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Biomaterials Based Strategies for Engineering Tumor Microenvironment

Part of the Advanced Structured Materials book series (STRUCTMAT,volume 66)

Abstract

Tissue engineering aims to gain mechanistic insights into human diseases and to develop new treatment protocols. Although 2-dimensional (2-D) flat petri dish culture and in vivo disease-based models are the industrial gold standards for understanding the underlying disease pathophysiology and for drug screening/testing, they are associated with certain limitations. While the 2-D cell culture systems fail to mimic in vivo signaling, animal-based disease models are associated with long incubation period, high cost, ethical constraints as well as depiction of human pathology in different species. Therefore, there has been a paradigm shift towards the development of 3-dimensional (3-D) based in vitro disease models. These models act as bridging gaps between the aforementioned conventional strategies thereby fastening clinical translation. In this regard, biomedical engineering plays a key role towards the development of tissue engineering based 3-D disease models. These models have demonstrated success in recapitulating human diseases in terms of in vivo morphology and signaling. This chapter will present examples of biomaterials-based 3-D engineered disease models with a focus on cancer.

Keywords

  • Tissue engineering
  • In vitro disease models
  • 3-dimensional
  • Spheroids
  • Scaffolds

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Abbreviations

2-D:

Two-dimensional

3-D:

Three-dimensional

α-SMA:

α-smooth muscle actin

ABC:

ATP-binding cassette

bFGF:

Basic fibroblast growth factor

CAFs:

Cancer-associated fibroblasts

CAM-DR:

Cell-adhesion mediated drug resistance

CCL2:

Chemokine CC-motive ligand 2

CNS:

Central nervous system

CSCs:

Cancer stem cells

CSFs:

Colony stimulating factors

CSF1:

Colony stimulating factor 1

DCIS:

Ductal carcinoma in situ

DEAE:

Diethylaminoethyl

E-cad:

Epithelial-cadherin

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial to mesenchymal transition

EPC:

Endothelial progenitor cell

FAP:

Fibroblast activation protein

Fe3O4 :

Iron oxide

GA:

Glutaraldehyde

GAG:

Glycosaminoglycan

G-CSF:

Granulocyte colony stimulating factor

GEMs:

Global eukaryotic microcarriers

GM-CSF:

Granulocyte macrophage colony stimulating factor

HA:

Hyaluronic acid

HCC:

Hepatocellular carcinoma cells

HGF:

Hepatocyte growth factor

HIF-1:

Hypoxia-inducible transcription factor 1

HMF:

Human mammary fibroblasts

HPV 16:

Human papilloma virus 16

HTS:

High throughput screening

IGF1:

Insulin-like growth factor 1

IL-6:

Interleukin-6

IL-8:

Interleukin-8

MFs:

Myofibroblasts

MMPs:

Matrix metalloproteases

MP:

Microparticles

N-cad:

Neural-cadherin

NO:

Nitric oxide

NSCLS:

Non-small cell lung cancer

PCL:

Poly(ε-caprolactone)

PDGF:

Platelet-derived growth factor

PDT:

Photodyanmic therapy

PEG:

Polyethylene glycol

PHEMA:

Polyhydroxyethylmethacrylate

PLA:

Polylactide

PLG:

Poly(lactide-co-glycolide)

PLGA:

Polylactic-co-glycolide

PLLA-b-PEG-folate:

Polyl-lactic acid-b-polyethylene glycol-folate

PVA:

Polyvinyl alcohol

RCCS:

Rotary cell culture system/bioreactor

RGD:

Arginine-glycine-aspartic acid

RTK:

Receptor tyrosine kinase

SCLC:

Small cell lung cancer

SDF1:

Stromal-cell derived factor 1

sECM:

Synthetic ECM

SV-40:

Simian virus 40

TAMs:

Tumor associated macrophages

TCPS:

Tissue culture polystyrene

TE:

Tissue engineering

TGFβ:

Transforming growth factor β

TNF-α:

Tumor necrosis factor α

VEGF:

Vascular endothelial growth factor

VPF:

Vascular permeability factor

ZnPcSmix :

Zinc sulfophthalocyanine

References

  • Aimetti AA, Tibbitt MW, Anseth KS (2009) Human neutrophil elastase responsive delivery from poly(ethylene glycol) hydrogels. Biomacromolecules 10(6):1484–1489

    Google Scholar 

  • Al-Husein B et al (2012) Antiangiogenic therapy for cancer: an update. Pharmacotherapy 32(12):1095–1111

    CrossRef  Google Scholar 

  • Amann A et al (2014) Development of an innovative 3D cell culture system to study tumour—Stroma interactions in non-small cell lung cancer cells. PLoS ONE 9(3)

    Google Scholar 

  • Amit-Cohen BC, Rahat MM, Rahat MA (2013) Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN. Front Physiol 4:1–16

    Google Scholar 

  • Ananthanarayanan B, Kim Y, Kumar S (2011) Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform. Biomaterials 32(31):7913–7923

    CrossRef  Google Scholar 

  • Anastasov N et al (2015) A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment. BMC Cancer 15:466

    Google Scholar 

  • Arnott S et al (1974) The agarose double helix and its function in agarose gel structure. J Mol Biol 90(2):269–284

    CrossRef  Google Scholar 

  • Artzner F et al (2007) Interactions between Poloxamers in Aqueous Solutions: Micellization and Gelation Studied by Differential Scanning Calorimetry, Small angle scattering and rheology. Langmuir 26:5085–5092

    CrossRef  Google Scholar 

  • Arya N et al (2009) Electrospraying: a facile technique for synthesis of chitosan-based micro/nanospheres for drug delivery applications. J Biomed Mater Res Part B: Appl Biomater 88(1):17–31

    CrossRef  Google Scholar 

  • Arya N et al (2012) Recapitulating tumour microenvironment in chitosan-gelatin three-dimensional scaffolds: an improved in vitro tumour model. J R Soc Interface 9(77):3288–3302

    CrossRef  Google Scholar 

  • Arya N, Sharma P, Katti DS (2010) Designing nanofibrous scaffolds for tissue engineering. In: Advanced biomaterials: fundamentals, processing, and applications. John Wiley & Sons, Inc., pp 435–497

    Google Scholar 

  • Asghar W et al (2015) Engineering cancer microenvironments for in vitro 3-D tumor models. Mater Today 18(10):539–553

    Google Scholar 

  • Asghar W et al (2014) Preserving human cells for regenerative, reproductive, and transfusion medicine 9(7):895–903

    Google Scholar 

  • Assal R El et al (2014) Bio-inspired Cryo-ink preserves red blood cell phenotype and function during nanoliter vitrification. Adv Mater 26(33):5815–5822

    Google Scholar 

  • Assal R El, Chen P, Demirci U (2015) Highlights from the latest articles in advanced biomanufacturing at micro- and nano-scale. Nanomed (Lond) 6(2):356–372

    Google Scholar 

  • Azevedo H, Reis R (2005) Understanding the enzymatic degradation of biodegradable polymers and strategies to control their degradation rate. In: Reis RL, Román JS (eds) Biodegradable systems in tissue engineering and regenerative medicine, CRC Press, FL, pp 177–201

    Google Scholar 

  • Balachander GM et al (2015) Enhanced metastatic potential in a 3D tissue scaffold toward a comprehensive in vitro model for breast cancer metastasis. ACS Appl Mater Interfaces 7(50):27810–27822

    CrossRef  Google Scholar 

  • Barrila J et al (2010) Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions. Nat Rev Microbiol 8(11):791–801

