Biomimetic scaffolds are appealing products for the repair of bone defects using tissue engineering strategies. In the present study, novel biomimetic composite scaffolds, with similar properties to natural bone, were prepared, blended and cross-linked with bioactive glass, type I collagen and phosphatidylserine. When exposed to cell culture solution in the absence of a cellular source, the composite scaffolds form crystals with octahedral structure. These crystals are similar to the products derived from MC3T3-E1 cell mineralization within the composite scaffolds, with respect to both composition and morphology. Furthermore, crystals with octahedral structure were observed to develop into plate-like hydroxyapatite. The bio-mineralization behavior of the composite scaffolds is likely influenced by inorganic components. Finally, a rabbit tibia defect model shows that the highly bioactive properties of the investigated composites result in excellent bone repair.