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用于同时抑制肿瘤、修复骨骼和消除感染的高活性壳聚糖/纳米羟基磷灰石/唑来膦酸支架

High-activity chitosan/nano hydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inhibition, bone repair and infection eradication.

作者信息

Lu Yao, Li Mei, Li Lihua, Wei Shuzhen, Hu Xiaoming, Wang Xiaolan, Shan Guiqiu, Zhang Yu, Xia Hong, Yin Qingshui

机构信息

Southern Medical University, No. 1023, South Shatai Road, Baiyun District, Guangzhou, Guangdong 510515, China; Guangdong Key Laboratory of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Department of Orthopedics, Guangzhou General Hospital of Guangzhou Military Command of PLA, No. 111, Liuhua Road, Yuexiu District, Guangzhou, Guangdong 510010, China.

Guangdong Key Laboratory of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Department of Orthopedics, Guangzhou General Hospital of Guangzhou Military Command of PLA, No. 111, Liuhua Road, Yuexiu District, Guangzhou, Guangdong 510010, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2018 Jan 1;82:225-233. doi: 10.1016/j.msec.2017.08.043. Epub 2017 Aug 12.

DOI:10.1016/j.msec.2017.08.043
PMID:29025652
Abstract

Implanted biomaterials combined tumor inhibition and bone repair property are urgently needed to address the huge bone destruction and the high local recurrence following primary surgery in bone tumor therapy. In this work, a high-activity chitosan/nano hydroxyapatite (CS/nHA) scaffold containing zoledronic acid (CS/nHA/Zol) was prepared with a facile method. The prepared CS/nHA/Zol scaffolds exhibited excellent tumor inhibition property towards giant cell tumor of bone (GCT) in vitro through inducing cells apoptosis by up-regulating pro-apoptosis genes expression and reducing the osteoclastic activity of tumor cells by down-regulating osteoclastic genes. Meanwhile, the prepared scaffolds possessed well biocompatibility and osteoinductivity as compared to pure CS/nHA scaffolds. Furthermore, the prepared scaffolds also presented outstanding antibacterial activity against clinical pathogenic S. aureus and E. coli. These overall findings successfully demonstrated the prepared CS/nHA/Zol scaffolds had a multifunction of tumor therapy, bone repair, and antibacterium, which provides a new approach possessed promising advantages in bone tumor therapy.

摘要

在骨肿瘤治疗中,迫切需要植入性生物材料兼具肿瘤抑制和骨修复特性,以应对原发性手术后巨大的骨破坏和高局部复发率。在这项工作中,采用简便方法制备了含唑来膦酸的高活性壳聚糖/纳米羟基磷灰石(CS/nHA)支架(CS/nHA/Zol)。所制备的CS/nHA/Zol支架在体外对骨巨细胞瘤(GCT)表现出优异的肿瘤抑制特性,通过上调促凋亡基因表达诱导细胞凋亡,并通过下调破骨细胞基因降低肿瘤细胞的破骨细胞活性。同时,与纯CS/nHA支架相比,所制备的支架具有良好的生物相容性和骨诱导性。此外,所制备的支架对临床致病性金黄色葡萄球菌和大肠杆菌也表现出出色的抗菌活性。这些总体研究结果成功证明,所制备的CS/nHA/Zol支架具有肿瘤治疗、骨修复和抗菌的多功能性,为骨肿瘤治疗提供了一种具有潜在优势的新方法。

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