Self-Assembly of Metallo-Nucleoside Hydrogels for Injectable Materials That Promote Wound Closure

Injectable hydrogels are increasingly being used as scaffolds for in situ tissue engineering and wound healing. Most of these injectable hydrogels are made from polymers, and there are fewer examples of such soft materials made via self-assembly of low-molecular weight gelators. We report the room-temperature synthesis of a functional hydrogel formed by mixing cytidine (C) with 0.5 equiv each of B(OH)₃ and AgNO₃. The structural basis for this supramolecular hydrogel (C-B-C·Ag⁺) involves orthogonal formation of cytidine borate diesters (C-B-C) and Ag⁺-stabilized C-C base pairs, namely, the C·Ag⁺·C dimer. The C-B-C·Ag⁺ hydrogels, which can have high water content (at least 99.6%), are stable (no degradation after 1 year in the light), stimuli-responsive, and self-supporting, with elastic moduli of up to 10⁴ Pa. Incorporation of Ag⁺ ions into the gel matrix endows the C-B-C·Ag⁺ hydrogel with significant antibacterial capability. Importantly, the rapid switching between the sol and gel states for this supramolecular hydrogel, as a response to shear stress, enables 3D printing of a flexible medical patch made from the C-B-C·Ag⁺ hydrogel. The C-B-C·Ag⁺ hydrogel was used to promote the closure of burn wounds in a mouse model.