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Cited by 2493D Printing in Biomedical ResearchHydrogels: synthesis, properties, applicationsCellular Mechanics and Interactions

Design of spherically structured 3D in vitro tumor models -Advances and prospects

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Ferreira, L.P., Gaspar, V.M., Mano, J.F.·2018·Acta Biomaterialia
DOI 10.1016/j.actbio.2018.05.034PMC PMC7617007
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Abstract

Three-dimensional multicellular tumor models are receiving an ever-growing focus as preclinical drug-screening platforms due to their potential to recapitulate major physiological features of human tumors in vitro. In line with this momentum, the technologies for assembly of 3D microtumors are rapidly evolving towards a comprehensive inclusion of tumor microenvironment elements. Customized spherically structured platforms, including microparticles and microcapsules, provide a robust and scalable technology to imprint unique biomolecular tumor microenvironment hallmarks into 3D in vitro models. Herein, a comprehensive overview of novel advances on the integration of tumor-ECM components and biomechanical cues into 3D in vitro models assembled in spherical shaped platforms is provided. Future improvements regarding spatiotemporal/mechanical adaptability, and degradability, during microtumors in vitro 3D culture are also critically discussed considering the realistic potential of these platforms to mimic the dynamic tumor microenvironment. From a global perspective, the production of 3D multicellular spheroids with tumor ECM components included in spherical models will unlock their potential to be used in high-throughput screening of therapeutic compounds. It is envisioned, in a near future, that a combination of spherically structured 3D microtumor models with other advanced microfluidic technologies will properly recapitulate the flow dynamics of human tumors in vitro. Statement of significance The ability to correctly mimic the complexity of the tumor microenvironment in vitro is a key aspect for the development of evermore realistic in vitro models for drug-screening and fundamental cancer biology studies. In this regard, conventional spheroid-based 3D tumor models, combined with spherically structured biomaterials, opens the opportunity to precisely recapitulate complex cell-extracellular matrix interactions and tumor compartmentalization. This review provides an in-depth focus on current developments regarding spherically structured scaffolds engineered into in vitro 3D tumor models, and discusses future advances toward all-encompassing platforms that may provide an improved in vitro/in vivo correlation in a foreseeable future.

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  • The mechanical properties of BME cannot be tailored, rendering it unable to study mechanotransduction during organogenesis.

    “the mechanical properties of BME cannot be tailored, rendering it unable to study mechanotransduction during organogenesis.”

    From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [65]

    The Scaffold-Based 3D Models Production section says that Matrigel™, a basement-membrane extract, can be formulated at different protein concentrations to produce gels with tunable elastic moduli. It says dynamic control of stiffness is not possible, but that narrower limitation does not support the claim that its mechanical properties cannot be tailored at all. The cited passage does not address mechanotransduction during organogenesis. (LLM, conf=0.88)

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  • Conventional in vitro 3D cancer models provide a valuable alternative to animal models and have enabled important advances in cancer research in the last two decades.

    “The conventional in vitro 3D cancer models are static systems (i.e., they are not based on microfluidics) [102], but they do provide a valuable alternative to animal models and have enabled important advances in cancer research in the last two decades [5,103].”

    From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [103]

    The Introduction describes 3D tumor models as increasingly useful in cancer research and suitable as tumor surrogates for preclinical testing; the Conclusions and Future Perspective describes their contributions to drug research. Our copy does not establish that conventional 3D models are an alternative specifically to animal models or that they enabled important advances over the last two decades. The sentence’s separate claim that conventional models are static is attached to a different citation. (LLM, conf=0.78)

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  • Various tumor spheroids have been fabricated by embedding cancer cells into protein-based hydrogels such as Matrigel, fibrin, and collagen as they incorporate specific cell-adhesive motifs and enzymatic-mediated matrix degradation beneficial to cell proliferation.

    “Currently, various tumor spheroids have been fabricated by embedding cancer cells into protein‐based hydrogels such as Matrigel,[ 64 ] fibrin,[ 65 ] and collagen[ 66 ] as they incorporate specific cell‐adhesive motifs and enzymatic‐mediated matrix degradation which are beneficial to cell proliferation.”

    From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [65]

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Research works printed but not linked: 208

