The effects of a microgravity environment on the myriad types of immune cells present within the human body have been assessed both by bench-scale simulation and suborbital methods, as well as in true spaceflight. Macrophages have garnered increased research interest in this context in recent years. Their functionality in both immune response and tissue remodeling makes them a unique cell to investigate in regards to gravisensitive effects as well as parameters of interest that could impact astronaut health. Here, we review and summarize the literature investigating the effects of microgravity on macrophages and monocytes regarding the microgravity environment simulation/generation methods, cell sources, experiment durations, and parameters of interest utilized within the field. We discuss reported findings on the impacts of microgravity on macrophage/monocyte structure, adhesion and migration, proliferation, genetic expression, cytokine secretion, and reactive oxygen species production, as well as polarization. Based on this body of data, we make recommendations to the field for careful consideration of experimental design to complement existing reports, as the multitude of disparate study methods previously published can make drawing direct comparisons difficult. However, the breadth of different testing methodologies can also lend itself to attempting to identify the most robust and consistent responses to microgravity across various testing conditions.

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As humans age, there is an increased risk for developing age-associated diseases. Many of these diseases, such as cardiovascular disease, involve dysfunction in the vasculature. Cardiovascular disease stems from endothelial cell dysfunction and reduction in vascularization. Macrophages, prominent innate immune cells involved in orchestrating inflammation and wound healing, have a significant influence on vascularization. While much recent work has investigated the crosstalk between endothelial cells and macrophages, it is still not well defined. The interactions between the cell types are even less understood in specific disease states such as advanced age. Understanding how age influences macrophage/endothelial cell interaction is essential for understanding cardiovascular disease development in the elderly. In the polyethylene glycol (PEG)-based hydrogel system, we model the effects of age on vascularization by encapsulating endothelial cells, pericytes, and human donor macrophages. We created a biomaterial model system in which macrophages, either from young (<35 years old) or old (>65 years old) donors, interact with the modeled vasculature, termed microvessels. Confocal image analysis of vessel density, vessel length, and branch points were used to quantify microvessel growth depending on the age of the macrophage donor. Alongside this, soluble factor secretion and gene expression were evaluated using ELISA and NanoString to showcase biological mechanisms based on the age of each donor. Endothelial cells cultured with macrophages from old donors have reduced microvessel density. There also is reduced soluble factor secretion by the macrophages from old donors, which likely influenced microvessel growth. Altogether, we establish our PEG-based hydrogel vascular model as a system to evaluate patient-specific cell function as well as proposed mechanisms for how age influences microvessels.