Self-Assembled Herbal Medicine Encapsulated by an Oxidation-Sensitive Supramolecular Hydrogel for Chronic Wound Treatment

Inflammation has been assumed to affect the pathology of wound healing and is associated with many nonhealing chronic wounds. Naturally derived herbal medicines with anti-inflammatory properties are of interest because of their effectiveness and affordability in clinical treatment. Herein, we report a supramolecular hydrogel comprising self-assembled natural herb rhein and an oxidative responsive cross-linked network based on ferrocene and β-cyclodextrin host-guest recognitions. Rhein can directly self-assemble into fibrils, exerting better anti-inflammation efficiency than its free drug form. The adaption of the supramolecular network can greatly improve the stability and retain the structural integrity of encapsulated self-assembled rhein. In addition, host-guest recognition confers dissolution of the hydrogel under oxidative stress, thereby delivering self-assembled rhein to the wound site and exerting better therapeutic efficiency. Evaluations in diabetic mice indicate that the resultant hydrogel promoted chronic wound healing by suppressing excess reactive oxygen species, facilitating the transition of the wound healing process, and restoring the normal wound-repair process. Therefore, the proposed hydrogel has a potential value as an herbal-based dressing for future clinical chronic wound management.