Engineered culture models for studies of tumor-microenvironment interactions

Annual Review of Biomedical Engineering

Volumn 15, Issue , 2013, Pages 29-53

  Infanger, David W ^a   Lynch, Maureen E ^a   Fischbach, Claudia ^a  

^a Cornell University   (United States)

Author keywords

3D culture; biomaterials; cancer; drug delivery; microfabrication; tissue engineering

Indexed keywords

3-D CULTURES; CANCER; CANCER PATHOGENESIS; CLINICAL STUDY; MICROENVIRONMENTS; THERAPEUTIC COMPOUNDS; TUMOR MICROENVIRONMENT; TUMOR MODELS;

BIOLOGICAL MATERIALS; BIOMATERIALS; CELL CULTURE; CELL SIGNALING; DISEASES; DRUG DELIVERY; MICROFABRICATION; MODELS; TISSUE ENGINEERING;

TUMORS;

BIOMATERIAL;

ACIDOSIS; ARTICLE; CANCER GROWTH; CARCINOGENESIS; CELL FUNCTION; CELL INTERACTION; CELL MIGRATION; CELL PROLIFERATION; EXTRACELLULAR MATRIX; FLUID FLOW; HUMAN; HYPOXIA; MECHANICAL STIMULATION; NONHUMAN; PHYSICAL CHEMISTRY; TISSUE ENGINEERING; TUMOR CELL; TUMOR MICROENVIRONMENT;

ACIDOSIS; ANIMALS; ANOXIA; BIOCOMPATIBLE MATERIALS; CELL CULTURE TECHNIQUES; EXTRACELLULAR MATRIX; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; SIGNAL TRANSDUCTION; STRESS, MECHANICAL; TISSUE ENGINEERING;

EID: 84880531962     PISSN: 15239829     EISSN: 15454274     Source Type: Book Series    
DOI: 10.1146/annurev-bioeng-071811-150028     Document Type: Article

References (180)

