Skip to main content

Advertisement

Springer Nature Link
Log in

Vascularized organoid-on-a-chip: design, imaging, and analysis

  • Review Paper
  • Published:
Angiogenesis Aims and scope Submit manuscript

Abstract

Vascularized organoid-on-a-chip (VOoC) models achieve substance exchange in deep layers of organoids and provide a more physiologically relevant system in vitro. Common designs for VOoC primarily involve two categories: self-assembly of endothelial cells (ECs) to form microvessels and pre-patterned vessel lumens, both of which include the hydrogel region for EC growth and allow for controlled fluid perfusion on the chip. Characterizing the vasculature of VOoC often relies on high-resolution microscopic imaging. However, the high scattering of turbid tissues can limit optical imaging depth. To overcome this limitation, tissue optical clearing (TOC) techniques have emerged, allowing for 3D visualization of VOoC in conjunction with optical imaging techniques. The acquisition of large-scale imaging data, coupled with high-resolution imaging in whole-mount preparations, necessitates the development of highly efficient analysis methods. In this review, we provide an overview of the chip designs and culturing strategies employed for VOoC, as well as the applicable optical imaging and TOC methods. Furthermore, we summarize the vascular analysis techniques employed in VOoC, including deep learning. Finally, we discuss the existing challenges in VOoC and vascular analysis methods and provide an outlook for future development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Ma C, Peng Y, Li H, Chen W (2021) Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol Sci 42(2):119–133. https://doi.org/10.1016/j.tips.2020.11.009

    Article  CAS  PubMed  Google Scholar 

  2. Ingber DE (2022) Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet 23(8):467–491. https://doi.org/10.1038/s41576-022-00466-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32(8):760–772. https://doi.org/10.1038/nbt.2989

    Article  CAS  PubMed  Google Scholar 

  4. Jain RK, Au P, Tam J, Duda DG, Fukumura D (2005) Engineering vascularized tissue. Nat Biotechnol 23(7):821–823. https://doi.org/10.1038/nbt0705-821

    Article  CAS  PubMed  Google Scholar 

  5. Shirure VS, Hughes CCW, George SC (2021) Engineering vascularized organoid-on-a-chip models. Annu Rev Biomed Eng 23:141–167. https://doi.org/10.1146/annurev-bioeng-090120-094330

    Article  CAS  PubMed  Google Scholar 

  6. Park SE, Georgescu A, Huh D (2019) Organoids-on-a-chip. Science 364(6444):960–965. https://doi.org/10.1126/science.aaw7894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sonntag F, Schilling N, Mader K, Gruchow M, Klotzbach U, Lindner G, Horland R, Wagner I, Lauster R, Howitz S, Hoffmann S, Marx U (2010) Design and prototyping of a chip-based multi-micro-organoid culture system for substance testing, predictive to human (substance) exposure. J Biotechnol 148(1):70–75. https://doi.org/10.1016/j.jbiotec.2010.02.001

    Article  CAS  PubMed  Google Scholar 

  8. Chen YY, Silva PN, Syed AM, Sindhwani S, Rocheleau JV, Chan WC (2016) Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis. Proc Natl Acad Sci U S A 113(52):14915–14920. https://doi.org/10.1073/pnas.1609569114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Grist SM, Nasseri SS, Poon T, Roskelley C, Cheung KC (2016) On-chip clearing of arrays of 3-D cell cultures and micro-tissues. Biomicrofluidics 10(4):044107. https://doi.org/10.1063/1.4959031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dekkers JF, Alieva M, Wellens LM, Ariese HCR, Jamieson PR, Vonk AM, Amatngalim GD, Hu H, Oost KC, Snippert HJG, Beekman JM, Wehrens EJ, Visvader JE, Clevers H, Rios AC (2019) High-resolution 3D imaging of fixed and cleared organoids. Nat Protoc 14(6):1756–1771. https://doi.org/10.1038/s41596-019-0160-8

    Article  CAS  PubMed  Google Scholar 

  11. Ma H, Chen J, Deng Z, Sun T, Luo Q, Gong H, Li X, Long B (2022) Multiscale analysis of cellular composition and morphology in intact cerebral organoids. Biology (Basel) 11(9):1270. https://doi.org/10.3390/biology11091270

    Article  CAS  PubMed  Google Scholar 

  12. Zhang Y, Shin Y, Sung K, Yang S, Chen H, Wang H, Teng D, Rivenson Y, Kulkarni RP, Ozcan A (2017) 3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy. Sci Adv 3(8):e1700553. https://doi.org/10.1126/sciadv.1700553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Silva Santisteban T, Rabajania O, Kalinina I, Robinson S, Meier M (2017) Rapid spheroid clearing on a microfluidic chip. Lab Chip 18(1):153–161. https://doi.org/10.1039/c7lc01114h

    Article  CAS  PubMed  Google Scholar 

  14. Ahn J, Kim DH, Koo DJ, Lim J, Park TE, Lee J, Ko J, Kim S, Kim M, Kang KS, Min DH, Kim SY, Kim Y, Jeon NL (2023) 3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing. Acta Biomater 165:153–167. https://doi.org/10.1016/j.actbio.2022.10.009

    Article  CAS  PubMed  Google Scholar 

  15. Susaki EA, Ueda HR (2016) Whole-body and whole-organ clearing and imaging techniques with single-cell resolution: toward organism-level systems biology in mammals. Cell Chem Biol 23(1):137–157. https://doi.org/10.1016/j.chembiol.2015.11.009

    Article  CAS  PubMed  Google Scholar 

  16. Zhao S, Todorov MI, Cai R, Maskari RA, Steinke H, Kemter E, Mai H, Rong Z, Warmer M, Stanic K, Schoppe O, Paetzold JC, Gesierich B, Wong MN, Huber TB, Duering M, Bruns OT, Menze B, Lipfert J, Puelles VG, Wolf E, Bechmann I, Erturk A (2020) Cellular and molecular probing of intact human organs. Cell 180(4):796–812e719. https://doi.org/10.1016/j.cell.2020.01.030

  17. LeCun Y, Bengio Y, Hinton G (2015) Deep learning. Nature 521(7553):436–444. https://doi.org/10.1038/nature14539

    Article  CAS  PubMed  Google Scholar 

  18. Mencattini A, Di Giuseppe D, Comes MC, Casti P, Corsi F, Bertani FR, Ghibelli L, Businaro L, Di Natale C, Parrini MC, Martinelli E (2020) Discovering the hidden messages within cell trajectories using a deep learning approach for in vitro evaluation of cancer drug treatments. Sci Rep 10(1):7653. https://doi.org/10.1038/s41598-020-64246-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bannon D, Moen E, Schwartz M, Borba E, Kudo T, Greenwald N, Vijayakumar V, Chang B, Pao E, Osterman E, Graf W, Van Valen D (2021) DeepCell Kiosk: scaling deep learning-enabled cellular image analysis with Kubernetes. Nat Methods 18(1):43–45. https://doi.org/10.1038/s41592-020-01023-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Haberl MG, Churas C, Tindall L, Boassa D, Phan S, Bushong EA, Madany M, Akay R, Deerinck TJ, Peltier ST, Ellisman MH (2018) CDeep3M-Plug-and-Play cloud-based deep learning for image segmentation. Nat Methods 15(9):677–680. https://doi.org/10.1038/s41592-018-0106-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rota A, Possenti L, Offeddu GS, Senesi M, Stucchi A, Venturelli I, Rancati T, Zunino P, Kamm RD, Costantino ML (2023) A three-dimensional method for morphological analysis and flow velocity estimation in microvasculature on-a-chip. Bioeng Transl Med 8(5):e10557. https://doi.org/10.1002/btm2.10557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tetteh G, Efremov V, Forkert ND, Schneider M, Kirschke J, Weber B, Zimmer C, Piraud M, Menze BH (2020) DeepVesselNet: vessel segmentation, centerline prediction, and bifurcation detection in 3-D angiographic volumes. Front Neurosci 14:592352. https://doi.org/10.3389/fnins.2020.592352

    Article  PubMed  PubMed Central  Google Scholar 

  23. Qiu Y, Ahn B, Sakurai Y, Hansen CE, Tran R, Mimche PN, Mannino RG, Ciciliano JC, Lamb TJ, Joiner CH, Ofori-Acquah SF, Lam WA (2018) Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease. Nat Biomed Eng 2:453–463. https://doi.org/10.1038/s41551-018-0224-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li Q, Niu K, Wang D, Xuan L, Wang X (2022) Low-cost rapid prototyping and assembly of an open microfluidic device for a 3D vascularized organ-on-a-chip. Lab Chip 22(14):2682–2694. https://doi.org/10.1039/d1lc00767j

