The Influence of Polysaccharides‐Based Material on Macrophage Phenotypes

Abstract Macrophage polarization is a key factor in determining the success of implanted tissue engineering scaffolds. Polysaccharides (derived from plants, animals, and microorganisms) are known to modulate macrophage phenotypes by recognizing cell membrane receptors. Numerous studies have developed polysaccharide‐based materials into functional biomaterial substrates for tissue regeneration and pharmaceutical application due to their immunostimulatory activities and anti‐inflammatory response. They are used as hydrogel substrates, surface coatings, and drug delivery carriers. In addition to their innate immunological functions, the newly endowed physical and chemical properties, including substrate modulus, pore size/porosity, surface binding chemistry, and the mole ratio of polysaccharides in hybrid materials may regulate macrophage phenotypes more precisely. Growing evidence indicates that the sulfation pattern of glycosaminoglycans and proteoglycans expressed on polarized macrophages leads to the changes in protein binding, which may alter macrophage phenotype and influence the immune response. A comprehensive understanding of how different types of polysaccharide‐based materials alter macrophage phenotypic changes can be beneficial to predict transplantation/implantation outcomes. This review focuses on recent advances in promoting wound healing and balancing macrophage phenotypes using polysaccharide‐based substrates/coatings and new directions to address the limitations in the current understanding of macrophage responses to polysaccharides.