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核黄素光交联法提高生物心脏瓣膜中弹性蛋白稳定性和减少钙化。

Riboflavin photo-cross-linking method for improving elastin stability and reducing calcification in bioprosthetic heart valves.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.

出版信息

Xenotransplantation. 2019 Mar;26(2):e12481. doi: 10.1111/xen.12481. Epub 2019 Jan 4.

DOI:10.1111/xen.12481
PMID:30609151
Abstract

BACKGROUND

Glutaraldehyde cross-linked bioprosthetic heart valves might fail due to progressive degradation and calcification.

METHODS

In this study, we developed a new BHVs preparation strategy named as "HPA/TRA/FMN" that utilized 3,4-hydroxyphenylpropionic acid (HPA)/tyramine (TRA) conjugated pericardium and riboflavin 5'-monophosphate (FMN) initiated photo-cross-linking method. HPA/TRA-pericardium conjugation would provide extra phenol groups for FMN initiated photo-cross-linking.

RESULTS

The feeding ratio of riboflavin 5'-monophosphate was optimized. The collagenase and elastase enzymatic degradation in vitro, biomechanics, calcification, elastin stability in vivo, and macrophage marker CD68 were characterized. We demonstrated that riboflavin photo-cross-linked pericardiums had great collagen and elastin stability, improved mechanical properties, better resistance for calcification, and less CD68 positive macrophages in rat subdermal implantation study.

CONCLUSIONS

This new riboflavin photo-cross-linking strategy would be a promising method to make BHVs which have better elastin stability, less calcification, and reduced inflammatory response.

摘要

背景

戊二醛交联生物瓣可能由于渐进性降解和钙化而失效。

方法

在这项研究中,我们开发了一种新的 BHVs 制备策略,名为“HPA/TRAFMN”,该策略利用了 3,4- 羟基苯丙酸(HPA)/酪胺(TRA)共轭心包和核黄素 5'-单磷酸(FMN)引发的光交联方法。HPA/TRA-心包的缀合将为 FMN 引发的光交联提供额外的酚基。

结果

优化了核黄素 5'-单磷酸的进料比。对胶原酶和弹性蛋白酶的体外降解、生物力学、钙化、体内弹性蛋白稳定性以及巨噬细胞标志物 CD68 进行了表征。我们证明,核黄素光交联的心包膜具有更好的胶原和弹性蛋白稳定性、改善的机械性能、更好的抗钙化能力,以及在大鼠皮下植入研究中 CD68 阳性巨噬细胞较少。

结论

这种新的核黄素光交联策略将是一种有前途的制备 BHVs 的方法,具有更好的弹性蛋白稳定性、更少的钙化和减轻炎症反应。

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