    Article  CAS  PubMed  Google Scholar 

  25. Kim Y, Ko J, Shin N, Park S, Lee SR, Kim S, Song J, Lee S, Kang KS, Lee J, Jeon NL (2022) All-in-one microfluidic design to integrate vascularized tumor spheroid into high-throughput platform. Biotechnol Bioeng 119(12):3678–3693. https://doi.org/10.1002/bit.28221

    Article  CAS  PubMed  Google Scholar 

  26. Myers DR, Lam WA (2021) Vascularized microfluidics and their untapped potential for discovery in diseases of the microvasculature. Annu Rev Biomed Eng 23:407–432. https://doi.org/10.1146/annurev-bioeng-091520-025358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Farahat WA, Wood LB, Zervantonakis IK, Schor A, Ong S, Neal D, Kamm RD, Asada HH (2012) Ensemble analysis of angiogenic growth in three-dimensional microfluidic cell cultures. PLoS ONE 7(5):e37333. https://doi.org/10.1371/journal.pone.0037333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zeinali S, Bichsel CA, Hobi N, Funke M, Marti TM, Schmid RA, Guenat OT, Geiser T (2018) Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro. Angiogenesis 21(4):861–871. https://doi.org/10.1007/s10456-018-9631-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim J, Lee KT, Lee JS, Shin J, Cui B, Yang K, Choi YS, Choi N, Lee SH, Lee JH, Bahn YS, Cho SW (2021) Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood–brain barrier. Nat Biomed Eng 5(8):830–846. https://doi.org/10.1038/s41551-021-00743-8

    Article  PubMed  Google Scholar 

  30. Wang L, Tao T, Su W, Yu H, Yu Y, Qin J (2017) A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice. Lab Chip 17(10):1749–1760. https://doi.org/10.1039/c7lc00134g

    Article  CAS  PubMed  Google Scholar 

  31. Vulto P, Podszun S, Meyer P, Hermann C, Manz A, Urban GA (2011) Phaseguides: a paradigm shift in microfluidic priming and emptying. Lab Chip 11(9):1596–1602. https://doi.org/10.1039/c0lc00643b

    Article  CAS  PubMed  Google Scholar 

  32. Kramer B, Corallo C, van den Heuvel A, Crawford J, Olivier T, Elstak E, Giordano N, Vulto P, Lanz HL, Janssen RAJ, Tessari MA (2022) High-throughput 3D microvessel-on-a-chip model to study defective angiogenesis in systemic sclerosis. Sci Rep 12(1):16930. https://doi.org/10.1038/s41598-022-21468-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hajal C, Offeddu GS, Shin Y, Zhang S, Morozova O, Hickman D, Knutson CG, Kamm RD (2022) Engineered human blood–brain barrier microfluidic model for vascular permeability analyses. Nat Protoc 17(1):95–128. https://doi.org/10.1038/s41596-021-00635-w

    Article  CAS  PubMed  Google Scholar 

  34. van Duinen V, Zhu D, Ramakers C, van Zonneveld AJ, Vulto P, Hankemeier T (2019) Perfused 3D angiogenic sprouting in a high-throughput in vitro platform. Angiogenesis 22(1):157–165. https://doi.org/10.1007/s10456-018-9647-0

    Article  CAS  PubMed  Google Scholar 

  35. Soragni C, Queiroz K, Ng CP, Stok A, Olivier T, Tzagkaraki D, Heijmans J, Suijker J, de Ruiter SPM, Olczyk A, Bokkers M, Schavemaker F, Trietsch SJ, Lanz HL, Vulto P, Joore J (2023) Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay. Angiogenesis. https://doi.org/10.1007/s10456-023-09888-3

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wevers NR, Nair AL, Fowke TM, Pontier M, Kasi DG, Spijkers XM, Hallard C, Rabussier G, van Vught R, Vulto P, de Vries HE, Lanz HL (2021) Modeling ischemic stroke in a triculture neurovascular unit on-a-chip. Fluids Barriers CNS 18(1):59. https://doi.org/10.1186/s12987-021-00294-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lyu Z, Park J, Kim KM, Jin HJ, Wu H, Rajadas J, Kim DH, Steinberg GK, Lee W (2021) A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke. Nat Biomed Eng 5(8):847–863. https://doi.org/10.1038/s41551-021-00744-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bonanini F, Kurek D, Previdi S, Nicolas A, Hendriks D, de Ruiter S, Meyer M, ClapesCabrer M, Dinkelberg R, Garcia SB, Kramer B, Olivier T, Hu H, Lopez-Iglesias C, Schavemaker F, Walinga E, Dutta D, Queiroz K, Domansky K, Ronden B, Joore J, Lanz HL, Peters PJ, Trietsch SJ, Clevers H, Vulto P (2022) In vitro grafting of hepatic spheroids and organoids on a microfluidic vascular bed. Angiogenesis 25(4):455–470. https://doi.org/10.1007/s10456-022-09842-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Trietsch SJ, Naumovska E, Kurek D, Setyawati MC, Vormann MK, Wilschut KJ, Lanz HL, Nicolas A, Ng CP, Joore J, Kustermann S, Roth A, Hankemeier T, Moisan A, Vulto P (2017) Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes. Nat Commun 8(1):262. https://doi.org/10.1038/s41467-017-00259-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wong JF, Mohan MD, Young EWK, Simmons CA (2020) Integrated electrochemical measurement of endothelial permeability in a 3D hydrogel-based microfluidic vascular model. Biosens Bioelectron 147:111757. https://doi.org/10.1016/j.bios.2019.111757

    Article  CAS  PubMed  Google Scholar 

  41. Wevers NR, Kasi DG, Gray T, Wilschut KJ, Smith B, van Vught R, Shimizu F, Sano Y, Kanda T, Marsh G (2018) A perfused human blood–brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport. Fluids Barriers CNS 15(1):1–12. https://doi.org/10.1186/s12987-018-0108-3

    Article  CAS  Google Scholar 

  42. Sobrino A, Phan DT, Datta R, Wang X, Hachey SJ, Romero-Lopez M, Gratton E, Lee AP, George SC, Hughes CC (2016) 3D microtumors in vitro supported by perfused vascular networks. Sci Rep 6:31589. https://doi.org/10.1038/srep31589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Phan DTT, Wang X, Craver BM, Sobrino A, Zhao D, Chen JC, Lee LYN, George SC, Lee AP, Hughes CCW (2017) A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab Chip 17(3):511–520. https://doi.org/10.1039/c6lc01422d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang X, Phan DT, Sobrino A, George SC, Hughes CC, Lee AP (2016) Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab Chip 16(2):282–290. https://doi.org/10.1039/c5lc01050k

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hachey SJ, Movsesyan S, Nguyen QH, Burton-Sojo G, Tankazyan A, Wu J, Hoang T, Zhao D, Wang S, Hatch MM, Celaya E, Gomez S, Chen GT, Davis RT, Nee K, Pervolarakis N, Lawson DA, Kessenbrock K, Lee AP, Lowengrub J, Waterman ML, Hughes CCW (2021) An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy. Lab Chip 21(7):1333–1351. https://doi.org/10.1039/d0lc01216e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yue T, Zhao D, Phan DTT, Wang X, Park JJ, Biviji Z, Hughes CCW, Lee AP (2021) A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks. Microsyst Nanoeng 7:4. https://doi.org/10.1038/s41378-020-00229-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Winkelman MA, Kim DY, Kakarla S, Grath A, Silvia N, Dai G (2021) Interstitial flow enhances the formation, connectivity, and function of 3D brain microvascular networks generated within a microfluidic device. Lab Chip 22(1):170–192. https://doi.org/10.1039/d1lc00605c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pauty J, Nakano S, Usuba R, Nakajima T, Johmura Y, Omori S, Sakamoto N, Kikuchi A, Nakanishi M, Matsunaga YT (2021) A 3D tissue model-on-a-chip for studying the effects of human senescent fibroblasts on blood vessels. Biomater Sci 9(1):199–211. https://doi.org/10.1039/d0bm01297a

