AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.5732
REVIEW

3D bioprinting and label-free imaging: Bridging innovations for organoid research

Linbin Zha1 Saewoon Shin1 Chulhong Kim2 Jong-Chan Park1,3,4* Byullee Park1,3,4*
Show Less
1 Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea
2 Departments of Electrical Engineering, Convergence IT Engineering, Medical Science and Engineering, Mechanical Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology (POSTECH), Cheongam-ro 77, Nam-gu, Pohang, Gyeongbuk, 37673, Republic of Korea
3 Department of Metabiohealth, Sungkyunkwan University, Suwon, 16419, Republic of Korea
4 Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
Submitted: 30 October 2024 | Accepted: 10 December 2024 | Published: 10 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Organoids are three-dimensional (3D) and multicellular structures that more closely mimic the architecture and functions of human organs. These in vitro systems are derived from pluripotent stem cells, tissue-resident stem cells, or organ-specific progenitors. Despite their potential, conventional organoid development methods are limited by inconsistencies in formation and the absence of complete microenvironmental cues, which reduce reproducibility in larger organ models. In contrast, 3D bioprinting techniques offer a precise layer-by-layer construction approach that enables superior spatial control, scalability, and uniformity in organoid formation. In this review, we examine the principles, strengths, applications, and limitations of these imaging methods, offering insights into their potential to drive further innovations in the rapidly evolving field of organoid imaging. To track the dynamic processes of cell growth, differentiation, and organization during organoid development and maturation, advanced imaging technologies are crucial. Traditional optical imaging methods, however, require exogenous labeling agents to enhance contrast, which can damage samples through photobleaching and phototoxicity. Label-free and real-time imaging modalities, by contrast, offer non-invasive and non-destructive monitoring of organoids, preserving sample integrity and enabling longitudinal studies. This review highlights the benefits of bioprinting technologies in overcoming current limitations in organoid development and provides a comprehensive overview of label-free and real-time imaging technologies for organoids. In this review, we examine the principles, strengths, applications, and limitations of these imaging methods, offering insights into their potential to drive further innovations in the rapidly evolving field of organoid imaging.

Graphical abstract
Keywords
Organoids
3D bioprinting
Optical imaging
Label-free imaging
Real-time imaging
Funding
This work was mainly supported by the National Research Foundation (NRF) grant (RS-2023-00210682, RS- 2023-00266110, No. RS-2024-00462912) funded by the Ministry of Science and ICT of the Korean government and the Ministry of Education (2020R1A6A1A03047902, BK21 FOUR program, Glocal 30 University Project). This work was also supported by the NRF grant funded by the Korea government (MSIT) for J-C.P. (No. NRF- 2022R1C1C2012736 and RS-2023-00266110).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Zhao Z, Chen X, Dowbaj A, et al. Organoids. Nat Rev Methods Primers. 2022;2(1):94. doi: 10.1038/s43586-022-00174-y
  2. Lancaster M, Renner M, Martin CA, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013;501(7467):373-379. doi: 10.1038/nature12517
  3. Hofer M, Lutolf M. Engineering organoids. Nat Rev Mater. 2021;6(5):402-420. doi: 10.1038/s41578-021-00279-y
  4. Paşca SP. Assembling human brain organoids. Science. 2019;363(6423):126-127. doi: 10.1126/science.aau5729
  5. Lullo E, Kriegstein AR. The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci. 2017;18(10):573-584. doi: 10.1038/nrn.2017.107
  6. Puschhof J, Pleguezuelos-Manzano C, Martinez-Silgado A, et al. Intestinal organoid cocultures with microbes. Nat Protoc. 2021;16(10):4633-4649. doi: 10.1038/s41596-021-00589-z
