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.

β-type TiNbSn Alloy Plates With Low Young Modulus Accelerates Osteosynthesis in Rabbit Tibiae

“…The images were merged using Adobe Photoshop Element version 2020 (Adobe) to create an overall image of the osteotomy site. The areas of newly formed bone and cartilage (in mm 2 ) were measured in a 20-mm-long area centered on the osteotomy site, using the image analysis software Image J, version 1.53e (National Institutes of Health) [1].…”

Bone Tissue Response to Different Grown Crystal Batches of Octacalcium Phosphate in Rat Long Bone Intramedullary Canal Area

“…The implantation of OCPs into rat tibia defects followed previously reported procedures [ 16 , 20 ]. After inhalation of isoflurane, the rats were anesthetized with three types of mixed anesthetic agents (5 μL/g) consisting of medetomidine (7.5 μg/mL), midazolam (0.4 mg/mL), and butorphanol (0.5 mg/mL).…”

“…OCP can be complexed with various polymers, such as gelatin and poly lactide-co-glycolide acid (PLGA). Even in the complexes, the solubility and ionic behavior of OCP change cellular activity and osteoconductivity [ 20 , 21 ].…”

Assessment of bone repair in animal models with suppressed osteoclast function by pretreatment of bisphosphonates

“…In contrast, it is not common to leave bone defect untreated, and bone grafting of artificial bone or autogenous bone is used for the treatment of bone defects in actual clinical practice. We have reported the effect of octacalcium phosphate artificial bone on bone repair in a rat ovariectomized osteoporosis model [4]. In the future, it might be worthwhile to study the inhibitory effect of long-term bisphosphonate administration on bone repair by bone grafting, comparing autogenous bone with artificial bone.…”