骨骼肌芯片及其在生物医学领域的研究进展

王达庆; 陶婷婷; 张旭; 李洪敬

doi:10.12211/2096-8280.2024-065

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骨骼肌芯片及其在生物医学领域的研究进展

特约评述 | 更新时间：2025-03-19

- 骨骼肌芯片及其在生物医学领域的研究进展
- Advances in skeletal muscle-on-a-chip for biomedical research
- 合成生物学 2024年5卷第4期页码：867-882
- 作者机构：
  
  1.大连医科大学附属第一医院，辽宁大连 116011
  2.中国科学院大连化学物理研究所，辽宁大连 116023
- 作者简介：
  
  [ "王达庆（1997—），男，骨科学博士研究生。研究方向为关节外科与运动医学。-mail：wangdaqing2020@gmail.com" ]
  [ "张旭（1986—），男，博士，副研究员。研究方向为基于器官芯片的心血管疾病研究。E-mail：zhangxu6@dicp.ac.cn" ]
  [ "李洪敬（1968—），男，医学博士，教授，主任医师，博士生导师。研究方向为关节外科及运动医学。E-mail：lhj68430@163.com" ]
- 基金信息：
  
  国家自然科学基金(82102229);大连市“登峰计划”科研项目(DF2023004)
- DOI：10.12211/2096-8280.2024-065
  中图分类号： Q816
- 收稿：2024-08-22，
  
  修回：2024-08-28，
  
  纸质出版：2024-08-31
- 稿件说明：
移动端阅览
王达庆，陶婷婷，张旭，李洪敬. 骨骼肌芯片及其在生物医学领域的研究进展［J］. 合成生物学， 2024， 5（4）： 867-882

WANG Daqing， TAO Tingting， ZHANG Xu， LI Hongjing. Advances in skeletal muscle-on-a-chip for biomedical research［J］. Synthetic Biology Journal， 2024， 5（4）： 867-882
王达庆，陶婷婷，张旭，李洪敬. 骨骼肌芯片及其在生物医学领域的研究进展［J］. 合成生物学， 2024， 5（4）： 867-882 DOI： 10.12211/2096-8280.2024-065.

WANG Daqing， TAO Tingting， ZHANG Xu， LI Hongjing. Advances in skeletal muscle-on-a-chip for biomedical research［J］. Synthetic Biology Journal， 2024， 5（4）： 867-882 DOI： 10.12211/2096-8280.2024-065.

摘要

骨骼肌作为人体最丰富的组织之一，是人体运动功能的主要承担者，并且在能量代谢、免疫调节和衰老过程中发挥重要作用。骨骼肌所处的微环境结构复杂，包括多种细胞类型、独特的三维结构以及力学特征。因此，建立高仿生的骨骼肌模型具有一定的挑战性。器官芯片可以精确地模拟人体组织的关键结构和功能特性，从而为骨骼肌模型的建立提供了一种新的途径。本文综述了目前骨骼肌芯片的构建及其在疾病建模、药物评价与再生医学等生物医学研究中的应用。依据人体骨骼肌组织微环境的特点，重点介绍了构建骨骼肌芯片的关键要素，包括动态培养环境、机械刺激、电刺激、血管化与神经化，以及其他工程策略包括各向异性支架的制备与两端锚定的策略等。目前的骨骼肌芯片在细胞来源及功能等方面仍存在一定的局限性。未来通过与基因编辑、生物传感等技术相结合，骨骼肌芯片有望在生物医学研究领域发挥更重要的作用。

Abstract

Skeletal muscle

one of the most abundant tissues in the human body

plays a crucial role in motor function

energy metabolism

immune regulation

and the aging process. The skeletal muscle tissue microenvironment is highly complex

involving a variety of cell types

a three-dimensional architecture

and specific m

echanical properties. Replicating these intricate features

in vitro

to create a biomimetic skeletal muscle model has long posed significant challenges. The advent of organ-on-a-chip technology

which integrates microfluidics with 3D cell culture

offers a groundbreaking approach to faithfully replicate the key structural and functional characteristics of human skeletal muscle tissue. The organ-on-a-chip technology enables precise control over the microenvironment

facilitating the study of skeletal muscle development

disease progression

and drug screening in a highly controlled in vitro setting. The skeletal muscle-on-a-chip (SMoC) has been utilized to investigate a variety of muscle-related diseases

including Duchenne muscular dystrophy and amyotrophic lateral sclerosis

offering valuable insights into disease mechanisms and potential therapeutic strategies. Additionally