  7. Harrison S, Baumgarten S, Verma R, Lunov O, Dejneka A, Sullivan GJ. Liver organoids: recent developments, limitations and potential. Front Med. 2021;8:574047. doi: 10.3389/fmed.2021.574047
  8. Takasato M, Er PX, Chiu HS, Little MH. Generation of kidney organoids from human pluripotent stem cells. Nat Protoc. 2016;11(9):1681-1692. doi: 10.1038/nprot.2016.098
  9. Lewis-Israeli Y, Wasserman A, Gabalski M, et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat Commun. 2021;12(1):5142. doi: 10.1038/s41467-021-25329-5
  10. Ogundipe V, Groen A, Hosper N, et al. Generation and differentiation of adult tissue-derived human thyroid organoids. Stem Cell Reports. 2021;16(4):913-925. doi: 10.1016/j.stemcr.2021.02.011
  11. Völkner M, Zschätzsch M, Rostovskaya M, et al. Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem Cell Reports. 2016;6(4):525-538. doi: 10.1016/j.stemcr.2016.03.001
  12. Fernández P, Buchmann B, Goychuk A, et al. Surface-tension-induced budding drives alveologenesis in human mammary gland organoids. Nat Phys. 2021;17(10):1130-1136. doi: 10.1038/s41567-021-01336-7
  13. Perrone F, Zilbauer M. Biobanking of human gut organoids for translational research. Exp Mol Med. 2021;53(10):1451-1458. doi: 10.1038/s12276-021-00606-x
  14. Miller A, Dye B, Ferrer-Torres D, et al. Generation of lung organoids from human pluripotent stem cells in vitro. Nat Protoc. 2019;14(2):518-540. doi: 10.1038/s41596-018-0104-8
  15. Murphy S, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773-785. doi: 10.1038/nbt.2958
  16. Kolesky D, Truby R, Gladman A, et al. 3D bioprinting of vascularized, heterogeneous cell‐laden tissue constructs. Adv Materi. 2014;26(19):3124-3130. doi: 10.1002/adma.201305506
  17. Lawlor K, Vanslambrouck J, Higgins J, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater. 2021;20(2):260-271. doi: 10.1038/s41563-020-00853-9
  18. Lee A, Hudson A, Shiwarski D, et al. 3D bioprinting of collagen to rebuild components of the human heart. Science. 2019;365(6452):482-487. doi: 10.1126/science.aav9051
  19. Rios A, Clevers H. Imaging organoids: a bright future ahead. Nat Methods. 2018;15(1):24-26. doi: 10.1038/nmeth.4537
  20. Beghin A, Grenci G, Sahni G, et al. Automated high-speed 3D imaging of organoid cultures with multi-scale phenotypic quantification. Nat Methods. 2022;19(7):881-892. doi: 10.1038/s41592-022-01508-0
  21. Okkelman I, Foley T, Papkovsky D, et al. Live cell imaging of mouse intestinal organoids reveals heterogeneity in their oxygenation. Biomaterials. 2017;146:86-96. doi: 10.1016/j.biomaterials.2017.08.043
  22. Keshara R, Kim Y, Grapin-Botton A. Organoid imaging: seeing development and function. Annu Rev Cell Dev Biol. 2022;38(1):447-466. doi: 10.1146/annurev-cellbio-120320-035146
  23. Medeiros G, Ortiz R, Strnad P, et al. Multiscale light-sheet organoid imaging framework. Nat Commun. 2022;13(1): 4864. doi: 10.1038/s41467-022-32465-z
  24. Dmitriev R, Okkelman I. Multi-parameter fluorescence lifetime imaging microscopy (FLIM) for imaging metabolism in the intestinal Organoids model. Biophys J. 2020;118(3): 330a. doi: 10.1016/j.bpj.2019.11.1846
  25. Dekkers J, Alieva M, Wellens L, et al. High-resolution 3D imaging of fixed and cleared organoids. Nat Protoc. 2019;14(6):1756-1771. doi: 10.1038/s41596-019-0160-8
  26. Chen Y, Chauhan S, Gong C, et al. Low-cost and scalable projected light-sheet microscopy for the high-resolution imaging of cleared tissue and living samples. Nat Biomed Eng. 2024;8:1109-1123. doi: 10.1038/s41551-024-01249-9
  27. Shaked N, Boppart S, Wang L, et al. Label-free biomedical optical imaging. Nat Photonics. 2023;17(12):1031-1041. doi: 10.1038/s41566-023-01299-6
  28. Stanly T, Suman R, Rani G, O’Toole PJ, Kaye P, Hitchcock IS. Quantitative optical diffraction tomography imaging of mouse platelets. Front Physiol. 2020;11:568087. doi: 10.3389/fphys.2020.568087
