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基于抗凝血细胞外基质的纳米复合心脏瓣膜叶的开发。

Development of Antithrombogenic ECM-Based Nanocomposite Heart Valve Leaflets.

机构信息

Nanotechnology and Nanomedicine Division, Institute of Science, Hacettepe University, Beytepe, 06800, Ankara, Turkey.

Bioengineering Division, Institute of Science, Hacettepe University, Beytepe, 06800, Ankara, Turkey.

出版信息

ACS Appl Bio Mater. 2022 Aug 15;5(8):3883-3895. doi: 10.1021/acsabm.2c00423. Epub 2022 Jul 15.

Abstract

Thrombogenicity, which is commonly encountered in artificial heart valves after replacement surgeries, causes valvular failure. Even life-long anticoagulant drug use may not be sufficient to prevent thrombogenicity. In this study, it was aimed to develop a heart valve construct with antithrombogenic properties and suitable mechanical strength by combining multiwalled carbon nanotubes within a decellularized bovine pericardium. In this context, the decellularization process was performed by using the combination of freeze-thawing and sodium dodecyl sulfate (SDS). Evaluation of decellularization efficiency was determined by histology (Hematoxylin and Eosin, DAPI and Masson's Trichrome) and biochemical (DNA, sGAG and collagen) analyses. After the decellularization process of the bovine pericardium, composite pericardial tissues were prepared by incorporating -COOH-modified multiwalled carbon nanotubes (MWCNTs). Characterization of MWCNT incorporation was performed by ATR-FTIR, TGA, and mechanical analysis, while SEM and AFM were used for morphological evaluations. Thrombogenicity assessments were studied by platelet adhesion test, Calcein-AM staining, kinetic blood clotting, hemolysis, and cytotoxicity analyses. As a result of this study, the composite pericardial material revealed improved mechanical and thermal stability and hemocompatibility in comparison to decellularized pericardium, without toxicity. Approximately 100% success is achieved in preventing platelet adhesion. In addition, kinetic blood-coagulation analysis demonstrated a low rate and slow coagulation kinetics, while the hemolysis index was below the permissible limit for biomaterials.

摘要

在人工心脏瓣膜置换手术后,常发生血栓形成,导致瓣膜失效。即使长期使用抗凝药物也可能不足以预防血栓形成。本研究旨在通过在去细胞化牛心包中结合多壁碳纳米管来开发具有抗血栓形成特性和合适机械强度的心脏瓣膜结构。在这方面,通过使用冻融和十二烷基硫酸钠(SDS)的组合来进行去细胞化过程。通过组织学(苏木精和伊红、DAPI 和 Masson 三色)和生化(DNA、sGAG 和胶原蛋白)分析来确定去细胞化效率的评估。在牛心包的去细胞化过程之后,通过掺入-COOH 修饰的多壁碳纳米管(MWCNT)来制备复合心包组织。通过 ATR-FTIR、TGA 和机械分析来进行 MWCNT 掺入的表征,而 SEM 和 AFM 用于形态评估。通过血小板黏附试验、Calcein-AM 染色、动力学凝血、溶血和细胞毒性分析来研究血栓形成性。与去细胞化心包相比,复合心包材料显示出改善的机械和热稳定性以及血液相容性,而没有毒性。大约 100%成功地防止了血小板黏附。此外,动力学凝血分析显示出低速率和缓慢的凝血动力学,而溶血指数低于生物材料的允许限值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e145/9382671/fa8b4452c60e/mt2c00423_0001.jpg

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