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

Qingqing Xu; Shengqiang Chen; Lingdong Jiang; Chao Xia; Lingting Zeng; Xiaoqing Cai; Zhaokui Jin; Shucun Qin; Wenjiang Ding; Qianjun He

doi:10.1093/nsr/nwad063

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

Natl Sci Rev. 2023 Mar 6;10(5):nwad063. doi: 10.1093/nsr/nwad063. eCollection 2023 May.

Authors

Qingqing Xu^{1

2}, Shengqiang Chen², Lingdong Jiang², Chao Xia², Lingting Zeng^{2

3}, Xiaoqing Cai², Zhaokui Jin², Shucun Qin¹, Wenjiang Ding³, Qianjun He^{1

2

3}

Affiliations

¹ Taishan Institute for Hydrogen Biomedical Research, School of Basic Medical Sciences, The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an 271000, China.
² Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen 518060, China.
³ Shanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Abstract

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. H₂ 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 H₂ 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.

Keywords: biofilm; diabetic foot; hydrogen therapy; nanocatalytic medicine; piezoelectric catalysis.