SMoC serves as a powerful tool for testing the efficacy and toxicity of new drugs

as well as exploring tissue repair and regeneration techniques. Recent advances in the design and fabrication of SMoCs have further enhanced their physiological relevance

including the incorporation of anisotropic scaffolds to guide muscle fiber alignment and the use of electrical and mechanical stimulation to mimic the native muscle environment. These improvements have led to more accurate disease models and more reliable drug testing platforms

making SMoC a versatile and promising tool in biomedical research. In the end

the prospects and challenges facing the future development of SMoC were discussed. Currently

SMoC still exhibit limitations in terms of cell sources and functionalities. However

the integration with emerging technologies such as gene editing and biosensing in the future could pave the way for significant advancements and breakthroughs. The development of SMoC is expected to further promote the process of translational medicine

with potential applications extending beyond basic research into clinical settings

where it c

ould revolutionize personalized medicine

regenerative therapy and precision drug development.

关键词

Keywords

references

FRONTERA W R , OCHALA J . Skeletal muscle: a brief review of structure and function [J ] . Calcified Tissue International , 2015 , 96 ( 3 ): 183 - 195 .

HAY M , THOMAS D W , CRAIGHEAD J L , et al . Clinical development success rates for investigational drugs [J ] . Nature Biotechnology , 2014 , 32 ( 1 ): 40 - 51 .

WANG J , KHODABUKUS A , RAO L J , et al . Engineered skeletal muscles for disease modeling and drug discovery [J ] . Biomaterials , 2019 , 221 : 119416 .

ORTEGA M A , FERNÁNDEZ-GARIBAY X , CASTAÑO A G , et al . Muscle-on-a-chip with an on-site multiplexed biosensing system for in situ monitoring of secreted IL-6 and TNF-α [J ] . Lab on a Chip , 2019 , 19 ( 15 ): 2568 - 2580 .

BAKER M . Tissue models: a living system on a chip [J ] . Nature , 2011 , 471 ( 7340 ): 661 - 665 .

UZEL S G M , PAVESI A , KAMM R D . Microfabrication and microfluidics for muscle tissue models [J ] . Progress in Biophysics and Molecular Biology , 2014 , 115 ( 2-3 ): 279 - 293 .

SMOAK M M , PEARCE H A , MIKOS A G . Microfluidic devices for disease modeling in muscle tissue [J ] . Biomaterials , 2019 , 198 : 250 - 258 .

HUH D , HAMILTON G A , INGBER D E . From 3D cell culture to organs-on-chips [J ] . Trends in Cell Biology , 2011 , 21 ( 12 ): 745 - 754 .

ZHAO M Q , LIU H T , ZHANG X , et al . Advances in skeletal muscle engineering in biomedical research [J ] . Advanced Materials Technologies , 2023 , 8 ( 22 ): 2300595 .

MA C , PENG Y S , LI H T , et al . Organ-on-a-chip: a new paradigm for drug development [J ] . Trends in Pharmacological Sciences , 2021 , 42 ( 2 ): 119 - 133 .

SACKMANN E K , FULTON A L , BEEBE D J . The present and future role of microfluidics in biomedical research [J ] . Nature , 2014 , 507 ( 7491 ): 181 - 189 .

MEHLINGM , TAY S . Microfluidic cell culture [J ] . Current Opinion in Biotechnology , 2014 , 25 : 95 - 102 .

ZHANG X , HABIBALLA L , AVERSA Z , et al . Characterization of cellular senescence in aging skeletal muscle [J ] . Nature Aging , 2022 , 2 ( 7 ): 601 - 615 .

