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Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-01-21 , DOI: 10.1016/j.msec.2021.111877
Ying-Zheng Zhao , Rui Chen , Peng-Peng Xue , Lan-Zi Luo , Bin Zhong , Meng-Qi Tong , Bin Chen , Qing Yao , Jian-Dong Yuan , He-Lin Xu

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 vitro cell 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 effect in 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.



中文翻译:

载有SPIONs的PLGA磁性微球通过在外部磁场下调节骨间充质干细胞来促进骨缺损的重建

已经提出了超顺磁性氧化铁纳米粒子(SPIONs)来调节磁场(MF)下骨间充质干细胞(BMSCs)的迁移和成骨分化。但是,大量暴露的SPIONs在骨缺损处的毒性和短停留时间损害了它们的实际应用。在此,将SPIONs封装到PLGA微球中以克服这些缺点。通过调节SPIONs的进料量,制备了三种类型的PLGA微球(PFe-I,PFe-II和PFe-III),其中SPIONs的实际负载量分别为1.83%,1.38%和1.16%。制备的微球的平均直径为160μm至200μm,具有通过SEM显示的多孔和粗糙表面。此外,他们表现出的磁性能具有0.16 emu / g的饱和磁化强度。体外细胞研究表明,共培养2天后,大多数BMSCs粘附在PFe-II微球表面。此外,共培养2周后,PFe-II微球显着促进了BMSCs的成骨细胞分化,这通过检测ALP,COL 单键I,OPN和OCN的成骨相关蛋白表达来表明。之后,将PFe-II微球通过手术植入大鼠股骨缺损区,然后暴露于外部MF,以评估其在体内的骨修复效果。用PFe-II + MF治疗后第6周,骨矿物质密度(BMD,263.97±25.99 mg / cm 3),缺损区的小梁厚度(TB.TH,0.58±0.08 mm)和骨组织体积/总组织体积(BV / TV,78.28±5.01%)明显高于单独的PFe-II微球( BMD,194.34±26.71mg / cm 3; TB.TH,0.41±0.07mm; BV / TV,50.49±6.41%。此外,单键在修复性骨中显示了PFe-II + MF组中ALP,COL I,OPN和OCN的较高表达。总的来说,磁性PLGA微球和MF可能是修复骨缺损的有前途的策略。

更新日期:2021-01-28
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