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Show COLLEGE OF PHARMACY Amanda E. Brooks MACROPHAGE BEHAVIOR INVESTIGATED USING MICROFLUIDICS David Au (Amanda E. Brooks, David W. Grainger) Department of Bioengineering Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah Biomedical implants are essential to modern medical practice, improving not only health but also quality of life. Unfortunately, even the most essential biomedical implants trigger the foreign body response (FBR); a host response characterized by chronic inflammation and compromised healing. Macrophages are key effector cells not only in the foreign body response (FBR) but also during an infectious onslaught. Thus, macrophages must be able to prioritize multiple cellular signals to coordinate the immune response under diverse conditions. The biomaterial's host protein coating (Figure 1) is a key factor in this response or lack thereof. Consequently, macrophage surface adhesion under flow conditions is altered by the protein surface coating. As macrophages extravagate across the endothetial layer toward a site of injury, infection, or biomedical implantation, they undergo dynamic shear stresses based on fluid flow. Thus, microfluidic technology was employed during this study to more closely mimic the in vivo condition and assess the ability of macrophages to adhere to differentially-coated protein surface. Proteins often associated with the FBR (collagen, fibrinogen, and albumin) were applied to the surface of a glass slide to model an implanted biomaterial. Subsequently, macrophages were microfluidically printed, using a cyclic laminar flow process, on the protein-coated surface. Multiple flow rates were investigated to determine the optimal conditions for printing and cellular adhesion. Importantly, the microfluidics system used is integrated with an optics system to allow real-time visualization of cellular adhesion. Ultimately, this work will allow a systematic understanding of macrophage response prioritization to dynamic cytotactic cues (protein surface coating, bacterial endotoxin (LPS), etc). David W. Grainger |
