Metal-Phenolic Modified Coaxial Electrospun Biomembrane Combined with the Photothermal Effect Enhances Bone Regeneration by Ameliorating Oxidative Stress and Mitochondrial Dysfunction via the PI3K/Akt Signaling Pathway

Abstract

Critical-sized bone defect regeneration remains a significant clinical challenge due to the complex cascade of biological processes involved. To address this, we developed a sophisticated hierarchical biomembrane (PCS@MPN10) designed to modulate the osteogenic microenvironment. Using coaxial electrospinning, we fabricated a core-shell structure with polylactic acid (PLA) as the membrane base, incorporating simvastatin in the core and chitosan in the shell. The membrane surface was further modified with a tannic acid-iron metal-polyphenol network coating. Our results demonstrated that the biomembrane exhibits excellent biocompatibility, photothermal properties, and significant antibacterial activity. Additionally, the membrane regulates the microenvironment by promoting M1-to-M2 macrophage polarization, showing strong osteogenic potential both in vitro and in vivo. Furthermore, PCS@MPN10+NIR modulates mitochondrial function through the PI3K-AKT pathway, clears mitochondrial reactive oxygen species (ROS), and alleviates cellular oxidative stress, thereby enhancing bone regeneration. Overall, these findings suggest that this biomembrane holds great promise as a strategy for improving bone regeneration in critical-sized defects.