Cell function to form bone would be influenced by local environment, such as mechanical stress and tissue fluid constituents over intracellular signal transduction to macroscopic order. For example, osteoblasts and osteocytes respond to mechanical stimuli by changing their metabolism, proliferation, and differentiation. Our recent study showed that the elevated extracellular calcium stimulated secretion of osteogenic bone morphogenetic protein-2 by a macrophage cell line. The macrophage-like cells appeared near bioresorbable bone substitute such as octacalcium phosphate (OCP). OCP has been identified an intermediate to various biological apatite crystals. If OCP were implanted into the living animals, bio-resorbable OCP would modify local environment during bone regeneration by irreversibly transforming to bone-like apatite, which accompanied with calcium uptake and phosphate release. Recently, we have developed a synthetic bone regenerative material constructed of synthetic OCP and porcine atelocollagen (OCP/Collagen). OCP/Collagen enhanced bone regeneration more than OCP per se. OCP/Collagen constructed three-dimensional scaffold for bone regeneration.