Optimal poly(L-lysine) grafting density in hydrogels for promoting neural progenitor cell functions.
Optimal poly(L-lysine) grafting density in hydrogels for promoting neural progenitor cell functions.
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DOI：
10.1021/bm300381d
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发表时间：
2012-05-14
影响因子：
6.2
通讯作者：
Wang, Shanfeng
中科院分区：
文献类型：
--
作者：
Cai, Lei;Lu, Jie;Sheen, Volney;Wang, Shanfeng
最近，我们开发了一种可光聚合的聚赖氨酸（PLL），它可以共价结合到聚乙二醇二丙烯酸酯（PEGDA）水凝胶中，通过提供正电荷来提高其生物活性。为了探索这些PLL接枝的PEGDA水凝胶作为细胞递送载体和神经导管内腔填充剂用于外周和中枢神经再生的潜力，我们通过光交联PEGDA，将PLL （PLL）的重量组成分别为0、1%、2%、3%和5%来改变水凝胶中悬垂的PLL链的数量。我们进一步研究了PLL移植密度对E14小鼠神经祖细胞（NPC）行为的影响，包括细胞活力、附着、增殖、分化和基因表达。实际接枝的PLL数量和电荷密度随进料成分的增加呈比例增加。在包封后第7天和第14天，NPC在3D水凝胶中的存活率以PLL接枝密度依赖的方式显著提高。同样，当浓度增加至2%时，接枝pll的水凝胶也能促进鼻咽癌的附着和增殖。更有趣的是，水凝胶中接枝PLL链的数量显著改变了NPC的谱系承诺。鼻窦分化表现出抛物线或非单调依赖于ϕPLL，导致细胞主要分化为成熟神经元，具有广泛的神经突形成和星形胶质细胞而不是少突胶质细胞，而中性水凝胶和pll移植的水凝胶具有较高的5%的ϕPLL则不支持鼻窦分化。谱系标记的基因表达进一步说明了这一趋势，表明具有最佳的2%的pll的pll嫁接水凝胶可能是一种有前途的细胞载体，可以促进NPC功能治疗神经损伤。
Recently we have developed a photo-polymerizable poly(l-lysine) (PLL) that can be covalently incorporated into poly(ethylene glycol) diacrylate (PEGDA) hydrogels to improve their bioactivity by providing positive charges. To explore the potential of these PLL-grafted PEGDA hydrogels as a cell delivery vehicle and luminal filler in nerve guidance conduits for peripheral and central nerve regeneration, we varied the amount of pendent PLL chains in the hydrogels by photo-crosslinking PEGDA with weight compositions of PLL (ϕPLL) of 0, 1%, 2%, 3%, and 5%. We further investigated the effect of PLL grafting density on E14 mouse neural progenitor cell (NPC) behavior including cell viability, attachment, proliferation, differentiation, and gene expression. The amount of actually grafted PLL and charge densities were characterized, showing a proportional increase with the feed composition ϕPLL. NPC viability in 3D hydrogels was significantly improved in a PLL grafting density-dependent manner at days 7 and 14 post-encapsulation. Similarly, NPC attachment and proliferation were promoted on the PLL-grafted hydrogels with increasing ϕPLL up to 2%. More intriguingly, NPC lineage commitment was dramatically altered by the amount of grafted PLL chains in the hydrogels. NPC differentiation demonstrated a parabolic or non-monotonic dependence on ϕPLL, resulting in cells mostly differentiated toward mature neurons with extensive neurite formation and astrocytes rather than oligodendrocytes on the PLL-grafted hydrogels with ϕPLL of 2%, whereas the neutral hydrogels and PLL-grafted hydrogels with higher ϕPLL of 5% support NPC differentiation less. Gene expression of lineage markers further illustrated this trend, indicating that PLL-grafted hydrogels with an optimal ϕPLL of 2% could be a promising cell carrier that promoted NPC functions for treatment of nerve injuries.
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影响因子：
14
作者：
Crompton, K. E.;Goud, J. D.;Forsythe, J. S.
通讯作者：
Forsythe, J. S.
影响因子：
14
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1163/156856207781494368
发表时间：
2007-08-01
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
3.4
作者：
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