The Effect of Antibody Size and Mechanical Loading on Solute Diffusion Through the Articular Surface of Cartilage

2017 ◽  
Vol 139 (9) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Andrew Goodearl ◽  
Anna Yarilina ◽  
Victor Sun ◽  
Soumya Mitra ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Articular Surface ◽  
Solute Diffusion ◽  
Cartilage Tissue ◽  
Tissue Penetration ◽  
Transport Enhancement ◽  
Healthy Cartilage ◽  
Heterogeneous Nature ◽  
Therapeutic Molecules

Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.

Cyclic Mechanical Loading Enhances Transport of Antibodies Into Articular Cartilage

2016 ◽  
Vol 139 (1) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Zhen Xiang Wang ◽  
Lawrence J. Bonassar
Keyword(s):  
Finite Element ◽  
Articular Cartilage ◽  
Mechanical Loading ◽  
Mechanical Stimulation ◽  
Mechanical Load ◽  
Linear Trend ◽  
Fluid Velocity ◽  
Cartilage Tissue ◽  
Clinical Value ◽  
Maximum Enhancement

The goal of this study was to characterize antibody penetration through cartilage tissue under mechanical loading. Mechanical stimulation aids in the penetration of some proteins, but this effect has not characterized molecules such as antibodies (>100 kDa), which may hold some clinical value for treating osteoarthritis (OA). For each experiment, fresh articular cartilage plugs were obtained and exposed to fluorescently labeled antibodies while under cyclic mechanical load in unconfined compression for several hours. Penetration of these antibodies was quantified using confocal microscopy, and finite element (FE) simulations were conducted to predict fluid flow patterns within loaded samples. Transport enhancement followed a linear trend with strain amplitude (0.25–5%) and a nonlinear trend with frequency (0.25–2.60 Hz), with maximum enhancement found to be at 5% cyclic strain and 1 Hz, respectively. Regions of highest enhancement of transport within the tissue were associated with the regions of highest interstitial fluid velocity, as predicted from finite-element simulations. Overall, cyclic compression-enhanced antibody transport by twofold to threefold. To our knowledge, this is the first study to test how mechanical stimulation affects the diffusion of antibodies in cartilage and suggest further study into other important factors regarding macromolecular transport.

scholarly journals Preparation and Characterization of Poly(vinyl alcohol)-chondroitin Sulphate Hydrogel as Scaffolds for Articular Cartilage Regeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Shivani Nanda ◽  
Nikhil Sood ◽  
B. V. K. Reddy ◽  
Tanmay S. Markandeywar
Keyword(s):  
Articular Cartilage ◽  
Chondroitin Sulphate ◽  
Articular Surface ◽  
Rheological Behaviour ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Poly Vinyl Alcohol ◽  
Cross Linking ◽  
Articular Cartilage Regeneration

The aim of the study was to develop PVA-CS hydrogel scaffolds using glutaraldehyde as a cross-linking agent by chemical cross-linking method in order to obtain biomimetic scaffolds for articular cartilage regeneration. The introduction of PVA enhances the mechanical and bioadhesive properties to the native tissue while chondroitin sulphate enhances the glycosaminoglycan content of extracellular matrix. The role of hydrogel as cartilage regeneration scaffold was evaluated by swelling study, porosity, rheological behaviour, in vitro degradation, and quantification of released chondroitin sulphate. In vivo results showed that cross-linked hydrogels repaired defects with no sign of inflammation as it was well anchored to tissue in the formation of new articular surface. It may be concluded that the addition of chondroitin sulphate to the PVA polymer develops a novel composite with significant applications in cartilage tissue engineering.

scholarly journals The Relationship Between Proteoglycan Loss, Overloading-Induced Collagen Damage, and Cyclic Loading in Articular Cartilage