1. Paget S. 1889. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev. 8(2):98-101
2. Mintz B, Illmensee K. 1975. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl. Acad. Sci. USA 72(9):3585-89
3. Dolberg DS, Bissell MJ. 1984. Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309(5968):552-56
4. Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge JS, et al. 2007. Engineering tumors with 3D scaffolds. Nat. Methods 4(10):855-60
5. Kenny PA,Lee GY, MyersCA, Neve RM, Semeiks JR, et al. 2007. Themorphologies of breast cancer cell lines in three-Dimensional assays correlate with their profiles of gene expression. Mol. Oncol. 1(1):84-96
6. Wang F, WeaverVM,PetersenOW,Larabell CA,Dedhar S, et al. 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(25):14821-26
7. Hosseinkhani H, Hosseinkhani M, Tian F, Kobayashi H, Tabata Y. 2006. Osteogenic differentiation of mesenchymal stem cells in self-Assembled peptide-Amphiphile nanofibers. Biomaterials 27(22):4079-86
8. Rhodes NP, Srivastava JK, Smith RF, Longinotti C. 2004. Metabolic and histological analysis of mesenchymal stem cells grown in 3-D hyaluronan-based scaffolds. J. Mater. Sci. Mater. Med. 15(4):391-95
9. Jain RK, Duda DG, Clark JW, Loeffler JS. 2006. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat. Clin. Pract. Oncol. 3(1):24-40
10. Hartung T. 2008. Thoughts on limitations of animal models. Parkinsonism Relat. Disord. 14 (Suppl. 2):S81-83
11. Hanahan D,Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144(5):646-74
12. Jemal A, Siegel R, Xu J,Ward E. 2010. Cancer statistics. CA: Cancer J. Clin. 60(5):277-300
13. Weinberg RA. 2007. The Biology of Cancer. New York: Garland Science
14. Bissell MJ, Hines WC. 2011. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 17(3):320-29
15. Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, et al. 2004. TGF-βsignaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303(5659):848-51
16. Kaplan RN, Rafii S, Lyden D. 2006. Preparing the "soil": The premetastatic niche. Cancer Res. 66(23):11089-93
17. Hazan RB, Qiao R, Keren R, Badano I, Suyama K. 2004. Cadherin switch in tumor progression. Ann. N.Y. Acad. Sci. 1014:155-63
18. OtrantoM, Sarrazy V, Bonte F,Hinz B, Gabbiani G, et al. 2012. The role of the myofibroblast in tumor stroma remodeling. Cell Adhes. Migr. 6(3):203-19
19. Chandler EM, Seo BR, Califano JP, Andresen Eguiluz RC, Lee JS, et al. 2012. Implanted adipose progenitor cells as physicochemical regulators of breast cancer. Proc. Natl. Acad. Sci. USA 109(25):9786-91
20. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M. 2009. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139(5):891-906
21. Chandler EM, SaundersMP, Yoon CJ,Gourdon D, Fischbach C. 2011. Adipose progenitor cells increase fibronectin matrix strain and unfolding in breast tumors. Phys. Biol. 8(1):015008
22. Bridgman JF, Summerskill J, Buckler JMH, Hellman B, Rosen SM. 1975. Insulin and growth hormone secretion in the nephrotic syndrome. Q. J. Med. 44(173):115-23
23. Pathak A, Kumar S. 2012. Independent regulation of tumor cell migration by matrix stiffness and confinement. Proc. Natl. Acad. Sci. USA 109(26):10334-39
24. Shweiki D, Itin A, Soffer D, Keshet E. 1992. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359(6398):843-45
25. Kumar R, Kuniyasu H, Bucana CD, Wilson MR, Fidler IJ. 1998. Spatial and temporal expression of angiogenic molecules during tumor growth and progression. Oncol. Res. 10(6):301-11
26. Znati CA, Rosenstein M, Boucher Y, Epperly MW, Bloomer WD, et al. 1996. Effect of radiation on interstitial fluid pressure and oxygenation in a human tumor xenograft. Cancer Res. 56(5):964-68
27. McDonald DM, Baluk P. 2002. Significance of blood vessel leakiness in cancer. Cancer Res. 62(18):5381-85
28. DiResta GR, Nathan SS, Manoso MW, Casas-Ganem J, Wyatt C, et al. 2005. Cell proliferation of cultured human cancer cells are affected by the elevated tumor pressures that exist in vivo. Ann. Biomed. Eng. 33(9):1270-80
29. Nathan SS, DiResta GR, Casas-Ganem JE, Hoang BH, Sowers R, et al. 2005. Elevated physiologic tumor pressure promotes proliferation and chemosensitivity in human osteosarcoma. Clin. Cancer Res. 11(6):2389-97
