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

Carbonate apatite-coated calcium carbonate (CO₃Ap/CaCO₃) was fabricated through a dissolution–precipitation reaction using CaCO₃ granules as a precursor to accelerate bone replacement based on superior osteoconductivity of the CO₃Ap shell, along with Ca²⁺ release from the CaCO₃ core and quicker resorption of the CaCO₃ core. In the present study, CaCO₃, 10% CO₃Ap/CaCO₃, 30% CO₃Ap/CaCO₃, and CO₃Ap 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 6 days compared with CO₃Ap. Interestingly, in a rabbit femur defect model, 10% CO₃Ap/CaCO₃ induced significantly higher new bone formation and higher material resorption compared with CO₃Ap at 8 weeks. Nevertheless, CO₃Ap showed a superior osteoconductive potential compared with 10% CO₃Ap/CaCO₃ at 8 weeks. All tested granules were most likely resorbed by cell mediation including multinucleated giant cell functions. Therefore, we conclude that CO₃Ap/CaCO₃ has a positive potential for bone tissue engineering based on well-controlled calcium release, bone formation, and material resorption.