Oxygen-Releasing Janus Nanofiber Membrane Based on Dendrobium officinale Polysaccharide to Promote Diabetic Wound Healing

Abstract

The mechanism of the difficulty in healing of diabetic foot ulcers (DFUs) involves imbalanced macrophage polarization, excessive accumulation of reactive oxygen species (ROS), and local hypoxic microenvironment in the wound. Therefore, regulating macrophage polarization to M2, removing excessive reactive oxygen species, and improving tissue oxygen supply have become key therapeutic strategies to promote the healing of DFUs. In this study, a Janus nanofibrous membrane (Janus NFM) wound dressing composed of a hydrophilic layer (poly(vinyl alcohol)-chitosan-Dendrobium officinale polysaccharide) and a hydrophobic layer (polycaprolactone-calcium peroxide) was designed. DOP was esterified with adipic acid (AA) to form the backbone material while functioning therapeutically. Janus NFM has a porous microstructure and excellent physical and chemical properties. The optimized electrospinning process improves the stability of the interface between the hydrophilic and hydrophobic layers and the controllability of oxygen release. D. officinale polysaccharide has significant ROS scavenging ability and can induce macrophage polarization to the anti-inflammatory and pro-repair M2 phenotype; through a hydrolysis reaction, calcium peroxide constantly releases oxygen, significantly reducing the wound’s hypoxic condition, and demonstrating broad-spectrum antibacterial activity. Janus NFM exhibits good biocompatibility both in vitro and in vivo. Animal experiments showed that the Janus NFM treatment group significantly promoted wound angiogenesis and collagen deposition compared with the control group, ultimately accelerating the wound closure rate (achieved a healing rate of 99.1 ± 0.5% (mean ± SD) by day 14). In summary, Janus NFM exhibits synergistic therapeutic advantages by maintaining steady-state ROS, balancing macrophage polarization and continuous oxygen delivery, and has potential clinical translational value.