Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate

Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms poses a major therapeutic challenge due to persistent infection and bone loss. Optimizing anti-infection and promoting bone repair are the main goals to improve the efficiency of osteomyelitis treatment. Herein, we p...

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Main Authors: Yang Wu, Bei Chen, Xia Chen, Guoqiang Zhu, Wei Du, Liming Qing, Panfeng Wu, Zhenxing Wang, Juyu Tang, Hui Xie
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-09-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001537
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author Yang Wu
Bei Chen
Xia Chen
Guoqiang Zhu
Wei Du
Liming Qing
Panfeng Wu
Zhenxing Wang
Juyu Tang
Hui Xie
author_facet Yang Wu
Bei Chen
Xia Chen
Guoqiang Zhu
Wei Du
Liming Qing
Panfeng Wu
Zhenxing Wang
Juyu Tang
Hui Xie
author_sort Yang Wu
collection DOAJ
description Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms poses a major therapeutic challenge due to persistent infection and bone loss. Optimizing anti-infection and promoting bone repair are the main goals to improve the efficiency of osteomyelitis treatment. Herein, we present an ultrasound (US)-actived Cu-BTO@Gua composite piezoelectric sonosensitizer, created by conjugating guanidine (Gua) groups, a component that permeates the biofilm matrix, onto US-absorbing Cu-doped barium titanate (BTO). The guanidine groups demonstrate strong affinity for matrices abundant in negatively charged components, facilitating deeper biofilm penetration. Cu doping not only amplifies the piezoelectric effect, but also introduces abundant oxygen vacancies to suppress electron-hole pair recombination. Under US irradiation, the nanocomposite catalyzes the substrate to produce toxic ROS in the acidic infection microenvironment, while Cu depletes glutathione to aggravate oxidative stress, leading to bacterial toxin inactivation, biofilm disintegration, and bacterial death. Additionally, Cu-BTO@Gua promotes the polarization of M1 macrophages to the M2 phenotype by inhibiting nuclear factor-κB, which subsequently activates the transforming growth factor β (TGF-β) signaling pathway to support osteogenesis. This dual-action approach offers a promising strategy for improving clinical outcomes of complex bone infections.
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spelling doaj-art-0b67ce2b77904ee586d5731fc46e99cc2025-08-20T03:18:20ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-09-015145046810.1016/j.bioactmat.2025.04.014Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanateYang Wu0Bei Chen1Xia Chen2Guoqiang Zhu3Wei Du4Liming Qing5Panfeng Wu6Zhenxing Wang7Juyu Tang8Hui Xie9Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Ångmedicine, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Orthopedics, Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Ångmedicine, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Ångmedicine, Changsha, Hunan, 410008, China; Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Ångmedicine, Changsha, Hunan, 410008, China; Corresponding author. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Department of Orthopedics, Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Corresponding author. Department of Orthopedics, Hand & Microsurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Ångmedicine, Changsha, Hunan, 410008, China; Corresponding author. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms poses a major therapeutic challenge due to persistent infection and bone loss. Optimizing anti-infection and promoting bone repair are the main goals to improve the efficiency of osteomyelitis treatment. Herein, we present an ultrasound (US)-actived Cu-BTO@Gua composite piezoelectric sonosensitizer, created by conjugating guanidine (Gua) groups, a component that permeates the biofilm matrix, onto US-absorbing Cu-doped barium titanate (BTO). The guanidine groups demonstrate strong affinity for matrices abundant in negatively charged components, facilitating deeper biofilm penetration. Cu doping not only amplifies the piezoelectric effect, but also introduces abundant oxygen vacancies to suppress electron-hole pair recombination. Under US irradiation, the nanocomposite catalyzes the substrate to produce toxic ROS in the acidic infection microenvironment, while Cu depletes glutathione to aggravate oxidative stress, leading to bacterial toxin inactivation, biofilm disintegration, and bacterial death. Additionally, Cu-BTO@Gua promotes the polarization of M1 macrophages to the M2 phenotype by inhibiting nuclear factor-κB, which subsequently activates the transforming growth factor β (TGF-β) signaling pathway to support osteogenesis. This dual-action approach offers a promising strategy for improving clinical outcomes of complex bone infections.http://www.sciencedirect.com/science/article/pii/S2452199X25001537MRSA-mediated osteomyelitisEnhanced piezoelectric effectBiofilm disintegrationTGF-β signaling pathwayBone regeneration
spellingShingle Yang Wu
Bei Chen
Xia Chen
Guoqiang Zhu
Wei Du
Liming Qing
Panfeng Wu
Zhenxing Wang
Juyu Tang
Hui Xie
Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
Bioactive Materials
MRSA-mediated osteomyelitis
Enhanced piezoelectric effect
Biofilm disintegration
TGF-β signaling pathway
Bone regeneration
title Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
title_full Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
title_fullStr Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
title_full_unstemmed Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
title_short Enhanced piezocatalytic therapy of MRSA-infected osteomyelitis using ultrasound-triggered copper nanocrystals-doped barium titanate
title_sort enhanced piezocatalytic therapy of mrsa infected osteomyelitis using ultrasound triggered copper nanocrystals doped barium titanate
topic MRSA-mediated osteomyelitis
Enhanced piezoelectric effect
Biofilm disintegration
TGF-β signaling pathway
Bone regeneration
url http://www.sciencedirect.com/science/article/pii/S2452199X25001537
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