ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy

Hypoxic deep-seated infections in refractory environments impede wound healing and exacerbate antibiotic resistance. Sonodynamic therapy (SDT) shows promise in combating pathogenic bacteria; however, the excessive reactive oxygen species (ROS) generated during the process often induce severe inflamm...

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Main Authors: Jiani Xu, Fanshangming Zhou, Lingyan Cao, Huilin Wang, Jiani Hu, Shuo Qiu, Yulan Liu, Yan Zhang, Jie Wang, Xinquan Jiang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-10-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25002257
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author Jiani Xu
Fanshangming Zhou
Lingyan Cao
Huilin Wang
Jiani Hu
Shuo Qiu
Yulan Liu
Yan Zhang
Jie Wang
Xinquan Jiang
author_facet Jiani Xu
Fanshangming Zhou
Lingyan Cao
Huilin Wang
Jiani Hu
Shuo Qiu
Yulan Liu
Yan Zhang
Jie Wang
Xinquan Jiang
author_sort Jiani Xu
collection DOAJ
description Hypoxic deep-seated infections in refractory environments impede wound healing and exacerbate antibiotic resistance. Sonodynamic therapy (SDT) shows promise in combating pathogenic bacteria; however, the excessive reactive oxygen species (ROS) generated during the process often induce severe inflammatory responses, hindering tissue regeneration. To overcome these limitations, we have developed a multifunctional hydrogel, inspired by the dynamic regulatory mechanisms of rhizobia. GSH-SF/PeMA/MXene-TiO2 (SP-MT) hydrogel was synthesized through the thiol-ene click chemistry mechanism. Methacrylated pectin (PeMA) and GSH-modified silk fibroin (GSH-SF) were combined with MXene-TiO2 addition. This hydrogel exhibited favorable injectability, mechanical properties, swelling and degradation performance. In addition, this hydrogel can employ ultrasound-triggered dynamic ROS modulation to enable spatiotemporal regulation of antibacterial activity and promote tissue regeneration, effectively addressing the dual challenges of infection management and oxidative stress. Under ultrasound stimulation, SP-MT hydrogel can rapidly eradicate bacteria by disrupting membrane integrity and electron transport chains (ETCs) while simultaneously generating substantial ROS. Once the ultrasound stimulation ceased, the hydrogel and its degradation products eliminated residual ROS. In vivo studies further demonstrated that the nanohydrogel can accelerate soft tissue regeneration and periodontal bone regeneration by eradicating bacterial biofilms, promoting angiogenesis, and activating the TGF-β/SMAD signaling pathway. Therefore, this work introduces a novel strategy for equipping hydrogels with programmed antibacterial and anti-inflammatory functionalities, providing an innovative solution for treating deep-seated infections, particularly in periodontitis therapy.
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spelling doaj-art-83c5ec8e1741484783d23441ebc0a8eb2025-08-24T05:13:38ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015244045910.1016/j.bioactmat.2025.05.031ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapyJiani Xu0Fanshangming Zhou1Lingyan Cao2Huilin Wang3Jiani Hu4Shuo Qiu5Yulan Liu6Yan Zhang7Jie Wang8Xinquan Jiang9Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaCollege of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaDepartment of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR ChinaSchool of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai, 201620, PR China; Corresponding author. School of Material Engineering, Shanghai University of Engineering Science, Shanghai, 201620, PR China.Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR China; Corresponding author. Department of Prosthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.Shanghai Stomatological Hospital Fudan University, Shanghai, 201100, PR China; Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, PR China; Corresponding author. Shanghai Stomatological Hospital Fudan University, Shanghai, 201100, PR China.Hypoxic deep-seated infections in refractory environments impede wound healing and exacerbate antibiotic resistance. Sonodynamic therapy (SDT) shows promise in combating pathogenic bacteria; however, the excessive reactive oxygen species (ROS) generated during the process often induce severe inflammatory responses, hindering tissue regeneration. To overcome these limitations, we have developed a multifunctional hydrogel, inspired by the dynamic regulatory mechanisms of rhizobia. GSH-SF/PeMA/MXene-TiO2 (SP-MT) hydrogel was synthesized through the thiol-ene click chemistry mechanism. Methacrylated pectin (PeMA) and GSH-modified silk fibroin (GSH-SF) were combined with MXene-TiO2 addition. This hydrogel exhibited favorable injectability, mechanical properties, swelling and degradation performance. In addition, this hydrogel can employ ultrasound-triggered dynamic ROS modulation to enable spatiotemporal regulation of antibacterial activity and promote tissue regeneration, effectively addressing the dual challenges of infection management and oxidative stress. Under ultrasound stimulation, SP-MT hydrogel can rapidly eradicate bacteria by disrupting membrane integrity and electron transport chains (ETCs) while simultaneously generating substantial ROS. Once the ultrasound stimulation ceased, the hydrogel and its degradation products eliminated residual ROS. In vivo studies further demonstrated that the nanohydrogel can accelerate soft tissue regeneration and periodontal bone regeneration by eradicating bacterial biofilms, promoting angiogenesis, and activating the TGF-β/SMAD signaling pathway. Therefore, this work introduces a novel strategy for equipping hydrogels with programmed antibacterial and anti-inflammatory functionalities, providing an innovative solution for treating deep-seated infections, particularly in periodontitis therapy.http://www.sciencedirect.com/science/article/pii/S2452199X25002257Hypoxic deep infectionsSonodynamic therapyBio-heterojunctionReactive oxygen speciesTissue regeneration
spellingShingle Jiani Xu
Fanshangming Zhou
Lingyan Cao
Huilin Wang
Jiani Hu
Shuo Qiu
Yulan Liu
Yan Zhang
Jie Wang
Xinquan Jiang
ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
Bioactive Materials
Hypoxic deep infections
Sonodynamic therapy
Bio-heterojunction
Reactive oxygen species
Tissue regeneration
title ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
title_full ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
title_fullStr ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
title_full_unstemmed ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
title_short ROS-balancing-engineered bio-heterojunction hydrogel accelerated the infected bone regeneration based on Sono-chemo dynamic therapy
title_sort ros balancing engineered bio heterojunction hydrogel accelerated the infected bone regeneration based on sono chemo dynamic therapy
topic Hypoxic deep infections
Sonodynamic therapy
Bio-heterojunction
Reactive oxygen species
Tissue regeneration
url http://www.sciencedirect.com/science/article/pii/S2452199X25002257
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