Charge-patterned glycosaminoglycan-mimetic polysaccharides for infection-resistant tissue repair: Growth-factor...

Chronic and infected wounds expose a structural deficit in regenerative biomaterials: the native glycosaminoglycan (GAG) machinery that organizes growth-factor gradients, restrains proteolysis, and sets immune tone is absent, degraded, or pathologically remodeled. GAG-mimetic polysaccharides sulfated marine, microbial, and engineered carbohydrates that reproduce the charge chemistry of heparin, heparan sulfate, and chondroitin sulfate without their supply and safety liabilities offer a route to rebuild that machinery on demand. This review explores the carbohydrate-polymer logic linking primary structure to repair outcome. Sulfation degree and, more consequentially, sulfation position and charge patterning govern the affinity and selectivity with which these polymers capture FGF-2, VEGF, TGF-beta, PDGF, and BMPs, and the extent to which they competitively sequester chemokines, complement components and matrix proteins. The same anionic, hydrated interfaces that concentrate morphogens also resist bacterial adhesion, perturb biofilm assembly, and serve as depots for antimicrobial peptides, thereby coupling pro-regenerative and anti-infective functions within a single backbone. We evaluate heparin, heparan sulfate, hyaluronan, chondroitin and dermatan sulfate, fucoidan, carrageenan, ulvan, and sulfated cellulose, chitosan, and alginate, alongside defined synthetic glycopolymers, and trace how molecular weight, chain flexibility, and hydrogel presentation modulate angiogenesis, fibroblast and keratinocyte behavior, and macrophage polarization. Persistent translational barriers uncontrolled anticoagulation, oversulfated-contaminant toxicity, immunogenicity, batch heterogeneity, and degradation mismatch are examined critically. We emphasize that position-resolved sulfation control, not maximal charge, is the decisive design variable for the next generation of infection-resistant regenerative matrices. Binding is treated here as a property of the pair rather than of the polysaccharide alone: clustered basic residues, reversible monomer-dimer equilibria and higher-order oligomerisation on the morphogen side determine how growth factors and chemokines are sequestered, how haptotactic gradients form, and how neutrophils are recruited, and these traits constrain which mimetic structures can work. Chemokine sequestration is defined mechanistically rather than invoked, and the practical constraints specific to marine-derived complex polysaccharides-structural heterogeneity, process-written sulfation, contaminant carry-over and the absence of mammalian catabolic machinery are set out alongside the characterisation each one demands.