The early replacement of host bone with bone-filling materials is essential in bone regeneration therapy. The development of Harversian canals and angiogenesis are necessary to maintain normal bone metabolism in biomaterials at the site of bone regeneration, so that metabolism continues in the bone that forms, thereby contributing to its maintenance. Various bone-filling materials and bone formationaccelerating agents have been developed and successfully applied to clinical settings. However, the histological structure of bone regenerated using current filling materials often differs from that by normal bone metabolism. In the beginning of osteogenesis, the extracellular matrix proteins, such as collagen, gives an optimal environment structure for cell proliferation and differentiation to histogenesis following cell aggregation. Furthermore, some difficulties associated with complete treatments for bone defects have not yet been overcome. Delay of normal bone remodeling due to HA, premature absorption of collagen and TCP, and difficulty of controlling the regeneration volume with platelet-rich plasma (PRP) and bone morphogenic protein-2 (BMP-2) have been reported. These cytokines have been used in combination with scaffolds in order to stimulate the differentiation of a certain number of immature cells present in the bone microenvironment in the local tissues surrounding bone. However, controlling the quantity of cells and their activities at local sites is challenging, which may result in adverse effects in patients, and these cytokines are also expensive.Previous findings prompted us to consider the importance of an effective artificial extracellular matrix (ECM) in the induction of bone. Matrices have been categorized according to their (a) physical, (b) chemical, and (c) biochemical properties. A fourth property, (d) geometry, has also been proposed . The superiority of honeycombshaped structures with numerous straight tunnels with diameters of 0.3-0.4 mm made from hydroxyapatite ceramics and collagenous preparations has indicated the suitability of this geometry for bone formation. We previously reported that less bone was generated in the absence of a cell transfer scaffold with an appropriate geometric structure. Bone must form in a uniform manner, and achieving this represents a challenge in the field of biological tissue engineering.