  1. [1]Cox MC Reese LM Bickford LR Verbridge SS Toward the Broad Adoption of 3D Tumor Models in the Cancer Drug Pipeline ACS Biomater Sci Eng 2015 1 877 894 33429520
  2. [4]Chwalek K Bray LJ Werner C Tissue-engineered 3D tumor angiogenesis models: Potential technologies for anti-cancer drug discovery Adv Drug Deliv Rev 2014 79 30 39 24819220
  3. [5]Fong ELS Harrington DA Farach-Carson MC Yu H Heralding a new paradigm in 3D tumor modeling Biomaterials 2016 108 197 213 10.1016/j.biomaterials.2016.08.052 27639438 PMC5730082 · DOI
  4. [6]Friedrich J Seidel C Ebner R Kunz-Schughart LA Spheroid-based drug screen: considerations and practical approach Nat Protoc 2009 4 309 324 19214182
  5. [7]Hickman JA Graeser R de Hoogt R Vidic S Brito C Gutekunst M van der Kuip H Imi Predect consortium Three-dimensional models of cancer for pharmacology and cancer cell biology: Capturing tumor complexity in vitro/ex vivo Biotechnol J 2014 9 1115 1128 25174503
  6. [8]Katt ME Placone AL Wong AD Xu ZS Searson PC In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform Front Bioeng Biotechnol 2016 4 12 10.3389/fbioe.2016.00012 26904541 PMC4751256 · DOI · Paper page
  7. [9]Chatzinikolaidou M Cell spheroids: the new frontiers in in vitro models for cancer drug validation Drug Discov Today 2016 21 1553 1560 27371506
  8. [10]Dittmer A Hohlfeld K Lützkendorf J Müller LP Dittmer J Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10 Cell Mol Life Sci 2009 66 3053 3065 10.1007/s00018-009-0089-0 19603142 PMC11115486 · DOI
  9. [11]Karlsson H Fryknäs M Larsson R Nygren P Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system Exp Cell Res 2012 318 1577 1585 22487097
  10. [12]Beckermann BM Kallifatidis G Groth A Frommhold D Apel A Mattern J Salnikov AV Moldenhauer G Wagner W Diehlmann A Saffrich R VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma Br J Cancer 2008 99 622 631 10.1038/sj.bjc.6604508 18665180 PMC2527820 · DOI · Paper page
  11. [13]Han H-W Hsu S Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells Acta Biomater 2016 42 157 167 27296841
  12. [14]Pickup MW Mouw JK Weaver VM The extracellular matrix modulates the hallmarks of cancer EMBO Rep 2014 15 1243 1253 10.15252/embr.201439246 25381661 PMC4264927 · DOI
  13. [15]Klemm F Joyce JA Microenvironmental regulation of therapeutic response in cancer Trends Cell Biol 2015 25 198 213 10.1016/j.tcb.2014.11.006 25540894 PMC5424264 · DOI
  14. [16]Kang AR Park JS Ju J Jeong GS Lee SH Cell encapsulation via microtechnologies Biomaterials 2014 35 2651 2663 24439405
  15. [17]Ahrens CC Dong Z Li W Engineering Cell Aggregates through Incorporated Polymeric Microparticles Acta Biomater 2017 62 64 81 28782721
  16. [18]Correia CR Pirraco RP Cerqueira MT Marques AP Reis RL Mano JF Semipermeable capsules wrapping a multifunctional and self-regulated co-culture microenvironment for osteogenic differentiation Sci Rep 2016 6 1 12 10.1038/srep21883 26905619 PMC4764811 · DOI
  17. [19]Thiele J Ma Y Bruekers SMC Ma S Huck WTS 25th anniversary article: Designer hydrogels for cell cultures: A materials selection guide Adv Mater 2014 26 125 148 24227691
  18. [20]Zanoni M Piccinini F Arienti C Zamagni A Santi S Polico R Bevilacqua A Tesei A 3D tumor spheroid models for in vitro therapeutic screening: A systematic approach to enhance the biological relevance of data obtained Sci Rep 2016 6 19103 10.1038/srep19103 26752500 PMC4707510 · DOI · Paper page
  19. [21]Lee J Abdeen AA Wycislo KL Fan TM Kilian KA Interfacial geometry dictates cancer cell tumorigenicity Nat Mater 2016 15 856 862 27043781
  20. [22]Costa EC Moreira AF de Melo-Diogo D Gaspar VM Carvalho MP Correia IJ 3D tumor spheroids: an overview on the tools and techniques used for their analysis Biotechnol Adv 2016 34 1427 1441 27845258
  21. [23]Vulcano F Milazzo L Ciccarelli C Eramo A Sette G Mauro A Macioce G Martinelli A La Torre R Casalbore P Hassan HJ Wharton’s jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer Exp Cell Res 2016 345 190 198 27343631
  22. [24]Rayahin JE Buhrman JS Zhang Y Koh TJ Gemeinhart RA High and Low Molecular Weight Hyaluronic Acid Differentially Influence Macrophage Activation ACS Biomater Sci Eng 2015 1 481 493 10.1021/acsbiomaterials.5b00181 26280020 PMC4533115 · DOI
  23. [25]Murdoch C Muthana M Coffelt SB Lewis CE The role of myeloid cells in the promotion of tumour angiogenesis Nat Rev Cancer 2008 8 618 631 18633355
  24. [26]Chaturvedi P Gilkes DM Takano N Semenza GL Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment Proc Natl Acad Sci 2014 111 E2120 E2129 10.1073/pnas.1406655111 24799675 PMC4034192 · DOI · Paper page
  25. [27]Astashkina A Grainger DW Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments Adv Drug Deliv Rev 2014 69–70 1 18 24613390
  26. [28]Alemany-Ribes M Semino CE Bioengineering 3D environments for cancer models Adv Drug Deliv Rev 2014 79 40 49 24996134
  27. [29]Estrada MF Rebelo SP Davies EJ Pinto MT Pereira H Santo VE Smalley MJ Barry ST Gualda EJ Alves PM Anderson E Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression Biomaterials 2016 78 50 61 26650685
  28. [30]Sasser AK Mundy BL Smith KM Studebaker AW Axel AE Haidet AM Fernandez SA Hall BM Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3D tumor environments Cancer Lett 2007 254 255 264 17467167
  29. [31]Ivascu A Kubbies M Rapid Generation of Single-Tumor Spheroids for High-Throughput Cell Function and Toxicity Analysis J Biomol Screen 2006 11 922 932 16973921
  30. [32]Foty R A Simple Hanging Drop Cell Culture Protocol for Generation of 3D Spheroids J Vis Exp 2011 20 4 7 10.3791/2720 21587162 PMC3197119 · DOI · Paper page
  31. [33]Neto AI Correia CR Custõdio CA Mano JF Biomimetic miniaturized platform able to sustain arrays of liquid droplets for high-throughput combinatorial tests Adv Funct Mater 2014 24 5096 5103 10.1002/adfm.201400503 · DOI
  32. [34]Dangles-Marie V Pocard M Richon S Weiswald LB Assayag F Saulnier P Judde JG Janneau JL Auger N Validire P Dutrillaux B Establishment of human colon cancer cell lines from fresh tumors versus xenografts: Comparison of success rate and cell line features Cancer Res 2007 67 398 407 17210723
