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Low-Intensity Pulsed Ultrasound Responsive Scaffold Promotes Intramembranous and Endochondral Ossification via Ultrasonic, Thermal, and Electrical Stimulation
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    Low-Intensity Pulsed Ultrasound Responsive Scaffold Promotes Intramembranous and Endochondral Ossification via Ultrasonic, Thermal, and Electrical Stimulation
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    • Wanru Jia
      Wanru Jia
      Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
      College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200025, P.R. China
      More by Wanru Jia
    • Tianlong Wang
      Tianlong Wang
      Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
    • Feng Chen*
      Feng Chen
      Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 201102, P.R. China
      *E-mail: [email protected]
      More by Feng Chen
    • Zhiqing Liu
      Zhiqing Liu
      Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
      More by Zhiqing Liu
    • Xiaodong Hou
      Xiaodong Hou
      Department of Orthopedics, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming 650032, P.R. China
      More by Xiaodong Hou
    • Wentao Cao
      Wentao Cao
      Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai 201102, P.R. China
      More by Wentao Cao
    • Xinyu Zhao
      Xinyu Zhao
      Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
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    • Bingqiang Lu
      Bingqiang Lu
      Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
      More by Bingqiang Lu
    • Yan Hu
      Yan Hu
      Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
      More by Yan Hu
    • Yijie Dong
      Yijie Dong
      Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
      College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200025, P.R. China
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    • Jianqiao Zhou*
      Jianqiao Zhou
      Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
      College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200025, P.R. China
      *E-mail: [email protected]
    • Zifei Zhou*
      Zifei Zhou
      Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
      *E-mail: [email protected]
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    • Weiwei Zhan*
      Weiwei Zhan
      Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
      College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200025, P.R. China
      *E-mail: [email protected]
      More by Weiwei Zhan
    Other Access OptionsSupporting Information (1)

    ACS Nano

    Cite this: ACS Nano 2025, 19, 4, 4422–4439
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    https://doi.org/10.1021/acsnano.4c13357
    Published January 21, 2025
    Copyright © 2025 American Chemical Society

    Abstract

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    Multiple physical stimuli are expected to produce a synergistic effect to promote bone tissue regeneration. Low-intensity pulsed ultrasound (LIPUS) has been clinically used in bone repair for the mechanical stimulation that it provides. In addition, LIPUS can also excite the biomaterials to generate other physical stimuli such as thermal or electrical stimuli. In this study, a scaffold based on decellularized adipose tissue (DAT) is established by incorporating polydopamine-modified multilayer black phosphorus nanosheets (pDA-mBP@DAT). Their effect on bone repair under LIPUS stimulation and the potential mechanisms are further investigated. This scaffold possesses piezoelectric properties and generates a mild thermogenic stimulus when stimulated by LIPUS. With superior properties, this scaffold is demonstrated to have good cytocompatibility in vitro and in vivo. Simultaneously, LIPUS promotes cell attachment, migration, and osteogenic differentiation in the pDA-mBP@DAT scaffold. Furthermore, the combined use of pDA-mBP@DAT and LIPUS significantly affects the regenerative effect in rat models of critical-sized calvarial defects. The possible mechanisms include promoting osteogenesis and neovascularization and activating the Piezo1. This study presents insight into speeding up bone regeneration by the synergistic combination of LIPUS and pDA-mBP@DAT scaffolds.

    Copyright © 2025 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.4c13357.

    • SEM images of mBP nanosheets (Figure S1); different UV–vis spectrum of mBP and pDA-mBP nanosheets (Figure S2); UV–vis spectrum of pDA-mBP nanosheets with different concentrations and the standard curve of UV–vis values at 280 nm for pDA-mBP (Figure S3); degradation test of mBP and pDA-mBP nanosheets for 28 days (Figure S4 and S5); statistical analysis of the piezoelectric constant d33 (Figure S6); subcutaneous implantation of DAT and pDA-mBP@DAT scaffolds to evaluate their biocompatibility in vivo (Figure S7); The H&E staining for acquired samples of in vivo experiment in weeks 4 and 8 (Figure S8); OPN immunofluorescence staining of the BMSCs on the DAT and pDA-mBP@DAT scaffolds with or without LIPUS stimulation on day 14 and day 21 (Figure S9); image showing the procedure of animal anesthesia and LIPUS stimulation (Figure S10); H&E staining of major organs for the evaluation of biosafety of DAT, pDA-mBP@DAT, andpDA-mBP@DATLIPUS groups (Figure S11); immunohistochemical staining of collagen type II (Col−II) expression for the control, DAT, pDA-mBP@DAT, and pDA-mBP@DATLIPUS groups in vivo (Figure S12); immunofluorescence staining of OPN expression in the control, DAT, pDA-mBP@DAT, and pDA-mBP@DATLIPUS groups in vivo (Figure S13) ; immunofluorescence staining of VEGF expression for the control, DAT, pDA-mBP@DAT, and pDA-mBP@DATLIPUS groups in weeks 4 and 8 (Figure S14) (PDF)

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    ACS Nano

    Cite this: ACS Nano 2025, 19, 4, 4422–4439
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.4c13357
    Published January 21, 2025
    Copyright © 2025 American Chemical Society

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