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Bio-Design and Manufacturing  2023 Vol.6 No.5 P.507–521

http://doi.org/10.1007/s42242-023-00240-8


Benidipine-loaded nanoflower-like magnesium silicate improves bone regeneration


Author(s):  Jingyi Lu, Miao Sun, Jingyu Zhang, Xiaofu Yang, Minyi Dong, Huihui He, An Liu, Mengfei Yu, Baixiang Wang & Huiming Wang

Affiliation(s):  The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310000, China; more

Corresponding email(s):   yumengfei@zju.edu.cn, wangbaixiang@zju.edu.cn, whmwhm@zju.edu.cn

Key Words:  Nanoparticles, Benidipine, Bone tissue engineering, Endocytosis


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Jingyi Lu, Miao Sun, Jingyu Zhang, Xiaofu Yang, Minyi Dong, Huihui He, An Liu, Mengfei Yu, Baixiang Wang & Huiming Wang. Benidipine-loaded nanoflower-like magnesium silicate improves bone regeneration[J]. Journal of Zhejiang University Science D, 2023, 6(5): 507–521.

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Abstract: 
Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts. Here, we propose a novel strategy combining benidipine, an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects. Loose and porous benidipineloaded magnesium silicate nanoparticles were prepared and validated for their biosafety. The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus. After internalization into cells, the nanosystem is degraded by lysosomes, and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine, silicon and magnesium ions. Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to be more appropriate for the bone regeneration in preosteoblasts, indicating that it might be a potential approach in guiding bone repair in clinical applications.

浙江大学医学院附属口腔医院王慧明等 | 载贝尼地平的纳米花样硅酸镁促进骨组织再生

本研究论文聚焦于负载药物的杂化纳米载体制备及应用研究。高血压是过早死亡的首要风险因素,常由心血管并发症引起。近年来,越来越多的研究发现高血压会影响钙摄入并加速骨丧失,因此临床上常用的抗高血压药对骨代谢的影响也值得被密切关注。其中,二氢吡啶类降压药贝尼地平具有抗氧化和细胞保护作用,对骨代谢也有积极影响。但由于贝尼地平的生物利用度低,局部大剂量应用会造成组织损伤。此外,大块骨缺损难以自愈,往往需要成骨因子的持续释放。将纳米制剂引入骨组织工程策略实现了药物的持续控释,有望加速骨缺损的愈合与再生。本研究以二氧化硅为模板,氯化镁为镁源,通过化学蚀刻技术合成硅酸镁纳米粒子,并将贝尼地平负载于粒子的中空结构中,构建出具有成骨效应的纳米花样制剂。通过理化表征检测到载贝尼地平的硅酸镁纳米粒子(BD-MSNs)显示出较高的封装效率和长效释放能力。通过荧光纳米粒子示踪、内吞途径抑制剂前处理和荧光强度检测等手段对其内化机制进行探索,发现BD-MSNs能够通过网格蛋白介导的内吞途径被细胞高效摄取并促进其向成骨方向分化。最终,具有自身治疗特性的硅酸镁纳米粒子通过负载贝尼地平,实现了二者的效应叠加,协同促进了大鼠颅骨缺损区的骨组织再生。本研究采用金属掺杂和药物负载制备的花状纳米制剂为高血压病理状况下的骨修复提供了新的策略。

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