    Article  CAS  PubMed  Google Scholar 

  49. Pauty J, Usuba R, Cheng IG, Hespel L, Takahashi H, Kato K, Kobayashi M, Nakajima H, Lee E, Yger F, Soncin F, Matsunaga YT (2018) A vascular endothelial growth factor-dependent sprouting angiogenesis assay based on an in vitro human blood vessel model for the study of anti-angiogenic drugs. EBioMedicine 27:225–236. https://doi.org/10.1016/j.ebiom.2017.12.014

    Article  PubMed  Google Scholar 

  50. Chen SW, Blazeski A, Zhang S, Shelton SE, Offeddu GS, Kamm RD (2023) Development of a perfusable, hierarchical microvasculature-on-a-chip model. Lab Chip 23(20):4552–4564. https://doi.org/10.1039/d3lc00512g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Selahi A, Fernando T, Chakraborty S, Muthuchamy M, Zawieja DC, Jain A (2022) Lymphangion-chip: a microphysiological system which supports co-culture and bidirectional signaling of lymphatic endothelial and muscle cells. Lab Chip 22(1):121–135. https://doi.org/10.1039/d1lc00720c

    Article  CAS  Google Scholar 

  52. Nothdurfter D, Ploner C, Coraca-Huber DC, Wilflingseder D, Muller T, Hermann M, Hagenbuchner J, Ausserlechner MJ (2022) 3D bioprinted, vascularized neuroblastoma tumor environment in fluidic chip devices for precision medicine drug testing. Biofabrication 14(3):035002. https://doi.org/10.1088/1758-5090/ac5fb7

    Article  CAS  Google Scholar 

  53. Andrique L, Recher G, Alessandri K, Pujol N, Feyeux M, Bon P, Cognet L, Nassoy P, Bikfalvi A (2019) A model of guided cell self-organization for rapid and spontaneous formation of functional vessels. Sci Adv 5(6):eaau6562. https://doi.org/10.1126/sciadv.aau6562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim D, Hwang KS, Seo EU, Seo S, Lee BC, Choi N, Choi J, Kim HN (2022) Vascularized lung cancer model for evaluating the promoted transport of anticancer drugs and immune cells in an engineered tumor microenvironment. Adv Healthc Mater 11(12):e2102581. https://doi.org/10.1002/adhm.202102581

    Article  CAS  PubMed  Google Scholar 

  55. Paek J, Park SE, Lu Q, Park KT, Cho M, Oh JM, Kwon KW, Yi YS, Song JW, Edelstein HI, Ishibashi J, Yang W, Myerson JW, Kiseleva RY, Aprelev P, Hood ED, Stambolian D, Seale P, Muzykantov VR, Huh D (2019) Microphysiological engineering of self-assembled and perfusable microvascular beds for the production of vascularized three-dimensional human microtissues. ACS Nano 13(7):7627–7643. https://doi.org/10.1021/acsnano.9b00686

    Article  CAS  PubMed  Google Scholar 

  56. Liu J, Zheng H, Dai X, Poh PSP, Machens HG, Schilling AF (2020) Transparent PDMS bioreactors for the fabrication and analysis of multi-layer pre-vascularized hydrogels under continuous perfusion. Front Bioeng Biotechnol 8:568934. https://doi.org/10.3389/fbioe.2020.568934

    Article  PubMed  PubMed Central  Google Scholar 

  57. Zhao N, Guo Z, Kulkarni S, Norman D, Zhang S, Chung TD, Nerenberg RF, Linville R, Searson P (2022) Engineering the human blood–brain barrier at the capillary scale using a double-templating technique. Adv Funct Mater 32(30):2110289. https://doi.org/10.1002/adfm.202110289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Peng B, Tong Z, Tong WY, Pasic PJ, Oddo A, Dai Y, Luo M, Frescene J, Welch NG, Easton CD, Thissen H, Voelcker NH (2020) In Situ surface modification of microfluidic blood–brain–barriers for improved screening of small molecules and nanoparticles. ACS Appl Mater Interfaces 12(51):56753–56766. https://doi.org/10.1021/acsami.0c17102

    Article  CAS  PubMed  Google Scholar 

  59. Seo S, Jang M, Kim H, Sung JH, Choi N, Lee K, Kim HN (2022) Neuro-glia-vascular-on-a-chip system to assess aggravated neurodegeneration via brain endothelial cells upon exposure to diesel exhaust particles. Adv Funct Mater 33(12):2210123. https://doi.org/10.1002/adfm.202210123

    Article  CAS  Google Scholar 

  60. Orellano I, Thomas A, Herrera A, Brauer E, Wulsten D, Petersen A, Kloke L, Duda GN (2022) Engineering vascular self-assembly by controlled 3D-printed cell placement. Adv Funct Mater 32(52):2208325. https://doi.org/10.1002/adfm.202208325

    Article  CAS  Google Scholar 

  61. Meng F, Meyer CM, Joung D, Vallera DA, McAlpine MC, Panoskaltsis-Mortari A (2019) 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments. Adv Mater 31(10):e1806899. https://doi.org/10.1002/adma.201806899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bischel LL, Young EW, Mader BR, Beebe DJ (2013) Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials 34(5):1471–1477. https://doi.org/10.1016/j.biomaterials.2012.11.005

    Article  CAS  PubMed  Google Scholar 

  63. Bischel LL, Lee S-H, Beebe DJ (2012) A practical method for patterning lumens through ECM hydrogels via viscous finger patterning. J Lab Autom 17(2):96–103. https://doi.org/10.1177/2211068211426694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. de Graaf MNS, Vivas A, Kasi DG, van den Hil FE, van den Berg A, van der Meer AD, Mummery CL, Orlova VV (2022) Multiplexed fluidic circuit board for controlled perfusion of 3D blood vessels-on-a-chip. Lab Chip 23(1):168–181. https://doi.org/10.1039/d2lc00686c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jiang H, Li X, Chen T, Liu Y, Wang Q, Wang Z, Jia J (2023) Bioprinted vascular tissue: assessing functions from cellular, tissue to organ levels. Mater Today Bio 23:100846. https://doi.org/10.1016/j.mtbio.2023.100846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Terpstra ML, Li J, Mensinga A, de Ruijter M, van Rijen MH, Androulidakis C, Galiotis C, Papantoniou I, Matsusaki M, Malda J (2022) Bioink with cartilage-derived extracellular matrix microfibers enables spatial control of vascular capillary formation in bioprinted constructs. Biofabrication 14(3):034104. https://doi.org/10.1088/1758-5090/ac6282

    Article  CAS  Google Scholar 

  67. Koch L, Deiwick A, Chichkov B (2021) Capillary-like formations of endothelial cells in defined patterns generated by laser bioprinting. Micromachines (Basel). https://doi.org/10.3390/mi12121538

    Article  PubMed  Google Scholar 

  68. Nikolaev M, Mitrofanova O, Broguiere N, Geraldo S, Dutta D, Tabata Y, Elci B, Brandenberg N, Kolotuev I, Gjorevski N (2020) Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585(7826):574–578. https://doi.org/10.1038/s41586-020-2724-8

    Article  CAS  PubMed  Google Scholar 

  69. Enrico A, Voulgaris D, Ostmans R, Sundaravadivel N, Moutaux L, Cordier A, Niklaus F, Herland A, Stemme G (2022) 3D microvascularized tissue models by laser-based cavitation molding of collagen. Adv Mater 34(11):e2109823. https://doi.org/10.1002/adma.202109823

    Article  CAS  PubMed  Google Scholar 

  70. Rajasekar S, Lin DSY, Abdul L, Liu A, Sotra A, Zhang F, Zhang B (2020) IFlowPlate—a customized 384-well plate for the culture of perfusable vascularized colon organoids. Adv Mater 32(46):e2002974. https://doi.org/10.1002/adma.202002974

    Article  CAS  PubMed  Google Scholar 

  71. Mao M, He J, Lu Y, Li X, Li T, Zhou W, Li D (2018) Leaf-templated, microwell-integrated microfluidic chips for high-throughput cell experiments. Biofabrication 10(2):025008. https://doi.org/10.1088/1758-5090/aaa900

    Article  CAS  PubMed  Google Scholar 

  72. Mao M, Chen P, He J, Zhu G, Li X, Li D (2022) Deciphering fluid transport within leaf-inspired capillary networks based on a 3D computational model. Small 18(16):e2108102. https://doi.org/10.1002/smll.202108102