    Google Scholar 

  • Barron JA et al (2004) Biological laser printing: a novel technique for creating heterogeneous 3-dimensional cell patterns. Biomed Microdevices 6(2):139–147

    CrossRef  Google Scholar 

  • Benton G et al (2014) Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv Drug Deliv Rev 79:3–18

    CrossRef  Google Scholar 

  • Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch 3:401–410

    Google Scholar 

  • Bernard AB, Chapman RZ, Anseth KS (2014) Controlled local presentation of matrix proteins in microparticle-laden cell aggregates. Biotechnol Bioeng 111(5):1028–1037

    CrossRef  Google Scholar 

  • Bersini S et al (2014) Biomaterials a micro fluidic 3D in vitro model for specificity of breast cancer metastasis to bone 35:2454–2461

    Google Scholar 

  • Bhardwaj N, Kundu SC (2010) Electrospinning: a fascinating fiber fabrication technique. Biotechnol Adv 28(3):325–347

    CrossRef  Google Scholar 

  • Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32(8):760–772

    Google Scholar 

  • Bhattacharya M et al (2012) Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. J Control Release: Official J Control Release Soc 164(3):291–298

    CrossRef  Google Scholar 

  • Bian L et al (2013) The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. Biomaterials 34(2):413–421

    CrossRef  Google Scholar 

  • Bischel LL, Beebe DJ, Sung KE (2015) Microfluidic model of ductal carcinoma in situ with 3D, organotypic structure. BMC Cancer 15(1):12

    Google Scholar 

  • Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1(1):46–54

    Google Scholar 

  • Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15(12):786–801

    CrossRef  Google Scholar 

  • Bouck N, Stellmach V, Hsu SC (1996) How tumors become angiogenic. Adv Cancer Res 69:135–174

    CrossRef  Google Scholar 

  • Braun B et al (2004) Expression of G-CSF and GM-CSF in human meningiomas correlates with increased tumor proliferation and vascularization. J Neurooncol 68(2):131–140

    CrossRef  Google Scholar 

  • Brennen WN, Isaacs JT, Denmeade SR (2012) Rationale behind targeting fibroblast activation protein–expressing carcinoma-associated fibroblasts as a novel chemotherapeutic strategy. Mol Cancer Ther 11(2):257–266

    CrossRef  Google Scholar 

  • Brizel DM et al (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56(5):941–943

    Google Scholar 

  • Bruce A et al (2015) Three-dimensional microfluidic tri-culture model of the bone marrow microenvironment for study of acute lymphoblastic leukemia. PLoS ONE 10(10):1–16

    CrossRef  Google Scholar 

  • Burkoth AK, Anseth KS (2000) A review of photocrosslinked polyanhydrides: in situ forming degradable networks. Biomaterials 21(23):2395–2404

    Google Scholar 

  • Burns JS et al (2011) Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction. PLoS ONE 6(7)

    Google Scholar 

  • Butcher DT, Alliston T, Weaver VM (2009) A tense situation: forcing tumour progression. Nat Rev Cancer 9(2):108–122

    CrossRef  Google Scholar 

  • Cai S et al (2013) Novel 3D electrospun scaffolds with fibers oriented randomly and evenly in three dimensions to closely mimic the unique architectures of extracellular matrices in soft tissues: Fabrication and mechanism study. Langmuir 29(7):2311–2318

    CrossRef  Google Scholar 

  • Campbell PG et al (2005) Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell organization. Biomaterials 26(33):6762–6770

    CrossRef  Google Scholar 

  • Cantin K et al (2011) H-bonding-driven gel formation of a phenylacetylene macrocycle. Org Biomol Chem 9(12):4440–4443

    CrossRef  Google Scholar 

  • Carey SP et al (2012) Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture. Biomaterials 33(16):4157–4165

    CrossRef  Google Scholar 

  • Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    CrossRef  Google Scholar 

  • Catlett-Falcone R et al (1999) Constitutive activation of Stat 3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10(1):105–115

    Google Scholar 

  • Cekanova M (2014) Animal models and therapeutic molecular targets of cancer : utility and limitations 1911–1922

    Google Scholar 

  • Chaudhuri O et al (2014) Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat Mater 13(June):1–35

    Google Scholar 

  • Chauhan D et al (1997) Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood 89:227–234

    Google Scholar 

  • Chauhan H et al (2003) There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions. J Clin Pathol 56(4):271–276

    CrossRef  Google Scholar 

  • Chen L et al (2012) The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials 33(5):1437–1444

    Google Scholar 

  • Chen Y-C et al (2015) High-throughput cancer cell sphere formation for characterizing the efficacy of photo dynamic therapy in 3D cell cultures. Sci Rep 5:12175

    Google Scholar 

  • Cherry RS, Papoutsakis ET (1988) Physical mechanisms of cell damage in microcarrier cell culture bioreactors. Biotechnol Bioeng 32(8):1001–1014

    Google Scholar 

  • Choh S, Cross D, Wang C (2011) Facile synthesis and characterization of disulfide-cross-linked hyaluronic acid hydrogels for protein delivery and cell encapsulation. Biomacromolecules 1126–1136

    Google Scholar 

  • Cirri P, Chiarugi P (2011) Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res 1(4):482–497

    Google Scholar 

  • Cohen DL et al (2006) Direct freeform fabrication of seeded hydrogels in arbitrary geometries. Tissue Eng 12(5):1325–1335

    CrossRef  Google Scholar 

  • Coussens LM et al (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13(11):1382–1397

    CrossRef  Google Scholar 

  • Coussens LM et al (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103(3):481–490

    CrossRef  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer 420:860–867

    Google Scholar 

  • Cox TR, Erler JT (2011) Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Models Mech 4(2):165–178

    CrossRef  Google Scholar 

  • Croix B St, Kerbel RS (1997) Cell adhesion and drug resistance in cancer. Curr Opin Oncol 9(6)

    Google Scholar 

  • Cui X et al (2012a) Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul 6(2):149–155

    Google Scholar 

  • Cui X et al (2012b) Direct human cartilage repair using 3D bioprinting technology. Tissue Eng 18(11–12):1304–1312

    CrossRef  Google Scholar 

  • Dahlmann J et al (2013) Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering. Biomaterials 34(4):940–951

    CrossRef  Google Scholar 

  • Dalton WS (1999) The tumor microenvironment as a determinant of drug response and resistance. Drug Resist. Updat. 2:285–288

    CrossRef  Google Scholar 

  • Daquinag AC, Souza GR, Kolonin MG (2013) Adipose tissue engineering in three-dimensional levitation tissue culture system based on magnetic nanoparticles. Tissue Eng Part C Methods 19(5):336–344

    Google Scholar 

  • Davies PF (1981) Microcarrier culture of vascular plastic on solid beads vascular endothelial cell culture is now firmly established as a valuable research approach to the pathophysiology of blood vessels

    Google Scholar 

  • Dean M (2009) ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 14(1):3–9

    CrossRef  Google Scholar 

  • Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284

    CrossRef  Google Scholar 

  • DeForest CA, Polizzotti BD, Anseth KS (2009) Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat Mater 8(8):659–664

    CrossRef  Google Scholar 

  • Demirci U, Montesano G (2007) Single cell epitaxy by acoustic picolitre droplets. Lab Chip 7(9):1139–1145

    CrossRef  Google Scholar 

  • Denduluria SK et al (2015) Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis 2(2):13–25

    CrossRef  Google Scholar 

  • Desorme M et al (2013) Spinning of hydroalcoholic chitosan solutions. Carbohydr Polym 98(1):50–63

