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Macrophages in a contaminated environment
Introduction
Biomaterials are used widely in reparative and regenerative medicine. However, in an environment at risk of contamination, surgeons are reluctant to use biomaterials owing to a higher risk of complications. A feared postoperative complication of biomaterial implantation is infection of the biomaterial and surrounding tissue by bacteria, reported in up to 16 per cent of patients(1). The risk of infection is even higher in some circumstances, such as in surgery of the gastrointestinal tract or nasal cavity, as well as in the presence of peritonitis. The risk of infection also depends on the type of biomaterial, such as its con guration, hydrophobicity and whether it is made from mono lament or multi lament(1-3). All biomaterials elicit a foreign body reaction, and the degree of this reaction varies depending on the nature of the biomaterials. At present, the foreign body reaction in an environment with a high risk of contamination is not well characterized.
Macrophages play a pivotal role in the foreign body reaction(1, 4, 5). The phenotype of the macrophages can change in response to environmental factors, giving rise to di erent populations of macrophages with distinct functions, which can force the foreign body reaction into tolerance of the biomaterial or into a state of in ammation. Classically activated macrophages, or M1 macrophages, have been characterized and desribed most thoroughly. They propagate proin ammatory responses by producing cytokines such as interleukin (IL) 1b, tumour necrosis factor (TNF) a and IL-6(6-8). Another macrophage phenotype is represented by the alternatively activated macrophages, referred to as M2 macrophages. These cells can arise when exposed to IL-4 or immune complexes. They express scavenger receptors and IL-1 receptor antagonist (IL-1RA). M2 macrophages also produce IL-10 and chemokines, such as CCL18 and macrophage-derived chemokine (MDC, or CCL22)(6-8), and are able to produce growth factors, thus promoting angiogenesis and tissue repair(6). During wound healing, M1 macrophages are normally present from day 1, and accumulate and dominate the wound site after 2–3 days. After cleaning the wound site by phagocytosis, macrophages change towards an M2 phenotype. Persistent in ammation can cause an imbalance of M1 to M2 macrophages and lead to brosis. Synthetic biomaterials can induce the formation of brous wound healing tissue within 2–4 weeks. Macrophages
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