Impact of vitronectin adsorption on macrophage mediated degradation of poly(trimethylene carbonate)

dc.contributor.authorMacMillan, Owen D.
dc.contributor.departmentChemical Engineering
dc.contributor.supervisorAmsden, Brian's University at Kingstonen
dc.description.abstractMacrophages are known to exhibit different responses when cultured on different materials. This phenomenon is hypothesized to be directly related to the composition and configuration of the layer of adsorbed proteins on the material’s surface that forms following exposure to proteincontaining medium (i.e., blood, plasma, serum, etc.). However, the impact of specific proteins on unstimulated macrophage behaviour is an area of research in which little is known. Relative differences in quantity of specific adsorbed proteins has previously been shown to exist between poly(trimethylene carbonate) (PTMC) and crosslinked, acrylated star poly(D,L-lactide-co-ϵ-caprolactone) (ELAS) with similar mechanical properties. Further, PTMC and ELAS have been shown to undergo different degradation behaviour in the presence of macrophages, with PTMC degrading and ELAS resisting macrophage mediated surface erosion. Vitronectin, an integrinbinding glycoprotein present in plasma, has been found to be associated with monocyte/macrophage attachment, proliferation, interleukin-4 (IL-4) induced macrophage FBGC formation, and adsorb to ELAS in relatively higher quantities vs. PTMC. This work investigates the impact of PTMC surfaces pre-adsorbed with vitronectin on subsequent macrophage behaviour. Cell number, production of reactive oxygen species (ROS), and enzymatic activity were measured for macrophages cultured on PTMC and ELAS. Vitronectin-adsorbed PTMC (VN-PTMC) and ELAS samples exhibited similar properties at early time points with significantly decreased cell number and significantly increased enzymatic activity compared to non-adsorbed PTMC. Interestingly, all significance in the secretion of degradative species disappeared by day 7 of the 14-day degradation study. It is proposed that the macrophage’s diminishing enzymatic activity was due to a change in the adsorbed protein layer via competitive protein adsorption replacing or altering the conformation of adsorbed proteins, or by the degradation of the initially adsorbed protein layer corresponding to the vitronectin-signalled increase in enzymatic activity. This work provides insight into the impact of adsorbed vitronectin on macrophage behaviour, polymer degradation, and is a first look into the response of unstimulated macrophages to specific proteins.
dc.relation.ispartofseriesCanadian thesesen
dc.subjectBiodegradable Polymers
dc.subjectProtein Adsorption
dc.titleImpact of vitronectin adsorption on macrophage mediated degradation of poly(trimethylene carbonate)
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