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载阿仑膦酸盐的羟基磷灰石-TiO纳米管用于改善骨质疏松兔的骨形成

Alendronate-loaded hydroxyapatite-TiO nanotubes for improved bone formation in osteoporotic rabbits.

作者信息

Shen Xinkun, Ma Pingping, Hu Yan, Xu Gaoqiang, Xu Kui, Chen Weizhen, Ran Qichun, Dai Liangliang, Yu Yonglin, Mu Caiyun, Cai Kaiyong

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.

出版信息

J Mater Chem B. 2016 Feb 28;4(8):1423-1436. doi: 10.1039/c5tb01956g. Epub 2016 Feb 1.

DOI:10.1039/c5tb01956g
PMID:32263109
Abstract

Early mechanical fixation between an implant and native bone is critically important for successful orthopedic implantation, especially for hosts suffering osteoporosis with reduced bone mass. To endow a titanium-based implant with a desirable local anti-osteoporosis property for enhancing its early osseointegration, alendronate-loaded hydroxyapatite-TiO nanotube (TNT-HA-Aln) substrates were fabricated and systematically characterized in this study. The results of Aln/Ca release and Ca concentration in an osteoclast medium verified that the release of Aln was significantly accelerated along with the acidity rise caused by osteoclast differentiation. Other in vitro tests, such as CCK-8, alkaline phosphatase (ALP), mineralization, gene expression (Runx2, Osterix, ALP, Col I, OPN, OC, OPG and RANKL), protein production (OPG and RANKL) and tartrate-resistant acid phosphatase (TRAP), proved that TNT-HA-Aln substrates have great potential for improving osteoblast proliferation/differentiation and inhibiting osteoclast differentiation. Moreover, in vivo tests, such as the push-out test, micro-CT and H&E staining proved that TNT-HA-Aln implants could efficiently improve local osseointegration after implantation for 3 months. The study provides an alternative to exploiting drug-device combinations to enhance early osseointegration in osteoporosis.

摘要

植入物与天然骨之间的早期机械固定对于成功的骨科植入至关重要,尤其是对于患有骨质疏松症且骨量减少的宿主。为了赋予钛基植入物理想的局部抗骨质疏松特性以增强其早期骨整合,本研究制备了载有阿仑膦酸盐的羟基磷灰石 - 二氧化钛纳米管(TNT - HA - Aln)基底并进行了系统表征。破骨细胞培养基中阿仑膦酸盐/钙释放和钙浓度的结果证实,随着破骨细胞分化引起的酸度升高,阿仑膦酸盐的释放显著加速。其他体外试验,如CCK - 8、碱性磷酸酶(ALP)、矿化、基因表达(Runx2、Osterix、ALP、Col I、OPN、OC、OPG和RANKL)、蛋白质产生(OPG和RANKL)以及抗酒石酸酸性磷酸酶(TRAP),证明TNT - HA - Aln基底在改善成骨细胞增殖/分化和抑制破骨细胞分化方面具有巨大潜力。此外,体内试验,如推出试验、显微CT和苏木精 - 伊红染色证明,TNT - HA - Aln植入物在植入3个月后可有效改善局部骨整合。该研究为开发药物 - 器械组合以增强骨质疏松症中的早期骨整合提供了一种替代方法。

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