  29. Bouma B, Boer J, Huang D, et al. Optical coherence tomography. Nat Rev Methods Primers. 2022;2(1):79. doi: 10.1038/s43586-022-00162-2
  30. Barulin A, Park H, Park B, Kim I. Dual-wavelength UV-visible metalens for multispectral photoacoustic microscopy: A simulation study. Photoacoustics. 2023;32: 100545. doi: 10.1016/j.pacs.2023.100545
  31. Park B, Han M, Kim H, et al. Shear‐force photoacoustic microscopy: toward super‐resolution near‐field imaging. Laser Photonics Rev. 2022;16(12):2200296. doi: 10.1002/lpor.202200296
  32. Kim J, Heo D, Cho S, et al. Enhanced dual-mode imaging: superior photoacoustic and ultrasound microendoscopy in live pigs using a transparent ultrasound transducer. Sci Adv. 2024;10(47):eadq9960. doi: 10.1126/sciadv.adq9960
  33. Choi W, Park E, Jeon S, et al. Three-dimensional multistructural quantitative photoacoustic and US imaging of human feet in vivo. Radiology. 2022;303(2):467-473. doi: 10.1148/radiol.211029
  34. Ahn J, Baik J, Kim D, et al. In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia. Photoacoustics. 2023;30:100485. doi: 10.1016/j.pacs.2023.100485
  35. Ahn J, Baik W, Kim Y, et al. Fully integrated photoacoustic microscopy and photoplethysmography of human in vivo. Photoacoustics. 2022;27:100374. doi: 10.1016/j.pacs.2022.100374
  36. Sivitilli A, Gosio J, Ghoshal B, et al. Robust production of uniform human cerebral organoids from pluripotent stem cells. Life Sci Alliance. 2020;3(5):202000707. doi: 10.26508/lsa.202000707
  37. Yang F, Bevilacqua C, Hambura S, et al. Pulsed stimulated brillouin microscopy enables high-sensitivity mechanical imaging of live and fragile biological specimens. Nat Methods. 2023;20(12):1971-1979. doi: 10.1038/s41592-023-02054-z
  38. Liang W, Chen D, Guan H, et al. Label-free metabolic imaging in vivo by two-photon fluorescence lifetime endomicroscopy. ACS Photonics. 2022;9(12):4017-4029. doi: 10.1021/acsphotonics.2c01493
  39. Scholler J, Groux K, Goureau O, et al. Dynamic full-field optical coherence tomography: 3D live-imaging of retinal organoids. Light Sci Appl. 2020;9(1):140. doi: 10.1038/s41377-020-00375-8
  40. Englert L, Lacalle‐Aurioles M, Mohamed N, et al. Fast 3D optoacoustic mesoscopy of neuromelanin through entire human midbrain organoids at single‐cell resolution. Laser Photonics Rev. 2023;17(8):2300443. doi: 10.1002/lpor.202300443
  41. Xue Y, Browne A, Tang W, et al. Retinal organoids long-term functional characterization using two-photon fluorescence lifetime and hyperspectral microscopy. Front Cell Neurosci. 2021;15:796903. doi: 10.3389/fncel.2021.796903
  42. Lee M, Lee J, Ha J, et al. Long-term three-dimensional high-resolution imaging of live unlabeled small intestinal organoids via low-coherence holotomography. Exp Mol Med. 2024;56:2162-2170. doi: 10.1038/s12276-024-01312-0
  43. Quadrato G, Brown J, Arlotta P. The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nat Med. 2016;22(11):1220-1228. doi: 10.1038/nm.4214
  44. Velasco S, Kedaigle AJ, Simmons SK, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature. 2019;570(7762):523-527. doi: 10.1038/s41586-019-1289-x
  45. Hughes C, Postovit L, Lajoie G. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics. 2010;10(9):1886-1890. doi: 10.1002/pmic.200900758
  46. Benton G, Arnaoutova I, George J, Kleinman H, Koblinski J. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv Drug Deliv Rev. 2014;79:3-18. doi: 10.1016/j.addr.2014.06.005
  47. Gjorevski N, Lutolf M. Synthesis and characterization of well-defined hydrogel matrices and their application to intestinal stem cell and organoid culture. Nat Protoc. 2017;12(11):2263-2274. doi: 10.1038/nprot.2017.095
  48. Cleaver O, Melton D. Endothelial signaling during development. Nat Med. 2003;9(6):661-668. doi: 10.1038/nm0603-661
  49. Grebenyuk S, Ranga A. Engineering organoid vascularization. Front Bioeng Biotechnol. 2019;7:39. doi: 10.3389/fbioe.2019.00039
  50. Cakir B, Xiang Y, Tanaka Y, et al. Engineering of human brain organoids with a functional vascular-like system. Nat Methods. 2019;16(11):1169-1175. doi: 10.1038/s41592-019-0586-5
