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Technical Brief

The Effect of Charge and Mechanical Loading on Antibody Diffusion Through the Articular Surface of Cartilage

[+] Author and Article Information
Chris D. DiDomenico

Meinig School of Biomedical Engineering,
Cornell University,
Ithaca, NY 14853

Lawrence J. Bonassar

Professor
Meinig School of Biomedical Engineering,
Sibley School of Mechanical and Aerospace Engineering,
Cornell University,
149 Weill Hall,
Ithaca, NY 14853
email: lb244@cornell.edu

1Corresponding author.

Manuscript received April 17, 2018; final manuscript received October 3, 2018; published online November 19, 2018. Assoc. Editor: David Corr.

J Biomech Eng 141(1), 014502 (Nov 19, 2018) (5 pages) Paper No: BIO-18-1187; doi: 10.1115/1.4041768 History: Received April 17, 2018; Revised October 03, 2018

Molecular transport of osteoarthritis (OA) therapeutics within articular cartilage is influenced by many factors, such as solute charge, that have yet to be fully understood. This study characterizes how solute charge influences local diffusion and convective transport of antibodies within the heterogeneous cartilage matrix. Three fluorescently tagged solutes of varying isoelectric point (pI) (4.7–5.9) were tested in either cyclic or passive cartilage loading conditions. In each case, local diffusivities were calculated based on local fluorescence in the cartilage sample, as observed by confocal microscopy. In agreement with past research, local solute diffusivities within the heterogeneous cartilage matrix were highest around 200–275 μm from the articular surface, but 3–4 times lower at the articular surface and in the deeper zones of the tissue. Transport of all 150 kDa solutes was significantly increased by the application of mechanical loading at 1 Hz, but local transport enhancement was not significantly affected by changes in solute isoelectric point. More positively charged solutes (higher pI) had significantly higher local diffusivities 200–275 μm from the tissue surface, but no other differences were observed. This implies that there are certain regions of cartilage that are more sensitive to changes in solute charge than others, which could be useful for future development of OA therapeutics.

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Figures

Grahic Jump Location
Fig. 1

Cartilage cylinders were bisected and then sliced to obtain a final sample dimension of 4 × 2 × 1.15 mm (A). Samples were loaded in a way that caused fluid flow to be perpendicular to the articular surface (AS) and deep zone (DZ) (B). Representative image from confocal microscopy showing the fluorescence gradient perpendicular to the AS (C). The red box (∼1000 μm wide, 500 μm tall) indicates the region of interest that was examined for this study. Diffusion perpendicular to the deep zone was not examined for this study.

Grahic Jump Location
Fig. 2

Fluorescence curves for all solutes (passive condition) tested (left) and local diffusivities (right), which includes historical data (*) for a neutral antibody from a previous study [16]. Error bars denote standard deviations with n = 5–7 for all solutes. On average, diffusivities for the pI 4.7, pI 5.4, and pI 5.9, were 3.8, 4.5, 4.6 μm2/s at 50 μm, but pI did not affect diffusivity significantly within this region (p = 0.25). Diffusivities increased to a maximum of 15.0, 16.9, and 19.0 μm2/s for the pI 4.7, pI 5.4, and pI 5.9 solutes respectively, between 200 and 275 μm. Calculated diffusivities at 125 μm, 200 μm, and 275 μm were higher than all other diffusivities in the tissue, for all solutes (#: p < 0.001). Diffusivities for pI 5.9 were higher than that of pI 4.7, between 200 and 375 μm (p < 0.02). Values obtained from 50 μm and 425 and 800 μm range were not different from each other, for any solute (p > 0.3).

Grahic Jump Location
Fig. 3

Fluorescence curves for pI 5.9 and 5% cyclic loading (left) and local diffusivities for all solutes at 5% cyclic loading (right). Error bars denote standard deviations with n = 5–7 for all solutes. Orange solid line denotes average passive diffusivity levels in the passive condition for all solutes. Cyclic loading at 5% cyclic strain and at 1 Hz increased fluorescence values between 150 and 400 μm. Solutes did not experience any significant differences in diffusivity values or trends at this loading amplitude (p > 0.1). Additionally, there were no differences between solute diffusivities at 1.25% or 2.5% (shown in supplement). However, maximal transport enhancement increased for all solutes with increasing loading amplitude, as expected.

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