scholarly journals Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis

2019 ◽  
Vol 20 (5) ◽  
pp. 1008 ◽  
Author(s):  
Paolo Alberton ◽  
Hans Dugonitsch ◽  
Bastian Hartmann ◽  
Ping Li ◽  
Zsuzsanna Farkas ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degeneration ◽  
Biomechanical Properties ◽  
Cartilage Tissue ◽  
Gene Encoding ◽  
Adult Mice ◽  
Skeletal Malformations ◽  
Wide Range ◽  
Normal Expression ◽  
Cartilage Erosion

The gene encoding the proteoglycan aggrecan (Agc1) is abundantly expressed in cartilage during development and adulthood, and the loss or diminished deposition of the protein results in a wide range of skeletal malformations. Furthermore, aggrecan degradation is a hallmark of cartilage degeneration occurring in osteoarthritis. In the present study, we investigated the consequences of a partial loss of aggrecan in the postnatal skeleton and in the articular cartilage of adult mice. We took advantage of the previously described Agc1tm(IRES-CreERT2) mouse line, which allows for conditional and timely-regulated deletion of floxed, cartilage-expressed genes. As previously reported, the introduction of the CreERT2 cassette in the 3’UTR causes a disruption of the normal expression of Agc1 resulting in a hypomorphic deposition of the protein. In homozygous mice, we observed a dwarf phenotype, which persisted throughout adulthood supporting the evidence that reduced aggrecan amount impairs skeletal growth. Homozygous mice exhibited reduced proteoglycan staining of the articular cartilage at 6 and 12 months of age, increased stiffening of the extracellular matrix at six months, and developed severe cartilage erosion by 12 months. The osteoarthritis in the hypomorph mice was not accompanied by increased expression of catabolic enzymes and matrix degradation neoepitopes. These findings suggest that the degeneration found in homozygous mice is likely due to the compromised mechanical properties of the cartilage tissue upon aggrecan reduction.

scholarly journals Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4199
Author(s):  
Mahshid Hafezi ◽  
Saied Nouri Khorasani ◽  
Mohadeseh Zare ◽  
Rasoul Esmaeely Neisiany ◽  
Pooya Davoodi
Keyword(s):  
Tissue Engineering ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Biomechanical Properties ◽  
Tissue Growth ◽  
Cartilage Tissue ◽  
Self Healing ◽  
Advantages And Disadvantages ◽  
Wide Range

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications.

scholarly journals Assessment of Native Human Articular Cartilage: A Biomechanical Protocol

Cartilage ◽  
2020 ◽  
pp. 194760352097324
Author(s):  
Wassif Kabir ◽  
Claudia Di Bella ◽  
Peter F.M. Choong ◽  
Cathal D. O’Connell
Keyword(s):  
Articular Cartilage ◽  
Poisson Ratio ◽  
Cartilage Tissue Engineering ◽  
Biomechanical Properties ◽  
Cartilage Tissue ◽  
Loading Frequency ◽  
Human Articular Cartilage ◽  
Compression Tests ◽  
Human Knee ◽  
Viscoelastic Parameters

Objectives 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. Design 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. Results 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). Conclusions 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.

The Effect of Storage on the Biomechanical Behavior of Articular Cartilage—A Large Strain Study

1992 ◽  
Vol 114 (1) ◽  
pp. 149-153 ◽  
Author(s):  
M. K. Kwan ◽  
S. A. Hacker ◽  
S. L.-Y. Woo ◽  
J. S. Wayne
Keyword(s):  
Articular Cartilage ◽  
Culture Media ◽  
Large Strain ◽  
Biomechanical Properties ◽  
Cartilage Tissue ◽  
Total Joint Replacements ◽  
Strain Behavior ◽  
Biomechanical Behavior ◽  
Tissue Culture Media ◽  
Osteochondral Allografts

