Abstract

Backgroundβ-Tricalcium phosphate (β-TCP) is a popular synthetic bone graft substitute with excellent osteoconductive properties and bioabsorbability. However, its osteoinductive properties are inferior to those of autologous or allogeneic bone. Trace elements such as strontium (Sr), silica (Si), and zinc (Zn) have been reported to promote osteogenesis in materials. In this study, we aimed to determine whether a Si/Zn-substituted Sr apatite coating of β-TCP could enhance osteoinductive properties.MethodsThe apatite-coated β-TCP disks were prepared using nanoparticle suspensions of silicate-substituted Sr apatite (SrSiP) or silicate- and Zn-co-substituted Sr apatite (SrZnSiP).Bone marrow mesenchymal cells (BMSCs) from rat femur were cultured and subsequently seeded at a density of 1.0 × 106/cm2 onto apatite-coated and non-coated β-TCP disks.In vitro, the β-TCP disks were then placed in osteogenic medium, and lactate dehydrogenase (LDH) activity was measured from supernatants after culture for 2 days. Additionally, after culture for 14 days, the mRNA expression of genes encoding osteocalcin (OC), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was evaluated by qRT-PCR. In vivo, the β-TCP disks were transplanted subcutaneously into rats that were sacrificed after 4 weeks. Then, the harvested disks were evaluated biochemically (ALP activity, OC content, mRNA expression of OC, ALP, BMP-2, and VEGF measured by qRT-PCR), radiologically, and histologically.ResultsSignificantly higher mRNA expression of almost all evaluated osteogenic and angiogenic genes was observed in the SrZnSiP and SrSiP groups than in the non-coated group, with no significant cytotoxicity elicited by the apatite coating in vitro. Moreover, in vivo, the SrZnSiP and SrSiP groups showed significantly higher osteogenic and angiogenic gene expression and higher ALP activity and OC content than the non-coated group (P < 0.05). Radiological and histopathological findings revealed abundant bone formation in the apatite-coated group.ConclusionsOur findings indicate that apatite coating of β-TCP improves osteoinductive properties without inducing significant cytotoxicity.

Highlights

  • Calcium phosphate ceramics have excellent biocompatibility because their composition is similar to that of natural bone, making them ideal and widely used synthetic bone graft substitutes in the field of orthopedic surgery [1, 2]

  • Our findings indicate that apatite coating of β-tricalcium phosphate (β-TCP) improves osteoinductive properties without inducing significant cytotoxicity

  • scanning electron microscope (SEM)/energy dispersive X-ray spectrometer (EDS) analysis of Sr apatite-coated β-TCP SEM of the Silicate- and Zn-co-substituted Sr apatite (SrZnSiP) and Silicate-substituted Sr apatite (SrSiP) groups revealed that the pores of the β-TCP disks had not collapsed, and that the microarchitecture of the disks was retained after heating at high temperatures, similar to that of the control (Fig. 2a)

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Summary

Introduction

Calcium phosphate ceramics have excellent biocompatibility because their composition is similar to that of natural bone, making them ideal and widely used synthetic bone graft substitutes in the field of orthopedic surgery [1, 2]. Among the commonly employed calcium phosphate ceramics, β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) are representative synthetic bones. Β-TCP has high porosity and improved osteoconductive properties with a solubility that is approximately 30-fold higher than that of HA, making it more bioabsorbable and convenient for clinical application [5]. Β-TCP grafts have a functional life expectancy of 12 to 16 months, and generally, they are completely replaced by natural bone within 3 years of grafting [6]. Β-TCP has minimal or no osteoinductive properties, which stimulate bone marrow mesenchymal cells (BMSCs) to differentiate into osteoblasts and chondroblasts; its osteogenic capacity is limited compared with that of autologous or allogenic bone grafts [1, 7]

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