  51. Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013;494(7436):247-250. doi: 10.1038/nature11826
  52. Prior N, Inacio P, Huch M. Liver organoids: from basic research to therapeutic applications. Gut. 2019;68(12):2228-2237. doi: 10.1136/gutjnl-2019-319256
  53. Czerniecki S, Cruz N, Harder J, et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell stem cell. 2018;22(6): 929-940.e4. doi: 10.1016/j.stem.2018.04.022
  54. Combes A, Zappia L, Er P, Oshlack A, Little M. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. Genome Med. 2019;11:1-15. doi: 10.1186/s13073-019-0615-0
  55. Sato T, Clevers H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science. 2013;340(6137):1190-1194. doi: 10.1126/science.1234852
  56. Sachs N, Papaspyropoulos A, Zomer‐van Ommen D, et al. Long‐term expanding human airway organoids for disease modeling. EMBO J. 2019;38(4):e100300. doi: 10.15252/embj.2018100300
  57. Zhang Y, Haghiashtiani G, Hübscher T, et al. 3D extrusion bioprinting. Nat Rev Methods Primers. 2021;1(1):75. doi: 10.1038/s43586-021-00073-8
  58. Ramesh S, Harrysson O, Rao P, et al. Extrusion bioprinting: recent progress, challenges, and future opportunities. Bioprinting. 2021;21:e00116. doi: 10.1016/j.bprint.2020.e00116
  59. Ng L, Shkolnikov V. Jetting-based bioprinting: process, dispense physics, and applications. Bio-Design Manufactur. 2024;7(5):771-799. doi: 10.1007/s42242-024-00285-3
  60. Levato R, Dudaryeva O, Garciamendez-Mijares CE, et al. Light-based vat-polymerization bioprinting. Nat Rev Methods Primers. 2023;3(1):47. doi: 10.1038/s43586-023-00231-0
  61. Mohammadrezaei D, Podina L, De Silva J, Kohandel M. Cell viability prediction and optimization in extrusion-based bioprinting via neural network-based Bayesian optimization models. Biofabrication. 2024;16(2):025016. doi: 10.1088/1758-5090/ad17cf
  62. Xu T, Zhao W, Zhu J, Albanna MZ, Yoo J, Atala A. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. Biomaterials. 2013;34(1):130-139. doi: 10.1016/j.biomaterials.2012.09.035
  63. Li X, Liu B, Pei B, et al. Inkjet bioprinting of biomaterials. Chem Rev. 2020;120(19):10793-10833. doi: 10.1021/acs.chemrev.0c00008
  64. Keriquel V, Oliveira H, Rémy M, et al. In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for in vivo bone regeneration applications. Sci Rep. 2017; 7(1):1778. doi: 10.1038/s41598-017-01914-x
  65. Koch L, Deiwick A, Schlie S, et al. Skin tissue generation by laser cell printing. Biotechnol Bioeng. 2012;109(7):1855-1863. doi: 10.1002/bit.24455
  66. Kérourédan O, Hakobyan D, Rémy M, et al. In situ prevascularization designed by laser-assisted bioprinting: effect on bone regeneration. Biofabrication. 2019;11(4):045002. doi: 10.1088/1758-5090/ab2620
  67. Chartrain N, Williams C, Whittington A. A review on fabricating tissue scaffolds using vat photopolymerization. Acta Biomater. 2018;74:90-111. doi: 10.1016/j.actbio.2018.05.010
  68. Li W, Mille L, Robledo J, Uribe T, Huerta V, Zhang Y. Recent advances in formulating and processing biomaterial inks for vat polymerization‐based 3D printing. Adv Healthc Mater. 2020;9(15):2000156. doi: 10.1002/adhm.202000156
  69. Jakab K, Norotte C, Marga F, Murphy K, Vunjak-Novakovic G, Forgacs G. Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication. 2010;2(2): 022001. doi: 10.1088/1758-5082/2/2/022001
  70. Ning L, Chen X. A brief review of extrusion‐based tissue scaffold bio‐printing. Biotechnol J. 2017;12(8):1600671. doi: 10.1002/biot.201600671
  71. Nair K, Gandhi M, Khalil S, et al. Characterization of cell viability during bioprinting processes. Biotechnol J. 2009;4(8):1168-77. doi: 10.1002/biot.200900004
  72. Gao Q, He Y, Fu J, Liu A, Ma L. Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Biomaterials. 2015;61:203-215. doi: 10.1016/j.biomaterials.2015.05.031
  73. Malda J, Visser J, Melchels F, et al. 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater. 2013;25(36):5011-5028. doi: 10.1002/adma.201302042
