Macrophage response mediated by extracellular matrix: recent progress

Biomaterials are one of efficient treatment options for tissue defects in regenerative medicine. Compared to synthetic materials which tend to induce chronic inflammatory response and fibrous capsule, extracellular matrix (ECM) scaffold materials composed of biopolymers are thought to be capable of inducing a pro-regenerative immune microenvironment and facilitate wound healing. Immune cells are the first line of response to implanted biomaterials. In particular, macrophages greatly affect cell behavior and the ultimate treatment outcome based on multiple cell phenotypes with various functions. The macrophage polarization status is considered as a general reflection of the characteristics of the immune microenvironment. Since numerous reports has emphasized the limitation of classical M1/M2 nomenclature, high-resolution techniques such as single-cell sequencing has been applied to recognize distinct macrophage phenotypes involved in host responses to biomaterials. After reviewing latest literatures that explored the immune microenvironment mediated by ECM scaffolds, this paper describe the behaviors of highly heterogeneous and plastic macrophages subpopulations which affect the tissue regeneration. The mechanisms by which ECM scaffolds interact with macrophages are also discussed from the perspectives of the ECM ultrastructure along with the nucleic acid, protein, and proteoglycan compositions, in order to provide targets for potential therapeutic modulation in regenerative medicine.