The influence of Sr doses on the in vitro biocompatibility and in vivo degradability of single-phase Sr-incorporated HAP cement

State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
Journal of Biomedical Materials Research Part A (Impact Factor: 3.37). 09/2008; 86(4):947-58. DOI: 10.1002/jbm.a.31687
Source: PubMed


In previous studies, we developed a new type of Sr-incorporated hydroxyapatite cement (Sr-HAC), which was shown to have many excellent physiochemical properties, by an ionic cement route (Guo et al., Biomaterials 2005;26:4073-4083). As a further study, the main aims of this article were to examine the Sr-HAC's in vitro biocompatibility, including acute toxicity, hemolytic reaction, pyrogen reaction, and cytoxicity, to evaluate its in vivo degradability during intramuscular and femur implantation, and also to investigate the influence of Sr doses on these properties. The in vitro results show that all of the Sr-HAC samples exhibit satisfactory biocompatibility, and the Sr/(Sr+Ca) molar ratio has an important effect on these properties. For example, the Sr-HAC with a Sr/(Sr+Ca) molar ratio of 5% (5% Sr-HAC) has higher biocompatibility than both the one with a Sr/(Sr+Ca) molar ratio of 10% (10% Sr-HAC) and the Sr-free one. The in vivo results of both the rabbit intramuscular and femur implantation experiments show that the Sr-HAC samples exhibit a much faster degradation rate than the Sr-free one, and that this also depends on the Sr/(Sr+Ca) molar ratio. Specifically, the mean degradation rate of the 10% Sr-HAC increases by an amplitude of 73.9 wt % compared with that of the Sr-free HAC. In addition, the optical transmission photographs show that the Sr doses play an important role on the interface between the implants and the new bone. The energy dispersion X-ray spectrum analysis indicates that there exists a gradient distribution of Sr element in the tight and bioactive interface between the implants and new bone, indicating that the Sr element takes a share in the mineralization of the new bone together with Ca element.

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    • "Calcium phosphate bone cements can integrate into the physiological bone remodelling process due to their solubility and bio-degradability and are therefore ideal to locally release Sr 2+ into a defect of the bone [21]. Thus, the effect of Sr 2+ incorporated into different bone cement formulations has been investigated in several studies [22] [23] [24] [25] [26] [27]. However, most of these approaches involve the synthesis of Sr-containing calcium phosphate species and therefore require high temperature processing or elaborate precipitation techniques. "
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    ABSTRACT: In the present study, the in vitro effects of novel strontium-modified calcium phosphate bone cements (SrCPC), prepared using two different approaches on human bone-marrow derived mesenchymal stem cells (hMSC) were evaluated. Strontium ions, known to stimulate bone formation and therefore already used in systemic osteoporosis therapy, were incorporated into a hydroxyapatite forming calcium phosphate bone cement via two simple approaches: Incorporation of strontium carbonate crystals or substitution of Ca2+- by Sr2+-ions during cement setting. All modified cements released 0.03-0.07 mM Sr2+ under in vitro conditions, concentrations that were shown not to impair the proliferation or osteogenic differentiation of hMSC. Furthermore, strontium-modification led to a reduced medium acidification and Ca2+-depletion in comparison to the standard calcium phosphate cement. In indirect and direct cell culture experiments with the novel SrCPC significantly enhanced cell proliferation and differentiation was observed. In conclusion, the SrCPC described here could be beneficial for the local treatment of defects especially in the osteoporotic bone.
    No preview · Article · Jul 2013 · Acta Biomaterialia
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    • "Another calcium phosphate cement containing strontium and acrylate was developed by Lu, Cheung, and co-workers, which also exhibited direct contact between bone and strontium-containing cement [29,30]. Guo Dagang and co-workers [31,32] demonstrated biocompatibility and degradability of their strontium-containing hydroxyapatite in rabbit muscle and cancellous bone. "
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    ABSTRACT: Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone. Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine. Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups. The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.
    Full-text · Article · Jun 2013 · Journal of Orthopaedic Surgery and Research
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    • "Indeed, because of the bone formation stimulation effect of Sr, oral administration of Sr salts is used in the treatment of osteoporotic patients to increase bone mass and reduce the incidence of fractures [15] [16] [17]. Additionally, a hydroxyapatite bioactive cement incorporating Sr(Sr-HA) has recently been investigated for bone repair [18] [19] [20]. It was shown that the solubility and mineralization ability of Sr-HA exhibited Sr dose-dependent behavior. "
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    ABSTRACT: Magnesium alloys have shown potential as biodegradable metallic materials for orthopedic applications due to their degradability, resemblance to cortical bone and biocompatible degradation/corrosion products. However, the fast corrosion rate and the potential toxicity of their alloying element limit the clinical application of Mg alloys. From the viewpoint of both metallurgy and biocompatibility, strontium (Sr) was selected to prepare hot rolled Mg-Sr binary alloys (with a Sr content ranging from 1 to 4 wt.%) in the present study. The optimal Sr content was screened with respect to the mechanical and corrosion properties of Mg-Sr binary alloys and the feasibility of the use of Mg-Sr alloys as orthopedic biodegradable metals was investigated by in vitro cell experiments and intramedullary implantation tests. The mechanical properties and corrosion rates of Mg-Sr alloys were dose dependent with respect to the added Sr content. The as-rolled Mg-2Sr alloy exhibited the highest strength and slowest corrosion rate, suggesting that the optimal Sr content was 2 wt.%. The as-rolled Mg-2Sr alloy showed Grade I cytotoxicity and induced higher alkaline phosphatase activity than the other alloys. During the 4 weeks implantation period we saw gradual degradation of the as-rolled Mg-2Sr alloy within a bone tunnel. Micro-computer tomography and histological analysis showed an enhanced mineral density and thicker cortical bone around the experimental implants. Higher levels of Sr were observed in newly formed peri-implant bone compared with the control. In summary, this study shows that the optimal content of added Sr is 2 wt.% for binary Mg-Sr alloys in the rolled state and that the as-rolled Mg-2Sr alloy in vivo produces an acceptable host response.
    Full-text · Article · Mar 2012 · Acta biomaterialia
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