Lei Yong, Xu Zhengliang, Ke Qinfei, Yin Wenjing, Chen Yixuan, Zhang Changqing, Guo Yaping
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Mater Sci Eng C Mater Biol Appl. 2017 Mar 1;72:134-142. doi: 10.1016/j.msec.2016.11.063. Epub 2016 Nov 18.
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, CaSr(PO)(OH)]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x 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 than Ca, while the crystal sizes of SrHAP decrease from 70.4nm to 46.7nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100-400μm, 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 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 and Sr ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering.
为了实现生物材料与间充质干细胞（MSCs）相结合的骨组织工程的临床应用，骨支架应具备优异的生物相容性和骨诱导性，以加速骨缺损的修复。在此，通过冷冻干燥法制备了羟基磷灰石锶[SrHAP，CaSr(PO)(OH)]/壳聚糖（CS）纳米复合支架。x值分别为0、1、5和10的SrHAP纳米晶体分别缩写为HAP、Sr1HAP、Sr5HAP和Sr10HAP。随着x值从0增加到10，由于Sr的离子半径大于Ca，SrHAP的晶胞体积和轴向长度逐渐增大，而SrHAP的晶体尺寸从70.4nm减小到46.7nm。SrHAP/CS纳米复合支架呈现出孔径为100 - 400μm的三维（3D）相互连通大孔，且SrHAP纳米晶体均匀分散在支架内。体外细胞实验表明，所有的HAP/CS、Sr1HAP/CS、Sr5HAP/CS和Sr10HAP/CS纳米复合支架对人骨髓间充质干细胞（hBMSCs）均具有优异的细胞相容性，hBMSCs具有良好的黏附、铺展和增殖能力。支架中的Sr5HAP纳米晶体不影响hBMSCs的黏附、铺展，但对细胞增殖和成骨分化有显著促进作用。与HAP/CS纳米复合支架相比，SrHAP/CS纳米复合支架释放的Sr离子增强了碱性磷酸酶（ALP）活性、细胞外基质（ECM）矿化以及成骨相关的COL - Ⅰ和ALP表达水平。特别是，由于Ca和Sr离子之间的协同作用，Sr5HAP/CS纳米复合支架在四组中表现出最佳的骨诱导性。因此，具有优异细胞相容性和成骨性能的Sr5HAP/CS纳米复合支架在骨组织工程中具有广阔的应用前景。
