Abstract
Cancer is characterized by a high fatality rate, complex molecular mechanism, and costly therapies. The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells, stromal cells, and extracellular matrix plays a key role in tumor initiation, development, angiogenesis, invasion and metastasis. To better understand the biological features of tumor and reveal the critical factors of therapeutic treatments against cancer, it is of great significance to build in vitro tumor models that could recapitulate the stages of tumor progression and mimic tumor behaviors in vivo for efficient and patient-specific drug screening and biological studies. Since conventional tissue engineering methods of constructing tumor models always fail to simulate the later stages of tumor development due to the lack of ability to build complex structures and angiogenesis potential, three-dimensional (3D) bioprinting techniques have gradually found its applications in tumor microenvironment modeling with accurate composition and well-organized spatial distribution of tumor-related cells and extracellular components in the past decades. The capabilities of building tumor models with a large range of scale, complex structures, multiple biomaterials and vascular network with high resolution and throughput make 3D bioprinting become a versatile platform in bio-manufacturing as well as in medical research. In this review, we will focus on 3D bioprinting strategies, design of bioinks, current 3D bioprinted tumor models in vitro classified with their structures and propose future perspectives.
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References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
Egeblad M, Nakasone ES, Werb Z (2010) Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18:884–901
Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67
Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 316:1324–1331
Polyak K, Haviv I, Campbell IG (2009) Co-evolution of tumor cells and their microenvironment. Trends Genet TIG 25:30–38
Ma L, Zhang B, Zhou C, Li Y, Li B, Yu M, Luo Y, Gao L, Zhang D, Xue Q, Qiu Q, Lin B, Zou J, Yang H (2018) The comparison genomics analysis with glioblastoma multiforme (GBM) cells under 3D and 2D cell culture conditions. Colloids Surf B Biointerfaces 172:665–673
Zhang YS, Duchamp M, Oklu R, Ellisen LW, Langer R, Khademhosseini A (2016) Bioprinting the cancer microenvironment. ACS Biomater Sci Eng 2:1710–1721
Zhang B, Luo YC, Ma L, Gao L, Li YT, Xue Q, Yang HY, Cui ZF (2018) 3D bioprinting: an emerging technology full of opportunities and challenges. Bio-Des Manuf 1:2–13
Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785
Zhang B, Gao L, Ma L, Luo Y, Yang H, Cui Z (2019) 3D bioprinting: a novel avenue for manufacturing tissues and organs. Engineering 5:777–794
Nakamura M, Kobayashi A, Takagi F, Watanabe A, Hiruma Y, Ohuchi K, Iwasaki Y, Horie M, Morita I, Takatani S (2005) Biocompatible inkjet printing technique for designed seeding of individual living cells. Tissue Eng 11:1658–1666
Boland T, Xu T, Damon B, Cui X (2006) Application of inkjet printing to tissue engineering. Biotechnol J 1:910–917
Lee H, Yoo JJ, Kang HW, Cho DW (2016) Investigation of thermal degradation with extrusion-based dispensing modules for 3D bioprinting technology. Biofabrication 8:015011
Chang CC, Boland ED, Williams SK, Hoying JB (2011) Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J Biomed Mater Res B Appl Biomater 98:160–170
Guillotin B, Souquet A, Catros S, Duocastella M, Pippenger B, Bellance S, Bareille R, Remy M, Bordenave L, Amedee J, Guillemot F (2010) Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials 31:7250–7256
Gaebel R, Ma N, Liu J, Guan J, Koch L, Klopsch C, Gruene M, Toelk A, Wang W, Mark P, Wang F, Chichkov B, Li W, Steinhoff G (2011) Patterning human stem cells and endothelial cells with laser printing for cardiac regeneration. Biomaterials 32:9218–9230