  74. Xu T, Jin J, Gregory C, Hickman J, Boland T. Inkjet printing of viable mammalian cells. Biomaterials. 2005;26(1):93-99. doi: 10.1016/j.biomaterials.2004.04.011
  75. Cui X, Boland T, Lima D, K. Lotz M. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul. 2012;6(2):149-155. doi: 10.2174/187221112800672949
  76. Derby B. Bioprinting: inkjet printing proteins and hybrid cell-containing materials and structures. J Mater Chem. 2008;18(47):5717-5721. doi: 10.1039/B807560C
  77. Saunders R, Derby B. Inkjet printing biomaterials for tissue engineering: bioprinting. Int Mater Rev. 2014;59(8):430-448. doi: 10.1179/1743280414Y.0000000040
  78. Lee W, Debasitis J, Lee VK, et al. Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. Biomaterials. 2009;30(8):1587-1595. doi: 10.1016/j.biomaterials.2008.12.009
  79. Horváth L, Umehara Y, Jud C, Blank F, Petri-Fink A, Rothen- Rutishauser B. Engineering an in vitro air-blood barrier by 3D bioprinting. Sci Rep. 2015;5(1):7974. doi: 10.1038/srep07974
  80. Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT. The bioink: a comprehensive review on bioprintable materials. Biotechnol Adv. 2017;35(2):217-239. doi: 10.1016/j.biotechadv.2016.12.006
  81. Ozbolat I, Yu Y. Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng. 2013; 60(3):691-699. doi: 10.1109/TBME.2013.2243912
  82. Liu W, Zhong Z, Hu N, et al. Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments. Biofabrication. 2018; 10(2):024102. doi: 10.1088/1758-5090/aa9d44
  83. Melchels P, Feijen J, Grijpma D. A review on stereolithography and its applications in biomedical engineering. Biomaterials. 2010;31(24):6121-6130. doi: 10.1016/j.biomaterials.2010.04.050
  84. Chimene D, Lennox K, Kaunas R, Gaharwar A. Advanced bioinks for 3D printing: a materials science perspective. Ann Biomed Eng. 2016;44:2090-2102. doi: 10.1007/s10439-016-1638-y
  85. Lim K, Levato R, Costa P, et al. Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. Biofabrication. 2018;10(3):034101. doi: 10.1088/1758-5090/aac00c
  86. Tumbleston J, Shirvanyants D, Ermoshkin N, et al. Continuous liquid interface production of 3D objects. Science. 2015;347(6228):1349-1352. doi: 10.1126/science.aaa2397
  87. Grigoryan B, Paulsen S, Corbett D, et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science. 2019;364(6439):458-464. doi: 10.1126/science.aav9750
  88. Sharifi S, Sharifi H, Akbari A, Chodosh J. Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA). Sci Rep. 2021;11:23276. doi: 110.1038/s41598-021-02830-x
  89. Williams C, Malik A, Kim T, Manson P, Elisseeff J. Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. Biomaterials. 2005;26(11):1211-1218. doi: 10.1016/j.biomaterials.2004.04.024
  90. Fairbanks B, Schwartz M, Bowman C, Anseth K. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2, 4, 6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials. 2009;30(35):6702-6707. doi: 10.1016/j.biomaterials.2009.08.055
  91. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254-71. doi: 10.1016/j.biomaterials.2015.08.045
  92. Reid J, Mollica P, Bruno R, Sachs P. Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform. Breast Cancer Res. 2018;20:1-13. doi: 10.1186/s13058-018-1045-4
  93. Noor N, Shapira A, Edri R, Gal I, Wertheim L, Dvir T. 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv Sci. 2019;6(11):1900344. doi: 10.1002/advs.201900344
  94. Pham M, Pollock K, Rose M, et al. Generation of human vascularized brain organoids. Neuroreport. 2018;29(7):588-593. doi: 10.1097/WNR.0000000000001014
  95. Lee J, Cuddihy M, Kotov N. Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev. 2008;14(1):61-86. doi: 10.1089/teb.2007.0150
  96. Caliari S, Burdick J. A practical guide to hydrogels for cell culture. Nat Methods. 2016;13(5):405-414. doi: 10.1038/nmeth.3839
  97. Heinrich M, Bansal R, Lammers T, Zhang Y, Michel Schiffelers R, Prakash J. 3D‐bioprinted mini‐brain: a glioblastoma model to study cellular interactions and therapeutics. Adv Mater. 2019;31(14):1806590. doi: 10.1002/adma.201806590
