We have engineered a scaffold constructed of synthetic octacalcium phosphate (OCP) and collagen composites (OCP-collagen) and report that OCP-collagen significantly enhanced bone regeneration more than the implantation of OCP. We hypothesized that the dehydrothermal treatment (DHT) during the fabrication of OCP-collagen might influence bone regeneration by OCP-collagen. To examine this hypothesis, bone regeneration by the implantation of OCP-collagen with DHT [OCP/Col(+)] was compared with that by OCP-collagen without DHT [OCP/Col(-)]. It was confirmed that both OCP/Col(+) and OCP/Col(-) contained the characteristics of OCP structure in X-ray diffraction. Before implantation, calcium deposition derived from OCP was observed within the collagen of both OCP/Col(+) and OCP/Col(-) by undecalcified histological sections. OCP/Col(+) or OCP/Col(-) was implanted into the critical-sized defects in rat crania. Radiographic and histological examination was performed and the percentage of newly formed bone (n-Bone%) in the defect was determined by a histomorphometrical analysis. N-Bone% treated with OCP/Col(+) was significantly higher than that with OCP/Col(-) at 4 and 12 weeks after implantation, because fast degradation of the implanted collagen of OCP/Col(-) elicited disappearance of the scaffold for bone regeneration. The stiffness of the calcified collagen in OCP-collagen would be more important than the existence of calcified collagen to enhance the bone regeneration by OCP-collagen composites. The present study suggests that the dehydrothermal treatment would influence effective bone regeneration by OCP-collagen.