Cysteamine/Amberlyst-15-Mediated Cellulose Dissolution for Engineering Antioxidative Nanodrug in Diabetic Wound Therapy

Cellulose-based materials offer sustainable potential but require greener processes for advanced applications. Here, we developed a deep eutectic solvent-liked system for dissolving cellulose, composed of molten cysteamine hydrochloride (CysHCl) combined with solid acid Amberlyst-15 (A15). Through a concise precipitation separation process, cysteamine-modified cellulose nanospheres (Cys-Cel NS) were synthesized in the cellulose solvent system with all reagents being recycled. Different characterizations indicate that Cys-Cel NS retains cysteamine primarily through hydrogen bonds, which facilitate the sustained release of cysteamine and reactive oxygen species (ROS) scavenging. By virtue of Cys-Cel NS's high biocompatibility, negligible cytotoxicity, and excellent antioxidative capability, a diabetic cutaneous ulcer drug was prepared by combining Cys-Cel NS with a thermosensitive gel (Cys-Cel NS Gel). In vivo animal assessments further confirmed that Cys-Cel NS Gel reduces ROS levels, modulates the oxidative microenvironment at diabetic wound sites, and enhances wound healing. After a 13-day treatment with Cys-Cel NS Gel, the wound sites healed substantially, and Cys-Cel NS Gel exhibited superior efficacy compared to the commercial gel drug. This work developed a feasible shortcut for dissolving cellulose and synthesizing antioxidative nanocellulose materials, which could be further extended for the treatment of other diseases associated with excessive oxidative stress.