Abstract

We developed a procedure for fabricating movable biological cell structures using biodegradable materials on a microfluidic chip. A photo-cross-linkable biodegradable hydrogel gelatin methacrylate (GelMA) was used to fabricate arbitrary microstructure shapes under a microscope using patterned ultraviolet light. The GelMA microstructures were movable inside the microfluidic channel after applying a hydrophobic coating material. The fabricated microstructures were self-assembled inside the microfluidic chip using our method of fluid forcing. The synthesis procedure of GelMA was optimized by changing the dialysis temperature, which kept the GelMA at a suitable pH for cell culture. RLC-18 rat liver cells (Riken BioResource Research Center, Tsukuba, Japan) were cultured inside the GelMA and on the GelMA microstructures to check cell growth. The cells were then stretched for 1 day in the cell culture and grew well on the GelMA microstructures. However, they did not grow well inside the GelMA microstructures. The GelMA microstructures were partially dissolved after 4 days of cell culture because of their biodegradability after the cells were placed on the microstructures. The results indicated that the proposed procedure used to fabricate cell structures using GelMA can be used as a building block to assemble three-dimensional tissue-like cell structures in vitro inside microfluidic devices.

Highlights

  • Cell-assembly technologies for tissue engineering and organs-on-a-chip have gained increasing attention [1,2,3] with the development of pluripotent stem cells [4,5]

  • We developed a procedure for fabricating movable biological cell structures using a biodegradable material in a microfluidic chip, in which cells are cultured on microstructures to achieve 2D cell structures

  • Excess methacrylic acid in the gelatin methacrylate (GelMA) was removed during dialysis so that the dialysis could be conducted at 40 °C

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Summary

Introduction

Cell-assembly technologies for tissue engineering and organs-on-a-chip have gained increasing attention [1,2,3] with the development of pluripotent stem cells [4,5]. Various assemblies of three-dimensional (3D) cell structures have been proposed in the literature. Two-dimensional (2D) cell sheets can be used to create thicker cell structures by picking them up and placing them layer by layer [9,10]. To achieve 3D cell structures of larger size, robotics technologies have been applied. A bio-printing method based on inkjet technologies was recently developed [11,12,13,14,15] to increase the fabrication speed and the strength of cell structures. Fabrication speeds are limited, especially when the fabricated structure becomes larger, because the 3D printer must fabricate 3D structures from one-dimensional dots (i.e., droplets)

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