  98. Kratochvil M, Seymour A, Li TL, Paşca S, Kuo C, Heilshorn S. Engineered materials for organoid systems. Nat Rev Mater. 2019;4(9):606-622. doi: 10.1038/s41578-019-0129-9
  99. Wang H, Yu H, Zhou X, et al. An overview of extracellular matrix-based bioinks for 3D bioprinting. Front Bioeng Biotechnol. 2022;10:905438. doi: 10.3389/fbioe.2022.905438
  100. Bülow A, Schäfer B, Beier J. Three-dimensional bioprinting in soft tissue engineering for plastic and reconstructive surgery. Bioengineering. 2023;10(10):1232. doi: 10.3390/bioengineering10101232
  101. Andersen J, Revah O, Miura Y, et al. Generation of functional human 3D cortico-motor assembloids. Cell. 2020;183(7):1913-1929.e26. doi: 10.1016/j.cell.2020.11.017
  102. Qian X, Jacob F, Song M, Nguyen H, Song H, Ming Gl. Generation of human brain region–specific organoids using a miniaturized spinning bioreactor. Nat Protoc. 2018;13(3):565-580. doi: 10.1038/nprot.2017.152
  103. Wolf K, Weiss J, Uzel S, Skylar-Scott M, Lewis J. Biomanufacturing human tissues via organ building blocks. Cell Stem Cell. 2022;29(5):667-677. doi: 10.1016/j.stem.2022.04.012
  104. Mironov V, Mironov V. Organ printing: tissue spheroids as building blocks. Gene Cell. 2010;5(3):41. doi: 10.23868/gc121746
  105. Bagley J, Reumann D, Bian S, Lévi-Strauss J, Knoblich JA. Fused cerebral organoids model interactions between brain regions. Nat Methods. 2017;14(7):743-751. doi: 10.1038/nmeth.4304
  106. Lancaster M, Knoblich J. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 2014;9(10):2329-2340. doi: 10.1038/nprot.2014.158
  107. Driehuis E, Kretzschmar K, Clevers H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat Protoc. 2020;15(10):3380-3409. doi: 10.1038/s41596-020-0379-4
  108. Heydari Z, Moeinvaziri F, Agarwal T, et al. Organoids: a novel modality in disease modeling. Biodes Manuf. 2021;4: 689-716. doi: 10.1007/s42242-021-00150-7
  109. Grassi L, Alfonsi R, Francescangeli F, et al. Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases. Cell Death Dis. 2019;10(3):201. doi: 10.1038/s41419-019-1453-0
  110. Maharjan S, Ma C, Singh B, et al. Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications. Adv Drug Deliv Rev. 2024:115237. doi: 10.1016/j.addr.2024.115237
  111. Langer M, Cloetens P, Peyrin F. Regularization of phase retrieval with phase-attenuation duality prior for 3-D holotomography. IEEE Trans Image Process. 2010;19(9):2428-2436. doi: 10.1109/TIP.2010.2048608
  112. Jo J, Baek D, Hugonnet H, et al. 3D Measurements and characterizations of refractive index distributions of volume holographic gratings using low‐coherence holotomography. Adv Opt Mate. 2024;12(13):2302048. doi: 10.1002/adom.202302048
  113. Salucci S, Battistelli M, Burattini S, Sbrana F, Falcieri E. Holotomographic microscopy: a new approach to detect apoptotic cell features. Microsc Res Tech. 2020;83(12): 1464-1470. doi: 10.1002/jemt.23539
  114. Kim G, Hugonnet H, Kim K, et al. Holotomography. Nat Rev Methods Primers. 2024;4(1):51 doi: 10.1038/s43586-024-00327-1
  115. Park D, Lee D, Kim Y, et al. Cryobiopsy: a breakthrough strategy for clinical utilization of lung cancer organoids. Cells. 2023;12(14):1854. doi: 10.3390/cells12141854
  116. Ziemczonok M, Desissaire S, Neri J, et al. Tailored 3D microphantoms: an essential tool for quantitative phase tomography analysis of organoids. arXiv preprint arXiv: 240916888. 2024; doi: 10.48550/arXiv.2409.16888
  117. Kim D, Oh N, Kim K, et al. Label-free high-resolution 3D imaging of gold nanoparticles inside live cells using optical diffraction tomography. Methods. 2018;136:160-167. doi: 10.1016/j.ymeth.2017.07.008
  118. Kim K, Lee S, Yoon J, Heo J, Choi C, Park Y. Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes. Sci Rep. 2016;6(1):36815. doi: 10.1038/srep36815
  119. Gao W, Wu X. Differences between time domain and Fourier domain optical coherence tomography in imaging tissues. J Microsc. 2017;268(2):119-128. doi: 10.1111/jmi.12592
