The effect of synthetic octacalcium phosphate in a collagen scaffold on the osteogenicity of mesenchymal stem cells

Abstract

Although the effi cacy of the in vivo osteogenic capabilities of synthetic octacalcium phosphate (OCP) crystal implantation can be explained through its stimulatory capacity for the differentiation of the host osteoblastic cell lineage, direct evidence that OCP supports bone regeneration by osteogenic cells in vivo has not been shown. Mesenchymal stem cells (MSCs) isolated from 4-week-old male Wistar rat long bones were pre-incubated in osteogenic or maintenance medium in the presence or absence of basic fi broblast growth factor (bFGF). OCP/Collagen (OCP/Col) or collagen disks were seeded with MSCs that had been pre-incubated in osteogenic medium containing bFGF, which exhibited the highest differentiation induction, and then incubated for an additional day. The disks were implanted in critical-sized calvaria defects of 12-weekold male Wistar rats and the specimens were analysed radiographically, histologically, histomorphometrically, and by micro-computed tomography (CT) imaging at 4 and 8 weeks after the implantation. The OCP/Col·MSCs group rapidly induced more bone regeneration, even within 4 weeks, compared to the OCP/Col group without MSCs. The bone mineral density of the OCP/Col·MSCs group was also greater than the OCP/Col group. The Col·MSCs group did not exhibit prominent osteogenicity. These results indicate that OCP crystals in a collagen matrix effi ciently promote exogenously introduced osteogenic cells to initiate bone regeneration if the cells are pre-treated in a suitable differentiation condition.

Histochemical and Radiological Study of Bone Regeneration by the Combinatorial Use of Tetrapod-Shaped Artificial Bone and Collagen

“…In the control group, the defect was filled with fibrous connective tissue with a few calcified bodies. These results were compatible with previous results, whose rat calvarial defect was implanted with -TCP particle with or without collagen 15) . Thus, our histological analysis also suggests a synergistic effect of TB and collagen on bone regeneration.…”

“…These results suggest that the combinatorial application of TB and collagen results in a synergistic effect on bone formation. A similar finding has been reported by using synthetic octacalcium phosphate and collagen 15,18) . Quantitative analysis of 3D micro-CT image revealed that the bone volume was found to be significantly higher in the collagen and combination groups, than in the TB group.…”

“…An earlier report showed that -TCP particle implantation resulted high density areas at the defect margin and between the particles 17) . Moreover, collagen implantation resulted sporadic calcification in the defects 15) . These findings were compatible with those obtained in the TB group and collagen group of current study.…”

“…Collagen implantation has been shown to promote bone formation in the calvarial bone defect in rats 14) . The transplanted complex of collagen and octacalcium phosphate at the rat calvarial bone defect sites also induces a significant amount of bone formation 15) .…”

Stimulatory Capacity of an Octacalcium Phosphate/Gelatin Composite on Bone Regeneration in a Rabbit Tibia Defect Model

“…[4][5][6][7][8] From the viewpoint of bone regenerative properties, autologous bone is still the first choice for filling defects due to its superior osteoconductivity, since autologous bone consists of osteoblastic cells, growth factors, such as bone morphogenetic proteins, and matrix materials, including collagen and hydroxyapatite (HA) crystals. Although the tissue-engineering technique by introducing exogenous cells into the OCP-based material certainly increases the osteogenic capability of the material, 9 the use of bone-substitute materials that have biological activity compatible with that of autologous bone, with the stimulation of host osteoblastic cells around OCP crystals, is still preferable from the viewpoint of reducing the complex handling and the cost of the preparation of an implant form. We recently succeeded in synthesizing such material 10 with bone regenerative capability approaching that of autologous bone to repair a critically sized rat calvaria defect composed of an OCP co-precipitated gelatin (Gel) composite obtained through OCP crystal growth in a solution containing Gel molecules.…”