REFERENCES
1. Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330:55-60.
2. Ranade SS, Woo SH, Dubin AE, et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature. 2014;516:121-5.
3. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816-24.
5. Kalukula Y, Ciccone G, Mohammed D, et al. Unlocking the therapeutic potential of cellular mechanobiology. Sci Adv. 2025;11:eaea6817.
6. Di X, Gao X, Peng L, et al. Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets. Signal Transduct Target Ther. 2023;8:282.
7. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19:213-28.
8. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.
9. Zeng Y, Cui X, Li H, Wang Y, Cheng M, Zhang X. Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases. Regen Ther. 2024;26:1069-77.
10. Shah N, Morsi Y, Manasseh R. From mechanical stimulation to biological pathways in the regulation of stem cell fate. Cell Biochem Funct. 2014;32:309-25.
11. Bai C, Ren H, Zhang F, et al. Normal stress on surface of mesenchymal stem cells boosts extracellular vesicle secretion and regenerative bioactivity. J Nanobiotechnology. 2025;23:476.
12. Xiao F, Zuo B, Tao B, et al. Exosomes derived from cyclic mechanical stretch-exposed bone marrow mesenchymal stem cells inhibit RANKL-induced osteoclastogenesis through the NF-κB signaling pathway. Ann Transl Med. 2021;9:798.
13. Qu F, Zhang YF, Wang YY, et al. Cyclic stretch-induced exosomes from periodontal ligament cells promote osteoblasts osteogenic differentiation via the miR-181d-5p/TNF signaling pathway. Arch Oral Biol. 2024;157:105843.
14. Morrell AE, Brown GN, Robinson ST, et al. Mechanically induced Ca2+ oscillations in osteocytes release extracellular vesicles and enhance bone formation. Bone Res. 2018;6:6.
15. Hou Z, Deng L, Fang F, et al. Endothelial cells under disturbed flow release extracellular vesicles to promote inflammatory polarization of macrophages and accelerate atherosclerosis. BMC Biol. 2025;23:20.
16. Li C, Fang F, Wang E, et al. Engineering extracellular vesicles derived from endothelial cells sheared by laminar flow for anti-atherosclerotic therapy through reprogramming macrophage. Biomaterials. 2025;314:122832.
17. Xia B, Gao J, Li S, et al. Mechanical stimulation of Schwann cells promote peripheral nerve regeneration via extracellular vesicle-mediated transfer of microRNA 23b-3p. Theranostics. 2020;10:8974-95.
18. Ye K, Li Z, Yin Y, et al. LIPUS-SCs-Exo promotes peripheral nerve regeneration in cavernous nerve crush injury-induced ED rats via PI3K/Akt/FoxO signaling pathway. CNS Neurosci Ther. 2023;29:3239-58.
19. Welsh JA, Goberdhan DCI, O’Driscoll L, et al. ; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404.
20. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654-9.
21. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255-89.
22. Katzmann DJ, Babst M, Emr SD. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001;106:145-55.
23. Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244-7.
24. van Niel G, Charrin S, Simoes S, et al. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21:708-21.
25. Stuffers S, Sem Wegner C, Stenmark H, Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic. 2009;10:925-37.
26. Ostrowski M, Carmo NB, Krumeich S, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19-30.
27. Hsu C, Morohashi Y, Yoshimura S, et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol. 2010;189:223-32.
28. Liu C, Liu D, Wang S, Gan L, Yang X, Ma C. Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion. J Extracell Vesicles. 2023;12:e12356.
29. Muralidharan-Chari V, Clancy J, Plou C, et al. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol. 2009;19:1875-85.
30. Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q. Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc Natl Acad Sci U S A. 2012;109:4146-51.
31. Chang YJ, Li YS, Wu CC, et al. Extracellular microRNA-92a mediates endothelial cell-macrophage communication. Arterioscler Thromb Vasc Biol. 2019;39:2492-504.
32. Takafuji Y, Tatsumi K, Kawao N, Okada K, Muratani M, Kaji H. Effects of fluid flow shear stress to mouse muscle cells on the bone actions of muscle cell-derived extracellular vesicless. PLoS One. 2021;16:e0250741.
