Magnetic Hierarchical Micro/Nanofibrous Artificial Periosteum Promotes Bone Regeneration under a Static Magnetic Field

Abstract

The periosteum provides a highly organized osteogenic microenvironment that orchestrates cellular recruitment, vascularization, and bone regeneration. However, its clinical application is limited by donor scarcity and infection risks. Herein, a hierarchical micro/nanofibrous artificial periosteum was fabricated by integrating electrospun polycaprolactone (PCL) fibers with self-assembled nanofibers derived from alkali-dissolved chitosan (CS). Magnetic hydroxyapatite nanoparticles (MHNPs) and the osteoinductive agent icariin (ICA) were incorporated to enhance osteogenic activity. The biomimetic micro/nanofibrous architecture improved hydrophilicity, mechanical properties, and cellular responses, while MHNPs endowed the artificial periosteum with magnetic responsiveness. In a rat critical-sized cranial defect model, micro-CT analysis demonstrated that, under a static magnetic field (SMF), the PCL-CS-MHNPs-ICA group exhibited the highest bone volume fraction and nearly complete defect closure at 8 weeks postimplantation. Histological and immunohistochemical analyses further revealed enhanced collagen deposition, more mature lamellar bone formation, and upregulated expression of the osteogenesis-related marker (OCN), accompanied by improved angiogenesis. Overall, the magnetic artificial periosteum, in combination with SMF stimulation, effectively established a favorable osteogenic microenvironment and markedly accelerated bone regeneration, highlighting its potential as a promising strategy for the treatment of critical-sized bone defects.