Controlled release and gradient formation of human glial-cell derived neurotrophic factor from heparinated poly(ethylene glycol) microsphere-based scaffolds.
Controlled release and gradient formation of human glial-cell derived neurotrophic factor from heparinated poly(ethylene glycol) microsphere-based scaffolds.
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DOI：
10.1016/j.biomaterials.2014.04.027
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发表时间：
2014-08
期刊：
影响因子：
14
通讯作者：
Elbert, Donald L.
中科院分区：
文献类型：
--
作者：
Roam, Jacob L.;Nguyen, Peter K.;Elbert, Donald L.
引入蛋白质的空间模式，同时保留活性和可释放性，对于再生医学领域至关重要。许多生物分子表现出的与肝素的可逆结合是实现这一目标的一个潜在途径。我们已经将肝素共价结合到聚乙二醇（PEG）微球上，以在支架中产生有用的胶质细胞源性人神经营养因子（GDNF）空间模式，从而促进周围神经再生。将标记的GDNF与肝素化微球一起孵育，随后将其离心成含有不同浓度GDNF的不同层的圆柱形支架。然后允许GDNF扩散出支架，并通过荧光扫描共聚焦显微镜跟踪释放。将测得的释放曲线与预测的Fickian模型进行比较。反应扩散方程的解表明，GDNF在每个离散层中的浓度将导致在支架的大部分长度上几乎线性的浓度梯度。预测和测量的GDNF浓度梯度之间的协议是高的。具有不同量的肝素和GDNF以及不同交联密度的多层支架允许设计各种梯度和释放动力学。此外，由于微球溶液与胶凝溶液相比粘度低，制造比典型的梯度形成系统简单得多且更稳健，这可能容易导致过早胶凝或神经引导导管捕获气泡。基于微球的方法提供了一个框架，用于在设计用于增强神经再生的导管中产生特定的生长因子梯度。
Introduction of spatial patterning of proteins, while retaining activity and releasability, is critical for the field of regenerative medicine. Reversible binding to heparin, which many biological molecules exhibit, is one potential pathway to achieving this goal. We have covalently bound heparin to poly(ethylene glycol) (PEG) microspheres to create useful spatial patterns of glial-cell derived human neurotrophic factor (GDNF) in scaffolds to promote peripheral nerve regeneration. Labeled GDNF was incubated with heparinated microspheres that were subsequently centrifuged into cylindrical scaffolds in distinct layers containing different concentrations of GDNF. The GDNF was then allowed to diffuse out of the scaffold, and release was tracked via fluorescent scanning confocal microscopy. The measured release profile was compared to predicted Fickian models. Solutions of reaction-diffusion equations suggested the concentrations of GDNF in each discrete layer that would result in a nearly linear concentration gradient over much of the length of the scaffold. The agreement between the predicted and measured GDNF concentration gradients was high. Multilayer scaffolds with different amounts of heparin and GDNF and different crosslinking densities allow the design of a wide variety of gradients and release kinetics. Additionally, fabrication is much simpler and more robust than typical gradient-forming systems due to the low viscosity of the microsphere solutions compared to gelating solutions, which can easily result in premature gelation or the trapping of air bubbles with a nerve guidance conduit. The microsphere-based method provides a framework for producing specific growth factor gradients in conduits designed to enhance nerve regeneration.
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影响因子：
19
作者：
Cosson, Steffen;Kobel, Stefan A.;Lutolf, Matthias P.
通讯作者：
Lutolf, Matthias P.
DOI：
10.1073/pnas.0801866105
发表时间：
2008-07-15
影响因子：
11.1
作者：
Du, Yanan;Lo, Edward;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
41.2
作者：
Luo, Y;Shoichet, MS
通讯作者：
Shoichet, MS
影响因子：
4.7
作者：
Boland, Thomas;Xu, Tao;Cui, Xiaofeng
通讯作者：
Cui, Xiaofeng
影响因子：
14
作者：
Almany, L;Seliktar, D
通讯作者：
Seliktar, D