AccScience Publishing / IJB / Volume 9 / Issue 5 / DOI: 10.18063/ijb.748
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

3D bioprinting strategy for engineering vascularized tissue models

Suhun Chae1 Dong-Heon Ha1* Hyungseok Lee2,3*
Show Less
1 EDmicBio Inc., Seoul 02458, Republic of Korea
2 Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon 24341, Republic of Korea
3 Department of Smart Health Science and Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
Submitted: 16 February 2023 | Accepted: 28 March 2023 | Published: 9 May 2023
(This article belongs to the Special Issue 3D Printing of Advanced Biomedical Devices)
© 2023 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 ( )

Leveraging three-dimensional (3D) bioprinting in the fields of tissue engineering and regenerative medicine has rapidly accelerated progress toward the development of living tissue constructs and biomedical devices. Ongoing vigorous research has pursued the development of 3D in vitro tissue models to replicate the key aspects of human physiology by incorporating relevant cell populations and adequate environmental cues. Given their advantages of being able to intimately mimic the heterogeneity and complexity of their native counterparts, 3D in vitro models hold promise as alternatives to conventional cell cultures or animal models for translational application to model human physiology/pathology and drug screening. Research has highlighted the importance of in vitro models, and a sophisticated biomanufacturing strategy is vitally required. In particular, vascularization is critical for the prolonged survival and functional maturation of the engineered tissues, which has remained one of the major challenges in the establishment of physiologically relevant 3D in vitro models. To this end, 3D bioprinting can efficiently generate solid and reproducible vascularized tissue models with high architectural and compositional similarity to the native tissues, leading to improve the structural maturation and tissue-specific functionality. Multiple bioprinting strategies have been developed to vascularize in vitro tissues by spatially controlled patterning of vascular precursors or generating readily perfusable vascular structures. This review presents an overview of the advanced 3D bioprinting strategies for vascularized tissue model development. We present the key elements for rebuilding functional vasculature in 3D-bioprinted tissue models and discuss the recent achievements in the engineering of 3D vascularized in vitro models using 3D bioprinting. Finally, we delineate the current challenges and future outlooks of 3D bioprinting-based vascularized tissue models.

3D bioprinting
Vascular tissue models
In vitro models

Leung CM, de Haan P, Ronaldson-Bouchard K, et al., 2022, A guide to the organ-on-a-chip. Nat Rev Methods Primers, 2(1): 33.

Wu Q, Liu J, Wang X, et al., 2020, Organ-on-a-chip: Recent breakthroughs and future prospects. Biomed Eng Online, 19(1): 9.

Fetah K, Tebon P, Goudie MJ, et al., 2019, The emergence of 3D bioprinting in organ-on-chip systems. Prog Biomed Eng, 1(1): 012001.

Yi H-G, Kim H, Kwon J, et al., 2021, Application of 3D bioprinting in the prevention and the therapy for human diseases. Signal Transduct Target Ther, 6(1): 177.

Ingber DE, 2022, Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet, 23(8): 467–491.

Mota C, Camarero-Espinosa S, Baker MB, et al., 2020, Bioprinting: From tissue and organ development to in vitro models. Chem Rev, 120(19): 10547–10607.

O’Connor C, Brady E, Zheng Y, et al., 2022, Engineering the multiscale complexity of vascular networks. Nat Rev Mater, 7(9): 702–716.

Grebenyuk S, Abdel Fattah AR, Kumar M, et al., 2023, Large-scale perfused tissues via synthetic 3D soft microfluidics. Nat Commun, 14(1): 193.

Fleischer S, Tavakol DN, Vunjak-Novakovic G, 2020, From arteries to capillaries: Approaches to engineering human vasculature. Adv Funct Mater, 30(37): 1910811.

Li S, Jin J, Zhang C, et al., 2023, 3D bioprinting vascular networks in suspension baths. Appl Mater Today, 30: 101729.

Seah T, Wong WL, Beh C, 2022, Vascularization strategies for bioprinting. Mater Today, 70: 638–642.

Yang Q, Lian Q, Xu F, 2017, Perspective: Fabrication of integrated organ-on-a-chip via bioprinting. Biomicrofluidics, 11(3): 031301.

Zhang Q, Bosch-Rué È, Pérez RA, et al., 2021, Biofabrication of tissue engineering vascular systems. APL Bioeng, 5(2): 021507.

Hedegaard CL, Mata A, 2020, Integrating self-assembly and biofabrication for the development of structures with enhanced complexity and hierarchical control. Biofabrication, 12(3): 032002.


Wu Y, Fortunato GM, Okesola BO, et al., 2021, An interfacial self-assembling bioink for the manufacturing of capillary-like structures with tuneable and anisotropic permeability. Biofabrication, 13(3): 035027.

Wu Y, Okesola BO, Xu J, et al., 2020, Disordered protein-graphene oxide co-assembly and supramolecular biofabrication of functional fluidic devices. Nat Commun, 11(1): 1182.