  33. [35]Breslin S O’Driscoll L Three-dimensional cell culture: The missing link in drug discovery Drug Discov Today 2013 18 240 249 23073387
  34. [36]Weiswald LB Bellet D Dangles-Marie V Spherical cancer models in tumor biology Neoplasia 2015 17 1 15 10.1016/j.neo.2014.12.004 25622895 PMC4309685 · DOI
  35. [37]Sung SY Hsieh CL Law A Zhau HE Pathak S Multani AS Lim S Coleman IM Wu LC Figg WD Dahut WL Coevolution of prostate cancer and bone stroma in three-dimensional coculture: Implications for cancer growth and metastasis Cancer Res 2008 68 9996 10003 10.1158/0008-5472.CAN-08-2492 19047182 PMC3105756 · DOI
  36. [38]Sutherland RM Mccredie JA Growth of Multicell Spheroids in Tissue Culture as a Model of Nodular Carcinomas JNCI J Natl Cancer Inst 1971 113 120 5101993
  37. [39]Tung Y-C Hsiao AY Allen SG Torisawa Y Ho M Takayama S High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array Analyst 2011 136 473 478 10.1039/c0an00609b 20967331 PMC7454010 · DOI · Paper page
  38. [40]Amaral RLF Miranda M Marcato PD Swiech K Comparative analysis of 3D bladder tumor spheroids obtained by forced floating and hanging drop methods for drug screening Front Physiol 2017 8 10.3389/fphys.2017.00605 28878686 PMC5572239 · DOI
  39. [41]Gencoglu MF Barney LE Hall CL Brooks EA Schwartz AD Corbett DC Stevens KR Peyton SR Comparative Study of Multicellular Tumor Spheroid Formation Methods and Implications for Drug Screening ACS Biomater Sci Eng 2017 acsbiomaterials.7b00069 10.1021/acsbiomaterials.7b00069 29527571 PMC5843470 · DOI
  40. [42]Rodday B Hirschhaeuser F Walenta S Mueller-Klieser W Semiautomatic Growth Analysis of Multicellular Tumor Spheroids J Biomol Screen 2011 16 1119 1124 21908797
  41. [43]Oliveira MB Salgado CL Song W Mano JF Combinatorial on-chip study of miniaturized 3D porous scaffolds using a patterned superhydrophobic platform Small 2013 9 768 778 23169604
  42. [44]Neto AI Correia CR Oliveira MB Rial-Hermida MI Alvarez-Lorenzo C Reis RL Mano JF A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening Biomater Sci 2015 3 581 585 26222417
  43. [46]Majety M Pradel LP Gies M Ries CH Fibroblasts influence survival and therapeutic response in a 3D co-culture model PLoS One 2015 10 1 18 10.1371/journal.pone.0127948 26053043 PMC4460080 · DOI
  44. [47]Oskarsson T Acharyya S Zhang XHF Vanharanta S Tavazoie SF Morris PG Downey RJ Manova-Todorova K Brogi E Massagué J Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs Nat Med 2011 17 867 874 10.1038/nm.2379 21706029 PMC4020577 · DOI · Paper page
  45. [48]Barzegari A Saei AA An update to space biomedical research: Tissue engineering in microgravity bioreactors BioImpacts 2012 2 23 32 10.5681/bi.2012.003 23678438 PMC3648913 · DOI
  46. [49]Picollet-D’hahan N Dolega ME Liguori L Marquette C Le Gac S Gidrol X Martin DK A 3D Toolbox to Enhance Physiological Relevance of Human Tissue Models Trends Biotechnol 2016 34 757 769 27497676
  47. [50]Granet C Laroche N Vico L Alexandre C Lafage-Proust MH Rotating-wall vessels, promising bioreactors for osteoblastic cell culture: Comparison with other 3D conditions Med Biol Eng Comput 1998 36 513 519 10198539
  48. [51]Kimlin LC Casagrande G Virador VM In vitro three-dimensional (3D) models in cancer research: An update Mol Carcinog 2013 52 167 182 22162252
  49. [52]Villasante A Vunjak-Novakovic G Tissue-engineered models of human tumors for cancer research Expert Opin Drug Discov 2015 10 257 268 10.1517/17460441.2015.1009442 25662589 PMC4479424 · DOI
  50. [53]Massai D Isu G Madeddu D Cerino G Falco A Frati C Gallo D Deriu MA Labate GFDU Quaini F Audenino A A versatile bioreactor for dynamic suspension cell culture. Application to the culture of cancer cell spheroids PLoS One 2016 11 1 16 10.1371/journal.pone.0154610 27144306 PMC4856383 · DOI
  51. [54]Hirschhaeuser F Leidig T Rodday B Lindemann C Mueller-Klieser W Test system for trifunctional antibodies in 3D MCTS culture J Biomol Screen Off J Soc Biomol Screen 2009 14 980 990 19675312
  52. [55]Ferrarini M Steimberg N Ponzoni M Belloni D Berenzi A Girlanda S Caligaris-Cappio F Mazzoleni G Ferrero E Ex-Vivo Dynamic 3-D Culture of Human Tissues in the RCCS™ Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy PLoS One 2013 8 1 10 10.1371/journal.pone.0071613 23990965 PMC3753321 · DOI
  53. [56]Hsiao AY Tung YC Qu X Patel LR Pienta KJ Takayama S 384 hanging drop arrays give excellent Z-factors and allow versatile formation of co-culture spheroids Biotechnol Bioeng 2012 109 1293 1304 10.1002/bit.24399 22161651 PMC3306496 · DOI
  54. [57]Oliveira MB Neto AI Correia CR Rial-Hermida MI Alvarez-Lorenzo C Mano JF Superhydrophobic chips for cell spheroids high-throughput generation and drug screening ACS Appl Mater Interfaces 2014 6 9488 9495 24865973
  55. [58]Oliveira NM Martins-Cruz C Oliveira MB Reis RL Mano JF Coculture of Spheroids/2D Cell Layers Using a Miniaturized Patterned Platform as a Versatile Method to Produce Scaffold-Free Tissue Engineering Building Blocks Adv Biosyst 2017 1700069 1700069 10.1002/adbi.201700069 · DOI
  56. [59]Correia AL Bissell MJ The tumor microenvironment is a dominant force in multidrug resistance Drug Resist Updat 2012 15 39 49 10.1016/j.drup.2012.01.006 22335920 PMC3658318 · DOI
  57. [60]Rozario T DeSimone DW The extracellular matrix in development and morphogenesis: A dynamic view Dev Biol 2010 341 126 140 10.1016/j.ydbio.2009.10.026 19854168 PMC2854274 · DOI
  58. [61]Barcus CE O’Leary KA Brockman JL Rugowski DE Liu Y Garcia N Yu M Keely PJ Eliceiri KW Schuler LA Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells Breast Cancer Res 2017 19 9 10.1186/s13058-017-0801-1 28103936 PMC5244528 · DOI
  59. [63]Wu M Cao M He Y Liu Y Yang C Du Y Wang W Gao F A novel role of low molecular weight hyaluronan in breast cancer metastasis FASEB J 2015 29 1290 1298 25550464
  60. [64]Misra S Hascall VC Markwald RR Ghatak S Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer Front Immunol 2015 6 10.3389/fimmu.2015.00201 25999946 PMC4422082 · DOI
