High-Throughput Blood- and Lymph-Capillaries with Open-Ended Pores Which Allow the Transport of Drugs and Cells.
High-throughput screening of drug diffusion and cell transports from the blood-/lymph-capillary (BC/LC) networks to the peripheral cells in 3D engineered tissues using a microplate would make a powerful tool for in vitro pharmacokinetic assessments. Here, perfusable BC/LC networks embedded in 3D-tissues inside a 24-microplate using a cell-coating technology are reported which allows location control of cell layers. Arrangement of an endothelial cell layer at the top, middle, and bottom of dermal fibroblast tissues provides an interconnected BC/LC networks possessing open pores on both surfaces. When fluorescently labeled dextran, microparticles, and red blood cells are applied to the top surfaces, diffusion and penetration through the networks are observed depending on the size of the substances. Moreover, BC networks mimick a series of in vivo processes of cancer metastasis, extravasation, growth, and growth suppression with drug treatment. The perfusable networks existing in 3D-tissues show great potential for in vitro pharmacokinetic studies.
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Daichi
D
Hikimoto
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Akihiro
A
Nishiguchi
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.|JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
Michiya
M
Matsusaki
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Mitsuru
M
Akashi
D001692:Biological Transport; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology; D020405:Dermis / Q000098:blood supply* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016062:Porosity; D023822:Tissue Engineering
drug transport; perfusable blood and lymph capillaries; regenerative medicine; tissue engineering