    CrossRef  Google Scholar 

  • Dimanche-Boitrel MT et al (1994) In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts. Int J Cancer. J Int du Cancer 56(4):512–521

    CrossRef  Google Scholar 

  • Ding C et al (2010) Dually responsive injectable hydrogel prepared by in situ cross-linking of glycol chitosan and benzaldehyde-capped PEO-PPO-PEO. Biomacromolecules 11(4):1043–1051

    CrossRef  Google Scholar 

  • Discher DE, Mooney DJ, Zandstra PW (2009) Growth factors, matrices, and forces combine and control stem cells. Sci (NY) 324(5935):1673–1677

    CrossRef  Google Scholar 

  • Duan B et al (2013) 3D Bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. J Biomed Mater Res Part A 101 A(5):1255–1264

    Google Scholar 

  • van Duinen V et al (2015) Microfluidic 3D cell culture: from tools to tissue models. Curr Opin Biotechnol 35:118–126

    Google Scholar 

  • Ehrmann RL, Knoth M (1968) Choriocarcinoma. Trans filter stimulation of vasoproliferation in the hamster cheek pouch. Studied by light and electron microscopy. J Nat Cancer Inst 41(6):1329–1341

    Google Scholar 

  • Elenbaas B, A.Weinberg R (2001) Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp Cell Res 264:169–184

    CrossRef  Google Scholar 

  • Emans PJ et al (2010) Autologous engineering of cartilage. Proc Natl Acad Sci USA 107(8):3418–3423

    CrossRef  Google Scholar 

  • Enea D et al (2011) Extruded collagen fibres for tissue engineering applications: Effect of crosslinking method on mechanical and biological properties. J Mater Sci—Mater Med 22(6):1569–1578

    CrossRef  Google Scholar 

  • Engler AJ et al (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    CrossRef  Google Scholar 

  • Falkenberg N et al (2016) Three-dimensional microtissues essentially contribute to preclinical validations of therapeutic targets in breast cancer. Cancer Med 5(4):703–710

    Google Scholar 

  • Fang Y et al (2012) Rapid generation of multiplexed cell cocultures using acoustic droplet ejection followed by aqueous two-phase exclusion patterning. Tissue Eng Part C: Methods 18(9):647–657

    CrossRef  Google Scholar 

  • Faute MA dit et al (2002) Distinctive alterations of invasiveness, drug resistance and cell–cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant. Clinical Exp Metastasis 19(2):161–167

    Google Scholar 

  • Fischbach C et al (2007) Engineering tumors with 3D scaffolds. Nat Methods 4(10):855–860

    CrossRef  Google Scholar 

  • Fisher OZ et al (2010) Bioinspired materials for controlling stem cell fate. Acc Chem Res 43(3):419–428

    CrossRef  Google Scholar 

  • Fisher SA et al (2015) Tuning the Microenvironment: Click-crosslinked hyaluronic acid-based hydrogels provide a platform for studying breast cancer cell invasion. Adv Funct Mater 25(46):7163–7172

    CrossRef  Google Scholar 

  • Florczyk SJ et al (2012) 3D porous chitosan–alginate scaffolds: a new matrix for studying prostate cancer cell–lymphocyte interactions In Vitro. Adv Healthc Mater 1(5):590–599

    Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. The New Engl J Med 285:1182–1186

    CrossRef  Google Scholar 

  • Fong ELS et al (2013) Modeling ewing sarcoma tumors in vitro with 3D scaffolds. Proc Natl Acad Sci USA 110(16):6500–6505

    CrossRef  Google Scholar 

  • Frese KK, Tuveson DA (2007) Maximizing mouse cancer models. Nat Rev Cancer 7(9):654–658

    Google Scholar 

  • Gabbiani G, Ryan GB, Majno G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27(5):549–550

    Google Scholar 

  • Gill BJ et al (2012) A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model. Cancer Res 72(22):6013–6023

    CrossRef  Google Scholar 

  • Gillette BM et al (2008) In situ collagen assembly for integrating microfabricated three-dimensional cell-seeded matrices. Nat Mater 7(8):636–640

    CrossRef  Google Scholar 

  • Girard YK et al (2013) A 3D fibrous scaffold inducing tumoroids: a platform for anticancer drug development. PLoS ONE 8(10)

    Google Scholar 

  • Giussani M et al (2015) Tumor-extracellular matrix interactions: identification of tools associated with breast cancer progression. Semin Cancer Biol 35:3–10

    CrossRef  Google Scholar 

  • Godugu C et al (2013) AlgiMatrixTM based 3D cell culture system as an in-vitro tumor model for anticancer studies. PLoS ONE 8(1)

    Google Scholar 

  • Goodwin TJ et al (1993) Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. J Cell Biochem 51(3):301–311

    CrossRef  Google Scholar 

  • Göppert B et al (2016) Superporous Poly (ethylene glycol) Diacrylate Cryogel with a defined elastic modulus for prostate cancer cell research. Small 1–10

    Google Scholar 

  • Gottesman MM, Fojo T, Bates SE (2001) Multidrug resistance in cancer: role of atp-dependent transporters, 2(January), pp 1–11

    Google Scholar 

  • Granja P, Jéso B De, Bareille R (2005) Mineralization of regenerated cellulose hydrogels induced by human bone marrow stromal cells. Eur Cell … 31–39

    Google Scholar 

  • Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7(3):211–224

    Google Scholar 

  • Grover GN, Braden RL, Christman KL (2013) Oxime cross-linked injectable Hydrogels for catheter delivery. Adv Mater 25(21):2937–2942

    Google Scholar 

  • Gruene M et al (2011) Laser printing of stem cells for biofabrication of scaffold-free autologous grafts. Tissue Eng Part C: Methods 17(1):79–87

    CrossRef  Google Scholar 

  • Grundy TJ et al (2016) Differential response of patient- derived primary glioblastoma cells to environmental stiffness. Nature Publishing Group, (Nov 2015), pp 4–13

    Google Scholar 

  • Guillemot F et al (2010) High-throughput laser printing of cells and biomaterials for tissue engineering. Acta Biomater 6(7):2494–2500

    CrossRef  Google Scholar 

  • Guillotin B et al (2010) Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials 31(28):7250–7256

    CrossRef  Google Scholar 

  • Guillotin B, Guillemot F (2011) Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol 29(4):183–190

    CrossRef  Google Scholar 

  • Gullino PM (1978) Angiogenesis and oncogenesis. J Natl Cancer Inst 61(3):639

    Google Scholar 

  • Guo Y-S et al (1998) Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol 175(2):141–148

    Google Scholar 

  • Gurkan UA et al (2012) Emerging technologies for assembly of microscale hydrogels. Adv Healthc Mater 1(2):149–158

    CrossRef  Google Scholar 

  • Gurkan UA et al (2014) Engineering anisotropic biomimetic fibrocartilage microenvironment by bioprinting mesenchymal stem cells in Nanoliter Gel Droplets. Mol Pharm 11:2151–2159

    CrossRef  Google Scholar 

  • Gurski LA et al (2009) Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells. Biomaterials 30(30):6076–6085

    CrossRef  Google Scholar 

  • Guven S et al (2015) Multiscale assembly for tissue engineering and regenerative medicine. Trends Biotechnol 33(5):37–54

    CrossRef  Google Scholar 

  • Guzman A, Ziperstein MJ, Kaufman LJ (2014) The effect of fibrillar matrix architecture on tumor cell invasion of physically challenging environments. Biomaterials 35(25):6954–6963

    CrossRef  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The Hallmarks of Cancer Review University of California at San Francisco. Cell Press 100(7):57–70

