Radboud University Nijmegen, Institute for Molecules and Materials, Bio-organic Chemistry, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
J Mater Chem B. 2020 Jul 15;8(27):5912-5920. doi: 10.1039/d0tb01042a.
The biocompatible, injectable and high water-swollen nature of hydrogels makes them a popular candidate to imitate the extracellular matrix (ECM) for tissue engineering both in vitro and in vivo. However, commonly used covalently cross-linked hydrogels, despite their stability and tunability, are elastic and deteriorate as bulk material degrades which would impair proper cell function. To improve these deficiencies, here, we present a self-recovering cross-linked hydrogel formed instantaneously with functionalized poly(ethylene glycol) as a basis. We combine covalent cross-links introduced via a strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction and non-covalent links between phosphonate groups and calcium ions. By adjusting the ratios of non-covalent and covalent cross-links, we synthesized these dual cross-linked (DC) hydrogels that displayed storage moduli below ∼2000 Pa and relaxation times from seconds to minutes. The gels recovered to 41-96% of their initial mechanical properties after two subsequent strain failures. Cryo-scanning electron microscopy revealed that DC hydrogels containing approximately equal amounts of covalent and non-covalent cross-links displayed phase separation. Finally, we functionalized the DC hydrogels by incorporating an integrin binding motif, RGDS, to provide a biocompatible environment for human mesenchymal stem cells (HMSCs) by facilitating adhesion inside the gel network. Inside these DC gels HSMCs displayed a viability up to 73% after five days of cell culture.
水凝胶具有生物相容性、可注射性和高吸水性，因此成为在体外和体内模拟细胞外基质（ECM）的组织工程的热门候选材料。然而，常用的共价交联水凝胶尽管具有稳定性和可调性，但作为块状材料降解时会弹性变差，从而影响细胞的正常功能。为了改善这些缺陷，在这里，我们提出了一种基于功能化聚乙二醇的自恢复交联水凝胶。我们结合了应变促进叠氮-炔环加成（SPAAC）点击反应引入的共价交联和膦酸基团与钙离子之间的非共价键。通过调整非共价和共价交联的比例，我们合成了这些双重交联（DC）水凝胶，其储能模量低于约 2000 Pa，弛豫时间从秒到分钟不等。在两次应变失效后，凝胶恢复到初始力学性能的 41-96%。冷冻扫描电子显微镜显示，含有等量共价和非共价交联的 DC 水凝胶显示出相分离。最后，我们通过掺入整合素结合基序 RGDS 对 DC 水凝胶进行功能化，通过促进凝胶网络内的黏附为人类间充质干细胞（HMSCs）提供生物相容性环境。在这些 DC 凝胶中，HSMCs 在细胞培养五天后显示出高达 73%的存活率。
