Department: Bioengineering
Faculty Advisor(s):
Robert Sah
Primary Student
Name: Jennifer Hwang
Email: jehwang @ ucsd.edu
Phone: 858-534-5682
Grad Year: 2009
Abstract
Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage and changes in the underlying subchondral bone plate (ScBP). OA pathogenesis is associated with abnormal mineralization activity producing new regions of calcified cartilage (CC) and increased vasculature. Vascular canals in CC may modulate the load-bearing behavior of articular cartilage by contributing to the hydraulic conductance of the ScBP. We hypothesized that increased hydraulic conductance of the ScBP is associated with the progression of OA. The objectives of this study were: (1) to determine and compare the ScBP hydraulic conductance and structure for different grades of erosion of the osteoarthritic human femoral condyle, and (2) to evaluate the contribution of residual cartilage to the hydraulic conductance of fully eroded ScBP. Methods. Osteochondral cores were harvested from the medial femoral condyles of tissue donors and discarded knee pieces from surgery patients with IRB approval. Tissue donor cores were considered normal, and OA cores were graded as having partial or full erosion to bone. Uncalcified cartilage was removed by papain digestion. PBS was perfused through each sample while measuring the pressure drop across the sample, and hydraulic conductance was estimated using Darcy's law. Fully eroded cores were tested at harvest and again after removal of residual cartilage by papain. Osteochondral fragments for histology were trimmed to 3mm2 blocks, fixed and decalcified before being fluorescently stained with Eosin-Y, embedded in resin and imaged at (2.24)3 voxel resolution. Stereological methods were used to measure CC and ScBP thickness and vasculature penetrating the CC/bone interface. Results. Hydraulic conductance of the ScBP increased with severity of OA erosion. Conductance estimates in different flow directions were also strongly correlated. Papain digestion increased hydraulic conductance in some fully eroded OA samples but had no effect in others. OA samples exhibited large variations in CC thickness, with fully eroded samples having a thickened ScBP. Discussion. Hydraulic conductance properties across the bone-cartilage interface are altered in osteoarthritic disease states. Delineation of the fluid transport characteristics of the bone-cartilage interface will help to understand the interaction between the microenvironments of subchondral bone and deep zone-cartilage.
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