Collagen-derived peptide, DGEA, inhibits pro-inflammatory macrophages in biofunctional hydrogels

Macrophages are innate immune cells that play important roles in wound healing. Particularly, M1 macrophages are considered pro‐inflammatory and promote initial phases of inflammation. Long-term exposure to inflammatory stimuli causes an increase in M1 macrophages, which contributes to chronic inflammation. Activated M1 macrophages have been shown to upregulate integrin α2β1 expression. To interfere with α2β1 binding, we designed a biofunctional hydrogel utilizing a collagen I-derived peptide, DGEA (Asp-Gly-Glu-Ala). We hypothesize that M1 macrophage activation can be reduced in the presence of DGEA. Effects of DGEA on M1 macrophages were studied via soluble delivery and immobilization within poly(ethylene glycol) (PEG) hydrogels. We demonstrate that M1 macrophage activation is reduced both via soluble delivery of DGEA in 2D and via immobilized DGEA in a 3D PEG-DGEA hydrogel. This novel biomaterial can manipulate inflammatory macrophage activation and can be applied to prevent chronic inflammatory conditions via macrophage manipulation. GRAPHICAL ABSTRACT: [Image: see text]