首页> 外文期刊>Journal of tissue engineering and regenerative medicine >Fabrication of blood-derived elastogenic vascular grafts using electrospun fibrinogen and polycaprolactone composite scaffolds for paediatric applications
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Fabrication of blood-derived elastogenic vascular grafts using electrospun fibrinogen and polycaprolactone composite scaffolds for paediatric applications

机译:使用电纺纤维蛋白原和聚己内酯复合支架进行小儿应用的血液衍生弹性血管移植物的制备

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The development of tissue-engineered vascular grafts (TEVGs) for paediatric applications must consider unique factors associated with this patient cohort. Although the increased elastogenic potential of neonatal cells offers an opportunity to overcome the long-standing challenge of in vitro elastogenesis, neonatal patients have a lower tolerance for autologous tissue harvest and require grafts that exhibit growth potential. The purpose of this study was to apply a multipronged strategy to promote elastogenesis in conjunction with umbilical cord-derived materials in the production of a functional paediatric TEVG. An initial proof-of-concept study was performed to extract fibrinogen from human umbilical cord blood samples and, through electrospinning, to produce a nanofibrous fibrinogen scaffold. This scaffold was seeded with human umbilical artery-derived smooth muscle cells (hUASMCs), and neotissue formation within the scaffold was examined using immunofluorescence microscopy. Subsequently, a polycaprolactone-reinforced porcine blood-derived fibrinogen scaffold (isolated using the same protocol as cord blood fibrinogen) was used to develop a rolled-sheet graft that employed topographical and biochemical guidance cues to promote elastogenesis and cellular orientation. This approach resulted in a TEVG with robust mechanical properties and biomimetic arrangement of extracellular matrix (ECM) with rich expression of elastic fibre-related proteins. The results of this study hold promise for further development of paediatric TEVGs and the exploration of the effects of scaffold microstructure and nanostructure on vascular cell function and ECM production.
机译:组织工程血管移植物(TEVGS)的儿科应用的发展必须考虑与该患者队列相关的独特因素。尽管新生儿细胞弹性生成潜能的增加为克服体外弹性生成的长期挑战提供了机会,但新生儿患者对自体组织收获的耐受性较低,需要具有生长潜能的移植物。本研究的目的是采用多管齐下的策略,结合脐带衍生材料促进弹性发生,以生产功能性儿科TEVG。进行了初步的概念验证研究,从人脐血样本中提取纤维蛋白原,并通过静电纺丝制备纳米纤维纤维蛋白原支架。将人脐动脉来源的平滑肌细胞(HUASMC)植入该支架,并使用免疫荧光显微镜检查支架内的新组织形成。随后,使用聚己内酯增强的猪血源性纤维蛋白原支架(使用与脐血纤维蛋白原相同的方案分离)来开发卷板移植物,该移植物利用地形和生化指导线索来促进弹性生成和细胞定向。这种方法产生的TEVG具有强大的机械性能和细胞外基质(ECM)的仿生排列,富含弹性纤维相关蛋白的表达。本研究结果有望进一步开发儿科TEVG,探索支架微观结构和纳米结构对血管细胞功能和ECM生成的影响。

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