    Google Scholar 

  • Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2(1):38–47

    Google Scholar 

  • Hartman O et al (2009) Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications. Biomacromolecules 10(8):2019–2032

    CrossRef  Google Scholar 

  • Heldin CH et al (2004) High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer 4(10):806–813

    Google Scholar 

  • Hideshima T et al (2001) Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene 20(42):5991–6000

    Google Scholar 

  • Higuchi A et al (2005) Temperature-dependent cell detachment on Pluronic gels. Biomacromolecules 6(2):691–696

    CrossRef  Google Scholar 

  • Hirschhaeuser F et al (2009) Test system for trifunctional antibodies in 3D MCTS culture. J Biomol Screen: Official J Soc Biomol Screen 14(8):980–990

    CrossRef  Google Scholar 

  • Ho WJ et al (2010) Incorporation of multicellular spheroids into 3-D polymeric scaffolds provides an improved tumor model for screening anticancer drugs. Cancer Sci 101(12):2637–2643

    CrossRef  Google Scholar 

  • Höckel M et al (1999) Hypoxic cervical cancers with low apoptotic index are highly aggressive. Cancer Res 59(18):4525–4528

    Google Scholar 

  • Höckel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93(4):266–276

    CrossRef  Google Scholar 

  • Holliday DL et al (2009) Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression. Breast Cancer Res: BCR 11(1):R3

    CrossRef  Google Scholar 

  • Hopp B et al (2005) Survival and proliferative ability of various living cell types after laser-induced forward transfer. Tissue Eng 11(11–12):1817–1823

    Google Scholar 

  • Horman SR et al (2013) High-content analysis of three-dimensional tumor spheroids: investigating signaling pathways using small hairpin RNA. Nat Meth10(10)

    Google Scholar 

  • Horning JL et al (2008) 3-D tumor model for in vitro evaluation of anticancer drugs. Mol Pharm 5(5):849–862

    CrossRef  Google Scholar 

  • Hoyt DG et al (1996) Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells. Cancer Res 56(18):4146–4149

    Google Scholar 

  • Hsiao AY et al (2012) 384 hanging drop arrays give excellent Z-factors and allow versatile formation of co-culture spheroids. Biotechnol Bioeng 109(5):1293–1304

    CrossRef  Google Scholar 

  • Huang ZM et al (2003) A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol 63(15):2223–2253

    CrossRef  Google Scholar 

  • Huh D et al (2012) A human disease model of drug toxicity—induced pulmonary edema in a lung-on-a-chip microdevice. Sci Trans Med 4(159):1–9

    CrossRef  Google Scholar 

  • Hull CW (1986) Apparatus for production of three-dimensional objects by stereolithography

    Google Scholar 

  • Hutmacher DW (2010) Biomaterials offer cancer research the third dimension. Nat Mater 9(2):90–93

    Google Scholar 

  • Hutmacher DW et al (2010) Can tissue engineering concepts advance tumor biology research? Trends Biotechnol 28(3):125–133

    CrossRef  Google Scholar 

  • Imamura Y et al (2015) Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. Oncol Rep 33(4):1837–1843

    Google Scholar 

  • Iwami K et al (2010) Bio rapid prototyping by extruding/aspirating/refilling thermoreversible hydrogel. Biofabrication 2(1):014108

    CrossRef  Google Scholar 

  • Jabbari E et al (2015) Optimum 3D matrix stiffness for maintenance of cancer stem cells is dependent on tissue origin of cancer cells. PLoS ONE 10(7):1–21

    CrossRef  Google Scholar 

  • Jaganathan H et al (2014) Three-dimensional in vitro co-culture model of breast tumor using magnetic levitation. Sci Rep 4:6468

    CrossRef  Google Scholar 

  • Jahangir A, Chen G, Chang H (2013) Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget 4(12):2186–2207

    CrossRef  Google Scholar 

  • Jain RK (1996) Delivery of molecular medicine to solid tumors. Sci (NY) 271(5252):1079–1080

    CrossRef  Google Scholar 

  • Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706):58–62

    Google Scholar 

  • Jang J, Yi H-G, Cho D-W (2016) 3D printed tissue models: present and future. ACS Biomater Sci Eng p.acsbiomaterials.6b00129

    Google Scholar 

  • Jewett JC, Sletten EM, Bertozzi CR (2010) Rapid Cu-free click chemistry with readily synthesized biarylazacyclooctynones. J Am Chem Soc 132(11):3688–3690

    CrossRef  Google Scholar 

  • Jo D (1996) Breast development in puberty. In: Angeli A DL, Bradlow HL (eds) Endocrinology of the breast: Basic and clinical aspects. Annals of the New York Academy of Sciences. The New York Academy of Sciences, New York, pp 58–66

    Google Scholar 

  • Jo YS et al (2010) Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides. J Biomed Mater Res, Part A 93(3):870–877

    Google Scholar 

  • Johns RA et al (1995) Halothane and isoflurane inhibit endothelium-derived relaxing factor-dependent cyclic guanosine monophosphate accumulation in endothelial cell-vascular smooth muscle co-cultures independent of an effect on guanylyl cyclase activation. J Am Soc Anesthesiologists 83(4):823–834

    Google Scholar 

  • Julia T et al (2013) Fibroblast activation protein expression by stromal cells and tumor-associated macrophages in human breast cancer. Hum Pathol 44(11):2549–2557

    CrossRef  Google Scholar 

  • Kacinski BM (1997) CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract. Mol Reprod Dev 46:71–74

    CrossRef  Google Scholar 

  • Kacinski BM (1995) CSF-1 and its receptor in ovarian, endometrial and breast cancer. Ann Med 27(1):79–85

    Google Scholar 

  • Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6(5):392–401

    CrossRef  Google Scholar 

  • Kang SW, Bae YH (2009) Cryopreservable and tumorigenic three-dimensional tumor culture in porous poly(lactic-co-glycolic acid) microsphere. Biomaterials 30(25):4227–4232

    Google Scholar 

  • Keely P, Nain A (2015) Capturing relevant extracellular matrices for investigating cell migration. F1000 Res 4(May)

    Google Scholar 

  • Kelm JM et al (2003) Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83(2):173–180

    CrossRef  Google Scholar 

  • Kerbel RS (2003) Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2(4 Suppl 1)

    Google Scholar 

  • Keriquel V et al (2010) In vivo bioprinting for computer- and robotic-assisted medical intervention: preliminary study in mice. Biofabrication 2(1):014101

    Google Scholar 

  • Kerkar SP, Restifo NP (2012) Cellular constituents of immune escape within the tumor microenvironment. Cancer Res 72(13):3125–3130

    CrossRef  Google Scholar 

  • Kim B, Forbes NS (2007) Flux analysis shows that hypoxia-inducible- factor-1-alpha minimally affects intracellular metabolism in tumor spheroids. Biotechnol Bioeng 96(6):1167–1182

    CrossRef  Google Scholar 

  • Kim J et al (2011) NONOates–polyethylenimine hydrogel for controlled nitric oxide release and cell proliferation modulation. Bioconjug Chem 22(6):1031–1038

    CrossRef  Google Scholar 

  • Kim J Bin (2005) Three-dimensional tissue culture models in cancer biology. Semin Cancer Biol 15(5):365–377

    CrossRef  Google Scholar 

  • Kim YJ et al (2009) Three-dimensional gastric cancer cell culture using nanofiber scaffold for chemosensitivity test. Int J Biol Macromol 45(1):65–71