33. Brown SR, Radcliffe ME, Danner JT, et al. Extracellular vesicle-mediated modulation of stem-like phenotype in breast cancer cells under fluid shear stress. Biomolecules. 2024;14:757.
34. Feng T, Li B, Zhang C, et al. Fluid shear stress-mediated upregulated exosomal-IGF2 promotes hepatocellular carcinoma cell migration and metastasis. Am J Cancer Res. 2025;15:4570-85.
35. Wang K, Wei Y, Liu W, et al. Mechanical stress-dependent autophagy component release via extracellular nanovesicles in tumor cells. ACS Nano. 2019;13:4589-602.
36. Guo S, Debbi L, Zohar B, et al. Stimulating extracellular vesicles production from engineered tissues by mechanical forces. Nano Lett. 2021;21:2497-504.
37. Pang A, Cui Y, Chen Y, et al. Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation. Blood. 2018;132:533-43.
38. Liu W, Wang X, Zhang X, Yang Y, Bai S. Shear stress-mediated downregulation of miR-423-5p in M2 macrophage exosomes promotes osteogenic differentiation of bone marrow mesenchymal stem cells. Int Immunopharmacol. 2025;164:115298.
39. Seo Y, Kang H, Park J. Shear stress-induced influx of extracellular calcium ions: a pivotal trigger amplifying the production of mesenchymal stem cell-derived extracellular vesicles. Nanoscale. 2025;17:3861-72.
40. Coly PM, Chatterjee S, Mezine F, et al. Low fluid shear stress stimulates the uptake of noxious endothelial extracellular vesicles via MCAM and PECAM-1 cell adhesion molecules. J Extracell Vesicles. 2024;13:e12414.
41. Bratengeier C, Johansson L, Liszka A, Bakker AD, Hallbeck M, Fahlgren A. Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect. FASEB J. 2024;38:e23323.
42. Gao W, Gu K, Ma L, et al. Interstitial fluid shear stress induces the synthetic phenotype switching of VSMCs to release pro-calcified extracellular vesicles via EGFR-MAPK-KLF5 pathway. Int J Biol Sci. 2024;20:2727-47.
43. Chung J, Kim KH, Yu N, An SH, Lee S, Kwon K. Fluid shear stress regulates the landscape of microRNAs in endothelial cell-derived small extracellular vesicles and modulates the function of endothelial cells. Int J Mol Sci. 2022;23.
44. Kardani A, Hemmer J, Diesel B, et al. Laminar flow alters EV composition in HUVECs: a study of culture medium optimization and molecular profiling of vesicle cargo. Small Methods. 2025;9:e2401841.
45. Li L, Wen J, Li H, et al. Exosomal circ-1199 derived from EPCs exposed to oscillating shear stress acts as a sponge of let-7g-5p to promote endothelial-mesenchymal transition of EPCs by increasing HMGA2 expression. Life Sci. 2023;312:121223.
46. Yun K, Seo Y, Oh Y, et al. Lysyl-tRNA synthetase 1 promotes atherogenesis via autophagy-related secretion and inflammation. Sci Rep. 2025;15:11099.
47. Martins CS, Maggio M, Gorgun C, et al. Mechanical cues and lineage commitment govern the angiogenic potential of mesenchymal cell-derived extracellular vesicles. Adv Biol. 2026;10:e00544.
48. Lee SJ, Jung DK, Im S, et al. Ank-mediated pyrophosphate regulates shear stress-induced small extracellular vesicle production in 3D-cultured osteocytes. Anim Cells Syst. 2024;28:495-505.
49. Sangha GS, Weber CM, Sapp RM, et al. Mechanical stimuli such as shear stress and piezo1 stimulation generate red blood cell extracellular vesicles. Front Physiol. 2023;14:1246910.
50. Wu B, Zhang T, Chen H, et al. Exosomes derived from bone marrow mesenchymal stem cell preconditioned by low-intensity pulsed ultrasound stimulation promote bone-tendon interface fibrocartilage regeneration and ameliorate rotator cuff fatty infiltration. J Orthop Translat. 2024;48:89-106.
