Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Stuttgart, Germany.
Christian Doppler Laboratory for Advanced Polymers for Biomaterials and 3D Printing, Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria.
Sci Rep. 2021 Feb 5;11(1):3256. doi: 10.1038/s41598-021-82393-z.
Gelatin methacryloyl (GM) hydrogels have been investigated for almost 20 years, especially for biomedical applications. Recently, strengthening effects of a sequential cross-linking procedure, whereby GM hydrogel precursor solutions are cooled before chemical cross-linking, were reported. It was hypothesized that physical and enhanced chemical cross-linking of the GM hydrogels contribute to the observed strengthening effects. However, a detailed investigation is missing so far. In this contribution, we aimed to reveal the impact of physical and chemical cross-linking on strengthening of sequentially cross-linked GM and gelatin methacryloyl acetyl (GMA) hydrogels. We investigated physical and chemical cross-linking of three different GM(A) derivatives (GM10, GM2A8 and GM2), which provided systematically varied ratios of side-group modifications. GM10 contained the highest methacryloylation degree (DM), reducing its ability to cross-link physically. GM2 had the lowest DM and showed physical cross-linking. The total modification degree, determining the physical cross-linking ability, of GM2A8 was comparable to that of GM10, but the chemical cross-linking ability was comparable to GM2. At first, we measured the double bond conversion (DBC) kinetics during chemical GM(A) cross-linking quantitatively in real-time via near infrared spectroscopy-photorheology and showed that the DBC decreased due to sequential cross-linking. Furthermore, results of circular dichroism spectroscopy and differential scanning calorimetry indicated gelation and conformation changes, which increased storage moduli of all GM(A) hydrogels due to sequential cross-linking. The data suggested that the total cross-link density determines hydrogel stiffness, regardless of the physical or chemical nature of the cross-links.
明胶甲基丙烯酰基（GM）水凝胶已经研究了将近 20 年，特别是在生物医学应用方面。最近，有报道称通过顺序交联程序可以增强 GM 水凝胶的强度，即 GM 水凝胶前体溶液在化学交联之前先冷却。研究人员假设 GM 水凝胶的物理和增强的化学交联有助于观察到的增强效果。然而，目前还缺乏详细的研究。在本研究中，我们旨在揭示物理和化学交联对顺序交联 GM 和明胶甲基丙烯酰基乙酰基（GMA）水凝胶增强的影响。我们研究了三种不同 GM(A)衍生物（GM10、GM2A8 和 GM2）的物理和化学交联，这些衍生物系统地改变了侧基修饰的比例。GM10 具有最高的甲基丙烯酰化程度（DM），降低了其物理交联的能力。GM2 的 DM 最低，表现出物理交联。GM2A8 的总修饰程度决定了其物理交联能力，与 GM10 相当，但化学交联能力与 GM2 相当。首先，我们通过近红外光谱光流变学实时定量测量 GM(A)化学交联过程中的双键转化率（DBC），并发现由于顺序交联，DBC 降低。此外，圆二色光谱和差示扫描量热法的结果表明，凝胶化和构象变化增加了所有 GM(A)水凝胶的储能模量，这是由于顺序交联。数据表明，总交联密度决定了水凝胶的硬度，而与交联的物理或化学性质无关。
