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.

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Titanium (Ti) represents a promising new material for microelectromechanical systems (MEMS) because of its unique properties. Recently, this has been made possible with the advent of processes that enable deep reactive ion etching (DRIE) of high-aspect-ratio (HAR) structures in bulk Ti substrates. However, to date, these processes have been limited to minimum feature sizes (MFS) ≥750 nm. Although this is sufficient for many applications, MFS reduction to the deep submicrometer range opens potential for further device miniaturization and an opportunity for endowing devices with unique functionalities that are derived from precisely defined structures within this length scale regime. Herein, we report results from studies seeking to create means for realizing such opportunities through extension of Ti DRIE to the deep submicrometer scale. The effects of key process parameters on etch performance were investigated, and the understanding gained from these studies formed the development of a new ultrahigh resolution (UHR) Ti DRIE process. Using this process, we demonstrate, for the first time, fabrication of HAR structures in bulk Ti substrates with 150 nm MFS, smooth vertical sidewalls (88°), good etch rate (587 nm/min), and mask selectivity (11.1). This represents a fivefold or greater improvement in MFS relative to our previously reported processes and a 29-fold or greater improvement over more recent processes reported by others. As such, the UHR Ti DRIE process extends the state-of-the-art considerably, and it opens important new opportunities for Ti MEMS, particularly in the implantable medical device realm.

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