Bone regeneration by octacalcium phosphate and collagen composites

Octacalcium phosphate (Ca₈H₂(PO₄)₆·5H₂O; OCP) is a calcium phosphate and has been suggested to be a precursor of biological apatite crystals in bones and teeth. The importance of synthetic OCP as a bone substitute material was recently recognized in the field of tissue engineering for bone regeneration. Our previous studies elucidated the below-mentioned phenomena by using a rat calvarial defect model. OCP irreversibly converts to the apatitic phase, and the process of OCP-apatite conversion is involved in bone regeneration. Implanted OCP enhances bone regeneration more than hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), which have already been used clinically as a scaffold for bone regeneration. OCP can be used as an effective scaffold for growth factors, such as bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β₁ (TGF-β₁), to enhance bone regeneration. Although OCP possesses many desirable properties, OCP cannot be molded by a sintering process, unlike bioceramics, such as HA or β-TCP. To improve the performance of bone regeneration and handling performance, a composite synthetic bone substitute constructed of synthetic OCP and porcine atelocollagen sponge (OCP/Col) has been developed. The synergistic effects of OCP/Col on bone regeneration are the result of bone nucleation by OCP and cell infiltration by collagen, and OCP/Col shows stable bone regeneration. OCP/Col significantly enhances bone regeneration more than OCP per se, β-TCP collagen composite, and HA collagen composite if implanted into a critical-sized defect model in a rat calvarium. During optimization of OCP/Col, it was confirmed that bone regeneration by OCP/Col was influenced by dehydrothermal treatment in the fabrication of OCP/Col or the composition of OCP and collagen. As OCP/Col is applicable without cell transplantation and exogenous osteogenic cytokines, costeffective bone regenerative therapy is expected in the future.