title: Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking--contribution of steric and electrostatic effects.
abstract: OBJECTIVE
  To investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage.
  
  
  METHODS
  Osteochondral plugs (Ø=6mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24h of immersion. Fixed charge density (FCD), water content, contents of proteoglycans, total collagen, hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent) cross-links were determined as a reference.
  
  
  RESULTS
  The equilibrium partitioning of ioxaglate (group I) was significantly (p=0.018) lower (-23.4%) in threose-treated than control samples while the equilibrium partitioning of iodixanol (group II) was unaffected by the threose-treatment. FCD in the middle and deep zones of the cartilage (p<0.05) and contents of Pent and LP (p=0.001) increased significantly due to the treatment. However, the proteoglycan concentration was not systematically altered after the treatment. Water content was significantly (-3.5%, p=0.007) lower after the treatment.
  
  
  CONCLUSIONS
  Since non-ionic iodixanol showed no changes in partition after cross-linking, in contrast to anionic ioxaglate, we conclude that the cross-linking induced changes in charge distribution have greater effect on diffusion compared to the cross-linking induced changes in steric hindrance.
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland. katariina.kulmala@uef.fi
authors.forename: K A M
authors.initials: KA
authors.lastname: Kulmala
authors.forename: H M
authors.initials: HM
authors.lastname: Karjalainen
authors.forename: H T
authors.initials: HT
authors.lastname: Kokkonen
authors.forename: V
authors.initials: V
authors.lastname: Tiitu
authors.forename: V
authors.initials: V
authors.lastname: Kovanen
authors.forename: M J
authors.initials: MJ
authors.lastname: Lammi
authors.forename: J S
authors.initials: JS
authors.lastname: Jurvelin
authors.forename: R K
authors.initials: RK
authors.lastname: Korhonen
authors.forename: J
authors.initials: J
authors.lastname: Töyräs
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism*; D004058:Diffusion; D055672:Static Electricity; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D003094:Collagen
keywords: Cartilage ageing; Computed tomography; Contrast agent; Cross-linking