Pretreated exosomes by electrical stimulation accelerate bone regeneration

Bone tissue engineering has attracted significant attention from both the research and clinical communities. Inspired by the inherent bioelectric properties of bone tissue, electrical stimulation is widely recognized as an external intervention that can induce osteogenesis, mineralization, and accel...

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Main Authors: Jialu Chen, Jian Chen, Jiahao Chen, Renjie Lu, Ziyuan Liu, Yang Zhang, Chi Zhang
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/S2452199X25001574
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author Jialu Chen
Jian Chen
Jiahao Chen
Renjie Lu
Ziyuan Liu
Yang Zhang
Chi Zhang
author_facet Jialu Chen
Jian Chen
Jiahao Chen
Renjie Lu
Ziyuan Liu
Yang Zhang
Chi Zhang
author_sort Jialu Chen
collection DOAJ
description Bone tissue engineering has attracted significant attention from both the research and clinical communities. Inspired by the inherent bioelectric properties of bone tissue, electrical stimulation is widely recognized as an external intervention that can induce osteogenesis, mineralization, and accelerate bone regeneration. However, the clinical application of electrical stimulation is limited by the complexity of the procedures and the use of cumbersome, invasive equipment. Exosomes, as an alternative to seed cells, can overcome many of the limitations associated with stem cell transplantation. Researchers aim to enhance exosomes' therapeutic potential for bone regeneration. While various pretreatments have been studied, there is currently no research investigating the role of exosomes pretreated with electrical stimulation in bone tissue regeneration. In this study, we pretreated bone marrow mesenchymal stem cells (BMSCs) with electrical stimulation and isolated the resulting exosomes (Elec-exo). A series of in vitro experiments determined that 150 μA is the optimal condition for electrical stimulation. Mechanistically, proteomic analysis revealed an enrichment of proteins involved in “Oxidative Phosphorylation” regulation within Elec-exo, and transcriptomic analysis indicated the activation of Pl3k-Akt and MAPK bone formation-related signaling pathways in the effector cells. Hydrogels, as a sustained-release scaffold, were used to deliver Elec-exo in vivo. In a rat femur defect model, Elec-exo loaded into chondroitin sulfate methacrylate (CSMA) hydrogel accelerated early bone tissue regeneration. In summary, our study explores the mechanisms by which electrical stimulation pretreatment enhances bone tissue regeneration and broadens the therapeutic application of exosomes in accelerating bone regeneration.
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spelling doaj-art-037bbad40f33475b85145cb9fbf3d0852025-08-20T03:43:02ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-09-015138339810.1016/j.bioactmat.2025.04.019Pretreated exosomes by electrical stimulation accelerate bone regenerationJialu Chen0Jian Chen1Jiahao Chen2Renjie Lu3Ziyuan Liu4Yang Zhang5Chi Zhang6Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200236, China; Nanomedicine and Intestinal Microecology Research Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, ChinaDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200236, China; Nanomedicine and Intestinal Microecology Research Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200236, China; Nanomedicine and Intestinal Microecology Research Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, ChinaNanomedicine and Intestinal Microecology Research Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Eighth People’s Hospital, Shanghai, China; Corresponding author.Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China; Corresponding author. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 100 Haining Street, Shanghai, 200080, China.Bone tissue engineering has attracted significant attention from both the research and clinical communities. Inspired by the inherent bioelectric properties of bone tissue, electrical stimulation is widely recognized as an external intervention that can induce osteogenesis, mineralization, and accelerate bone regeneration. However, the clinical application of electrical stimulation is limited by the complexity of the procedures and the use of cumbersome, invasive equipment. Exosomes, as an alternative to seed cells, can overcome many of the limitations associated with stem cell transplantation. Researchers aim to enhance exosomes' therapeutic potential for bone regeneration. While various pretreatments have been studied, there is currently no research investigating the role of exosomes pretreated with electrical stimulation in bone tissue regeneration. In this study, we pretreated bone marrow mesenchymal stem cells (BMSCs) with electrical stimulation and isolated the resulting exosomes (Elec-exo). A series of in vitro experiments determined that 150 μA is the optimal condition for electrical stimulation. Mechanistically, proteomic analysis revealed an enrichment of proteins involved in “Oxidative Phosphorylation” regulation within Elec-exo, and transcriptomic analysis indicated the activation of Pl3k-Akt and MAPK bone formation-related signaling pathways in the effector cells. Hydrogels, as a sustained-release scaffold, were used to deliver Elec-exo in vivo. In a rat femur defect model, Elec-exo loaded into chondroitin sulfate methacrylate (CSMA) hydrogel accelerated early bone tissue regeneration. In summary, our study explores the mechanisms by which electrical stimulation pretreatment enhances bone tissue regeneration and broadens the therapeutic application of exosomes in accelerating bone regeneration.http://www.sciencedirect.com/science/article/pii/S2452199X25001574Electrical stimulationPretreatedExosomeBone regenerationBone tissue engineering
spellingShingle Jialu Chen
Jian Chen
Jiahao Chen
Renjie Lu
Ziyuan Liu
Yang Zhang
Chi Zhang
Pretreated exosomes by electrical stimulation accelerate bone regeneration
Bioactive Materials
Electrical stimulation
Pretreated
Exosome
Bone regeneration
Bone tissue engineering
title Pretreated exosomes by electrical stimulation accelerate bone regeneration
title_full Pretreated exosomes by electrical stimulation accelerate bone regeneration
title_fullStr Pretreated exosomes by electrical stimulation accelerate bone regeneration
title_full_unstemmed Pretreated exosomes by electrical stimulation accelerate bone regeneration
title_short Pretreated exosomes by electrical stimulation accelerate bone regeneration
title_sort pretreated exosomes by electrical stimulation accelerate bone regeneration
topic Electrical stimulation
Pretreated
Exosome
Bone regeneration
Bone tissue engineering
url http://www.sciencedirect.com/science/article/pii/S2452199X25001574
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AT renjielu pretreatedexosomesbyelectricalstimulationaccelerateboneregeneration
AT ziyuanliu pretreatedexosomesbyelectricalstimulationaccelerateboneregeneration
AT yangzhang pretreatedexosomesbyelectricalstimulationaccelerateboneregeneration
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