SCHIAFFINO S , REGGIANI C . Fiber types in mammalian skeletal muscles [J ] . Physiological Reviews , 2011 , 91 ( 4 ): 1447 - 1531 .

LUO W B , LIU H , WANG C Y , et al . Bioprinting of human musculoskeletal interface [J ] . Advanced Engineering Materials , 2019 , 21 ( 7 ): 1900019 .

SEFTON E M , KARDON G . Connecting muscle development, birth defects, and evolution: an essential role for muscle connective tissue [J ] . Current Topics in Developmental Biology , 2019 , 132 : 137 - 176 .

ROSSI D , BARONE V , GIACOMELLO E , et al . The sarcoplasmic reticulum: an organized patchwork of specialized domains [J ] . Traffic , 2008 , 9 ( 7 ): 1044 - 1049 .

HANSON J , HUXLEY H E . Structural basis of the cross-striations in muscle [J ] . Nature , 1953 , 172 ( 4377 ): 530 - 532 .

HUXLEY H E . Electron microscope studies of the organisation of the filaments in striated muscle [J ] . Biochimica et Biophysica Acta , 1953 , 12 ( 1/2 ): 387 - 394 .

OSTROVIDOV S , SALEHI S , COSTANTINI M , et al . 3D bioprinting in skeletal muscle tissue engineering [J ] . Small , 2019 , 15 ( 24 ): e1805530 .

OLIVER C E , PATEL H , HONG J , et al . Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells [J ] . Journal of Tissue Engineering and Regenerative Medicine , 2022 , 16 ( 2 ): 128 - 139 .

MONTARRAS D , MORGAN J , COLLINS C , et al . Direct isolation of satellite cells for skeletal muscle regeneration [J ] . Science , 2005 , 309 ( 5743 ): 2064 - 2067 .

CHOI K H , YOON J W , KIM M S , et al . Muscle stem cell isolation and in vitro culture for meat production: a methodological review [J ] . Comprehensive Reviews in Food Science and Food Safety , 2021 , 20 ( 1 ): 429 - 457 .

RAJABIAN N , SHAHINI A , ASMANI M , et al . Bioengineered skeletal muscle as a model of muscle aging and regeneration [J ] . Tissue Engineering Part A , 2021 , 27 ( 1-2 ): 74 - 86 .

ZHAO M Q , LIU H T , ZHANG X , et al . A flexible microfluidic strategy to generate grooved microfibers for guiding cell alignment [J ] . Biomaterials Science , 2021 , 9 ( 14 ): 4880 - 4890 .

EBRAHIMI M , LAD H , FUSTO A , et al . De novo revertant fiber formation and therapy testing in a 3D culture model of Duchenne muscular dystrophy skeletal muscle [J ] . Acta Biomaterialia , 2021 , 132 : 227 - 244 .

FERREIRA M J S , MANCINI F E , HUMPHREYS P A , et al . Pluripotent stem cells for skeletal tissue engineering [J ] . Critical Reviews in Biotechnology , 2022 , 42 ( 5 ): 774 - 793 .

RAO L J , QIAN Y , KHODABUKUS A , et al . Engineering human pluripotent stem cells into a functional skeletal muscle tissue [J ] . Nature Communications , 2018 , 9 ( 1 ): 126 .

ABUJAROUR R , VALAMEHR B . Generation of skeletal muscle cells from pluripotent stem cells: advances and challenges [J ] . Frontiers in Cell and Developmental Biology , 2015 , 3 : 29 .

URCIUOLO A , SERENA E , GHUA R , et al . Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale [J ] . PLoS One , 2020 , 15 ( 5 ): e0232081 .

CHEESBROUGH A , SCISCIONE F , RICCIO F , et al . Biobased elastomer nanofibers guide light-controlled human-iPSC-derived skeletal myofibers [J ] . Advanced Materials , 2022 , 34 ( 18 ): e2110441 .

