Electrospun multilayer nanofibers with modified antibacterial alginate derivative for enhanced spinnability and drug sustained release

The inherent molecular rigidity of alginate, which limits chain flexibility and prevents effective entanglement, has long hindered its direct electrospinning into uniform nanofibers from aqueous solutions. To overcome this limitation and expand the application of alginate in infection-prone wound repair, this study introduces a novel antibacterial alginate derivative (RA-OSA-APA) synthesized via oxidation-reductive amination using 6-aminopenicillanic acid (6-APA) as a hydrophobic modifier. Leveraging this functional polymer, RA-OSA-APA was blended with water-soluble polyvinyl alcohol (PVA) to successfully fabricate RA-OSA-APA/PVA composite nanofibers through electrospinning. Furthermore, a sequential multilayer electrospinning strategy was employed to sequentially co-spun chitosan (CS) and gelatin (GT) onto the surface of RA-OSA-APA/PVA composite nanofibers, resulting in RA-OSA-APA/PVA/CS/GT electrospun multilayer composite nanofibers. Comprehensive characterization results demonstrated that chemical modification disrupted alginate’s hydrogen bonding network, enhanced molecular flexibility, and facilitated chain entanglement with PVA, significantly improving electrospinnability. Although bead-free nanofibers could not be electrospun from pure RA-OSA-APA aqueous solution, its content was effectively increased within the uniform RA-OSA-APA/PVA composite nanofibers. Furthermore, the sequential layering of CS and GT onto the RA-OSA-APA/PVA composite nanofibers via multilayer electrospinning not only yielded uniform fibrous morphologies stabilized by intermolecular hydrogen bonding but also created a unique physical barrier effect. This architectural innovation effectively reduced water absorption, achieved the effective loading and controlled release of triclosan (TCA), and synergized with the inherent antibacterial functions and robust cytocompatibility of CS and GT to enhance biological performance. With their favorable physicochemical and controlled-release properties, the RA-OSA-APA/PVA/CS/GT composite nanofibers represent a promising multifunctional wound dressing platform for managing infected wounds.