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

Abstract

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 towards 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 nano-patterned 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 nano-patterned grooves influenced macrophage elongation, which peaked on substrates with 400-500 nm wide grooves. Surface grooves did not affect inflammatory activation, but drove macrophages towards 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.

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

“…3 days versus 28 days post tissue injury) (Avula et al 2016; Helton et al ; Helton et al). Also, it has recently been suggested that biomaterial geometry, size and shape are players to dictate macrophage behavior (Luu et al 2015). An even more complicating factor is that a variety of CCL2 or CCR2 mutant/KO mice have been used in various implant/biomaterial studies.…”

Overcoming foreign-body reaction through nanotopography: Biocompatibility and immunoisolation properties of a nanofibrous membrane

“…It is possible that the cells may only change shape and spread when the fiber thickness is above a certain threshold. The response of spreading is then associated with the activation of macrophage cells, as described in the literature [33]. The nanofibers also differs from microfibers in terms of surface protein adsorption and mechanical properties, which may also cause different tissue responses [7,34,35].…”

The Topography of Silica Films Modulates Primary Macrophage Morphology and Function

“…[7] Macrophages with spindle-like morphology are more likely to have a pro-healing phenotype, which contributes to tissue repair and wound healing, whereas the rounded "fried-egg" morphology shows pro-inflammatory behavior. [9] Surface patterns such as microgrooves, [10][11][12][13] wrinkles, [14] and concave/convex microstructures [15] have been reported to alter inflammatory responses of macrophages. [9] Surface patterns such as microgrooves, [10][11][12][13] wrinkles, [14] and concave/convex microstructures [15] have been reported to alter inflammatory responses of macrophages.…”

“…For example, it has been observed that 2 and 10 µm width grooves in fused silica result in the elongation of macrophages and improved phagocytosis of microbeads compared with flat surfaces. [9] The effect of a wide range of materials including titanium, [11,17,20,21] polyvinylidene fluoride, [22] perfluoropolyether, [23] PDMS, [10,14,15] fused silica, [16] poly(ε-caprolactone) (PCL), and poly(lactic acid) (PLA) [10] with micro-and nanostructures have been investigated on macrophage morphology and inflammatory responses with conflicting results. [15] Modification of surface chemistry such as charge and hydrophobicity can also impact macrophage phenotype; [17][18][19] however, topographical effects are believed to override the influence of surface chemistry.…”