丝素蛋白对聚左旋乳酸-共-ε-己内酯电纺丝支架体内降解及生物相容性的作用  

Effect of silk fibroin on degradation and in vivo biocompatibility of poly (L-lactic-co-ε-caprolactone) electronspun nanofibrous scaffolds

作　　者：程自申[1] 杨成伟[1] 刘莉[2] 杨洋[1] 邓国英[1] 叶晓健[1] 

机构地区：[1]第二军医大学长征医院骨科,上海200003 [2]河北省保定市第一中心医院妇产科,保定071000

出　　处：《第二军医大学学报》2015年第5期500-506,共7页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81472071)~~

摘　　要：目的探讨丝素蛋白(SF)对聚左旋乳酸-共-ε-己内酯[P(LLA-CL)]电纺丝支架的体内降解及生物相容性的作用。方法运用静电纺丝技术分别制备[P(LLA-CL),(w/w=1∶1)及混有含25%SF的P(LLA-CL)[SF/P(LLA-CL)]纳米纤维支架,将两种支架分别植入至45只6个月龄大鼠皮下6个月,以观察评估SF对P(LLA-CL)降解及生物相容性的影响。结果病理切片显示,支架植入3个月时,P(LLA-CL)支架明显肿胀,并开始分层,6个月时支架已支离破碎;而SF/P(LLA-CL)支架植入6个月时仍能保持相对完整的结构。免疫组化切片显示,在支架植入1个月时P(LLA-CL)支架表面及内部有大量的巨噬细胞,3个月时仍有大量的巨噬细胞,同时伴有异物巨细胞生成;而SF/P(LLA-CL)支架组巨噬细胞及异物巨细胞在各个时间点表达均不明显。炎症基因相对表达结果显示,在支架植入1周时P(LLA-CL)支架组TNF-α及IL-10相对表达高于SF/P(LLA-CL)支架组(P<0.05),1个月时P(LLA-CL)支架组TNF-α、IL-1β及IL-10相对表达高于SF/P(LLA-CL)支架组(P<0.05),2个月时P(LLA-CL)支架组TNF-α及IL-10相对表达高于SF/P(LLA-CL)支架组(P<0.05),3个月时P(LLA-CL)支架组TGF-β相对表达高于SF/P(LLA-CL)支架组(P<0.05),6个月时P(LLA-CL)支架组IL-1β及TGF-β相对表达高于SF/P(LLA-CL)支架组(P<0.05)。结论 SF能延缓P(LLA-CL)降解,减轻炎症反应,改善生物相容性。Objective To investigate the effect of silk fibroin （SF） on degradation and biocompatibility of poly （L-lactic acid-co-ε-caprolactone）（P[LLA-CL]） in vivo. Methods The scaffolds of P（LLA-CL） （w/w=l：1） blended with 25% of SF （SF/P[LLA-CL]） and P（LLA-CL） were prepared by electrospinning. Both kinds of scaffolds were subcutaneously implanted in 45 6-month-old rats for up to 6 months to evaluate their degradation and biocompatibility characteristics. Results Pathological sections showed P（LLA-CL） scaffold become swollen and began to separate into different layers after 3 months, and then become broken after 6 months while SF/P （LLA-CL） scaffold largely maintained its structure after 6 months. lmmunohistochemical staining showed a large number of macrophages on the surface and in P（LLA-CL） scaffolds 1 month after implantation, and they could still be found 3 months after implantation, accompanied by foreign body giant cells; while no obvious macrophages or foreign body giant cells were found in SF/P（LLA-CL） scaffolds at different time points. Examination of inflammatory gene expression showed that TNF-a and IL-10 expression in P（LLA-CL） scaffolds was significantly higher than that in SF/P（LLA-CL） scaffolds 1 week after implantation （P〈0. 05）, the same was also true for TNF-a, IL-lβ and IL-10 expression 1 month after implantation （P〈0. 05）, for TNF-a and IL-IO expression 2 months after implantation （P〈0. 05）,for TGF-β expression 3 months after implantation （P〈0. 05）, and for IL-Iβ and TGF-β expression 6 months after implantation （P〈0. 05）. Conclusion SF incorporation can delay degradation, reduce inflammation, and improve the biocompatibility of P（LLA-CL） scaffolds, which may provide reference for scaffold design in tissue engineering.

关 键 词：丝素蛋白 聚左旋乳酸-共-ε-己内酯 降解 炎症反应 巨噬细胞 异物巨细胞 生物相容性 

分 类 号：R318.1[医药卫生—生物医学工程]