Direct Fabrication of a Hybrid Cell/Hydrogel Construct by a Double-nozzle Assembling Technology

Abstract

Assembling multitype cells and biomimic extracellular matrix materials in a single construct is a promising method to regenerate complex tissues/organs in vitro. A new double-nozzle assembling technique was used to fabricate a hybrid cell/hydrogel construct with a vascular-like network to perform as a mass exchange conduit. Using a digital model to mimic an anatomical liver structure, adipose-derived stromal cells (ADSC) were combined within a gelatin/alginate/fibrinogen hydrogel to form a vascular-like network and hepatocytes combined gelatin/alginate/chitosan were placed around it. The construct was stabilized in a thrombin/CaCl₂/Na₅P₃O₁₀ solution after assembly. The ADSC were induced to differentiate into endothelial-like cells with endothelial growth factor. The albumin secretion level of the embedded hepatocytes increased during the 2 weeks culture, while the levels of urea and alanine transaminase were decreased after an increasing profile. These preliminary results indicate that this double-nozzle assembling technique could be a powerful tool for fabricating complex constructs with special intrinsic/ extrinsic structures. This technology has the potential to be widely used in medical regeneration and drug screening.