The transplantation of stored shell osteochondral allografts is a potentially useful alternative to total joint replacements for the treatment of joint ailments. The maintenance of normal cartilage properties of the osteochondral allografts during storage is important for the allograft to function properly and survive in the host joint. Since articular cartilage is normally under large physiological stresses, this study was conducted to investigate the biomechanical behavior under large strain conditions of cartilage tissue stored for various time periods (i.e., 3, 7, 28, and 60 days) in tissue culture media. A biphasic large strain theory developed for soft hydrated connective tissues was used to describe and determine the biomechanical properties of the stored cartilage. It was found that articular cartilage stored for up to 60 days maintained the ability to sustain large compressive strains of up to 40 percent or more, like normal articular cartilage. Moreover, the equilibrium stress-strain behavior and compressive modulus of the stored articular cartilage were unchanged after up to 60 days of storage.

scholarly journals BENEFICIAL EFFECTS OF EXOGENOUS CROSSLINKING AGENTS ON SELF-ASSEMBLED TISSUE ENGINEERED CARTILAGE CONSTRUCT BIOMECHANICAL PROPERTIES

2011 ◽  
Vol 11 (02) ◽  
pp. 433-443 ◽  
Author(s):  
BENJAMIN D. ELDER ◽  
ARVIND MOHAN ◽  
KYRIACOS A. ATHANASIOU
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Cartilage Tissue Engineering ◽  
Biomechanical Properties ◽  
Cartilage Tissue ◽  
Engineering Approach ◽  
Tissue Engineering Approach ◽  
Crosslinking Agents

Background. As articular cartilage is unable to repair itself, there is a tremendous clinical need for a tissue engineered replacement tissue. Current tissue engineering efforts using the self-assembly process have demonstrated promising results, but the biomechanical properties remain at roughly 50% of native tissue. Methodology/Principal Findings. The objective of this study was to determine the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties of a scaffoldless cartilage tissue engineering approach. Four crosslinking agents (glutaraldehyde, ribose, genipin, and methylglyoxal) were applied each at a single concentration and single application time. It was determined that ribose application resulted in a significant 69% increase in Young's modulus, a significant 47% increase in ultimate tensile strength, as well as a trend toward a significant increase in aggregate modulus. Additionally, methylglyoxal application resulted in a significant 58% increase in Young's modulus. No treatments altered the biochemical content of the tissue. Conclusions/Significance. To our knowledge, this is the first study to examine the use of exogenous crosslinking agents on any tissue formed using a scaffoldless tissue engineering approach. In particular, this study demonstrates that a one-time treatment with crosslinking agents can be employed effectively to enhance the biomechanical properties of tissue engineered articular cartilage. The results are exciting, as they demonstrate the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties without the need for increased glycosaminoglycan (GAG) and collagen content.

Application of Microforming to Create Chondrocyte Home Sites in a Natural Cartilage Matrix

2014 ◽  
Author(s):  
Theodore W. Vandenberg ◽  
Christopher R. Nehme ◽  
Thomas P. James
Keyword(s):  
Articular Cartilage ◽  
Statistical Significance ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Tissue ◽  
Pathological Feature ◽  
The Matrix ◽  
Controlling Processes ◽  
Articular Cartilage Degeneration

