Abstract

In this study, a cell-free bone tissue engineering scaffold based on core–sheath fibers with micro/submicro-scale structures were fabricated for bone regeneration. The composite fibers were prepared by coaxial electrospinning with cellulose acetate (CA) core solution and a sheath solution consisting of a mixture of silk fibroin (SF) and polyethylene oxide (PEO) loaded with nano-hydroxyapatite (nHAP) and bone morphogenetic protein 2 (BMP-2). The scanning electron microscopy results indicated that a submicro-scaled elliptical pattern formed throughout the entire sheath surface and that these patterned fibers formed a scaffold with microscale interconnected micropores. The fabricated scaffolds with micro/submicro-scale structures displayed good biocompatibility and increased mechanical properties compared to scaffolds based on single-component SF fibers without CA as the core. The results obtained with enzyme-linked immunosorbent assays (ELISAs) indicated that rapid initial release of BMP-2 from the scaffold occurs during the first few days, followed by slow and sustained release for as long as three weeks. The scaffold had a more profound effect on the attachment, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro compared to scaffolds without nHAP and BMP-2. Furthermore, in vivo studies indicated that this scaffold markedly enhanced bone regeneration at 12 weeks post-implantation. Taken together, our findings suggest that the hierarchical micro/submicro-scale structure scaffold consisting of core–sheath fibers acted as a good carrier for sustained BMP-2 release and that it can be used as a replacement material for bone grafts.