51. Ma X, Yamaguchi A, Maeshige N, et al. Facilitatory effect of low-pulse repetition frequency ultrasound on release of extracellular vesicles from cultured myotubes. J Med Ultrason. 2024;51:397-405.
52. Li W, Saleh NA, Gao C, et al. Dynamic reorganization of multivesicular bodies and exosome production impacted by sonoporation. Sci Rep. 2024;14:27432.
53. Zheng Y, Xu P, Pan C, et al. Production and biological effects of extracellular vesicles from adipose-derived stem cells were markedly increased by low-intensity ultrasound stimulation for promoting diabetic wound healing. Stem Cell Rev Rep. 2023;19:784-806.
54. Yamaguchi A, Maeshige N, Noguchi H, et al. Pulsed ultrasound promotes secretion of anti-inflammatory extracellular vesicles from skeletal myotubes via elevation of intracellular calcium level. Elife. 2023;12:RP89512.
55. Xia P, Wang Q, Song J, et al. Low-intensity pulsed ultrasound enhances the efficacy of bone marrow-derived MSCs in osteoarthritis cartilage repair by regulating autophagy-mediated exosome release. Cartilage. 2022;13:19476035221093060.
56. Deng Z, Wang J, Xiao Y, et al. Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-β-induced neurotoxicity. Theranostics. 2021;11:4351-62.
57. Maeshige N, Langston PK, Yuan ZM, Kondo H, Fujino H. High-intensity ultrasound irradiation promotes the release of extracellular vesicles from C2C12 myotubes. Ultrasonics. 2021;110:106243.
58. Peng D, Reed-Maldonado AB, Zhou F, et al. Exosome released from schwann cells may be involved in microenergy acoustic pulse-associated cavernous nerve regeneration. J Sex Med. 2020;17:1618-28.
59. Wang Y, Liu Z, Pan C, et al. Ultrasound-driven healing: unleashing the potential of chondrocyte-derived extracellular vesicles for chondrogenesis in adipose-derived stem cells. Biomedicines. 2023;11:2836.
60. Li X, Li X, Lin J, Sun X, Ding Q. Exosomes derived from low-intensity pulsed ultrasound-treated dendritic cells suppress tumor necrosis factor-induced endothelial inflammation. J Ultrasound Med. 2019;38:2081-91.
61. Li X, Zhong Y, Zhou W, et al. Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles. Cell Mol Biol Lett. 2023;28:9.
62. Zhang T, Chen Z, Zhu M, et al. Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis. Genes Dis. 2023;10:1613-25.
63. Sun P, Li Y, Li Y, et al. Low-intensity pulsed ultrasound protects from inflammatory dilated cardiomyopathy through inciting extracellular vesicles. Cardiovasc Res. 2024;120:1177-90.
64. Xiang M, Guo Q, Liu Y, et al. Low-intensity pulsed ultrasound enhances the osteogenic potential of PDLSCs-derived extracellular vesicles through COMP/PI3K/AKT. FASEB J. 2025;39:e70299.
65. August Ambattu L, Ramesan S, Dekiwadia C, et al. High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium- dependent mechanism. Biophys J. 2021;120:111a.
66. Yuana Y, Jiang L, Lammertink BHA, et al. Microbubbles-assisted ultrasound triggers the release of extracellular vesicles. Int J Mol Sci. 2017;18.
67. Jiang R, Wang H, Zhong F, et al. Low-intensity pulsed ultrasound as a strategy to boost exosome secretion by adipose-derived stem cells and uptake for myocardial infarction therapy. Biomed Mater. 2025;20:045025.
68. Zeng Q, Hong S, Wang X, Cheng Y, Sun J, Xia W. Regulation of exosomes secretion by low-intensity pulsed ultrasound in lung cancer cells. Exp Cell Res. 2019;383:111448.
69. Yin X, Yi J, Mao F, et al. Identification of key miRNAs and target genes in extracellular vesicles derived from low-intensity pulsed ultrasound-treated stem cells. Front Genet. 2024;15:1407671.
