Control of growth and inflammatory response of macrophages and foam cells with nanotopography

Mohammed Mohiuddin,Guewha Steven Huang,Yao-Ching Hung,Hsu-An Pan

doi:10.1186/1556-276x-7-394

Abstract

Macrophages play an important role in modulating the immune function of the human body, while foam cells differentiated from macrophages with subsequent fatty streak formation play a key role in atherosclerosis. We hypothesized that nanotopography modulates the behavior and function of macrophages and foam cells without bioactive agent. In the present study, nanodot arrays ranging from 10‐ to 200‐nm were used to evaluate the growth and function of macrophages and foam cells. In the quantitative analysis, the cell adhesion area in macrophages increased with 10- to 50-nm nanodot arrays compared to the flat surface, while it decreased with 100- and 200-nm nanodot arrays. A similar trend of adhesion was observed in foam cells. Immunostaining, specific to vinculin and actin filaments, indicated that a 50-nm surface promoted cell adhesion and cytoskeleton organization. On the contrary, 200-nm surfaces hindered cell adhesion and cytoskeleton organization. Further, based on quantitative real-time polymerase chain reaction data, expression of inflammatory genes was upregulated for the 100- and 200-nm surfaces in macrophages and foam cells. This suggests that nanodots of 100‐ and 200‐nm triggered immune inflammatory stress response. In summary, nanotopography controls cell morphology, adhesions, and proliferation. By adjusting the nanodot diameter, we could modulate the growth and expression of function-related genes in the macrophages and foam cell system. The nanotopography-mediated control of cell growth and morphology provides potential insight for designing cardiovascular implants.

Highlights

Recent fabrication of nanostructured materials with different surface properties has generated a great deal of interest for developing implant materials, i.e., cardiovascular, dental, orthopedic, percutaneous, subcutaneous, and auditory [1,2,3,4,5]
Nanotopography-modulated morphology and cell spread of macrophages and foam cells To characterize how the macrophages and foam cells interact with the aforementioned nanodot arrays, the cells were cultured for 72 h on nanodot arrays of different diameters including flat substrate as a control
Apoptosis-like appearance and reduction in surface area with extended lamellipodia were seen with cells seeded on the 200-nm nanodot arrays

Summary

Introduction

Recent fabrication of nanostructured materials with different surface properties has generated a great deal of interest for developing implant materials, i.e., cardiovascular, dental, orthopedic, percutaneous, subcutaneous, and auditory [1,2,3,4,5]. Macrophages play a critical role during innate and acquired immune responses through the phagocytosis of foreign material. The earliest detectable lesions, called fatty streaks, contain macrophage foam cells that are derived from recruited monocytes. The formation of these foam cells correlates to inflammatory responses [9,10,11]. Immune cells such as monocytes and macrophages play a key role in mediating host tissue response to implants in the foreign body reaction.One study demonstrated that the macrophage receptor with collagenous structure (MARCO) displayed limited expression in healthy cells but increased in expression around the synovial fluid following hip replacements [12]. This study indicated that the presence of a foreign body can generate an immune response, and the continued presence of the foreign body can potentially lead to macrophage buildup and production of foam cells

Methods

Results

Conclusion