Macrophage reaction against biomaterials in the mouse model - Phenotypes, functions and markers

Abstract

The foreign body reaction (FBR) is a response of the host tissue against more or less degradation-resistant foreign macromolecular material. The reaction is divided into five different phases which involve most aspects of the innate and the adaptive immune system: protein adsorption, acute and chronic inflammation, foreign body giant cell formation and fibrosis. It is long known, that macrophages play a central role in all of these phases except for protein adsorption. Initially it was believed that the macrophage driven FBR has a complete negative effect on biocompatibility. Recent progress in biomaterial and macrophage research however describe macrophages as more than pure antigen phagocytosing and presenting cells and thus pro-inflammatory cells involved in biomaterial encapsulation and failure. Quite contrary, both, pro-inflammatory M1 macrophages, the diverse regulatory M2 macrophage subtypes and even foreign body giant cells (FBGC) are after necessary for integration of non-degradable biomaterials and degradation and replacement of degradable biomaterials. This review gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed.

Statement of significance: The view on role of macrophages in the foreign body reaction against biomaterials is rapidly changing. Despite the initial idea that macrophage are mainly involved in undesired degradation and biomaterial rejection it becomes now clear that they are nevertheless necessary for proper integration of non-degradable biomaterials and degradation of placeholder, degradable biomaterials. As a pathologist I experienced a lack on a good summary on the current taxonomy, functions and phenotypes of macrophages in my recent projects on the biocompatibility of biomaterials in the mouse model. The submitted review therefore intends to gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed.

Keywords: Biocompatibility; Biomaterials; Foreign body reaction; In vivo; Macrophages.