Synergistic delivery of bFGF and BMP-2 from poly(l-lactic-co-glycolic acid)/graphene oxide/hydroxyapatite nanofibre scaffolds for bone tissue engineering applications

Abstract

One of the goals of bone tissue engineering is to create scaffolds with excellent biocompatibility, osteoinductive ability and mechanical properties. The application of bioactive proteins, such as bone morphogenetic protein (BMP)-2 and basic fibroblast growth factor (bFGF), has been showed to be an effective way to improve the osteoinductivity and biocompatibility of bone scaffold materials. Therefore, the development of novel materials capable of delivering multiple growth factors is urgent and essential for bone defect repair. In this study, a composite nanofibre scaffold composed of poly(L-lactic-co-glycolic acid) (PLGA), hydroxyapatite (HA), and graphene oxide (GO) has been fabricated to deliver basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) simultaneously. The data show that the incorporation of GO and HA into PLGA nanofibres significantly improved the mechanical properties and hydrophilicity of the nanofibre scaffolds. More importantly, compared to PLGA and PLGA/HA nanofibre scaffolds, the PLGA/HA/GO nanofibre scaffolds could more efficiently immobilize bFGF and BMP-2. Moreover, biological assays indicated that the loaded bFGF and BMP-2 loaded in the composite nanofibre scaffolds have a synergistic differentiation effect on the cell adhesion, proliferation, and osteogenesis differentiation of MC3T3-E1 cells. In contrast to the PLGA/HA/GO/bFGF and PLGA/HA/GO/BMP-2 nanofibre scaffolds, the PLGA/HA/GO/bFGF/BMP-2 scaffolds have shown higher ALP activity and higher expression levels of osteogenesis-related genes. In summary, our findings indicated that the incorporation of GO into nanofibre scaffolds is an effective method to immobilize growth factors onto biomaterial surfaces, and the synergistic effects of a combination of BMP-2 and bFGF may have potential use in bone regenerative therapeutics.