30. Barkefors I, Le Jan S, Jakobsson L, Hejll E, Carlson G, et al. 2008. Endothelial cell migration in stable gradients of vascular endothelial growth factor A and fibroblast growth factor 2: Effects on chemotaxis and chemokinesis. J. Biol. Chem. 283(20):13905-12
31. Warburg O. 1956. On the origin of cancer cells. Science 123(3191):309-14
32. Boucher Y, Baxter LT, Jain RK. 1990. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: Implications for therapy. Cancer Res. 50(15):4478-84
33. Vaupel P, Kallinowski F, Okunieff P. 1989. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res. 49(23):6449-65
34. Shi Q, Le X, Wang B, Abbruzzese JL, Xiong Q, et al. 2001. Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene 20(28):3751-56
35. Fukumura D, Xu L, Chen Y, Gohongi T, Seed B, et al. 2001. Hypoxia and acidosis independently upregulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res. 61(16):6020-24
36. Elias AP, Dias S. 2008. Microenvironment changes (in pH) affect VEGF alternative splicing. Cancer Microenviron. 1(1):131-39
37. Wolf K, Friedl P. 2006. Molecular mechanisms of cancer cell invasion and plasticity. Br. J. Dermatol. 154(Suppl. 1):11-15
38. Wirtz D, Konstantopoulos K, Searson PC. 2011. The physics of cancer: The role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11(7):512-22
39. Orr FW, Wang HH, Lafrenie RM, Scherbarth S, Nance DM. 2000. Interactions between cancer cells and the endothelium in metastasis. J. Pathol. 190(3):310-29
40. Pathi SP, Kowalczewski C, Tadipatri R, Fischbach C. 2010. A novel 3-D mineralized tumor model to study breast cancer bone metastasis. PLoS One 5(1):e8849
41. Ruppender NS, Merkel AR, Martin TJ, Mundy GR, Sterling JA, et al. 2010. Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells. PLoS One 5(11):e15451
42. Pagnotti GM, Adler BJ, Green DE, Chan ME, Frechette DM, et al. 2012. Low magnitude mechanical signals mitigate osteopenia without compromising longevity in an aged murine model of spontaneous granulosa cell ovarian cancer. Bone 51(3):570-77
43. Erler JT, Bennewith KL, Cox TR, LangG, BirdD, et al. 2009. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15(1):35-44
44. Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, et al. 1997. Reversion of the malignant phenotype of human breast cells in three-Dimensional culture and in vivo by integrin blocking antibodies. J. Cell Biol. 137(1):231-45
45. Weaver VM, Lelièvre S, Lakins JN, ChrenekMA, Jones JCR, et al. 2002. β4 integrin-Dependent formation of polarized three-Dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2(3):205-16
46. Rizki A, Weaver VM, Lee SY, Rozenberg GI, Chin K, et al. 2008. A human breast cell model of preinvasive to invasive transition. Cancer Res. 68(5):1378-87
47. Fraley SI, Feng Y, Krishnamurthy R, Kim DH, Celedon A, et al. 2010. A distinctive role for focal adhesion proteins in three-Dimensional cell motility. Nat. Cell Biol. 12(6):598-604
48. Fischbach C, Kong HJ, Hsiong SX, Evangelista MB, Yuen W, et al. 2009. Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement. Proc. Natl. Acad. Sci. USA 106(2):399-404
49. Pickl M, Ries CH. 2009. Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab. Oncogene 28(3):461-8
50. Nelson CM, Chen CS. 2002. Cell-cell signaling by direct contact increases cell proliferation via a PI3Kdependent signal. FEBS Lett. 514(2-3):238-42
51. Tan CP, Seo BR, Brooks DJ, Chandler EM, Craighead HG, et al. 2009. Parylene peel-off arrays to probe the role of cell-cell interactions in tumour angiogenesis. Integr. Biol. (Camb.) 1(10):587-94
52. Shen CJ, Raghavan S, Xu Z, Baranski JD, Yu X, et al. 2011. Decreased cell adhesion promotes angiogenesis in a Pyk2-Dependent manner. Exp. Cell Res. 317(13):1860-71
53. Gray DS, Liu WF, Shen CJ, Bhadriraju K, Nelson CM, et al. 2008. Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton. Exp. Cell Res. 314(15):2846-54
54. Ryan PL, Foty RA, Kohn J, Steinberg MS. 2001. Tissue spreading on implantable substrates is a competitive outcome of cell-cell versus cell-substratum adhesivity. Proc. Natl. Acad. Sci. USA 98(8):4323-27
