Engineering Organs-on-Chips and Organoids from the Perspective of Compartmentalization

Yi Zeng; Zhongze Gu; Huafu Chen; Xu Deng

doi:10.1016/j.eng.2025.12.011

Engineering ›› :202512011 DOI: 10.1016/j.eng.2025.12.011

Views & Comments

research-article

Engineering Organs-on-Chips and Organoids from the Perspective of Compartmentalization

Yi Zeng ^a
, Zhongze Gu ^d^,^*
, Huafu Chen ^a^,^*
, Xu Deng ^b^,^c^,^*

Author information +

History +

PDF (2083KB)

Cite this article

Download citation ▾

Yi Zeng, Zhongze Gu, Huafu Chen, Xu Deng. Engineering Organs-on-Chips and Organoids from the Perspective of Compartmentalization. Engineering 202512011 DOI:10.1016/j.eng.2025.12.011

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Zambuto SG, Scott AK, Oyen ML. FDA modernization act 2.0 and reproductive research. Nat Rev Bioeng 2024; 2(12):984-6.

[2]	Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010; 328(5986):1662-8.

[3]	Ugodnikov A, Persson H, Simmons CA. Bridging barriers: advances and challenges in modeling biological barriers and measuring barrier integrity in organ-on-chip systems. Lab Chip 2024; 24(13):3199-225.

[4]	Carvalho AM, Bansal R, Barrias CC, Sarmento B. The material world of 3D-bioprinted and microfluidic-chip models of human liver fibrosis. Adv Mater 2024; 36(2):2307673.

[5]	Shakeri A, Khan S, Didar TF. Conventional and emerging strategies for the fabrication and functionalization of PDMS-based microfluidic devices. Lab Chip 2021; 21(16):3053-75.

[6]	Leng Y, Li X, Zheng F, Liu H, Wang C, Wang X, et al. Advances in in vitro models of neuromuscular junction: focusing on organ-on-a-chip, organoids, and biohybrid robotics. Adv Mater 2023; 35(41):2211059.

[7]	Zhao Y, Wang EY, Lai FBL, Cheung K, Radisic M. Organs-on-a-chip: a union of tissue engineering and microfabrication. Trends Biotechnol 2023; 41(3):410-24.

[8]	Wu Z, Liu R, Shao N, Zhao Y. Developing 3D bioprinting for organs-on-chips. Lab Chip 2025; 25(5):1081-96.

[9]	Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S, Matsumura M, et al. Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 2008; 3(5):519-32.

[10]	Sato T, Vries RG, Snippert HJ, Van De Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459(7244):262-5.

[11]	Chen Y, Hui L. Organoids and their applications. 1st ed. Shanghai: Shanghai Scientific & Technical Publishers; 2023. Chinese.

[12]	LeSavage BL, Suhar RA, Broguiere N, Lutolf MP, Heilshorn SC. Next-generation cancer organoids. Nat Mater 2022; 21(2):143-59.

[13]	Zhang W, Li J, Zhou J, Rastogi A, Ma S. Translational organoid technology—the convergence of chemical, mechanical, and computational biology. Trends Biotechnol 2022; 40(9):1121-35.

[14]	Tenreiro MF, Branco MA, Cotovio JP, Cabral JMS, Fernandes TG, Diogo MM. Advancing organoid design through co-emergence, assembly, and bioengineering. Trends Biotechnol 2023; 41(7):923-38.

[15]	Sundaram S, Chen CS. Next-generation engineered microsystems for cell biology: a systems-level roadmap. Trends Cell Biol 2022; 32(6):490-500.

[16]	Yang J, Wang P, Zhang Y, Zhang M, Sun Q, Chen H, et al. Photo-tunable hydrogels reveal cellular sensing of rapid rigidity changes through the accumulation of mechanical signaling molecules. Cell Stem Cell 2025; 32(1):121-36.

[17]	Liu X, Zhang M, Wang P, Zheng K, Wang X, Xie W, et al. Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus. Proc Natl Acad Sci USA 2025; 122(10):e2501264122.

[18]	Kozlowski MT, Crook CJ, Ku HT. Towards organoid culture without Matrigel. Commun Biol 2021; 4(1):1387.

