Combined delivery of bone morphogenetic protein-2 and insulin-like growth factor-1 from nano-poly (γ-glutamic acid)/β-tricalcium phosphate-based calcium phosphate cement and its effect on bone regeneration in vitro

Abstract

In this study, nano-doped calcium phosphate cement delivery systems (poly (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramics and nano (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramic) were fabricated, and low doses (10 µg/g) of two growth factors, insulin-like growth factor-1 and bone morphogenetic protein-2, were encapsulated then sequentially released. We characterized the delivery systems using Fourier transform infrared spectroscopy and X-ray diffraction and measured washout resistance and compressive strength, and thus optimized the most appropriate proportioning of delivery systems for the two growth factors. One of the growth factors was absorbed by the nano-poly (γ-glutamic acid)/β-tricalcium phosphate, which was then mixed into the calcium phosphate ceramic solid phase to create a new solid phase calcium phosphate ceramic. Nano-poly (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramic carriers were then prepared by blending the new calcium phosphate ceramic solid phase powder with a solution of the remaining growth factor. The effects of different release patterns (studying sequential behavior) of insulin-like growth factor-1 and bone morphogenetic protein-2 on osteogenic proliferation and differentiation of the MC3t3-E1 mouse osteoblast cell were investigated. This combinational delivery system provided a controlled release of the two growth factors, in which nano-doping significantly affected their release kinetics. The incorporation of dual growth factors could potentially stimulate bone healing and promoting bone ingrowth processes at a low dose.