Current Osteoporosis Reports

, Volume 15, Issue 4, pp 247–254 | Cite as

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

  • Kristin A. Kwakwa
  • Joseph P. Vanderburgh
  • Scott A. Guelcher
  • Julie A. SterlingEmail author
Cancer-induced Musculoskeletal Diseases (M Reagan and E Keller, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Cancer-induced Musculoskeletal Diseases


Purpose of Review

Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical.

Recent Findings

3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone.


3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.


3D models Bone tumors Bone 3D printing Tumor microenvironment 



This work was supported by 1I01BX001957 (JAS), 1R01CA163499 (SAG/JAS), 5R01 AR064772 (SAG), and 5T32CA009592 (KAK).

Compliance with Ethical Standards

Conflict of Interest

Kristin Kwakwa, Joseph Vanderburgh, Julie Sterling, and Scott Guelcher declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Ma XH, Piao S, Wang D, Mcafee QW, Nathanson KL, Lum JJ, et al. Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma. Clin Cancer Res. 2011;17:3478–89.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Lee JM, Mhawech-Fauceglia P, Lee N, Parsanian LC, Lin YG, Gayther SA, et al. A three-dimensional microenvironment alters protein expression and chemosensitivity of epithelial ovarian cancer cells in vitro. Lab Investig. 2013;93:528–42.PubMedGoogle Scholar
  3. 3.
    Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, et al. Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. Oncol Rep. 2015;33:1837–43.PubMedGoogle Scholar
  4. 4.
    Vantangoli MM, Madnick SJ, Huse SM, Weston P, Boekelheide K. MCF-7 human breast cancer cells form differentiated microtissues in scaffold-free hydrogels. PLoS One. 2015;10:1–20.Google Scholar
  5. 5.
    Härmä V, Virtanen J, Mäkelä R, Happonen A, Mpindi JP, Knuuttila M, et al. A comprehensive panel of three-dimensional models for studies of prostate cancer growth, invasion and drug responses. PLoS One. 2010;5:e10431.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Cichon MA, Gainullin VG, Zhang Y, Radisky DC. Growth of lung cancer cells in three-dimensional microenvironments reveals key features of tumor malignancy. Integr Biol. 2012;4:440–8.Google Scholar
  7. 7.
    Luca AC, Mersch S, Deenen R, Schmidt S, Messner I, Schäfer KL, et al. Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS One. 2013;8:e59689.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Sokol ES, Miller DH, Breggia A, Spencer KC, Arendt LM, Gupta PB. Growth of human breast tissues from patient cells in 3D hydrogel scaffolds. Breast Cancer Res. 2016;18:1–13.Google Scholar
  9. 9.
    Xu X, Gurski LA, Zhang C, Harrington DA, Farach-Carson MC, Jia X. Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids. Biomaterials. 2012;33:9049–60.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Szot CS, Buchanan CF, Freeman JW, Rylander MN. 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials. 2011;32:7905–12.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Riching KM, Cox BL, Salick MR, Pehlke C, Riching AS, Ponik SM, et al. 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Biophys J. 2014;107:2546–58.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005;15:378–86.PubMedGoogle Scholar
  13. 13.
    Lovitt CJ, Shelper TB, Avery VM. Evaluation of chemotherapeutics in a three-dimensional breast cancer model. J Cancer Res Clin Oncol. 2015;141:951–9.PubMedGoogle Scholar
  14. 14.
    Hughes CS, Postovit LM, Lajoie GA. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics. 2010;10:1886–90.PubMedGoogle Scholar
  15. 15.
    Chung IM, Enemchukwu NO, Khaja SD, Murthy N, Mantalaris A, García AJ. Bioadhesive hydrogel microenvironments to modulate epithelial morphogenesis. Biomaterials. 2008;29:2637–45.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Gurski LA, Petrelli NJ, Jia X, Farach-Carson MC. 3D matrices for anti-cancer drug testing and development. Oncol Issues. 2010;25:20–5.Google Scholar
