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UBC Theses and Dissertations

Novel grooved substrata stimulate macrophage fusion, CCL2 and MMP-9 secretion Moon, Hai-Sle


Monocyte-derived macrophages arrive early at a newly implanted device and affect the performance of implants by regulating immune responses. Macrophages are “plastic” cells that exhibit a spectrum of functions between two quintessential phenotypes: (1) the classically activated (M1) phenotype associated with classical inflammatory responses and (2) the alternatively activated (M2) phenotype involved in wound healing or immunoregulatory behavior. Rough surface topographies on implants attract macrophages but the influence of topography on macrophage fusion to produce multinucleated giant cells (MGCs) and foreign body giant cells (FBGCs) is unclear. Previous studies have shown topography induced macrophage polarization and changes in cell shape as well as differential activation of cell signaling pathways. In this study, the effects of novel grooved substrata, G1 and G2, on changes in cell shape, gene expression, cyto/chemokine secretion and cell fusion were studied. G1 and G2 surfaces were fabricated by anisotropic etching of silicon <110> crystals, without the use of photolithographic patterning, and extensively characterized by optical profilometry to determine the roughness parameter Ra and isotropy parameters Str and Sal (G1: Ra 0.10 μm, Str 0.03, Sal 2.1 μm; G2: Ra 1.2 μm, Str 0.08, Sal 5.8 μm). RAW 264.7 macrophages were cultured on G1, G2, and smooth control (Pol) epoxy substrata for one and five days. Cells on the grooved surfaces exhibited cell morphology similar to M2 macrophages that were produced by IL-4 treatment. Cell alignment with the grooves increased with surface directionality and roughness as well as time in culture. Expression of macrophage chemoattractants CCL2 and CCL4 increased at the gene and protein level and the secretion of fusion mediators CCL2 and MMP-9 increased with time on the grooved surfaces. Relative to the Pol surface, an increased proportion of multinucleated cells was observed on the grooved surfaces at Day 5. Collectively, these in vitro results demonstrated that topography dependent macrophage responses resulted in differential secretion of macrophage attractant chemokines and soluble mediators involved in cell fusion that may explain the observed accumulation of macrophages and MGCs on rough surfaced implants in vivo.

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Attribution-NonCommercial-NoDerivs 2.5 Canada