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Arterial Decellularized Scaffolds Produced Using an Innovative Automatic System

机译:使用创新的自动系统产生的动脉脱细胞化支架

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There is still an unmet clinical need for small-caliber artery substitution. Decellularized scaffolds in tissue engineering represent a promising solution. We have developed an innovative system for the automatic decellularization of blood vessels, used to process pig arteries. The system is able to automatically drive a decellularization process in a safe and reliable environment, with complex time patterns, using up to three different decellularization solutions, and providing at the same time a physical stress to improve the decellularization. The decellularization of pig arteries was evaluated by means of histology, DNA quantification and mechanical testing. Outcomes showed scaffolds with no cellular or nuclear remnants and a well-preserved tissue structure, corroborated by mechanical properties similar to native tissue. Decellularized scaffolds were seeded on the inner layer with human endothelial cells and implanted as iliac artery replacement in 4 pharmacologically immune-compromised pigs. This chimeric model was performed as a very preliminary evaluation to investigate the performances of these scaffolds in vivo, and to investigate the fate of seeded cells. Recipients were sacrificed on day 14 and day 70 after surgery, and vessels were found to be patent and with no evidence of thrombi formation. The inner layer was covered by endothelial cells, and the migration of cells positive for alpha-smooth-muscle actin was observed from the outer layer towards the tunica media. Intriguingly, the endothelial cells on explanted vessels were entirely derived from the host while the seeded cells were lost. In conclusion, this work presents a novel tool for a safe and controlled production of arterial scaffolds, with good decellularization outcomes and a good performance in a short-term, large-animal implantation. (C) 2015 S. Karger AG, Basel
机译:小口径动脉替代仍有未满足的临床需求。组织工程中的脱细胞化支架代表了一个有前途的解决方案。我们开发了一种用于血管自动脱细胞的创新系统,用于处理猪动脉。该系统能够在安全可靠的环境中自动驱动脱细胞化过程,具有复杂的时间模式,使用多达三种不同的脱细胞化解决方案,并同时提供物理应力来改善脱细胞化。通过组织学,DNA定量和机械测试评估猪动脉的脱细胞。结果表明,没有细胞或核残余物的支架和保存完好的组织结构,通过类似于天然组织的机械性能证实。用人内皮细胞接种在内层上的脱细胞化支架,并在4个药理学免疫损害猪中植入髂动脉替代。这种嵌合模型作为初步评估,以研究体内这些支架的性能,并研究种子细胞的命运。在手术后第14天和第70天处死接受者,并且发现血管是专利,没有血栓形成的证据。内皮细胞覆盖内层,并且从外层朝向Tunica培养基观察到α-光滑肌肌动蛋白的细胞阳性的迁移。有趣的是,外皮细胞在外皮细胞上完全来自主体,而种子细胞丢失。总之,这项工作提出了一种用于安全和控制的动脉支架生产的新型工具,具有良好的脱细胞化结果和短期大动物植入的良好表现。 (c)2015年S. Karger AG,巴塞尔

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