    Article  CAS  PubMed  Google Scholar 

  73. Yu J, Lee S, Song J, Lee SR, Kim S, Choi H, Kang H, Hwang Y, Hong YK, Jeon NL (2022) Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening. Nano Converg 9(1):16. https://doi.org/10.1186/s40580-022-00306-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ko J, Ahn J, Kim S, Lee Y, Lee J, Park D, Jeon NL (2019) Tumor spheroid-on-a-chip: a standardized microfluidic culture platform for investigating tumor angiogenesis. Lab Chip 19(17):2822–2833. https://doi.org/10.1039/c9lc00140a

    Article  CAS  PubMed  Google Scholar 

  75. Riddle RB, Jennbacken K, Hansson KM, Harper MT (2022) Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model. Sci Rep 12(1):6855. https://doi.org/10.1038/s41598-022-10849-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pampaloni F, Reynaud EG, Stelzer EH (2007) The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 8(10):839–845. https://doi.org/10.1038/nrm2236

    Article  CAS  PubMed  Google Scholar 

  77. Rodrigues J, Heinrich MA, Teixeira LM, Prakash J (2021) 3D in vitro model (r)evolution: unveiling tumor–stroma interactions. Trends Cancer 7(3):249–264. https://doi.org/10.1016/j.trecan.2020.10.009

    Article  CAS  PubMed  Google Scholar 

  78. Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, Johnston S, Parylak SL, Jin X, Gage FH (2018) An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36(5):432–441. https://doi.org/10.1038/nbt.4127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Garreta E, Prado P, Tarantino C, Oria R, Fanlo L, Marti E, Zalvidea D, Trepat X, Roca-Cusachs P, Gavalda-Navarro A, Cozzuto L, Campistol JM, Izpisua Belmonte JC, Hurtado Del Pozo C, Montserrat N (2019) Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nat Mater 18(4):397–405. https://doi.org/10.1038/s41563-019-0287-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tamai M, Adachi E, Kawase M, Tagawa YI (2022) Syngeneic implantation of mouse hepatic progenitor cell-derived three-dimensional liver tissue with dense collagen fibrils. World J Gastroenterol 28(14):1444–1454. https://doi.org/10.3748/wjg.v28.i14.1444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cortez AR, Poling HM, Brown NE, Singh A, Mahe MM, Helmrath MA (2018) Transplantation of human intestinal organoids into the mouse mesentery: A more physiologic and anatomic engraftment site. Surgery 164(4):643–650. https://doi.org/10.1016/j.surg.2018.04.048

    Article  PubMed  Google Scholar 

  82. Shankar AS, Du Z, Tejeda Mora H, Boers R, Cao W, van den Bosch TPP, Korevaar SS, Boers J, van IJcken WFJ, Bindels EMJ, Eussen B, de Klein A, Pan Q, Oudijk L, Clahsen-van Groningen MC, Hoorn EJ, Baan CC, Gribnau J, Hoogduijn MJ (2022) Kidney organoids are capable of forming tumors, but not teratomas. Stem Cells 40(6):577–591. https://doi.org/10.1093/stmcls/sxac009

    Article  PubMed  PubMed Central  Google Scholar 

  83. Hu Z, Cao Y, Galan EA, Hao L, Zhao H, Tang J, Sang G, Wang H, Xu B, Ma S (2022) Vascularized tumor spheroid-on-a-chip model verifies synergistic vasoprotective and chemotherapeutic effects. ACS Biomater Sci Eng 8(3):1215–1225. https://doi.org/10.1021/acsbiomaterials.1c01099

    Article  CAS  PubMed  Google Scholar 

  84. Fang G, Chen YC, Lu H, Jin D (2023) Advances in spheroids and organoids on a chip. Adv Funct Mater 33(19):2215043. https://doi.org/10.1002/adfm.202215043

    Article  CAS  Google Scholar 

  85. Maffioletti SM, Sarcar S, Henderson ABH, Mannhardt I, Pinton L, Moyle LA, Steele-Stallard H, Cappellari O, Wells KE, Ferrari G, Mitchell JS, Tyzack GE, Kotiadis VN, Khedr M, Ragazzi M, Wang W, Duchen MR, Patani R, Zammit PS, Wells DJ, Eschenhagen T, Tedesco FS (2018) Three-dimensional human iPSC-derived artificial skeletal muscles model muscular dystrophies and enable multilineage tissue engineering. Cell Rep 23(3):899–908. https://doi.org/10.1016/j.celrep.2018.03.091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Salmon I, Grebenyuk S, Abdel Fattah AR, Rustandi G, Pilkington T, Verfaillie C, Ranga A (2022) Engineering neurovascular organoids with 3D printed microfluidic chips. Lab Chip 22(8):1615–1629. https://doi.org/10.1039/d1lc00535a

    Article  CAS  PubMed  Google Scholar 

  87. Zhang S, Wan Z, Kamm RD (2021) Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature. Lab Chip 21(3):473–488. https://doi.org/10.1039/d0lc01186j

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nashimoto Y, Hayashi T, Kunita I, Nakamasu A, Torisawa YS, Nakayama M, Takigawa-Imamura H, Kotera H, Nishiyama K, Miura T, Yokokawa R (2017) Integrating perfusable vascular networks with a three-dimensional tissue in a microfluidic device. Integr Biol (Camb) 9(6):506–518. https://doi.org/10.1039/c7ib00024c

    Article  PubMed  Google Scholar 

  89. Nashimoto Y, Okada R, Hanada S, Arima Y, Nishiyama K, Miura T, Yokokawa R (2020) Vascularized cancer on a chip: the effect of perfusion on growth and drug delivery of tumor spheroid. Biomaterials 229:119547. https://doi.org/10.1016/j.biomaterials.2019.119547

    Article  CAS  PubMed  Google Scholar 

  90. Park J, Kim S, Hong J, Jeon JS (2022) Enabling perfusion through multicellular tumor spheroids promoting lumenization in a vascularized cancer model. Lab Chip 22(22):4335–4348. https://doi.org/10.1039/d2lc00597b

    Article  CAS  PubMed  Google Scholar 

  91. Haase K, Offeddu GS, Gillrie MR, Kamm RD (2020) Endothelial regulation of drug transport in a 3D vascularized tumor model. Adv Funct Mater 30(48):2002444. https://doi.org/10.1002/adfm.202002444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Tan SY, Jing Q, Leung Z, Xu Y, Cheng LKW, Tam SST, Wu AR (2022) Transcriptomic analysis of 3D vasculature-on-a-chip reveals paracrine factors affecting vasculature growth and maturation. Lab Chip 22(20):3885–3897. https://doi.org/10.1039/d2lc00570k

    Article  CAS  PubMed  Google Scholar 

  93. Nashimoto Y, Teraoka Y, Banan Sadeghian R, Nakamasu A, Arima Y, Hanada S, Kotera H, Nishiyama K, Miura T, Yokokawa R (2018) Perfusable vascular network with a tissue model in a microfluidic device. J Vis Exp 134:57242. https://doi.org/10.3791/57242

    Article  CAS  Google Scholar 

  94. Wan Z, Floryan MA, Coughlin MF, Zhang S, Zhong AX, Shelton SE, Wang X, Xu C, Barbie DA, Kamm RD (2023) New strategy for promoting vascularization in tumor spheroids in a microfluidic assay. Adv Healthc Mater 12(14):e2201784. https://doi.org/10.1002/adhm.202201784

    Article  CAS  PubMed  Google Scholar 

  95. Li C, Li S, Du K, Li P, Qiu B, Ding W (2021) On-chip replication of extremely early-stage tumor behavior. ACS Appl Mater Interfaces 13(17):19768–19777. https://doi.org/10.1021/acsami.1c03740

    Article  CAS  PubMed  Google Scholar 

  96. Wang HF, Liu Y, Wang T, Yang G, Zeng B, Zhao CX (2020) Tumor-microenvironment-on-a-chip for evaluating nanoparticle-loaded macrophages for drug delivery. ACS Biomater Sci Eng 6(9):5040–5050. https://doi.org/10.1021/acsbiomaterials.0c00650

