The aim of this study was to design a new natural/synthetic bioactive bone scaffold for potential use in bone replacement applications. We developed a tri-component osteogenic composite scaffold made of collagen (Coll), hydroxyapatite (HA) and poly(l-lactide-co-ɛ-caprolactone) (PLCL). This Coll/HA/PLCL composite scaffold was combined with human osteoblast-like cells obtained by differentiation of dental pulp stem cells (DPSCs) to engineer bone tissue in vitro. Results show that the 3D Coll/HA/PLCL composite scaffold was highly porous, thereby enabling osteoblast-like cell adhesion and growth. Cultured in the Coll/HA/PLCL scaffold, the osteoblast-like cells expressed different osteogenic genes, produced alkaline phosphatase and formed nodules more than did PLCL alone. Micro-CT analyses revealed a significant (30%) increase of tissue mineralisation on the surface as well as inside of the Coll/HA/PLCL scaffold, thus confirming its effectiveness as a bone regeneration platform.