Sibilio S, De Gregorio V, Urciuolo F, Netti P A, Imparato G
Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, P.le Tecchio 80, Naples, 80125, Italy.
Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci n. 53, Naples, 80125, Italy.
Mater Today Bio. 2019 Sep 19;4:100027. doi: 10.1016/j.mtbio.2019.100027. eCollection 2019 Sep.
The intestine is a highly heterogeneous hollow organ with biological, mechanical and chemical differences between lumen and wall. A functional human intestine model able to recreate the dynamic nature as well as the native tissue morphology is demanded for disease research and drug discovery. Here, we present a system, which combines an engineered three-dimensional (3D) tubular-shaped intestine model (3D In-tube) with a custom-made microbioreactor to impart the key aspects of the microenvironment of the human intestine, mimicking the rhythmic peristaltic movement. We adapted a previously established bottom-up tissue engineering approach, to produce the 3D tubular-shaped lamina propria and designed a glass microbioreactor to induce the air-liquid interface condition and peristaltic-like motion. Our results demonstrate the production of a villi-like protrusion and a correct spatial differentiation of the intestinal epithelial cells in enterocyte-like as well as mucus-producing-like cells on the lumen side of the 3D In-tube. This dynamic platform offers a proof-of-concept model of the human intestine.
肠道是一个高度异质性的中空器官，管腔和肠壁在生物学、力学和化学方面存在差异。疾病研究和药物发现需要一个能够重现动态特性以及天然组织形态的功能性人体肠道模型。在此，我们展示了一种系统，该系统将工程化的三维（3D）管状肠道模型（3D管内模型）与定制的微生物反应器相结合，以赋予人体肠道微环境的关键特征，模拟有节奏的蠕动运动。我们采用了先前建立的自下而上的组织工程方法来制备3D管状固有层，并设计了一个玻璃微生物反应器来诱导气液界面条件和类蠕动运动。我们的结果表明，在3D管内模型的管腔侧产生了绒毛状突起，并且肠道上皮细胞在肠细胞样以及黏液分泌样细胞中实现了正确的空间分化。这个动态平台提供了一个人体肠道的概念验证模型。
