Electrospun multicomponent and multifunctional nanofibrous bone tissue engineering scaffolds

Abstract

Electrospinning has attracted great interest for making tissue engineering scaffolds. Given that bone morphogenetic protein-2 (BMP-2) can induce osteogenic differentiation of mesenchymal stem cells (MSCs) and synthetic calcium phosphates (Ca-P) are osteoconductive, electrospun scaffolds incorporating both BMP-2 and Ca-P could have a synergistic effect on bone formation. Besides, scaffold vascularization is of great importance during the bone regeneration process. Therefore, electrospun scaffolds having balanced angiogenic properties, osteoinductivity and osteoconductivity are desirable for inducing bone tissue regeneration. Here, novel tricomponent nanofibrous scaffolds incorporating recombinant human vein endothelial growth factor (rhVEGF), recombinant human BMP-2 (rhBMP-2) and Ca-P nanoparticles were made to recreate extracellular matrix-like microstructures with balanced angiogenic properties, osteoinductivity and osteoconductivity, for enhanced bone regeneration. The morphology, structure, wettability and chemical composition of the scaffolds were investigated. The in vitro release behaviour of growth factors was studied. By changing the polymer matrices, simultaneous or sequential release of rhVEGF and rhBMP-2 was obtained. After 3-day culture, both human umbilical vein endothelial cells (HUVECs) and murine pluripotent mesenchymal cells (C3H10T1/2) showed high viability on the scaffolds. The tricomponent scaffolds not only induced distinct HUVEC proliferation, migration and tube formation but also enhanced the osteogenic differentiation of C3H10T1/2 cells by showing up-regulated alkaline phosphatase expression, calcium deposition and gene expression of osteogenic markers.