A carrier-free injectable hydrogel self-assembled using natural thymol and glycyrrhizin for MRSA-infected wound healing in rats

Abstract

A carrier-free, self-assembled, injectable hydrogel was developed as wound dressing to deal with skin wound bleeding, bacterial infections, and wound healing. Natural thymol (THY) and glycyrrhizin were used to construct THY-loaded glycymicelles (THY@glycymicelles), which greatly improved the aqueous solubility of THY. Optimal THY@glycymicelles had a high encapsulation efficiency of THY and a uniform nanoparticle size. Interestingly, THY@glycymicelles could reversibly transform into THY@glycyrrhizin hydrogel (THY@glycygel) by adjusting neutral pH to skin pH (pH ∼ 4.9), and vice versa. THY@glycygel had a dense porous sponge microstructure and showed many excellent features, including injectable, hemostatic, antibacterial, and anti-inflammatory properties. In vitro antibacterial evaluation, THY@glycygel showed lower minimum inhibitory concentration to three tested bacteria than free THY. In terms of antibacterial mechanism, THY@glycygel could destroy the bacterial cell wall and membrane, increasing the extracellular alkaline phosphatase release, and inhibiting biofilm. THY@glycygel had strong hemostatic ability and exhibited great potential for antimicrobial activity and improving wound healing infected by methicillin-resistant Staphylococcus aureus (MRSA). Mechanisms including antimicrobial, promoting hair follicle growth, improving epidermis remolding and collagen deposition, decreasing inflammatory cytokine levels, and increasing growth factor levels promoted the MRSA-infected skin wound healing process of THY@glycygel. Totally, this novel hydrogel has great potential as wound dressing.