Orthogonal click reactions enable the synthesis of ECM-mimetic PEG hydrogels without multi-arm precursors†,Journal of Materials Chemistry B

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Orthogonal click reactions enable the synthesis of ECM-mimetic PEG hydrogels without multi-arm precursors†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-07-09 00:00:00 , DOI: 10.1039/c8tb01399c
Faraz Jivan ₁ , Natalia Fabela ₁ , Zachary Davis ₂ , Daniel L Alge _{1,

3}

Affiliation

Click chemistry reactions have become an important tool for synthesizing user-defined hydrogels consisting of poly(ethylene glycol) (PEG) and bioactive peptides for tissue engineering. However, because click crosslinking proceeds via a step-growth mechanism, multi-arm telechelic precursors are required, which has some disadvantages. Here, we report for the first time that this requirement can be circumvented to create PEG–peptide hydrogels solely from linear precursors through the use of two orthogonal click reactions, the thiol–maleimide Michael addition and thiol–norbornene click reaction. The rapid kinetics of both click reactions allowed for quick formation of norbornene-functionalized PEG–peptide block copolymers via Michael addition, which were subsequently photocrosslinked into hydrogels with a dithiol linker. Characterization and in vitro testing demonstrated that the hydrogels have highly tunable physicochemical properties and excellent cytocompatibility. In addition, stoichiometric control over the crosslinking reaction can be leveraged to leave unreacted norbornene groups in the hydrogel for subsequent hydrogel functionalization via bioorthogonal inverse-electron demand Diels–Alder click reactions with s-tetrazines. After selectively capping norbornene groups in a user-defined region with cysteine, this feature was leveraged for protein patterning. Collectively, these results demonstrate that our novel chemical strategy is a simple and versatile approach to the development of hydrogels for tissue engineering that could be useful for a variety of applications.

中文翻译：

正交点击反应无需多臂前体即可合成 ECM 模拟 PEG 水凝胶†

点击化学反应已成为合成用户定义的水凝胶的重要工具，该水凝胶由聚乙二醇（PEG）和用于组织工程的生物活性肽组成。然而，由于点击交联是通过逐步增长机制进行的，因此需要多臂遥爪前体，这有一些缺点。在这里，我们首次报道，通过使用两个正交点击反应，即硫醇-马来酰亚胺迈克尔加成和硫醇-降冰片烯点击反应，可以绕过这一要求，仅从线性前体创建PEG-肽水凝胶。两种点击反应的快速动力学允许通过迈克尔加成快速形成降冰片烯功能化的PEG-肽嵌段共聚物，随后通过二硫醇连接体光交联成水凝胶。表征和体外测试表明，水凝胶具有高度可调的理化性质和优异的细胞相容性。此外，可以利用对交联反应的化学计量控制，在水凝胶中留下未反应的降冰片烯基团，以便通过与s-四嗪的生物正交逆电子需求狄尔斯-阿尔德点击反应进行后续水凝胶功能化。在用半胱氨酸选择性地封闭用户定义区域中的降冰片烯基团后，该功能被用于蛋白质图案化。总的来说，这些结果表明，我们的新颖化学策略是一种简单且通用的方法来开发用于组织工程的水凝胶，可用于多种应用。

更新日期：2018-07-09

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