Abstract

In this study, a cell-free bone tissue engineering system based on a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was developed, in which two bioactive molecules , stromal cell derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2), were embedded and released in a sequential and controlled manner to facilitate cell recruitment and bone formation, respectively. BMP-2 was initially loaded into SF microspheres , and these BMP-2 containing microspheres were subsequently encapsulated into the SF/nHAp scaffolds, which were successively functionalized with SDF-1 via physical adsorption. The results indicated rapid initial release of SDF-1 during the first few days, followed by slow and sustained release of BMP-2 for as long as three weeks. The composite scaffold significantly promoted the recruitment of bone marrow mesenchymal stem cells (BMSCs) and osteogenic differentiation of them in vitro . Further, the in vivo studies using D-Luciferin-labeled BMSCs indicated that implantation of this composite scaffold markedly promoted the recruitment of BMSCs to the implanted sites. Enhanced bone regeneration was identified at 12 weeks' post-implantation. Taken together, our findings suggested that the sequential and sustained release of SDF-1 and BMP-2 from the SF/nHAp scaffolds resulted in a synergistic effect on bone regeneration. Such a composite system , therefore, shows promising potential for cell-free bone tissue engineering applications .