  61. [65]Gandavarapu NR Azagarsamy MA Anseth KS Photo-click living strategy for controlled, reversible exchange of biochemical ligands Adv Mater 2014 26 2521 2526 10.1002/adma.201304847 24523204 PMC4528616 · DOI
  62. [66]Rosales AM Vega SL DelRio FW Burdick JA Anseth KS Hydrogels with Reversible Mechanics to Probe Dynamic Cell Microenvironments Angew Chemie - Int Ed 2017 56 12132 12136 10.1002/anie.201705684 28799225 PMC5668133 · DOI
  63. [67]Conklin MW Eickhoff JC Riching KM Pehlke CA Eliceiri KW Provenzano PP Friedl A Keely PJ Aligned collagen is a prognostic signature for survival in human breast carcinoma Am J Pathol 2011 178 1221 1232 10.1016/j.ajpath.2010.11.076 21356373 PMC3070581 · DOI
  64. [68]Kumar S Cellular mechanotransduction: Stiffness does matter Nat Mater 2014 13 918 920 25241671
  65. [69]Riching KM Cox BL Salick MR Pehlke C Riching AS Ponik SM Bass BR Crone WC Jiang Y Weaver AM Eliceiri KW 3D collagen alignment limits protrusions to enhance breast cancer cell persistence Biophys J 2015 107 2546 2558 10.1016/j.bpj.2014.10.035 25468334 PMC4255204 · DOI · Paper page
  66. [70]Chen L Xiao Z Meng Y Zhao Y Han J Su G Chen B Dai J The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs Biomaterials 2012 33 1437 1444 22078807
  67. [71]Lü WD Zhang L Wu CL Liu ZG Lei GY Liu J Gao W Hu YR Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering PLoS One 2014 9 10.1371/journal.pone.0103672 25072252 PMC4114977 · DOI
  68. [72]Benton G Kleinman HK George J Arnaoutova I Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with cancer cells Int J Cancer 2011 128 1751 1757 21344372
  69. [73]Croll TI O’Connor AJ Stevens GW Cooper-White JJ A blank slate? Layer-by-layer deposition of hyaluronic acid and chitosan onto various surfaces Biomacromolecules 2006 7 1610 1622 16677046
  70. [74]Gurski LA Jha AK Zhang C Jia X Farach-Carson MC Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells Biomaterials 2009 30 6076 6085 10.1016/j.biomaterials.2009.07.054 19695694 PMC2782556 · DOI · Paper page
  71. [75]Arya N Sardana V Saxena M Rangarajan A Katti DS Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional scaffolds: an improved in vitro tumour model J R Soc Interface 2012 9 3288 3302 10.1098/rsif.2012.0564 22977099 PMC3481596 · DOI
  72. [76]Xing Q Zhao F Chen S McNamara J DeCoster MA Lvov YM Porous biocompatible three-dimensional scaffolds of cellulose microfiber/gelatin composites for cell culture Acta Biomater 2010 6 2132 2139 20035906
  73. [77]Xiong G Flynn TJ Chen J Trinkle C Xu R Development of an ex vivo breast cancer lung colonization model utilizing a decellularized lung matrix Integr Biol 2015 7 1518 1525 10.1039/c5ib00157a 26563425 PMC4673658 · DOI
  74. [78]Hoshiba T Tanaka M Decellularized matrices as in vitro models of extracellular matrix in tumor tissues at different malignant levels: Mechanism of 5-fluorouracil resistance in colorectal tumor cells Biochim Biophys Acta - Mol Cell Res 2016 1863 2749 2757 27558478
  75. [79]Chen MCW Gupta M Cheung KC Alginate-based microfluidic system for tumor spheroid formation and anticancer agent screening Biomed Microdevices 2010 12 647 654 20237849
  76. [80]Liu C Liu Y Xu X xi Wu H Xie H guo Chen L Lu T Yang L Guo X Sun G wei Wang W Potential effect of matrix stiffness on the enrichment of tumor initiating cells under three-dimensional culture conditions Exp Cell Res 2015 330 123 134 25108138
  77. [81]Tsao CT Kievit FM Wang K Erickson AE Ellenbogen RG Zhang M Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies Mol Pharm 2014 11 2134 2142 10.1021/mp5002119 24779767 PMC4096230 · DOI
  78. [82]Wang K Kievit FM Florczyk SJ Stephen ZR Zhang M 3D Porous Chitosan-Alginate Scaffolds as an in Vitro Model for Evaluating Nanoparticle-Mediated Tumor Targeting and Gene Delivery to Prostate Cancer Biomacromolecules 2015 16 3362 3372 10.1021/acs.biomac.5b01032 26347946 PMC4831622 · DOI
  79. [83]Talukdar S Kundu SC A non-mulberry silk fibroin protein based 3D in vitro tumor model for evaluation of anticancer drug activity Adv Funct Mater 2012 22 4778 4788 10.1002/adfm.201200375 · DOI
  80. [84]Talukdar S Mandal M Hutmacher DW Russell PJ Soekmadji C Kundu SC Engineered silk fibroin protein 3D matrices for in vitro tumor model Biomaterials 2011 32 2149 2159 21167597
  81. [85]Soman P Kelber JA Lee JW Wright TN Vecchio KS Klemke RL Chen S Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness Biomaterials 2012 33 7064 7070 10.1016/j.biomaterials.2012.06.012 22809641 PMC3420339 · DOI
  82. [86]Sahoo SK Panda AK Labhasetwar V Characterization of porous PLGA/PLA microparticles as a scaffold for three dimensional growth of breast cancer cells Biomacromolecules 2005 6 1132 1139 15762686
  83. [87]Liu Z Vunjak-Novakovic G Modeling tumor microenvironments using custom-designed biomaterial scaffolds Curr Opin Chem Eng 2016 11 94 105 10.1016/j.coche.2016.01.012 27152253 PMC4852888 · DOI
  84. [88]Calimeri T Battista E Conforti F Neri P Di Martino MT Rossi M Foresta U Piro E Ferrara F Amorosi A Bahlis N A unique three-dimensional SCID-polymeric scaffold (SCID-synth-hu) model for in vivo expansion of human primary multiple myeloma cells Leukemia 2011 25 707 711 10.1038/leu.2010.300 21233838 PMC3089835 · DOI
  85. [89]Rabionet M Yeste M Puig T Ciurana J Electrospinning PCL scaffolds manufacture for three-dimensional breast cancer cell culture Polymers (Basel) 2017 9 1 15 10.3390/polym9080328 30971005 PMC6418676 · DOI
  86. [90]Fischbach C Kong HJ Hsiong SX Evangelista MB Yuen W Mooney DJ Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement Proc Natl Acad Sci U S A 2009 106 399 404 10.1073/pnas.0808932106 19126683 PMC2626714 · DOI
  87. [91]Xu X Farach-Carson MC Jia X Three-dimensional in vitro tumor models for cancer research and drug evaluation Biotechnol Adv 2014 32 1256 1268 10.1016/j.biotechadv.2014.07.009 25116894 PMC4171250 · DOI
  88. [92]Orgovan N Peter B Bosze S Ramsden JJ Szabó B Horvath R Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor Sci Rep 2014 4 10.1038/srep04034 24503534 PMC3916899 · DOI
