Three-Dimensional RAW264.7 Cell Model on Electrohydrodynamic Printed Poly(ϵ-Caprolactone) Scaffolds for in Vitro Study of Anti-Inflammatory Compounds

Wang，Xiang1; Cao，Yujia1; Jing，Linzhi3; Chen，Siyu1; Leng，Bin1,3; Yang，Xin1; Wu，Zhiyuan2; Bian，Jinsong2,3,4; Banjerdpongchai，Ratana5; Poofery，Juthathip5; Huang，Dejian1,3

2021

10.1021/acsabm.1c00889

ACS Applied Bio Materials   影响因子和分区

2576-6422

2576-6422

Inflammation plays an essential role in the human immune system, and anti-inflammatory compounds are important to promote health. However, the in vitro screening of these compounds is largely dependent on flat biology. Herein, we report our efforts in establishing a 3D inflammation murine macrophage model. Murine macrophage RAW 264.7 cells were cultured on poly(ϵ-caprolactone) (PCL) scaffolds fabricated through an electrohydrodynamic jetting 3D printer and their behavior were examined. Cells on PCL scaffolds showed a 3D shape and morphology with multilayers and a lower proliferation rate. Moreover, macrophages were not activated by scaffold material PCL and 3D microenvironment. The 3D cells showed greater sensitivity to lipopolysaccharide stimulation with higher production activity of nitric oxide (NO), nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2). Additionally, the 3D macrophage model showed lower drug sensitivity to commercial anti-inflammatory drugs including aspirin, ibuprofen, and dexamethasone, and natural flavones apigenin and luteolin with higher IC50 for NO production and lower iNOS and COX-2 inhibition efficacy. Overall, the 3D macrophage model showed promise for higher accurate screening of anti-inflammatory compounds. We developed, for the first time, a 3D macrophage model based on a 3D-printed PCL scaffold that provides an extracellular matrix environment for cells to grow in the 3D dimension. 3D-grown RAW 264.7 cells showed different sensitivities and responses to anti-inflammatory compounds from its 2D model. The 3D cells have lower sensitivity to both commercial and natural anti-inflammatory compounds. Consequently, our 3D macrophage model could be applied to screen anti-inflammatory compounds more accurately and thus holds great potential in next-generation drug screening applications.

3D cell culture model anti-inflammatory compounds EHDJ flavones inflammation murine macrophages

ESCI ; EI

英语

其他

Singapore Ministry of Education[R-160-000-B04-114]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Biomaterials

WOS:000720776800023

AMER CHEMICAL SOC

20214311080159

3D modeling ; 3D printers ; Cell culture ; Drug products ; Electrohydrodynamics ; Flavonoids ; Nitric oxide ; Pathology ; Scaffolds (biology) ; Three dimensional computer graphics

Biomedical Engineering:461.1 ; Medicine and Pharmacology:461.6 ; Immunology:461.9.1 ; Data Processing and Image Processing:723.2 ; Computer Applications:723.5 ; Printing Equipment:745.1.1 ; Organic Compounds:804.1 ; Inorganic Compounds:804.2

2-s2.0-85117856394

Scopus

1.Department of Food Science and Technology,National University of Singapore,Singapore,2 Science Drive 2,117542,Singapore
2.Department of Pharmacology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,117600,Singapore
3.National University of Singapore (Suzhou) Research Institute,Suzhou,377 Linquan Street, Jiangsu,215123,China
4.Department of Pharmacology,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
5.Department of Biochemistry,Faculty of Medicine,Chiang Mai University,Chiang Mai,50200,Thailand

Wang，Xiang,Cao，Yujia,Jing，Linzhi,et al. Three-Dimensional RAW264.7 Cell Model on Electrohydrodynamic Printed Poly(ϵ-Caprolactone) Scaffolds for in Vitro Study of Anti-Inflammatory Compounds[J]. ACS Applied Bio Materials,2021,4(11):7967-7978.

Wang，Xiang.,Cao，Yujia.,Jing，Linzhi.,Chen，Siyu.,Leng，Bin.,...&Huang，Dejian.(2021).Three-Dimensional RAW264.7 Cell Model on Electrohydrodynamic Printed Poly(ϵ-Caprolactone) Scaffolds for in Vitro Study of Anti-Inflammatory Compounds.ACS Applied Bio Materials,4(11),7967-7978.

Wang，Xiang,et al."Three-Dimensional RAW264.7 Cell Model on Electrohydrodynamic Printed Poly(ϵ-Caprolactone) Scaffolds for in Vitro Study of Anti-Inflammatory Compounds".ACS Applied Bio Materials 4.11(2021):7967-7978.