Microalgae-based bioactive hydrogel loaded with quorum sensing inhibitor promotes infected wound healing

Abstract

Interaction between bacterial species is through quorum sensing (QS), a process that regulates and coordinates genes in virulence activities and biofilm formation. QS contributes to the slowdown of tissue repair during the wound healing process by inducing chronic inflammation of the wound. Here, we developed a multifunctional QS inhibitor based on a bioactive hydrogel system to interrupt the QS of bacteria, relieve hypoxia, and destroy biofilms, and thus accelerate the healing of infected wounds in diabetic mice. We loaded berberine (BBR, a QS inhibitor, and antibacterial agent) into a natural living microalgae Spirulina platensis (SP) to form a bioactive hydrogel (BBR@SP gel) in combination with carboxymethyl chitosan/sodium alginate. Under laser irradiation, the BBR@SP gel could constantly release BBR and produce reactive oxygen species, resulting in a synergistic QS inhibition against methicillin-resistant Staphylococcus aureus (MRSA) combined chemo-photodynamic therapy. The BBR@SP gel also suppresses and destroys biofilm formation and down-regulates the expression of virulence factors. We found that the BBR@SP gel could accelerate MRSA-infected diabetic wound healing by promoting angiogenesis, skin regeneration, and suppressing the inflammatory response. Our work presents an innovative antimicrobial strategy that eliminates drug-resistant bacteria by synergistic chemo-photodynamic killing effect, relieving biofilm hypoxia, and blocking QS simultaneously, which may open up new prospects in solving antimicrobial drug resistance and combating biofilm-related infections.