Polysaccharide-based bioactive materials for diabetes integrating translational design mechanisms and clinical applications

Polysaccharide-based bioactive materials have emerged as versatile and biocompatible platforms at the intersection of pharmacy, biomedicine, and engineering, offering innovative solutions for complex diseases such as diabetes. In this comprehensive review, we discuss the translational design of polysaccharide-based biomaterials (spanning smart drug delivery systems, 3D scaffolds, and injectable hydrogels), elucidate their mechanistic insights in therapeutic contexts, and evaluate their clinical prospects, with a particular focus on diabetes management. Evidence from recent studies indicates that polysaccharide carriers can enable controlled and stimulus-responsive delivery of anti-diabetic agents (e.g. insulin, GLP-1 analogs), enhance tissue engineering approaches for diabetic wound healing and pancreatic islet transplantation, and even exert direct anti-hyperglycemic effects by modulating biological pathways. Mechanistically, these polymers can mimic extracellular matrix functions, promote cell adhesion and angiogenesis, modulate immune responses, and respond to physiological triggers (such as glucose or pH) to release therapeutics on-demand. Clinically, polysaccharide-based hydrogels (e.g. alginate and hyaluronic acid dressings) are already in use or trials for chronic wounds, and encapsulated-cell therapies are being explored to improve glycemic control without immunosuppression. Ongoing interdisciplinary research and numerous clinical studies underscore the translational potential of these bioactive materials in improving outcomes for diabetes and related complications. The future outlook is optimistic, as polysaccharide biomaterials continue to advance toward smarter, more personalized medicine, bridging the gap from bench to bedside. Graphical abstract