Fig. 2

ECM alterations and immune response. Decellularization-derived damages to the extracellular matrix affect its immunogenicity via exposing/producing immunogenic particles or depleting immunomodulatory molecules. (1) Decellularization may destroy immunosuppressive traits of high molecular weight hyaluronic acids (HMWHAs) by breaking them into low molecular weight hyaluronic acids (LMWHAs). HMWHAs induce a regulatory phenotype in T cells and macrophages while suppressing humoral immunity and dendritic cell maturation. (2) LMWHAs are demonstrated to interact with CD44 and toll-like receptors of leukocytes and invoke inflammatory responses such as enhancing leukocyte chemotaxis, dendritic cell maturation and polarization of naïve macrophages toward M1 phenotype. (3) Collagen denaturation during decellularization may expose some cryptic antigenic sites and trigger antibody production, or (4) upregulate immune system activity through the depletion of RGD motives, which impede leucocytes chemotaxis and take part in the M2 polarization of macrophages. (5) Elastin particles are released upon elastin damage and provoke monocyte chemotaxis, antibody-mediated immune response, and T helper cell differentiation toward inflammatory phenotypes