New Electrospun Tricomponent Scaffolds for Inducing Angiogenesis and Osteogenesis

Abstract

Composite scaffolds have been proven desirable porous structures in scaffold-based tissue engineering. For bone tissue engineering, our research has shown that electrospun bicomponent scaffolds consisting of fibers containing osteoconductive calcium phosphate (Ca-P) nanoparticles and fibers incorporated with osteoinductive recombinant human bone morphogenetic protein (rhBMP-2) can significantly promote the adhesion, proliferation and differentiation of osteoblasts as well as the osteogenic differentiation of mesenchymal stem cells. Apart from osteogenesis, angiogenesis is highly important for bone tissue regeneration. For desired good vascularization during new bone formation, vascular endothelial growth factor (VEGF), an angiogenic growth factor, is normally encapsulated in scaffolds for their later release. In this investigation, using our dual-power multi-source electrospinning technology, new tricomponent fibrous scaffolds were designed and made for bone tissue engineering. Monocomponent scaffolds were also produced for comparative studies. The scaffolds were then assessed for various properties using a variety of techniques. In tri- and monocomponent scaffold fabrication, emulsion electrospinning was employed to incorporate rhBMP-2 into poly(lactic-co-glycolic acid) (PLGA) fibers and recombinant human VEGF (rhVEGF) into poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) blend polymer fibers while Ca-P/PLGA nanocomposite fibers were made via blend electrospinning. The structure and properties of tri- and monocomponent scaffolds were studied. The in vitro release profiles of rhVEGF, rhBMP-2 and Ca2+ ions and the in vitro degradation behaviour of scaffolds were investigated. A faster rhVEGF release including an initial burst release followed by a sustained release was observed in the 24-day release tests. rhBMP-2 exhibited a more sustained release with a much reduced initial burst release. Biological studies of scaffolds were conducted using human umbilical vein endothelial cells (HUVECs) and human bone marrow-derived MSCs (hBMSCs). It was found that both HUVECs and hBMSCs proliferated well on mono- and tricomponent scaffolds. rhVEGF released from mono- or tricomponent scaffolds facilitated the migration of HUVECs while rhBMP-2 and Ca2+ ions released from mono- or tricomponent scaffolds promoted alkaline phosphatase expression and mineralization of hBMSCs. The combined delivery of rhVEGF, rhBMP-2 and Ca further enhanced the osteogenic differentiation of hBMSCs.