  17. 17.
    Gill BJ, Gibbons DL, Roudsari LC, Saik JE, Rizvi ZH, Roybal JD, et al. A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model. Cancer Res. 2012;72:6013–23.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Del Bufalo F, Manzo T, Hoyos V, Yagyu S, Caruana I, Jacot J, et al. 3D modeling of human cancer: a PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus. Biomaterials. 2016;84:76–85.PubMedGoogle Scholar
  19. 19.
    Pradhan S, Hassani I, Seeto WJ, Lipke EA. PEG-fibrinogen hydrogels for three-dimensional breast cancer cell culture. J Biomed Mater Res Part A. 2017;105:236–52.Google Scholar
  20. 20.
    Feder-Mengus C, Ghosh S, Reschner A, Martin I, Spagnoli GC. New dimensions in tumor immunology: what does 3D culture reveal? Trends Mol Med. 2008;14:333–40.PubMedGoogle Scholar
  21. 21.
    Zanoni M, Piccinini F, Arienti C, Zamagni A, Santi S, Polico R, et al. 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained. Sci Rep. 2016;6:19103.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Court W, et al. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol. 2012;10:1–20.Google Scholar
  23. 23.
    Breslin S, O’Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today. 2013;18:240–9.PubMedGoogle Scholar
  24. 24.
    Yip D, Cho CH. A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Biochem Biophys Res Commun. 2013;433:327–32.PubMedGoogle Scholar
  25. 25.
    Tung Y-C, Hsiao AY, Allen SG, Torisawa Y, Ho M, Takayama S. High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst. 2011;136:473–8.PubMedGoogle Scholar
  26. 26.
    Amann A, Zwierzina M, Gamerith G, Bitsche M, Huber JM, Vogel GF, et al. Development of an innovative 3D cell culture system to study tumour—stroma interactions in non-small cell lung cancer cells. PLoS One. 2014;9:e92511.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Raghavan S, Ward MR, Rowley KR, Wold RM, Takayama S, Buckanovich RJ, et al. Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays. Gynecol Oncol. 2015;138:181–9.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Raghavan S, Mehta P, Horst EN, Ward MR, Rowley KR, Mehta G. Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity. Oncotarget. 2016;7:16948–61.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Aboulafia AJ, Levine AM, Schmidt D, Aboulafia D. Surgical therapy of bone metastases. Semin Oncol. 2007;34:206–14.PubMedGoogle Scholar
  30. 30.
    Johnson RW, Schipani E, Giaccia AJ. HIF targets in bone remodeling and metastatic disease. Pharmacol Ther. 2015;150:169–77.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Guelcher SA, Sterling JA. Contribution of bone tissue modulus to breast cancer metastasis to bone. Cancer Microenviron. 2011;4:247–59.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Page JM, Merkel AR, Ruppender NS, Guo R, Dadwal UC, Cannonier SA, et al. Matrix rigidity regulates the transition of tumor cells to a bone-destructive phenotype through integrin β3 and TGF-β receptor type II. Biomaterials. 2015;64:33–44.PubMedPubMedCentralGoogle Scholar
  33. 33.
    García-Alvarez R, Izquierdo-Barba I, Vallet-Regí M. 3D scaffold with effective multidrug sequential release against bacteria biofilm. Acta Biomater. 2016;49:113–26.PubMedGoogle Scholar
  34. 34.
    Sundelacruz S, Li C, Choi YJ, Levin M, Kaplan DL. Bioelectric modulation of wound healing in a 3D invitro model of tissue-engineered bone. Biomaterials. 2013;34:6695–705.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Lee JH, Gu Y, Wang H, Lee WY. Microfluidic 3D bone tissue model for high-throughput evaluation of wound-healing and infection-preventing biomaterials. Biomaterials. 2012;33:999–1006.PubMedGoogle Scholar
  36. 36.
