Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes

Xinyi Fang, Jun Wang, Chengxinyue Ye, Jiu Lin, Jinhui Ran, Zhanrong Jia, Jinglei Gong, Yiming Zhang, Jie Xiang, Xiong Lu, Chaoming Xie () and Jin Liu ()
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Xinyi Fang: Sichuan University
Jun Wang: Sichuan University
Chengxinyue Ye: Sichuan University
Jiu Lin: Sichuan University
Jinhui Ran: Southwest Jiaotong University
Zhanrong Jia: Southwest Jiaotong University
Jinglei Gong: Sichuan University
Yiming Zhang: Southwest Jiaotong University
Jie Xiang: Sichuan University
Xiong Lu: Southwest Jiaotong University
Chaoming Xie: Southwest Jiaotong University
Jin Liu: Sichuan University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Date: 2024
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DOI: 10.1038/s41467-024-53290-6

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