Cartilage ◽  
2019 ◽  
pp. 194760351988500
Author(s):  
Lorenza Henao-Murillo ◽  
Maria-Ioana Pastrama ◽  
Keita Ito ◽  
Corrinus C. van Donkelaar
Keyword(s):  
Articular Cartilage ◽  
Cyclic Loading ◽  
Mechanical Loading ◽  
Mechanical Tests ◽  
Repeated Loading ◽  
Healthy Cartilage ◽  
Before And After ◽  
Damage Grades ◽  
The Relationship ◽  
Phosphate Buffered Saline

Objective The interaction between proteoglycan loss and collagen damage in articular cartilage and the effect of mechanical loading on this interaction remain unknown. The aim of this study was to answer the following questions: (1) Is proteoglycan loss dependent on the amount of collagen damage and does it depend on whether this collagen damage is superficial or internal? (2) Does repeated loading further increase the already enhanced proteoglycan loss in cartilage with collagen damage? Design Fifty-six bovine osteochondral plugs were equilibrated in phosphate-buffered saline for 24 hours, mechanically tested in compression for 8 hours, and kept in phosphate-buffered saline for another 48 hours. The mechanical tests included an overloading step to induce collagen damage, creep steps to determine tissue stiffness, and cyclic loading to induce convection. Proteoglycan release was measured before and after mechanical loading, as well as 48 hours post-loading. Collagen damage was scored histologically. Results Histology revealed different collagen damage grades after the application of mechanical overloading. After 48 hours in phosphate-buffered saline postloading, proteoglycan loss increased linearly with the amount of total collagen damage and was dependent on the presence but not the amount of internal collagen damage. In samples without collagen damage, repeated loading also resulted in increased proteoglycan loss. However, repeated loading did not further enhance the proteoglycan loss induced by damaged collagen. Conclusion Proteoglycan loss is enhanced by collagen damage and it depends on the presence of internal collagen damage. Cyclic loading stimulates proteoglycan loss in healthy cartilage but does not lead to additional loss in cartilage with damaged collagen.

scholarly journals Chondrogenic Differentiation of Human Adipose-Derived Stem Cells: A New Path in Articular Cartilage Defect Management?

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jan-Philipp Stromps ◽  
Nora Emilie Paul ◽  
Björn Rath ◽  
Mahtab Nourbakhsh ◽  
Jürgen Bernhagen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Adipose Derived Stem Cells ◽  
Age Related ◽  
Healthy Cartilage ◽  
Control And Prevention ◽  
Articular Cartilage Defects

According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs) and provides an outlook on promising future strategies.

The Effect of Charge and Mechanical Loading on Antibody Diffusion Through the Articular Surface of Cartilage

2018 ◽  
Vol 141 (1) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Lawrence J. Bonassar
Keyword(s):  
Mechanical Loading ◽  
Isoelectric Point ◽  
Articular Surface ◽  
Molecular Transport ◽  
Past Research ◽  
Convective Transport ◽  
Cartilage Matrix ◽  
Cartilage Sample ◽  
Transport Enhancement ◽  
Positively Charged

Molecular transport of osteoarthritis (OA) therapeutics within articular cartilage is influenced by many factors, such as solute charge, that have yet to be fully understood. This study characterizes how solute charge influences local diffusion and convective transport of antibodies within the heterogeneous cartilage matrix. Three fluorescently tagged solutes of varying isoelectric point (pI) (4.7–5.9) were tested in either cyclic or passive cartilage loading conditions. In each case, local diffusivities were calculated based on local fluorescence in the cartilage sample, as observed by confocal microscopy. In agreement with past research, local solute diffusivities within the heterogeneous cartilage matrix were highest around 200–275 μm from the articular surface, but 3–4 times lower at the articular surface and in the deeper zones of the tissue. Transport of all 150 kDa solutes was significantly increased by the application of mechanical loading at 1 Hz, but local transport enhancement was not significantly affected by changes in solute isoelectric point. More positively charged solutes (higher pI) had significantly higher local diffusivities 200–275 μm from the tissue surface, but no other differences were observed. This implies that there are certain regions of cartilage that are more sensitive to changes in solute charge than others, which could be useful for future development of OA therapeutics.

scholarly journals Main and Minor Types of Collagens in the Articular Cartilage: The Role of Collagens in Repair Tissue Evaluation in Chondral Defects

