Sugar-coated immunometabolism: functionalized biomaterials as metabolic regulators of immune responses

Immunometabolism, the intersection of immune function and cellular metabolism, has emerged as a powerful lens for understanding and directing host response to biomaterials. Upon implantation, biomaterials often provoke immune activation, potentially leading to chronic inflammation, fibrotic encapsulation, and impaired integration. Recent advances point to sugar functionalization as a promising strategy to steer immunometabolic pathways, enhance biocompatibility, and promote regenerative outcomes. Naturally derived monosaccharides (e.g., mannose, glucose, galactose), polysaccharides (e.g., dextran, chitosan), and glycosaminoglycans (e.g., hyaluronic acid, heparin) engage distinct immune receptors to induce targeted metabolic reprogramming in macrophages, dendritic cells, and other innate effectors. This minireview synthesizes recent breakthroughs in the field, elucidating how distinct sugar classes reshape immunometabolism by modulating glycolysis, oxidative phosphorylation, fatty acid metabolism, and associated inflammatory pathways and highlighting their translational applications in precision medicine. We discuss design considerations for sugar-functionalized scaffolds and outline future directions centered on precision glycoengineering, integrated metabolic analyses, and personalized therapeutic platforms.