    Article  CAS  PubMed  Google Scholar 

  97. Zhou Y, Wu Y, Paul R, Qin X, Liu Y (2023) Hierarchical vessel network-supported tumor model-on-a-chip constructed by induced spontaneous anastomosis. ACS Appl Mater Interfaces 15(5):6431–6441. https://doi.org/10.1021/acsami.2c19453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wu Y, Zhao Y, Zhou Y, Islam K, Liu Y (2023) Microfluidic droplet-assisted fabrication of vessel-supported tumors for preclinical drug discovery. ACS Appl Mater Interfaces 15(12):15152–15161. https://doi.org/10.1021/acsami.2c23305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sotra A, Jozani KA, Zhang B (2023) A vascularized crypt-patterned colon model for high-throughput drug screening and disease modelling. Lab Chip 23(15):3370–3387. https://doi.org/10.1039/d3lc00211j

    Article  CAS  PubMed  Google Scholar 

  100. Pollet A, den Toonder JMJ (2020) Recapitulating the vasculature using organ-on-chip technology. Bioengineering (Basel). https://doi.org/10.3390/bioengineering7010017

    Article  PubMed  Google Scholar 

  101. Henderson AR, Choi H, Lee E (2020) Blood and lymphatic vasculatures on-chip platforms and their applications for organ-specific in vitro modeling. Micromachines (Basel). https://doi.org/10.3390/mi11020147

    Article  PubMed  Google Scholar 

  102. Tronolone JJ, Jain A (2021) Engineering new microvascular networks on-chip: ingredients, assembly, and best practices. Adv Funct Mater. https://doi.org/10.1002/adfm.202007199

    Article  PubMed  PubMed Central  Google Scholar 

  103. Shaji M, Tamada A, Fujimoto K, Muguruma K, Karsten SL, Yokokawa R (2024) Deciphering potential vascularization factors of on-chip co-cultured hiPSC-derived cerebral organoids. Lab Chip 24(4):680–696. https://doi.org/10.1039/d3lc00930k

    Article  CAS  Google Scholar 

  104. Ferrari D, Sengupta A, Heo L, Petho L, Michler J, Geiser T, de JesusPerez VA, Kuebler WM, Zeinali S, Guenat OT (2023) Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip. iScience 26(3):106198. https://doi.org/10.1016/j.isci.2023.106198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Carvalho MR, Barata D, Teixeira LM, Giselbrecht S, Reis RL, Oliveira JM, Truckenmuller R, Habibovic P (2019) Colorectal tumor-on-a-chip system: a 3D tool for precision onco-nanomedicine. Sci Adv 5(5):eaaw1317. https://doi.org/10.1126/sciadv.aaw1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Zhang S, Wan Z, Pavlou G, Zhong AX, Xu L, Kamm RD (2022) Interstitial flow promotes the formation of functional microvascular networks in vitro through upregulation of matrix metalloproteinase-2. Adv Funct Mater 32(43):2206767. https://doi.org/10.1002/adfm.202206767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wan Z, Zhong AX, Zhang S, Pavlou G, Coughlin MF, Shelton SE, Nguyen HT, Lorch JH, Barbie DA, Kamm RD (2022) A robust method for perfusable microvascular network formation in vitro. Small Methods 6(6):e2200143. https://doi.org/10.1002/smtd.202200143

    Article  PubMed  PubMed Central  Google Scholar 

  108. Wang X, Liu X, Liu W, Liu Y, Li A, Qiu D, Zheng X, Gu Q (2023) 3D bioprinting microgels to construct implantable vascular tissue. Cell Prolif 56(5):e13456. https://doi.org/10.1111/cpr.13456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Liu T, Zhou C, Ji J, Xu X, Xing Z, Shinohara M, Sakai Y, Sun T, Feng X, Yu Z (2023) Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages. Biofabrication 15(4):044102. https://doi.org/10.1088/1758-5090/ace3f9

    Article  Google Scholar 

  110. Le HT, Phan HL, Lenshof A, Duong VT, Choi C, Cha C, Laurell T, Koo KI (2023) Ultrasound standing wave spatial patterning of human umbilical vein endothelial cells for 3D micro-vascular networks formation. Biofabrication. https://doi.org/10.1088/1758-5090/ad03be

    Article  PubMed  Google Scholar 

  111. Kumar M, Rauthan R, Chakraborty D, Arumugam S (2023) Visualization of 3D organoids through the latest advancements in microscopy. In: Gopalakrishnan J (ed) Brain organoid research. Neuromethods. Springer, New York, pp 43–66. https://doi.org/10.1007/978-1-0716-2720-4_3

    Chapter  Google Scholar 

  112. Ji N (2017) Adaptive optical fluorescence microscopy. Nat Methods 14(4):374–380. https://doi.org/10.1038/nmeth.4218

    Article  CAS  PubMed  Google Scholar 

  113. Rakotoson I, Delhomme B, Djian P, Deeg A, Brunstein M, Seebacher C, Uhl R, Ricard C, Oheim M (2019) Fast 3-D imaging of brain organoids with a new single-objective planar-illumination two-photon microscope. Front Neuroanat 13:77. https://doi.org/10.3389/fnana.2019.00077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Hushka EA, Yavitt FM, Brown TE, Dempsey PJ, Anseth KS (2020) Relaxation of extracellular matrix forces directs crypt formation and architecture in intestinal organoids. Adv Healthc Mater 9(8):e1901214. https://doi.org/10.1002/adhm.201901214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Lai Benjamin FL, Lu Rick X, Hu Y, Davenport HL, Dou W, Wang EY, Radulovich N, Tsao MS, Sun Y, Radisic M (2020) Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature. Adv Funct Mater 30(48):2000545. https://doi.org/10.1002/adfm.202000545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yildirim M, Delepine C, Feldman D, Pham VA, Chou S, Ip J, Nott A, Tsai LH, Ming GL, So PTC, Sur M (2022) Label-free three-photon imaging of intact human cerebral organoids for tracking early events in brain development and deficits in Rett syndrome. eLife 11:e78079. https://doi.org/10.7554/eLife.78079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Stelzer EH (2015) Light-sheet fluorescence microscopy for quantitative biology. Nat Methods 12(1):23–26. https://doi.org/10.1038/nmeth.3219

    Article  CAS  PubMed  Google Scholar 

  118. Gong H, Xu D, Yuan J, Li X, Guo C, Peng J, Li Y, Schwarz LA, Li A, Hu B, Xiong B, Sun Q, Zhang Y, Liu J, Zhong Q, Xu T, Zeng S, Luo Q (2016) High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level. Nat Commun 7:12142. https://doi.org/10.1038/ncomms12142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Li A, Gong H, Zhang B, Wang Q, Yan C, Wu J, Liu Q, Zeng S, Luo Q (2010) Micro-optical sectioning tomography to obtain a high-resolution atlas of the mouse brain. Science 330(6009):1404–1408. https://doi.org/10.1126/science.1191776

    Article  CAS  PubMed  Google Scholar 

  120. Gong H, Zeng S, Yan C, Lv X, Yang Z, Xu T, Feng Z, Ding W, Qi X, Li A, Wu J, Luo Q (2013) Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution. Neuroimage 74:87–98. https://doi.org/10.1016/j.neuroimage.2013.02.005

    Article  PubMed  Google Scholar 

  121. Ondatje BN, Sances S, Workman MJ, Svendsen CN (2022) Tissue clearing of human iPSC-derived organ-chips enables high resolution imaging and analysis. Lab Chip 22(21):4246–4255. https://doi.org/10.1039/d2lc00116k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Bissardon C, Mermet X, Quintard C, Sanjuan F, Fouillet Y, Bottausci F, Carriere M, Rivera F, Blandin P (2022) Selective plane illumination microscope dedicated to volumetric imaging in microfluidic chambers. Biomed Opt Express 13(10):5261–5274. https://doi.org/10.1364/BOE.455377

    Article  PubMed  PubMed Central  Google Scholar 

  123. Rusch H, Brammerloh M, Stieler J, Sonntag M, Mohammadi S, Weiskopf N, Arendt T, Kirilina E, Morawski M (2022) Finding the best clearing approach—towards 3D wide-scale multimodal imaging of aged human brain tissue. Neuroimage 247:118832. https://doi.org/10.1016/j.neuroimage.2021.118832

