Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety

Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety
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DOI:
10.1089/ten.tea.2015.0354
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发表时间:
2016-05-01
影响因子:
4.1
通讯作者:
Kohn, Joachim
Kohn, Joachim
中科院分区:
医学3区
文献类型:
--
作者:
Ezra, Mindy;Bushman, Jared;Kohn, Joachim

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经常探索用水凝胶预填充的神经导管以试图促进神经再生。本研究检查了导管壁的孔隙率和用于填充导管的水凝胶的生物活性水平之间的体内相互作用。在小鼠股神经修复模型中,比较了多孔(P)或无孔(NP)导管中的神经再生,所述导管仅填充有胶原蛋白或用共价连接的聚糖人自然杀伤细胞抗原-1(m-HNK)的促神经突肽模拟物增强的胶原蛋白。虽然胶原蛋白是一种细胞友好的基质,不区分神经和非神经细胞,m-HNK增强的胶原蛋白特异性地促进轴突生长和适当的运动神经元靶向。在本研究中,基于一系列组织形态学观察结果和功能恢复参数,用填充有m-HNK(胶原HNK)移植胶原的NP导管治疗的动物具有最佳的总体功能恢复。我们的数据表明,在某些条件下,使用胶原蛋白等通常对细胞友好的填充剂可能会限制神经再生。考虑到胶原基水凝胶作为神经导管填充物的频繁使用,这一发现是重要的。
Nerve conduits prefilled with hydrogels are frequently explored in an attempt to promote nerve regeneration. This study examines the interplay in vivo between the porosity of the conduit wall and the level of bioactivity of the hydrogel used to fill the conduit. Nerve regeneration in porous (P) or nonporous (NP) conduits that were filled with either collagen only or collagen enhanced with a covalently attached neurite-promoting peptide mimic of the glycan human natural killer cell antigen-1 (m-HNK) were compared in a 5 mm critical size defect in the mouse femoral nerve repair model. Although collagen is a cell-friendly matrix that does not differentiate between neural and nonneural cells, the m-HNK-enhanced collagen specifically promotes axon growth and appropriate motor neuron targeting. In this study, animals treated with NP conduits filled with collagen grafted with m-HNK (CollagenHNK) had the best overall functional recovery, based on a range of histomorphometric observations and parameters of functional recovery. Our data indicate that under some conditions, the use of generally cell friendly fillers such as collagen may limit nerve regeneration. This finding is significant, considering the frequent use of collagen-based hydrogels as fillers of nerve conduits.