Fabrication of Biomimetic 3D Liver Tissue by Photodegradable Hydrogels and Perfusion Culture in a Microfluidic Device

Yanagawa, Fumiki ;   Sugiura, Shinji ;   Takagi, Toshiyuki ;   Sumaru, Kimio ;   Kanamori, Toshiyuki

This paper reports a novel technique to fabricate perfusable 3D liver tissue in a microfluidic device using photodegradable hydrogels prepared with gelatin. Also, we performed the perfusion culture of human hepatocellular carcinoma (HepG2) cells encapsulated in the patterned hydrogels. To perform long-term cultivation of engineered 3D thick tissue, medium perfusion to the 3D tissue is necessary for supplying oxygen, nutrients, and other soluble factors for cell growth. Many research groups have reported fabrication of perfusable 3D tissue structure within hydrogels using biocompatible hydrogels such as gelatin. Recently, photodegradable hydrogels have attracted significant attention because of their tunable material properties. We reported an activated-ester-type photocleavable crosslinker, NHS-PC-4armPEG, which is convenient material to prepare photodegradable hydrogels through simple two-component mixing reaction using a biocompatible polymer containing amino moieties such as gelatin. In this study, we applied this gelatin-based photodegradable hydrogels to construct biomimetic 3D liver tissue in a microfluidics device with a manner of photolithography. This platform enabled microscale fabrication of perfusable tissues with designed geometry in a microfluidic device.