School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287, USA.
Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281, USA.
Chembiochem. 2021 May 14;22(10):1755-1760. doi: 10.1002/cbic.202100030. Epub 2021 Feb 25.
Biomaterials with dynamically tunable properties are critical for a range of applications in regenerative medicine and basic biology. In this work, we show the reversible control of gelatin methacrylate (GelMA) hydrogel stiffness through the use of DNA crosslinkers. We replaced some of the inter-GelMA crosslinks with double-stranded DNA, allowing for their removal through toehold-mediated strand displacement. The crosslinks could be restored by adding fresh dsDNA with complementary handles to those on the hydrogel. The elastic modulus (G') of the hydrogels could be tuned between 500 and 1000 Pa, reversibly, over two cycles without degradation of performance. By functionalizing the gels with a second DNA strand, it was possible to control the crosslink density and a model ligand in an orthogonal fashion with two different displacement strands. Our results demonstrate the potential for DNA to reversibly control both stiffness and ligand presentation in a protein-based hydrogel, and will be useful for teasing apart the spatiotemporal behavior of encapsulated cells.
具有动态可调特性的生物材料对于再生医学和基础生物学的一系列应用至关重要。在这项工作中，我们通过使用 DNA 交联剂展示了明胶甲基丙烯酰胺 (GelMA) 水凝胶硬度的可逆控制。我们用双链 DNA 替代了部分 GelMA 交联，通过引发链置换可以将其去除。通过添加带有与水凝胶上互补手柄的新鲜 dsDNA，可以恢复交联。水凝胶的弹性模量 (G') 可以在两个循环之间在 500 到 1000 Pa 之间进行可逆调节，而不会降低性能。通过用第二 DNA 链对凝胶进行功能化，可以以正交方式控制交联密度和模型配体，使用两条不同的置换链。我们的结果表明，DNA 有可能在基于蛋白质的水凝胶中可逆地控制硬度和配体呈现，这对于剖析封装细胞的时空行为将非常有用。
