Aminoglycoside hydrogels based on dynamic covalent bonds with pH sensitivity, biocompatibility, self-healing, and antibacterial ability

Despite aminoglycosides (AGs) have superior antibacterial ability, all approved AGs by FDA are associated with adverse effects such as ototoxicity and nephrotoxicity. To solve these problems, AGs hydrogels based on dynamic covalent bond cross-linking were quickly prepared within 25 s by using AGs, aldehyde hyaluronic acid (A-HA), and adipic acid dihydrazide graft hyaluronic acid (HA-ADH) as materials. FT-IR, thermal analysis, and SEM results exhibited that A-HA/HA-ADH/AGs hydrogels were successfully synthesized with highly porous and interconnected network structure. The water absorption ratio of the hydrogels increased with the decreasing pH and temperature, indicating the hydrogels were pH- and temp-responsive. The pH-dependent degradation also demonstrated pH sensitivity of the hydrogels. Rheology and self-healing analysis assessment displayed that AGs hydrogels had good mechanical property, self-healing ability, and injectability. The hydrogels had no cytotoxicity to L929 cells and their hemolysis ratios were between 0.7% and 1.3%, which reached a nontoxic level. Most importantly, inhibition zones results demonstrated that the hydrogels had excellent and sustained antibacterial performance against Escherichia coli and Staphylococcus aureus. Therefore, A-HA/HA-ADH/AGs hydrogels are potential dressings for wound healing. Further plans including antibacterial and in vivo wound healing assays will be shown in the next work.