Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage

Bansal, Prashant N.; Stewart, Rachel C.; Entezari, Vahid; Snyder, Brian D.; Grinstaff, Mark W.

doi:10.1016/j.joca.2011.04.004

Cited by 82 publications

(118 citation statements)

References 48 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…From each patient, cores were exposed to a three different concentration of CA4+ (3,6, and 24 mgI/ml; n = 3 per concentration) and imaged with CEµCT in several time points (0, 1, 3, 5, 9, 18, 24, 32, 40, and 48 h). The CA4+ concentrations used in this study were selected based on the previous studies using CA4+ for animal AC (concentration ranged between 8 and 27 mgI/ml) [5,6,10] and our preliminary trials with the human AC.…”

Section: Sample Preparation and Contrast Agent Stainingmentioning

confidence: 99%

“…Cationic contrast agents (especially CA4+), compared to anionic ones, demonstrate strong positive correlation to GAG content and reveal GAG distribution in articular cartilage even when used at low concentrations [5][6][7]. Successful application of these cationic contrast agents in ex vivo and in vivo studies [7,8] indicate significant research potential.…”

Section: Introductionmentioning

confidence: 99%

“…Successful application of these cationic contrast agents in ex vivo and in vivo studies [7,8] indicate significant research potential. The distribution of CA4+ in AC is based on the attraction between the positive CA4+ and the negatively charged GAG macromolecules [5]. Cationic dyes are routinely used in histology (e.g., Safranin O, Toluidine blue, Alcian blue) to stain the proteoglycans of AC.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, we hypothesize that cationic CA4+ will accumulate in the chondrons or in the close proximity of the chondrons. However, the previous studies using CA4+ enhanced micro-computed tomography (µCT) [5][6][7][8][9] have been conducted with insufficient resolution to answer this hypothesis. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low resolution µCT setups.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

et al. 2017

View full text Add to dashboard Cite

Contrast-enhanced micro-computed tomography (CEµCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g., CA4+) compared to anionic stains (e.g., Hexabrix ® ), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution µCT setups. In this study, we use high-resolution µCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo µCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml) and imaged with high-resolution µCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG Karhula et al. CA4+ Accumulation in Human Cartilagecontent detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples and the relative difference between the interterritorial matrix and segmented chondron area was less than 4%. To conclude, our results suggest that GAG quantification with CEµCT is not affected by the chondron uptake of CA4+. This further confirms the use of CA4+ for macro-scale assessment of GAG throughout the AC, and highlight the capability of studying chondron properties in 3D at the micro scale.

show abstract

Section: Sample Preparation and Contrast Agent Stainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Precise chemical mimicry of GAG, with its abundant negative charges, is not optimal as negatively charged monomers equilibrate in lower concentration within the tissue relative to the concentration in surrounding fluid. [10] Positively charged monomers, in contrast, are electrostatically attracted to diffuse into the tissue, [11] but many cationic molecules elicit undesirable toxicity. [12] Therefore, the zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine (MPC) (Figure 1, right), exhibiting no net molecular charge yet possessing charged phosphate and trimethylammonium functional groups, was selected as it is known to demonstrate biocompatibility [13] and a high degree of hydration, [14] even under extreme compressive loads.…”

mentioning

confidence: 99%

A Tissue‐Penetrating Double Network Restores the Mechanical Properties of Degenerated Articular Cartilage

et al. 2016

View full text Add to dashboard Cite

Incorporation of an interpenetrating polymer network into an existing single polymer network enables augmentation of the original substrate’s mechanical properties, and translation of this concept from purely synthetic materials to natural-synthetic hybrid systems provides the opportunity to reinforce mechanical properties of bulk biological substrates. In many disease states, bodily tissues experience a deterioration of mechanical properties which renders them prone to further material failure. Herein, a tissue-supplementing technique is described in which an interpenetrating biomimetic hydrogel is polymerized in situ throughout cartilage tissue. The treatment restores the inferior compressive properties of osteoarthritic cartilage to that of healthy cartilage, preferentially localizing to weaker regions of tissue. Furthermore, the treatment technique preserves cartilage under harsh articulation conditions, showing promise as a materials-based treatment for early-stage osteoarthritis.

show abstract

Tantalum Oxide Nanoparticles for the Imaging of Articular Cartilage Using X‐Ray Computed Tomography: Visualization of Ex Vivo/In Vivo Murine Tibia and Ex Vivo Human Index Finger Cartilage

et al. 2014

View full text Add to dashboard Cite

The synthesis and characterization of tantalum oxide (Ta2O5) nanoparticles (NPs) as new X‐ray contrast media for microcomputed tomography (μCT) imaging of articular cartilage are reported. NPs, approximately 5–10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.

show abstract

Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage

Cited by 82 publications

References 48 publications

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

A Tissue‐Penetrating Double Network Restores the Mechanical Properties of Degenerated Articular Cartilage

Tantalum Oxide Nanoparticles for the Imaging of Articular Cartilage Using X‐Ray Computed Tomography: Visualization of Ex Vivo/In Vivo Murine Tibia and Ex Vivo Human Index Finger Cartilage

Contact Info

Product

Resources

About