Format

Send to

Choose Destination
J Biomech Eng. 2019 Sep 1. doi: 10.1115/1.4044892. [Epub ahead of print]

Combined Experimental Approach and Finite Element Modeling of Small Molecule Transport Through Joint Synovium to Measure Effective Diffusivity.

Author information

1
Department of Biomedical Engineering, Washington University in St. Louis, Whitaker Hall, 1 Brookings Dr., St. Louis, MO, 63130.
2
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, 63110.
3
Center for Cellular Imaging, Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110.
4
Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, 63110.
5
Department of Neuroscience, Department Cell Biology & Physiology and Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110; Department of Biomedical Engineering, Washington University in St. Louis, Whitaker Hall, 1 Brookings Dr., St. Louis, MO, 63130.

Abstract

Trans-synovial solute transport plays a critical role in the clearance of intra-articularly delivered drugs. In this study, we present a computational finite element model of solute transport through the synovium validated by experiments on synovial explants. Unsteady diffusion of urea, a small uncharged molecule, was measured through devitalized porcine and human synovium using custom-built diffusion chambers. A multiphasic computational model was constructed and optimized with the experimental data to extract effective diffusivity for urea within the synovium. A monotonic decrease in urea concentration was observed in the donor bath over time, with an effective diffusivity found to be an order of magnitude lower in synovium versus that measured in free solution. Parametric studies incorporating an intimal cell layer with varying thickness and varying effective diffusivities were performed, revealing a dependence of drug clearance kinetics on both parameters. The findings of this study indicate that the synovial matrix impedes urea solute transport out of the joint with little retention of the solute in the matrix.

PMID:
31536113
DOI:
10.1115/1.4044892

Supplemental Content

Loading ...
Support Center