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Poly(ε-caprolactone) (PCL), a biocompatible and biodegradable polymer, has been approved to be used as bone substitutes. Taking into account the osteoconductivity of hydroxyapatite (HAp) and the osteoinductivity of crude bone protein (CBP), sponge scaffolds of PCL without and with the presence of HAp or CBP-loaded HAp nanoparticles were prepared by solvent casting/particulate leaching techniques. The osteoblastic activity of the PCL, PCL-HAp, and PCL-HAp/CBP sponge scaffolds was investigated in vitro with mouse-calvaria-derived preosteoblastic cells (MC3T3-E1) in terms of attachment, proliferation, alkaline phosphatase (ALP) activity, and mineralization of the cells that were cultured on the scaffolds. The results were compared with those on corresponding electrospun nanofibrous scaffolds and tissue-culture polystyrene plate (TCPS). Although the three types of sponge and nanofibrous scaffolds supported the proliferation and spreading of MC3T3-E1 cells, the PCL-HAp/CBP sponge scaffold produced the highest level of ALP activity and mineralization. Therefore, the obtained PCL-HAp/CBP sponge scaffold has a high potential to be used as a synthetic substitute for bone regeneration.