Injectable Carrier-Free Hydrogel Dressing with Anti-Multidrug-Resistant Staphylococcus aureus and Anti-Inflammatory Capabilities for Accelerated Wound Healing.

ABSTRACT

Antibacterial hydrogels have gradually become a powerful weapon to treat bacterially infected wounds and accelerate healing. In this paper, we designed a small-molecule self-healing antibacterial hydrogel containing 100% drug-loaded benzyl 3ß-amino-11-oxo-olean-12-en-30-oate (GN-Bn), which was governed by π-π stacking, hydrogen bonding, and van der Waals forces. Due to the carrier-free design concept, the problems of interbatch variability during sample preparation and carrier-related toxicity can be effectively avoided. Moreover, the GN-Bn hydrogel exhibited promising antibacterial activities against multidrug-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration (MIC) of the GN-Bn hydrogel was 1.5625 nmol/mL, which was lower than those against clinical agents such as norfloxacin, penicillin, and tetracycline. This is attributed to its unique antibacterial mechanism that aims at killing bacteria or preventing their growth by regulating arginine biosynthesis and metabolism through both transcriptomic (RNA-seq) analysis and quantitative polymerase chain reaction (qPCR) analysis. In addition, the GN-Bn hydrogel can also inhibit proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) to promote wound healing. Collectively, the GN-Bn hydrogel elicited dual therapeutic effects on an MRSA-infected full-thickness skin wound model through its antibacterial and anti-inflammatory activities, which is attributed to the fact that the GN-Bn hydrogel has multiple advantages including sufficient mechanical stability, biocompatibility, and unique antibacterial mechanisms, making it significantly accelerate MRSA-infected full-thickness skin wound healing as a wound dressing. In a word, the GN-Bn antibacterial hydrogel dressing with an anti-inflammatory and antibacterial bifunctional material holds great potential in clinical application.