Coaxial Fibrous Dressing Enabling Sequential NO/H2 Release for Temporally Programmed Antibacterial and Healing-Promoting Functions in Infected Diabetic Wound Treatment

Abstract

Infected diabetic wounds have become a major global health threat due to their complex conditions, making them difficult to heal. Herein, a coaxial fibrous dressing capable of sequential release of nitric oxide (NO) and molecular hydrogen (H₂) was designed for the treatment of infected diabetic wounds. The outer layer of the coaxial fibers was physically loaded with the NO donor, enabling the first stage of rapid and high-level NO release (over 170 μM). The released NO contributed to the antibacterial function of the dressing (in vitro antibacterial assays demonstrated eradication rates of 99.99% and 99.04% against S. aureus and E. coli, respectively), thus facilitating accelerated transition of the wound through the inflammatory phase. The inner layer of coaxial fibers becomes progressively exposed following structural disintegration, enabling the hydrolysis of encapsulated H₂ donor to achieve on-demand release of H₂ under near-infrared (NIR) irradiation. The released H₂ could promote wound healing through reactive oxygen species (ROS) scavenging and macrophage M2 polarization, as validated by in vitro cell assessments. In vivo infected full-thickness skin defect model in diabetic mice demonstrated that the NO/H₂ sequential release coaxial fibrous dressing significantly accelerated healing of infected wounds through rapid bactericidal action via substantial NO release, followed by further sequential H₂ release promoting repairing and regeneration. This temporally sequential delivery of antibacterial and healing-promoting functions significantly accelerated the healing of infected diabetic wounds.