SHIMA A , MORIMOTO Y , SWEENEY H L , et al . Three-dimensional contractile muscle tissue consisting of human skeletal myocyte cell line [J ] . Experimental Cell Research , 2018 , 370 ( 1 ): 168 - 173 .

VAN DER WAL E , IULIANO A , IN 'T GROEN S L M , et al . Highly contractile 3D tissue engineered skeletal muscles from human iPSCs reveal similarities with primary myoblast-derived tissues [J ] . Stem Cell Reports , 2023 , 18 ( 10 ): 1954 - 1971 .

WANG Z H , LIU S T , HAN M Y , et al . 3D printing-electrospinning hybrid nanofibrous scaffold as LEGO-like bricks for modular assembling skeletal muscle-on-a-chip functional platform [J/OL ] . Advanced Fiber Materials . ( 2024-06-04 )[ 2024-08-01 ] . https://doi.org/10.1007/s42765-024-00433-5 https://doi.org/10.1007/s42765-024-00433-5 .

NISHIYORI M , UEDA H . Prolonged gabapentin analgesia in an experimental mouse model of fibromyalgia [J ] . Molecular Pain , 2008 , 4 : 52 .

CHOI J S , LEE S J , CHRIST G J , et al . The influence of electrospun aligned poly( Epsilon -caprolactone)/collagen nanofiber meshes on the formation of self-aligned skeletal muscle myotubes [J ] . Biomaterials , 2008 , 29 ( 19 ): 2899 - 2906 .

PARAFATI M , GIZA S , SHENOY T S , et al . Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight [J ] . NPJ Microgravity , 2023 , 9 ( 1 ): 77 .

SERENA E , ZATTI S , ZOSO A , et al . Skeletal muscle differentiation on a chip shows human donor mesoangioblasts' efficiency in restoring dystrophin in a Duchenne muscular dystrophy model [J ] . Stem Cells Translational Medicine , 2016 , 5 ( 12 ): 1676 - 1683 .

FUJIE T , SHI X T , OSTROVIDOV S , et al . Spatial coordination of cell orientation directed by nanoribbon sheets [J ] . Biomaterials , 2015 , 53 : 86 - 94 .

JACOT J G , MCCULLOCH A D , OMENS J H . Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes [J ] . Biophysical Journal , 2008 , 95 ( 7 ): 3479 - 3487 .

ENGLER A J , GRIFFIN M A , SEN S , et al . Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments [J ] . Journal of Cell Biology , 2004 , 166 ( 6 ): 877 - 887 .

ZHANG X , HONG S , YEN R , et al . A system to monitor statin-induced myopathy in individual engineered skeletal muscle myobundles [J ] . Lab on a Chip , 2018 , 18 ( 18 ): 2787 - 2796 .

RANGARAJAN S , MADDEN L , BURSAC N . Use of flow, electrical, and mechanical stimulation to promote engineering of striated muscles [J ] . Annals of Biomedical Engineering , 2014 , 42 ( 7 ): 1391 - 1405 .

FERNÁNDEZ-COSTA J M , TEJEDERA-VILAFRANCA A , FERNÁNDEZ-GARIBAY X , et al . Muscle-on-a-chip devices: a new era for in vitro modelling of muscular dystrophies [J ] . Disease Models & Mechanisms , 2023 , 16 ( 6 ): dmm050107 .

OKANO T , MATSUDA T . Hybrid muscular tissues: preparation of skeletal muscle cell-incorporated collagen gels [J ] . Cell Transplantation , 1997 , 6 ( 2 ): 109 - 118 .

JACKMAN C P , CARLSON A L , BURSAC N . Dynamic culture yields engineered myocardium with near-adult functional output [J ] . Biomaterials , 2016 , 111 : 66 - 79 .

SHADRIN I Y , ALLEN B W , QIAN Y , et al . Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues [J ] . Nature Communications , 2017 , 8 ( 1 ): 1825 .

JUHAS M , ENGELMAYR G C JR , FONTANELLA A N , et al . Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivo [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2014 , 111 ( 15 ): 5508 - 5513 .

