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具有抗细菌潜力的3D打印三元素掺杂羟基磷灰石/聚己内酯复合支架用于骨肉瘤治疗和骨再生

3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration.

作者信息

Huang Hao, Qiang Lei, Fan Minjie, Liu Yihao, Yang Anchun, Chang Dongbiao, Li Jinsheng, Sun Tong, Wang Yiwei, Guo Ruoyi, Zhuang Hanjie, Li Xiangyu, Guo Tailin, Wang Jinwu, Tan Huan, Zheng Pengfei, Weng Jie

机构信息

Key Laboratory of Advanced Technologies of Materials (MOE), School of Materials Science and Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, PR China.

Department of Orthopaedic Surgery, Children's Hospital of Nanjing Medical University, Nanjing 210008, PR China.

出版信息

Bioact Mater. 2023 Aug 4;31:18-37. doi: 10.1016/j.bioactmat.2023.07.004. eCollection 2024 Jan.

Abstract

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO, osteogenic effects of Sr and Zn, and antibacterial effects of SeO and Zn. studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.

摘要

恶性骨肉瘤切除术后常导致大段骨缺损,残留细胞会促使肿瘤复发。因此,骨肉瘤的治疗是临床实践中的一项重大挑战。骨肉瘤治疗的理想目标是彻底消除肿瘤,修复由此产生的骨缺损并避免细菌感染。在此,我们通过水热法制备了硒/锶/锌掺杂的羟基磷灰石(Se/Sr/Zn-HA)粉末,然后将其与聚己内酯(PCL)作为墨水通过3D打印构建复合支架,最后将其应用于恶性骨肉瘤诱导的骨缺损修复。所得复合支架具有多种功能,包括抗肿瘤、成骨和抗菌潜力,主要归因于SeO的抗肿瘤作用、Sr和Zn的成骨作用以及SeO和Zn的抗菌作用。研究证实,Se/Sr/Zn-HA浸提液可诱导骨肉瘤细胞凋亡、间充质干细胞分化以及MC3T3-E1细胞增殖,同时具有优异的抗菌性能。实验表明,注射Se/Sr/Zn-HA 8天后可显著抑制肿瘤生长,植入Se/Sr/Zn-HA-PCLs支架3个月后可有效修复股骨缺损。综上所述,本研究开发的Se/Sr/Zn-HA-PCLs复合支架在肿瘤治疗、骨缺损修复和术后抗感染方面均有效,具有成为骨肉瘤切除简便治疗材料的巨大潜力。

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