Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels

Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels
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DOI:
10.1016/j.biomaterials.2005.06.034
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发表时间:
2006-01-01
期刊:
影响因子:
14
通讯作者:
Langer, R
Langer, R
中科院分区:
工程技术1区
文献类型:
--
作者:
Burdick, JA;Ward, M;Langer, R

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可降解水凝胶是输送生长因子以促进患病或受损组织再生的有用载体。在中枢神经系统中,神经营养素的输送在许多情况下在组织修复方面具有巨大潜力,特别是对于治疗脊髓损伤。在这项工作中,研究了通过光引发聚合形成的基于聚乙二醇的水凝胶用于神经营养素的递送。这些因子的释放动力学由网络交联密度的变化控制,这影响神经营养素的扩散和随后从凝胶中的释放,总释放时间从几周到几个月不等。通过基于细胞的增殖测定和视网膜外植体神经突生长测定来评估一种神经营养因子——睫状神经营养因子(CNTF)的释放和活性。从移植视网膜上方的可降解水凝胶释放的 CNTF 能够刺激比没有 CNTF 的对照明显更多数量的神经突生长。最后,开发了独特的微球/水凝胶复合材料,可以以单独的释放速率同时递送多种神经营养素。 (c) 2005 Elsevier Ltd. 保留所有权利。
Degradable hydrogels are useful vehicles for the delivery of growth factors to promote the regeneration of diseased or damaged tissue. In the central nervous system, there are many instances where the delivery of neurotrophins has great potential in tissue repair, especially for treatment of spinal cord injury. In this work, hydrogels based on poly(ethylene glycol) that form via a photoinitiated polymerization were investigated for the delivery of neurotrophins. The release kinetics of these factors are controlled by changes in the network crosslinking density, which influences neurotrophin diffusion and subsequent release from the gels with total release times ranging from weeks to several months. The release and activity of one neurotrophic factor, ciliary-neurotrophic factor (CNTF), was assessed with a cell-based proliferation assay and an assay for neurite outgrowth from retinal explants. CNTF released from a degradable hydrogel above an explanted retina was able to stimulate outgrowth of a significantly higher number of neurites than controls without CNTF. Finally, unique micro sphere/hydrogel composites were developed to simultaneously deliver multiple neurotrophins with individual release rates. (c) 2005 Elsevier Ltd. All rights reserved.