Additive manufacturing of a 3D vascular chip based on cytocompatible hydrogel

Abstract

Development of a three-dimensional (3D) vascular microfluidic chip is one of the important challenges for the study vascular-related diseases and new drugs. To date, however, realization of in vivo-like blood vessel chips based on soft- or photo-lithographic fabrication methods have limitations such as complex fabrication processes, tedious manual labor, and frequent assembly failure. In this study, we describe the development of a 3D cell culture chip by utilizing a stereolithographic printer. The microfluidic chip was fabricated using a resin made of 30% (v/v in water) poly(ethylene glycol) diacrylate (MW = 700) (30% PEG-DA-700), a UV initiator (Irgacure-819 (IRG)) and a photosensitizer (2-isopropylthioxanthone (ITX)) for constructing a cytocompatible hydrogel structure. The 3D-printed cell culture chip is transparent, enabling cell culture and observation of cell proliferation. Endothelial cells were cultured to mimic in vivo-like blood vessel architecture within the 3D-printed chip. After EAhy926 cell cultivation, cell viability was confirmed by a live/dead cell assay and cultured cells were stained with Calcein-AM (Green) and Ethidium homodim-1 (Red). In addition, endothelial cells were successfully cultured in a 3D-printed vascular tube-like architecture in PEG-DA-700. Creating a vascular microfluidic chip with 30% PEG-DA-700 hydrogel using automated 3D-printing processes reduces fabrication steps and time, avoids any assembly and bonding, and economizes manufacturing cost. We believe our stereolithographic 3D-printing method for fabricating a 3D-printed vascular chip provides a cost-effective, convenient, simple, and reproducible route to vascular-related disease modelling and drug screening analyses.