[19]	Trantidou T, Friddin M, Elani Y, Brooks NJ, Law RV, Seddon JM, et al. Engineering compartmentalized biomimetic micro-and nanocontainers. ACS Nano 2017; 11(7):6549-65.

[20]	Floris E, Piras A, Dall’Asta L, Gamba A, Hirsch E, Campa CC. Physics of compartmentalization: how phase separation and signaling shape membrane and organelle identity. Comput Struct. Biotechnol J 2021;19:3225-33.

[21]	Chen AH, Silver PA. Designing biological compartmentalization. Trends Cell Biol 2012; 22(12):662-70.

[22]	Takahashi S. Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit. Neuropathology 2020; 40(2):121-37.

[23]	Schot M, Araújo-Gomes N, van Loo B, Kamperman T, Leijten J. Scalable fabrication, compartmentalization and applications of living microtissues. Bioact Mater 2023;19:392-405.

[24]	Li X, Yilmaz LS, Walhout AJM. Compartmentalization of metabolism between cell types in multicellular organisms: a computational perspective. Curr Opin Syst Biol 2022;29:100407.

[25]	Bar-Peled L, Kory N. Principles and functions of metabolic compartmentalization. Nat Metab 2022; 4(10):1232-44.

[26]	Wang X, Luo Y, Ma Y, Wang P, Yao R. Converging bioprinting and organoids to better recapitulate the tumor microenvironment. Trends Biotechnol 2024; 42(5):648-63.

[27]	Zhang YS, Dolatshahi-Pirouz A, Orive G. Regenerative cell therapy with 3D bioprinting. Science 2024; 385(6709):604-6.

[28]	Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater 2021; 6(5):402-20.

[29]	Nikolaev M, Mitrofanova O, Broguiere N, Geraldo S, Dutta D, Tabata Y, et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 2020; 585(7826):574-8.

[30]	Gjorevski N, Nikolaev M, Brown TE, Mitrofanova O, Brandenberg N, DelRio FW, et al. Tissue geometry drives deterministic organoid patterning. Science 2022; 375(6576):eaaw9021.

[31]	Sriram G, Alberti M, Dancik Y, Wu B, Wu R, Feng Z, et al. Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function. Mater Today 2018; 21(4):326-40.

[32]	Liu J, Du C, Chen J, Tang B, Liu S, Tan J, et al. Hydrogel microspheres empowering organ-on-a-chip systems: innovations and applications. Small 2025; 2504563(44):2504563.

[33]	Liu H, Wang Y, Cui K, Guo Y, Zhang X, Qin J. Advances in hydrogels in organoids and organs-on-a-chip. Adv Mater 2019; 31(50):1902042.

[34]	Wang J, Qiao H, Wang Z, Zhao W, Chen T, Li B, et al. Rational design and acoustic assembly of human cerebral cortex-like microtissues from hiPSC-derived neural progenitors and neurons. Adv Mater 2023; 35(32):2210631.

[35]	Parfenov VA, Khesuani YD, Petrov SV, Karalkin PA, Koudan EV, Nezhurina EK, et al. Magnetic levitational bioassembly of 3D tissue construct in space. Sci Adv 2020; 6(29):eaba4174.

[36]	Sneh T, Corsetti S, Notaros M, Kikkeri K, Voldman J, Notaros J. Optical tweezing of microparticles and cells using silicon-photonics-based optical phased arrays. Nat Commun 2024; 15(1):8493.

[37]	Melde K, Athanassiadis AG, Missirlis D, Shi M, Seneca S, Fischer P. Ultrasound-assisted tissue engineering. Nat Rev Bioeng 2024; 2(6):486-500.

[38]	Vighetto V, Pascucci E, Savino G, Rosso G, Percivalle NM, Conte M, et al. The multifunctional purposes of ultrasound in 3D models. Adv Ther 2024; 7(10):2400161.

[39]	Rufo J, Zhang P, Zhong R, Lee LP, Huang TJ. A sound approach to advancing healthcare systems: the future of biomedical acoustics. Nat Commun 2022; 13(1):3459.

[40]	Ma Z, Holle AW, Melde K, Qiu T, Poeppel K, Kadiri VM, et al. Acoustic holographic cell patterning in a biocompatible hydrogel. Adv Mater 2020; 32(4):1904181.

[41]	Chansoria P, Shirwaiker R. 3D bioprinting of anisotropic engineered tissue constructs with ultrasonically induced cell patterning. Addit Manuf 2020;32:101042.

