Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents.

Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix®) or 100% gadobenate dimeglumine (MultiHance®). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged samples. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 µg/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 µg/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix® and MultiHance® while differentiating the underlying subchondral bone.

Biaxial mechanics of 3D fiber deposited ply-laminate scaffolds for soft tissue engineering part I: Experimental evaluation.

Tissue engineering strategies require the provision of a micromechanical state of stress that is conducive to the generation and maintenance of healthy mature tissue. Of particular interest, angle-ply biomimetic scaffolds augmented with cellular content have been proposed for annulus fibrosus (AF) engineering in order to repair the intervertebral disc. However, the influence of the inherent variability of fabricated constructs and physiological conditions on overall scaffold mechanics, micromechanical environment within the scaffold, and consequent cellular differentiation is relatively unknown. In this study, melt extrusion 3D fiber-deposition (3DF) was used to fabricate five different polycaprolactone angle-ply scaffold architectures which were subject to multiaxial tensile testing and linear elastic orthotropic constitutive fitting. All scaffold groups predicted stiffnesses similar to previously reported native AF moduli in biaxial and uniaxial tensile strain. However, no single scaffold group in this study simultaneously achieved all target AF mechanics in all loading regimes. In equibiaxial tension, the biaxial stiffness ratio of native AF (EEr = 0.55 to 0.62) was predicted between fiber angles of 30° and 35°, which is similar to the collagen orientation in native AF. In global equibiaxial loading, an apparent asymptote in the transverse moduli (EEx ranging -380 MPa to 700 MPa) was observed near the 40° fiber angle scaffolds in equibiaxial tensile strain, attributed to stiffening from the transverse loading. These results highlight that tissue engineering scaffold designs should target replication of physiologically-relevant native tissue mechanics and demonstrate the importance of designing constructs that are unaffected by anticipated variations in manufacturing and clinical application.