    Chatterjee K, Lin-Gibson S, Wallace WE, Parekh SH, Lee YJ, Cicerone MT, et al. The effect of 3D hydrogel scaffold modulus on osteoblast differentiation and mineralization revealed by combinatorial screening. Biomaterials. 2010;31:5051–62.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Guo R, Lu S, Page JM, Merkel AR, Basu S, Sterling JA, et al. Fabrication of 3D scaffolds with precisely controlled substrate modulus and pore size by templated-fused deposition modeling to direct osteogenic differentiation. Adv Healthc Mater. 2015;4:1826–32.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Sun L, Parker ST, Syoji D, Wang X, Lewis JA, Kaplan DL. Direct-write assembly of 3D silk/hydroxyapatite scaffolds for bone co-cultures. Adv Healthc Mater. 2012;1:729–35.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Bidan CM, Kommareddy KP, Rumpler M, Kollmannsberger P, Fratzl P, Dunlop JWC. Geometry as a factor for tissue growth: towards shape optimization of tissue engineering scaffolds. Adv Healthc Mater. 2013;2:186–94.PubMedGoogle Scholar
  40. 40.
    Gamsjager E, Bidan CM, Fischer FD, Fratzl P, Dunlop JWC. Modelling the role of surface stress on the kinetics of tissue growth in confined geometries. Acta Biomater. 2013;9:5531–43.PubMedGoogle Scholar
  41. 41.
    Sterling JA, Guelcher SA. Bone structural components regulating sites of tumor metastasis. Curr Osteoporos Rep. 2011;9:89–95.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Yamada KM, Cukierman E. Modeling tissue morphogenesis and cancer in 3D. Cell. 2007;130:601–10.PubMedGoogle Scholar
  43. 43.
    Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge JS, Polverini PJ, et al. Engineering tumors with 3D scaffolds. Nat Methods. 2007;4:855–60.PubMedGoogle Scholar
  44. 44.
    Schuessler TK, Chan XY, Chen HJ, Ji K, Park KM, Roshan-Ghias A, et al. Biomimetic tissue-engineered systems for advancing cancer research: NCI strategic workshop report. Cancer Res. 2014;74:5359–63.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Temple JP, Hutton DL, Hung BP, Huri PY, Cook CA, Kondragunta R, et al. Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds. J Biomed Mater Res Part A. 2014;102:4317–25.Google Scholar
  46. 46.
    Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials. 2005;26:4817–27.PubMedGoogle Scholar
  47. 47.
    Petrie Aronin CE, Cooper JA, Sefcik LS, Tholpady SS, Ogle RC, Botchwey EA. Osteogenic differentiation of dura mater stem cells cultured in vitro on three-dimensional porous scaffolds of poly(epsilon-caprolactone) fabricated via co-extrusion and gas foaming. Acta Biomater. 2008;4:1187–97.PubMedGoogle Scholar
  48. 48.
    Guillaume O, Geven MA, Sprecher CM, Stadelmann VA, Grijpma DW, Tang TT, et al. Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair. Acta Biomater. 2017;54:386–98.PubMedGoogle Scholar
  49. 49.
    Gay S, Arostegui S, Lemaitre J. Preparation and characterization of dense nanohydroxyapatite/PLLA composites. Mater Sci Eng C. 2009;29:172–7.Google Scholar
  50. 50.
    Grinberg O, Binderman I, Bahar H, Zilberman M. Highly porous bioresorbable scaffolds with controlled release of bioactive agents for tissue-regeneration applications. Acta Biomater Acta Materialia Inc. 2010;6:1278–87.Google Scholar
  51. 51.
    Horning JL, Sahoo SK, Vijayaraghavalu S, Dimitrijevic S, Vasir JK, Jain TK, et al. 3-D tumor model for in vitro evaluation of anticancer drugs. Mol Pharm. 2008;5:849–62.PubMedGoogle Scholar
  52. 52.
    Zhang P, Wu H, Wu H, Lù Z, Deng C, Hong Z, et al. RGD-conjugated copolymer incorporated into composite of poly(lactide-co-glycotide) and poly(L-lactide)-grafted nanohydroxyapatite for bone tissue engineering. Biomacromolecules. 2011;12:2667–80.PubMedGoogle Scholar
  53. 53.
    Guelcher SA. Biodegradable polyurethanes: synthesis and applications in regenerative medicine. Tissue Eng Part B Rev. 2008;14:3–17.PubMedGoogle Scholar
