Organic-inorganic hybrid biomaterials stand as a promise for combining bone bonding and bone mineral-forming ability, stimulation of osteogenic cells and adequate mechanical properties. Bioactive glass (BG)polycaprolactone (PCL) hybrids are of special interest as they gather the ability of BG to enhance osteoblast-mediated bone formation with the slow degradation rate and the toughness of PCL. In this study, BG-PCL hybrids were synthesized in the form of scaffold owing a dual cortical/trabecular structure mimicking the bone architecture. Their biological potential was evaluated both in vitro using rat primary osteoblasts (RPO) and in vivo in a mice model of critical-size calvarial defects. BG-PCL were compared to Lubboc TM (BTB), a commercial purified bovine xenograft widely used in orthopedics and periodontal procedures and known for its efficiency. BG-PCL hybrids were found to facilitate RPO adhesion at their surface and to enhance RPO differentiation when compared to BTB. In vivo micro-CT study demonstrates a higher bone ingrowth with BG-PCL scaffolds and a complete chemical conversion of remaining BG-PCL after 3 months 2 implantation, while histological data show the vascularization of BG-PCL scaffolds and confirm the well-advanced bone regeneration with ongoing remodeling. Finally, we evidence the complete chemical conversion of remaining BG-PCL into a bone-like mineral.