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J Biomech Eng. 2017 Sep 1;139(9). doi: 10.1115/1.4037202.

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

Author information

1
Meinig School of Biomedical Engineering, Cornell University, 145 Weill Hall, Ithaca, NY 14853 e-mail: cdd72@cornell.edu.
2
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail: andrew.goodearl@abbvie.com.
3
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail: anna.yarilina@abbvie.com.
4
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail: victor.sun@abbvie.com.
5
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail: soumya.mitra@abbvie.com.
6
AbbVie Inc., 100 Research Drive, Worcester, MA 01605 e-mail: annette.schwartz@abbvie.com.
7
Professor Meinig School of Biomedical Engineering, Sibley School of Mechanical and Aerospace Engineering, Cornell University, 149 Weill Hall, Ithaca, NY 14853; e-mail: lb244@cornell.edu.

Abstract

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.

PMID:
28672295
DOI:
10.1115/1.4037202
[Indexed for MEDLINE]

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