LAUSR

Tremendous advances have been made toward accurate recapitulation of the human intestinal system in vitro to understand its developmental process, and disease progression. However, current in vitro models are often confined to 2D or 2.5D microarchitectures, which is difficult to mimic the systemic level of complexity of the native tissue. To overcome this problem, we develop physiologically relevant intestinal models with a 3D hollow tubular structure using 3D bioprinting strategy. A tissue-specific biomaterial, colon-derived decellularized extracellular matrix (Colon dECM) has been developed and it provides significant maturation-guiding potential to human intestinal cells. To fabricate a perfusable tubular model, we develop a simultaneous printing process of multiple materials through concentrically assembled nozzles and employ a light-activated Colon dECM bioink by supplementing with ruthenium/sodium persulfate as a photoinitiator. The bioprinted intestinal tissue models show spontaneous 3D morphogenesis of the human intestinal epithelium without any external stimuli. In consequence, the printed cells form multicellular aggregates and cysts and then differentiate into several types of enterocytes, building junctional networks. This system can serve as a platform to evaluate the effects of potential drug-induced toxicity on the human intestinal tissue and create a co-culture model with commensal microbes and immune cells for future therapeutics. This article is protected by copyright. All rights reserved.