Chronic wounds are often complicated by multidrug-resistant infections and biofilms, while ineffective local antimicrobial presentation limits treatment success. Here, we developed biopolymer-based hydrogel wound dressings based on an oxidized hyaluronic acid/carboxymethyl chitosan (OHA/CMC) matrix, in which SAAP- 148, a potent antimicrobial peptide (AMP), was covalently conjugated via Schiff-base chemistry.

OHA was synthesized with degrees of oxidation of 10% and 30% to evaluate their impact on physicochemical properties, peptide coupling, and free-peptide release. SAAP-148 conjugation and distinct structural properties of the resulting materials were supported by SEC-MALS, ¹H/¹³C-NMR, FTIR, and SEM. Rheological analysis showed tunable viscoelastic behavior, supporting adaptability to wound shape. Free-peptide release assays were used to assess SAAP-148 retention within the polymeric matrices. Compared with the HA-SAAP-148 reference material, which released 32-50% peptide over 48 h, OHA-based systems limited free SAAP-148 release to <18%, indi­ cating more efficient peptide retention. Among the tested derivatives, OHA10%-based conjugates were selected as the most promising candidates, showing low toxicity and minimal hemolytic activity. The selected conjugates displayed strong antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, achieving an LC99.9 of 0.7 µg/mL. Overall, this platform provides a versatile strategy for local polymer-bound AMP pre­ sentation and may support further development of conjugated antimicrobial wound dressings.