55. Mareel M, Vleminckx K, Vermeulen S, Bracke M, Van Roy F. 1992. E-cadherin expression: A counterbalance for cancer cell invasion. Bull. Cancer 79(4):347-55
56. Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, et al. 2010. Mechanical tugging force regulates the size of cell-cell junctions. Proc. Natl. Acad. Sci. USA 107(22):9944-49
57. Tang X, Ali MY, Saif MT. 2012. A novel technique for micro-patterning proteins and cells on polyacrylamide gels. Soft Matter 8(27):7197-206
58. Albrecht DR, Underhill GH,Wassermann TB, Sah RL, Bhatia SN. 2006. Probing the role of multicellular organization in three-Dimensional microenvironments. Nat. Methods 3(5):369-75
59. Fedorovich NE, Oudshoorn MH, van Geemen D, Hennink WE, Alblas J, et al. 2009. The effect of photopolymerization on stem cells embedded in hydrogels. Biomaterials 30(3):344-53
60. Hess R, Jaeschke A, Neubert H, Hintze V, Moeller S, et al. 2012. Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs. Biomaterials 33(35):8975-85
61. Huang C-W, Chen H-Y, Yen M-H, Chen JJW, Young T-H, Cheng J-Y. 2011. Gene expression of human lung cancer cell line CL1-5 in response to a direct current electric field. PLoS One 6(10):e25928
62. Hui EE, Bhatia SN. 2007. Micromechanical control of cell-cell interactions. Proc. Natl. Acad. Sci. USA 104(14):5722-26
63. LutolfMP, Doyonnas R,Havenstrite K, Koleckar K, Blau HM. 2009. Perturbation of single hematopoietic stem cell fates in artificial niches. Integr. Biol: Quant. Biosci. Nano Macro 1(1):59-69
64. PlodinecM, LoparicM,Monnier CA, Obermann EC, Zanetti-Dallenbach R, et al. 2012. The nanomechanical signature of breast cancer. Nat. Nanotechnol. 7(11):757-65
65. Andreasson-Ochsner M, Romano G, Hakanson M, Smith ML, Leckband DE, et al. 2011. Single cell 3-D platform to study ligand mobility in cell-cell contact. Lab Chip 11(17):2876-83
66. Friedl P, Wolf K. 2010. Plasticity of cell migration: A multiscale tuning model. J. Cell Biol. 188(1):11-19
67. Ochsner M, DusseillerMR, Grandin HM, Luna-Morris S, TextorM, et al. 2007. Micro-well arrays for 3D shape control and high resolution analysis of single cells. Lab Chip 7(8):1074-77
68. Kubow KE, Klotzsch E, Smith ML,Gourdon D, LittleWC, Vogel V. 2009. Crosslinking of cell-Derived 3D scaffolds up-regulates the stretching and unfolding of new extracellular matrix assembled by reseeded cells. Integr. Biol. 1(11-12):635-48
69. Cukierman E, Pankov R, Stevens DR, Yamada KM. 2001. Taking cell-matrix adhesions to the third dimension. Science 294(5547):1708-12
70. Anselme K, Ponche A, Bigerelle M. 2010. Relative influence of surface topography and surface chemistry on cell response to bone implant materials. Part 2: Biological aspects. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 224(12):1487-507
71. Ulrich TA, Jain A, Tanner K, MacKay JL, Kumar S. 2010. Probing cellular mechanobiology in threedimensional culture with collagen-Agarose matrices. Biomaterials 31(7):1875-84
72. Fischbach C, Mooney DJ. 2007. Polymers for pro-And anti-Angiogenic therapy. Biomaterials 28(12):2069-76
73. Benton G, Kleinman HK, George J, Arnaoutova, I. 2011. Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with cancer cells. Int. J. Cancer 128(8):1751-57
74. Kratzke RA, Shimizu E, Geradts J, Gerster JL, Segal S, et al. 1993. RB-mediated tumor suppression of a lung cancer cell line is abrogated by an extract enriched in extracellular matrix. Cell Growth Differ. 4(8):629-35
75. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, et al. 2005. Tensional homeostasis and the malignant phenotype. Cancer Cell 8(3):241-54
76. Guelcher SA, Sterling JA. 2011. Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer Microenviron. 4(3):247-59
77. Paszek MJ,Weaver VM. 2004. The tension mounts: Mechanics meets morphogenesis and malignancy. J. Mammary Gland Biol. Neoplasia 9(4):325-42
78. Hsiong SX, Huebsch N, Fischbach C, Kong HJ, Mooney DJ. 2008. Integrin-Adhesion ligand bond formation of preosteoblasts and stem cells in three-DimensionalRGDpresenting matrices. Biomacromolecules 9(7):1843-51
