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3D 打印具有肿瘤治疗和骨构建功能的金属-有机骨架纳米片结构支架

3D printing of metal-organic framework nanosheets-structured scaffolds with tumor therapy and bone construction.

机构信息

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

出版信息

Biofabrication. 2020 Jan 31;12(2):025005. doi: 10.1088/1758-5090/ab5ae3.

Abstract

After surgical resection for a bone tumor, the uncleared bone tumor cells can multiply and cause recurrence of the bone tumor. It is worthwhile to design a scaffold that kills the remaining bone tumor cells and repairs bone defects that were given rise to by surgical resection. Additionally, it is extremely important to consider the function of angiogenesis in the process of bone regeneration because the newly formed blood vessels can offer the nutrients for bone regeneration. In this work, a novel metal-organic framework Cu-TCPP nanosheets interface-structured β-tricalcium phosphate (TCP) (Cu-TCPP-TCP) scaffold was successfully prepared through integrating a 3D-printing technique with an in-situ growth method in a solvothermal system. Owing to the excellent photothermal effect of Cu-TCPP nanosheets, Cu-TCPP-TCP scaffolds that were illuminated by near-infrared (NIR) light demonstrated photothermal performance, which was well regulated through varying the contents of Cu-TCPP nanosheets, and the ambient humidity and power density of NIR light. When cultured with osteosarcoma cells, Cu-TCPP-TCP scaffolds killed a significant quantity of osteosarcoma cells through released heat energy after exposure to NIR light with power density 1.0 W cm and duration 10 min. Similarly, Cu-TCPP-TCP scaffolds ablated subcutaneous bone tumor tissues on the backs of naked mice and suppressed their growth because of the heat energy transformed from NIR light. I n-vitro studies found that Cu-TCPP-TCP scaffolds ably supported the attachments of both human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs), and significantly stimulated expressions of osteogenesis differentiation-related genes in HBMSCs and angiogenesis differentiation-related genes in HUVECs. After implanting Cu-TCPP-TCP scaffolds into the bone defects of rabbits, they effectively promoted bone regeneration. Thus, the integration of the bone-forming bioactivity of TCP scaffolds with the photothermal properties of Cu-TCPP nanosheets and angiogenesis activity of Cu ions makes Cu-TCPP-TCP scaffolds multifunctional, representing a new horizon to develop biomaterials for simultaneously curing bone tumors and repairing bone defects.

摘要

在骨肿瘤切除术后,未清除的骨肿瘤细胞可能会增殖并导致骨肿瘤复发。设计一种支架来杀死残留的骨肿瘤细胞并修复手术切除引起的骨缺损是值得的。此外,在骨再生过程中考虑血管生成的功能极为重要,因为新形成的血管可以为骨再生提供营养。在这项工作中,通过在溶剂热体系中整合 3D 打印技术和原位生长方法,成功制备了一种新型的金属有机骨架 Cu-TCPP 纳米片界面结构的 β-磷酸三钙(TCP)(Cu-TCPP-TCP)支架。由于 Cu-TCPP 纳米片的优异光热效应,Cu-TCPP-TCP 支架在近红外(NIR)光照射下表现出光热性能,通过改变 Cu-TCPP 纳米片的含量、环境湿度和 NIR 光的功率密度,可以很好地调节光热性能。当与骨肉瘤细胞共培养时,Cu-TCPP-TCP 支架在暴露于功率密度为 1.0 W cm 和持续时间为 10 min 的 NIR 光下会通过释放热能杀死大量骨肉瘤细胞。同样,Cu-TCPP-TCP 支架在裸鼠背部消融皮下骨肿瘤组织并抑制其生长,这是因为 NIR 光转化的热能。体外研究发现,Cu-TCPP-TCP 支架能够很好地支持人骨髓基质细胞(HBMSCs)和人脐静脉内皮细胞(HUVECs)的附着,并显著刺激 HBMSCs 中骨向分化相关基因和 HUVECs 中血管生成分化相关基因的表达。将 Cu-TCPP-TCP 支架植入兔骨缺损后,能有效促进骨再生。因此,TCP 支架的成骨生物活性与 Cu-TCPP 纳米片的光热性能和 Cu 离子的血管生成活性的结合使 Cu-TCPP-TCP 支架具有多功能性,为同时治疗骨肿瘤和修复骨缺损的生物材料的开发提供了新的思路。

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