Dopants play critical roles in controlling the physical, mechanical, degradation kinetics, and
in vivo
properties of calcium phosphates. The aim of the present study was to evaluate the effects of Silicon (Si) and Zinc (Zn) dopants on physico-mechanical, and
in vivo
osteogenesis properties of brushite cements (BrCs) alone and in combination with insulin like growth factor 1(IGF-1). Although addition of 0.5 wt.% Si did not alter the setting time, β-TCP content, and compressive strength of BrCs significantly, 0.25 wt. % Zn incorporation was accompanied by a significant decrease in mechanical strength from 4.78±0.21 MPa for pure BrC to 3.78±0.59 MPa and 3.28±0.22 MPa for Zn-BrC and Si/Zn-BrC, respectively. The
in vivo
bone regeneration properties of doped BrCs alone and in combination with IGF-1 were assessed and compared using chronological radiography, histology, scanning electron microscopy and fluorochrome labeling after 2 and 4 months post implantation in rabbit femoral defect model. Based on different
in vivo
characterization, better osteogenesis and vasculogenesis was observed for Si-BrC and Si/Zn-BrC, whereas moderate bone regeneration was found in Zn-BrC as compared to pure BrCs. Excellent bone regeneration was observed when doped BrCs were combined with IGF-1. Our findings signify that addition of Si and/or Zn alters the physico-mechanical properties of BrCs and promotes the early stage
in vivo
osseointegration and bone remodeling properties. Moreover, addition of IGF-1 further improved the performance of BrCs in terms of bone regeneration in animal model