The acellular myocardial flap: a novel extracellular matrix scaffold enriched with patent microvascular networks and biocompatible cell niches.
The acellular myocardial flap: a novel extracellular matrix scaffold enriched with patent microvascular networks and biocompatible cell niches.
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脱细胞心肌瓣：一种新型细胞外基质支架，富含专利微血管网络和生物相容性细胞生态位。
DOI：
10.1089/ten.tec.2012.0536
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Simionescu,DanT
中科院分区：
文献类型：
--
作者：
Schulte,JasonB;Simionescu,Agneta;Simionescu,DanT
因此，人们迫切需要一种无细胞的、完全血管化的、生物相容性良好的心肌支架，这种支架能够为体外和体内应用提供合适的生物学、营养学和生物力学环境。我们制作了包括猪左前心室心肌及其相关冠状动脉和静脉的心肌瓣支架，并研究了十二烷基硫酸钠（SDS）和氢氧化钠（NaOH）灌注对心肌细胞外基质（ECM）和血管ECM的组合效应。结果显示，所有支架均显示出完全完整和通畅的脉管系统，动脉破裂压与天然冠状动脉难以区分，灌注达到毛细血管水平。支架不含细胞蛋白，保留胶原蛋白和弹性蛋白ECM组分，表现出优异的机械性能，并且对相关的接种细胞具有细胞相容性。SDS灌注保存IV型胶原蛋白，层粘连蛋白和纤连蛋白以及，但仅减少33%的DNA含量，然而，这是进一步改善后SDS核酸酶处理。相比之下，NaOH在去除细胞方面非常有效，并消除了超过95%的组织DNA，但也显著降低了层粘连蛋白和纤连蛋白的水平。这样的结构可以很容易地修剪，以匹配梗死的大小，并可能能够在宿主心肌功能整合，并通过与宿主自身的血管直接吻合连接得到营养，它们也可能是有用的生理学准确的模型，用于心脏生理学和病理学的体外研究。
There is a great need for acellular, fully vascularized, and biocompatible myocardial scaffolds that provide agreeable biological, nutritional, and biomechanical niches for reseeded cells forin vitroandin vivoapplications. We generated myocardial flap scaffolds comprising porcine left-anterior ventricular myocardium and its associated coronary arteries and veins and investigated the combinatorial effects of sodium dodecyl sulfate (SDS) and sodium hydroxide (NaOH) perfusion on both the myocardial extracellular matrix (ECM) and the vascular ECM. Results showed that all scaffolds displayed a fully intact and patent vasculature, with arterial burst pressures indistinguishable from native coronary arteries and perfusion to the level of capillaries. Scaffolds were free of cellular proteins and retained collagen and elastin ECM components, exhibited excellent mechanical properties, and were cytocompatible toward relevant seeded cells. SDS perfusion preserved collagen IV, laminin, and fibronectin well, but only reduced DNA content by 33%; however, this was further improved by post-SDS nuclease treatments. By comparison, NaOH was very effective in removing cells and eliminated more than 95% of tissue DNA, but also significantly reduced levels of laminin and fibronectin. Such constructs can be readily trimmed to match the size of the infarct and might be able to functionally integrate within host myocardium and be nourished by direct anastomotic connection with the host's own vasculature; they might also be useful as physiologically accurate models forin vitrostudies of cardiac physiology and pathology.
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