Glabridin-loaded PCL/silk fibroin core-shell nanofibers with immunomodulatory and antioxidant activities for cutaneous wound healing.

Abstract

Oxidative stress and immune microenvironment dysregulation are key pathological mechanisms underlying impaired wound healing, particularly in chronic non-healing wounds such as diabetic ulcers. Developing dressings that synergistically scavenge reactive oxygen species (ROS) while correcting aberrant immune responses is therefore of significant clinical value. Electrospun nanofibers, due to their high specific surface area and ECM-mimicking porous architecture, are promising candidates for wound repair. In this study, a biocompatible, biodegradable core-shell nanofiber scaffold (PCL-GA/SF, PGS) was fabricated via coaxial electrospinning, with a polycaprolactone (PCL) core loaded with glabridin (GA) and a silk fibroin (SF) shell. PGS exhibited a uniform, interconnected network morphology with an average diameter of 433 ± 264 nm, a tensile strength of 1.82 ± 0.13 MPa, and a water contact angle of 48.1° ± 14.2°, which was favorable for wound healing. In vitro, PGS significantly promoted L929 fibroblast adhesion and proliferation, effectively scavenged ROS, and attenuated H2O2-induced oxidative cytotoxicity. Mechanistically, PGS remodeled the local microenvironment by driving macrophage polarization from the pro-inflammatory M1 phenotype to the pro-regenerative M2 phenotype, synergistically enhancing fibroblast function. In vivo, PGS scaffolds markedly accelerated skin tissue reconstruction and promoted regeneration of cutaneous appendages, including hair follicles and sweat glands. In conclusion, through rational core-shell design, this study integrates antioxidant and immunomodulatory functions within a single coaxially electrospun scaffold, offering a clinically translatable strategy for chronic diabetic wound repair and the comprehensive structural and functional reconstruction of skin tissue.