Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth.
Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth.
复制标题
具有高特征频率的光聚合微图案克服了化学脉冲边界以引导神经突生长。
DOI：
10.1002/term.2527
复制
发表时间：
2018
影响因子：
3.3
通讯作者：
Hansen,MarlanR
中科院分区：
文献类型：
--
作者：
Tuft,BradleyW;Xu,Linjing;Leigh,Braden;Lee,Daniel;Guymon,CAllan;Hansen,MarlanR
发育和再生的神经突响应于其微环境中的各种生物物理和生物化学线索，以到达靶细胞并建立适当的突触。定义这两种类型的线索的层次关系，以指导神经突起的生长进行神经发育，再生，特别是工程的神经假体，提高组织与天然神经网络的整合具有广泛的意义。在这项工作中，化学排斥的生化边界上建立了一系列的表面微观特征，以确定潜在的物理线索，以克服冲突的生化线索的基板。使用光掩模技术制造物理微图案以在空间上控制聚合的光引发事件。反应的时间控制允许在特征频率或周期性的范围内产生具有相同幅度的微特征。然后用层粘连蛋白与EphA 4-Fc或腱生蛋白C之间的排斥性化学边界修饰微图案化基底，所述排斥性化学边界与表面微特征竞争以指导神经突生长。螺旋神经节和三叉神经元的神经突的行为在生化边界上以交叉、转向、停止或排斥事件为特征。化学边界和物理模式显着影响神经突寻路。在未图案化的表面上，大多数起源于层粘连蛋白的神经突被腱生蛋白C或EphA 4-Fc的边界所阻止。重要的是，具有频繁的微图案特征的基底克服了化学排斥边界的影响，以主导神经突轨迹。设计具有适当表面特征的假体界面可以允许体内空间组织的神经突生长，即使在天然靶组织中存在冲突的生化线索。
Developing and regenerating neurites respond to a variety of biophysical and biochemical cues in their micro‐environment to reach target cells and establish appropriate synapses. Defining the hierarchal relationship of both types of cues to direct neurite growth carries broad significance for neural development, regeneration, and, in particular, engineering of neural prostheses that improve tissue integration with native neural networks. In this work, chemorepulsive biochemical borders are established on substrates with a range of surface microfeatures to determine the potential of physical cues to overcome conflicting biochemical cues. Physical micropatterns are fabricated using photomasking techniques to spatially control photoinitiation events of the polymerization. Temporal control of the reaction allows for generation of microfeatures with the same amplitude across a range of feature frequencies or periodicities. The micropatterned substrates are then modified with repulsive chemical borders between laminin and either EphA4‐Fc or tenascin C that compete with the surface microfeatures to direct neurite growth. Behaviour of neurites from spiral ganglion and trigeminal neurons is characterized at biochemical borders as cross, turn, stop, or repel events. Both the chemical borders and physical patterns significantly influence neurite pathfinding. On unpatterned surfaces, most neurites that originate on laminin are deterred by the border with tenascin C or EphA4‐Fc. Importantly, substrates with frequent micropattern features overcome the influence of the chemorepulsive border to dominate neurite trajectory. Designing prosthesis interfaces with appropriate surface features may allow for spatially organized neurite outgrowth in vivo even in the presence of conflicting biochemical cues in native target tissues.