Granular Honeycombs Composed of Carbonate Apatite, Hydroxyapatite, and β-Tricalcium Phosphate as Bone Graft Substitutes: Effects of Composition on Bone Formation and Maturation.

Material composition and porous structure are important factors in the formation and maturation of newly formed bone and replacement of materials by new bone. Conventional bone graft materials often lack suitability for bone generation because of the complexity of their macroporous structures, which can interfere with the penetration of cells related to bone remodeling and angiogenesis in the materials. In the present study, carbonate apatite (CO3Ap), hydroxyapatite (HAp), and β-tricalcium phosphate (TCP) honeycomb granules (HCGs) with uniformly sized macropores (∼115 μm) were fabricated. These HCG macropores were arranged in a regular fashion and penetrated straight into the granules. They were implanted into a rabbit femur defect for further evaluation. In the CO3Ap HCG implantation group, mature bone formed within CO3Ap HCG macropores by 4 weeks after grafting, and a large portion of CO3Ap HCGs was replaced by new bone at 12 weeks. By contrast, in the β-TCP HCG implantation group, new bone was not always formed in the regions after β-TCP HCG disappearance, and immature bone was present within β-TCP HCG macropores even after 12 weeks. HAp HCGs were not resorbed, and their macropores were filled with immature bone. The area of mature bone in the CO3Ap HCG implantation group was 3.3 and 1.6 times higher at 4 weeks and 2.2 and 1.7 times higher at 12 weeks compared with the HAp and β-TCP HCG implantation groups, respectively. Furthermore, the degrees of bone maturation for CO3Ap, HAp, and β-TCP HCGs were 100, 34, and 64% at 4 weeks, and 100, 54, and 69% at 12 weeks, respectively. Thus, the composition of the HCGs affected bone formation and maturation.