Polysaccharide–Peptide Conjugates as Precision Biomaterials: Conjugation Chemistry, Structural Design, and Biomedical Applications

Polysaccharide–peptide conjugates are modular biomaterials that combine hydrated carbohydrate frameworks with peptide domains capable of mediating molecular recognition, degradability, antimicrobial activity, and biological signaling. In this review, we discuss how covalent, bioorthogonal, and enzymatic conjugation strategies regulate peptide density, orientation, accessibility, and stability within polysaccharide-based matrices. These chemical choices are analyzed in relation to network architecture, viscoelasticity, ligand presentation, degradation behavior, and cell–material interactions. Representative systems based on hyaluronic acid, alginate, chitosan, dextran, cellulose, and glycosaminoglycans are examined to illustrate how peptide functionalization can transform otherwise passive scaffolds into adhesive, degradable, antimicrobial, or therapeutically responsive platforms. We further highlight dynamic and enzyme-responsive materials, localized drug delivery systems, antimicrobial coatings, and antibiofilm interfaces as key biomedical applications of these conjugates. The review also addresses translational challenges associated with structural heterogeneity, stability, immunogenicity, sterilization, batch-to-batch reproducibility, and clinical feasibility. Taken together, the evidence discussed here indicates that the performance of polysaccharide–peptide conjugates depends on reproducible structure–function relationships linking conjugation chemistry, macromolecular architecture, and biological activity under application-relevant conditions.