2021 ◽  
Vol 22 (24) ◽  
pp. 13329
Author(s):  
Lourdes Alcaide-Ruggiero ◽  
Verónica Molina-Hernández ◽  
M. M. Granados ◽  
J. M. Domínguez
Keyword(s):  
Articular Cartilage ◽  
Hyaline Cartilage ◽  
Cartilage Tissue ◽  
Type Ii ◽  
Collagen Types ◽  
Chondral Defects ◽  
Healthy Cartilage ◽  
Hyaline Articular Cartilage

Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less abundant collagens are type III, IV, V, VI, X, XII, XIV, XVI, XXII, and XXVII collagens. All these collagens have been found to play a key role in healthy cartilage, regardless of whether they are more or less abundant. Additionally, an exhaustive evaluation of collagen fibrils in a repaired cartilage tissue after a chondral lesion is necessary to determine the quality of the repaired tissue and even whether or not this repaired tissue is considered hyaline cartilage. Therefore, this review aims to describe in depth all the collagen types found in the normal articular cartilage structure, and based on this, establish the parameters that allow one to consider a repaired cartilage tissue as a hyaline cartilage.

scholarly journals Resilience to height loss of articular cartilage of osteoarthritic stifle joints of old pigs, compared with healthy cartilage from young pigs in a tribological pin—on—plate exposure, revealing similar friction forces

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250244
Author(s):  
Jan P. Engelhardt ◽  
Andy Schütte ◽  
Svetlana Hetjens ◽  
Gregor Reisig ◽  
Markus L. Schwarz
Keyword(s):  
Shear Stress ◽  
Articular Cartilage ◽  
Cartilage Tissue ◽  
Height Loss ◽  
Stress Exposure ◽  
Friction Forces ◽  
Young Pigs ◽  
Healthy Cartilage ◽  
Before And After ◽  
Wear And Tear

Introduction We saw a lack of data on the biomechanical behavior of degenerated articular cartilage (OA) compared with that of healthy cartilage, even though the susceptibility to wear and tear of articular cartilage plays a key role in the progression of osteoarthritis (OA). Therefore, we performed a comparison between naturally occurring OA and healthy cartilage from pigs, before and after tribological stress. Aim The aim of the study was to compare OA-cartilage with healthy cartilage and to analyze the resilience to tribological shear stress, which will be measured as height loss (HL), and to friction forces of the cartilage layers. The findings will be substantiated in macro- and microscopical evaluations before and after tribological exposure. Methods We assessed stifle joints of fifteen old and sixteen young pigs from the local abattoir radiologically, macroscopically and histologically to determine possible OA alterations. We put pins from the femoral part of the joints and plates from the corresponding tibial plateaus in a pin-on-plate tribometer under stress for about two hours with about 1108 reciprocating cycles under a pressure of approximately 1 MPa. As a surrogate criterion of wear and tear, the HL was recorded in the tribometer. The heights of the cartilage layers measured before and after the tribological exposure were compared histologically. The condition of the cartilage before and after the tribological exposure was analyzed both macroscopically with an adapted ICRS score and microscopically according to Little et al. (2010). We assessed the friction forces acting between the surfaces of the cartilage pair–specimens. Results Articular cartilage taken from old pigs showed significant degenerative changes compared to that taken from the young animals. The macroscopic and microscopic scores showed strong alterations of the cartilage after the tribological exposure. There was a noticeable HL of the cartilage specimens after the first 100 to 300 cycles. The HL after tribological exposure was lower in the group of the old animals with 0.52 mm ± 0.23 mm than in the group of the young animals with 0.86 mm ± 0.26 mm (p < 0.0001). The data for the HL was validated by the histological height measurements with 0.50 mm ± 0.82 mm for the old and 0.79 mm ±0.53 mm for the young animals (p = 0.133). The friction forces measured at the cartilage of the old animals were 2.25 N ± 1.15 N and 1.89 N ± 1.45 N of the young animals (p = 0.3225). Conclusion Unlike articular cartilage from young pigs, articular cartilage from old pigs showed OA alterations. Tribological shear stress exposure revealed that OA cartilage showed less HL than healthy articular cartilage. Tribological stress exposure in a pin–on–plate tribometer seemed to be an appropriate way to analyze the mechanical stability of articular cartilage, and the applied protocol could reveal weaknesses of the assessed cartilage tissue. Friction and HL seemed to be independent parameters when degenerated and healthy articular cartilage were assessed under tribological exposure in a pin–on- plate tribometer.

