Preliminary investigation of novel bone graft substitutes based on strontium–calcium–zinc–silicate glasses

Abstract

Bone graft procedures typically require surgeons to harvest bone from a second site on a given patient (Autograft) before repairing a bone defect. However, this results in increased surgical time, excessive blood loss and a significant increase in pain. In this context a synthetic bone graft with excellent histocompatibility, built in antibacterial efficacy and the ability to regenerate healthy tissue in place of diseased tissue would be a significant step forward relative to current state of the art philosophies. We developed a range of calcium-strontium-zinc-silicate glass based bone grafts and characterised their structure and physical properties, then evaluated their in vitro cytotoxicity and in vivo biocompatibility using standardised models from the literature. A graft (designated BT109) of composition 0.28SrO/0.32ZnO/0.40 SiO(2) (mol fraction) was the best performing formulation in vitro shown to induce extremely mild cytopathic effects (cell viability up to 95%) in comparison with the commercially available bone graft Novabone (cell viability of up to 72%). Supplementary to this, the grafts were examined using the standard rat femur healing model on healthy Wister rats. All grafts were shown to be equally well tolerated in bone tissue and new bone was seen in close apposition to implanted particles with no evidence of an inflammatory response within bone. Complimentary to this BT109 was implanted into the femurs of ovariectomized rats to monitor the response of osteoporotic tissue to the bone grafts. The results from this experiment indicate that the novel grafts perform equally well in osteoporotic tissue as in healthy tissue, which is encouraging given that bone response to implants is usually diminished in ovariectomized rats. In conclusion these materials exhibit significant potential as synthetic bone grafts to warrant further investigation and optimisation.

Reprint of: Review of bioactive glass: From Hench to hybrids

“…It is thought to have antibacterial properties [300] and some studies report beneficial cellular response [301,302], but it can also cause toxicity [303].…”

Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells

“…In vivo studies with different bioactive glasses containing Sr have shown biocompatibility, osteoconductivity and bone formation, offering advantages also in osteoporotic animals (Boyd et al 2009;Gorustovich et al 2010b). These observations are indicative that the currently used materials encourage cell adhesion and provide a certain degree of bone healing capacity even without exhibiting a nanostructure.…”

Analysis of γ-irradiated synthetic bone grafts by 29Si MAS-NMR spectroscopy, calorimetry and XRD

“…Calcium-Strontium-Zinc-Silicate glasses have potential as both constituents of bone cements [1][2][3][4][5][6][7] and, independently, as bone grafts [1,2].…”

“…The authors have previously reported the synthesis and preliminary biological evaluation of grafts based on the Ca-Sr-Zn-Si system [1]. The biological evaluation examined both in vitro response using the MTT assay with L929 mouse fibroblast cells, and in vivo response using both healthy and ovariectomized female Wistar rats [1,2].…”