CHEEMA U , YANG S Y , MUDERA V , et al . 3-D in vitro model of early skeletal muscle development [J ] . Cell Motility and the Cytoskeleton , 2003 , 54 ( 3 ): 226 - 236 .

CHEEMA U , BROWN R , MUDERA V , et al . Mechanical signals and IGF -Ⅰ gene splicing in vitro in relation to development of skeletal muscle [J ] . Journal of Cellular Physiology , 2005 , 202 ( 1 ): 67 - 75 .

HANDSCHIN C , MORTEZAVI A , PLOCK J , et al . External physical and biochemical stimulation to enhance skeletal muscle bioengineering [J ] . Advanced Drug Delivery Reviews , 2015 , 82-83 : 168 - 175 .

DUGAN J M , CARTMELL S H , GOUGH J E . Uniaxial cyclic strain of human adipose-derived mesenchymal stem cells and C2C12 myoblasts in coculture [J ] . Journal of Tissue Engineering , 2014 , 5 : 2041731414530138 .

BOONEN K J , LANGELAAN M L , POLAK R B , et al . Effects of a combined mechanical stimulation protocol: value for skeletal muscle tissue engineering [J ] . Journal of Biomechanics , 2010 , 43 ( 8 ): 1514 - 1521 .

HEHER P , MALEINER B , PRÜLLER J , et al . A novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain [J ] . Acta Biomaterialia , 2015 , 24 : 251 - 265 .

CHEN Z W , LI B J , ZHAN R Z , et al . Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle [J ] . Science Advances , 2021 , 7 ( 4 ): eabd9502 .

KHODABUKUS A , BAAR K . Defined electrical stimulation emphasizing excitability for the development and testing of engineered skeletal muscle [J ] . Tissue Engineering Part C , Methods, 2012 , 18 ( 5 ): 349 - 357 .

KHODABUKUS A , BAEHR L M , BODINE S C , et al . Role of contraction duration in inducing fast-to-slow contractile and metabolic protein and functional changes in engineered muscle [J ] . Journal of Cellular Physiology , 2015 , 230 ( 10 ): 2489 - 2497 .

HUANG Y C , DENNIS R G , BAAR K . Cultured slow vs . fast skeletal muscle cells differ in physiology and responsiveness to stimulation [J ] . American Journal of Physiology Cell Physiology , 2006 , 291 ( 1 ): C11 - C17 .

EKEN T , ELDER G C B , LØMO T . Development of tonic firing behavior in rat soleus muscle [J ] . Journal of Neurophysiology , 2008 , 99 ( 4 ): 1899 - 1905 .

BANAN SADEGHIAN R , EBRAHIMI M , SALEHI S . Electrical stimulation of microengineered skeletal muscle tissue: effect of stimulus parameters on myotube contractility and maturation [J ] . Journal of Tissue Engineering and Regenerative Medicine , 2018 , 12 ( 4 ): 912 - 922 .

BIAN W N , BURSAC N . Soluble miniagrin enhances contractile function of engineered skeletal muscle [J ] . FASEB Journal , 2012 , 26 ( 2 ): 955 - 965 .

HARDMAN D , NGUYEN M L , DESCROIX S , et al . Mathematical modelling of oxygen transport in a muscle-on-chip device [J ] . Interface Focus , 2022 , 12 ( 5 ): 20220020 .

WAN L , FLEGLE J , OZDOGANLAR B , et al . Toward vasculature in skeletal muscle-on-a-chip through thermo-responsive sacrificial templates [J ] . Micromachines , 2020 , 11 ( 10 ): 907 .

ARRIGONI C , PETTA D , BERSINI S , et al . Engineering complex muscle-tissue interfaces through microfabrication [J ] . Biofabrication , 2019 , 11 ( 3 ): 032004 .

SU W W , YANG Q , LI T , et al . Electrospun aligned nanofiber yarns constructed biomimetic M-type interface integrated into precise co-culture system as muscle-tendon junction-on-a-chip for drug development [J ] . Small Methods , 2024 : e2301754 .

