All-natural aggregation-induced emission-active glycyrrhizic acid hydrogels for drug-resistant bacteria-infected wound healing

• All-natural robust GN-BR AIE-active hydrogels were developed for the first time. • GN-BR hydrogels show strong and stimuli-responsive fluorescence features. • GN-BR AIE-active hydrogels possess a high synergy photodynamic antibacterial ability and anti-inflammatory capacity. • GN-BR AIE-active hydrogels can efficiently promote MRSA-infected skin wound healing . Aggregation-induced emission-active (AIE-active) hydrogels with a unique integration of both luminescence behavior and gel properties have attracted increasing attention due to their advanced functionalities and applications. However, the development of biocompatible AIE-active hydrogels with superior luminescence performances and sufficient mechanical strength remains a big challenge in the biomedical field, and particularly, bioactive AIE hydrogels from naturally occurring small molecules are highly desirable for use as ideal dressings in clinical practice of infected wound healing, in terms of their strong intrinsic biological activities, good biocompatibility, as well as facile and environmentally friendly processes. Here, for the first time, we report an all-natural robust AIE-active hydrogel consisting of two natural Chinese herbal molecules, i.e. glycyrrhizic acid (GA) and berberine (BR), which can be developed as green dressings for accelerating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. This GN-BR hydrogel is constructed from the self-assembly of supramolecular GA nanofibrils (GN) as well as their interactions with BR molecules, leading to the formation of an aggregated fibrillar network embedded with the GN-BR particles, which endow the hydrogels with a strong fluorescence emission, excellent mechanical strength and structural recovery capacity, and interesting stimuli-responsive fluorescence features. More importantly, benefiting from the intrinsic immunoregulatory effects of GA and BR and the unique AIE properties of GN-BR assembles, the hydrogels exhibit high anti-inflammation and antibacterial abilities, especially effective photodynamic antibacterial capacity through generating reactive oxygen species under visible light. In vivo studies show that the AIE-active GN-BR hydrogels can promote MRSA-infected skin wound healing by reducing bacterial infection, inducing macrophage phenotype transformation from M1 to M2, downregulating inflammatory response, facilitating collagen deposition, and enhancing angiogenesis. This all-natural GN-BR herb hydrogel is an ideal and versatile hydrogel dressing exhibiting inherent bioactivities and remarkable AIE properties and has great potential in treating wounds infected with drug-resistant bacteria.