Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital , Harvard Medical School , Cambridge , Massachusetts 02139 , United States.
MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering , Harbin Institute of Technology , Harbin 150001 , P.R. China.
Nano Lett. 2019 Jun 12;19(6):3603-3611. doi: 10.1021/acs.nanolett.9b00583. Epub 2019 May 7.
Due to the combined advantages of cellulose and nanoscale (diameter 20-60 nm), bacterial cellulose possesses a series of attractive features including its natural origin, moderate biosynthesis process, good biocompatibility, and cost-effectiveness. Moreover, bacterial cellulose nanofibers can be conveniently processed into three-dimensional (3D) intertwined structures and form stable paper devices after simple drying. These advantages make it suitable as the material for construction of organ-on-a-chip devices using matrix-assisted sacrificial 3D printing. We successfully fabricated various microchannel structures embedded in the bulk bacterial cellulose hydrogels and retained their integrity after the drying process. Interestingly, these paper-based devices containing hollow microchannels could be rehydrated and populated with relevant cells to form vascularized tissue models. As a proof-of-concept demonstration, we seeded human umbilical vein endothelial cells (HUVECs) into the microchannels to obtain the vasculature and inoculated the MCF-7 cells onto the surrounding matrix of the paper device to build a 3D paper-based vascularized breast tumor model. The results showed that the microchannels were perfusable, and both HUVECs and MCF-7 cells exhibited favorable proliferation behaviors. This study may provide a new strategy for constructing simple and low-cost in vitro tissue models, which may find potential applications in drug screening and personalized medicine.
由于纤维素和纳米级（直径 20-60nm）的综合优势，细菌纤维素具有一系列吸引人的特性，包括其天然来源、适度的生物合成过程、良好的生物相容性和成本效益。此外，细菌纤维素纳米纤维可以方便地加工成三维（3D）交织结构，并在简单干燥后形成稳定的纸张器件。这些优点使其适合作为用于基质辅助牺牲 3D 打印的器官芯片器件构建的材料。我们成功地在块状细菌纤维素水凝胶中制造了各种嵌入的微通道结构，并在干燥过程后保留了其完整性。有趣的是，这些含有中空微通道的纸基器件可以再水合并用相关细胞填充以形成血管化组织模型。作为概念验证演示，我们将人脐静脉内皮细胞（HUVEC）接种到微通道中以获得血管，并将 MCF-7 细胞接种到纸器件的周围基质上以构建 3D 纸基血管化乳腺癌模型。结果表明，微通道可灌注，并且 HUVEC 和 MCF-7 细胞都表现出良好的增殖行为。本研究可能为构建简单且低成本的体外组织模型提供了一种新策略，该策略可能在药物筛选和个性化医疗方面具有潜在应用。