Gauvin R, Chen YC, Lee JW, Soman P, Zorlutuna P, Nichol JW, Bae H, Chen S, Khademhosseini A (2012) Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography. Biomaterials 33:3824–3834
Soman P, Chung PH, Zhang AP, Chen S (2013) Digital microfabrication of user-defined 3D microstructures in cell-laden hydrogels. Biotechnol Bioeng 110:3038–3047
Ma X, Qu X, Zhu W, Li YS, Yuan S, Zhang H, Liu J, Wang P, Lai CS, Zanella F, Feng GS, Sheikh F, Chien S, Chen S (2016) Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc Natl Acad Sci USA 113:2206–2211
Gou M, Qu X, Zhu W, Xiang M, Yang J, Zhang K, Wei Y, Chen S (2014) Bio-inspired detoxification using 3D-printed hydrogel nanocomposites. Nat Commun 5:3774
Lee MP, Cooper GJ, Hinkley T, Gibson GM, Padgett MJ, Cronin L (2015) Development of a 3D printer using scanning projection stereolithography. Sci Rep 5:9875
Ahadian S, Khademhosseini A (2018) A perspective on 3D bioprinting in tissue regeneration. Bio-Des Manuf 1:157–160
Malda J, Visser J, Melchels FP, Jungst T, Hennink WE, Dhert WJ, Groll J, Hutmacher DW (2013) 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater 25:5011–5028
Skardal A, Atala A (2015) Biomaterials for integration with 3-D bioprinting. Ann Biomed Eng 43:730–746
Pati F, Jang J, Ha DH, Won Kim S, Rhie JW, Shim JH, Kim DH, Cho DW (2014) Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 5:3935
Zhang YS, Yue K, Aleman J, Moghaddam KM, Bakht SM, Yang J, Jia W, Dell’erba V, Assawes P, Shin SR, Dokmeci MR, Oklu R, Khademhosseini A (2017) 3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 45:148–163
Colosi C, Shin SR, Manoharan V, Massa S, Costantini M, Barbetta A, Dokmeci MR, Dentini M, Khademhosseini A (2016) Microfluidic bioprinting of heterogeneous 3D tissue constructs using low-viscosity bioink. Adv Mater 28:677–684
Ying GL, Jiang N, Yu CJ, Zhang YS (2018) Three-dimensional bioprinting of gelatin methacryloyl (GelMA). Bio-Des Manuf 1:215–224
Yin J, Zhao DK, Liu JY (2019) Trends on physical understanding of bioink printability. Bio-Des Manuf 2:50–54
Xu F, Celli J, Rizvi I, Moon S, Hasan T, Demirci U (2011) A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform. Biotechnol J 6:204–212
Lee V, Dai G, Zou H, Yoo S (2015) Generation of 3-D glioblastoma-vascular niche using 3-D bioprinting. In: 41st Annual Northeast, biomedical engineering conference, Piscataway, pp 1–2
Heinrich MA, Bansal R, Lammers T, Zhang YS, Michel Schiffelers R, Prakash J (2019) 3D-bioprinted mini-brain: a glioblastoma model to study cellular interactions and therapeutics. Adv Mater 31:e1806590
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 26:608–623
Ling K, Huang G, Liu J, Zhang X, Ma Y, Lu T, Xu F (2015) Bioprinting-based high-throughput fabrication of three-dimensional MCF-7 human breast cancer cellular spheroids. Engineering 1:269–274
Kingsley DM, Roberge CL, Rudkouskaya A, Faulkner DE, Barroso M, Intes X, Corr DT (2019) Laser-based 3D bioprinting for spatial and size control of tumor spheroids and embryoid bodies. Acta Biomater 95:357–370
Grolman JM, Zhang D, Smith AM, Moore JS, Kilian KA (2015) Rapid 3D extrusion of synthetic tumor microenvironments. Adv Mater 27:5512–5517
Dai X, Liu L, Ouyang J, Li X, Zhang X, Lan Q, Xu T (2017) Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers. Sci Rep 7:1457
Wang X, Li X, Dai X, Zhang X, Zhang J, Xu T, Lan Q (2018) Coaxial extrusion bioprinted shell-core hydrogel microfibers mimic glioma microenvironment and enhance the drug resistance of cancer cells. Colloids Surf B Biointerfaces 171:291–299
Zhao Y, Yao R, Ouyang L, Ding H, Zhang T, Zhang K, Cheng S, Sun W (2014) Three-dimensional printing of Hela cells for cervical tumor model in vitro. Biofabrication 6:035001
