基于心肌瘢痕修复用组织工程支架的构建及性能研究
发布时间：2018-10-21 08:38
【摘要】：心肌瘢痕是指心肌梗死后死亡的心肌细胞纤维化形成的瘢痕区,无法自我修复,可导致心脏功能障碍、心室重构、渐进性心力衰竭。对于心肌瘢痕目前无成熟的治疗手段,研究表明心肌内干细胞注射疗法和心脏再同步化治疗法(cardiac resynchronization therapy,CRT)对恢复心肌功能都有一定效果,但接受再同步化疗法的患者中仍有三分之一的心脏功能无明显改善,干细胞注射疗法则由于干细胞低归巢率、存活率等原因使干细胞注射疗法只能在短期内改善心脏功能。壳聚糖/甘油磷酸钠(chitosan/glycerophosphate,CS/GP)温敏凝胶具有良好的生物相容性,已被广泛应用与组织工程领域的研究中,是优秀的组织工程支架材料,但其力学性能软而弱,远不及心肌所处力学环境。本课题拟通过对CS/GP凝胶改性,增强其力学性能,以构建一种具有能与干细胞一同注射至瘢痕区的,原位成型潜力的心肌组织工程支架材料,以提高干细胞归巢率及存活率。将羟丙基甲基纤维素(HPMC)、纳米丝素蛋白(n SF)、聚乙二醇(PEG)分别与壳聚糖/甘油磷酸钠体系进行液相共混,用倒置法评价共混后复合体系的在37℃下15min内的凝胶转变能力,结果显示n SF对复合体系凝胶转变行为有抑制作用;HPMC的添加增加体系粘度,但对体系凝胶转变速度无明显影响;PEG可加快体系凝胶转变速度。几种凝胶材料的断裂强度及断裂伸长率数据显示:向CS/GP温敏体系中加入PEG后,凝胶材料的力学性能提高最为明显。扫描电镜图像显示CS/GP/PEG凝胶材料具有作为组织工程支架材料所必须的贯通性多孔结构。红外光谱分析结果认为PEG与CS/GP之间无化学键合,以物理交联为主。基于上述研究,选择CS/GP/PEG、CS/GP/PEG/n SF作为主要对象,以CS/GP作为对照评价其生物学性能。四周体外降解试验显示复合材料在模拟体液环境下的降解速率较慢,但体系中的甘油磷酸钠会在短期内快速溶出造成材料在第一周迅速失重;聚乙二醇可减慢材料降解速度;纳米丝素蛋白可加快材料的降解速度。溶血实验及血小板粘附实验显示CS/GP、CS/GP/PEG和CS/GP/PEG/n SF三种材料都具有良好的血液相容性。细胞毒性实验评价结果表明三种复合凝胶材料的浸提液对L-929细胞无细胞毒性,且有促生长作用,但浸提液浓度过高时促细胞生长作用会降低。全身毒性试验的结果显示复合凝胶材料的浸提液对SD大鼠无全身急性毒性。研究表明,CS/GP/PEG复合材料具有作为体内成型的组织工程支架材料和应用于心肌疤痕修复的潜力。
[Abstract]:Myocardial scar refers to the scar area formed by myocardial fibrosis after myocardial infarction, which can lead to cardiac dysfunction, ventricular remodeling and progressive heart failure. There is no mature treatment for myocardial scar at present. Studies have shown that both intracardiac stem cell injection therapy and cardiac resynchronization therapy (cardiac resynchronization therapy,CRT) have certain effects on the recovery of myocardial function. However, 1/3 of the patients receiving resynchronization therapy had no significant improvement in cardiac function. Stem cell injection therapy could only improve cardiac function in the short term due to the low homing rate and survival rate of stem cells. Chitosan / sodium glycerophosphate (chitosan/glycerophosphate,CS/GP) thermo-sensitive gel has been widely used in the field of tissue engineering because of its good biocompatibility. It is an excellent scaffold material for tissue engineering, but its mechanical properties are soft and weak. It is far from the mechanical environment in which the myocardium is located. In order to improve the homing rate and survival rate of stem cells, we intend to improve their mechanical properties by modifying the gel of CS/GP to construct a scaffold with potential in situ forming of myocardial tissue engineering, which can be injected into scar region with stem cells. The hydroxy propyl methyl cellulose (HPMC),) nano-silk fibroin (n SF), polyethylene glycol (PEG) was blended with chitosan / sodium glycerophosphate in liquid phase respectively. The gel transition ability of the blend system in 15min at 37 鈩，
本文编号：2284564
[Abstract]:Myocardial scar refers to the scar area formed by myocardial fibrosis after myocardial infarction, which can lead to cardiac dysfunction, ventricular remodeling and progressive heart failure. There is no mature treatment for myocardial scar at present. Studies have shown that both intracardiac stem cell injection therapy and cardiac resynchronization therapy (cardiac resynchronization therapy,CRT) have certain effects on the recovery of myocardial function. However, 1/3 of the patients receiving resynchronization therapy had no significant improvement in cardiac function. Stem cell injection therapy could only improve cardiac function in the short term due to the low homing rate and survival rate of stem cells. Chitosan / sodium glycerophosphate (chitosan/glycerophosphate,CS/GP) thermo-sensitive gel has been widely used in the field of tissue engineering because of its good biocompatibility. It is an excellent scaffold material for tissue engineering, but its mechanical properties are soft and weak. It is far from the mechanical environment in which the myocardium is located. In order to improve the homing rate and survival rate of stem cells, we intend to improve their mechanical properties by modifying the gel of CS/GP to construct a scaffold with potential in situ forming of myocardial tissue engineering, which can be injected into scar region with stem cells. The hydroxy propyl methyl cellulose (HPMC),) nano-silk fibroin (n SF), polyethylene glycol (PEG) was blended with chitosan / sodium glycerophosphate in liquid phase respectively. The gel transition ability of the blend system in 15min at 37 鈩，
本文编号：2284564
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