3D printed biodegradable implants as an individualized drug delivery system for local chemotherapy of osteosarcoma

被引:92
|
作者
Wang, Yonghui [1 ]
Sun, Liang [2 ]
Mei, Zhigang [3 ]
Zhang, Fazhou [3 ]
He, Meifang [4 ]
Fletcher, Cameron [5 ]
Wang, Fenglong [6 ]
Yang, Jingjing [6 ]
Bi, Dongbin [2 ]
Jiang, Yanyan [6 ]
Liu, Ping [7 ]
机构
[1] Shandong First Med Univ, Shandong Prov Hosp, Dept Orthopaed, Jinan 250021, Peoples R China
[2] Shandong First Med Univ, Shandong Prov Hosp, Dept Urol, Jinan 250021, Peoples R China
[3] Guangzhou Sihe Biotechnol Co Ltd, Guangzhou 510530, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Lab Gen Surg, Guangzhou 510080, Peoples R China
[5] Univ New South Wales, Sch Chem Engn, Sydney, NSW 2052, Australia
[6] Shandong Univ, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Jinan 250061, Peoples R China
[7] Shandong First Med Univ, Shandong Prov Hosp, Dept Pharm, Jinan 250021, Peoples R China
基金
中国国家自然科学基金;
关键词
3D printing; Drug delivery implant; Individualized treatment; Controlled release; Local chemotherapy; Osteosarcoma; CHRONIC BONE; SCAFFOLDS; DEGRADATION; RESISTANCE; MICELLES; STRENGTH; FUTURE; TUMORS;
D O I
10.1016/j.matdes.2019.108336
中图分类号
T [工业技术];
学科分类号
08 ;
摘要
A 3D printing technique has been developed which enables the treatment of osteosarcoma via personalized local chemotherapy. A series of in vivo trials were conducted which closely mimicked real clinical chemotherapeutic conditions. We have shown that 3D printed poly L-lactic acid (PLLA) implants are exceptional carriers for anticancer drugs and can be designed with finely tuned physical morphologies and controllable micropore structures. Their favorable biodegradability, in vitro cytotoxicity, in vitro blood compatibility, in vivo subacute toxicity, and in vivo sensitization tests have confirmed their biocompatibility and pharmaceutical properties. Furthermore, we have demonstrated that local chemotherapy with the assistance of the as-prepared PLLA implant exhibits an anti-osteosarcoma efficacy superior to traditional chemotherapy through a series of in vivo anti-osteosarcoma tests according to clinical protocols. The proposed 3D printed drug delivery system can simultaneously realize individual local chemotherapy, multi-drug delivery, long-term sustainable drug release, and non-reoperation in osteosarcoma treatment. Our studies enable the utilization of the 3D printing technique in the treatment of osteosarcomas and guide future clinical trials. The established techniques and principles can also be adapted to the local chemotherapy of other tumors. (C) 2019 The Authors. Published by Elsevier Ltd.
引用
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页数:13
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