  120. Morishita R, Suzuki T, Mukherjee P, et al. Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography. Biomed Opt Express. 2023;14(5):2333-2351. doi: 10.1364/BOE.488097
  121. Gil D, Deming D, Skala M. Volumetric growth tracking of patient-derived cancer organoids using optical coherence tomography. Biomed Opt Express. 2021;12(7):3789-3805. doi: 10.1364/BOE.428197
  122. Bao D, Wang L, Zhou X, Yang S, He K, Xu M. Automated detection and growth tracking of 3D bio-printed organoid clusters using optical coherence tomography with deep convolutional neural networks. Front Bioeng Biotechnol. 2023;11:1133090. doi: 10.3389/fbioe.2023.1133090
  123. Dubois A, Vabre L, Boccara A, Beaurepaire E. High-resolution full-field optical coherence tomography with a Linnik microscope. Appl Opt. 2002;41(4):805-812. doi: 10.1364/ao.41.000805
  124. Hosseinaee Z, Tummon Simmons J, Reza P. Dual-modal photoacoustic imaging and optical coherence tomography. Front Phys. 2021;8:616618. doi: 10.3389/fphy.2020.616618
  125. Park B, Park S, Kim J, Kim C. Listening to drug delivery and responses via photoacoustic imaging. Adv Drug Deliv Rev. 2022;184:114235. doi: 10.1016/j.addr.2022.114235
  126. Cho S, Kim M, Ahn J, et al. An ultrasensitive and broadband transparent ultrasound transducer for ultrasound and photoacoustic imaging in-vivo. Nat Commun. 2024;15(1):1444. doi: 10.1038/s41467-024-45273-4
  127. Yoon C, Park E, Misra S, et al. Deep learning-based virtual staining, segmentation, and classification in label-free photoacoustic histology of human specimens. Light Sci Appl. 2024;13(1):226. doi: 10.1038/s41377-024-01554-7
  128. Park J, Choi S, Knieling F, et al. Clinical translation of photoacoustic imaging. Nat Rev Bioeng. 2024:1-20. doi: 10.1038/s44222-024-00240-y
  129. Park J, Park B, Ahn J, et al. Opto-ultrasound biosensor for wearable and mobile devices: realization with a transparent ultrasound transducer. Biomed Opt Express. 2022;13(9):4684-4692. doi: 10.1364/BOE.468969
  130. Park B, Han M, Park J, et al. A photoacoustic finder fully integrated with a solid-state dye laser and transparent ultrasound transducer. Photoacoustics. 2021;23:100290. doi: 10.1016/j.pacs.2021.100290
  131. Kim J, Lee J, Choi S, et al. 3d multiparametric photoacoustic computed tomography of primary and metastatic tumors in living mice. ACS Nano. 2024;18(28):18176-18190. doi: 10.1021/acsnano.3c12551
  132. Zhu X, Huang Q, DiSpirito A, et al. Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy. Light Sci Appl. 2022;11(1):138. doi: 10.1038/s41377-022-00836-2
  133. Park B, Bang C, Lee C, et al. 3D wide‐field multispectral photoacoustic imaging of human melanomas in vivo: a pilot study. J Eur Acad Dermatol Venereol. 2021;35(3):669-676. doi: 10.1111/jdv.16985
  134. Choi W, Park B, Choi S, Oh D, Kim J, Kim C. Recent advances in contrast-enhanced photoacoustic imaging: overcoming the physical and practical challenges. Chem Rev. 2023;123(11):7379-7419. doi: 10.1021/acs.chemrev.2c00627
  135. Park J, Park B, Kim TY, et al. Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer. Proc Natl Acad Sci USA. 2021;118(11):e1920879118. doi: 10.1073/pnas.1920879118
  136. Ma C, Li W, Li D, et al. Photoacoustic imaging of 3D-printed vascular networks. Biofabrication. 2022;14(2):025001. doi: 10.1088/1758-5090/ac49d5
  137. Monzel AS, Smits LM, Hemmer K, et al. Derivation of human midbrain-specific organoids from neuroepithelial stem cells. Stem Cell Reports. 2017;8(5):1144-1154. doi: 10.1016/j.stemcr.2017.03.010
  138. Breideband L, Wächtershäuser K, Hafa L, et al. Upgrading a consumer stereolithographic 3d printer to produce a physiologically relevant model with human liver cancer organoids. Adv Mater Technol. 2022;7(10):2200029. doi: 10.1002/admt.202200029
  139. Urciuolo A, Giobbe G, Dong Y, et al. Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures. Nat Commun. 2023;14(1):3128. doi: 10.1038/s41467-023-37953-4
  140. Dong Q, Su X, Li X, et al. In vitro construction of lung cancer organoids by 3D bioprinting for drug evaluation. Coll Surf A Physicochem Eng Aspects. 2023;666:131288. doi: 10.1016/j.colsurfa.2023.131288