BETTADAPUR A , SUH G C , GEISSE N A , et al . Prolonged culture of aligned skeletal myotubes on micromolded gelatin hydrogels [J ] . Scientific Reports , 2016 , 6 ( 1 ): 28855 .

KIM J H , SEOL Y J , KO I K , et al . 3D bioprinted human skeletal muscle constructs for muscle function restoration [J ] . Scientific Reports , 2018 , 8 ( 1 ): 12307 .

YEO M J , KIM G H . Micro/nano-hierarchical scaffold fabricated using a cell electrospinning/3D printing process for co-culturing myoblasts and HUVECs to induce myoblast alignment and differentiation [J ] . Acta Biomaterialia , 2020 , 107 : 102 - 114 .

NGUYEN M L , DEMRI N , LAPIN B , et al . Studying the impact of geometrical and cellular cues on myogenesis with a skeletal muscle-on-chip [J ] . Lab on a Chip , 2024 , 24 ( 17 ): 4147 - 4160 .

FAN T , WANG S , JIANG Z , et al . Controllable assembly of skeletal muscle-like bundles through 3D bioprinting [J ] . Biofabrication , 2021 , 14 ( 1 ): 015009 .

MONDRINOS M J , ALISAFAEI F , YI A Y , et al . Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue [J ] . Science Advances , 2021 , 7 ( 11 ): eabe9446 .

MILLS R J , PARKER B L , MONNOT P , et al . Development of a human skeletal micro muscle platform with pacing capabilities [J ] . Biomaterials , 2019 , 198 : 217 - 227 .

AFSHAR BAKOOSHLI M , LIPPMANN E S , MULCAHY B , et al . A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction [J ] . eLife , 2019 , 8 : e44530 .

AFSHAR M E , ABRAHA H Y , BAKOOSHLI M A , et al . A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength [J ] . Scientific Reports , 2020 , 10 ( 1 ): 6918 .

KHODABUKUS A , MADDEN L , PRABHU N K , et al . Electrical stimulation increases hypertrophy and metabolic flux in tissue-engineered human skeletal muscle [J ] . Biomaterials , 2019 , 198 : 259 - 269 .

KHODABUKUS A , KAZA A , WANG J , et al . Tissue-engineered human myobundle system as a platform for evaluation of skeletal muscle injury biomarkers [J ] . Toxicological Sciences , 2020 , 176 ( 1 ): 124 - 136 .

AGRAWAL G , AUNG A , VARGHESE S . Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury [J ] . Lab on a Chip , 2017 , 17 ( 20 ): 3447 - 3461 .

OSAKI T , UZEL S G M , KAMM R D . Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons [J ] . Science Advances , 2018 , 4 ( 10 ): eaat5847 .

VANDENBURGH H , SHANSKY J , BENESCH-LEE F , et al . Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts [J ] . FASEB Journal , 2009 , 23 ( 10 ): 3325 - 3334 .

GILBERT-HONICK J , IYER S R , SOMERS S M , et al . Engineering functional and histological regeneration of vascularized skeletal muscle [J ] . Biomaterials , 2018 , 164 : 70 - 79 .

LI J , ZHANG W H , LIU A Q , et al . An engineered anisotropic skeletal muscle organoid-on-a-chip for deciphering muscle response under intermittent hypoxia [J ] . Advanced Functional Materials , 2024 : 2401564 .

JUHL O J 4th , BUETTMANN E G , FRIEDMAN M A , et al . Update on the effects of microgravity on the musculoskeletal system [J ] . NPJ Microgravity , 2021 , 7 ( 1 ): 28 .

REN Z P , AHN E H , DO M , et al . Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues [J ] . NPJ Microgravity , 2024 , 10 ( 1 ): 18 .

KIM S C , AYAN B , SHAYAN M , et al . Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening [J ] . Stem Cell Reports , 2024 , 19 ( 8 ): 1061 - 1073 .

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肝器官芯片在生物医学研究中的应用进展

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