Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
Adv Healthc Mater. 2019 Sep;8(17):e1900644. doi: 10.1002/adhm.201900644. Epub 2019 Jul 25.
Here, the Fenton reaction is used to prepare silk hydrogels through oxidation of tyrosine residues in silk fibroin, leading to dityrosine crosslinking. At pH 5.7, gelation occurs rapidly within 30 s, and the resultant opaque gels show soft properties with a storage modulus of ≈100 Pa. The addition of ascorbic acid to the Fenton reaction increases the dityrosine bonds in the hydrogels but has little effect on the rheological or mechanical properties. The results indicate that Fe(III) ions significantly interacted with silk fibroin during the Fenton reaction, most likely binding to sites such as tyrosine, glutamate, and aspartate residues, triggering the formation of β-sheet structures that may impede dityrosine bond formation due to steric hindrance. The use of an iron chelator or the operation of the Fenton reaction at pH 9.2 enables control over the interaction of Fe(III) ions with silk fibroin, achieving a hydrogel with improved optical properties and enhanced dityrosine bond formation. Hydrogels prepared by the Fenton reaction are cytocompatible as L929 mouse fibroblasts remain viable and are proliferative when seeded on the hydrogels. The results offer a useful approach to generate chemically crosslinked silk fibroin hydrogels without the use of enzyme-catalyzed reactions for biomedical applications.
在这里，通过丝素蛋白中酪氨酸残基的氧化，利用芬顿反应来制备丝素水凝胶，导致二酪氨酸交联。在 pH 5.7 下，凝胶在 30 秒内迅速形成，所得不透明凝胶具有柔软的特性，储能模量约为 100 Pa。向芬顿反应中添加抗坏血酸会增加水凝胶中二酪氨酸键的数量，但对流变学或机械性能几乎没有影响。结果表明，Fe(III)离子在芬顿反应中与丝素蛋白发生显著相互作用，很可能与酪氨酸、谷氨酸和天冬氨酸残基等位点结合，触发β-折叠结构的形成，由于空间位阻可能阻碍二酪氨酸键的形成。使用铁螯合剂或在 pH 9.2 下操作芬顿反应，可以控制 Fe(III)离子与丝素蛋白的相互作用，从而获得具有改善的光学性质和增强的二酪氨酸键形成的水凝胶。通过芬顿反应制备的水凝胶具有细胞相容性，当接种在水凝胶上时，L929 小鼠成纤维细胞保持存活并增殖。该结果为用于生物医学应用的无需酶催化反应的化学交联丝素蛋白水凝胶的生成提供了一种有用的方法。
