Variations in rigidity and ligand density influence neuronal response in methylcellulose-laminin hydrogels.
Variations in rigidity and ligand density influence neuronal response in methylcellulose-laminin hydrogels.
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DOI：
10.1016/j.actbio.2011.07.026
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发表时间：
2011-12
影响因子：
9.7
通讯作者：
LaPlaca MC
中科院分区：
文献类型：
--
作者：
Stabenfeldt SE;LaPlaca MC
细胞不断地感知其物理和化学环境，与周围的微环境和细胞产生动态的相互作用。神经元特有的神经突生长受多种因素的影响，包括生长基质、力学特性和粘附信号。在设计用于神经再生的生物材料时，更好地了解基底材料、硬度和生物粘附对神经突生长的影响是很重要的。为此，我们开发并表征了一种可调的3-D甲基纤维素（MC）水凝胶聚合物体系，该体系与层粘连蛋白-1 （MC-x- ln）结合，覆盖了一系列底物刚度（G*范围= 50Pa至565Pa）和层粘连蛋白密度。以3-D MC水凝胶包埋的原代皮层神经元的活力和神经突生长作为细胞结局指标。培养4天后，与对照非生物活性MC相比，MC-x- ln的神经元活力随着硬度的增加而显著增强；然而，只有在复合模量为565Pa的MC水凝胶中才观察到神经突的生长。在保持恒定MC配方（G* = 565Pa）的情况下，改变LN显示了神经元活力的阈值反应，而在神经突生长方面，观察到LN密度的直接剂量依赖性反应。总的来说，这些数据证明了MC水凝胶中材料顺应性和生物活性配体浓度之间的协同作用。这些结果可以用来更好地理解介导神经元对mc基组织工程材料反应的粘附和机械因素。
Cells are continuously sensing their physical and chemical environment, generating dynamic interactions with the surrounding micro-environment and cells. Specific to neurons, neurite outgrowth is influenced by many factors, including the growth substrata mechanical properties and adhesive signals. In designing biomaterials for neural regeneration, it is important to better understand the influence of substrate material, rigidity, and bioadhesion on neurite outgrowth. To this end, we developed and characterized a tunable 3-D methylcellulose (MC) hydrogel polymeric system tethered to laminin-1 (MC-x-LN) across a range of substrate rigidities (G* range = 50Pa to 565Pa) and laminin densities. Viability and neurite outgrowth of primary cortical neurons plated within 3-D MC hydrogels were used as cell outcome measures. After four days in culture, neuronal viability was significantly augmented with increasing rigidity for MC-x-LN as compared to control non-bioactive MC; however, neurite outgrowth was only observed in MC hydrogels with complex moduli of 565Pa. Varying LN while maintaining a constant MC formulation (G* = 565Pa) revealed a threshold response for neuronal viability, whereas a direct dose-dependent response to LN density was observed for neurite outgrowth. Collectively, these data demonstrate the synergistic play between material compliance and bioactive ligand concentrations within MC hydrogels. Such results can be used to better understand the adhesive and mechanical factors that mediate neuronal response to MC-based tissue engineered materials.