Analysis of Cartilage Matrix Fixed Charge Density and Three-dimensional Morphology Via Contrast-enhanced Microcomputed Tomography
Overview
Affiliations
Small animal models of osteoarthritis are often used for evaluating the efficacy of pharmacologic treatments and cartilage repair strategies, but noninvasive techniques capable of monitoring matrix-level changes are limited by the joint size and the low radiopacity of soft tissues. Here we present a technique for the noninvasive imaging of cartilage at micrometer-level resolution based on detecting the equilibrium partitioning of an ionic contrast agent via microcomputed tomography. The approach exploits electrochemical interactions between the molecular charges present in the cartilage matrix and an ionic contrast agent, resulting in a nonuniform equilibrium partitioning of the ionic contrast agent reflecting the proteoglycan distribution. In an in vitro model of cartilage degeneration we observed changes in x-ray attenuation magnitude and distribution consistent with biochemical and histological analyses of sulfated glycosaminoglycans, and x-ray attenuation was found to be a strong predictor of sulfated glycosaminoglycan density. Equilibration with the contrast agent also permits direct in situ visualization and quantification of cartilage surface morphology. Equilibrium partitioning of an ionic contrast agent via microcomputed tomography thus provides a powerful approach to quantitatively assess 3D cartilage composition and morphology for studies of cartilage degradation and repair.
Paakkari P, Inkinen S, Mohammadi A, Nieminen M, Joenathan A, Grinstaff M Sci Rep. 2024; 14(1):29956.
PMID: 39622931 PMC: 11612382. DOI: 10.1038/s41598-024-78237-1.
Osteoarthritis early-, mid- and late-stage progression in the rat medial meniscus transection model.
McKinney J, Pucha K, Bernard F, Dixon J, Doan T, Willett N J Orthop Res. 2024; 43(1):102-116.
PMID: 39385586 PMC: 11615425. DOI: 10.1002/jor.25969.
Wei L, Pan Q, Teng J, Zhang H, Qin N Mater Today Bio. 2024; 24:100884.
PMID: 38173866 PMC: 10761803. DOI: 10.1016/j.mtbio.2023.100884.
Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.
Dudek M, Pathiranage D, Bano-Otalora B, Paszek A, Rogers N, Goncalves C Nat Commun. 2023; 14(1):7237.
PMID: 37963878 PMC: 10646113. DOI: 10.1038/s41467-023-42056-1.
Lin A, Reece D, Thote T, Sridaran S, Stevens H, Willett N Front Bioeng Biotechnol. 2023; 11:1224141.
PMID: 37744252 PMC: 10512062. DOI: 10.3389/fbioe.2023.1224141.