  89. [93]Maheshwari G Brown G Lauffenburger Da Wells a Griffith LG Cell adhesion and motility depend on nanoscale RGD clustering J Cell Sci 2000 113 Pt 1 1677 1686 10769199
  90. [94]Pradhan S Clary JM Seliktar D Lipke EA A three-dimensional spheroidal cancer model based on PEG-fibrinogen hydrogel microspheres Biomaterials 2017 115 141 154 27889665
  91. [95]Pradhan S Hassani I Seeto WJ Lipke EA PEG-fibrinogen hydrogels for three-dimensional breast cancer cell culture J Biomed Mater Res - Part A 2017 105 236 252 27615742
  92. [96]Lou J Stowers R Nam S Xia Y Chaudhuri O Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture Biomaterials 2018 154 213 222 29132046
  93. [97]Mehr NG Li X Chen G Favis BD Hoemann CD Pore size and LbL chitosan coating influence mesenchymal stem cell in vitro fibrosis and biomineralization in 3D porous poly(epsilon-caprolactone) scaffolds J Biomed Mater Res - Part A 2015 103 2449 2459 25504184
  94. [98]Lee HWHJHW Kook Y-M Lee HWHJHW Park H Koh W-G A three-dimensional co-culture of HepG2 spheroids and fibroblasts using double-layered fibrous scaffolds incorporated with hydrogel micropatterns RSC Adv 2014 4 61005 61011 10.1039/C4RA12269K · DOI
  95. [99]Samavedi S Joy N 3D printing for the development of in vitro cancer models Curr Opin Biomed Eng 2017 2 35 42 10.1016/j.cobme.2017.06.003 · DOI
  96. [100]Xu F Celli J Rizvi I Moon S Hasan T Demirci U A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform Biotechnol J 2011 6 204 212 10.1002/biot.201000340 21298805 PMC3780785 · DOI · Paper page
  97. [101]Caliari SR Burdick JA A practical guide to hydrogels for cell culture Nat Methods 2016 13 405 414 10.1038/nmeth.3839 27123816 PMC5800304 · DOI · Paper page
  98. [102]Zhang YS Khademhosseini A Advances in engineering hydrogels Science (80-.) 2017 356 eaaf3627 10.1126/science.aaf3627 28473537 PMC5841082 · DOI · Paper page
  99. [103]Webber MJ Khan OF Sydlik SA Tang BC Langer R A Perspective on the Clinical Translation of Scaffolds for Tissue Engineering Ann Biomed Eng 2015 43 641 656 10.1007/s10439-014-1104-7 25201605 PMC4785597 · DOI
  100. [104]Kleinman HK Martin GR Matrigel: Basement membrane matrix with biological activity Semin Cancer Biol 2005 15 378 386 15975825
  101. [105]Li L LaBarbera DV 3D High-Content Screening of Organoids for Drug Discovery Compr Med Chem III 2017 388 415 10.1016/B978-0-12-409547-2.12329-7 · DOI
  102. [106]Baker LA Tiriac H Clevers H Tuveson DA Modeling Pancreatic Cancer with Organoids Trends in Cancer 2016 2 176 190 10.1016/j.trecan.2016.03.004 27135056 PMC4847151 · DOI
  103. [107]Li L Lu Y Optimizing a 3D culture system to study the interaction between epithelial breast cancer and its surrounding fibroblasts J Cancer 2011 2 458 466 10.7150/jca.2.458 21915190 PMC3171896 · DOI
  104. [108]Badylak SF Freytes DO Gilbert TW Reprint of: Extracellular matrix as a biological scaffold material: Structure and function Acta Biomater 2015 23 S17 S26 26235342
  105. [109]Pampaloni F Reynaud EG Stelzer EHK The third dimension bridges the gap between cell culture and live tissue Nat Rev Mol Cell Biol 2007 8 839 845 17684528
  106. [110]Nyga A Cheema U Loizidou M 3D tumour models: Novel in vitro approaches to cancer studies J Cell Commun Signal 2011 5 239 248 10.1007/s12079-011-0132-4 21499821 PMC3145874 · DOI
  107. [111]Sieminski AL Mackellar D Gong H Kamm RD Wells A Lauffenburger DA Zaman MH Trapani LM Sieminski AL Mackellar D Gong H Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis Proc Natl Acad Sci 2006 103 13897 13897 10.1073/pnas.0604460103 16832052 PMC1544144 · DOI
  108. [112]Fraley SI Wu P He L Feng Y Krisnamurthy R Longmore GD Wirtz D Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions Sci Rep 2015 5 14580 10.1038/srep14580 26423227 PMC4589685 · DOI
  109. [113]Kievit FM Cooper A Jana S Leung MC Wang K Edmondson D Wood D Lee JSH Ellenbogen RG Zhang M Aligned Chitosan-Polycaprolactone Polyblend Nanofibers Promote the Migration of Glioblastoma Cells Adv Healthc Mater 2013 2 1651 1659 10.1002/adhm.201300092 23776187 PMC3859701 · DOI
  110. [114]Kievit FM Wang K Erickson AE Lan Levengood SK Ellenbogen RG Zhang M Modeling the tumor microenvironment using chitosan-alginate scaffolds to control the stem-like state of glioblastoma cells Biomater Sci 2016 4 610 613 10.1039/c5bm00514k 26688867 PMC4803622 · DOI
  111. [115]Moreau JE Anderson K Mauney JR Nguyen T Kaplan DL Rosenblatt M Tissue-engineered bone serves as a target for metastasis of human breast cancer in a mouse model Cancer Res 2007 67 10304 10308 17974972
  112. [116]Talukdar S Kundu SC Engineered 3D silk-based metastasis models: Interactions between human breast adenocarcinoma, mesenchymal stem cells and osteoblast-like cells Adv Funct Mater 2013 23 5249 5260 10.1002/adfm.201300312 · DOI
  113. [117]Tan PHS Aung KZ Toh SL Goh JCH Nathan SS Three-dimensional porous silk tumor constructs in the approximation of in vivo osteosarcoma physiology Biomaterials 2011 32 6131 6137 21621837
  114. [118]Seib FP Berry JE Shiozawa Y Taichman RS Kaplan DL Tissue engineering a surrogate niche for metastatic cancer cells Biomaterials 2015 51 313 319 10.1016/j.biomaterials.2015.01.076 25771021 PMC4367489 · DOI
  115. [119]Ragelle H Naba A Larson BL Zhou F Prijic M Whittaker CA Del Rosario A Langer R Hynes RO Anderson DG Comprehensive proteomic characterization of stem cell-derived extracellular matrices Biomaterials 2017 128 147 159 10.1016/j.biomaterials.2017.03.008 28327460 PMC8191742 · DOI
  116. [121]Worthington P Pochan DJ Langhans SA Peptide Hydrogels – Versatile Matrices for 3D Cell Culture in Cancer Medicine Front Oncol 2015 5 92 10.3389/fonc.2015.00092 25941663 PMC4403249 · DOI
  117. [122]Wang F Li Y Shen Y Wang A Wang S Xie T The functions and applications of RGD in tumor therapy and tissue engineering Int J Mol Sci 2013 14 13447 13462 10.3390/ijms140713447 23807504 PMC3742196 · DOI
