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Fibronectin promotes elastin deposition, elasticity and mechanical strength in cellularised collagen-based scaffolds
Biomaterials ( IF 14.0 ) Pub Date : 2018-07-12 , DOI: 10.1016/j.biomaterials.2018.07.013
Daniele Pezzoli , Joseph Di Paolo , Heena Kumra , Giulia Fois , Gabriele Candiani , Dieter P. Reinhardt , Diego Mantovani

One of the tightest bottlenecks in vascular tissue engineering (vTE) is the lack of strength and elasticity of engineered vascular wall models caused by limited elastic fiber deposition. In this study, flat and tubular collagen gel-based scaffolds were cellularised with vascular smooth muscle cells (SMCs) and supplemented with human plasma fibronectin (FN), a known master organizer of several extracellular matrix (ECM) fiber systems. The consequences of FN on construct maturation was investigated in terms of geometrical contraction, viscoelastic mechanical properties and deposition of core elastic fiber proteins. FN was retained in the constructs and promoted deposition of elastin by SMCs as well as of several proteins required for elastogenesis such as fibrillin-1, lysyl oxidase, fibulin-4 and latent TGF-β binding protein-4. Notably, gel contraction, tensile equilibrium elastic modulus and elasticity were strongly improved in tubular engineered tissues, approaching the behaviour of native arteries. In conclusion, this study demonstrates that FN exerts pivotal roles in directing SMC-mediated remodeling of scaffolds toward the production of a physiological-like, elastin-containing ECM with excellent mechanical properties. The developed FN-supplemented systems are promising for tissue engineering applications where the generation of mature elastic tissue is desired and represent valuable advanced in vitro models to investigate elastogenesis.



中文翻译:

纤连蛋白可促进细胞化胶原基支架中的弹性蛋白沉积,弹性和机械强度

血管组织工程(vTE)中最严峻的瓶颈之一是由于弹性纤维沉积受限而导致的工程化血管壁模型缺乏强度和弹性。在这项研究中,将基于扁平和管状胶原凝胶的支架与血管平滑肌细胞(SMC)细胞化,并补充人血浆纤连蛋白(FN),这是几种细胞外基质(ECM)纤维系统的已知主要组织者。从几何收缩,粘弹性力学性能和核心弹性纤维蛋白的沉积方面研究了FN对结构成熟的影响。FN保留在构建体中,并促进SMCs弹力蛋白的沉积以及弹性生成所需的几种蛋白质(如原纤维蛋白-1,赖氨酰氧化酶,fibulin-4和潜在的TGF-β结合蛋白-4)的沉积。尤其,在管状工程组织中,凝胶收缩,拉伸平衡弹性模量和弹性得到了显着改善,接近了自然动脉的行为。总而言之,这项研究表明FN在指导SMC介导的支架重塑走向具有良好机械性能的生理性,含弹性蛋白的ECM的生产中发挥着关键作用。所开发的FN补充系统有望用于组织工程应用,在这些应用中,需要生成成熟的弹性组织并代表有价值的先进技术。这项研究表明,FN在指导SMC介导的支架重塑向具有生理学特性,含弹性蛋白的ECM的产生具有重要的机械性能方面发挥着关键作用。所开发的FN补充系统有望用于组织工程应用,在这些应用中,需要生成成熟的弹性组织并代表有价值的先进技术。这项研究表明,FN在指导SMC介导的支架重塑向具有生理学特性,含弹性蛋白的ECM的产生具有重要的机械性能方面发挥着关键作用。所开发的FN补充系统有望用于组织工程应用,在这些应用中,需要生成成熟的弹性组织并代表有价值的先进技术。体外模型研究弹性发生。

更新日期:2018-07-14
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