Articular cartilage degeneration is a central pathological feature of osteoarthritis. Cartilage in the adult does not regenerate in vivo and, as a result, cartilage damage in osteoarthritis is irreversible. With our ever-aging population, osteoarthritis has become a leading cause of disability and unfortunately, no optimal treatments for osteoarthritis are currently available. To address this problem, a research community is focused on the development of both natural and synthetic biodegradable tissue scaffolds. The scaffolds must contain depressions or holes for the purpose of chondrocyte seeding and growth in order to create an implantable construct. In addition to chondrocytes, cartilage tissue consists of the extracellular matrix (ECM). Studies of many tissue types have established that ECM plays an important role in regulating cell behavior and controlling processes such as tissue differentiation and tumor progression. Unlike most natural tissues, adult cartilage ECM is exceptionally dense and lacking in vascularity, which makes it difficult for chondrocytes to be transplanted directly into the matrix. Current methods of creating cell home sites through chemical decellularization of the ECM degrade the mechanical integrity of the cartilage tissue. The research conducted here used a mechanical, rather than chemical, method to create cell home sites. A novel micropunching machine was developed to fabricate 200 μm diameter holes in cartilage, thereby creating a porous natural scaffold while maintaining a healthy ECM. Equine articular cartilage slices were harvested from the cadaver’s back knee joint and cryo-sectioned into 100 μm thick slices. Using die clearances of 3.7%, 6.8%, and 8.9%, the results indicate that micro-scale holes can be mechanically punched in cartilage tissue. The maximum punching force showed a slight trend of decreasing as die clearance increased, but there was no statistical significance. Punching force, as well as hole size, was highly dependent on sample hydration. Upon inspection, the resulting hole sizes were approximately 50 μm to 150 um, indicating 25% to 75% shrinkage in reference to the male punch diameter. Finally, the resulting hole shape was observed to be slightly non-circular and the edges of the hole exhibited a raggedness, which was indicative of the cartilage tearing during hole punching.

scholarly journals Nanoscale quantitative surface roughness measurement of articular cartilage using second-order statistical-based biospeckle

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246395
Author(s):  
Doaa Youssef ◽  
Salah Hassab-Elnaby ◽  
Hatem El-Ghandoor
Keyword(s):  
Surface Roughness ◽  
Articular Cartilage ◽  
Quantitative Measurement ◽  
Principal Component ◽  
Cartilage Degeneration ◽  
Second Order ◽  
Joint Disease ◽  
Cartilage Tissue ◽  
Diagnostic Tools ◽  
Highly Correlated

Quantitative measurement of nanoscale surface roughness of articular cartilage tissue is significant to assess the surface topography for early treatment of osteoarthritis, the most common joint disease worldwide. Since it was not established by clinical diagnostic tools, the current studies have been suggesting the use of alternative diagnostic tools using pre-clinical methods. This study aims to measure the nanoscale surface roughness of articular cartilage tissue utilizing biospeckle which is used as a non-destructive and non-contact optical imaging technique. An experimental setup was implemented to capture biospeckle images from twelve cross-section areas of articular cartilage tissue gathered from bovine knee joints at 632 nm wavelength laser radiation. Then, to analyze the biospeckle image, a second-order statistical-based method was proposed through the combination of 308 highly correlated statistical features extracted from implemented gray-level co-occurrence matrices by employing principal component analysis. The result indicated that the measurement of the nanoscale surface roughness based on the first principal component only is able to provide accurate and precise quantitative measurement of early signs of articular cartilage degeneration up to 2500 nm.

scholarly journals Expression and Localization of Thrombospondins, Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee

2021 ◽  
Vol 22 (6) ◽  
pp. 3073
Author(s):  
Daniela Mählich ◽  
Anne Glasmacher ◽  
Ilka Müller ◽  
Johannes Oppermann ◽  
David Grevenstein ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Actin Cytoskeleton ◽  
Matrix Protein ◽  
Cartilage Degeneration ◽  
Staining Intensity ◽  
Lateral Compartment ◽  
Cartilage Tissue ◽  
Varus Knee ◽  
Knee Oa ◽  
Topographical Analysis

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.

scholarly journals BMP signaling is necessary and sufficient for osteoarthritis and a target for disease modifying therapy

2021 ◽  
Author(s):  
Akrit Pran Jaswal ◽  
Anke J Roelofs ◽  
Amaresh Kumar Singh ◽  
Bhupendra Kumar ◽  
Anna H.K. Riemen ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degeneration ◽  
Bmp Signaling ◽  
Endochondral Bone ◽  
Local Inhibition ◽  
Adult Mice ◽  
Disease Modifying Therapy ◽  
Cartilage Differentiation ◽  
Ectopic Activation ◽  
Disease Modifying