  118. [123]Lu T Li Y Chen T Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering Int J Nanomedicine 2013 8 337 350 10.2147/IJN.S38635 23345979 PMC3551462 · DOI
  119. [124]Shen Y-I Abaci HE Krupski Y Weng L-C Burdick JA Gerecht S Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting Biomater Sci 2014 2 655 10.1039/C3BM60274E 24748963 PMC3987918 · DOI
  120. [125]Imparato G Urciuolo F Casale C Netti PA The role of microscaffold properties in controlling the collagen assembly in 3D dermis equivalent using modular tissue engineering Biomaterials 2013 34 7851 7861 23891518
  121. [126]Fang M Yuan J Peng C Li Y Collagen as a double-edged sword in tumor progression Tumor Biol 2014 35 2871 2882 10.1007/s13277-013-1511-7 24338768 PMC3980040 · DOI · Paper page
  122. [127]Stewart DA Cooper CR Sikes RA Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer Reprod Biol Endocrinol 2004 2 2 10.1186/1477-7827-2-2 14711377 PMC320496 · DOI
  123. [128]Carvalho MP Costa EC Miguel SP Correia IJ Tumor spheroid assembly on hyaluronic acid-based structures: A review Carbohydr Polym 2016 150 139 148 27312623
  124. [129]Becker JC Andersen MH Schrama D Thor Straten P Immune-suppressive properties of the tumor microenvironment Cancer Immunol Immunother 2013 62 1137 1148 10.1007/s00262-013-1434-6 23666510 PMC11029603 · DOI
  125. [130]Adamia S Pilarski PM Belch AR Pilarski LM Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets Curr Cancer Drug Targets 2013 13 347 361 23517594
  126. [131]Stern R Hyaluronan metabolism: A major paradox in cancer biology Pathol Biol 2005 53 372 382 16085113
  127. [132]Pradhan S Hassani I Clary JM Lipke EA Polymeric Biomaterials for In Vitro Cancer Tissue Engineering and Drug Testing Applications Tissue Eng Part B Rev 2016 22 470 484 27302080
  128. [133]Xu X xi Liu C Liu Y Li N Guo X Wang S jun Sun G wei Wang W Ma X jun Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model Exp Cell Res 2013 319 2135 2144 23707395
  129. [134]Correia CR Sher P Reis RL Mano JF Liquified chitosan–alginate multilayer capsules incorporating poly(l-lactic acid) microparticles as cell carriers Soft Matter 2013 9 2125 2130 10.1039/C2SM26784E · DOI
  130. [135]Wu Z Su X Xu Y Kong B Sun W Mi S Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation Sci Rep 2016 6 1 10 10.1038/srep24474 27091175 PMC4835808 · DOI
  131. [136]Kim I-Y Seo S-J Moon H-S Yoo M-K Park I-Y Kim B-C Cho C-S Chitosan and its derivatives for tissue engineering applications Biotechnol Adv 2008 26 1 21 17884325
  132. [138]Kievit FM Florczyk SJ Leung MC Wang K Wu JD Silber JR Ellenbogen RG Lee JSH Zhang M Proliferation and enrichment of CD133+ glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds Biomaterials 2014 35 9137 9143 10.1016/j.biomaterials.2014.07.037 25109438 PMC4167581 · DOI
  133. [139]Yu D Li S Wang S Li X Zhu M Huang S Sun L Zhang Y Liu Y Wang S Development and characterization of VEGF165-chitosan nanoparticles for the treatment of radiation-induced skin injury in rats Mar Drugs 2016 14 10.3390/md14100182 27727163 PMC5082330 · DOI
  134. [140]Park YJ Kim KH Lee JY Ku Y Lee SJ Min BM Chung CP Immobilization of bone morphogenetic protein-2 on a nanofibrous chitosan membrane for enhanced guided bone regeneration Biotechnol Appl Biochem 2006 43 17 15910285
  135. [141]Bray LJ Suzuki S Harkin DG Chirila TV Incorporation of Exogenous RGD Peptide and Inter-Species Blending as Strategies for Enhancing Human Corneal Limbal Epithelial Cell Growth on Bombyx mori Silk Fibroin Membranes 2013 4 74 88 10.3390/jfb4020074 24955953 PMC4030899 · DOI
  136. [142]Salamanna F Contartese D Maglio M Fini M A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario? Oncotarget 2016 7 44803 44820 10.18632/oncotarget.8394 27027241 PMC5190136 · DOI
  137. [143]Gill BJ Gibbons DL Roudsari LC Saik JE Rizvi ZH Roybal JD Kurie JM West JL A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model Cancer Res 2012 72 6013 6023 10.1158/0008-5472.CAN-12-0895 22952217 PMC3632398 · DOI
  138. [144]Ravi M Paramesh V Kaviya SR Anuradha E Paul Solomon FD 3D cell culture systems: Advantages and applications J Cell Physiol 2015 230 16 26 24912145
  139. [145]Eap S Ferrand A Machi V Ball V Huck O Benkirane-Jessel N Polydopamine Particles Effect on Melanoma Cells Proliferation and Melanin Secretion Adv Chem Eng Sci 2013 03 1 10 10.4236/aces.2013.33A1001 · DOI
  140. [146]Parajó Y d’Angelo I Welle A Garcia-Fuentes M Alonso MJ Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB Drug Deliv 2010 17 596 604 20883178
  141. [147]Del Bufalo F Manzo T Hoyos V Yagyu S Caruana I Jacot J Benavides O Rosen D Brenner MK 3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus Biomaterials 2016 84 76 85 26826297
  142. [148]Weiss MS Bernabé BP Shikanov A Bluver DA Mui MD Shin S Broadbelt LJ Shea LD The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells Biomaterials 2012 33 3548 3559 10.1016/j.biomaterials.2012.01.055 22341213 PMC3288720 · DOI
  143. [149]Zhu J Bioactive Modification of Poly(ethylenglykol) Hydrogels for Tissue Engineering Biomaterials 2010 31 4639 4656 10.1016/j.biomaterials.2010.02.044 20303169 PMC2907908 · DOI · Paper page
  144. [150]Roudsari LC Jeffs SE Witt AS Gill BJ West JL A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior Sci Rep 2016 6 32726 10.1038/srep32726 27596933 PMC5011743 · DOI
  145. [151]Zhu W Wang M Fu Y Castro NJ Fu SW Zhang LG Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study Acta Biomater 2015 14 164 174 25528534
  146. [153]Hirt C Papadimitropoulos A Muraro MG Mele V Panopoulos E Cremonesi E Ivanek R Schultz-Thater E Droeser RA Mengus C Heberer M Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed “in vivo” Biomaterials 2015 62 138 146 26051518
  147. [154]Shamloo A Amirifar L A microfluidic device for 2D to 3D and 3D to 3D cell navigation J Micromechanics Microengineering 2016 26 015003 10.1088/0960-1317/26/1/015003 · DOI
  148. [155]Carvalho MR Lima D Reis RL Correlo VM Oliveira JM Evaluating Biomaterial- and Microfluidic-Based 3D Tumor Models Trends Biotechnol 2015 33 667 678 26603572
