Sonocatalytic hydrogen/hole-combined therapy for anti-biofilm and infected diabetic wound healing

A concept of sonocatalytic hydrogen/hole-combined 'inside/outside-cooperation' anti-biofilm is proposed for efficient hydrogen generation and local polysaccharide/NADH oxidation, which inhibits bacterial aspiration inside biofilm and destroys the surface structure of biofilm, respectively. It is a great challenge to effectively eradicate biofilm and cure biofilm-infected diseases because dense extracellular polymeric substance matrix prevents routine antibacterial agents from penetrating into biofilm. H-2 is an emerging energy-regulating molecule possessing both high biosafety and high tissue permeability. In this work, we propose a concept of sonocatalytic hydrogen/hole-combined 'inside/outside-cooperation' anti-biofilm for promoting bacteria-infected diabetic wound healing based on two-dimensional piezoelectric nanomaterials. Proof-of-concept experiments using C3N4 nanosheets as a representative piezoelectric catalyst with wide band gap and high biosafety have verified that sonocatalytically generated H-2 and holes rapidly penetrate into biofilm to inhibit bacterial energy metabolism and oxidatively deprive polysaccharides/NADH in biofilm to destroy the bacterial membrane/electron transport chain, respectively, inside/outside-cooperatively eradicating biofilm. A bacteria-infected diabetic wound model is used to confirm the excellent in vivo antibacterial performance of sonocatalytic hydrogen/hole-combined therapy, remarkably improving bacteria-infected diabetic wound healing. The proposed strategy of sonocatalytic hole/hydrogen-combined 'inside/outside-cooperation' will make a highway for treatment of deep-seated biofilm infection.

Automated summary

A concept of sonocatalytic hydrogen/hole-combined 'inside/outside-cooperation' anti-biofilm is proposed for efficient eradication of biofilm. The concept involves the use of two-dimensional piezoelectric nanomaterials to promote bacteria-infected diabetic wound healing by inhibiting bacterial energy metabolism and destroying the bacterial membrane/electron transport chain. In vivo experiments have shown that this sonocatalytic therapy significantly improves bacteria-infected diabetic wound healing, making it a promising strategy for deep-seated biofilm infection treatment.