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

A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction
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DOI:
10.1016/j.biomaterials.2017.01.012
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发表时间:
2017-04-01
期刊:
影响因子:
14
通讯作者:
Liu, Wenguang
Liu, Wenguang
中科院分区:
工程技术1区
文献类型:
--
作者:
Bao, Rui;Tan, Baoyu;Liu, Wenguang

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先前的研究表明,较硬的水凝胶系统表现出更好的性能,以促进心肌梗死(MI)后的心脏功能。然而,心肌的性质,一个组织,交替收缩和放松与电脉冲,使我们假设,一个软的和导电的水凝胶可能有利于机械和电信号的传输,以增强心肌梗死后的心脏功能。在这项工作中,π-π共轭相互作用首次用于生产具有导电性能的软可注射水凝胶。以具有π-π共轭环的三聚氰胺为核,合成了多臂交联剂PEGDA 700-三聚氰胺(PEG-MEL),该交联剂可与巯基化透明质酸(HA-SH)快速交联形成可注射水凝胶。通过引入氧化石墨烯(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和导电性能(G = 2.84 X 10(-4)S/cm)。将包裹脂肪组织来源的基质细胞(ADSCs)的水凝胶注射到大鼠MI区。cc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递。心功能明显改善,射血分数(EF)明显增加,梗死面积缩小,纤维化面积减少,血管密度增加。(C)2017爱思唯尔有限公司版权所有
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, pi-pi conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with pi-pi 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 x 10(-4) S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in cc Smooth Muscle Actin (alpha-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. (C) 2017 Elsevier Ltd. All rights reserved.