Multifunctional IL-Based Hydrogel Modulator for the Synergistic Acceleration of Wound Healing: Optimizing Drug Solubility, Antioxidant, and Anti-Inflammatory Effects

Inflammatory infection can cause the chronic nonhealing of wounds, posing considerable challenges to skin tissue reconstruction. Thus, an injectable wound dressing hydrogel with multiple functions such as remodelability, self-healing, and enhanced bioavailability has been developed to promote defect tissue regeneration, thereby offering great biomedical value for clinical application. In this study, the etodolac (ETC)-based ionic liquid (IL), LCE, was utilized for the first time as a drug template to enhance the bioavailability of the reference drug (ETC). Silk sericin (SS)/poly­(vinyl alcohol) (PVA) hydrogel substrates were used to prepare a novel LCE-loaded hydrogel modulator, Gel-LCE. Additionally, LCE as a main functional group, which exhibited excellent antioxidant activity and high water solubility, was immobilized on the SS/PVA hydrogel via the formation of stable hydrogen bonds, and the fabricated Gel-LCE exhibited excellent biocompatibility and drug utilization, as well as synergistic anti-inflammatory behaviors. Furthermore, this versatile hydrogel (Gel-LCE) could completely fit the irregular wound shape geometry during drug injection, thereby preventing secondary infections. More strikingly, the hydrogel facilitated excellent wound recovery in an experiment involving an animal wound model, reflecting its ability to significantly accelerate wound healing, as further demonstrated by its robust reactive oxygen species (ROS) scavenging capacity, as well as comparable levels of control over inflammatory cytokines (TNF-α and PGE-2). Therefore, this IL-based hydrogel, Gel-LCE, can become a very attractive and popular multifunctional wound dressing material, which can optimize the solubility of the drug to further exert stronger biomedical value.