Strontium sintered calcium sulfate bone graft for enhancing osteogenesis in a rat femoral defect model

Strontium-containing calcium sulfate hemihydrate has been widely investigated in bone tissue engineering in recent years. The sensitive dose-dependent effect of strontium ions limits the clinical applications due to the uncontrollable release property of fabricated bone substitutes. The purpose of our study was to design a novel strontium sintered calcium sulfate anhydrate scaffold possessing a tailored released concentration and further in vivo bone regeneration. The in vitro biocompatibility, toxicity and differentiation of MC3T3E1 cells were evaluated by using different concentrations of SrCl2 and various weight ratios of strontium sintered calcium sulfate scaffolds. For the in vivo studies, we designed a critical-sized femoral defect model of rats transplanted with different weight ratios of strontium-substituted scaffolds to study new bone regeneration. In vitro data suggested that a Sr2+ concentration below 10(-4) M had a positive effect on the osteogenic differentiation of MC3T3E1 cells. The enhanced cell viability, osteogenic profiles, bone mineralization and promising cellular proliferation were measured in 1% and 5% weight ratios of strontium-substituted scaffolds. Runt-related transcription factor 2 (RUNX2)-mediated osteogenesis was associated with the activation of extracellular signal-related kinase (ERK) signaling pathways in MC3T3E1 cells cultured in scaffold extracts. The in vivo experiments revealed that these sintered scaffolds showed acceptable biodegradability in X-ray and micro-CT images at the 12th week. Histological analysis showed intact surrounding bone regeneration, more osteoid formation, neovascularization and less fibrotic tissue in the 1% weight ratio of strontium sintered calcium sulfate scaffolds, suggesting that this sintered scaffolds weight ratio possesses potential for application in bone tissue engineering.

Automated summary

The study aimed to design a novel strontium sintered calcium sulfate anhydrate scaffold for controlled release and in vivo bone regeneration. In vitro experiments showed positive effects on osteogenic differentiation with Sr2+ concentrations below 10(-4) M, and enhanced cell viability, osteogenic profiles, and bone mineralization in 1% and 5% weight ratios of strontium-substituted scaffolds. In vivo experiments demonstrated acceptable biodegradability and improved bone regeneration with the 1% weight ratio of strontium sintered calcium sulfate scaffolds, suggesting potential for bone tissue engineering applications.