    Article  CAS  PubMed  Google Scholar 

  124. Schneidereit D, Brollochs A, Ritter P, Kreiss L, Mokhtari Z, Beilhack A, Kronke G, Ackermann JA, Faas M, Gruneboom A, Schurmann S, Friedrich O (2021) An advanced optical clearing protocol allows label-free detection of tissue necrosis via multiphoton microscopy in injured whole muscle. Theranostics 11(6):2876–2891. https://doi.org/10.7150/thno.51558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kirst C, Skriabine S, Vieites-Prado A, Topilko T, Bertin P, Gerschenfeld G, Verny F, Topilko P, Michalski N, Tessier-Lavigne M, Renier N (2020) Mapping the fine-scale organization and plasticity of the brain vasculature. Cell 180(4):780–795e725. https://doi.org/10.1016/j.cell.2020.01.028

  126. He Z, Maynard A, Jain A, Gerber T, Petri R, Lin HC, Santel M, Ly K, Dupre JS, Sidow L, Sanchis Calleja F, Jansen SMJ, Riesenberg S, Camp JG, Treutlein B (2022) Lineage recording in human cerebral organoids. Nat Methods 19(1):90–99. https://doi.org/10.1038/s41592-021-01344-8

    Article  CAS  PubMed  Google Scholar 

  127. Cho AN, Jin Y, An Y, Kim J, Choi YS, Lee JS, Kim J, Choi WY, Koo DJ, Yu W, Chang GE, Kim DY, Jo SH, Kim J, Kim SY, Kim YG, Kim JY, Choi N, Cheong E, Kim YJ, Je HS, Kang HC, Cho SW (2021) Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids. Nat Commun 12(1):4730. https://doi.org/10.1038/s41467-021-24775-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Langer EM, Allen-Petersen BL, King SM, Kendsersky ND, Turnidge MA, Kuziel GM, Riggers R, Samatham R, Amery TS, Jacques SL, Sheppard BC, Korkola JE, Muschler JL, Thibault G, Chang YH, Gray JW, Presnell SC, Nguyen DG, Sears RC (2019) Modeling tumor phenotypes in vitro with three-dimensional bioprinting. Cell Rep 26(3):608–623e606. https://doi.org/10.1016/j.celrep.2018.12.090

  129. Zhu T, Nie J, Yu T, Zhu D, Huang Y, Chen Z, Gu Z, Tang J, Li D, Fei P (2023) Large-scale high-throughput 3D culture, imaging, and analysis of cell spheroids using microchip-enhanced light-sheet microscopy. Biomed Opt Express 14(4):1659–1669. https://doi.org/10.1364/BOE.485217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rafiei N, Moghadam MG, Au A, Regeenes R, Chidambaram S, Liang T, Wang Y, Yip CM, Gaisano H, Rocheleau JV (2022) Design of a versatile microfluidic device for imaging precision-cut-tissue slices. Biofabrication 14(4):041001. https://doi.org/10.1088/1758-5090/ac7eea

    Article  CAS  Google Scholar 

  131. Atlas Y, Gorin C, Novais A, Marchand MF, Chatzopoulou E, Lesieur J, Bascetin R, Binet-Moussy C, Sadoine J, Lesage M, Opsal-Vital S, Peault B, Monnot C, Poliard A, Girard P, Germain S, Chaussain C, Muller L (2021) Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs. Biomaterials 268:120594. https://doi.org/10.1016/j.biomaterials.2020.120594

    Article  CAS  PubMed  Google Scholar 

  132. Kress S, Baur J, Otto C, Burkard N, Braspenning J, Walles H, Nickel J, Metzger M (2018) Evaluation of a Miniaturized Biologically Vascularized Scaffold in vitro and in vivo. Sci Rep 8(1):4719. https://doi.org/10.1038/s41598-018-22688-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Steuwe C, Vaeyens MM, Jorge-Penas A, Cokelaere C, Hofkens J, Roeffaers MBJ, Van Oosterwyck H (2020) Fast quantitative time lapse displacement imaging of endothelial cell invasion. PLoS ONE 15(1):e0227286. https://doi.org/10.1371/journal.pone.0227286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kaushik G, Gil DA, Torr E, Berge ES, Soref C, Uhl P, Fontana G, Antosiewicz-Bourget J, Edington C, Schwartz MP, Griffith LG, Thomson JA, Skala MC, Daly WT, Murphy WL (2019) Quantitative Label-Free Imaging of 3D Vascular Networks Self-Assembled in Synthetic Hydrogels. Adv Healthc Mater 8(2):e1801186. https://doi.org/10.1002/adhm.201801186

    Article  CAS  PubMed  Google Scholar 

  135. Ueda HR, Dodt HU, Osten P, Economo MN, Chandrashekar J, Keller PJ (2020) Whole-brain profiling of cells and circuits in mammals by tissue clearing and light-sheet microscopy. Neuron 106(3):369–387. https://doi.org/10.1016/j.neuron.2020.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R (2019) Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods 16(3):255–262. https://doi.org/10.1038/s41592-019-0325-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Ueda HR, Erturk A, Chung K, Gradinaru V, Chedotal A, Tomancak P, Keller PJ (2020) Tissue clearing and its applications in neuroscience. Nat Rev Neurosci 21(2):61–79. https://doi.org/10.1038/s41583-019-0250-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhu J, Liu X, Deng Y, Li D, Yu T, Zhu D (2021) Tissue optical clearing for 3D visualization of vascular networks: a review. Vascul Pharmacol 141:106905. https://doi.org/10.1016/j.vph.2021.106905

    Article  CAS  PubMed  Google Scholar 

  139. Yu T, Zhu J, Li D, Zhu D (2021) Physical and chemical mechanisms of tissue optical clearing. Science 24(3):102178. https://doi.org/10.1016/j.isci.2021.102178

    Article  CAS  Google Scholar 

  140. Xia Q, Li D, Yu T, Zhu J, Zhu D (2023) In vivo skin optical clearing for improving imaging and light-induced therapy: a review. J Biomed Opt 28(6):060901. https://doi.org/10.1117/1.JBO.28.6.060901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Xu C (2022) Optical clearing of the mouse skull. Light Sci Appl 11(1):284. https://doi.org/10.1038/s41377-022-00989-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Li D, Hu Z, Zhang H, Yang Q, Zhu L, Liu Y, Yu T, Zhu J, Wu J, He J, Fei P, Xi W, Qian J, Zhu D (2022) A Through-Intact-Skull (TIS) chronic window technique for cortical structure and function observation in mice. eLight 2(1):15. https://doi.org/10.1186/s43593-022-00022-2

    Article  Google Scholar 

  143. Oh MS, Khawar IA, Lee DW, Park JK, Kuh HJ (2020) Three-dimensional imaging for multiplex phenotypic analysis of pancreatic microtumors grown on a minipillar array chip. Cancers (Basel) 12(12):3662. https://doi.org/10.3390/cancers12123662

    Article  CAS  PubMed  Google Scholar 

  144. Yu T, Zhong X, Yang Q, Gao C, Chen W, Liu X, Liu Z, Zhu T, Li D, Fei P, Chen Z, Gu Z, Zhu D (2023) On-chip clearing for live imaging of 3D cell cultures. Biomed Opt Express 14(6):3003–3017. https://doi.org/10.1364/BOE.489219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7):676–682. https://doi.org/10.1038/nmeth.2019

    Article  CAS  PubMed  Google Scholar 

  146. Lee S, Chung M, Lee SR, Jeon NL (2020) 3D brain angiogenesis model to reconstitute functional human blood–brain barrier in vitro. Biotechnol Bioeng 117(3):748–762. https://doi.org/10.1002/bit.27224

    Article  CAS  PubMed  Google Scholar 

  147. Haase K, Gillrie MR, Hajal C, Kamm RD (2019) Pericytes contribute to dysfunction in a human 3D model of placental microvasculature through VEGF-Ang-Tie2 signaling. Adv Sci (Weinh) 6(23):1900878. https://doi.org/10.1002/advs.201900878

    Article  CAS  PubMed  Google Scholar 

  148. Kempers L, van der Bijl I, van Stalborch AD, Ponsioen B, Margadant C (2021) Fast in vitro protocol for the visualization and quantitative high-throughput analysis of sprouting angiogenesis by confocal microscopy. STAR Protoc 2(3):100690. https://doi.org/10.1016/j.xpro.2021.100690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Orlova VV, Nahon DM, Cochrane A, Cao X, Freund C, van den Hil F, Westermann CJJ, Snijder RJ, Ploos van Amstel JK, Ten Dijke P, Lebrin F, Mager HJ, Mummery CL (2022) Vascular defects associated with hereditary hemorrhagic telangiectasia revealed in patient-derived isogenic iPSCs in 3D vessels on chip. Stem Cell Rep 17(7):1536–1545. https://doi.org/10.1016/j.stemcr.2022.05.022

