Skip to main content
×
×
Home

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

  • Samantha E. Holt (a1), E. Sally Ward (a2), Raimund J. Ober (a1) (a2) and Daniel L. Alge (a1) (a3)
Abstract
Abstract

Tissue engineering holds great promise for advancing cancer research and achieving the goals of the Cancer Moonshot by providing better models for basic research and testing novel therapeutics. This paper focuses on the use of hydrogel biomaterials due to their unique ability to entrap cells in three-dimensional (3D) matrix that mimics tissues and can be programmed with physical and chemical cues to recreate key aspects of tumor microenvironments. The chemistry of some commonly used hydrogel platforms is discussed, and important examples of their use in tissue engineering 3D cancer models are highlighted. Challenges and opportunities for future research are also discussed.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics
      Available formats
      ×
Copyright
Corresponding author
Address all correspondence to D. L. Alge at dalge@tamu.edu
References
Hide All
1. Hanahan D. and Weinberg R.A.: Hallmarks of cancer: the next generation. Cell 144, 646 (2011).
2. Schuessler T.K., Chan X.Y., Chen H.J., Ji K., Park K.M., Roshan-Ghias A., Sethi P., Thakur A., Tian X., Villasante A., Zervantonakis I.K., Moore N.M., Nagahara L.A., and Kuhn N.Z.: Biomimetic tissue-engineered systems for advancing cancer research: NCI strategic workshop report. Cancer Res. 74, 5359 (2014).
3. Hahn W.C., Stewart S.A., Brooks M.W., York S.G., Eaton E., Kurachi A., Beijersbergen R.L., Knoll J.H.M., Meyerson M., and Weinberg R.A.: Inhibition of telomerase limits the growth of human cancer cells. Nat. Med. 5, 1164 (1999).
4. Leight J.L., Wozniak M.A., Chen S., Lynch M.L., and Chen C.S.: Matrix rigidity regulates a switch between TGF-β1-induced apoptosis and epithelial-mesenchymal transition. Mol. Biol. Cell 23, 781 (2012).
5. Heyer J., Kwong L.N., Lowe S.W., and Chin L.: Non-germline genetically engineered mouse models for translational cancer research. Nat. Rev. Cancer 10, 470 (2010).
6. Sharpless N.E. and DePinho R.A.: The mighty mouse: genetically engineered mouse models in cancer drug development. Nat. Rev. Drug Discov. 5, 741 (2006).
7. Rangarajan A. and Weinberg R.A.: Comparative biology of mouse versus human cells: modelling human cancer in mice. Nat. Rev. Cancer 3, 952 (2003).
8. Mak I.W.Y., Evaniew N., and Ghert M.: Lost in translation: animal models and clinical trials in cancer treatment. Am. J. Transl. Res. 6, 114 (2014).
9. Petersen O.W., Rønnov-Jessen L., Howlett A.R., and Bissell M.J.: Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 89, 9064 (1992).
10. Debnath J., Muthuswamy S.K., and Brugge J.S.: Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30, 256 (2003).
11. Albini A., Iwamoto I., Kleinman H.K., Martin G.R., Aaronson S.A., Kozlowski J.M., and McEwan R.N.: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 47, 3239 (1987).
12. Hughes C.S., Postovit L.M., and Lajoie G.A.: Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886 (2010).
13. Hoffman A.S.: Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 64, 18 (2012).
14. Magin C.M., Alge D.L., and Anseth K.S.: Bio-inspired 3D microenvironments: a new dimension in tissue engineering. Biomed. Mater. 11, 22001 (2016).
15. Azagarsamy M.A. and Anseth K.S.: Bioorthogonal click chemistry: an indispensable tool to create multifaceted cell culture scaffolds. ACS Macro Lett. 2, 5 (2013).
16. Nguyen K.T. and West J.L.: Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23, 4307 (2002).
