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Conjugating homogenized liver-extracellular matrix into decellularized hepatic scaffold for liver tissue engineering.
Journal of Biomedical Materials Research Part A ( IF 4.9 ) Pub Date : 2020-06-24 , DOI: 10.1002/jbm.a.36920
Tarek Saleh 1 , Ebtehal Ahmed 1 , Lina Yu 1 , Su-Hyeon Song 1 , Kyung-Mee Park 2 , Ho-Hyun Kwak 1 , Heung-Myong Woo 1
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The generation of a transplantable liver scaffold is crucial for the treatment of end‐stage liver failure. Unfortunately, decellularized liver scaffolds suffer from lack of bioactive molecules and functionality. In this study, we conjugated homogenized liver‐extracellular matrix (ECM) into a decellularized liver in a rat model to improve its structural and functional properties. The homogenized ECM was prepared, characterized, and subsequently perfused into ethyl carbodiimide hydrochloride (EDC)/N‐hydroxysuccinimide (NHS) activated liver scaffolds. Various techniques were performed to confirm the improvements that were accomplished through the conjugation process; these included micro/ultra‐structural analyses, biochemical analysis of ECM components, DNA quantification, swelling ratio, structural stability, calcification properties, platelet activation study, static and dynamic seeding with EAhy926 endothelial cells and HepG2 hepatocarcinoma cells, subcutaneous implantation and intrahepatic transplantation. The results showed that the conjugated scaffolds have superior micro‐ and ultrastructural and biochemical characteristics. In addition, DNA contents, swelling ratios, calcification properties, platelet reactions, and host inflammatory reactions were not altered with the conjugation process. The conjugated scaffolds revealed better cellular spreading and popularity compared to the non‐conjugated scaffolds. Intrahepatic transplantation showed that the conjugated scaffold had higher popularity of hepatic regenerative cells with better angiogenesis. The conjugation of the decellularized liver scaffold with homogenized liver‐ECM is a promising tool to improve the quality of the generated scaffold for further transplantation.

中文翻译:

将均质化的肝细胞外基质结合到用于肝组织工程的脱细胞肝支架中。

可移植肝支架的产生对于治疗终末期肝功能衰竭至关重要。不幸的是,脱细胞肝支架缺乏生物活性分子和功能。在这项研究中,我们将均质化的肝细胞外基质 (ECM) 结合到大鼠模型中的脱细胞肝脏中,以改善其结构和功能特性。制备、表征均质的 ECM,然后灌注到乙基碳化二亚胺盐酸盐 (EDC)/ N-羟基琥珀酰亚胺(NHS)激活肝脏支架。执行了各种技术以确认通过缀合过程实现的改进;这些包括微/超结构分析、ECM 成分的生化分析、DNA 定量、膨胀率、结构稳定性、钙化特性、血小板活化研究、EAhy926 内皮细胞和 HepG2 肝癌细胞的静态和动态接种、皮下植入和肝内移植。结果表明,共轭支架具有优异的微结构和超微结构以及生化特性。此外,结合过程未改变 DNA 含量、膨胀率、钙化特性、血小板反应和宿主炎症反应。与非共轭支架相比,共轭支架显示出更好的细胞扩散和普及性。肝内移植表明,结合支架具有更好的血管生成的肝再生细胞的普及率更高。脱细胞肝支架与均质肝 ECM 的结合是一种有前途的工具,可提高生成的支架质量以供进一步移植。
更新日期:2020-06-24
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