A culture model to analyze the acute biomaterial-dependent reaction of human primary macrophages

Abstract

Macrophages are important in foreign body reactions. We devised a culture model with human primary macrophages to evaluate the acute response of macrophages to biomaterials. First we selected proteins representative for pro-inflammatory (M1) or anti-inflammatory/repair (M2) response of monocytes isolated from blood of healthy human donors by exposing them to LPS+IFNγ or IL-4. A relative M1/M2 index was calculated using IL-1β, IL-6, tumor necrosis factor (TNF)α, monocyte chemotactic protein (MCP)-3 and macrophage inflammatory protein (MIP)-1α as M1 markers, and IL-1 receptor antagonist (IL-1RA), CCL18, regulated and normal T-cell expressed and secreted (RANTES), and macrophage-derived chemokine (MDC) as M2 markers. Then monocytes were cultured for 3days on 4 materials selected for known different foreign body reactions: Permacol™, Parietex™ Composite, multifilament polyethylene terephthalate and multifilament polypropylene. Macrophages on polypropylene produced high levels of anti-inflammatory proteins with a low M1/M2 index. Macrophages on Parietex™ Composite produced high levels of inflammatory and anti-inflammatory proteins, with a high M1/M2 index. Macrophages on polyethylene terephthalate also resulted in a high M1/M2 index. Macrophages on Permacol™ produced a low amount of all proteins, with a low M1/M2 index. This model with human primary macrophages and the panel of read-out parameters can be used to evaluate the acute reaction of macrophages to biomaterials in vitro to get more insight in the foreign body reaction.