Ha D-H, Chae S, Lee JY, et al., 2021, Therapeutic effect of decellularized extracellular matrix-based hydrogel for radiation esophagitis by 3D printed esophageal stent. Biomaterials, 266: 120477.

Chae S, Yong U, Park W, et al., 2023, 3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration. Bioact Mater, 19: 611–625.

Bliley JM, Shiwarski DJ, Feinberg AW, 2022, 3D-bioprinted human tissue and the path toward clinical translation. Sci Transl Med, 14(666): eabo7047.

Zhang Y, Kumar P, Lv S, et al., 2021, Recent advances in 3D bioprinting of vascularized tissues. Mater Design, 199: 109398.

Song HHG, Rumma RT, Ozaki CK, et al., 2018, Vascular tissue engineering: progress, challenges, and clinical promise. Cell Stem Cell, 22(3): 340–354.

Chae S, Cho D-W, 2022, Three-dimensional bioprinting with decellularized extracellular matrix-based bioinks in translational regenerative medicine. MRS Bull, 47(1): 70–79.

Li J, Wu C, Chu PK, et al., 2020, 3D printing of hydrogels: Rational design strategies and emerging biomedical applications. Mater Sci Eng R Rep, 140: 100543.

Chae S, Cho D-W, 2023, Biomaterial-based 3D bioprinting strategy for orthopedic tissue engineering. Acta Biomater, 156: 4–20.

Daly AC, Prendergast ME, Hughes AJ, et al., 2021, Bioprinting for the biologist. Cell, 184(1): 18–32.

Jang J, Park H-J, Kim S-W, et al., 2017, 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair. Biomaterials, 112: 264–274.

Maiullari F, Costantini M, Milan M, et al., 2018, A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes. Sci Rep, 8(1): 13532.

Homan KA, Kolesky DB, Skylar-Scott MA, et al., 2016, Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep, 6(1): 34845.

Kolesky DB, Truby RL, Gladman AS, et al., 2014, 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater, 26(19): 3124–3130.

Miller JS, Stevens KR, Yang MT, et al., 2012, Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater, 11(9): 768–774.

Skylar-Scott MA, Uzel SGM, Nam LL, et al., 2019, Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci Adv, 5(9): eaaw2459.

Ouyang L, Armstrong JPK, Chen Q, et al., 2020, Void-free 3D bioprinting for in situ endothelialization and microfluidic perfusion. Adv Funct Mater, 30(1): 1908349.

Lee A, Hudson AR, Shiwarski DJ, et al., 2019, 3D bioprinting of collagen to rebuild components of the human heart. Science, 365(6452): 482–487.

Noor N, Shapira A, Edri R, et al., 2019, 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv Sci, 6(11): 1900344.

Choi Y-J, Jun Y-J, Kim DY, et al., 2019, A 3D cell printed muscle construct with tissue-derived bioink for the treatment of volumetric muscle loss. Biomaterials, 206: 160–169.


Zhang W, Feng C, Yang G, et al., 2017, 3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration. Biomaterials, 135: 85–95.

Gao Q, Liu Z, Lin Z, et al., 2017, 3D bioprinting of vessel-like structures with multilevel fluidic channels. ACS Biomater Sci Eng, 3(3): 399–408.

Gao Q, He Y, Fu J-z, et al., 2015, Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Biomaterials, 61: 203–215.

Jia W, Gungor-Ozkerim PS, Zhang YS, et al., 2016, Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. Biomaterials, 106: 58–68.

Gao G, Park W, Kim BS, et al., 2021, Construction of a novel in vitro atherosclerotic model from geometry-tunable artery equivalents engineered via in-bath coaxial cell printing. Adv Funct Mater, 31(10): 2008878.

Xiang Y, Miller K, Guan J, et al., 2022, 3D bioprinting of complex tissues in vitro: State-of-the-art and future perspectives. Arch Toxicol, 96(3): 691–710.

Kolesky DB, Homan KA, Skylar-Scott MA, et al., 2016, Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci, 113(12): 3179–3184.

Gao G, Park JY, Kim BS, et al., 2018, Coaxial cell printing of freestanding, perfusable, and functional in vitro vascular models for recapitulation of native vascular endothelium pathophysiology. Adv Healthc Mater, 7(23): 1801102.


Son J, Hong SJ, Lim JW, et al., 2021, Engineering tissue-specific, multiscale microvasculature with a capillary network for prevascularized tissue. Small Methods, 5(10): 2100632.

Ma L, Wu Y, Li Y, et al., 2020, Current advances on 3D-bioprinted liver tissue models. Adv Healthc Mater, 9(24): 2001517.


Lee H, Chae S, Kim JY, et al., 2019, Cell-printed 3D liver-on-a-chip possessing a liver microenvironment and biliary system. Biofabrication, 11(2): 025001.

Liu X, Wang X, Zhang L, et al., 2021, 3D liver tissue model with branched vascular networks by multimaterial bioprinting. Adv Healthc Mater, 10(23): 2101405.


