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Cryogenic 3D printing of porous scaffolds for in situ delivery of 2D black phosphorus nanosheets, doxorubicin hydrochloride and osteogenic peptide for treating tumor resection-induced bone defects.
Biofabrication ( IF 9 ) Pub Date : 2020-04-08 , DOI: 10.1088/1758-5090/ab6d35
Chong Wang 1 , Xinyu Ye , Yitao Zhao , Lu Bai , Zhi He , Qing Tong , Xiaoqiong Xie , Huangrong Zhu , Daozhang Cai , Yun Zhou , Bingheng Lu , Yen Wei , Lin Mei , Denghui Xie , Min Wang
Affiliation  

Tumor resection is widely used to prevent tumor growth. However, the defected tissue at the original tumor site also causes tissue or organ dysfunction which lowers the patient's life quality. Therefore, regenerating the tissue and prevent tumor recurrence are highly important. Herein, according to the concept of "first kill and then regenerate", a versatile scaffold-based tissue engineering strategy based on cryogenic 3D printing of water-in-oil polyester emulsion inks containing multiple functional agents was developed,in order to realize the elimination of tumor cells with recurrence suppression and improved tissue regeneration sequentially. To illustrate our strategy, water/poly(lactic-co-glycolic acid)/dichloromethane emulsions containing β-tricalcium phosphate (β-TCP), 2D black phosphorus (BP) nanosheets, low-dose doxorubicin hydrochloride (DOX) and high-dose osteogenic peptide were cryogenically 3D printed into hierarchically porous and mechanically strong nanocomposite scaffolds,with multiple functions to treat bone tumor resection-induced tissue defects. Prompt tumor ablation and long-term suppression of tumor recurrence could be achieved due to the synergistic effects of photothermotherapy and chemotherapy, and improved bone regeneration was obtained eventually due to the presence of bony environment and sustained peptide release. Notably, BP nanosheets in scaffolds significantly reduced the long-term toxicity phenomenon of released DOX during in vivo bone regeneration. Our study also provides insights for the design of multi-functional tissue engineering scaffolds for treating other tumor resection-induced tissue defects.

中文翻译:

多孔支架的低温3D打印,用于原位递送2D黑磷纳米片,阿霉素盐酸盐和成骨肽,用于治疗肿瘤切除引起的骨缺损。

肿瘤切除术广泛用于防止肿瘤生长。然而,原始肿瘤部位处的缺损组织也会引起组织或器官功能障碍,从而降低患者的生活质量。因此,使组织再生并防止肿瘤复发非常重要。在此,根据“先杀死后再再生”的概念,开发了一种基于支架的多用途组织工程策略,该策略基于低温3D打印包含多种功能剂的油包水型聚酯乳液油墨,以实现消除具有复发抑制作用的肿瘤细胞并依次改善组织再生。为了说明我们的策略,含有β-磷酸三钙(β-TCP),二维黑磷(BP)纳米片的水/聚(乳酸-乙醇酸共聚物)/二氯甲烷乳液,将低剂量的阿霉素盐酸盐(DOX)和大剂量的成骨肽深冷3D打印到具有层次结构的多孔且机械强度高的纳米复合材料支架中,该支架具有多种功能来治疗骨肿瘤切除所致的组织缺损。由于光热疗法和化学疗法的协同作用,可以实现迅速的肿瘤消融和长期的肿瘤复发抑制,最终由于骨环境的存在和持续的肽释放而获得了更好的骨再生。值得注意的是,支架中的BP纳米片大大降低了体内骨骼再生过程中释放的DOX的长期毒性现象。我们的研究还为设计多功能组织工程支架以治疗其他肿瘤切除引起的组织缺陷提供了见识。
更新日期:2020-04-20
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