Single-dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical-sized calvarial defect

Octacalcium phosphate and collagen composite (OCP/Col) achieves stable bone regeneration without cell transplantation in preclinical studies. Recently, a sponsor-initiated clinical trial was conducted to commercialize the material. The present study investigated bone regeneration by OCP/Col with the single local administration of teriparatide (parathyroid hormone 1-34; TPTD). OCP/Col was prepared by mixing sieved granules of OCP and atelocollagen for medical use and a disk was molded. After the creation of a rodent critical-sized calvarial defect, OCP/Col or OCP/Col with dripped TPTD solution (1.0 or 0.1 mu g; OCP/Col/TPTDd1.0 or OCP/Col/TPTDd0.1) was implanted into the defect. Six defects in each group were fixed 12 weeks after implantation. Radiographic examinations indicated that radiopaque figures in defects treated with OCP/Col with TPTD (OCP/Col/TPTDd) occupied a wider range than those treated with OCP/Col. Histological results demonstrated that most of the defect in OCP/Col/TPTDd was filled with newly formed bone. A histomorphometrical examination indicated that the percentage of newly formed bone was significantly higher in the defects of OCP/Col/TPTDd 1.0 (53.6 +/- 4.3%) and OCP/Col/TPTDd 0.1 (52.2 +/- 7.4%) than in those of OCP/Col (40.1 +/- 8.4%), whereas no significant differences were observed between OCP/Col/TPTDd1.0 and OCP/Col/TPTDd0.1. These results suggest that OCP/Col with the single local administration of TPTD enhances bone regeneration in a rodent calvarial critical-sized bone defect. (c) 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1851-1857, 2018.