Effects of collagen 1, fibronectin, laminin and hyaluronic acid concentration in multi-component gels on neurite extension
Effects of collagen 1, fibronectin, laminin and hyaluronic acid concentration in multi-component gels on neurite extension
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DOI：
10.1163/156856207781494377
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Schmidt, Christine E.
中科院分区：
文献类型：
--
作者：
Deister, Curt;Aljabari, Samer;Schmidt, Christine E.
周围神经损伤后的恢复仍然是一个重大的挑战。细胞外基质蛋白和细胞外基质组分的水凝胶已经显示出改善周围神经神经再生模型中的再生，特别是在长距离上。水凝胶的化学性质、配体身份和密度以及机械性质可以影响神经突延伸。然而，在几种细胞外基质组分的共凝胶中不同组分之间的组合效应的重要性尚不清楚。在这项研究中，我们研究了神经突起的延伸，从再生的背根神经节内培养的共凝胶由层粘连蛋白，纤连蛋白，胶原蛋白1和透明质酸。层粘连蛋白有一个强大的，剂量依赖性的影响神经突起的长度和生长。纤连蛋白对神经突起延伸有轻微的抑制作用，但一般不显著。胶原1和透明质酸的浓度对神经突起的延伸没有显著影响。四种组分间的组合效应是加性而非协同效应。用1.5mg/ml胶原蛋白1和1.5mg/ml层粘连蛋白制成的共凝胶在本研究中是最佳的，导致平均神经突长度为1532 +/-91 μ m，而对照组为976 +/-32 μ m，总体积生长（反映神经突长度和分支）比对照组增加85.9 +/-9.3%。这种共凝胶提供了具有高配体密度和生物化学亲和力的机械稳定的支架。本研究的结果支持使用层粘连蛋白和胶原蛋白1的共凝胶促进周围神经损伤的再生，并表明水凝胶组分之间的相互作用并不显著。
Recovery after peripheral nerve injury remains a significant challenge. Extracellular matrix proteins and hydrogels of extracellular matrix components have been shown to improve regeneration in peripheral nerve entubulation models, especially over long distances. The chemical properties, ligand identity and density, and mechanical properties of the hydrogel can affect neurite extension. However, the importance of combinatorial effects between different components in co-gels of several extracellular matrix components is unclear. In this study, we investigated neurite extension from explanted dorsal root ganglia cultured within co-gels made from laminin, fibronectin, collagen 1 and hyaluronic acid. Laminin had a strong, dose-dependent effect on both neurite length and outgrowth. Fibronectin was slightly, but generally not significantly, inhibitory to neurite extension. The concentration of collagen 1 and hyaluronic acid did not have significant effects on neurite extension. The combinatorial effects among the four components were additive rather than synergistic. A co-gel made with 1.5 mg/ml collagen 1 and 1.5 mg/ml laminin was optimum in this study, resulting in an average neurite length of 1532 +/- 91 mu m versus 976 +/- 32 mu m for controls, and an increase in overall volume outgrowth (reflecting neurite length and branching) of 85.9 +/- 9.3% over controls. This co-gel provides a mechanically stable scaffold with high ligand density and biochemical affinity. The results of this study support the use of co-gels of laminin and collagen 1 for promoting regeneration in peripheral nerve injuries and suggest that interactions among hydrogel components are not significant.