70. Lei Z, Jiang H, Liu J, et al. Audible acoustic wave promotes EV formation and secretion from adherent cancer cells via mechanical stimulation. ACS Appl Mater Interfaces. 2023;15:53859-70.
71. Qiu Y, Lv Z, Zhu X, Yang X, Wan J. 3D mechanical stimulation modulates endothelial exosomes to promote fibroblast activation. Tissue Cell. 2026;99:103316.
72. Wang Z, Maruyama K, Sakisaka Y, et al. Cyclic stretch force induces periodontal ligament cells to secrete exosomes that suppress IL-1β production through the inhibition of the NF-κB signaling pathway in macrophages. Front Immunol. 2019;10:1310.
73. Wu Y, Qu F, Zhang Y, et al. Exosomes from cyclic stretched periodontal ligament cells induced periodontal inflammation through miR-9-5p/SIRT1/NF-κB signaling Pathway. J Immunol. 2023;210:2001-15.
74. Tian L, Zhang D, Wang Z, et al. MiR-877, an exosomal miRNA from mechanical stretch induced adipose derived stromal cells, enhances fracture healing in nonunion rats with type 2 diabetes mellitus. Stem Cell Res Ther. 2025;16:575.
75. Wang F, Li S, Kong L, et al. Tensile stress-activated and exosome-transferred YAP/TAZ-notch circuit specifies type H endothelial cell for segmental bone regeneration. Adv Sci. 2024;11:e2309133.
76. Xu N, Cui G, Zhao S, et al. Therapeutic effects of mechanical stress-induced C2C12-derived exosomes on glucocorticoid-induced osteoporosis through miR-92a-3p/PTEN/AKT signaling pathway. Int J Nanomedicine. 2023;18:7583-603.
77. Mullen M, Williams K, LaRocca T, et al. Mechanical strain drives exosome production, function, and miRNA cargo in C2C12 muscle progenitor cells. J Orthop Res. 2023;41:1186-97.
78. Najrana T, Mahadeo A, Abu-Eid R, et al. Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells. J Cell Physiol. 2020;235:8210-23.
79. Shaver M, Gomez K, Kaiser K, Hutcheson JD. Mechanical stretch leads to increased caveolin-1 content and mineralization potential in extracellular vesicles from vascular smooth muscle cells. BMC Mol Cell Biol. 2024;25:8.
80. Wang Y, Goliwas KF, Severino PE, et al. Mechanical strain induces phenotypic changes in breast cancer cells and promotes immunosuppression in the tumor microenvironment. Lab Invest. 2020;100:1503-16.
81. Xie F, Wen G, Sun W, et al. Mechanical stress promotes angiogenesis through fibroblast exosomes. Biochem Biophys Res Commun. 2020;533:346-53.
82. Chen YW, Lin YH, Ho CC, et al. High-yield extracellular vesicle production from HEK293T cells encapsulated in 3D auxetic scaffolds with cyclic mechanical stimulation for effective drug carrier systems. Biofabrication. 2024;16:045035.
83. Chen M, Li Y, Yang Z, et al. M2-exo promote orthodontic bone remodeling via the MeCP2-TCF20-HDAC1 axis. Stem Cell Res Ther. 2025;16:569.
84. Huang S, Kuri P, Zou J, et al. Stress vesicles link epidermal mechanotransduction to stem cell differentiation. Nat Commun. 2026;17:1578.
85. Pu P, Wu S, Zhang K, et al. Mechanical force induces macrophage-derived exosomal UCHL3 promoting bone marrow mesenchymal stem cell osteogenesis by targeting SMAD1. J Nanobiotechnology. 2023;21:88.
86. Zheng X, Zhao N, Peng L, et al. Biological characteristics of microRNAs secreted by exosomes of periodontal ligament stem cells due to mechanical force. Eur J Orthod. 2023;45:408-17.
87. Hao R, Hu S, Zhang H, et al. Mechanical stimulation on a microfluidic device to highly enhance small extracellular vesicle secretion of mesenchymal stem cells. Mater Today Bio. 2023;18:100527.
