In the absence of any surfactants, organic solvents or template-directing reagents, the strontium substituted hydroxyapatite (SrHAp) microspheres with hierarchically mesoporous structures and 1.17-5.60 mol.% of Sr substitution were successfully fabricated via hydrothermal method. The morphology observation showed that the fabricated SrHAp porous microspheres in diameters of 50-65 mu m were assembled by two-dimensional single-crystal nano-sheets with 30-70 nm in thickness, and up to 3 mu m in width and length. The ionic extracts of SrHAp porous microspheres promoted the proliferation, osteogenic differentiation and angiogenic factor expression of human osteoblast-like cells (MG-63), and the microspheres with 3.22 mol.% of Sr substitution showed the best potentially therapeutic applications in bone regeneration field. In addition, the novel 3D architectures of SrHAp resulted in favorable drug loading and sustained release properties. Our study indicated that the fabricated multifunctional SrHAp porous microspheres might be a potential candidate as bioactive bone-regeneration and drug-delivery material. (c) 2013 Elsevier B.V. All rights reserved.