[42]	Luo Y, Gao H, Zhou M, Xiao L, Xu T, Zhang X. Integrated acoustic chip for culturing 3D cell arrays. ACS Sens 2022; 7(9):2654-60.

[43]	Zhang P, Bachman H, Ozcelik A, Huang TJ. Acoustic microfluidics. Annu Rev Anal Chem 2020; 13(1):17-43.

[44]	Deshmukh DV, Reichert P, Zvick J, Labouesse C, Künzli V, Dudaryeva O, et al. Continuous production of acoustically patterned cells within hydrogel fibers for musculoskeletal tissue engineering. Adv Funct Mater 2022; 32(30):2113038.

[45]	Ao Z, Cai H, Wu Z, Ott J, Wang H, Mackie K, et al. Controllable fusion of human brain organoids using acoustofluidics. Lab Chip 2021; 21(4):688-99.

[46]	Seo JY, Park S, Kim SY, Seo GJ, Jang HK, Lee TJ, et al. Acoustic and magnetic stimuli-based three-dimensional cell culture platform for tissue engineering. Tissue Eng Regen Med 2023; 20(4):563-80.

[47]	Holden MA, Needham D, Bayley H. Functional bionetworks from nanoliter water droplets. J Am Chem Soc 2007; 129(27):8650-5.

[48]	Alcinesio A, Meacock OJ, Allan RG, Monico C, Schild VR, Cazimoglu I, et al. Controlled packing and single-droplet resolution of 3D-printed functional synthetic tissues. Nat Commun 2020; 11(1):2105.

[49]	Hoskin CEG, Schild VR, Vinals J, Bayley H. Parallel transmission in a synthetic nerve. Nat Chem 2022; 14(6):650-7.

[50]	Chong Z, Zeng Y, Kang Y, Ding K, Du X, Gu Z. Advances in networking droplets. Droplet 2025; 4(2):e173.

[51]	Zhou L, Wolfes AC, Li Y, Chan DCW, Ko H, Szele FG, et al. Lipid-bilayer-supported 3D printing of human cerebral cortex cells reveals developmental interactions. Adv Mater 2020; 32(31):2002183.

[52]	Kesse CR, Giaever I. Cell growth on liquid microcarriers. Science 1983; 219(4591):1448-9.

[53]	Jia X, Song J, Lv W, Hill JP, Nakanishi J, Ariga K. Adaptive liquid interfaces induce neuronal differentiation of mesenchymal stem cells through lipid raft assembly. Nat Commun 2022; 13(1):3110.

[54]	Jia X, Minami K, Uto K, Chang AC, Hill JP, Nakanishi J, et al. Adaptive liquid interfacially assembled protein nanosheets for guiding mesenchymal stem cell fate. Adv Mater 2020; 32(4):1905942.

[55]	Kong D, Peng L, Di Cio S, Novak P, Gautrot JE. Stem cell expansion and fate decision on liquid substrates are regulated by self-assembled nanosheets. ACS Nano 2018; 12(9):9206-13.

[56]	Leung CM, de Haan P, Ronaldson-Bouchard K, Kim GA, Ko J, Rho HS, et al. A guide to the organ-on-a-chip. Nat Rev Methods Primers 2022; 2(1):1-29.

[57]	Komarnisky RM, Wootten S, Friedman N, Nikkhah M. Organ-on-a-chip: key industry insights, challenges, and opportunities from 100+ NSF I-Corps interviews. Lab Chip 2025; 25(19):4828-43.

[58]	Yi SA, Zhang Y, Rathnam C, Pongkulapa T, Lee KB. Bioengineering approaches for the advanced organoid research. Adv Mater 2021; 33(45):2007949.

[59]	Andrews MG, Kriegstein AR. Challenges of organoid research. Annu Rev Neurosci 2022; 42(1):23-39.

[60]	He CF, Qiao TH, Wang GH, Sun Y, He Y. High-resolution projection-based 3D bioprinting. Nat Rev Bioeng 2025; 3(2):143-58.

[61]	Guida L, Cavallaro M, Levi M. Advancements in high-resolution 3D bioprinting: exploring technological trends, bioinks and achieved resolutions. Bioprinting 2024;44:e00376.