Chlorhexidine Surface-Immobilized via a Carboxylated Polymer Layer on ZnO Nanoparticle-Containing Polycaprolactone Fibers for Wound Dressings.

We developed electrospun polycaprolactone (PCL) membranes containing 1-5 wt % ZnO nanoparticles (NPs), the surface of which was plasma-functionalized with carboxyl groups for covalent immobilization of chlorhexidine (CHX) via carbodiimide chemistry. Quantum-chemical analysis revealed that carboxyl functionalization, followed by 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC) activation, significantly enhanced CHX sorption, while ZnO NPs promoted charge transfer and increased the electrophilicity of the PCL matrix. The PCL-3%ZnO-CHX membranes exhibited high tensile strength (18.6 MPa), improved wettability, and prolonged Zn2+ release. The optimized composition demonstrated potent antibacterial and antifungal activity, achieving a 6-log reduction against S. aureus, E. faecium, E. coli, A. baumannii, and C. auris. In vitro studies confirmed excellent cytocompatibility toward human dermal fibroblasts, keratinocytes, and T-lymphocytes, with cell viability remaining above 93% throughout the study. Histological evaluation showed no chronic inflammation, necrosis, or foreign body reaction, while tissue organization in the PCL-3%ZnO-CHX group was comparable to the control. In a mouse tail amputation model, this material reduced blood loss and bleeding time by 6.6- and 1.5-fold, respectively. These results demonstrate that PCL-3%ZnO-CHX membranes combine mechanical strength, broad-spectrum antimicrobial activity, biocompatibility, immunocompatibility, and hemostatic performance, making them promising materials for wound dressings and tissue engineering.