【摘要】：心肌瘢痕是指心肌梗死后死亡的心肌細(xì)胞纖維化形成的瘢痕區(qū),無(wú)法自我修復(fù),可導(dǎo)致心臟功能障礙、心室重構(gòu)、漸進(jìn)性心力衰竭。對(duì)于心肌瘢痕目前無(wú)成熟的治療手段,研究表明心肌內(nèi)干細(xì)胞注射療法和心臟再同步化治療法(cardiac resynchronization therapy,CRT)對(duì)恢復(fù)心肌功能都有一定效果,但接受再同步化療法的患者中仍有三分之一的心臟功能無(wú)明顯改善,干細(xì)胞注射療法則由于干細(xì)胞低歸巢率、存活率等原因使干細(xì)胞注射療法只能在短期內(nèi)改善心臟功能。殼聚糖/甘油磷酸鈉(chitosan/glycerophosphate,CS/GP)溫敏凝膠具有良好的生物相容性,已被廣泛應(yīng)用與組織工程領(lǐng)域的研究中,是優(yōu)秀的組織工程支架材料,但其力學(xué)性能軟而弱,遠(yuǎn)不及心肌所處力學(xué)環(huán)境。本課題擬通過(guò)對(duì)CS/GP凝膠改性,增強(qiáng)其力學(xué)性能,以構(gòu)建一種具有能與干細(xì)胞一同注射至瘢痕區(qū)的,原位成型潛力的心肌組織工程支架材料,以提高干細(xì)胞歸巢率及存活率。將羥丙基甲基纖維素(HPMC)、納米絲素蛋白(n SF)、聚乙二醇(PEG)分別與殼聚糖/甘油磷酸鈉體系進(jìn)行液相共混,用倒置法評(píng)價(jià)共混后復(fù)合體系的在37℃下15min內(nèi)的凝膠轉(zhuǎn)變能力,結(jié)果顯示n SF對(duì)復(fù)合體系凝膠轉(zhuǎn)變行為有抑制作用;HPMC的添加增加體系粘度,但對(duì)體系凝膠轉(zhuǎn)變速度無(wú)明顯影響;PEG可加快體系凝膠轉(zhuǎn)變速度。幾種凝膠材料的斷裂強(qiáng)度及斷裂伸長(zhǎng)率數(shù)據(jù)顯示:向CS/GP溫敏體系中加入PEG后,凝膠材料的力學(xué)性能提高最為明顯。掃描電鏡圖像顯示CS/GP/PEG凝膠材料具有作為組織工程支架材料所必須的貫通性多孔結(jié)構(gòu)。紅外光譜分析結(jié)果認(rèn)為PEG與CS/GP之間無(wú)化學(xué)鍵合,以物理交聯(lián)為主�；谏鲜鲅芯�,選擇CS/GP/PEG、CS/GP/PEG/n SF作為主要對(duì)象,以CS/GP作為對(duì)照評(píng)價(jià)其生物學(xué)性能。四周體外降解試驗(yàn)顯示復(fù)合材料在模擬體液環(huán)境下的降解速率較慢,但體系中的甘油磷酸鈉會(huì)在短期內(nèi)快速溶出造成材料在第一周迅速失重;聚乙二醇可減慢材料降解速度;納米絲素蛋白可加快材料的降解速度。溶血實(shí)驗(yàn)及血小板粘附實(shí)驗(yàn)顯示CS/GP、CS/GP/PEG和CS/GP/PEG/n SF三種材料都具有良好的血液相容性。細(xì)胞毒性實(shí)驗(yàn)評(píng)價(jià)結(jié)果表明三種復(fù)合凝膠材料的浸提液對(duì)L-929細(xì)胞無(wú)細(xì)胞毒性,且有促生長(zhǎng)作用,但浸提液濃度過(guò)高時(shí)促細(xì)胞生長(zhǎng)作用會(huì)降低。全身毒性試驗(yàn)的結(jié)果顯示復(fù)合凝膠材料的浸提液對(duì)SD大鼠無(wú)全身急性毒性。研究表明,CS/GP/PEG復(fù)合材料具有作為體內(nèi)成型的組織工程支架材料和應(yīng)用于心肌疤痕修復(fù)的潛力。
[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，

本文編號(hào)：2284564