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基于动态培养构建蜘蛛丝蛋白小口径组织工程血管移植物及其性能评价。

Construction of spider silk protein small-caliber tissue engineering vascular grafts based on dynamic culture and its performance evaluation.

机构信息

College of Life Science and Technology, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, China.

College of Medical Engineering, Xinxiang Medical University, Xinxiang, China.

出版信息

J Biomed Mater Res A. 2023 Jan;111(1):71-87. doi: 10.1002/jbm.a.37447. Epub 2022 Sep 21.

Abstract

Tissue engineering is an alternative method for preparing small-caliber (<6 mm) vascular grafts. Dynamic mechanical conditioning is being researched as a method to improve mechanical properties of tissue engineered blood vessels. This method attempts to induce unique reaction in implanted cells that regenerate the matrix around them, thereby improving the overall mechanical stability of the grafts. In this study, we used a bioreactor to seed endothelial cells and smooth muscle cells into the inner and outer layers of the electrospun spider silk protein scaffold respectively to construct vascular grafts. The cell proliferation, mechanical properties, blood compatibility and other indicators of the vascular grafts were characterized in vitro. Furthermore, the vascular grafts were implanted in Sprague Dawley rats, and the vascular grafts' patency, extracellular matrix formation, and inflammatory response were evaluated in vivo. We aimed to construct spider silk protein vascular grafts with the potential for in vivo implantation by using a pulsating flow bioreactor. The results showed that, when compared with the static culture condition, the dynamic culture condition improved cell proliferation on vascular scaffolds and enhanced mechanical function of vascular scaffolds. In vivo experiments also showed that the dynamic culture of vascular grafts was more beneficial for the extracellular matrix deposition and anti-thrombogenesis, as well as reducing the inflammatory response of vascular grafts. In conclusion, dynamic mechanical conditioning aid in the resolution of challenges impeding the application of electrospun scaffolds and have the potential to construct small-caliber blood vessels with regenerative function for cardiovascular tissue repair.

摘要

组织工程是一种制备小口径(<6mm)血管移植物的替代方法。动态力学调节作为一种改善组织工程血管力学性能的方法正在被研究。这种方法试图诱导植入细胞产生独特的反应,使其周围的基质再生,从而提高移植物的整体机械稳定性。在这项研究中,我们使用生物反应器将内皮细胞和平滑肌细胞分别接种到静电纺丝蜘蛛丝蛋白支架的内、外层,构建血管移植物。体外对血管移植物的细胞增殖、力学性能、血液相容性等指标进行了表征。此外,将血管移植物植入 Sprague Dawley 大鼠体内,评估了血管移植物的通畅性、细胞外基质形成和炎症反应。我们旨在通过使用脉动流生物反应器构建具有体内植入潜力的蜘蛛丝蛋白血管移植物。结果表明,与静态培养条件相比,动态培养条件可促进血管支架上细胞的增殖,并增强血管支架的力学功能。体内实验也表明,血管移植物的动态培养更有利于细胞外基质的沉积和抗血栓形成,同时减少血管移植物的炎症反应。总之,动态力学调节有助于解决阻碍静电纺丝支架应用的挑战,并有可能构建具有再生功能的小口径血管,用于心血管组织修复。

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