Coral-inspired immunoreprogramming scaffold reverses the “immune-freeze” microenvironment to promote bone regeneration in steroid-induced osteonecrosis of the femoral head

Abstract

The core pathological mechanism of steroid-induced osteonecrosis of the femoral head (SONFH) is an “immune freeze” microenvironment—where corticosteroids continuously drive macrophages toward a pro-inflammatory M1 phenotype, inhibiting the conversion to reparative M2 macrophages, thereby impairing bone regeneration. To address this bottleneck, this study was inspired by the hierarchical pore structure of coral. Using low-temperature deposition 3D printing technology, we constructed an immunoreprogramming biomimetic scaffold that integrates multi-walled carbon nanotubes (MWCNT) and nano-hydroxyapatite (nHA) (MWCNT bionic scaffold). The scaffold leverages the active immune regulatory function of MWCNT to activate the PI3K-AKT signaling pathway, driving macrophages to transition from the M1 to M2 phenotype, effectively breaking the “immunological freeze” state and reshaping the pro-regenerative bone immune microenvironment. Meanwhile, the nHA component provides a biomimetic mineralization matrix and sustained release of calcium and phosphate ions, synergizing with the nanofiber structure of MWCNT to promote the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenesis. In vivo experiments confirm that scaffold implantation reverses the local “immune freeze” state, drives macrophage polarization toward the M2 phenotype, reduces inflammatory responses, and enhances the maturation and functional vascular network formation of new bone matrix in bone defect areas, ultimately achieving bone structural reconstruction. The coral-inspired immunoreprogramming strategy proposed in this study provides a new strategy for targeting the regulation of the pathological microenvironment in SONFH.