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弹性蛋白原涂层的 PLLA-PLGA 支架促进血管网络形成。

Tropoelastin coated PLLA-PLGA scaffolds promote vascular network formation.

机构信息

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Israel.

Life and Environmental Sciences, University of Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, NSW 2006, Australia; Bosch Institute, University of Sydney, NSW 2006, Australia.

出版信息

Biomaterials. 2017 Apr;122:72-82. doi: 10.1016/j.biomaterials.2017.01.015. Epub 2017 Jan 11.

Abstract

The robust repair of large wounds and tissue defects relies on blood flow. This vascularization is the major challenge faced by tissue engineering on the path to forming thick, implantable tissue constructs. Without this vasculature, oxygen and nutrients cannot reach the cells located far from host blood vessels. To make viable constructs, tissue engineering takes advantage of the mechanical properties of synthetic materials, while combining them with ECM proteins to create a natural environment for the tissue-specific cells. Tropoelastin, the precursor of the elastin, is the ECM protein responsible for elasticity in diverse tissues, including robust blood vessels. Here, we seeded endothelial cells with supporting cells on PLLA/PLGA scaffolds treated with tropoelastin, and examined the morphology, expansion and maturity of the newly formed vessels. Our results demonstrate that the treated scaffolds elicit a more expanded, complex and developed vascularization in comparison to the untreated group. Implantation of tropoelastin-treated scaffolds into mouse abdominal muscle resulted in enhanced perfusion of the penetrating vasculature and improved integration. This study points to the great potential of these combined materials in promoting the vascularization of implanted engineered constructs, which can be further exploited in the fabrication of clinically relevant engineered tissues.

摘要

大型伤口和组织缺损的稳健修复依赖于血流。血管化是组织工程在形成厚的、可植入组织构建体的道路上面临的主要挑战。如果没有这种脉管系统,氧气和营养物质就无法到达远离宿主血管的细胞。为了制造可行的构建体,组织工程利用了合成材料的机械性能,同时将其与细胞外基质蛋白结合,为组织特异性细胞创造一个自然环境。原弹性蛋白是弹性蛋白的前体,是多种组织(包括坚固的血管)中弹性的细胞外基质蛋白。在这里,我们将内皮细胞与支持细胞接种在经过原弹性蛋白处理的 PLLA/PLGA 支架上,观察新形成的血管的形态、扩张和成熟。我们的结果表明,与未处理组相比,处理过的支架引发了更扩展、更复杂和更成熟的血管化。将经过原弹性蛋白处理的支架植入小鼠腹部肌肉中,可增强穿透性血管的灌注和改善整合。这项研究表明,这些组合材料在促进植入的工程化构建体的血管化方面具有巨大的潜力,可以进一步用于制造临床相关的工程化组织。

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