    CrossRef  Google Scholar 

  • Kimura M et al (2004) Hydrogen-bonding-driven spontaneous gelation of water-soluble phospholipid polymers in aqueous medium. J Biomater Sci Polym Ed 15(5):631–644

    CrossRef  Google Scholar 

  • Kleinman HK, Martin GR (2005) Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol 15(5 SPEC. ISS.):378–386

    Google Scholar 

  • Koehler KC, Anseth KS, Bowman CN (2013) Diels-Alder mediated controlled release from a poly(ethylene glycol) based hydrogel. Biomacromolecules 14(2):538–547

    CrossRef  Google Scholar 

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

    CrossRef  Google Scholar 

  • Kraning-Rush CM, Reinhart-King CA (2012) Controlling matrix stiffness and topography for the study of tumor cell migration. Cell Adhes Migr 6(3):274–279

    CrossRef  Google Scholar 

  • Kraus AC et al (2002) In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene 21(57):8683–8695

    Google Scholar 

  • Kumar PR et al (2012) Nanofibers: effective generation by electrospinning and their applications. J Nanosci Nanotechnol 12(1):1–25

    CrossRef  Google Scholar 

  • Kunz-Schughart LA et al (2004) The Use of 3-D cultures for high-throughput screening. J Biomol Screen 9(4):273–285

    CrossRef  Google Scholar 

  • Kuo CY et al (2016) Development of a 3D printed, bioengineered placenta model to evaluate the role of trophoblast migration in preeclampsia. ACS Biomater Sci Eng 2(10):1817–1826

    Google Scholar 

  • Kuperwasser C et al (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Nat Acad Sci USA 101(14):4966–4971

    Google Scholar 

  • Laconte L, Nitin N, Bao G (2005) Magnetic nanoparticle probes. Mater Today 8(5):32–38

    Google Scholar 

  • Laguinge LM et al (2004) Nitrosative stress in rotated three-dimensional colorectal carcinoma cell cultures induces microtubule depolymerization and apoptosis. Cancer Res 64(8):2643–2648

    CrossRef  Google Scholar 

  • Lai J-Y (2012) Biocompatibility of genipin and glutaraldehyde cross-linked chitosan materials in the anterior chamber of the eye. Int J Mol Sci 13(9):10970–10985

    CrossRef  Google Scholar 

  • Lam CX et al (2008) Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions. Biomed Mater 3(3):034108

    Google Scholar 

  • Lamichhane SP et al (2016) Recapitulating epithelial tumor microenvironment in vitro using three dimensional tri-culture of human epithelial, endothelial, and mesenchymal cells. BMC cancer 16(1):581

    Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Sci (NY) 260(5110):920–926

    CrossRef  Google Scholar 

  • Lazard D et al (1993) Expression of smooth muscle-specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant human breast tissue. Proc Nat Acad Sci USA 90(3):999–1003

    Google Scholar 

  • Lee JW et al (2016a) Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering. Biofabrication 8(1):15007

    Google Scholar 

  • Lee BK, Yun Y, Park K (2016b) PLA micro- and nano-particles. Adv Drug Deliv Rev S0169–409X(16):30180–30186

    Google Scholar 

  • Lee E et al (2015) Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment. Expert Rev Mol Med 17:e3

    Google Scholar 

  • Lee S-H et al (2007) Poly(ethylene glycol) hydrogels conjugated with a collagenase-sensitive fluorogenic substrate to visualize collagenase activity during three-dimensional cell migration. Biomaterials 28(20):3163–3170

    CrossRef  Google Scholar 

  • Lee SY et al (2008) A novel self-sintering microparticle-based system for regenerative medicine. Eur Cells Mater 16(3):71

    Google Scholar 

  • Lee WR et al (2011) Magnetic levitating polymeric nano/microparticular substrates for three-dimensional tumor cell culture. Colloids Surf B 85(2):379–384

    CrossRef  Google Scholar 

  • Leu AJ et al (2000) Absence of functional lymphatics within a murine sarcoma : a molecular and functional evaluation advances in brief absence of functional lymphatics within a murine sarcoma : a molecular and functional evaluation 1. Cancer Res 4324–4327

    Google Scholar 

  • Leung M et al (2010) Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance. Pharm Res 27(9):1939–1948

    CrossRef  Google Scholar 

  • Levental KR et al (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139(5):891–906

    CrossRef  Google Scholar 

  • Lewis MP et al (2004) Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer 90(4):822–832

    CrossRef  Google Scholar 

  • Li G et al (2003) Function and regulation of melanoma–stromal fibroblast interactions: when seeds meet soil. Oncogene 22(20):3162–3171

    Google Scholar 

  • Li H, Fan X, Houghton J (2007) Tumor microenvironment: The role of the tumor stroma in cancer. J Cell Biochem 101(4):805–815

    CrossRef  Google Scholar 

  • Li X et al (2014a) Micro-scaffold array chip for upgrading cell-based high-throughput drug testing to 3D using benchtop equipment. Lab Chip 14(3):471–481

    CrossRef  Google Scholar 

  • Li Y et al (2014b) Effects of mechanical properties on tumor invasion: Insights from a cellular model. Conf Proc IEEE Eng Med Biol Soc 2014:6818–6821

    Google Scholar 

  • Li Y et al (2012) Well-defined, reversible boronate crosslinked nanocarriers for targeted drug delivery in response to acidic pH values and cis -Diols. Angew Chem 124(12):2918–2923

    CrossRef  Google Scholar 

  • Lichtenstein A et al (1996) Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol 162(2):248–255

    CrossRef  Google Scholar 

  • Lin EY et al (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193(6):727–740

    Google Scholar 

  • Lin CC, Raza A, Shih H (2011) PEG hydrogels formed by thiol-ene photo-click chemistry and their effect on the formation and recovery of insulin-secreting cell spheroids. Biomaterials 32(36):9685–9695

    CrossRef  Google Scholar 

  • Lin RZ, Chang HY (2008) Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J 3(9–10):1172–1184

    CrossRef  Google Scholar 

  • Lin RZ et al (2008) Magnetic reconstruction of three-dimensional tissues from multicellular spheroids. Tissue Eng Part C, Methods 14(3):197–205

    CrossRef  Google Scholar 

  • Liu C et al (2015) Role of three-dimensional matrix stiffness in regulating the chemoresistance of hepatocellular carcinoma cells. Biotechnol Appl Biochem 62(4):556–562

    CrossRef  Google Scholar 

  • Liu T et al (2014) Advanced micromachining of concave microwells for long term on-chip culture of multicellular tumor spheroids. ACS Appl Mater Interfaces 6(11):8090–8097

    CrossRef  Google Scholar 

  • Lozinsky VI et al (2003) Polymeric cryogels as promising materials of biotechnological interest. Trends Biotechnol 21(10):445–451

    CrossRef  Google Scholar 

  • Lozinsky VI, Plieva FM (1998) Poly(vinyl alcohol) cryogels employed as matrices for cell immobilization. 3. Overview of recent research and developments. Enzym Microb Technol 23(3–4):227–242

    CrossRef  Google Scholar 

  • Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 196(4):395–406

    CrossRef  Google Scholar 

  • Luo Y, Shoichet MS (2004) Light-activated immobilization of biomolecules to agarose hydrogels for controlled cellular response. Biomacromolecules 5(6):2315–2323

    CrossRef  Google Scholar 

  • Mak IW, Evaniew N, Ghert M (2014) Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6(2):114–118

    Google Scholar 

  • Malda J et al (2003) Expansion of bovine chondrocytes on microcarriers enhances redifferentiation. Tissue Eng 9(5):939–948

