自组装多肽凝胶联合可降解神经导管修复长节段周围神经损伤Combined used of self-assembly peptide and degradable nerve conduit for repair of peripheral nerve injury
张伟;岳靓;易红蕾;王传峰;陈家瑜;吴冰;魏显招;郯志清;李明;傅强;
摘要(Abstract):
[目的]探讨自组装多肽凝胶联合可降解神经导管修复长节段周围神经损伤的可行性及效果。[方法]选取新西兰大白兔48只,体重1 500 g左右,雌雄不限,按随机数字法分为A:自体神经移植组、B:神经导管+NSCs+NGF组、C:神经导管+IKVAV多肽凝胶+NSCs+NGF组;选取兔坐骨神经,暴露后人为造成10 mm缺损损伤,按照分组分别进行移植修复。术后3、6、9、12周观察兔下肢溃疡形成及愈合情况;术后12周对各组动物进行坐骨神经肌电图检查,处死后取标本观察神经再生情况、小腿三头肌湿重、组织学观察及神经干细胞存活情况。[结果]术后3组动物均出现不同程度的足底溃疡,恢复情况以A组最好,C组次之,B组最差。术后12周神经肌电图、肌肉湿重检测均显示自体神经移植组神经功能恢复良好,优于其余两组(P<0.05)。组织学观察显示C组神经再生情况接近自体神经移植组,明显优于B组。术后12周荧光显微镜下观察到在神经损伤处有绿色荧光蛋白(GFP)荧光表达,神经干细胞仍然存活。[结论]自组装多肽凝胶联合可降解神经导管修复长节段周围神经损伤可以取得良好的疗效。
关键词(KeyWords): 自组装多肽;神经导管;坐骨神经;神经干细胞;神经生长因子;组织工程
基金项目(Foundation): 国家自然科学基金面上项目(编号:30872629);; 全军医学科学技术基金十二五计划重点项目(编号:08G073)
作者(Author): 张伟;岳靓;易红蕾;王传峰;陈家瑜;吴冰;魏显招;郯志清;李明;傅强;
Email:
DOI:
参考文献(References):
- [1]Silva GA,Czeisler C,Niece KL,et al.Selective differentiation of neu-ral progenitor cells by high-epitope density nanofibers[J].Science,2004,5662:1352-1355.
- [2]Anderson DG,Burdick JA,Langer R.Smart biomaterials[J].Science,2004,5692:1923-1924.
- [3]Service RF.American chemical society meeting.Molecular scaffoldinghelps raise a crop of neurons[J].Science,2003,5642:46-47.
- [4]Tysseling-Mattiace VM,Sahni V,Niece KL,et al.Self-assemblingnanofibers inhibit glial scar formation and promote axon elongation af-ter spinal cord injury[J].J Neurosci,2008,14:3814-3823.
- [5]Kuo CK,Tuan RS.Tissue engineering with mesenchymal stem cells[J].IEEE Eng Med Biol Mag,2003,5:51-56.
- [6]Dezawa M,Takahashi I,Esaki M,et al.Sciatic nerve regeneration inrat induced by transplantation of in vitro differentiated bone-marrowstromal stem cells[J].Eur J Neurosci,2001,11:1171-1176.
- [7]侯赛云,朱家恺.大鼠骨髓基质干细胞体外诱导分化为类许旺细胞[J].中华显微外科杂志,2003,1:39-41.
- [8]侯赛云,朱家恺.经诱导的骨髓基质干细胞应用于组织工程化人工神经的实验研究[J].中华显微外科杂志,2003,2:112-115.
- [9]张伟,李明,傅强.静电纺丝纤维支架在神经组织工程中的应用进展[J].中华外科杂志,2010,20:1584-1587.
- [10]Gunatillake PA,Adhikari R.Biodegradable synthetic polymers for tis-sue engineering[J].Eur Cells Mater,2003,5:1-16.
- [11]蒋涛,任先军.组织工程脊髓支架材料的研究进展[J].中国矫形外科杂志,2010,15:1270-1273.
- [12]Hadlock T,Elisseeff J,Langer R,et al.A tissue engineered conduit forperipheral nerve repair[J].Arch Otolaryngol Head Neck Surg,1998,124:1081-1086.
- [13]Yoon SJ,Kim SH,Ha HJ,et al.Reduction of inflammatory reaction ofpoly(d,l-lactic-co-glycolic Acid)using demineralized bone particles[J].Tissue Eng Part A,2008,4:539-547.
- [14]Khor E,Lim LY.Implantable applications of chitin and hitosan[J].Biomaterials,2003,13:2339-2349.
- [15]Shieh SJ,Vacanti JP.State-of-the-art tissue engineering:from tissueengineering to organ building[J].Surgery,2005,1:1-7.
- [16]Smith RA,Orr DJ.The survival of adult mouse sensory neurons in vitrois enhanced by natural and synthetic substrata particularly fibronectin[J].J Neurosci Res,1987,3:265-270.
- [17]Chen YS,Hsieh CL,Tsai CC,et al.Peripheral nerve regeneration u-sing silicone rubber chambers filled with collagen,laminin and fi-bronectin[J].Biomaterials,2000,15:1541-1547.
- [18]Whitworth IH,Brown RA,Dore CJ,et al.Nerve growth factor enhancesnerve regeneration through fibronectin grafts[J].J Hand Surg Br,1996,4:514-522.