88. Haraszti RA, Miller R, Stoppato M, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol Ther. 2018;26:2838-47.
89. Kim M, Yun HW, Park DY, Choi BH, Min BH. Three-dimensional spheroid culture increases exosome secretion from mesenchymal stem cells. Tissue Eng Regen Med. 2018;15:427-36.
90. Cao J, Wang B, Tang T, et al. Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury. Stem Cell Res Ther. 2020;11:206.
91. Kim JY, Rhim WK, Cha SG, et al. Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media. Nano Converg. 2022;9:57.
92. Khan NLA, Muhandiram S, Dissanayake K, et al. Effect of 3D and 2D cell culture systems on trophoblast extracellular vesicle physico-chemical characteristics and potency. Front Cell Dev Biol. 2024;12:1382552.
93. Lenzini S, Debnath K, Joshi JC, et al. Cell-matrix interactions regulate functional extracellular vesicle secretion from mesenchymal stromal cells. ACS Nano. 2021;15:17439-52.
94. Mahadik P, Patwardhan S. ECM stiffness-regulated exosomal thrombospondin-1 promotes tunneling nanotubes-based cellular networking in breast cancer cells. Arch Biochem Biophys. 2023;742:109624.
95. Wu B, Liu DA, Guan L, et al. Stiff matrix induces exosome secretion to promote tumour growth. Nat Cell Biol. 2023;25:415-24.
96. Ferrara B, Bourgoin-Voillard S, Habert D, et al. Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines. Proteomics. 2024;24:e2400058.
97. Liu Z, Liu Y, Li Y, et al. ECM stiffness affects cargo sorting into MSC-EVs to regulate their secretion and uptake behaviors. J Nanobiotechnology. 2024;22:124.
98. Yang Z, Li R, An L, et al. Tumor mechanobiology-inspired nanomechanics: Piezo1 mediated tumor-associated macrophages reprogramming and exosome-driven immune amplification. ACS Nano. 2025;19:41746-64.
99. Yang J, Celebi LE, Hawthorne L, Ozcebe SG, Zorlutuna P. Substrate stiffness modulates fibroblast extracellular vesicle secretion via mechanotransduction pathways. Small. 2025;21:e05261.
100. Wang Z, Xie X, Zhou Y, et al. 3D nanofibrillar matrix stiffness modulates extracellular vesicle cargo and pro-tumour functions. J Extracell Vesicles. 2025;14:e70165.
101. Zhao Y, Yu H, Li J, et al. A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma. Nat Commun. 2025;16:1736.
102. Pironti G, Strachan RT, Abraham D, et al. Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circulation. 2015;131:2120-30.
103. Wang Z, Li Z, Wang L, et al. Cellular adaptation to mechanical stress emerges via cell shrinkage triggered by nonlinear calcium elevation. Adv Sci. 2025;12:e03659.
104. Parvanian S, Zha H, Su D, et al. Exosomal vimentin from adipocyte progenitors protects fibroblasts against osmotic stress and inhibits apoptosis to enhance wound healing. Int J Mol Sci. 2021;22:4678.
105. Liu G, Wang Y, Pan Y, et al. Hypertonicity induces mitochondrial extracellular vesicles (MEVs) that activate TNF-α and β-catenin signaling to promote adipocyte dedifferentiation. Stem Cell Res Ther. 2023;14:333.
106. Yoshikawa K, Saito S, Kadonosono T, Tanaka M, Okochi M. Osmotic stress induces the formation of migrasome-like vesicles. FEBS Lett. 2024;598:437-45.
107. Ene J, Liu C, Syed F, et al. Biomanufacturing and lipidomics analysis of extracellular vesicles secreted by human blood vessel organoids in a vertical wheel bioreactor. Stem Cell Res Ther. 2025;16:207.
108. Ene J, Muok L, Gonzalez V, et al. Biomanufacturing and curcumin-loading of human choroid plexus organoid-derived extracellular vesicles from a vertical-wheel bioreactor to alleviate neuro-inflammation. Biomedicines. 2025;13:1069.
