Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering

摘要

For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca_(10) - _xSr_x(PO_4)_6(OH)_2]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different × values of 0,1,5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing × values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr~(2+) than Ca~(2+), while the crystal sizes of SrHAP decrease from 70.4 nm to 46.7 nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100-400 urn, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr~(2+) ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca~(2+) and Sr~(2+) ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering.