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一种用于心肌梗死修复的新型可注射水凝胶
图1. 导电PEG-MEL/HA-SH/GO低模量可注射水凝胶制备及治疗大鼠心肌梗死的示意图 Biomaterials, 2017,122, 63-71. 心肌的本质是一种能传递电信号、刺激心脏跳动、交替进行扩展和收缩的电活性组织。虽然高模量的水凝胶有利于心肌梗死(MI）后心肌功能的修复，但由于低模量导电性水凝胶可以进行机械信号、电信号的传递，因此，更有利于心肌梗死后的再生修复和功能恢复。最近，天津大学材料科学与工程学院的刘文广教授研究团队首次将π-π共轭应用于制备具有低模量、导电性、可注射水凝胶中，以提高材料的导电性，进而用于大鼠心肌梗死后心脏功能的修复。凝胶的具体制备过程如下，首先通过迈克尔加成合成多臂交联剂PEGDA700-三聚氰胺（PEG-MEL）；接着通过点击反应和巯基改性的透明质酸（HA-SH），氧化石墨烯（GO）快速形成可注射水凝胶。制备的凝胶呈现出低模量（G’= 25Pa）、抗疲劳的机械性能和导电性能（G=2.84×10-4S/cm）；最后，在大鼠的MI区域注射载有脂肪组织来源的基质细胞(ADSC）的水凝胶。实验结果表明，材料对心肌功能的改善有很明显的作用，具体表现为显著提高α-平滑肌肌动蛋白（α-SMA）和连接蛋白43（Cx43）的表达，提高心脏的射血分数，减小心肌的梗死区域和纤维化面积，提高心肌内的血管密度等等。 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. Recently, Wenguang Liu who working in the school of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , made the following outcome. In this work, p-p conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with p-p 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 =2.84×10-4S/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 Con nexin 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. (闫欢欢）
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