109. Huang H, Xiao L, Fang L, et al. Static topographical cue combined with dynamic fluid stimulation enhances the macrophage extracellular vesicle yield and therapeutic potential for bone defects. ACS Nano. 2025;19:8667-91.
110. Muok L, Sun L, Esmonde C, et al. Extracellular vesicle biogenesis of three-dimensional human pluripotent stem cells in a novel Vertical-Wheel bioreactor. J Extracell Biol. 2024;3:e133.
111. Chen J, Zhang E, Wan Y, Huang T, Wang Y, Jiang H. A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment. J Nanobiotechnology. 2024;22:300.
112. Min Lim K, Kim S, Yeom J, et al. Advanced 3D dynamic culture system with transforming growth factor-β3 enhances production of potent extracellular vesicles with modified protein cargoes via upregulation of TGF-β signaling. J Adv Res. 2023;47:57-74.
113. Jeske R, Liu C, Duke L, et al. Upscaling human mesenchymal stromal cell production in a novel vertical-wheel bioreactor enhances extracellular vesicle secretion and cargo profile. Bioact Mater. 2023;25:732-47.
114. Yuan X, Sun L, Jeske R, et al. Engineering extracellular vesicles by three-dimensional dynamic culture of human mesenchymal stem cells. J Extracell Vesicles. 2022;11:e12235.
115. Wu J, Wu D, Wu G, et al. Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy. Biofabrication. 2022;14:045004.
116. Yan L, Liu G, Wu X. Exosomes derived from umbilical cord mesenchymal stem cells in mechanical environment show improved osteochondral activity via upregulation of LncRNA H19. J Orthop Translat. 2021;26:111-20.
117. Gobin J, Muradia G, Mehic J, et al. Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell. Stem Cell Res Ther. 2021;12:127.
118. de Almeida Fuzeta M, Bernardes N, Oliveira FD, et al. Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under Serum-/Xeno-Free conditions in a microcarrier-based bioreactor culture system. Front Cell Dev Biol. 2020;8:553444.
119. Yan L, Wu X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biol Toxicol. 2020;36:165-78.
120. Cha JM, Shin EK, Sung JH, et al. Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells. Sci Rep. 2018;8:1171.
122. Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol. 2009;10:75-82.
123. Cox CD, Bae C, Ziegler L, et al. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat Commun. 2016;7:10366.
124. Li Z, Lee H, Zhu C. Molecular mechanisms of mechanotransduction in integrin-mediated cell-matrix adhesion. Exp Cell Res. 2016;349:85-94.
125. Wei T, Wang ZZ. Integrin signaling and ECM proteins in hPSC maintenance and differentiation. Front Biosci. 2026;31:46332.
126. Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179-83.
128. Warboys CM. Mechanoactivation of Wnt/β-catenin pathways in health and disease. Emerg Top Life Sci. 2018;2:701-12.
129. Andreu I, Falcones B, Hurst S, et al. The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening. Nat Commun. 2021;12:4229.
130. Jansen KA, Donato DM, Balcioglu HE, Schmidt T, Danen EH, Koenderink GH. A guide to mechanobiology: Where biology and physics meet. Biochim Biophys Acta. 2015;1853:3043-52.
131. Wu D, Zhao X, Xie J, et al. Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine. Cell Prolif. 2024;57:e13630.
132. Thompson W, Papoutsakis ET. The role of biomechanical stress in extracellular vesicle formation, composition and activity. Biotechnol Adv. 2023;66:108158.
133. Parihar K, Liu DA, Hassan G, et al. Mechanical regulation of extracellular vesicle activity during tumour progression. Nat Biomed Eng. 2025;9:1202-21.
134. Williams JK, Ngo JM, Lehman IM, Schekman R. Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair. Elife. 2023;12:e86556.
135. Mercier V, Larios J, Molinard G, et al. Endosomal membrane tension regulates ESCRT-III-dependent intra-lumenal vesicle formation. Nat Cell Biol. 2020;22:947-59.
136. Sedgwick AE, Clancy JW, Olivia Balmert M, D’Souza-Schorey C. Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci Rep. 2015;5:14748.
