Nisin Z and cinnamaldehyde co-delivery via fiber-reinforced alginate hydrogels: A synergistic in vitro strategy against infected pressure ulcers

Infected pressure ulcers remain difficult to manage because conventional dressings cannot simultaneously provide mechanical robustness, sustained antimicrobial delivery, and a favorable healing environment. Here, sodium alginate (SA) hydrogels were engineered with a dual-reinforcement strategy, electrospun polycaprolactone (PCL) fibrous films versus their hydrolysis-derived fragments, to independently tune mechanical behavior while compartmentalizing two bioactive agents, Nisin Z (NZ) and cinnamaldehyde (CN), for combined antimicrobial and antioxidant function. This architecture-driven approach distinguishes the system from previous single-reinforcement or single-agent SA-based dressings. NZ was highly active against Gram-positive bacteria (S. aureus, S. epidermidis; MBC = 8 μg/mL) and less so against Gram-negative strains (E. coli, 128 μg/mL; P. aeruginosa, 32 μg/mL), with CN requiring 20-320 μg/mL. Combined, NZ and CN acted synergistically against S. aureus (FICI = 0.019). Film-reinforced hydrogels preserved compressive strength, while fragment-reinforced systems favored flexibility and recovery after 50% deformation, giving the platform tunable mechanics for different wound geometries. NZ and CN were released over 48 h through diffusion- and retention-dominated mechanisms, respectively, sustaining >90% bacterial reduction against Gram-positive strains, strong antibiofilm activity, and > 80% DPPH antioxidant scavenging, without compromising HaCaT keratinocyte viability (> 85%). By showing that reinforcement architecture and bioactive compartmentalization can be engineered jointly rather than independently, this work introduces a versatile SA-based platform for infected chronic wound management, with direct translational potential for pressure ulcer care.