Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Biomacromolecules. 2020 Aug 10;21(8):3152-3162. doi: 10.1021/acs.biomac.0c00576. Epub 2020 Jul 15.
The formation and rheological properties of hydrogels based on amphiphilic ABA triblock polyether copolymers are described, relying solely on the hydrophobic interaction of long-chain alkyl glycidyl ether (AlkGE)- based A-blocks that are combined with a hydrophilic poly(ethylene glycol) (PEG) midblock. Via anionic ring-opening copolymerization (AROP), ethylene oxide (EO) and long-chain alkyl glycidyl ethers (AlkGEs) were copolymerized, using deprotonated poly(ethylene glycol) (PEG) macroinitiators ( of 10, 20 kg mol). The polymerization afforded amphiphilic ABA triblock copolymers with molar masses in the range of 21-32 kg mol and dispersities () of = 1.07-1.17. Kinetic studies revealed random copolymerization of EO and AlkGE, indicating random spacing of the hydrophobic AlkGE units by polar EO units. Following this approach, the hydrophobicity of the apolar blocks of amphiphilic ABA triblock polyethers can be tailored. Detailed rheological measurements confirmed the successful formation of hydrogels at different pH values as a consequence of nonpolar interactions and alkyl chain crystallization. Hydrogel formation was also observed at different ionic strengths (i.e., varied salt concentration), based on the hydrophobic aggregates. This behavior is in contrast to other often-used supramolecular cross-linking strategies, such as Coulomb interactions, complexation, or hydrogen bonding. Micro-differential scanning calorimetry (μ-DSC) measurements of the hydrogels revealed crystalline hydrophobic domains with melting temperatures in the physiological temperature range. In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays, diblock copolymers possessing structural analogy to the triblock copolymers were studied to assess the general cytotoxicity of amphiphilic polyethers bearing long alkyl chains at the polyether backbone, using splenic immune cells. At intermediate polymer concentrations, no cytotoxic effects were observed. This indicates that long-chain alkyl glycidyl ethers are promising for the introduction of highly hydrophobic as well as crystalline motifs at the polyether backbone in hydrogels for biomedical purposes.
本文描述了基于两亲性 ABA 三嵌段聚醚共聚物的水凝胶的形成和流变性能，仅依靠长链烷基缩水甘油醚（AlkGE）基 A 嵌段的疏水相互作用，这些嵌段与亲水性聚乙二醇（PEG）中嵌段相结合。通过阴离子开环聚合（AROP），使用去质子化的聚乙二醇（PEG）大分子引发剂（10、20 kg/mol），将环氧乙烷（EO）和长链烷基缩水甘油醚（AlkGEs）共聚。聚合得到了摩尔质量在 21-32 kg/mol 范围内且分散度（）为 1.07-1.17 的两亲性 ABA 三嵌段共聚物。动力学研究表明 EO 和 AlkGE 的无规共聚，表明由极性 EO 单元随机间隔疏水 AlkGE 单元。通过这种方法，可以调整两亲性 ABA 三嵌段聚醚的非极性嵌段的疏水性。详细的流变测量证实，由于非极性相互作用和烷基链结晶，在不同 pH 值下成功形成了水凝胶。还观察到在不同的离子强度（即变化的盐浓度）下形成水凝胶，这是基于疏水聚集体。这种行为与其他常用的超分子交联策略（如库仑相互作用、络合或氢键）形成对比。水凝胶的微差示扫描量热法（μ-DSC）测量显示出具有在生理温度范围内的熔融温度的结晶疏水性域。在 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴化物（MTT）测定中，研究了具有与三嵌段共聚物结构类似的嵌段共聚物，以评估在含有长烷基链的聚醚主链上具有两亲性聚醚的一般细胞毒性，使用脾免疫细胞。在中等聚合物浓度下，没有观察到细胞毒性作用。这表明长链烷基缩水甘油醚有望在水凝胶中引入高度疏水性和结晶基序，用于生物医学目的。
