Abstract
Calcium phosphates (CaPs) are one of the most widely used synthetic materials for bone grafting applications in the orthopedic industry. Recent trends in synthetic bone graft applications have shifted towards the incorporation of metal trace elements that extend the performance of CaPs to have osteoinductive properties. The objective of this study is to investigate the effects of silicon (Si) and zinc (Zn) dopants in highly porous tricalcium phosphate (TCP) scaffolds on late-stage osteoblast cell differentiation markers. In this study, an oil emulsion method is utilized to fabricate highly porous SiO2 doped β-TCP (Si-TCP) and ZnO doped β-TCP (Zn-TCP) scaffolds through the incorporation of 0.5 wt.% SiO2 and 0.25 wt.% ZnO, respectively, to the β-TCP scaffold. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is utilized to analyze the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear kappa beta ligand (RANKL), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2) at the later stage of osteoblast differentiation, day 21 and day 28. Results show that the addition of Si and Zn to the β-TCP structure inhibited the β to α-TCP phase transformation and enhance the density without affecting the dissolution properties. Normal BMP-2 and Runx2 transcriptions are observed in both Si-TCP and Zn-TCP scaffolds at the initial time point, as demonstrated by RT-qPCR. Moreover, the addition of both Si and Zn positively regulate the osteoprotegerin: receptor activator of nuclear factor k-β ligand (OPG:RANKL) ratio at 21-days for Si-TCP and Zn-TCP scaffolds. These results demonstrate the effects of Si and Zn doped porous β-TCP scaffolds on the upregulation of osteoblast marker gene expression including OPG, RANKL, BMP-2, and Runx2, indicating the role of trace elements on the effective regulation of late-stage osteoblast cell differentiation markers.
Highlights
Calcium phosphate ceramics have been widely used in the orthopedic industry as synthetic bone graft substitutes, coating, and cement materials
While HA may last in the human body for over 10 years, β-tricalcium phosphate (TCP) has a functional lifetime of 12–16 months and is generally completely replaced by natural bone after 3 years [5,6]. β-tricalcium phosphate (β-TCP), is an ideal material to fill small bony voids created during surgery or for spinal fusion and non-union fracture healing. β-TCP is considered by many to be an osteoconductive material
We have studied the effects of Si and Zn dopants on the regulation of osteogenic markers such as OPG, receptor activator of nuclear kappa beta ligand (RANKL), RUNX2, and bone morphogenetic protein 2 (BMP2) at the late stage of osteoblastic differentiation
Summary
Calcium phosphate ceramics have been widely used in the orthopedic industry as synthetic bone graft substitutes, coating, and cement materials. They have an excellent biocompatibility and a compositional similarity to natural bone that make them ideal as bone graft substitutes [1,2]. Β-TCP is considered by many to be an osteoconductive material It provides support for new tissue formation and the migration of bone forming cells during the healing process. Demonstrate a paradigm shift from designing a functional material to a fully bioactive material It has been the goal of many researchers and industry leaders to further develop β-TCP grafting materials to give them osteoinductive properties. While much of these results have been extremely positive, growth factors have come under severe scrutiny of the public and the Food and Drug Administration (FDA) due to several serious possible side effects experienced in clinical off label use [12,13]
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