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The research conducted in our laboratory, located in the Research Center of the University of Ottawa Heart Institute and headed by Dr. Rosalind Labow, focuses on cell-material interaction. We are concerned with the degradation of materials—specifically polyurethanes used in the manufacture of implanted medical devices, such as pacemaker leads and ventricular assist devices. However, understanding and tailoring the extent of the foreign body's reaction to the materials' surface has become equally important for materials used in devices where controlled degradation is desirable, such as drug eluting stents for angioplasty and tissue-engineered blood vessels. The model polyurethanes, which vary in their susceptibility to degradation, are synthesized in Dr. Paul Santerre's laboratory at the University of Toronto. In the in vitro model cell system, monocytes are isolated from the whole blood of volunteers and are differentiated to mature monocyte-derived macrophages (MDMs) on tissue culture polystyrene (TCPS) and other material surfaces. By studying the effect of the materials on MDM function, it has been possible to assess the signaling pathways activated during cell-material interaction. By elucidating the pathways that are triggered during this interaction, it may be possible to modify the MDM phenotype, thereby optimizing medical devices for their intended use.
www.ottawaheart.ca/UOHI/Res_Taichman.do
The Technique
Since culture of many cell types takes place on TCPS, this material is used as a control surface when studying the mechanism of cell-material interaction. In the medical device manufacturing industry, polydimethylsiloxane (PDMS) is the material used as a reference for biocompatibility and is the measure of the ability of a material to perform its required function without adverse physiological reactions. In our paper we discuss functional parameters that relate to the extent of the foreign body reaction that we measured in MDM during in vitro cell culture on polyurethanes compared to TCPS and PDMS. The extent of MDM activation on both control surfaces should be of interest to anyone using cell culture in their research. When compared to polyurethanes, TCPS elicited the most activity of monocyte-specific esterase (MSE), an enzyme in MDM used in classifying a variety of pathological conditions (e.g., leukemia and gastric cancer). Acid phosphatase (AP), a lysosomal enzyme implicated in the innate immune response, increased the most in MDM on PDMS. Although nondegradable, both TCPS and PDMS should not be considered biologically inert, especially when using these materials as reference standards or controls.
Is cell culture stressful? Effects of degradable and nondegradable culture surfaces on U937 cell function, p. 744.
