Chemical Stability-Sensitive Osteoconductive Performance of Octacalcium Phosphate Bone Substitute in an Ovariectomized Rat Tibia Defect.

ABSTRACT

The purpose of this study was to investigate whether the chemical condition of osteoporotic serum affects the chemical stability of octacalcium phosphate (OCP) and its osteoconductive property. The in vitro chemical dissolution in osteoporotic ovariectomized (OVX)-simulated conditions was analyzed. OCP and its composite form with gelatin (OCP/Gel), containing specific amounts of OCP (either 17% or 44% by weight), were used as experimental materials. The degrees of supersaturation (DS) of the OVX-simulated buffer solutions, containing distinct inorganic phosphate (Pi) ion concentrations, after immersing OCP or OCP/Gel, were determined. The rod-shaped OCP/Gel was then implanted into the OVX and Sham rat tibia defects, exhibiting a similar shape and size, and assessed at 4, 8, and 12 weeks. Increasing Pi concentration in OVX-simulated buffer solution increased the DS, with respect to OCP, upon the introduction of OCP and 44% OCP/Gel, but decreased the DS to a slightly saturated condition with 17% OCP/Gel, indicating that increasing the OCP in the Gel matrix tends to inhibit the hydrolysis of OCP into hydroxyapatite (HA). Histomorphometric analyses of bone formation and the appearance of osteoblasts and osteoclast-like cells, together with OCP resorption, confirmed that while 44% OCP/Gel showed higher bone formation than 17% OCP/Gel at intramedullary bone defect sites in Sham rat tibia, both OCP/Gels tended to enhance cortical bone formation in the OVX group, concomitant with the higher resorption of OCP within 17% OCP/Gel. The appearance of osteoclast-like cells in the OVX group increased as the OCP dose decreased from 44% to 17% in the Gel matrix, with an approximately 4 times higher bone formation rate, 8-12 weeks after the implantation. Additional in vitro assays showed that bone marrow mesenchymal stem cells isolated from OVX and wild-type (WT) rats treated with OCP had similar proliferation and differentiation rates, up to 21 days. These results show that OCP can enhance cortical bone repair even in osteoporotic bone if suitable thermodynamic metastable dissolution conditions are provided in relation to the mass of OCP.