Osteoarthritis (OA) is among the leading causes of disability across the world. Presently no effective therapy of OA is available as neither the molecular mechanism of disease pathology nor the development and maintenance of articular cartilage is well understood. During OA, articular cartilage undergoes cellular and molecular changes reminiscent of transient cartilage, which is the embryonic precursor of endochondral bone. During endochondral ossification, a precise spatio-temporally regulated WNT-BMP signaling interplay dictates differentiation of a common progenitor pool to either articular or transient cartilage fate in adjacent domains. In the embryonic context, Wnt signaling promotes articular cartilage fate while transient cartilage differentiation is critically BMP signaling dependent. Moreover, any ectopic activation of BMP signaling leads to ectopic transient cartilage differentiation at the expense of articular cartilage. In this study, we show that BMP signaling is sufficient and necessary for the pathogenesis of OA by ectopically activating BMP signaling and depleting BMP ligands in adult mice articular cartilage, respectively. Analysis of human osteoarthritic specimens demonstrated association between OA and ectopic BMP signaling in the articular cartilage. Local inhibition of BMP signaling using a potent pharmacological inhibitor LDN-193189, when administered prophylactically, resulted in delayed onset and reduced severity of OA in mice. Additionally, the same treatment afforded protection against cartilage degeneration post onset of OA in a surgical model of OA in mice. Therefore, inhibiting BMP signaling and consequent block of transient cartilage differentiation within the cells of the joint cartilage can be a possible avenue for developing a disease modifying therapy for OA.

scholarly journals Infrared fiber optic spectroscopy detects bovine articular cartilage degeneration

2020 ◽  
Author(s):  
Vesa Virtanen ◽  
Ervin Nippolainen ◽  
Rubina Shaikh ◽  
Isaac Afara ◽  
Juha Töyräs ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Articular Cartilage ◽  
Fiber Optic ◽  
Mechanical Damage ◽  
Fourier Transform Infrared ◽  
Cartilage Degeneration ◽  
Cartilage Tissue ◽  
Support Vector ◽  
Joint Injuries ◽  
Atr Spectroscopy

AbstractArticular cartilage (AC) is a soft connective tissue that covers the ends of articulating bones. Joint injuries may lead to degeneration of cartilage tissue and initiate development of post-traumatic osteoarthritis (OA). Arthroscopic surgeries can be used to treat joint injuries, but arthroscopic evaluation of cartilage quality is subjective. Therefore, new methods are needed for objective assessment of cartilage degeneration. Fourier transform infrared (FTIR) spectroscopy can be used to assess tissue composition based on the fundamental molecular vibrations. When combined with fiber optics and attenuated total reflectance (ATR) crystal, the measurements can be done flexibly without any sample processing. We hypothesize that Fourier transform infrared attenuated total reflection (FTIR-ATR) spectroscopy can detect enzymatically and mechanically induced changes similar to changes occurring during progression of OA. Fresh bovine patellar cartilage plugs (n = 60) were extracted and degraded enzymatically and mechanically. Adjacent untreated control samples (n = 60) were utilized as controls. Enzymatic degradation was implemented by 90-min and 24-hour collagenase as well as 30-min trypsin treatments. Mechanical damage was induced by: 1) dropping a weight impactor on the cartilage plugs, and 2) abrading the cartilage surface with a rotating sandpaper. Fiber optic FTIR-ATR spectroscopic measurements were conducted for control and degraded samples, and spectral changes were assessed with random forest (RF), partial least squares discriminant analysis (PLS-DA), and support vector machine (SVM) classifiers. RF (accuracy 93.1 % to 79.2 %), PLS-DA (accuracy 95.8% to 81.9%), and SVM (accuracy 91.7% to 80.6%) all had excellent classification performance for detecting the different enzymatic and mechanical damage on cartilage matrix. The results suggest that fiber optic FTIR-ATR spectroscopy is a viable way to detect minor degeneration of AC.

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