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Controlling the interactions between macrophages and biomaterials is critical for modulating the response to implants. While it has long been thought that biomaterial surface chemistry regulates the immune response, recent studies have suggested that material geometry may in fact dominate. Our previous work demonstrated that elongation of macrophages regulates their polarization toward a pro-healing phenotype. In this work, we elucidate how surface topology might be leveraged to alter macrophage cell morphology and polarization state. Using a deep etch technique, we fabricated titanium surfaces containing micro- and nanopatterned grooves, which have been previously shown to promote cell elongation. Morphology, phenotypic markers, and cytokine secretion of murine bone marrow derived macrophages on different groove widths were analyzed. The results suggest that micro- and nanopatterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation but drove macrophages toward an anti-inflammatory, pro-healing phenotype. While secretion of TNF-alpha remained low in macrophages across all conditions, macrophages secreted significantly higher levels of anti-inflammatory cytokine, IL-10, on intermediate groove widths compared to cells on other Ti surfaces. Our findings highlight the potential of using surface topography to regulate macrophage function, and thus control the wound healing and tissue repair response to biomaterials.

Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype