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Heterotypic Scaffold Design Orchestrates Primary Cell Organization and Phenotypes in Cocultured Small Diameter Vascular Grafts

机译:异型支架设计编排共培养小直径血管移植物中的原代细胞组织和表型。

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To facilitate true regeneration, a vascular graft should direct the evolution of a neovessel to obtain the function of a native vessel. For this, scaffolds have to permit the formation of an intraluminal endothelial cell monolayer, mimicking the tunica intima. In addition, when attempting to mimic a tunica media-like outer layer, the stacking and orientation of vascular smooth muscle cells (vSMCs) should be recapitulated. An integral scaffold design that facilitates this has so far remained a challenge. A hybrid fabrication approach is introduced by combining solution electrospinning and melt electrowriting. This allows a tissue-structure mimetic, hierarchically bilayered tubular scaffold, comprising an inner layer of randomly oriented dense fiber mesh and an outer layer of microfibers with controlled orientation. The scaffold supports the organization of a continuous luminal endothelial monolayer and oriented layers of vSM-like cells in the media, thus facilitating control over specific and tissue-mimetic cellular differentiation and support of the phenotypic morphology in the respective layers. Neither soluble factors nor a surface bioactivation of the scaffold is needed with this approach, demonstrating that heterotypic scaffold design can direct physiological tissue-like cell organization and differentiation.
机译:为了促进真正的再生,血管移植物应指导新血管的进化以获得天然血管的功能。为此,支架必须允许腔内内皮细胞单层的形成,从而模仿内膜。此外,在尝试模仿中膜状外层时,应概述血管平滑肌细胞(vSMC)的堆积和方向。迄今为止,促进这种变化的整体支架设计仍然是一个挑战。通过将溶液电纺丝和熔融电写结合起来,引入了一种混合制造方法。这允许组织结构模拟的,分层的双层管状支架,其包括随机取向的致密纤维网的内层和具有受控取向的微纤维的外层。支架在培养基中支持连续的管腔内皮单层和vSM样细胞的定向层的组织,从而促进对特异性和组织模拟细胞分化的控制,并支持各层中的表型形态。用这种方法既不需要支架的可溶性因子也不需要表面生物活化,这表明异型支架设计可以指导生理性组织样细胞的组织和分化。

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