High-Strength and Injectable Supramolecular Hydrogel Self-Assembled by Monomeric Nucleoside for Tooth-Extraction Wound Healing

Hydrogels with high mechanical strength and injectability have attracted extensive attention in biomedical and tissue engineering. However, endowing a hydrogel with both properties is challenging because they are generally inversely related. In this work, by constructing a multi-hydrogen-bonding system, a high-strength and injectable supramolecular hydrogel is successfully fabricated. It is constructed by the self-assembly of a monomeric nucleoside molecular gelator (2-amino-2'-fluoro-2'-deoxyadenosine (2-FA)) with distilled water/phosphate buffered saline as solvent. Its storage modulus reaches 1 MPa at a concentration of 5.0 wt%, which is the strongest supramolecular hydrogel comprising an ultralow-molecular-weight (MW < 300) gelator. Furthermore, it exhibits excellent shear-thinning injectability, and completes the sol-gel transition in seconds after injection at 37 °C. The multi-hydrogen-bonding system is essentially based on the synergistic interactions between the double NH₂ groups, water molecules, and 2'-F atoms. Furthermore, the 2-FA hydrogel exhibits excellent biocompatibility and antibacterial activity. When applied to rat molar extraction sockets, compared to natural healing and the commercial hemorrhage agent gelatin sponge, the 2-FA hydrogel exhibits faster degradation and induces less osteoclastic activity and inflammatory infiltration, resulting in more complete bone healing. In summary, this study provides ideas for proposing a multifunctional, high-strength, and injectable supramolecular hydrogel for various biomedical engineering applications.