Programmable DNA Hydrogels Assembled from Multidomain DNA Strands Huiling Jiang, [a] Victor Pan, [a] Skanda Vivek, [b] Eric R. Weeks, [b] and Yonggang Ke* [a] Introduction Hydrogels, formed by crosslinking molecules in aqueous solu- tion, have attracted considerable attention as important bio- medical materials because of their desired properties, such as high water content, porosity, and tissue-like mechanics. [1] For example, hydrogels have been applied as three-dimensional carriers of mesenchymal stem cells due to their excellent bio- compatibility and ability to retain large amounts of water. [2] An- other important and widely explored application of hydrogels is drug delivery, [3] in which drugs can be incorporated into the interspace through chemical attachment or physical entrap- ment and subsequently released following various release stimuli, depending on the hydrogel properties. Both covalent and non-covalent interactions have been implemented for drug incorporation. Generally, multistep reactions are necessary for covalent functionalization, which are stable and irreversi- ble. [4] Meanwhile, reversible non-covalent interactions such as hydrogen bonding, ionic interactions, and hydrophobic inter- actions have also been applied to load organic small drug mol- ecules or inorganic nanoparticles into hydrogel systems. [5] DNA has emerged as a important programmable material for biomaterial engineering. [6] In DNA hydrogels formed by Watson–Crick base pairing, researchers have realized a variety of desirable properties, such as self-healing, mechanical stabili- ty, minimal toxicity, and excellent biocompatibility. [7] However, previously reported DNA hydrogels typically utilize multistrand designs, are relatively expensive, and often require labor-inten- sive multistep syntheses. [5, 8] Here we report a low-cost one-strand DNA hydrogel design. We show that this simple system offers excellent programma- bility, in which mechanical properties and cargo loading ca- pacity can be easily tuned by changing the strand sequences and lengths. We expect this new DNA hydrogel system will provide a new enabling platform for hydrogel-based biomedi- cal applications. Results and Discussion The formulation of multistrand DNA hydrogel design typically involves two steps. First, structurally well-defined motifs assem- ble from multiple DNA strands. Then, the hydrogel is formed by joining the motifs together by base pairing. Our one-strand (OS) hydrogels use a different design strategy (Scheme 1). A DNA strand is designed to contain multiple domains, indicated by different colors. Each domain contains a self-complementa- ry palindromic sequence. Hydrogel formation is a single-step Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to the programmabili- ty and biocompatibility of the material. We developed a series of low-cost one-strand DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palin- dromic domains. This new hydrogel design is simple and pro- grammable. Thermal stability, mechanical properties, and load- ing capacity of these one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains. Scheme 1. One-strand (OS) multidomain DNA hydrogel. An OS strand con- sists of multiple domains, each containing a self-complementary palindromic sequence. [a] Dr. H. Jiang, V. Pan, Prof. Y. Ke Wallace H. Coulter Department of Biomedical Engineering Emory School of Medicine 1760 Haygood Drive, Atlanta, Georgia 30322 (USA) E-mail: yonggang.ke@emory.edu [b] S. Vivek, Prof. E. R. Weeks Emory University, Department of Physics 400 Dowman Drive, Atlanta GA 30322-2430 (USA) Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.doi.org/10.1002/ cbic.201500686. This article is part of a Special Issue on DNA Nanotechnology ChemBioChem 2016, 17, 1156 – 1162 # 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1156 Full Papers DOI: 10.1002/cbic.201500686