  54. 54.
    Temenoff JS, Mikos AG. Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials. 2000;21:2405–12.PubMedGoogle Scholar
  55. 55.
    Kim K, Dean D, Mikos AG, Fisher JP. Effect of initial cell seeding density on early osteogenic signal expression of rat bone marrow stromal cells cultured on cross-linked poly(propylene fumarate) disks. Biomacromolecules. 2009;10:1810–7.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008;3:S131–9.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Chattopadhyay S, Raines RT. Collagen-based biomaterials for wound healing. Biopolymers. 2015;101:821–33.Google Scholar
  58. 58.
    Reagan MR, Mishima Y, Glavey SV, Zhang Y, Manier S, Lu ZN, et al. Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model. Blood. 2014;124:3250–9.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Vepari C, Kaplan DL. Silk as a biomaterial. Prog Polym Sci. 2007;32:991–1007.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Kwon H, Kim HJ, Rice WL, Subramanian B, Park S, Georgakoudi I, et al. Development of an in vitro model to study the impact of BMP-2 on metastasis to bone. J Tissue Eng Regen Med. 2010;4:590–9.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Mastro AM, Vogler EA. A three-dimensional osteogenic tissue model for the study of metastatic tumor cell interactions with bone. Cancer Res. 2009;69:4097–100.PubMedGoogle Scholar
  62. 62.
    Thein-Han W, Xu HHK. Prevascularization of a gas-foaming macroporous calcium phosphate cement scaffold via coculture of human umbilical vein endothelial cells and osteoblasts. Tissue Eng Part A. 2013;19:1675–85.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Annabi N, Fathi A, Mithieux SM, Martens P, Weiss AS, Dehghani F. The effect of elastin on chondrocyte adhesion and proliferation on poly (epsilon-caprolactone)/elastin composites. Biomaterials Elsevier Ltd. 2011;32:1517–25.Google Scholar
  64. 64.
    Akar B, Jiang B, Somo SI, Appel AA, Larson JC, Tichauer KM, et al. Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation. Biomaterials. 2015;72:61–73.PubMedGoogle Scholar
  65. 65.
    Zhang J, Zhou H, Yang K, Yuan Y, Liu C. RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration. Biomaterials. 2013;34:9381–92.PubMedGoogle Scholar
  66. 66.
    Fereshteh Z, Fathi M, Bagri A, Boccaccini AR. Preparation and characterization of aligned porous PCL/zein scaffolds as drug delivery systems via improved unidirectional freeze-drying method. Mater Sci Eng C. 2016;68:613–22.Google Scholar
  67. 67.
    Vanderburgh J, Sterling JA, Guelcher SA. 3D printing of tissue engineered constructs for in vitro modeling of disease progression and drug screening. Ann Biomed Eng. 2016;1–16.Google Scholar
  68. 68.
    Hutmacher DW, Schantz T, Zein I, Ng KW, Teoh SH, Tan KC. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J Biomed Mater Res. 2001;55:203–16.PubMedGoogle Scholar
  69. 69.
    Guo R, Merkel AR, Sterling JA, Davidson JM, Guelcher SA. Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling. Biomaterials. 2015;73:85–95.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Lee S-J, Nowicki M, Harris B, Zhang LG. Fabrication of a highly aligned neural scaffold via a table top stereolithography 3D printing and electrospinning. Tissue Eng Part A. 2017;Google Scholar
  71. 71.
    Li G, Cuidi L, Fangping C, Changsheng L. Fabrication and characterization of toughness-enhanced scaffolds comprising beta-TCP/POC using the freeform fabrication system with micro-droplet jetting. Biomed Mater. 2015;10:35009.Google Scholar
  72. 72.
    Kundu J, Shim JH, Jang J, Kim SW, Cho DW. An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering. J Tissue Eng Regen Med. 2015;9:1286–97.PubMedGoogle Scholar
  73. 73.
    Kang HW, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. 2016;34:312–9.Google Scholar