  149. [156]Gupta N Liu JR Patel B Solomon DE Vaidya B Gupta V Microfluidics-based 3D cell culture models: Utility in novel drug discovery and delivery research Bioeng Transl Med 2016 1 63 81 10.1002/btm2.10013 29313007 PMC5689508 · DOI
  150. [157]Wong KHK Chan JM Kamm RD Tien J Microfluidic Models of Vascular Functions Annu Rev Biomed Eng 2012 14 205 230 22540941
  151. [158]van Duinen V Trietsch SJ Joore J Vulto P Hankemeier T Microfluidic 3D cell culture: From tools to tissue models Curr Opin Biotechnol 2015 35 118 126 26094109
  152. [159]Arora J Sauer SJ Tarpley M Vermeulen P Rypens C Van Laere S Williams KP Devi GR Dewhirst MW Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies Oncotarget 2017 8 25848 25863 10.18632/oncotarget.15667 28460441 PMC5432221 · DOI
  153. [160]HAGEMANN J JACOBI C HAHN M SCHMID V WELZ C SCHWENK-ZIEGER S STAUBER R BAUMEISTER P BECKER S Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer Anticancer Res 2017 37 2201 2210 28476783
  154. [161]Kucinska M Murias M Nowak-Sliwinska P Beyond mouse cancer models: Three-dimensional human-relevant in vitro and non-mammalian in vivo models for photodynamic therapy Mutat Res - Rev Mutat Res 2017 773 242 262 28927532
  155. [162]Raghavan S Mehta P Horst EN Ward MR Rowley KR Mehta G Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity Oncotarget 2016 7 16948 61 10.18632/oncotarget.7659 26918944 PMC4941362 · DOI
  156. [165]Barbarisi M Marino G Armenia E Vincenzo Q Rosso F Porcelli M Barbarisi A Use of polycaprolactone (PCL) as scaffolds for the regeneration of nerve tissue J Biomed Mater Res Part A 2015 103 1755 1760 25202882
  157. [166]Shaheen NL Kataria E Antony J Galvan D Ballou Y Bryan BA Extracellular matrix composition modulates angiosarcoma cell attachment and proliferation Oncoscience 2017 4 10.18632/oncoscience.383 29344556 PMC5769982 · DOI
  158. [167]Khurana A Godugu C Alginate-Based Three-Dimensional In Vitro Tumor Models?: A Better Alternative to Current Two-Dimensional Cell Culture Models 2018 157 183 10.1007/978-981-10-6910-9_6 · DOI
  159. [168]Alonso-Nocelo M Abuín C López-López R De La Fuente M Development and characterization of a three-dimensional co-culture model of tumor T cell infiltration Biofabrication 2016 8 1 13 27078888
  160. [169]Liu D Shi M Duan C Chen H Hu Y Yang Z Duan H Guo N Downregulation of Erbin in Her2-overexpressing breast cancer cells promotes cell migration and induces trastuzumab resistance Mol Immunol 2013 56 104 112 23711387
  161. [170]Barkan D Green JE An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth J Vis Exp 2011 1 5 10.3791/2914 21860375 PMC3211127 · DOI
  162. [171]Yamanishi C Jen K Takayama S Techniques to Produce and Culture Lung Tumor Organoids Humana Press Cham 2018 1 15 10.1007/978-3-319-60511-1_1 · DOI
  163. [173]Liaw C-Y Ji S Guvendiren M Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models Adv Healthc Mater 2018 1701165 29345429
  164. [174]Skardal A Murphy SV Crowell K Mack D Atala A Soker S A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery J Biomed Mater Res - Part B Appl Biomater 2017 105 1986 2000 10.1002/jbm.b.33736 27351939 PMC9159053 · DOI
  165. [175]Poincloux R Collin O Lizárraga F Romao M Debray M Piel M Chavrier P Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel Proc Natl Acad Sci 2011 108 1943 1948 10.1073/pnas.1010396108 21245302 PMC3033302 · DOI
  166. [176]Marcello M Richards R Mason D Sée V Live Imaging of Cell Invasion Using a Multicellular Spheroid Model and Light-Sheet Microscopy Adv Exp Med Biol Springer Cham 2017 155 161 29080137
  167. [177]Spandidos D B. Ethnikon Hidryma Ereunōn (Greece) Wang B Chen C Xia Z Tang J Yuan Y Feng X Yin N Overexpression of LASP1 is associated with proliferation, migration and invasion in esophageal squamous cell carcinoma Oncol Rep 1994 29 1115 1123 23254782
  168. [179]SEARCHBreast SEARCHBreast workshop: 3D Modelling of breast cancer 2015 26753939
  169. [180]Sueoka E Sueoka N Okabe S Kozu T Komori A Ohta T Suganuma M Kim SJ Lim IK Fujiki H Expression of the tumor necrosis factor alpha gene and early response genes by nodularin, a liver tumor promoter, in primary cultured rat hepatocytes J Cancer Res Clin Oncol 1997 123 413 9 9292703 PMC12200472
  170. [182]Guo P Huang J Moses M Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip Popescu G Park Y Quant Phase Imaging IV, SPIE 2018 56 10.1117/12.2289006 · DOI
  171. [185]Lanz HL Saleh A Kramer B Cairns J Ng CP Yu J Trietsch SJ Hankemeier T Joore J Vulto P Weinshilboum R Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform BMC Cancer 2017 17 1 11 10.1186/s12885-017-3709-3 29096610 PMC5668957 · DOI · Paper page
  172. [189]Lovitt C Shelper T Avery V Advanced Cell Culture Techniques for Cancer Drug Discovery Biology (Basel) 2014 3 345 367 10.3390/biology3020345 24887773 PMC4085612 · DOI
  173. [190]Fang X Sittadjody S Gyabaah K Opara EC Balaji KC Novel 3D Co-Culture Model for Epithelial-Stromal Cells Interaction in Prostate Cancer PLoS One 2013 8 1 10 10.1371/journal.pone.0075187 24073251 PMC3779160 · DOI
  174. [191]Huang H Ding Y Sun XS Nguyen TA Peptide Hydrogelation and Cell Encapsulation for 3D Culture of MCF-7 Breast Cancer Cells PLoS One 2013 8 10.1371/journal.pone.0059482 23527204 PMC3603912 · DOI
  175. [193]LaBarbera DV Reid BG Yoo BH The multicellular tumor spheroid model for high-throughput cancer drug discovery Expert Opin Drug Discov 2012 7 819 830 22788761
  176. [194]Oliveira MB Mano JF Polymer-based microparticles in tissue engineering and regenerative medicine Biotechnol Prog 2011 27 897 912 21584949
  177. [195]Brancato V Gioiella F Profeta M Imparato G Guarnieri D Urciuolo F Melone P Netti PA 3D tumor microtissues as an in vitro testing platform for microenvironmentally-triggered drug delivery systems Acta Biomater 2017 57 47 58 28483691
  178. [196]Horning JL Sahoo SK Vijayaraghavalu S Dimitrijevic S Vasir JK Jain TK Panda AK Labhasetwar V 3-D tumor model for in vitro evaluation of anticancer drugs Mol Pharm 2008 5 849 862 18680382