  141. Conrad C, Gray K, Stroka K, Rizvi I, Scarcelli G. Mechanical characterization of 3D ovarian cancer nodules using Brillouin confocal microscopy. Cell Mol Bioeng. 2019;12:215-226. doi: 10.1007/s12195-019-00570-7
  142. Coker Z, Troyanova M, Steelman Z, et al. Brillouin microscopy monitors rapid responses in subcellular compartments. Photonix. 2024;5(1):9. doi: 10.1186/s43074-024-00123-w
  143. Prevedel R, Diz-Muñoz A, Ruocco G, Antonacci G. Brillouin microscopy: an emerging tool for mechanobiology. Nat Methods. 2019;16(10):969-977. doi: 10.1038/s41592-019-0543-3
  144. Kabakova I, Zhang J, Xiang Y, et al. Brillouin microscopy. Nat Rev Methods Primers. 2024;4(1):8. doi: 10.1038/s43586-023-00286-z
  145. Caiaffa C, Tukeman G, Delgado C, et al. Dolutegravir induces FOLR1 expression during brain organoid development. Front Mol Neurosci. 2024;17:1394058. doi: 10.3389/fnmol.2024.1394058
  146. Bouvet P, Clément F, Papoz A, Dehoux T, Baritaux J. Multimode fiber-coupled VIPA spectrometer for high-throughput Brillouin imaging of biological samples. J Phys Photonics. 2024;6(2):025010. doi: 10.1088/2515-7647/ad378c
  147. Park J, Gao L. Advancements in fluorescence lifetime imaging microscopy Instrumentation: towards high speed and 3D. Curr Opin Solid State Mater Sci. 2024;30: 101147. doi: 10.1016/j.cossms.2024.101147
  148. Becker W. Fluorescence lifetime imaging–techniques and applications. J Microsc. 2012;247(2):119-136. doi: 10.1111/j.1365-2818.2012.03618.x
  149. Jakobs S, Subramaniam V, Schönle A, Jovin T, Hell S. EGFP and DsRed expressing cultures of Escherichia coli imaged by confocal, two-photon and fluorescence lifetime microscopy. FEBS Lett. 2000;479(3):131-135. doi: 10.1016/s0014-5793(00)01896-2
  150. Ma Y, Park J, Huang L, et al. Light-field tomographic fluorescence lifetime imaging microscopy. Proc Natl Acad Sci USA. 2024;121(40):e2402556121. doi: 10.1073/pnas.2402556121
  151. Barroso M, Monaghan M, Niesner R, Dmitriev R. Probing organoid metabolism using fluorescence lifetime imaging microscopy (FLIM): the next frontier of drug discovery and disease understanding. Adv Drug Deliv Rev. 2023: 115081. doi: 10.1016/j.addr.2023.115081
  152. Walsh A, Cook R, Sanders M, et al. Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res. 2014;74(18):5184-5194. doi: 10.1158/0008-5472.CAN-14-0663
  153. Datta R, Heaster T, Sharick J, Gillette A, Skala M. Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications. J Biomed Opt. 2020;25(7):071203-071203. doi: 10.1117/1.JBO.25.7.071203
  154. Sharma U, Chang E, Yun S. Long-wavelength optical coherence tomography at 1.7 μm for enhanced imaging depth. Opt Express. 2008;16(24):19712-19723. doi: 10.1364/oe.16.019712
  155. Gröhl J, Schellenberg M, Dreher K, Maier-Hein L. Deep learning for biomedical photoacoustic imaging: a review. Photoacoustics. 2021;22:100241. doi: 10.1016/j.pacs.2021.100241
  156. Fei K, Zhang J, Yuan J, Xiao P. Present application and perspectives of organoid imaging technology. Bioengineering. 2022;9(3):121. doi: 10.3390/bioengineering9030121
  157. Pettinato G, Goughlan M, Zhang X, et al. Spectroscopic label-free microscopy of changes in live cell chromatin and biochemical composition in transplantable organoids. Sci Adv. 2021;7(34):eabj2800. doi: 10.1126/sciadv.abj2800
  158. Errico C, Pierre J, Pezet S, et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature. 2015;527:499-502. doi: 10.1038/nature16066
  159. Deben C, Hoz E, Compte M, et al. OrBITS: label-free and time-lapse monitoring of patient derived organoids for advanced drug screening. Cell Oncol. 2023;46(2):299-314. doi: 10.1007/s13402-022-00750-0
  160. Park E MS, Hwang D, et al. Unsupervised inter-domain transformation for virtually stained high-resolution mid-infrared photoacoustic microscopy using explainable deep learning. Nat Commun. 2024;(In press).

 

 

 

 

 

 

 

 

 



Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing