中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (15): 2315-2322.doi: 10.12307/2024.372

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

聚吡咯-壳聚糖导电复合水凝胶促进缺血-再灌注损伤后心脏功能的恢复

王馨竹1,王  琦1,郎丽敏2,何  生2   

  1. 1山西医科大学再生医学中心,出生缺陷与细胞再生山西省重点实验室,山西省太原市  030001;2山西医科大学第一医院影像科,山西省太原市  030001
  • 收稿日期:2023-03-02 接受日期:2023-06-05 出版日期:2024-05-28 发布日期:2023-09-19
  • 通讯作者: 何生,医学博士,主任医师,山西医科大学第一医院影像科,山西省太原市 030001
  • 作者简介:王馨竹,女,1998年生,辽宁省沈阳市人,汉族,硕士,主要从事心脏的再生治疗研究。
  • 基金资助:
    国家自然科学基金青年项目(81900279),项目负责人:何生;中国博士后基金面上项目(2021M691991),项目负责人:何生

Polypyrrole-chitosan conductive composite hydrogel promotes recovery of cardiac function after ischemia-reperfusion injury

Wang Xinzhu1, Wang Qi1, Lang Limin2, He Sheng2   

  1. 1Center for Regenerative Medicine, Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 2Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2023-03-02 Accepted:2023-06-05 Online:2024-05-28 Published:2023-09-19
  • Contact: He Sheng, MD, Chief physician, Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Wang Xinzhu, Master, Center for Regenerative Medicine, Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81900279 (to HS); China Postdoctoral Science Foundation, No. 2021M691991 (to HS)

摘要:


文题释义:

心肌缺血再灌注损伤:指冠状动脉部分或完全急性阻塞后,在一定时间又重新获得再通时,缺血心肌虽然得以恢复正常灌注,但其组织损伤反而呈进行性加重的病理过程。缺血期引起的心肌超微结构、能量代谢、心功能和电生理等一系列损伤性变化,在血管再通后表现得更为突出,甚至可发生严重的心律失常而导致猝死。
导电生物材料:被认为是传输心肌修复电信号的潜在候选者。其中,导电水凝胶表现出类似于正常心脏组织的机械和电性能,可以促进心脏收缩/松弛功能和电耦合,诱导梗死心脏心肌细胞的成熟,并防止其进展为心律失常。


背景:导电生物材料被认为是传输心肌修复电信号的潜在候选者,将基于细胞或无细胞的策略与导电生物材料相结合以补充心肌细胞和/或恢复电信号通路,成为一种有前途的心脏修复方法。

目的:评估聚吡咯-壳聚糖导电复合水凝胶对心肌缺血-再灌注损伤大鼠心功能的改善作用。
方法:采用化学氧化聚合法制备聚吡咯-壳聚糖导电复合水凝胶,表征水凝胶的微观形貌、生物相容性与导电性。取30只成年SD大鼠,利用夹闭心脏左前降支后再松解的方法建立心肌缺血-再灌注损伤模型,造模21 d后,采用随机数字表法将大鼠分为3组:空白组向左心室梗死区及梗死边缘区内注射生理盐水,普通水凝胶组向左心室梗死区及梗死边缘区内注射壳聚糖水凝胶,导电水凝胶组向左心室梗死区及梗死边缘区内注射聚吡咯-壳聚糖导电复合水凝胶,每组10只。设置造模后对应的时间点,分别进行心脏机械功能(超声心动图、压力-体积分析)、心脏电生理(心电图、程序性电刺激、光学映射技术、微电极阵列技术评估、八导联心电图、瘢痕区电阻率)及心脏组织学检测。

结果与结论:①导电复合水凝胶表面存在大量孔隙,导电率为(3.19±0.03)×10-3 mS/cm,与平滑肌细胞共培养具有良好的生物相容性。②造模后105 d的超声心动图与压力-体积分析检测显示,与空白组、普通水凝胶组比较,导电复合水凝胶可明显改善心肌缺血-再灌注损伤大鼠心脏的收缩功能。造模后105 d的心电图、程序性电刺激、光学映射技术、微电极阵列技术评估、八导联心电图、瘢痕区电阻率检查结果显示,与空白组、普通水凝胶组比较,导电复合水凝胶可明显改善心肌缺血-再灌注损伤大鼠心脏的电传导功能,降低心律失常的发生。造模后105 d的心脏组织Masson染色显示,3组大鼠心肌梗死区均出现不同程度的纤维化,与生理盐水组和普通水凝胶组相比,导电水凝胶组梗死区正常心肌组织较多、纤维化程度较小。③结果表明,聚吡咯-壳聚糖导电复合水凝胶可能通过提高梗死瘢痕区组织电传导速度、增加瘢痕厚度、增强心脏同步收缩、减少受损组织来促进缺血-再灌注损伤后梗死心肌的修复。

https://orcid.org/0009-0004-6075-7184(王馨竹)

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性组织工程

关键词: 导电生物材料, 聚吡咯, 壳聚糖, 水凝胶, 缺血-再灌注损伤, 心脏组织工程

Abstract: BACKGROUND: Conductive biomaterials are considered potential candidates for transmitting electrical signals for myocardial repair. Combining cell-based or cell-free strategies with conductive biomaterials to replenish cardiomyocytes and/or restore electrical signaling pathways is a promising approach for cardiac repair.
OBJECTIVE: To evaluate the effect of polypyrrole-chitosan conductive composite hydrogel on cardiac function in rats with myocardial ischemia-reperfusion injury.
METHODS: The polypyrrole-chitosan conductive composite hydrogel was prepared by chemical oxidative polymerization. The micromorphology, biocompatibility and conductivity of the hydrogels were characterized. Thirty adult SD rats were selected to establish a myocardial ischemia-reperfusion injury model by clamping the left anterior descending branch of the heart and then releasing it. After 21 days of modeling, the rats were divided into three groups by the random number table method: Normal saline was injected into the left ventricular infarction area and infarction margin area in the blank group. Chitosan hydrogel was injected into the left ventricular infarction area and infarction margin area in the ordinary hydrogel group. The polypyrrole-chitosan conductive composite hydrogel was injected into the left ventricular infarction area and infarction margin area, with 10 rats in each group. The corresponding time points after modeling were set, and cardiac mechanical function (echocardiogram, pressure-volume analysis), cardiac electrophysiology (electrocardiogram, programmed electrical stimulation, optical mapping technology, microelectrode array technology, eight-lead electrocardiogram, and electrical resistivity of the scar area) and cardiac histology were detected. 
RESULTS AND CONCLUSION: (1) There were a lot of pores on the surface of the conductive composite hydrogel, and the conductivity was (3.19±0.03)×10-3 mS/cm, which had good biocompatibility co-cultured with smooth muscle cells. (2) After 105 days of modeling, echocardiogram and pressure-volume analysis showed that compared with the blank group and the ordinary hydrogel group, the conductive composite hydrogel could significantly improve the contractile function of the heart of rats with myocardial ischemia-reperfusion injury. The results of electrocardiogram, programmed electrical stimulation, optical mapping technology, microelectrode array technology, eight-lead electrocardiogram, and electrical resistivity of the scar area examination at 105 days after modeling displayed that, compared with the blank group and the ordinary hydrogel group, the conductive composite hydrogel could significantly improve the electrical conduction function of the heart of rats with myocardial ischemia-reperfusion injury and reduce the occurrence of arrhythmia. Masson staining of heart tissue at 105 days after modeling exhibited that there were different degrees of fibrosis in the myocardial infarction area of the three groups. Compared with the normal saline group and the ordinary hydrogel group, the conductive hydrogel group had more normal myocardial tissue and less fibrosis in the myocardial infarction area. (3) The results verify that polypyrrole-chitosan conductive composite hydrogel may promote the repair of infarcted heart after ischemia-reperfusion injury by increasing the electrical conduction velocity of infarct scar area tissue, increasing scar thickness, enhancing synchronous cardiac contraction, and reducing damaged tissue. 

Key words: conductive biomaterial, polypyrrole, chitosan, hydrogel, ischemia-reperfusion injury, cardiac tissue engineering

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