Honeycomb blocks composed of carbonate apatite, β-tricalcium phosphate, and hydroxyapatite for bone regeneration: effects of composition on biological responses

Abstract Synthetic scaffolds exhibiting bone repair ability equal to that of autogenous bone are required in the fields of orthopedics and dentistry. A suitable synthetic bone graft substitute should induce osteogenic differentiation of mesenchymal stem cells, osteogenesis, and angiogenesis. In this study, three types of honeycomb blocks (HCBs), composed of hydroxyapatite (HAp), β-tricalcium phosphate (TCP), and carbonate apatite (CO3Ap), were fabricated, and the effects of HCB composition on bone formation and maturation were investigated. The HC structure was selected to promote cell penetration and tissue ingrowth. HAp and β-TCP HCBs were fabricated by extrusion molding followed by sintering. The CO3Ap HCBs were fabricated by extrusion molding followed by dissolution-precipitation reactions and sintering. These HCBs had similar macroporous structures: all harbored uniformly distributed macropores (∼160 μm) that were regularly arrayed and penetrated the blocks unidirectionally. Moreover, the volumes of macropores were nearly equal (∼0.15 cm3/g). The compressive strengths of CO3Ap, HAp, and β-TCP HCBs were 22.8 ± 3.5, 34.2 ± 3.3, and 24.4 ± 2.4 MPa, respectively. Owing to the honeycomb-type macroporous structure, the compressive strengths of these HCBs were higher than those of commercial scaffolds with intricate three-dimensional or unidirectional macroporous structure. Notably, bone maturation was markedly faster in CO3Ap HCB grafting than in β-TCP and HAp HCB grafting, and the mature bone area percentages for CO3Ap HCBs at post-surgery weeks 4 and 12 were 14.3- and 4.3-fold higher and 7.5- and 1.4-fold higher than those for HAp and β-TCP HCBs, respectively. The differences in bone maturation and formation were probably caused by the disparity in concentrations of calcium ions surrounding the HCBs, which were dictated by the inherent material resorption behavior and mechanism; generally, CO3Ap is resorbed only by osteoclastic resorption, HAp is not resorbed, and β-TCP is rapidly dissolved even in the absence of osteoclasts. Besides the composition, the microporous structure of HC struts, inevitably generated during the formation of HCBs of various compositions, may contribute to the differences in bone maturation and formation.