控释神经生长因子的阵列微管促进神经再生Nerve scaffold with longitudinally oriented micro-channels and controlled-release of NGF for promoting peripheral nerve regeneration
石晓伟,黄亮亮,夏冰,高楗勃,杨雨洁,罗卓荆,黄景辉
摘要(Abstract):
[目的]制备可控释神经生长因子(nerve growth factor, NGF)的阵列微管神经修复支架,并评价其促神经再生效能。[方法]采用梯度冷凝技术制备复合NGF的阵列微管神经修复支架,检测其机械特性和NGF释放规律。将新生SD大鼠的背根神经节(dorsal root ganglions, DRG)随机分为4组:无序支架组、复合NGF的无序支架组、阵列微管支架组和复合NGF的阵列微管支架组。将DRG植入各组支架中体外培养72 h,观察轴突生长情况。[结果]在机械强度方面,各组在横向压缩过程中的峰值载荷差异无统计学意义(P>0.05)。纵向牵拉测试中,神经支架组与自体神经组的应力-应变曲线类似。在NGF释放规律方面,阵列微管组和无序组的释放曲线类似,且不同时间点NGF浓度差异无统计意义(P>0.05)。在轴突生长方面,复合NGF的阵列微管支架组轴突长度为(1 025.41±175.33)μm,显著高于阵列微管支架组(857.58±233.14)μm、复合NGF无序支架组(341.73±52.27)μm、无序支架组(225.36±61.62)μm。[结论]复合NGF的阵列微管神经修复支架同时具有营养活性及引导结构,且具有良好的机械性能,在体外环境下可以引导大鼠DRG轴突定向延伸,在周围神经再生领域具有重要前景。
关键词(KeyWords): 丝素蛋白;神经生长因子;阵列微管;神经支架;背根神经节
基金项目(Foundation): 国家自然科学基金项目(编号:81672148;81201389);; 国家重点研发计划项目(编号:2016YFC1101700);; 国家重点基础研究项目(973计划,编号:2014CB542206);; 长江学者和创新发展团队计划项目(编号:IRT1053;IRT13051);; 全国优秀博士论文基金项目(编号:201480)
作者(Author): 石晓伟,黄亮亮,夏冰,高楗勃,杨雨洁,罗卓荆,黄景辉
参考文献(References):
- [1]Gaudin R,Knipfer C,Henningsen A,et al.Approaches to peripheral nerve repair:generations of biomaterial conduits yielding to replacing autologous nerve grafts in craniomaxillofacial surgery[J].Biomed Res Int,2016,2016(1-18):1-10.
- [2]Lohmeyer J,Siemers F,Machens H,et al.The clinical use of artificial nerve conduits for digital nerve repair:A prospective cohort study and literature review[J].J Reconstr Microsurg,2009,25(1):55-61.
- [3]Daly WT,Yao L,Abu-rub MT,et al.The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair[J].Biomaterials,2012,33(28):6660-6671.
- [4]Kim Y,Haftel VK,Kumar S,et al.The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps[J].Biomaterials,2008,29(21):3117-3127.
- [5]Cai J,Peng X,Nelson KD,et al.Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation[J].J Biomed Mater Res a,2005,75A(2):374-386.
- [6]Madduri S,Gander B.Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration[J].JPNS,2010,15(2):93-103.
- [7]Blesch A.Neurotrophic factors in neurodegeneration[J].Brain pathology(Zurich,Switzerland),2006,16(4):295-303.
- [8]Ramburrun P,Kumar P,Choonara YE,et al.A review of bioactive release from nerve conduits as a neurotherapeutic strategy for neuronal growth in peripheral nerve injury[J].Biomed Res Int,2014,2014:1-19.
- [9]Muheremu A,Ao Q.Past,present,and future of nerve conduits in the treatment of peripheral nerve injury[J].Biomed Res Int,2015,237507:1-10.
- [10]Li R,Liu Z,Pan Y,et al.Peripheral nerve injuries treatment:a systematic review[J].Cell Biochem Biophys,2014,68(3):449-454.
- [11]朱庆棠,郑灿镔,刘小林.周围神经缺损修复材料临床适应证的考虑[J].中华显微外科杂志,2013,(5):417-421.
- [12]Houdek MT,Shin AY.Management and complications of traumatic peripheral nerve injuries[J].Hand Clin,2015,31(2):151.
- [13]陈勇,范林,付贞,等.神经导管支架修复外周神经损伤的研究与现状[J].中国组织工程研究,2017,(30):4901-4907.
- [14]Dinis TM,Elia R,Vidal G,et al.3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration[J].J Mech Behav Biomed,2015,41(1):43-55.
- [15]Uebersax L,Mattotti M,Papaloizos M,et al.Silk fibroin matrices for the controlled release of nerve growth factor(NGF)[J].Biomaterials,2007,28(30):4449-4460.
- [16]Fan L,Li J,Cai Z,et al.Creating biomimetic anisotropic architectures with Co-Aligned nanofibers and macrochannels by manipulating ice crystallization[J].Acs Nano,2018,1:2-11.
- [17]Wu H,Fang Q,Liu J,et al.Multi-tubule conduit-filler constructs loaded with gradient-distributed growth factors for neural tissue engineering applications[J].Mech Behav Biomed,2018,77:671-682.
- [18]Wenk E,Merkle HP,Meinel L.Silk fibroin as a vehicle for drug delivery applications[J].J Control Release,2011,150(2):128-141.
- [19]Catrina S,Gander B,Madduri S.Nerve conduit scaffolds for discrete delivery of two neurotrophic factors[J].Eur J Pharm Biopharm,2013,85(1):139-142.