Abstract：
Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.
摘要：
人体肠道结构和功能在体外的准确复制对了解肠道的发育和疾病发生具有重要意义。然而,大多数体外研究通常局限于2D模型，2.5D器官芯片或3D类器官，不能完全概括组织结构，体内发现的微环境和细胞区室化。在这里，包含肠道特征的厘米级肠道组织，如中空管状结构，毛细血管和紧密相连的上皮，具有体内环状褶皱，地穴-绒毛,微绒毛是通过3D嵌入生物打印构建的。在我们的战略中,一种由甲基丙烯酸酯化明胶组成的新型光固化生物墨水，甲基丙烯酸酯化海藻酸钠和聚（乙二醇）二丙烯酸酯被开发用于制造肠道模型。通过模型的拓扑结构诱导植入腔内的Caco-2细胞产生微绒毛，地穴-绒毛,和紧密连接，模拟肠上皮屏障。模型内包裹的人脐静脉内皮细胞逐渐形成微血管，模仿肠道中密集的毛细血管网络。这个肠样组织,它非常类似于人类肠道的结构和细胞排列，可以作为预测新药对肠道的治疗和毒副作用的平台。
