Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium- hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold (Retracted article. See APR, 2023)
Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium- hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold (Retracted article. See APR, 2023)
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多孔纳米锂羟基磷灰石/明胶微球/促红细胞生成素复合支架增强糖皮质激素所致股骨头坏死骨缺损修复效果
DOI：
10.1039/c7bm00975e
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发表时间：
2018-03-01
影响因子：
6.6
通讯作者：
Kang, Pengde
中科院分区：
文献类型：
--
作者：
Li, Donghai;Xie, Xiaowei;Kang, Pengde
糖皮质激素性股骨头坏死（GIONFH）是一种常见的使人衰弱的疾病，好发于青壮年。髓芯减压植骨是治疗早期GIONFH的有效措施。然而，理想的骨移植物应具有生物活性以及生物力学性能。目前最常用的骨移植材料不能令人满意。在这项研究中，我们制造了一种复合支架，使用锂（Li）激活Writ信号通路和红细胞生成素（EPO）上调HIF-1/VEGF通路，以提高支架的成骨和血管生成效果。制备了多孔明胶/纳米羟基磷灰石/明胶微球/rhEPO（Li-nHA/GMs/rhEPO）复合支架，并对其力学性能、释放性能和体外生物活性进行了评价。然后将支架植入GIONFH兔股骨头髓芯减压术后，评价支架在体内的成骨和血管生成能力及其修复骨缺损的效果。结果表明，Li-nHA/GM/rhEPO支架具有良好的机械压缩强度，能够连续释放Li和rhEPO。此外，支架改善糖皮质激素处理的BMMSCs和血管内皮细胞的活力，并增加成骨和血管生成因子的表达。在体内实验中，复合支架促进了新骨形成，对GIONFH兔股骨头缺损具有修复作用。此外，成骨和血管生成因子随着Wnt信号通路和HIF-1/VEGF通路中因子的激活而沿着增加。结论：Li-nHA/GM/rhEPO支架可同时上调Wnt和HIF-1/VEGF通路，具有促进成骨和血管生成的作用，有利于GIONFH的修复。
Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common debilitating disease that occurs in young and middle-aged adults. To treat early GIONFH, core decompression and bone graft are regarded as effective measures. However, the ideal bone graft should possess bioactivity as well as biomechanical properties. The most commonly used bone graft materials are currently unsatisfactory. In this study, we fabricated a composited scaffold using lithium (Li) to activate the Writ signal pathway and erythrogenin (EPO) to upregulate the HIF-1/VEGF pathway to improve the osteogenic and angiogenic effects of the scaffold. We obtained the porous gelatin/nano-lithium-hydroxyapatite/gelatin microsphere/rhEPO (Li-nHA/GMs/rhEPO) composited scaffold and assessed its mechanical properties, release properties, and in vitro bioactivity. Then, we implanted the scaffold into the femoral heads of GIONFH rabbits after core decompression surgery and evaluated the osteogenic and angiogenic abilities of the scaffold in vivo as well as its bone defect repair efficacy. As the results show, the Li-nHA/GM/rhEPO scaffold possessed good mechanical compression strength and enabled continuous release of Li and rhEPO. Moreover, the scaffold improved the viability of glucocorticoid-treated BMMSCs and vascular endothelial cells and increased the expression of osteogenic and angiogenic factors. In the in vivo study, the composited scaffold improved new bone formation and exerted effects on repairing femoral head defects in GIONFH rabbits. Additionally, the osteogenic and angiogenic factors were increased along with the activation of factors in the Wnt signal pathway and the HIF-1/VEGF pathway. In conclusion, the Li-nHA/GM/rhEPO scaffold can upregulate the Wnt and HIF-1/VEGF pathways at same time and has effects on improving osteogenesis and angiogenesis, which benefits the repair of GIONFH.