Design of multi-layer electrospun poly(ε-caprolactone)/chitosan nanofiber scaffolds loaded with tigecycline for controlled drug release and antibacterial wound healing.

In this study, a novel multi-layer scaffold composed of poly(ε-caprolactone) (PCL) and chitosan (CS) was designed and fabricated via electrospinning, with tigecycline (Tig) incorporated as an antimicrobial agent in the middle layer. This nanofibrous multi-layer structure consisted of hydrophobic PCL outer and inner layers and a hydrophilic PCL-CS-Tig middle layer, designed to mimic the structural functionality of the native extracellular matrix. SEM analysis revealed that the fabricated nanofibrous layers were uniform, beadless fibers with diameters ranging from 689 ± 186 nm for the pure PCL layers to 125 ± 19 nm in the PCL-CS matrix loaded with Tig (single-layer), and further increased to 298 ± 98 nm in the multi-layer dressing. The addition of CS and Tig significantly enhanced the wettability and altered the surface roughness, improving cell interaction. The water contact angle decreased from 113 ± 3° to 106 ± 4° for the pure PCL layers and the multi-layer scaffold, respectively, indicating a modest improvement in surface wettability. Additionally, the fabricated electrospun membranes were characterized by DSC, mechanical, and porosity analyses to evaluate their functional suitability. The multi-layer scaffold exhibited a tensile strength of 7.44 MPa and minimal weight loss, confirming its mechanical robustness and high structural stability for wound dressing applications. In vitro drug release demonstrated a biphasic release profile, with the multi-layer dressing releasing approximately 38 % of Tig within the first 60 min. The release behavior followed Korsmeyer-Peppas kinetics, indicating a combination of diffusion and matrix relaxation mechanisms. All dressings types showed significant antibacterial activity against E. coli and S. aureus, while cytocompatibility tests using HUVECs demonstrated over 95 % cell viability on the multi-layer scaffold within two days. These findings suggest that the electrospun PCL-CS-based multi-layer dressing offers promising potential as a bioactive, antibacterial platform for advanced wound healing applications.