Chemically Modified Alginate Grafted Penicillanic Acid Derivatives for Antibacterial Electrospun Composite Nanofibers: Electrospinnability, Drug Delivery and Cytocompatibility

Electrospinning of pure alginate is challenging due to its rigid molecular conformation and high conductivity, while conventional blends with carrier polymers severely dilute its intrinsic bioactivity. To overcome this, we developed a chemical strategy to graft hydrophobic 6-aminopenicillanic acid (6-APA) onto alginate. Among three synthetic routes, the oxidative–reductive amination-derived alginate grafted penicillanic acid derivative (RA-OSA-APA) showed dramatically enhanced flexibility, with a 10-fold lower chain entanglement concentration and a 60-fold reduced rheological crossover frequency versus pristine alginate. Blending RA-OSA-APA with poly(vinyl alcohol) (PVA) enabled the production of bead-free nanofibers with high functional biopolymer content. These composite nanofibers exhibited high encapsulation efficiency (EE) for triclosan (TCA), tunable sustained release (73–86% over 810 min), excellent cell viability (>85%), and potent antibacterial activity against Staphylococcus aureus and Escherichia coli. This work establishes oxidative–reductive amination as an effective method to concurrently solve alginate’s electrospinning processability issue and engineer advanced multifunctionality for bioactive wound dressings.