Fabrication of Tissue-Engineered Cartilage Grafts With Anatomic Surface Contours for Repair of Large Focal Defects

2013 ◽  
Author(s):  
Brendan L. Roach ◽  
Andrea R. Tan ◽  
Aaron M. Stoker ◽  
James L. Cook ◽  
Keith J. Yeager ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Surgical Intervention ◽  
Articular Surface ◽  
Treatment Options ◽  
Cartilage Tissue ◽  
Osteochondral Grafts ◽  
Cartilage Grafts ◽  
Defect Site ◽  
Articular Surfaces ◽  
Engineered Cartilage

Articular cartilage exhibits a poor healing response to injury that necessitates surgical intervention to repair or replace damaged tissue. Treatment options, however, are dependent on the location and size of the defect site. For small focal defects (<2 cm 2), microfracture is the primary method of treatment [8] despite the production of biologically inferior cartilage. For lesions greater than 10 cm 2 where the articular cartilage loss and morphology of the condyle is distorted, a fresh osteoarticular allograft is most likely to succeed [3], while posing a significant surgical challenge related to the technical demands in restoring congruency of the articular surface (i.e., attaining a flush fit of the graft with the surrounding host cartilage tissue). This requires matching of the donor joint size to provide grafts with similar anatomical surface contours. As there is insufficient supply of suitable cartilage grafts to meet the clinical demand, the development of tissue engineered osteochondral grafts would have significant clinical impact for treatment of cartilage lesions and eventually entire articular surfaces.

scholarly journals Anatomy of the Intermetatarsal Facets of the Fourth and Fifth Metatarsals

2021 ◽  
Vol 6 (1) ◽  
pp. 247301142097570
Author(s):  
Mossub Qatu ◽  
George Borrelli ◽  
Christopher Traynor ◽  
Joseph Weistroffer ◽  
James Jastifer
Keyword(s):  
Articular Cartilage ◽  
Digital Imaging ◽  
Articular Surface ◽  
Implant Design ◽  
Joint Surface ◽  
Fracture Classification ◽  
Articular Damage ◽  
Metatarsal Fracture ◽  
Metatarsal Fractures ◽  
The Mean

Background: The intermetatarsal joint between the fourth and fifth metatarsals (4-5 IM) is important in defining fifth metatarsal fractures. The purpose of the current study was to quantify this joint in order to determine the mean cartilage area, the percentage of the articulation that is cartilage, and to give the clinician data to help understand the joint anatomy as it relates to fifth metatarsal fracture classification. Methods: Twenty cadaver 4-5 IM joints were dissected. Digital images were taken and the articular cartilage was quantified by calibrated digital imaging software. Results: For the lateral fourth proximal intermetatarsal articulation, the mean area of articulation was 188 ± 49 mm2, with 49% of the area composed of articular cartilage. The shape of the articular cartilage had 3 variations: triangular, oval, and square. A triangular variant was the most common (80%, 16 of 20 specimens). For the medial fifth proximal intermetatarsal articulation, the mean area of articulation was 143 ± 30 mm2, with 48% of the joint surface being composed of articular cartilage. The shape of the articular surface was oval or triangular. An oval variant was the most common (75%, 15 of 20 specimens). Conclusion: This study supports the notion that the 4-5 IM joint is not completely articular and has both fibrous and cartilaginous components. Clinical Relevance: The clinical significance of this study is that it quantifies the articular surface area and shape. This information may be useful in understanding fifth metatarsal fracture extension into the articular surface and to inform implant design and also help guide surgeons intraoperatively in order to minimize articular damage.

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