Elsevier

Acta Biomaterialia

Volume 6, Issue 10, October 2010, Pages 4167-4174
Acta Biomaterialia

Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of β-TCP ceramics

https://doi.org/10.1016/j.actbio.2010.05.012Get rights and content

Abstract

The objective of this study was to evaluate the influence of MgO and SrO doping on the mechanical and biological properties of β-tricalcium phosphate (β-TCP). β-TCP was doped with two different binary compositions, 0.25 and 1.0 wt.% SrO along with 1.0 wt.% MgO. MgO and SrO doping increased the β phase stability at a sintering temperature of 1250 °C and marginally decreased the compressive strength of β-TCP. An in vitro cell–material interaction study, using human fetal osteoblast cells (hFOB), indicated that doped β-TCP was non-toxic, and MgO/SrO dopants improved cell attachment and growth. β-TCP implants doped with 1.0 wt.% MgO and 1.0 wt.% SrO showed good in vivo biocompatibility when tested in male Sprague–Dawley rats for 16 weeks. Histomorphology analysis indicated that MgO/SrO-doped β-TCP promoted more osteogenesis than pure β-TCP. In vivo osteocalcin and type I collagen assay also revealed faster bone formation in rats with doped β-TCP implant compared to rats with pure β-TCP implant. Low Ca2+ concentration in the urine of rats with doped β-TCP implant confirmed slower degradation of MgO/SrO-doped β-TCP than pure β-TCP.

Introduction

Calcium phosphate-based ceramics have found extensive applications as bioresorbable materials and tissue engineering scaffolds. Among calcium phosphates, hydroxyapatite (HAP, Ca10(PO4)6(OH)2) and β-tricalcium phosphate (β-TCP, β-Ca3(PO4)2) are the most commonly used compositions [1], [2]. Owing to its time-dependent mechanical and dissolution characteristics, and excellent osseoconductive properties, β-TCP has been widely used as bone cement and implant material [3], [4], [5]. In many applications, the time-dependent properties make β-TCP an ideal material for implants: the ceramic supplies temporary support for bone ingrowth, and is eventually replaced by natural tissue [6]. Among several clinical applications involving β-TCP, posterior spinal fusion and craniomaxillofacial applications have attracted considerable attention [7]. β-TCP ceramics with improved mechanical properties and controlled resorbability can assist in designing optimal biodegradable bone substitutes for spinal fusion and craniomaxillofacial applications. Use of such bone substitutes also avoids the second surgery required for autograft harvesting.

Synthesis of metal ion-substituted calcium phosphates has drawn much scientific interest since metal ion substitution has been shown to improve the mechanical properties and bioactivity of implants [8], [9]. In our earlier studies [1], [10], [11], [12], [13], we have shown that addition of dopants such as NaF, TiO2, SiO2, CaO and Ag2O improves the mechanical properties of β-TCP without altering its inherent biocompatibility. We also found that doping with ZnO enhances the densification of β-TCP ceramics [13]. Incorporation of Sr and Mg ions in calcium phosphate is of great interest as they play an important role in new bone growth. In recent years, in vitro and in vivo studies have clearly indicated the beneficial effects of Sr on bone formation [14], [15]. Our previous work demonstrated that the presence of Sr in HAP promotes osteoblast function and subsequent bone formation [16]. Sr, at low dose, enhances the replication of preosteoblastic cells, and simulates bone formation. Furthermore, it has also been demonstrated that Sr suppresses bone resorption and maintains bone formation. In contrast, a high dose of Sr induces defective bone mineralization, and alters the mineral profile [17]. Qiu et al. reported calcium phosphate ceramics with 1.0% Sr to be the optimal proportion for most favorable osteoblastic cell growth [18]. Mg is also undoubtedly one of the most important bivalent ions associated with biological apatites [19], [20]. Substitution of Mg in calcium phosphate has received much attention due to its potential role in qualitative changes in bone matrix, and its indirect influence on mineral metabolism, promoting catalytic reactions and controlling biological functions [21], [22].

Considering the beneficial effects of Sr and Mg in bone formation, the aim of the present study was to evaluate the influence of simultaneous doping of SrO and MgO on the physical, mechanical and biological properties of β-TCP. SrO- and MgO-doped β-TCP were prepared by solid-state reaction and the phase composition, microstructure and mechanical properties of doped samples were studied in detail. The influences of doping on cell–material integration were investigated in vitro, using human osteoblast cells, and the bioactivity was evaluated in vivo by implanting samples in femurs of male Sprague–Dawley rats for 16 weeks.

Section snippets

Materials

β-TCP nanopowder was obtained from Berkeley Advanced Biomaterials Inc., Berkeley, CA, USA, with an average particle size of 550 nm. High-purity SrO (99.9% purity) was purchased from Aldrich, MO, USA, and MgO (Puratronic, 99.998%) was procured from Alfa Aesar, MA, USA. All other chemicals were of analytical grade and used without further purification.

Sample preparation

Based on our preliminary studies and previous works [9], [10], [16], three compositions of TCP were synthesized for this study: β-TCP, β-TCP doped

Phase identification

The XRD spectra of the samples sintered at 1250 °C are shown in Fig. 1. The spectrum of pure β-TCP (JCPDS No. 09–169) showed the presence of some α-TCP peaks, indicating β- to α-TCP (JCPDS No. 09–0348) phase transformation. However, no α-TCP peaks were detected in the spectra of MgO/SrO-doped samples. All the peaks observed were of β-TCP, signifying the presence of pure β-TCP phase, and no amorphous phase was detected. In addition, a small shift in peak positions was observed for doped samples.

ATR-IR analysis

Discussion

This study shows several beneficial effects derived from the simultaneous presence of MgO and SrO in β-TCP. The XRD patterns of sintered MgO/SrO-doped β-TCP samples confirm the presence of phase pure β-TCP, and the absence of any amorphous phase indicates complete incorporation of Mg2+ and Sr2+ into the β-TCP structure [27]. Shift in the 2θ and the d-spacing values for doped β-TCP further corroborates the substitution of Ca2+ with Mg2+ and Sr2+ in the β-TCP lattice. The change in the lattice

Conclusions

In this study, we have shown that both MgO and SrO can influence the mechanical and biological properties of β-TCP. Incorporation of Mg2+ and Sr2+ in the crystal structure of β-TCP suppressed β to α phase transition. Pure β-TCP and doped samples showed sintered densities of 96.17 ± 1.15%, 97.12 ± 1.61% and 97.26 ± 1.11% and compressive strengths of 419 ± 28, 341 ± 30 and 359 ± 10 MPa, respectively. Our in vitro cell–material interaction study demonstrated better cell attachment and proliferation for doped

Acknowledgements

The authors acknowledge financial support from the National Institutes of Health, NIBIB (Grant No. NIH-R01-EB-007351, program manager Dr. Albert Lee). The authors thank M. Roy, Dr. Sanjib Mukherjee, K. Vega-Villa and J. Takemoto for their technical assistance.

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