Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis.
Coiled polymeric growth factor gradients for multi-luminal neural chemotaxis.
复制标题
DOI：
10.1016/j.brainres.2015.01.055
复制
发表时间：
2015-09-04
期刊：
影响因子：
2.9
通讯作者：
Romero-Ortega MI
中科院分区：
文献类型：
--
作者：
Alsmadi NZ;Patil LS;Hor EM;Lofti P;Razal JM;Chuong CJ;Wallace GG;Romero-Ortega MI
在受损的成人神经系统中，重建促进生长的分子梯度可以诱导和引导神经修复。然而，在神经修复支架中结合三维趋化梯度，特别是在具有多腔结构的支架中，仍然极具挑战性。我们开发了一种方法，通过将释放生长因子的卷曲聚合物纤维锚定到胶原填充的水凝胶微通道的壁上，在多腔神经导管中建立高度可调的三维分子梯度。神经营养蛋白洗脱纤维卷曲的不同螺距产生持续的趋化梯度，随着神经生长因子（NGF）浓度的增加，适当地诱导嗜铬细胞瘤（PC12）细胞分化为神经样细胞。计算机模型估计了管腔胶原蛋白内分子梯度的稳定性，我们通过观察神经营养蛋白梯度对背根神经节（DRG）轴突生长的显着影响证实了这一点。与用线性生长因子浓度处理的神经元相比，在暴露于 NGF 梯度的微通道中生长的神经元的轴突长度增加了 60%。此外，观察到微通道内轴突生长的线性度增加了两倍，并通过单个轴突转角比的显着降低证实了这一点。这些数据证明了负载生长因子的聚合物卷曲纤维能够建立三维趋化梯度，以促进和指导神经系统中的神经再生，并为分子引导的组织修复提供独特的平台。
In the injured adult nervous system, re-establishment of growth-promoting molecular gradients is known to entice and guide nerve repair. However, incorporation of three-dimensional chemotactic gradients in nerve repair scaffolds, particularly in those with multi-luminal architectures, remains extremely challenging. We developed a method that establishes highly tunable three-dimensional molecular gradients in multi-luminal nerve guides by anchoring growth-factor releasing coiled polymeric fibers onto the walls of collagen-filled hydrogel microchannels. Differential pitch in the coiling of neurotrophin-eluting fibers generated sustained chemotactic gradients that appropriately induced the differentiation of Pheochromocytoma (PC12) cells into neural-like cells along an increasing concentration of nerve growth factor (NGF). Computer modeling estimated the stability of the molecular gradient within the luminal collagen, which we confirmed by observing the significant effects of neurotrophin gradients on axonal growth from dorsal root ganglia (DRG). Neurons growing in microchannels exposed to a NGF gradient showed a 60% increase in axonal length compared to those treated with a linear growth factor concentration. In addition, a two-fold increment in the linearity of axonal growth within the microchannels was observed and confirmed by a significant reduction in the turning angle ratios of individual axons. These data demonstrate the ability of growth factor-loaded polymeric coiled fibers to establish three-dimensional chemotactic gradients to promote and direct nerve regeneration in the nervous system and provides a unique platform for molecularly guided tissue repair.
登录
查看更多内容
DOI：
10.1523/jneurosci.2973-12.2013
发表时间：
2013-03-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Deng LX;Deng P;Ruan Y;Xu ZC;Liu NK;Wen X;Smith GM;Xu XM
通讯作者：
Xu XM
影响因子：
5.3
作者：
Hu, Xinhua;Cai, Jie;Yang, Jun;Smith, George M.
通讯作者：
Smith, George M.
影响因子：
3.4
作者：
Boyd, JG;Gordon, T
通讯作者：
Gordon, T
影响因子：
4.1
作者：
Gordon, Tessa
通讯作者：
Gordon, Tessa
DOI：
10.1002/neu.20075
发表时间：
2005-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Adams, DN;Kao, EYC;Letourneau, PC
通讯作者：
Letourneau, PC