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Two-dimensional Nb2C-based nanoplatform augmented sonodynamic antibacterial therapy and bone regeneration

基于二维Nb2C的纳米**台增**声动力抗菌治疗并促进骨修复

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Abstract

Rapid disinfection and promotion of bone regeneration are two crucial aspects of the clinical treatment of osteomyelitis. There is an urgent need to develop highly efficient bioactive sonosensitizers for sonodynamic therapy (SDT). Herein, a type of two-dimensional (2D) Nb2C nanosheet-decorated porphyrin metal–organic framework hollow nanotubes (HNTM/Nb2C) was designed to simultaneously eliminate infection and accelerate bone regeneration under ultrasound (US) irradiation. Building a Schottky junction between HNTM and Nb2C nanosheets allowed enough reactive oxygen species (ROS) to be produced because of the rapid charge transfer and suppressed recombination of electron-hole pairs under US irradiation. The sonosensitizer accelerated the osteoblastic differentiation of stem cells. RNA-seq indicated that the HNTM/Nb2C nanoplatform induced stem cell differentiation via cation transport and ATP-synthesis-coupled electron transport through an ultrasonic current. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the Nb ion may further improve osteogenesis via the activation of Wnt signaling. Our study provides novel strategies for improving SDT efficiency by simultaneously eliminating infections and promoting bone regeneration through US-current-combined ion therapy for osteomyelitis treatment.

摘要

快速消除感染和促进骨再生是骨髓炎临床治疗的两个关键环节. 当前迫切需要开发高效的生物活性声敏剂用于声动力治疗(SDT). 在此, 我们设计了一种二维Nb2C纳米片修饰的卟啉基金属有机框架纳米**台(HNTM/Nb2C)用于在超声辐照下同时消除感染和加速骨再生. 通过在HNTM和Nb2C纳米片之间构建肖特基结, 实现了超声辐照下快速的电荷转移并抑制电子-空穴对的重组, 从而产生丰富的活性氧. 这种新型的声敏剂可以加速干细胞向成骨细胞的分化. RNA测序表明, 该HNTM/Nb2C纳米**台通过阳离子释放及超声响应电流引起的ATP合成耦合的电子传递诱导干细胞分化. 此外, KEGG通路富集分析表明, Nb离子可能通过激活Wnt信号通路进一步促进成骨. 我们的研究为骨髓炎的高效SDT提供了新的策略, 该策略通过声响应电流联合离子疗法, 实现了感染的消除同时促进了骨再生.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81902261, 22175058, and 81772401), the Application Foundation and Advanced Program of Wuhan Science and Technology Bureau (2019020701011457), and the Fundamental Research Funds for the Central Universities (2019kfyXMBZ063).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Liang Ma  (马良), **aoguang Zhang  (张晓光), Hongchuan Wang  (王鸿钏), **aobo Feng  (冯晓波), Jie Lei  (雷捷), Yaqi He  (何雅琦), Junyu Wei  (魏君雨), Yukun Zhang  (张宇坤), Lei Tan  (谭磊) & Cao Yang  (杨操)

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  1. Liang Ma  (马良)
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Contributions

Author contributions Ma L, Zhang X and Wang H performed all the experiments. Ma L, He Y and Wei J conceived the study, designed the materials, completed the experiments and wrote the manuscript. Feng X and Lei J gave guidance on experiments and data processing. Tan L, Feng X and Lei J gave guidance on experimental design and reviewed the manuscript. Yang C and Tan L contributed to conceptualization, manuscript reviewing, supervision and project administration. All authors contributed to the general discussion.

Corresponding authors

Correspondence to Lei Tan  (谭磊) or Cao Yang  (杨操).

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Conflict of interest The authors declare that they have no conflict of interest.

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Supplementary information Supporting data are available in the online version of the paper.

Liang Ma is currently a doctor at the Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST). His research interests include bone regeneration, biomaterials and sonodynamic therapy.

**aoguang Zhang received his Bachelor’s degree from Zhengzhou University in 2017. He obtained his Master’s Degree from HUST and now he is a PhD student at HUST. His research interests include biomaterials and sonodynamic therapy.

Hongchuan Wang received his Bachelor’s degree from HUST. He is currently a postgraduate student at the Department of Orthopaedics, Union Hospital, Tongji Medical College, HUST. His research interests include biomaterials and bone regeneration.

Lei Tan received his PhD degree in polymer chemistry and physics from Wuhan University in 2016. Currently, he is an associate professor at the Department of Orthopaedics, Union Hospital, Tongji Medical College, HUST. His current research interests include ultrasound-responsive materials, antibacterial biomaterials and bone-repair materials.

Cao Yang is currently a professor at the Department of Orthopaedics, Union Hospital, Tongji Medical College, HUST. He received his PhD degree in orthopaedic surgery from Tongji Medical College, HUST, China in 2002. He served as an associated professor at the Orthopaedic Surgery Department of Stanford University Medical Center in 2007 and served as a research fellow at the Orthopaedic Center of Massachusetts General Hospital, Harvard University (2007–2009). He was rewarded the chief scientist of the National Key Research and Development Program of China. His research interests include spine diseases, intervertebral disc degeneration, additive manufacturing, andone regeneration.

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Ma, L., Zhang, X., Wang, H. et al. Two-dimensional Nb2C-based nanoplatform augmented sonodynamic antibacterial therapy and bone regeneration. Sci. China Mater. 66, 2913–2924 (2023). https://doi.org/10.1007/s40843-022-2413-4

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