  74. 74.
    Bancroft GN, Sikavitsas VI, van den Dolder J, Sheffield TL, Ambrose CG, Jansen JA, et al. Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci U S A. 2002;99:12600–5.PubMedPubMedCentralGoogle Scholar
  75. 75.
    • Krishnan V, Vogler EA, Mastro AM. Three-dimensional in vitro model to study osteobiology and osteopathology. J Cell Biochem. 2015;116:2715–23. This study uses a 3D bioreactor tri-culture model to demonstrate that tumor cells migrate towards sites of active bone remodeling which results in further degradation of osteoid matrix. PubMedGoogle Scholar
  76. 76.
    Talukdar S, Nguyen QT, Chen AC, Sah RL, Kundu SC. Effect of initial cell seeding density on 3D-engineered silk fibroin scaffolds for articular cartilage tissue engineering. Biomaterials. 2011;32:8927–37.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Talukdar S, Kundu SC. Engineered 3D silk-based metastasis models: interactions between human breast adenocarcinoma, mesenchymal stem cells and osteoblast-like cells. Adv Funct Mater. 2013;23:5249–60.Google Scholar
  78. 78.
    Mastro AM, Gay CV, Welch DR, Donahue HJ, Jewell J, Mercer R, et al. Breast cancer cells induce osteoblast apoptosis: a possible contributor to bone degradation. J Cell Biochem. 2004;91:265–76.PubMedGoogle Scholar
  79. 79.
    • Subia B, Dey T, Sharma S, Kundu SC. Target specific delivery of anticancer drug in silk fibroin based 3D distribution model of bone–breast cancer cells. ACS Appl Mater Interfaces. 2015;7:2269–79. This study reports that the viability, invasiveness, and angiogenic potential of cancer cells co-cultured with osteoblasts on silk scaffolds significantly decreases after nanoparticle-targeted delivery of doxorubicin; osteoblasts were mostly unaffected by treatment. PubMedGoogle Scholar
  80. 80.
    • Lynch ME, Chiou AE, Lee MJ, Marcott SC, Polamraju PV, Lee Y, et al. Three-dimensional mechanical loading modulates the osteogenic response of mesenchymal stem cells to tumor-derived soluble signals. Tissue Eng Part A. 2016;22:1006–15. This paper emphasizes the important role that mechanical stress plays on osteogenic cells cultured on HA-containing scaffolds in the presence of tumor-conditioned media. PubMedPubMedCentralGoogle Scholar
  81. 81.
    • Zhu W, Holmes B, Glazer RI, Zhang LG. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis. Nanomedicine Nanotechnol Biol Med. 2016;12:69–79. This study utilizes a novel stereolithography-based 3D printer to fabricate nanohydroxyapatite scaffolds that promote tumor spheroid formation, proliferation, and migration; tumor cells also exhibit more chemoresistance on 3D scaffolds. Google Scholar
  82. 82.
    Wang Y, Pivonka P, Buenzli PR, Smith DW, Dunstan CR. Computational modeling of interactions between multiple myeloma and the bone microenvironment. PLoS One. 2011;6:e27494.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Araujo A, Cook LM, Lynch CC, Basanta D. An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer. Cancer Res. 2014;14:2391–401.Google Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2017

Authors and Affiliations

  • Kristin A. Kwakwa
    • 1
    • 2
    • 3
  • Joseph P. Vanderburgh
    • 1
    • 2
    • 4
  • Scott A. Guelcher
    • 2
    • 4
    • 5
    • 6
  • Julie A. Sterling
    • 1
    • 2
    • 3
    • 5
    • 6
    Email author
  1. 1.Department of Veterans AffairsTennessee Valley Healthcare SystemNashvilleUSA
  2. 2.Vanderbilt Center for Bone BiologyVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of Cancer BiologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of Chemical and Biomolecular EngineeringVanderbilt UniversityNashvilleUSA
  5. 5.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  6. 6.Department of Medicine, Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleUSA

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