Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA.
Soft Matter. 2020 Nov 18;16(44):10158-10168. doi: 10.1039/d0sm01217c.
Supramolecular hydrogels formed by noncovalent self-assembly of low molecular weight (LMW) agents are promising next-generation biomaterials. Thixotropic shear response and mechanical stability are two emergent properties of hydrogels that are critical for biomedical applications including drug delivery and tissue engineering in which injection of the hydrogel will be necessary. Herein, we demonstrate that the emergent thixotropic properties of supramolecular phenylalanine-derived hydrogels are dependent on the conditions in which they are formulated. Specifically, hydrogels formed from fluorenylmethoxycarbonyl (Fmoc) modified phenylalanine derivatives, 3-fluorophenylalanine (Fmoc-3F-Phe) and pentafluorophenylalanine (Fmoc-F5-Phe), were characterized as a function of gelation conditions to examine how shear response and mechanical stability properties correlate to mode of gelation. Two distinct methods of gelation were compared. First, spontaneous self-assembly and gelation was triggered by a solvent exchange method in which a concentrated solution of the gelator in dimethylsulfoxide was diluted in water. Second, gelation was promoted by dissolution of the gelator in water at basic pH followed by gradual pH adjustment from basic to mildly acidic by the hydrolysis of glucono-delta-lactone. Hydrogels formed under solvent exchange conditions were mechanically unstable and poorly shear-responsive whereas hydrogels formed by gradual acidification were temporally stable and had highly shear-responsive viscoelastic character. These studies confirm that gelation environment and mechanism have a significant influence on the emergent properties of supramolecular hydrogels and offer insight into how gelation conditions can be used to tune hydrogel properties for specific applications.
由低分子量（LMW）试剂通过非共价自组装形成的超分子水凝胶是下一代有前途的生物材料。触变剪切响应和机械稳定性是水凝胶的两种新兴特性，对于包括药物输送和组织工程在内的生物医学应用至关重要，在这些应用中需要注射水凝胶。在此，我们证明了超分子苯丙氨酸衍生水凝胶的新兴触变特性取决于它们的配方条件。具体而言，研究了由芴甲氧羰基（Fmoc）修饰的苯丙氨酸衍生物，3-氟苯丙氨酸（Fmoc-3F-Phe）和五氟苯丙氨酸（Fmoc-F5-Phe）形成的水凝胶，作为凝胶形成条件的函数进行了表征，以检查剪切响应和机械稳定性与凝胶形成模式如何相关。比较了两种截然不同的凝胶化方法。首先，通过溶剂交换方法触发自发自组装和凝胶化，其中凝胶剂在二甲基亚砜中的浓溶液在水中稀释。其次，通过将凝胶剂在水中溶解并在碱性 pH 下促进凝胶化，然后通过戊二醛的水解逐渐将 pH 从碱性调节至微酸性。在溶剂交换条件下形成的水凝胶机械不稳定且剪切响应性差，而通过逐渐酸化形成的水凝胶具有时间稳定且具有高度剪切响应性的粘弹性特征。这些研究证实，凝胶化环境和机制对超分子水凝胶的新兴特性有重大影响，并深入了解如何可以根据特定应用来调节凝胶化条件以调节水凝胶的特性。