    CrossRef  Google Scholar 

  • Malik R, Lelkes PI, Cukierman E (2015) Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer. Trends Biotechnol 33(4):230–236

    CrossRef  Google Scholar 

  • Manabe Y et al (2003) Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer–stromal cell interactions. J Pathol 201(2):221–228

    Google Scholar 

  • Mann BK et al (2001) Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials 22(22):3045–3051

    CrossRef  Google Scholar 

  • Manoto SL, Houreld NN, Abrahamse H (2015) Resistance of lung cancer cells grown as multicellular tumour spheroids to zinc sulfophthalocyanine photosensitization. 10185–10200

    Google Scholar 

  • Marklein RA, Burdick JA (2010) Spatially controlled hydrogel mechanics to modulate stem cell interactions. Soft Matter 6(1):136–143

    Google Scholar 

  • Maubant S et al (2002) Altered adhesion properties and alphav integrin expression in a cisplatin-resistant human ovarian carcinoma cell line. Int J Cancer 97(2):186–194

    Google Scholar 

  • Maurer BJ et al (1999) Growth of human tumor cells in macroporous microcarriers results in p 53-independent, decreased cisplatin sensitivity relative to monolayers. Mol Pharmacol 55(5):938–947

    Google Scholar 

  • Mayer B et al (2001) Multicellular gastric cancer spheroids recapitulate growth pattern and differentiation phenotype of human gastric carcinomas. Gastroenterology 121(4):839–852

    Google Scholar 

  • Michael S et al (2013) Tissue engineered skin substitutes created by laser-assisted bioprinting form skin-like structures in the dorsal skin fold chamber in mice. PLoS ONE 8(3):e57741

    Google Scholar 

  • Mierke CT (2014) The fundamental role of mechanical properties in the progression of cancer disease and inflammation. Rep Prog Phys 77(7):076602

    CrossRef  Google Scholar 

  • Milosevic MF et al (1998) Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity, and relation to oxygen tension. Cancer 82:2418–2426

    CrossRef  Google Scholar 

  • Minchinton AI, Tannock IF (2006) Drug penetration in solid tumours. Nat Rev Cancer 6(8):583–592

    CrossRef  Google Scholar 

  • Miyake H et al (1998) Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer cell line. Cancer Lett 123(2):121–126

    Google Scholar 

  • Mueller MM, Fusenig NE (1999) Constitutive expression of G-CSF and GM-CSF in human skin carcinoma cells with functional consequence for tumor progression. Int J Cancer 83(6):780–789

    CrossRef  Google Scholar 

  • Mueller MM et al (1999) Autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor in human gliomas with tumor progression. Am J Pathol 155(5):1557–1567

    CrossRef  Google Scholar 

  • Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849

    Google Scholar 

  • Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785

    CrossRef  Google Scholar 

  • Nakajima M et al (2007) Combinatorial protein display for the cell-based screening of biomaterials that direct neural stem cell differentiation. Biomaterials 28(6):1048–1060

    CrossRef  Google Scholar 

  • Nimmo CM, Shoichet MS (2011) Regenerative biomaterials that “click”: simple, aqueous-based protocols for hydrogel synthesis, surface immobilization, and 3D patterning. Bioconjug Chem 22(11):2199–2209

    CrossRef  Google Scholar 

  • Nimmo CM, Owen SC, Shoichet MS (2011) Diels-Alder Click cross-linked hyaluronic acid hydrogels for tissue engineering. Biomacromolecules 12(3):824–830

    Google Scholar 

  • Norotte C et al (2009) Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 30(30):5910–5917

    CrossRef  Google Scholar 

  • Obermueller E et al (2004) Cooperative autocrine and paracrine functions of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the progression of skin carcinoma cells. Cancer Res 64(21):7801–7812

    Google Scholar 

  • Ogata A et al (1997) IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J Immunol (Baltimore, Md.: 1950) 159(Mm):2212–2221

    Google Scholar 

  • Ogawa T et al (2004) Regulation of biological activity of laminin-5 by proteolytic processing of gamma2 chain. J Cell Biochem 92(4):701–714

    CrossRef  Google Scholar 

  • Oliveira MB, Mano JF (2011) Polymer-based microparticles in tissue engineering and regenerative medicine. Biotechnol Prog 27(4):897–912

    CrossRef  Google Scholar 

  • Olumi AF et al (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium carcinoma-associated fibroblasts direct tumor progression of initiated human. 59(19):5002–5011

    Google Scholar 

  • Orimo A et al (2001) Cancer-associated myofibroblasts possess various factors to promote endometrial tumor progression. Clin Cancer Res 7(10):3097–3105

    Google Scholar 

  • Orimo A et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348

    CrossRef  Google Scholar 

  • Ozcelik B et al (2014) Highly porous and mechanically robust polyester poly(ethylene glycol) sponges as implantable scaffolds. Acta Biomater 10(6):2769–2780

    CrossRef  Google Scholar 

  • Paget S (1989) The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 8(2):98

    Google Scholar 

  • Park KH, Na K, Chung HM (2005) Enhancement of the adhesion of fibroblasts by peptide containing an Arg-Gly-Asp sequence with poly(ethylene glycol) into a thermo-reversible hydrogel as a synthetic extracellular matrix. Biotechnol Lett 27(4):227–231

    CrossRef  Google Scholar 

  • Paszek MJ et al (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8(3):241–254

    CrossRef  Google Scholar 

  • Patel A, Mequanint K (2011) Hydrogels Biomaterials. www.intechopen.com

  • Patrick AG, Ulijn RV (2010) Hydrogels for the detection and management of protease levels. Macromol Biosci 10(10):1184–1193

    CrossRef  Google Scholar 

  • Pavesi A et al (2016) Engineering a 3D microfluidic culture platform for tumor-treating field application. Sci Rep 6:1–10

    CrossRef  Google Scholar 

  • Phelps EA et al (2010) Bioartificial matrices for therapeutic vascularization. Proc Natl Acad Sci USA 107(8):3323–3328

    CrossRef  Google Scholar 

  • Phillippi JA et al (2008) Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations. Stem Cells 26(1):127–134

    CrossRef  Google Scholar 

  • Pickup MW, Mouw JK, Weaver VM (2014) The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 15(12):1243–1253

    CrossRef  Google Scholar 

  • Pirilä E et al (2003) Matrix metalloproteinases process the laminin-5 2-chain and regulate epithelial cell migration. Biochem Biophys Res Commun 303(4):1012–1017

    CrossRef  Google Scholar 

  • Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4:71–78

    CrossRef  Google Scholar 

  • Raeber GP, Lutolf MP, Hubbell JA (2007) Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs. Acta Biomater 3(5):615–629

    CrossRef  Google Scholar 

  • Rafii S, Heissig B, Hattori K (2002) Efficient mobilization and recruitment of marrow-derrived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther 9:631–641

    Google Scholar 

  • Re’em T, Tsur-Gang O, Cohen S (2010) The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGF??1-induced chondrogenesis of human mesenchymal stem cells. Biomaterials 31(26):6746–6755

    Google Scholar 

  • Reid B et al (2013) PEG hydrogel degradation and the role of the surrounding tissue environment. J Tissue Eng Regenerative Med 9(3):315–318

    Google Scholar 

  • Reilly GC, Engler AJ (2010) Intrinsic extracellular matrix properties regulate stem cell differentiation. J Biomech 43(1):55–62

    CrossRef  Google Scholar 

  • Rettig WJ (1993) Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin. Cancer Res 53:3327–3335