79. Rowe RG, Weiss SJ. 2008. Breaching the basement membrane: Who, when and how? Biophys. J. 18(11):560-74
80. Haga H, Irahara C, Kobayashi R, Nakagaki T, Kawabata K. 2005. Collective movement of epithelial cells on a collagen gel substrate. Biophys. J. 88(3):2250-56
81. Zeugolis DI, Paul RG, AttenburrowG. 2008. Factors influencing the properties of reconstituted collagen fibers prior to self-Assembly: Animal species and collagen extraction method. J. Biomed. Mater. Res. Part A 86(4):892-904
82. Friess W. 1998. Collagen -biomaterial for drug delivery. Eur. J. Pharmaceut. Biopharm. 45(2):113-36
83. Hanjaya-Putra D, Bose V, Shen YI, Yee J, Khetan S, et al. 2011. Controlled activation of morphogenesis to generate a functional human microvasculature in a synthetic matrix. Blood 118(3):804-15
84. Lutolf MP, Lauer-Fields JL, Schmoekel HG, Metters AT, Weber FE, et al. 2003. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cellinvasion characteristics. Proc. Natl. Acad. Sci. USA 100(9):5413-18
85. Toole BP. 2004. Hyaluronan: From extracellular glue to pericellular cue. Nat. Rev. Cancer 4(7):528-39
86. Roy R, Boskey A, Bonassar LJ. 2010. Processing of type I collagen gels using nonenzymatic glycation. J. Biomed. Mater. Res. Part A 93(3):843-51
87. Girton TS, Oegema TR, Tranquillo RT. 1999. Exploiting glycation to stiffen and strengthen tissue equivalents for tissue engineering. J. Biomed. Mater. Res. 46(1):87-92
88. Mason BN, Starchenko A, Williams RM, Bonassar LJ, Reinhart-King CA. 2013. Tuning threedimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior. Acta Biomater. 9(1):4635-44
89. Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, et al. 2002. Advanced glycation end products activate endothelium through signal-Transduction receptor RAGE: A mechanism for amplification of inflammatory responses. Circulation 105(7):816-22
90. Wierzbicka-Patynowski I, Mao Y, Schwarzbauer JE. 2007. Continuous requirement for pp60-Src and phospho-paxillin during fibronectin matrix assembly by transformed cells. J. Cell Physiol. 210(3):750-56
91. 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):7913-23
92. Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y. 2006. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp. Biol. Med. (Maywood) 231(1):20-27
93. Deryugina EI, Quigley JP. 2010. Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: Contrasting, overlapping and compensatory functions. Biochim. Biophys. Acta 1803(1):103-120
94. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, et al. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2(10):737-44
95. Kim J, Park Y, Tae G, Lee KB, Hwang SJ, et al. 2008. Synthesis and characterization of matrix metalloprotease sensitive-low molecular weight hyaluronic acid based hydrogels. J. Mater. Sci. Mater. Med. 19(11):3311-18
96. Wang YL, Pelham RJ Jr. 1998. Preparation of a flexible, porous polyacrylamide substrate for mechanical studies of cultured cells. Methods Enzymol. 298:489-96
97. Sieh S, Taubenberger AV, Rizzi SC, Sadowski M, Lehman ML, et al. 2012. Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment. PLoS One 7(9):e40217
98. Gill BJ,GibbonsDL, Roudsari LC, Saik JE, Rizvi ZH, 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):6013-23
99. Kraning-Rush CM, Califano JP, Reinhart-King CA. 2012. Cellular traction stresses increase with increasing metastatic potential. PLoS One 7(2):e32572
100. Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y, et al. 2012. Extracellular-matrix tethering regulates stem-cell fate. Nat. Mater. 11(7):642-49
101. Yang MT, Fu J, Wang YK, Desai RA, Chen CS. 2011. Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity. Nat. Protoc. 6(2):187-213
102. Leight JL,Wozniak MA, Chen S, Lynch ML, Chen CS. 2012. Matrix rigidity regulates a switch between TGF-β1-induced apoptosis and epithelial-mesenchymal transition. Mol. Biol. Cell 23(5):781-91
103. Brown AC, FioreVF, Sulchek TA, BarkerTH. 2013. Physical and chemical microenvironmental cues orthogonally control the degree and duration of fibrosis-Associated epithelial-To-mesenchymal transitions. J. Pathol. 229(1):25-35
