An injectable PEG hydrogel controlling neurotrophin-3 release by affinity peptides.
An injectable PEG hydrogel controlling neurotrophin-3 release by affinity peptides.
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DOI：
10.1016/j.jconrel.2020.12.045
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发表时间：
2021-02-10
期刊：
影响因子：
--
通讯作者：
Shea L
中科院分区：
文献类型：
--
作者：
Wang J;Youngblood R;Cassinotti L;Skoumal M;Corfas G;Shea L
神经营养因子-3生长因子可以改善耳蜗神经元的存活，将这种蛋白局部递送到中耳圆窗膜可能能够逆转感音神经性听力损失。因此，这项工作的目标是开发一种可注射的水凝胶递送系统，该系统可以以可控和持续的方式局部释放神经营养因子-3。我们确定了一种PEG水凝胶配方，该配方使用巯基乙烯砜迈克尔加成进行交联。这种可注射配方提供弹性水凝胶，具有更高的机械刚性，更好的生物粘附性和更长的停留时间，比目前临床研究的用于听力损失的波洛沙姆水凝胶。在体内，PEG水凝胶诱导的局部免疫反应与生物相容性波洛沙姆水凝胶相当，但它们在皮下区域释放有效载荷的速度要慢5倍。基于这种可注射的水凝胶配方，我们设计了一种基于亲和的蛋白质释放系统，通过修饰PEG水凝胶与神经营养因子-3蛋白特异性的亲和肽。我们证实了肽偶联PEG水凝胶中神经营养素-3的持续释放是由肽和蛋白质之间的可逆相互作用引起的。亲和控制的释放速率取决于聚合物的浓度、多肽的亲和和多肽与蛋白质的比率。总的来说，我们开发了一种可注射的水凝胶配方，用于局部递送神经营养因子-3，与波洛沙姆水凝胶相比，它具有亲和力控制释放和更长的递送时间。
Neurotrophin-3 growth factor can improve cochlear neuron survival, and localized delivery of this protein to the round window membrane in the middle ear may be able to reverse sensorineural hearing loss. Thus, the goal of this work was to develop an injectable hydrogel delivery system that can allow localized release of neurotrophin-3 in a controlled and sustained manner. We identified a PEG hydrogel formulation that uses thiol-vinyl sulfone Michael addition for crosslinking. This injectable formulation provides elastic hydrogels with higher mechanical rigidity, better bio-adhesion and longer residence time than Poloxamer hydrogels currently being investigated clinically for hearing loss. In vivo, PEG hydrogels induce local immune responses comparable to biocompatible Poloxamer hydrogels, yet they released payloads at a ~5-fold slower rate in the subcutaneous area. Based on this injectable hydrogel formulation, we designed an affinity-based protein release system by modifying PEG hydrogels with affinity peptides specific to neurotrophin-3 proteins. We verified the sustained release of neurotrophin-3 from peptide-conjugated PEG hydrogels resulting from the reversible interaction between peptides and proteins. The rate of affinity-controlled release depends on the polymer concentrations, the affinity of peptides and the peptide-to-protein ratios. Collectively, we developed an injectable hydrogel formulation for localized delivery of neurotrophin-3, which provides affinity-controlled release and longer delivery time compared to Poloxamer hydrogels.
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影响因子：
6.2
作者：
Park, Hansoo;Guo, Xuan;Temenoff, Johnna S.;Tabata, Yasuhiko;Caplan, Arnold I.;Kasper, F. Kurtis;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.
原位形成可注射水凝胶用于药物输送和伤口修复。
影响因子：
16.1
作者：
Dimatteo R;Darling NJ;Segura T
通讯作者：
Segura T
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
影响因子：
4.6
作者：
Chatani, Shunsuke;Nair, Devatha P.;Bowman, Christopher N.
通讯作者：
Bowman, Christopher N.
影响因子：
7.8
作者：
Keselowsky BG;Lewis JS
通讯作者：
Lewis JS