    Google Scholar 

  • Rezende R et al (2007) Experimental characterisation of the alginate gelation process for rapid prototyping. In: The eighth international conference on chemical & process engineering. vol 11. pp 509–514

    Google Scholar 

  • Rhee HW et al (2001) Permanent phenotypic and genotypic changes of prostate cancer cells cultured in a three-dimensional rotating-wall vessel. In Vitro Cell Dev Biol Anim 37(3):127–140

    Google Scholar 

  • Richmond A, Su Y (2008) Mouse xenograft models versus GEM models for human cancer therapeutics. Dis Models Mech 1(2–3):78–82

    CrossRef  Google Scholar 

  • Sahoo SK, Panda AK, Labhasetwar V (2005) Characterization of porous PLGA/PLA microparticles as a scaffold for three dimensional growth of breast cancer cells. Biomacromolecules 6(2):1132–1139

    Google Scholar 

  • Salinas CN, Anseth KS (2008) The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities. Biomaterials 29(15):2370–2377

    CrossRef  Google Scholar 

  • Sanabria-DeLong N et al (2006) Controlling hydrogel properties by crystallization of hydrophobic domains. Macromolecules 39(4):1308–1310

    CrossRef  Google Scholar 

  • Sansone P, Bromberg J (2012) Targeting the interleukin-6/jak/stat pathway in human malignancies. J Clin Oncol 30(9):1005–1014

    CrossRef  Google Scholar 

  • Sato T et al (2004) Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol Oncol 92(1):47–56

    CrossRef  Google Scholar 

  • Sawhney AS (1993) Bioerodible hydrogels based on Photopolymerized Poly(ethy1ene. Macromolecules 26:581–587

    CrossRef  Google Scholar 

  • Saxon E (2000) Cell surface engineering by a modified staudinger reaction. Science 287(5460):2007–2010

    CrossRef  Google Scholar 

  • Saxon E, Armstrong JI, Bertozzi CR (2000) A “traceless” Staudinger ligation for the chemoselective synthesis of amide bonds. Org Lett 2(14):2141–2143

    CrossRef  Google Scholar 

  • Schmidt M, Lichtner RB (2002) EGF receptor targeting in therapy-resistant human tumors. Drug Resist Updates 5(1):11–18

    CrossRef  Google Scholar 

  • Sekiguchi Y, Sawatari C, Kondo T (2003) A gelation mechanism depending on hydrogen bond formation in regioselectively substituted O-methylcelluloses. Carbohydr Polym 53(2):145–153

    CrossRef  Google Scholar 

  • Sell SA et al (2009) Electrospinning of collagen/biopolymers for regenerative medicine and cardiovascular tissue engineering. Adv Drug Deliv Rev 61(12):1007–1019

    CrossRef  Google Scholar 

  • Sethi T et al (1999) Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 5(6):662–668

    CrossRef  Google Scholar 

  • Shekhar MPV et al (2001) Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. Cancer Res 61(4):1320–1326

    Google Scholar 

  • Shikanov A et al (2011) Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture. Biomaterials 32(10):2524–2531

    CrossRef  Google Scholar 

  • Shor L et al (2009) Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication 1(1):015003

    CrossRef  Google Scholar 

  • Shu XZ et al (2002) Disulfide cross-linked hyaluronan hydrogels. Biomacromolecules 3(6):1304–1311

    Google Scholar 

  • Siegel R, Miller K, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29

    Google Scholar 

  • Sill TJ, von Recum HA (2008) Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 29(13):1989–2006

    CrossRef  Google Scholar 

  • Skardal A et al (2012) Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl Med 1(11):792–802

    CrossRef  Google Scholar 

  • Skardal A et al (2010) The generation of 3-D tissue models based on hyaluronan hydrogel-coated microcarriers within a rotating wall vessel bioreactor. Biomaterials 31(32):8426–8435

    CrossRef  Google Scholar 

  • Skobe M, Fusenig NE (1998) Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Nat Acad Sci USA 95(3):1050–1055

    Google Scholar 

  • Smalley KSM, Lioni M, Herlyn M (2006) Life isn’t flat: taking cancer biology to the next dimension. In vitro cellular & developmental biology. Animal 42(8–9):242–247

    Google Scholar 

  • Smeds KA et al (2001) Photocrosslinkable polysaccharides for in situ hydrogel formation. J Biomed Mater Res 54(1):115–121

    CrossRef  Google Scholar 

  • Smeriglio P et al (2015) 3D hydrogel scaffolds for articular chondrocyte culture and cartilage generation. J Visualized Exp 104:1–6

    Google Scholar 

  • Smith HO et al (1995) The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. Clin Cancer Res 1(3):313–325

    Google Scholar 

  • Smith SJ et al (2012) Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition. PLoS ONE 7(12):e52335

    Google Scholar 

  • Souza GR et al (2010) Three-dimensional tissue culture based on magnetic cell levitation. Nat Nanotechnol 5(4):291–296

    Google Scholar 

  • Stetler-Stevenson WG, Yu AE (2001) Proteases in invasion: matrix metalloproteinases. Semin Cancer Biol 11(2):143–152

    Google Scholar 

  • Sui X et al (2010) Preparation of a rapidly forming Poly(ferrocenylsilane)-Poly(ethylene glycol)-based hydrogel by a thiol-michael addition click reaction. Macromol Rapid Commun 31(23):2059–2063

    CrossRef  Google Scholar 

  • Sutherland RM (1988) Microregions: the spheroid model. Science 240:177–240

    CrossRef  Google Scholar 

  • Sutherland RM, Inch WR, McCredie JA (1970) A multi—component radiation survival curve using an in vitro tumour model Int J Rad Biol 18(5):491–495

    Google Scholar 

  • Takagi A et al (2007) Three-dimensional cellular spheroid formation provides human prostate tumor cells with tissue-like features. Anticancer Res 27(1 A):45–54

    Google Scholar 

  • Talukdar S et al (2011) Engineered silk fibroin protein 3D matrices for in vitro tumor model. Biomaterials 32(8):2149–2159

    Google Scholar 

  • Tam RY et al (2016) Transparent porous polysaccharide cryogels provide biochemically defined, biomimetic matrices for tunable 3D cell culture. Chem Mater 28(11):3762–3770

    Google Scholar 

  • Tannock IF et al (2002) Limited penetration of anticancer drugs through tumor tissue : a potential cause of resistance of solid tumors to chemotherapy limited penetration of anticancer drugs through tumor tissue : a potential cause of resistance of solid tumors to chemotherapy 1. Clin Cancer Res: Official J Am Assoc Cancer Res 8:878–884

    Google Scholar 

  • Tasoglu S et al (2014) Guided and magnetic self-assembly of tunable magnetoceptive gels. Nat Commun 5:4702

    Google Scholar 

  • Tasoglu S, Demirci U (2013) Bioprinting for stem cell research. Trends Biotechnol 6(2):149–155

    Google Scholar 

  • Tekin E, Smith PJ, Schubert US (2008) Inkjet printing as a deposition and patterning tool for polymers and inorganic particles. Soft Matter 4(4):703–713

    CrossRef  Google Scholar 

  • Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549

    Google Scholar 

  • Tong JZ et al (1992) Long-term culture of adult rat hepatocyte spheroids. Exp Cell Res 200(2):326–332

    CrossRef  Google Scholar 

  • Tripathi A, Melo JS (2015) Preparation of sponge-like biocomposite agarose-chitosan scaffold with primary hepatocytes for establishing an in-vitro 3D liver tissue model. RSC Adv 5:30701–30710

