Fabrication and evaluation of carbonate apatite-coated calcium carbonate bone substitutes for bone tissue engineering

Carbonate apatite-coated calcium carbonate (CO(3)Ap/CaCO3) was fabricated through a dissolution-precipitation reaction using CaCO3 granules as a precursor to accelerate bone replacement based on superior osteoconductivity of the CO(3)Ap shell, along with Ca2+ release from the CaCO3 core and quicker resorption of the CaCO3 core. In the present study, CaCO3, 10% CO(3)Ap/CaCO3, 30% CO(3)Ap/CaCO3, and CO(3)Ap granules were fabricated and examined histologically to evaluate their potential as bone substitutes. Larger contents of CaCO3 in the granules resulted in higher Ca2+ release and promoted cell proliferation of murine preosteoblasts at 6days compared with CO(3)Ap. Interestingly, in a rabbit femur defect model, 10% CO(3)Ap/CaCO3 induced significantly higher new bone formation and higher material resorption compared with CO(3)Ap at 8weeks. Nevertheless, CO(3)Ap showed a superior osteoconductive potential compared with 10% CO(3)Ap/CaCO3 at 8weeks. All tested granules were most likely resorbed by cell mediation including multinucleated giant cell functions. Therefore, we conclude that CO(3)Ap/CaCO3 has a positive potential for bone tissue engineering based on well-controlled calcium release, bone formation, and material resorption.