Effects of pore interconnectivity on bone regeneration in carbonate apatite blocks

Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO(3)Ap) through dissolution–precipitation reactions. Thus, CO(3)Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO(3)Ap-15 and CO(3)Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO(3)Ap-30, whereas little bone was formed in the center region of CO(3)Ap-15. At 12 weeks after implantation, a large portion of CO(3)Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO(3)Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.