104. Smith ML, Gourdon D, Little WC, Kubow KE, Eguiluz RA, et al. 2007. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 5(10):e268
105. Krammer A, Craig D, Thomas WE, Schulten K, Vogel V. 2002. A structural model for force regulated integrin binding to fibronectin's RGD-synergy site. Matrix Biol. 21(2):139-47
106. Shah PP, Fong MY, Kakar SS. 2012. PTTG inducesEMTthrough integrinαVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene 31(26):3124-35
107. Brown AC, Rowe JA, Barker TH. 2011. Guiding epithelial cell phenotypes with engineered integrinspecific recombinant fibronectin fragments. Tissue Eng. Part A 17(1-2):139-50
108. GuarnieriD,DeCapuaaA,Ventrea M, BorzacchiellobA,Pedonec C, et al. 2010. Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cellmigration parameters. Acta Biomater. 6(7):2532-39
109. Murphy WL, Kohn DH, Mooney DJ. 2000. Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffolds in vitro. J. Biomed. Mater. Res. 50(1):50-58
110. Pathi SP, Lin DD, Dorvee JR, Estroff LA, Fischbach C. 2011. Hydroxyapatite nanoparticle-containing scaffolds for the study of breast cancer bone metastasis. Biomaterials 32(22):5112-22
111. Fischbach C, Mooney DJ. 2006. Polymeric systems for bioinspired delivery of angiogenic molecules. Polym. Regen. Med. 203:191-221
112. Jain RA. 2000. The manufacturing techniques of various drug loaded biodegradable poly(lactide-coglycolide) (PLGA) devices. Biomaterials 21(23):2475-90
113. Richardson TP, Peters MC, Ennett AB, Mooney DJ. 2001. Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19(11):1029-34
114. Spink BC, Bennett JA, Pentecost BT, Lostritto N, EnglertNA, et al. 2009. Long-Term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol. Appl. Pharmacol. 240(3):355-66
115. Chen RR, Silva EA, Yuen WW, Brock AA, Fischbach C, et al. 2007. Integrated approach to designing growth factor delivery systems. FASEB J. 21(14):3896-903
116. Helm CL, Fleury ME, Zisch AH, Boschetti F, Swartz MA. 2005. Synergy between interstitial flow and VEGF directs capillary morphogenesis in vitro through a gradient amplification mechanism. Proc. Natl. Acad. Sci. USA 102(44):15779-84
117. Wylie RG, Shoichet MS. 2011. Three-Dimensional spatial patterning of proteins in hydrogels. Biomacromolecules 12(10):3789-96
118. Anderson SM, Shergill B, Barry ZT, Manousiouthakis E, Chen TT, et al. 2011. VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF. Integr. Biol. 3(9):887-96
119. YuenWW,Du NR, Chan CH, Silva EA, Mooney DJ. 2010. Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones. Proc. Natl. Acad. Sci. USA 107(42):17933-38
120. Kikuchi A, Okano T. 2002. Pulsatile drug release control using hydrogels. Adv. Drug Del. Rev. 54(1):53-77
121. Lee KY, Peters MC, Anderson KW, Mooney DJ. 2000. Controlled growth factor release from synthetic extracellular matrices. Nature 408(6815):998-1000
122. Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, et al. 2007. Microfluidic scaffolds for tissue engineering. Nat. Mater. 6(11):908-15
123. Ahmed T, Shimizu TS, Stocker R. 2010. Bacterial chemotaxis in linear and nonlinear steadymicrofluidic gradients. Nano Lett. 10(9):3379-85
124. Paszek MJ, Boettiger D, Weaver VM, Hammer DA. 2009. Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput. Biol. 5(12):e1000604
125. Miranti CK, Brugge JS. 2002. Sensing the environment: A historical perspective on integrin signal transduction. Nat. Cell Biol. 4(4):E83-90
126. Boontheekul T, Hill EE, Kong HJ, Mooney DJ. 2007. Regulating myoblast phenotype through controlled gel stiffness and degradation. Tissue Eng. 13(7):1431-42
127. Chandler EM, Berglund CM, Lee JS, Polacheck WJ, Gleghorn JP, et al. 2011. Stiffness of photocrosslinked RGD-Alginate gels regulates adipose progenitor cell behavior. Biotechnol. Bioeng. 108(7):1683-92
128. Silva EA, Kim ES, Kong HJ, Mooney DJ. 2008. Material-based deployment enhances efficacy of endothelial progenitor cells. Proc. Natl. Acad. Sci. USA 105(38):14347-52
