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一种含有π-π 共轭的柔软导电可注射聚合物水凝胶,可高效重建心肌梗死后的心脏功能。

A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction.

机构信息

School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300072, China.

School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300072, China.

出版信息

Biomaterials. 2017 Apr;122:63-71. doi: 10.1016/j.biomaterials.2017.01.012. Epub 2017 Jan 12.

Abstract

Previous studies suggested that a stiffer hydrogel system exhibited a better performance to promote heart function after myocardial infarction (MI). However, the nature of myocardium, a tissue that alternately contracts and relaxes with electrical impulses, leads us to hypothesize that a soft and conductive hydrogel may be in favor of mechanical and electrical signals transmission to enhance heart function after MI. In this work, π-π conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with π-π conjugation ring was used as a core to synthesize a multi-armed crosslinker PEGDA700-Melamine (PEG-MEL), which could crosslink with thiol-modified hyaluronic acid (HA-SH) to form an injectable hydrogel rapidly. By incorporating graphene oxide (GO), the injectable PEG-MEL/HA-SH/GO hydrogel exhibited a soft (G' = 25 Pa) and anti-fatigue mechanical property and conductive property (G = 2.84 × 10 S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in α-Smooth Muscle Actin (α-SMA) and Connexin 43 (Cx43) expression confirmed that the gel efficiently promoted the transmission of mechanical and electrical signals. Meanwhile, a significant improvement of heart functions, such as distinct increase of ejection fraction (EF), smaller infarction size, less fibrosis area, and higher vessel density, was achieved.

摘要

先前的研究表明,刚性水凝胶系统在促进心肌梗死后的心脏功能方面表现更好。然而,心肌的性质是一种通过电脉冲交替收缩和松弛的组织,这使我们假设,柔软且具有导电性的水凝胶可能有利于机械和电信号的传输,从而增强心肌梗死后的心脏功能。在这项工作中,首先利用π-π 共轭相互作用来制备具有导电性的柔软可注射水凝胶。具有π-π 共轭环的三聚氰胺被用作核心,合成了多臂交联剂 PEGDA700-三聚氰胺(PEG-MEL),它可以与巯基修饰的透明质酸(HA-SH)快速交联形成可注射水凝胶。通过掺入氧化石墨烯(GO),可注射的 PEG-MEL/HA-SH/GO 水凝胶表现出柔软(G'=25 Pa)和抗疲劳的机械性能以及导电性(G=2.84×10 S/cm)。将包封脂肪组织来源的基质细胞(ADSCs)的水凝胶注射到大鼠的心肌梗死区域。α-平滑肌肌动蛋白(α-SMA)和连接蛋白 43(Cx43)表达的显著增加证实了凝胶有效地促进了机械和电信号的传输。同时,心脏功能得到了显著改善,例如射血分数(EF)明显增加、梗死面积减小、纤维化面积减少和血管密度增加。

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