    Article  CAS  Google Scholar 

  150. Ryu H, Oh S, Lee HJ, Lee JY, Lee HK, Jeon NL (2015) Engineering a blood vessel network module for body-on-a-chip applications. J Lab Autom 20(3):296–301. https://doi.org/10.1177/2211068214562831

    Article  CAS  PubMed  Google Scholar 

  151. Lee S, Kim S, Koo DJ, Yu J, Cho H, Lee H, Song JM, Kim SY, Min DH, Jeon NL (2021) 3D microfluidic platform and tumor vascular mapping for evaluating anti-angiogenic RNAi-based nanomedicine. ACS Nano 15(1):338–350. https://doi.org/10.1021/acsnano.0c05110

    Article  CAS  PubMed  Google Scholar 

  152. Zudaire E, Gambardella L, Kurcz C, Vermeren S (2011) A computational tool for quantitative analysis of vascular networks. PLoS ONE 6(11):e27385. https://doi.org/10.1371/journal.pone.0027385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Rodoplu D, Matahum JS, Hsu CH (2022) A microfluidic hanging drop-based spheroid co-culture platform for probing tumor angiogenesis. Lab Chip 22(7):1275–1285. https://doi.org/10.1039/d1lc01177d

    Article  CAS  PubMed  Google Scholar 

  154. Ong LL, Dauwels J, Ang MH Jr, Asada HH (2014) A Bayesian filtering approach to incorporate 2D/3D time-lapse confocal images for tracking angiogenic sprouting cells interacting with the gel matrix. Med Image Anal 18(1):211–227. https://doi.org/10.1016/j.media.2013.10.008

    Article  PubMed  Google Scholar 

  155. Wang M, Ong LS, Dauwels J, Asada HH (2018) Multicell migration tracking within angiogenic networks by deep learning-based segmentation and augmented Bayesian filtering. J Med Imaging (Bellingham) 5(2):024005. https://doi.org/10.1117/1.JMI.5.2.024005

    Article  PubMed  Google Scholar 

  156. Wang M, Ong LS, Dauwels J, Asada HH (2017) Automated tracking and quantification of angiogenic vessel formation in 3D microfluidic devices. PLoS ONE 12(11):e0186465. https://doi.org/10.1371/journal.pone.0186465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Kuzmic N, Moore T, Devadas D, Young EWK (2019) Modelling of endothelial cell migration and angiogenesis in microfluidic cell culture systems. Biomech Model Mechanobiol 18(3):717–731. https://doi.org/10.1007/s10237-018-01111-3

    Article  PubMed  Google Scholar 

  158. Akbarpour Ghazani M, Nouri Z, Saghafian M, Soltani M (2020) Mathematical modeling reveals how the density of initial tumor and its distance to parent vessels alter the growth trend of vascular tumors. Microcirculation 27(1):e12584. https://doi.org/10.1111/micc.12584

    Article  PubMed  Google Scholar 

  159. Bates R, Irving B, Markelc B, Kaeppler J, Brown G, Muschel RJ, Brady SM, Grau V, Schnabel JA (2019) Segmentation of vasculature from fluorescently labeled endothelial cells in multi-photon microscopy images. IEEE Trans Med Imaging 38(1):1–10. https://doi.org/10.1109/TMI.2017.2725639

    Article  PubMed  Google Scholar 

  160. Solovyev R, Kalinin AA, Gabruseva T (2022) 3D convolutional neural networks for stalled brain capillary detection. Comput Biol Med 141:105089. https://doi.org/10.1016/j.compbiomed.2021.105089

    Article  PubMed  Google Scholar 

  161. Cheung CY, Xu D, Cheng CY, Sabanayagam C, Tham YC, Yu M, Rim TH, Chai CY, Gopinath B, Mitchell P, Poulton R, Moffitt TE, Caspi A, Yam JC, Tham CC, Jonas JB, Wang YX, Song SJ, Burrell LM, Farouque O, Li LJ, Tan G, Ting DSW, Hsu W, Lee ML, Wong TY (2021) A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal-vessel calibre. Nat Biomed Eng 5(6):498–508. https://doi.org/10.1038/s41551-020-00626-4

    Article  CAS  PubMed  Google Scholar 

  162. Li X, Tang Q, Yu J, Wang Y, Shi Z (2019) Microvascularity detection and quantification in glioma: a novel deep-learning-based framework. Lab Invest 99(10):1515–1526. https://doi.org/10.1038/s41374-019-0272-3

    Article  PubMed  Google Scholar 

  163. Todorov MI, Paetzold JC, Schoppe O, Tetteh G, Shit S, Efremov V, Todorov-Volgyi K, During M, Dichgans M, Piraud M, Menze B, Erturk A (2020) Machine learning analysis of whole mouse brain vasculature. Nat Methods 17(4):442–449. https://doi.org/10.1038/s41592-020-0792-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Haft-Javaherian M, Fang L, Muse V, Schaffer CB, Nishimura N, Sabuncu MR (2019) Deep convolutional neural networks for segmenting 3D in vivo multiphoton images of vasculature in Alzheimer disease mouse models. PLoS ONE 14(3):e0213539. https://doi.org/10.1371/journal.pone.0213539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Chen W, Yu S, Ma K, Ji W, Bian C, Chu C, Shen L, Zheng Y (2022) TW-GAN: topology and width aware GAN for retinal artery/vein classification. Med Image Anal 77:102340. https://doi.org/10.1016/j.media.2021.102340

    Article  PubMed  Google Scholar 

  166. Zhou Y, Sun SW, Liu QP, Xu X, Zhang Y, Zhang YD (2022) TED: Two-stage expert-guided interpretable diagnosis framework for microvascular invasion in hepatocellular carcinoma. Med Image Anal 82:102575. https://doi.org/10.1016/j.media.2022.102575

    Article  PubMed  Google Scholar 

  167. Jiang X, Li J, Kan Y, Yu T, Chang S, Sha X, Zheng H, Luo Y, Wang S (2021) MRI based radiomics approach with deep learning for prediction of vessel invasion in early-stage cervical cancer. IEEE/ACM Trans Comput Biol Bioinform 18(3):995–1002. https://doi.org/10.1109/TCBB.2019.2963867

    Article  CAS  PubMed  Google Scholar 

  168. Kuri PM, Pion E, Mahl L, Kainz P, Schwarz S, Brochhausen C, Aung T, Haerteis S (2022) Deep learning-based image analysis for the quantification of tumor-induced angiogenesis in the 3D In vivo tumor model-establishment and addition to laser speckle contrast imaging (LSCI). Cells 11(15):2321. https://doi.org/10.3390/cells11152321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Yan J, Li Z, Guo J, Liu S, Guo J (2022) Organ-on-a-chip: a new tool for in vitro research. Biosens Bioelectron 216:114626. https://doi.org/10.1016/j.bios.2022.114626

    Article  CAS  PubMed  Google Scholar 

  170. Riordon J, Sovilj D, Sanner S, Sinton D, Young EWK (2019) Deep learning with microfluidics for biotechnology. Trends Biotechnol 37(3):310–324. https://doi.org/10.1016/j.tibtech.2018.08.005

    Article  CAS  PubMed  Google Scholar 

  171. Urban G, Bache KM, Phan D, Sobrino A, Shmakov AK, Hachey SJ, Hughes C, Baldi P (2019) Deep learning for drug discovery and cancer research: automated analysis of vascularization images. IEEE/ACM Trans Comput Biol Bioinform 16(3):1029–1035. https://doi.org/10.1109/TCBB.2018.2841396

    Article  PubMed  Google Scholar 

  172. Chen Z, Huang J, Zhang J, Xu Z, Li Q, Ouyang J, Yan Y, Sun S, Ye H, Wang F, Zhu J, Wang Z, Chao J, Pu Y, Gu Z (2022) A storm in a teacup—a biomimetic lung microphysiological system in conjunction with a deep-learning algorithm to monitor lung pathological and inflammatory reactions. Biosens Bioelectron 219:114772. https://doi.org/10.1016/j.bios.2022.114772