    CrossRef  Google Scholar 

  • Tsubota Y et al (2000) Isolation and activity of proteolytic fragment of laminin-5 alpha3 chain. Biochem Biophys Res Commun 278(3):614–620

    CrossRef  Google Scholar 

  • Tung YC et al (2011) High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst 136(3):473–478

    Google Scholar 

  • Tuzlakoglu K, Reis RL (2009) Biodegradable polymeric fiber structures in tissue engineering. Tissue Eng Part B, Rev 5(1):17–27

    Google Scholar 

  • Ulrich TA, de Juan Pardo EM, Kumar S (2009) The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. Cancer Res 69(10):4167–4174

    CrossRef  Google Scholar 

  • Unsworth BR, Lelkes PI (1988) Growing Tissues Microgravity 4(8):901–907

    Google Scholar 

  • Visconti RP et al (2015) Towards organ printing: engineering an intra-organ branched vascular tree 10(3):409–420

    Google Scholar 

  • Visser J et al (2013) Biofabrication of multi-material anatomically shaped tissue constructs. Biofabrication 5(3):035007

    Google Scholar 

  • Wagner I et al (2013) A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip 13(18):3538–3547

    Google Scholar 

  • Wang F, Weaver VM, Pete OW (1998) Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: A different perspective in epithelial biology. Proc Natl Acad Sci USA 95:14821–14826

    CrossRef  Google Scholar 

  • Weaver VM et al (2002) Beta 4 integrin-dependent formation of polarized three- dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2:205–216

    Google Scholar 

  • Webber MM et al (1997) Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells. Carcinogenesis 18(6):1225–1231

    CrossRef  Google Scholar 

  • Wegiel B et al (2008) Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival. Int J Cancer 122(7):1521–1529

    CrossRef  Google Scholar 

  • Wenger MPE et al (2007) Mechanical properties of collagen fibrils. Biophys J 93(4):1255–1263

    CrossRef  Google Scholar 

  • West JL, Hubbell JA (1999) Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules 32(1):241–244

    CrossRef  Google Scholar 

  • West KA, Castillo SS, Dennis PA (2002) Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updates 5:234–248

    CrossRef  Google Scholar 

  • De Wever O et al (2004) Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. FASEB J 18(9):1016–1018

    Google Scholar 

  • De Wever O, Mareel M (2003) Role of tissue stroma in cancer cell invasion. J Pathol 200(4):429–447

    Google Scholar 

  • Williams DF (2008) On the mechanisms of biocompatibility. Biomaterials 29(20):2941–2953

    CrossRef  Google Scholar 

  • Wong JY et al (2003) Directed movement of vascular smooth muscle cells on gradient-compliant hydrogels. Langmuir 19:1908–1913

    CrossRef  Google Scholar 

  • Wong SY, Kumar S (2014) Matrix regulation of tumor-initiating cells. Prog Mol Biol Transl Sci 126:243–256

    Google Scholar 

  • Wylie RG et al (2011) Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nat Mater 10(10):799–806

    Google Scholar 

  • Xu F, Sridharan B et al (2011a) Embryonic stem cell bioprinting for uniform and controlled size embryoid body formation. Biomicrofluidics 5(2):1–8

    Google Scholar 

  • Xu F, Wu CAM et al (2011b) Three-dimensional magnetic assembly of microscale hydrogels. Adv Mater 23(37):4254–4260

    Google Scholar 

  • Xu F, Celli J et al (2011c) A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform. Biotechnol J 6(2):204–212

    CrossRef  Google Scholar 

  • Xu G et al (2014) In vitro ovarian cancer model based on three-dimensional agarose hydrogel. J Tissue Eng 5:2041731413520438

    CrossRef  Google Scholar 

  • Xu T et al (2013) Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. Biomaterials 34(1):130–139

    CrossRef  Google Scholar 

  • Xu T et al (2005) Inkjet printing of viable mammalian cells. Biomaterials 26(1):93–99

    CrossRef  Google Scholar 

  • Xu T et al (2006) Viability and electrophysiology of neural cell structures generated by the inkjet printing method. Biomaterials 27(19):3580–3588

    Google Scholar 

  • Xu X et al (2012) Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids. Biomaterials 33(35):9049–9060

    CrossRef  Google Scholar 

  • Xu Z et al (2013) Biomaterials Application of a micro fluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 34(16):4109–4117

    Google Scholar 

  • Yamada KM, Cukierman E (2007) Modeling tissue morphogenesis and cancer in 3D. Cell 130(4):601–610

    CrossRef  Google Scholar 

  • Yamada M et al (2015) Cell-sized condensed collagen microparticles for preparing microengineered composite spheroids of primary hepatocytes. Lab Chip 15(19):3941–3951

    CrossRef  Google Scholar 

  • Yang Y, Rossi FMV, Putnins EE (2007) Ex vivo expansion of rat bone marrow mesenchymal stromal cells on microcarrier beads in spin culture. Biomaterials 28(20):3110–3120

    CrossRef  Google Scholar 

  • Yang Z, Zhao X (2011) A 3D model of ovarian cancer cell lines on peptide nanofiber scaffold to explore the cell-scaffold interaction and chemotherapeutic resistance of anticancer drugs. Int J Nanomed 6:303–310

    CrossRef  Google Scholar 

  • Yuhas JM et al (1977) A simplified method for production and growth of multicellular tumor spheroids. Cancer Res 37:3639–3643

    Google Scholar 

  • Zanoni M et al (2016) 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained. Sci Rep 6(August 2015), p. 19103

    Google Scholar 

  • Zervantonakis IK et al (2012) Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci 109(34):13515–13520

    CrossRef  Google Scholar 

  • Zhao Y et al (2014) Three-dimensional printing of Hela cells for cervical tumor model in vitro. Biofabrication 6(3):035001

    Google Scholar 

  • Zhong H et al (1999) Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res 59(22):5830–5835

    Google Scholar 

  • Zhou Y et al (2011) Photopolymerized water-soluble chitosan-based hydrogel as potential use in tissue engineering. Int J Biol Macromol 48(3):408–413

    CrossRef  Google Scholar 

  • Zhu J (2010) Bioactive modification of Poly(ethylenglykol) Hydrogels for tissue engineering. Biomaterials 31(17):4639–4656

    CrossRef  Google Scholar 

  • Zhu J, Marchant RE (2011) Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices 8(5):607–626

    CrossRef  Google Scholar 

  • Zohora FT, Yousuf A, Anwarul M (2014) Inkjet printing: an emerging technology for 3D tissue or organ printing. Eur Sci J 10(30):339–352

    Google Scholar 

  • Zopf DA et al (2013) Bioresorbable airway splint created with a three-dimensional printer. New Engl J Med 368(21):2042–2043

    Google Scholar 

  • Zustiak SP (2015) The role of matrix compliance on cell responses to drugs and toxins: towards predictive drug screening platforms. Macromol Biosci 15(5):589–599

    Google Scholar 

  • Zustiak SP et al (2015) Three-dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins. Biotechnol Bioeng 113(2):443–452

    CrossRef  Google Scholar 

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Acknowledgement

NA would like to acknowledge the Department of Science and Technology, India for providing DST Inspire Faculty fellowship as well as All India Institute of Medical Sciences Bhopal, India as host institution. AF would like to acknowledge the University of South Australia as host institution.

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Arya, N., Forget, A. (2017). Biomaterials Based Strategies for Engineering Tumor Microenvironment. In: Tripathi, A., Melo, J. (eds) Advances in Biomaterials for Biomedical Applications. Advanced Structured Materials, vol 66. Springer, Singapore. https://doi.org/10.1007/978-981-10-3328-5_8

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