Pang Y, Mao SS, Yao R, He JY, Zhou ZZ, Feng L, Zhang KT, Cheng SJ, Sun W (2018) TGF-beta induced epithelial-mesenchymal transition in an advanced cervical tumor model by 3D printing. Biofabrication 10:044102
Zhou X, Zhu W, Nowicki M, Miao S, Cui H, Holmes B, Glazer RI, Zhang LG (2016) 3D bioprinting a cell-laden bone matrix for breast cancer metastasis study. ACS Appl Mater Interfaces 8:30017–30026
Zhou X, Liu C, Zhao X, Wang X (2016) A 3D bioprinting liver tumor model for drug screening. World J Pharm Pharmaceut Sci 5:196–213
Dai X, Ma C, Lan Q, Xu T (2016) 3D bioprinted glioma stem cells for brain tumor model and applications of drug susceptibility. Biofabrication 8:045005
Wang X, Zhang X, Dai X, Wang X, Li X, Diao J, Xu T (2018) Tumor-like lung cancer model based on 3D bioprinting. 3 Biotech 8:501
Lee H, Cho DW (2016) One-step fabrication of an organ-on-a-chip with spatial heterogeneity using a 3D bioprinting technology. Lab Chip 16:2618–2625
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:e1806899
Yi HG, Jeong YH, Kim Y, Choi YJ, Moon HE, Park SH, Kang KS, Bae M, Jang J, Youn H, Paek SH, Cho DW (2019) A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat Biomed Eng 3:509–519
Schmidt SK, Schmid R, Arkudas A, Kengelbach-Weigand A, Bosserhoff AK (2019) Tumor cells develop defined cellular phenotypes after 3D-bioprinting in different bioinks. Cells 8:1295
Swaminathan S, Hamid Q, Sun W, Clyne AM (2019) Bioprinting of 3D breast epithelial spheroids for human cancer models. Biofabrication 11:025003
Mirani B, Pagan E, Shojaei S, Duchscherer J, Toyota BD, Ghavami S, Akbari M (2019) A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma. Eur J Pharmacol 854:201–212
Blaeser A, Duarte Campos DF, Puster U, Richtering W, Stevens MM, Fischer H (2016) Controlling shear stress in 3D bioprinting is a key factor to balance printing resolution and stem cell integrity. Adv Healthc Mater 5:326–333
Blaeser ACD, Fischer H (2015) 3D–bioprinting induced shear stress strongly impacts human MSC survival and proliferation potential. Tissue Eng A 21:S322–S323
Ning L, Guillemot A, Zhao J, Kipouros G, Chen X (2016) Influence of flow behavior of alginate-cell suspensions on cell viability and proliferation. Tissue Eng C Methods 22:652–662
Li M, Tian X, Kozinski J, Chen X, Hwang D (2015) Modeling mechanical cell damage in the bioprinting process employing a conical needle. J Mech Med Biol 15:1550073
He Y, Xie M, Gao Q, Fu J (2019) Why choose 3D bioprinting? Part I: a brief introduction of 3D bioprinting for the beginners. Bio-Des Manuf 2:221–224
Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A (2016) A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol 34:312–319
Hardin JO, Ober TJ, Valentine AD, Lewis JA (2015) Microfluidic printheads for multimaterial 3D printing of viscoelastic inks. Adv Mater 27:3279–3284
Ober TJ, Foresti D, Lewis JA (2015) Active mixing of complex fluids at the microscale. Proc Natl Acad Sci USA 112:12293–12298
Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA (2014) 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 26:3124–3130
Acknowledgements
We would like to thank the support by National Key Research and Development Program of China (2018YFA0703000), Key Research and Development Projects of Zhejiang Province (Grant No. 2017C01054), Natural Science Foundation of China (Grant Nos. 51875518, 51821093), and the Fundamental Research Funds for the Central Universities (Grant Nos. 2019XZZX003-02, 2019FZA4002).
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Ma, L., Li, Y., Wu, Y. et al. The construction of in vitro tumor models based on 3D bioprinting. Bio-des. Manuf. 3, 227–236 (2020). https://doi.org/10.1007/s42242-020-00068-6
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DOI: https://doi.org/10.1007/s42242-020-00068-6