Taymour R, Chicaiza-Cabezas NA, Gelinsky M, et al., 2022, Core–shell bioprinting of vascularized in vitro liver sinusoid models. Biofabrication, 14(4): 045019.

Kang D, Hong G, An S, et al., 2020, Bioprinting of multiscaled hepatic lobules within a highly vascularized construct. Small, 16(13): 1905505.

Lee H, Kim J, Choi Y, et al., 2020, Application of gelatin bioinks and cell-printing technology to enhance cell delivery capability for 3D liver fibrosis-on-a-chip development. ACS Biomater Sci Eng, 6(4): 2469–2477.

Sakolish CM, Philip B, Mahler GJ, 2019, A human proximal tubule-on-a-chip to study renal disease and toxicity. Biomicrofluidics, 13(1): 014107.

Schutgens F, Rookmaaker MB, Margaritis T, et al., 2019, Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol, 37(3): 303–313.

Lin NYC, Homan KA, Robinson SS, et al., 2019, Renal reabsorption in 3D vascularized proximal tubule models. Proc Natl Acad Sci, 116(12): 5399–5404.

Singh NK, Han W, Nam SA, et al., 2020, Three-dimensional cell-printing of advanced renal tubular tissue analogue. Biomaterials, 232: 119734.

Yoon J, Singh NK, Jang J, et al., 2022, 3D bioprinted in vitro secondary hyperoxaluria model by mimicking intestinal-oxalate-malabsorption-related kidney stone disease. Appl Phys Rev, 9(4): 041408.

Jung M, Ghamrawi S, Du EY, et al., 2022, Advances in 3D bioprinting for cancer biology and precision medicine: From matrix design to application. Adv Healthc Mater, 11(24): 2200690.

Kang Y, Datta P, Shanmughapriya S, et al., 2020, 3D bioprinting of tumor models for cancer research. ACS Appl Biomater, 3(9): 5552–5573.

Neufeld L, Yeini E, Pozzi S, et al., 2022, 3D bioprinted cancer models: From basic biology to drug development. Nat Rev Cancer, 22(12): 679–692.

Yi H-G, Jeong YH, Kim Y, et al., 2019, A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng, 3(7): 509–519.

Neufeld L, Yeini E, Reisman N, et al., 2021, Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment. Sci Adv, 7(34): eabi9119.

Ozturk MS, Lee VK, Zou H, et al., 2020, High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment. Sci Adv, 6(10): eaay7513.

Meng F, Meyer CM, Joung D, et al., 2019, 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments. Adv Mater, 31(10): 1806899.

Kim BS, Cho W-W, Gao G, et al., 2021, Construction of tissue-level cancer-vascular model with high-precision position control via in situ 3D cell printing. Small Methods, 5(7): 2100072.


Obinu A, Gavini E, Rassu G, et al., 2018, Lymph node metastases: Importance of detection and treatment strategies. Expert Opin Drug Deliv, 15(5): 459–467.

Cao X, Ashfaq R, Cheng F, et al., 2019, A tumor-on-a-chip system with bioprinted blood and lymphatic vessel pair. Adv Funct Mater, 29(31): 1807173.

Cho W-W, Ahn M, Kim BS, et al., 2022, Blood-lymphatic integrated system with heterogeneous melanoma spheroids via in-bath three-dimensional bioprinting for modelling of combinational targeted therapy. Adv Sci, 9(29): 2202093.

Chiesa I, De Maria C, Lapomarda A, et al., 2020, Endothelial cells support osteogenesis in an in vitro vascularized bone model developed by 3D bioprinting. Biofabrication, 12(2): 025013.

Kim BS, Gao G, Kim JY, et al., 2019, 3D cell printing of perfusable vascularized human skin equivalent composed of epidermis, dermis, and hypodermis for better structural recapitulation of native skin. Adv Healthc Mater, 8(7): 1801019.

Chae S, Kim J, Yi H-G, et al., 2022, 3D bioprinting of an in vitro model of a biomimetic urinary bladder with a contract-release system. Micromachines, 13(2): 277.

Zhao Z, Chen X, Dowbaj AM, et al., 2022, Organoids. Nat Rev Methods Primers, 2(1): 94.

Chae S, Lee S-S, Choi Y-J, et al., 2021, 3D cell-printing of biocompatible and functional meniscus constructs using meniscus‐derived bioink. Biomaterials, 267: 120466.

Kim BS, Das S, Jang J, et al., 2020, Decellularized extracellular matrix-based bioinks for engineering tissue-and organ-specific microenvironments. Chem Rev, 120(19): 10608–10661.


Chae S, Sun Y, Choi Y-J, et al., 2021, 3D cell-printing of tendon-bone interface using tissue-derived extracellular matrix bioinks for chronic rotator cuff repair. Biofabrication, 13(3): 035005.

Chae S, Choi Y-J, Cho D-W, 2022, Mechanically and biologically promoted cell-laden constructs generated using tissue-specific bioinks for tendon/ligament tissue engineering applications. Biofabrication, 14(2): 025013.

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