Effects of macropore size in carbonate apatite honeycomb scaffolds on bone regeneration

The pore architecture of scaffolds is a critical factor for angiogenesis and bone regeneration. Although the effects of scaffold macropore size have been investigated, most scaffolds feature macropores with poor uniformity and interconnectivity, and other parameters (e.g., microporosity, chemical composition, and strut thickness) differ among scaffolds. To clarify the threshold of effective macropore size, we fabricated honeycomb scaffolds (HCSs) with distinct macropore (i.e., channel) sizes (~100, ~200, and ~300 μm). The HCSs were composed of AB-type carbonate apatite with ~8.5% carbonate ions, i.e., the same composition as human bone mineral. Their honeycomb architecture displayed uniformly sized and orderly arranged channels with extremely high interconnectivity, and all the HCSs displayed ~100-μm-thick struts and 0.06 cm³ g^-1 of micropore volume. The compressive strengths of HCSs with ~100-, ~200-, and ~300-μm channels were higher than those of reported scaffolds, and decreased with increasing channel size: 62 ± 6, 55 ± 9, and 43 ± 8 MPa, respectively. At four weeks after implantation in rabbit femur bone defects, new bone and blood vessels were formed in all the channels of these HCSs. Notably, the ~300-μm channels were extensively occupied by new bone. We demonstrated that high interconnectivity and uniformity of channels can decrease the threshold of effective macropore size, enabling the scaffolds to maintain high mechanical properties and osteogenic ability and serve as implants for weight-bearing areas.