Synergistic effect of strontium, bioactive glass and nano-hydroxyapatite promotes bone regeneration of critical-sized radial bone defects

Critical-sized bone defects constitute a major health issue in orthopedics and usually cause mal-unions due to an inadequate number of migrated progenitor cells into the defect site or their incomplete differentiation into osteogenic precursor cells. The current study aimed to develop an optimized osteoinductive and angiogenic scaffold by incorporation of strontium (Sr) and bioglass (BG) into gelatin/nano-hydroxyapatite (G/nHAp) seeded with bone marrow mesenchymal stem cells to enhance bone regeneration. The scaffolds were fabricated by a freeze-drying technique and characterized in terms of morphology, structure, porosity and degradation rate. The effect of fabricated scaffolds on cell viability, attachment and differentiation into osteoblastic lineages was evaluated under in vitro condition. Micro computed tomography scan, histological and histomorphometric analysis were performed after implantation of scaffolds into the radial bone defects in rat. RT-PCR analysis showed that G/nHAp/BG/Sr scaffold significantly increased the expression level of osteogenic and angiogenic markers in comparison to other groups (P < 0.05). Moreover, the defects treated with the BMSCs-seeded scaffolds showed superior bone formation and mechanical properties compared to the cell-free scaffolds 4 and 12 weeks post-implantation. Finally, the BMSCs-seeded G/nHAp/BG/Sr scaffold showed the greatest bone regenerative capacity which was more similar to autograft. It is concluded that combination of Sr, BG, and nHAp can synergistically enhance the bone regeneration process. In addition, our results demonstrated that the BMSCs have the potential to considerably increase the bone regeneration ability of osteoinductive scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 50-64, 2019.