  179. [197]Godugu C Patel AR Desai U Andey T Sams A Singh M AlgiMatrix Based 3D Cell Culture System as an In-Vitro Tumor Model for Anticancer Studies PLoS One 2013 8 e53708 10.1371/journal.pone.0053708 23349734 PMC3548811 · DOI
  180. [198]Kang S-WW Bae YH Cryopreservable and tumorigenic three-dimensional tumor culture in porous poly(lactic-co-glycolic acid) microsphere Biomaterials 2009 30 4227 4232 10.1016/j.biomaterials.2009.04.025 19446875 PMC2760435 · DOI
  181. [199]Singh A Brito I Lammerding J Beyond Tissue Stiffness and Bioadhesivity: Advanced Biomaterials to Model Tumor Microenvironments and Drug Resistance Trends in Cancer 2018 1 11 10.1016/j.trecan.2018.01.008 29606313 PMC5884450 · DOI
  182. [200]Rodenhizer D Dean T D’Arcangelo E McGuigan AP The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery? Adv Healthc Mater 2018 1701174 1701174 29350495
  183. [201]Brancato V Garziano A Gioiella F Urciuolo F Imparato G Panzetta V Fusco S Netti PA 3D is not enough: Building up a cell instructive microenvironment for tumoral stroma microtissues Acta Materialia Inc 2017 27721010
  184. [202]Lima AC Sher P Mano JF Production methodologies of polymeric and hydrogel particles for drug delivery applications Expert Opin Drug Deliv 2012 9 231 248 22250602
  185. [203]Pradhan S Chaudhury CS Lipke EA Dual-phase, surface tension-based fabrication method for generation of tumor millibeads Langmuir 2014 30 3817 3825 24617794
  186. [204]Zhang P Guan J Fabrication of Multilayered Microparticles by Integrating Layer-by-Layer Assembly and MicroContact Printing Small 2011 7 2998 3004 21901832
  187. [205]Deveza L Ashoken J Castaneda G Tong X Keeney M Han L-H Yang F Microfluidic Synthesis of Biodegradable Polyethylene-Glycol Microspheres for Controlled Delivery of Proteins and DNA Nanoparticles ACS Biomater Sci Eng 2015 1 157 165 33429514
  188. [206]Zhang XXXX Wang W Yu W Xie Y Zhang XXXX Zhang Y Ma X Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing Biotechnol Prog 2005 21 1289 1296 16080713
  189. [207]Ferreira LP Gaspar VM Henrique R Jerónimo C Mano JF Mesenchymal Stem Cells Relevance in Multicellular Bioengineered 3D In Vitro Tumor Models Biotechnol J 2017 1700079 1700079 28834355 PMC7617208
  190. [208]Yeung P Sin HS Chan S Chan GCF Chan BP Microencapsulation of neuroblastoma cells and mesenchymal stromal cells in collagen microspheres: A 3D model for cancer cell niche study PLoS One 2015 10 1 22 10.1371/journal.pone.0144139 26657086 PMC4682120 · DOI
  191. [209]Lu Y-C Song W An D Kim BJ Schwartz R Wu M Ma M Designing compartmentalized hydrogel microparticles for cell encapsulation and scalable 3D cell culture J Mater Chem B 2015 3 353 360 32262039
  192. [210]Rao W Zhao S Yu J Lu X Zynger DL He X Enhanced enrichment of prostate cancer stem-like cells with miniaturized 3D culture in liquid core-hydrogel shell microcapsules Biomaterials 2014 35 7762 7773 10.1016/j.biomaterials.2014.06.011 24952981 PMC4405503 · DOI
  193. [211]Wilson JL Mcdevitt TC Stem cell microencapsulation for phenotypic control, bioprocessing, and transplantation Biotechnol Bioeng 2013 110 667 682 10.1002/bit.24802 23239279 PMC4163548 · DOI
  194. [212]Sagot Y Tan SA Baetge E Schmalbruch H Kato AC Aebischer P Polymer Encapsulated Cell Lines Genetically Engineered to Release Ciliary Neurotrophic Factor Can Slow Down Progressive Motor Neuronopathy in the Mouse Eur J Neurosci 1995 7 1313 1322 7582105
  195. [213]Cui X Liu Y Hartanto Y Bi J Dai S Zhang H Multicellular Spheroids Formation and Recovery in Microfluidics-generated Thermoresponsive Microgel Droplets Colloids Interface Sci Commun 2016 14 4 7 10.1016/j.colcom.2016.09.001 · DOI
  196. [214]Alessandri K Sarangi BR Gurchenkov VV Sinha B Kiessling TR Fetler L Rico F Scheuring S Lamaze C Simon A Geraldo S Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro Proc Natl Acad Sci 2013 110 14843 14848 10.1073/pnas.1309482110 23980147 PMC3773746 · DOI
  197. [215]Yang S Guo LJ Microencapsulation of low-passage poorly-differentiated human mucoepidermoid carcinoma cells by alginate microcapsules: In vitro profiling of angiogenesis-related molecules Cancer Cell Int 2017 17 1 10 10.1186/s12935-017-0479-6 29200966 PMC5697357 · DOI
  198. [217]Xu X Prestwich GD Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three-dimensional lung cancer xenograft model Cancer 2010 116 1739 1750 10.1002/cncr.24907 20143443 PMC2847044 · DOI
  199. [218]Markvicheva E Zaytseva-Zotova D Akasov R Burov S Chevalot I Marc A Multicellular tumor spheroids in microcapsules as a novel 3D in vitro model in tumor biology BMC Proc 2013 7 116 10.1186/1753-6561-7-S6-P116 · DOI
  200. [219]Guzman A Sánchez Alemany V Nguyen Y Zhang CR Kaufman LJ A novel 3D in vitro metastasis model elucidates differential invasive strategies during and after breaching basement membrane Biomaterials 2017 115 19 29 27880891

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Cited by

Sorted by citations

Authors
Ferreira, L. P., Gaspar, V. M., & Mano, J. F.
Affiliations
University of Aveiro (PT)
Corresponding author
  • Gaspar, V.M.
  • Mano, J.F.
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2018-07
Volume
75
Pages
11-34
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2018.05.034
PMC
PMC7617007
OpenAlex
W2803362743
Cited by
249
References
10
Citations by year
2026: 22 · 2025: 25 · 2024: 38 · 2023: 43 · 2022: 32 · 2021: 32 · 2020: 31 · 2019: 23 · 2018: 3
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Biomaterialia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
Funders
  • European Research Council
  • Ministério da Educação e Ciência
  • Fundação para a Ciência e a Tecnologia (SFRH/BPD/119983/2016, UID/CTM/50011/2013)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
3D tumor models, tumor spheroids, tumor microenvironment, extracellular matrix, microtumors, microcapsules, microparticles, biomechanical cues, drug screening, microfluidics
MeSH terms
Animals, Humans, Models, Biological, Neoplasms, Spheroids, Cellular, Microfluidic Analytical Techniques, Tumor Microenvironment

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