix was imaged throughout the entire thickness of the cartilage sample, and local tissue strains were measured during the compression and relaxation phase. The axial compressive strains in the middle and superficial zones of cartilage were observed to increase during the relaxation phase: this was a new finding, suggesting the importance of further investigations on the real-time local behavior of cartilage. The compression system showed promising results for investigating the dynamic, real-time mechanical response of articular cartilage, and can now be used to reveal the instantaneous mechanical and biological responses of chondrocytes in response to dynamic loading conditions.