129. Martino MM, Tortelli F, Mochizuki M, Traub S, Ben-David D, et al. 2011. Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci. Transl. Med. 3(100):100ra89
130. Mitsi M, Hong Z, Costello CE, Nugent MA. 2006. Heparin-mediated conformational changes in fibronectin expose vascular endothelial growth factor binding sites. Biochemistry 45(34):10319-28
131. SundararaghavanHG, Saunders RL,Hammer DA, Burdick JA. 2013. Fiber alignment directs cell motility over chemotactic gradients. Biotechnol. Bioeng. 110:1249-54
132. Simon MC, Keith B. 2008. The role of oxygen availability in embryonic development and stem cell function. Nat. Rev. Mol. Cell Biol. 9(4):285-96
133. Hockel M, Vaupel P. 2001. Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects. J. Natl. Cancer Inst. 93(4):266-76
134. Oppegard SC, Nam KH, Carr JR, Skaalure SC, Eddington DT. 2009. Modulating temporal and spatial oxygenation over adherent cellular cultures. PLoS One 4(9):e6891
135. Verbridge SS, Choi NW, Zheng Y, Brooks DJ, Stroock AD, Fischbach C. 2010. Oxygen-controlled three-Dimensional cultures to analyze tumor angiogenesis. Tissue Eng. Part A 16(7):2133-41
136. Derda R, Laromaine A, Mammoto A, Tang SK, Mammoto T, et al. 2009. Paper-supported 3D cell culture for tissue-based bioassays. Proc. Natl. Acad. Sci. USA 106(44):18457-62
137. Gillies RJ, Martinez-Zaguilan R, Martinez GM, Serranot R, Perona R. 1990. Tumorigenic 3T3 cells maintain an alkaline intracellular pH under physiological conditions. Proc. Natl. Acad. Sci. USA 87(19):7414-18
138. Stubbs M, Rodrigues L, Howe FA, Wang J, Jeong KS, et al.1994. Metabolic consequences of a reversed pH gradient in rat tumors. Cancer Res. 54(15):4011-16
139. De Milito A, Fais S. 2005. Tumor acidity, chemoresistance and proton pump inhibitors. Future Oncol. 1(6):779-86
140. Morita T, Nagaki T, Fukuda I, Okumura K.1992. Clastogenicity of low pH to various cultured mammalian cells. Mutat. Res. 268(2):297-305
141. Martinez-Zaguilan R, Seftor EA, Seftor RE, Chu YW, Gillies RJ, et al. 1996. Acidic pH enhances the invasive behavior of human melanoma cells. Clin. Exp. Metastasis 14(2):176-86
142. Goerges AL, Nugent MA. 2003. Regulation of vascular endothelial growth factor binding and activity by extracellular pH. J. Biol. Chem. 278(21):19518-25
143. Goerges AL, Nugent MA. 2004. pH regulates vascular endothelial growth factor binding to fibronectin: A mechanism for control of extracellular matrix storage and release. J. Biol. Chem. 279(3):2307-15
144. Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, et al. 2006. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440(7088):1222-26
145. Wong CC, Gilkes DM, Zhang H, Chen J, Wei H, et al. 2011. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc. Natl. Acad. Sci. USA 108(39):16369-74
146. Bruzewicz DA, McGuigan AP, Whitesides GM. 2008. Fabrication of a modular tissue construct in a microfluidic chip. Lab Chip 8(5):663-71
147. Chrobak KM, Potter DR, Tien J. 2006. Formation of perfused, functional microvascular tubes in vitro. Microvasc. Res. 71(3):185-96
148. Song JW, Munn LL. 2011. Fluid forces control endothelial sprouting. Proc. Natl. Acad. Sci. USA 108(37):15342-47
149. David MerrymanW, Engler AJ. 2010. Innovations in cell mechanobiology. J. Biomech. 43(1):1
150. Ma D, Lu H, Xu L, Xu X, Xiao W. 2009. Mechanical loading promotes Lewis lung cancer cell growth through periostin. In vitro cellular&developmental biology. In Vitro Cell. Dev. Biol. Animal 45(8):467-72
151. Wehner S, Buchholz BM, Schuchtrup S, Rocke A, Schaefer N, et al. 2010. Mechanical strain and TLR4 synergistically induce cell-specific inflammatory gene expression in intestinal smooth muscle cells and peritoneal macrophages. Am. J. Physiol. Gastrointest. Liver Physiol. 299(5):G1187-97
152. Tolman CJ, Vaid T, Schreuder HWR. 2012. Extremely elevated CA-125 in benign ovarian disease due to stretch of the peritoneum. BMJ Case Rep. doi:10.1136/bcr-2012-006664
153. Rhee S, Jiang H, Ho CH, Grinnell F. 2007. Microtubule function in fibroblast spreading is modulated according to the tension state of cell-matrix interactions. Proc. Natl. Acad. Sci. USA 104(13):5425-30
