Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field
Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field
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负载SPIONs的磁性PLGA微球通过在外磁场下调节骨间充质干细胞促进骨缺损的重建
DOI：
10.1016/j.msec.2021.111877
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Xu He-Lin
中科院分区：
文献类型：
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作者：
Zhao Ying-Zheng;Chen Rui;Xue Peng-Peng;Luo Lan-Zi;Zhong Bin;Tong Meng-Qi;Chen Bin;Yao Qing;Yuan Jian-Dong;Xu He-Lin
超顺磁性氧化铁纳米粒子（SPION）被提出来调节磁场（MF）下骨髓间充质干细胞（BMSCs）的迁移和成骨分化。然而，大量暴露于骨缺损处的SPION的毒性和短暂停留影响了其实际应用。在此，SPION被封装到PLGA微球中以克服这些缺点。通过调节SPION的投料量，制备了PFe-I、PFe-II和PFe-III三种PLGA微球，其中SPION的实际载药量分别为1.83%、1.38%和1.16%。所制备的微球平均粒径为160 ~ 200 μm，SEM显示微球表面粗糙多孔。此外，他们显示的磁特性与饱和磁化强度为0.16 emu/g。体外研究表明，大多数骨髓基质细胞粘附在PFe-Ⅱ微球的表面后，共培养2天。结果表明，PFe-II微球能促进BMSCs向成骨细胞分化，并能促进成骨相关蛋白ALP、COLsingle bond I、OPN和OCN的表达。然后将PFe-Ⅱ微球植入大鼠股骨缺损区，体外微磁场暴露，评价其在体内的骨修复效果。PFe-Ⅱ + MF治疗6周后，骨密度（BMD）为263.97 ± 25.99 mg/cm 3，骨小梁厚度（TB.TH，0.58 ± 0.08 mm）和骨组织体积/总组织体积在缺损区的BV/TV（78.28 ± 5.01%）显著高于单独的PFe-Ⅱ微球骨密度（BMD）为194.34 ± 26.71mg/cm ~ 3，总骨密度（TB.TH）为0.41 ± 0.07mm，骨体积/骨体积（BV/TV）为50.49 ± 6.41%。PFe-Ⅱ + MF组ALP、COL single bond I、OPN、OCN在修复骨中的表达均高于对照组。因此，磁性PLGA微球与MF结合可能是一种有前途的骨缺损修复策略。
Superparamagnetic iron oxide nanoparticles (SPIONs) have been presented to regulate the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under magnetic field (MF). However, the toxicity and short residence for the massively exposed SPIONs at bone defects compromises their practical application. Herein, SPIONs were encapsulated into PLGA microspheres to overcome these shortcomings. Three types of PLGA microspheres (PFe-I, PFe-II and PFe-III) were prepared by adjusting the feeding amount of SPIONs, in which the practical SPIONs loading amounts was 1.83%, 1.38% and 1.16%, respectively. The average diameter of the fabricated microspheres ranged from 160 μm to 200 μm, having the porous and rough surfaces displayed by SEM. Moreover, they displayed the magnetic property with a saturation magnetization of 0.16 emu/g.In vitrocell studies showed that most of BMSCs were adhered on the surface of PFe-II microspheres after 2 days of co-culture. Moreover, the osteoblasts differentiation of BMSCs was significantly promoted by PFe-II microspheres after 2 weeks of co-culture, as shown by detecting osteogenesis-related proteins expressions of ALP, COLsingle bondI, OPN and OCN. Afterward, PFe-II microspheres were surgically implanted into the defect zone of rat femoral bone, followed by exposure to an external MF, to evaluate their bone repairing effectin vivo. At 6th week after treatment with PFe-II + MF, the bone mineral density (BMD, 263.97 ± 25.99 mg/cm3), trabecular thickness (TB.TH, 0.58 ± 0.08 mm), and bone tissue volume/total tissue volume (BV/TV, 78.28 ± 5.01%) at the defect zone were markedly higher than that of the PFe-II microspheres alone (BMD, 194.34 ± 26.71 mg/cm3; TB.TH, 0.41 ± 0.07 mm; BV/TV, 50.49 ± 6.41%). Moreover, the higher expressions of ALP, COLsingle bondI, OPN and OCN in PFe-II + MF group were displayed in the repairing bone. Collectively, magnetic PLGA microspheres together with MF may be a promising strategy for repairing bone defects.