137. Li Q, Ding Y, Shi Y, et al. 80 years of extracellular vesicles: from discovery to clinical translation. Extracell Vesicles Circ Nucl Acids. 2026;7:165-233.
138. Gelibter S, Marostica G, Mandelli A, et al. The impact of storage on extracellular vesicles: a systematic study. J Extracell Vesicles. 2022;11:e12162.
139. Geeurickx E, Lippens L, Rappu P, De Geest BG, De Wever O, Hendrix A. Recombinant extracellular vesicles as biological reference material for method development, data normalization and assessment of (pre-)analytical variables. Nat Protoc. 2021;16:603-33.
140. Dong L, Zieren RC, Horie K, et al. Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium. J Extracell Vesicles. 2020;10:e12044.
141. Williams S, Fernandez-Rhodes M, Law A, Peacock B, Lewis MP, Davies OG. Comparison of extracellular vesicle isolation processes for therapeutic applications. J Tissue Eng. 2023;14:20417314231174609.
142. Visan KS, Lobb RJ, Ham S, et al. Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles. J Extracell Vesicles. 2022;11:e12266.
143. Welsh JA, van der Pol E, Bettin BA, et al. Towards defining reference materials for measuring extracellular vesicle refractive index, epitope abundance, size and concentration. J Extracell Vesicles. 2020;9:1816641.
144. Dixson AC, Dawson TR, Di Vizio D, Weaver AM. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat Rev Mol Cell Biol. 2023;24:454-76.
145. Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013;4:2980.
146. Yang R, Feng K, Wang J, et al. Cell mechanical microenvironment modulates the secretion phenotype of mesenchymal stem cell-derived exosomes for diabetic wound therapy. Biomater Adv. 2026;180:214614.
147. Hergenreider E, Heydt S, Tréguer K, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14:249-56.
148. Dai W, Dong Y, Han T, Wang J, Gao B, et al. Microenvironmental cue-regulated exosomes as therapeutic strategies for improving chronic wound healing. NPG Asia Materials. 2022;14.
149. Zhang J, Li J, Hou Y, et al. Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor. Cell. 2024;187:3409-26.e24.
150. Xie F, Zhou X, Su P, et al. Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-β type II receptor signaling. Nat Commun. 2022;13:4461.
151. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285:17442-52.
152. Menck K, Sönmezer C, Worst TS, et al. Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane. J Extracell Vesicles. 2017;6:1378056.
153. Debnath K, Heras KL, Rivera A, Lenzini S, Shin JW. Extracellular vesicle-matrix interactions. Nat Rev Mater. 2023;8:390-402.
154. Kang M, Jordan V, Blenkiron C, Chamley LW. Biodistribution of extracellular vesicles following administration into animals: a systematic review. J Extracell Vesicles. 2021;10:e12085.
155. Verweij FJ, Revenu C, Arras G, et al. Live tracking of inter-organ communication by endogenous exosomes in vivo. Dev Cell. 2019;48:573-89.e4.
156. Bunne C, Roohani Y, Rosen Y, et al. How to build the virtual cell with artificial intelligence: priorities and opportunities. Cell. 2024;187:7045-63.
157. Fernandez-Sanchez ME, Brunet T, Röper JC, Farge E. Mechanotransduction’s impact on animal development, evolution, and tumorigenesis. Annu Rev Cell Dev Biol. 2015;31:373-97.
159. Scott IU, Campochiaro PA, Newman NJ, Biousse V. Retinal vascular occlusions. Lancet. 2020;396:1927-40.
160. Wang Y, Li Y, Feng J, Wang C, Wan Y, et al. Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion. eLife. 2024;13:RP98949.
161. Wang C, Chen X, Li Y, et al. Risks of stroke and myocardial infarction after retinal artery occlusion and their time dependence: a systematic review and meta-analysis. J Neurol. 2025;272:712.
162. Wan Y, Chen T, Li Y, et al. Clinical application of multicolor scanning laser ophthalmology in diagnosis and grading of central retinal artery occlusion. Front Neurosci. 2024;18:1327806.