    Article  CAS  PubMed  Google Scholar 

  173. Bian X, Li G, Wang C, Liu W, Lin X, Chen Z, Cheung M, Luo X (2021) A deep learning model for detection and tracking in high-throughput images of organoid. Comput Biol Med 134:104490. https://doi.org/10.1016/j.compbiomed.2021.104490

    Article  PubMed  Google Scholar 

  174. Matthews JM, Schuster B, Kashaf SS, Liu P, Ben-Yishay R, Ishay-Ronen D, Izumchenko E, Shen L, Weber CR, Bielski M, Kupfer SS, Bilgic M, Rzhetsky A, Tay S (2022) OrganoID: a versatile deep learning platform for tracking and analysis of single-organoid dynamics. PLoS Comput Biol 18(11):e1010584. https://doi.org/10.1371/journal.pcbi.1010584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Li J, Chen J, Bai H, Wang H, Hao S, Ding Y, Peng B, Zhang J, Li L, Huang W (2022) An overview of organs-on-chips based on deep learning. Research. https://doi.org/10.34133/2022/9869518

    Article  PubMed  PubMed Central  Google Scholar 

  176. Abdul L, Xu J, Sotra A, Chaudary A, Gao J, Rajasekar S, Anvari N, Mahyar H, Zhang B (2022) D-CryptO: deep learning-based analysis of colon organoid morphology from brightfield images. Lab Chip 22(21):4118–4128. https://doi.org/10.1039/d2lc00596d

    Article  CAS  PubMed  Google Scholar 

  177. Trossbach M, Akerlund E, Langer K, Seashore-Ludlow B, Joensson HN (2023) High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning. SLAS Technol. https://doi.org/10.1016/j.slast.2023.03.003

    Article  PubMed  Google Scholar 

  178. Kassis T, Hernandez-Gordillo V, Langer R, Griffith LG (2019) OrgaQuant: human intestinal organoid localization and quantification using deep convolutional neural networks. Sci Rep 9(1):12479. https://doi.org/10.1038/s41598-019-48874-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Beghin A, Grenci G, Sahni G, Guo S, Rajendiran H, Delaire T, Raffi SBM, Blanc D, de Mets R, Ong HT, Galindo X, Monet A, Acharya V, Racine V, Levet F, Galland R, Sibarita JB, Viasnoff V (2022) Automated high-speed 3D imaging of organoid cultures with multi-scale phenotypic quantification. Nat Methods 19(7):881–892. https://doi.org/10.1038/s41592-022-01508-0

    Article  CAS  PubMed  Google Scholar 

  180. de Medeiros G, Ortiz R, Strnad P, Boni A, Moos F, Repina N, Challet Meylan L, Maurer F, Liberali P (2022) Multiscale light-sheet organoid imaging framework. Nat Commun 13(1):4864. https://doi.org/10.1038/s41467-022-32465-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Benning L, Peintner A, Finkenzeller G, Peintner L (2020) Automated spheroid generation, drug application and efficacy screening using a deep learning classification: a feasibility study. Sci Rep 10(1):11071. https://doi.org/10.1038/s41598-020-67960-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Irisa T, Zhou H, Fujimoto K, Yokokawa R (2023) Developmental phases of on-chip vasculogenesis classified using a deep learning visual model. Paper presented at the 2023 IEEE 36th international conference on micro electro mechanical systems (MEMS), 15–19 January 2023. https://doi.org/10.1109/MEMS49605.2023.10052548

  183. Tronolone JJ, Mathur T, Chaftari CP, Jain A (2023) Evaluation of the morphological and biological functions of vascularized microphysiological systems with supervised machine learning. Ann Biomed Eng 51(8):1723–1737. https://doi.org/10.1007/s10439-023-03177-2

    Article  PubMed  Google Scholar 

  184. Strobel HA, Moss SM, Hoying JB (2022) Methods for vascularization and perfusion of tissue organoids. Mamm Genome 33(3):437–450. https://doi.org/10.1007/s00335-022-09951-2

    Article  PubMed  Google Scholar 

  185. O’Connor C, Brady E, Zheng Y, Moore E, Stevens KR (2022) Engineering the multiscale complexity of vascular networks. Nat Rev Mater 7(9):702–716. https://doi.org/10.1038/s41578-022-00447-8

    Article  PubMed  PubMed Central  Google Scholar 

  186. Morss Clyne A, Swaminathan S, Diaz Lantada A (2019) Biofabrication strategies for creating microvascular complexity. Biofabrication 11(3):032001. https://doi.org/10.1088/1758-5090/ab0621

    Article  CAS  PubMed  Google Scholar 

  187. Cao X, Ashfaq R, Cheng F, Maharjan S, Li J, Ying G, Hassan S, Xiao H, Yue K, Zhang YS (2019) A tumor-on-a-chip system with bioprinted blood and lymphatic vessel pair. Adv Funct Mater. https://doi.org/10.1002/adfm.201807173

    Article  PubMed  PubMed Central  Google Scholar 

  188. Fujimoto K, Erickson S, Nakayama M, Ihara H, Sugihara K, Nashimoto Y, Nishiyama K, Miura T, Yokokawa R (2023) Pericytes and shear stress each alter the shape of a self-assembled vascular network. Lab Chip 23(2):306–317. https://doi.org/10.1039/d2lc00605g

    Article  CAS  PubMed  Google Scholar 

  189. Adjei-Sowah EA, O’Connor SA, Veldhuizen J, Lo Cascio C, Plaisier C, Mehta S, Nikkhah M (2022) Investigating the interactions of glioma stem cells in the perivascular niche at single-cell resolution using a microfluidic tumor microenvironment model. Adv Sci (Weinh) 9(21):e2201436. https://doi.org/10.1002/advs.202201436

    Article  CAS  PubMed  Google Scholar 

  190. Liu Y, Li J, Zhou J, Liu X, Li H, Lu Y, Lin B, Li X, Liu T (2022) Angiogenesis and functional vessel formation induced by interstitial flow and vascular endothelial growth factor using a microfluidic chip. Micromachines (Basel) 13(2):225. https://doi.org/10.3390/mi13020225

    Article  PubMed  Google Scholar 

  191. Pradhan S, Smith AM, Garson CJ, Hassani I, Seeto WJ, Pant K, Arnold RD, Prabhakarpandian B, Lipke EA (2018) A microvascularized tumor-mimetic platform for assessing anti-cancer drug efficacy. Sci Rep 8(1):3171. https://doi.org/10.1038/s41598-018-21075-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Cui X, Morales RT, Qian W, Wang H, Gagner JP, Dolgalev I, Placantonakis D, Zagzag D, Cimmino L, Snuderl M, Lam RHW, Chen W (2018) Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials 161:164–178. https://doi.org/10.1016/j.biomaterials.2018.01.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (Grant No. 2017YFA0700501); the National Natural Science Foundation of China (Grant Nos. 61860206009, 62375096, 82361138569, 82372012); the Key Research and Development Project of Hubei Province (Grant No. 2022BCA023); and the Open Research Fund of WNLO (Grant No. 2022WNLOKF009); the Open Competition Project of Wuhan East Lake High-tech Development Zone (Grant Nos. 2023KJB224, 2023KJB213).

Author information

Author notes

  1. Tingting Yu and Qihang Yang have contributed equally to this study.

Authors and Affiliations

  1. Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China

    Tingting Yu, Qihang Yang & Dan Zhu

  2. Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China

    Tingting Yu, Qihang Yang & Dan Zhu

  3. Frontiers Science Center for Flexible Electronics, Xi’an Institute of Flexible Electronics (IFE) and Xi’an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi’an, Shanxi, 710072, China

    Bo Peng

  4. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China

    Zhongze Gu

  5. Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, Jiangsu, 215163, China

    Zhongze Gu

Authors
  1. Tingting Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qihang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhongze Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TY: Conceptualization; funding acquisition; visualization; writing—original draft; writing—review and editing of the manuscript. QY: Conceptualization; visualization; writing—original draft; writing—review and editing of the manuscript. Bo Peng: Funding acquisition; writing—review and editing of the manuscript. ZG: Supervision; writing—review and editing of the manuscript. DZ: conceptualization; funding acquisition; supervision; writing—review and editing of the manuscript.

Corresponding author

Correspondence to Dan Zhu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, T., Yang, Q., Peng, B. et al. Vascularized organoid-on-a-chip: design, imaging, and analysis. Angiogenesis 27, 147–172 (2024). https://doi.org/10.1007/s10456-024-09905-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10456-024-09905-z

Keywords

Search

Navigation