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Engineered cardiac micromodules for the in vitro fabrication of 3D endogenous macro-tissues

机译：用于3D内源性宏观组织的体外制造的工程心脏微芯片

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The in vitro fabrication of an endogenous cardiac muscle would have a high impact for both in vitro studies concerning cardiac tissue physiology and pathology, as well as in vivo application to potentially repair infarcted myocardium. To reach this aim, we engineered a new class of cardiac tissue precursor (CTP), specifically conceived in order to promote the synthesis and the assembly of a cardiac extracellular matrix (ECM). The CTPs were obtained by culturing a mixed cardiac cell population, composed of myocyte and non-myocyte cells, into porous gelatin microspheres in a dynamic bioreactor. By engineering the culture conditions, the CTP developed both beating properties and an endogenous immature cardiac ECM. By following a bottom-up approach, a macrotissue was fabricated by molding and packing the engineered tissue precursor in a maturation chamber. During the macrotissue formation, the tissue precursors acted as cardiac tissue depots by promoting the formation of an endogenous and interconnected cardiac network embedding the cells and the microbeads. The myocytes cell fraction pulled on ECM network and induced its compaction against the internal posts represented by the initial porous microbeads. This reciprocal interplay induced ECM consolidation without the use of external biophysical stimuli by leading to the formation of a beating and endogenous macrotissue. We have thus engineered a new class of cardiac micromodules and show its potential for the fabrication of endogenous cardiac tissue models useful for in vitro studies that involve the cardiac tissue remodeling.
机译：内源性心肌的体外制造对于有关心脏组织生理学和病理学的体外研究以及体内应用的体外研究具有很大的影响，以及潜在地修复梗死的心肌。为了实现这一目标，我们设计了一种新的心脏组织前体（CTP），特别是构思，以促进合成和心脏细胞外基质（ECM）的组装。通过将由肌细胞和非肌细胞细胞组成的混合心细胞群培养到动态生物反应器中的多孔明胶微球中获得CTP。通过工程培养条件，CTP开发出跳动性质和内源性未成复心脏ECM。通过遵循自下而上的方法，通过在成熟室中模制和填充工程化组织前体来制造宏观制造。在宏观形成期间，组织前体通过促进嵌入细胞和微珠的内源性和互连的心脏网络的形成而作用为心脏组织贮库。肌细胞细胞部分拉动在ECM网络上，并诱导其对由初始多孔微珠表示的内部柱的压实。这种相互相互作用在不使用外部生物物理刺激的情况下诱导ECM整合，从而导致形成搏动和内源性宏观。因此，我们已经设计了一类新的心脏微透模，并表明其适用于对体外研究有用的内源性心脏组织模型的潜力涉及心脏组织改造。

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