A covalently crosslinked alginate hydrogel platform with alginate oligosaccharide for tunable mechanics and enhanced antibacterial function

Abstract The performance of wound dressings is closely linked to their ability to provide appropriate mechanical support, moisture retention, and antibacterial protection. Here, we report a covalently crosslinked alginate hydrogel dressing designed to overcome ion leaching associated with conventional Ca 2 ⁺-crosslinked alginate and to enhance functional molecule efficacy through alginate oligosaccharide (AOS) incorporation. Covalent hydrogels were prepared using EDC/NHS chemistry with amino acid–based crosslinkers, and AOS was conjugated at varying concentrations. Compared with ionically crosslinked gels, covalent hydrogels exhibited reduced swelling and a compressive modulus of 2–5 kPa with ~ 40% hysteresis, approaching the lower range of skin elasticity. Although increasing AOS content further decreased re-swelling after drying, water-retention capacity was largely preserved. An antimicrobial peptide was covalently immobilized onto the hydrogel surface, imparting dose-dependent antibacterial activity. Notably, AOS incorporation significantly enhanced antibacterial efficacy, nearly doubling growth inhibition at lower peptide concentrations. Microstructural analysis revealed dense pore networks in ionically crosslinked gels, whereas AOS conjugation did not induce substantial structural changes in covalent hydrogels. This study demonstrates that AOS-conjugated, covalently crosslinked alginate hydrogels provide tunable mechanical properties and amplified antibacterial performance, offering a versatile platform for next-generation functional wound dressings. Graphical abstract