154. De Witt MT, Handley CJ, Oakes BW, Lowther DA. 1984. In vitro response of chondrocytes to mechanical loading: The effect of short term mechanical tension. Connect. Tissue Res. 12(2):97-109
155. Moraes C, Chen JH, Sun Y, Simmons CA. 2010. Microfabricated arrays for high-Throughput screening of cellular response to cyclic substrate deformation. Lab Chip 10(2):227-34
156. Shi ZD, Abraham G, Tarbell JM. 2010. Shear stress modulation of smooth muscle cell marker genes in 2-D and 3-D depends on mechanotransduction by heparan sulfate proteoglycans and ERK1/2. PLoS One 5(8):e12196
157. Fleury ME, Boardman KC, Swartz MA. 2006. Autologous morphogen gradients by subtle interstitial flow and matrix interactions. Biophys. J. 91(1):113-21
158. Folch A, Toner M. 2000. Microengineering of cellular interactions. Annu. Rev. Biomed. Eng. 2:227-56
159. Huh D, Hamilton GA, Ingber DE. 2011. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21(12):745-54
160. Zhu C, Yago T, Lou J, Zarnitsyna VI,McEver RP. 2008. Mechanisms for flow-enhanced cell adhesion. Ann. Biomed. Eng. 36(4):604-21
161. Chang KC, Hammer DA. 1999. The forward rate of binding of surface-Tethered reactants: Effect of relative motion between two surfaces. Biophys. J. 76(3):1280-92
162. Lim YC, Garcia-Cardena G, Allport JR, Zervoglos M, Connolly AJ, et al. 2003. Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment. Am. J. Pathol. 162(5):1591-601
163. Hida K, Hida Y, Amin DN, Flint AF, Panigrahy D, et al. 2004. Tumor-Associated endothelial cells with cytogenetic abnormalities. Cancer Res. 64(22):8249-55
164. Choe MM, Sporn PH, Swartz MA. 2006. Extracellular matrix remodeling by dynamic strain in a threedimensional tissue-engineered human airway wall model. Am. J. Respir. Cell Mol. Biol. 35(3):306-13
165. Bancroft GN, Sikavitsas VI, Mikos AG. 2003. Design of a flow perfusion bioreactor system for bone tissue-engineering applications. Tissue Eng. 9(3):549-54
166. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, et al. 2010. Reconstituting organlevel lung functions on a chip. Science 328(5986):1662-68
167. You L, Cowina SC, Schafflerb MB, Weinbaum S. 2001. A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J. Biomech. 34(11):1375-86
168. You L-D,Weinbaum S, Cowin SC, Schaffler MB. 2004. Ultrastructure of the osteocyte process and its pericellular matrix. Anat. Rec. Part A Discov. Mol. Cell. Evol. Biol. 278A(2):505-13
169. Fletcher DA, Mullins RD. 2010. Cell mechanics and the cytoskeleton. Nature 463(7280):485-92
170. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, et al. 2003. Cell migration: Integrating signals from front to back. Science 302(5651):1704-9
171. Kaplan RN, Riba RD,Zacharoulis S, BramleyAH, Vincent L, et al. 2005. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820-27
172. Esch MB, King TL, Shuler ML. 2011. The role of body-on-A-chip devices in drug and toxicity studies. Annu. Rev. Biomed. Eng. 13:55-72
173. Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, et al. 2010. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16:927-33
174. Visvader JE, Lindeman GJ. 2008. Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat. Rev. Cancer 8(10):755-68
175. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, et al. 2007. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235-39
176. KirbyBJ, JodariM,LoftusMS, Gakhar G, PrattED, et al. 2012. Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One 7(4):e35976
177. Bichsel CA, Gobaa S, Kobel S, Secondini C, Thalmann GN, et al. 2012. Diagnostic microchip to assay 3D colony-growth potential of captured circulating tumor cells. Lab Chip 12(13):2313-16
178. Haessler U, Teo JC, Foretay D, Renaud P, SwartzMA. 2012. Migration dynamics of breast cancer cells in a tunable 3D interstitial flow chamber. Integr. Biol. 4(4):401-9
179. Kloxin AM, Tibbitt MW, Anseth KS. 2010. Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nat. Protoc. 5(12):1867-87
180. Klotzsch E, Smith ML, Kubowa KE, Muntwyler S, LittleWC, et al. 2009. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl. Acad. Sci. USA 106(43):18267-72