17. Lee K.Y. and Mooney D.J.: Hydrogels for tissue engineering. Chem. Rev. 101, 1869 (2001).
18. Fairbanks B.D., Schwartz M.P., Bowman C.N., and Anseth K.S.: Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials 30, 6702 (2009).
19. Nimmo C.M. and Shoichet M.S.: Regenerative biomaterials that “click”: simple, aqueous-based protocols for hydrogel synthesis, surface immobilization, and 3D patterning. Bioconjug. Chem. 22, 2199 (2011).
20. Lin C.-C., Raza A., and Shih H.: PEG hydrogels formed by thiol-ene photo-click chemistry and their effect on the formation and recovery of insulin-secreting cell spheroids. Biomaterials 32, 9685 (2011).
21. Shubin A.D., Felong T.J., Graunke D., Ovitt C.E., and Benoit D.S.W.: Development of poly(ethylene glycol) hydrogels for salivary gland tissue engineering applications. Tissue Eng. A 21, 1733 (2015).
22. Parenteau-Bareil R., Gauvin R., and Berthod F.: Collagen-based biomaterials for tissue engineering applications. Materials (Basel) 3, 1863 (2010).
23. Loessner D., Meinert C., Kaemmerer E., Martine L.C., Yue K., Levett P.A., Klein T.J., Melchels F.P.W., Khademhosseini A., and Hutmacher D.W.: Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms. Nat. Protoc. 11, 727 (2016).
24. Xu X., Jha A.K., Harrington D.A., Farach-Carson M.C., and Jia X.: Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks. Soft Matter 8, 3280 (2012).
25. Augst A.D., Kong H.J., and Mooney D.J.: Alginate hydrogels as biomaterials. Macromol. Biosci. 6, 623 (2006).
26. Jeon O., Bouhadir K.H., Mansour J.M., and Alsberg E.: Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties. Biomaterials 30, 2724 (2009).
27. Zhu J.: Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31, 4639 (2010).
28. Lutolf M.P., Lauer-Fields J.L., Schmoekel H.G., Metters T., Weber F.E., Fields G.B., and Hubbell J.: Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. U. S. A. 100, 5413 (2003).
29. Phelps E.A., Enemchukwu N.O., Fiore V.F., Sy J.C., Murthy N., Sulchek T.A., Barker T.H., and Garcia A.J.: Maleimide cross-linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross-linking for cell encapsulation and in situ delivery. Adv. Mater. 24, 64 (2012).
30. Rydholm A.E., Anseth K.S., and Bowman C.N.: Effects of neighboring sulfides and pH on ester hydrolysis in thiol-acrylate photopolymers. Acta Biomater. 3, 449 (2007).
31. Fairbanks B.D., Schwartz M.P., Halevi A.E., Nuttelman C.R., Bowman C.N., and Anseth K.S.: A versatile synthetic extracellular matrix mimic via Thiol-Norbornene photopolymerization. Adv. Mater. 21, 5005 (2009).
32. Gill B.J., Gibbons D.L., Roudsari L.C., Saik J.E., Rizvi Z.H., Roybal J.D., Kurie J.M., and West J.L.: A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model. Cancer Res. 72, 6013 (2012).
33. Roudsari L.C., Jeffs S.E., Witt A.S., Gill B.J., and West J.L.: A 3D poly(ethylene glycol)-based tumor angiogenesis model to study the influence of vascular cells on lung tumor cell behavior. Sci. Rep. 6, 32726 (2016).
34. Ki C.S., Lin T.-Y., Korc M., and Lin C.-C.: Thiol-ene hydrogels as desmoplasia-mimetic matrices for modeling pancreatic cancer cell growth, invasion, and drug resistance. Biomaterials 35, 9668 (2014).
35. Liang Y., Jeong J., DeVolder R.J., Cha C., Wang F., Tong Y.W., and Kong H.: A cell-instructive hydrogel to regulate malignancy of 3D tumor spheroids with matrix rigidity. Biomaterials 32, 9308 (2011).
36. Xu X., Liu C., Liu Y., Li N., Guo X., Wang S., Sun G., Wang W., and Ma X.: Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model. Exp. Cell Res. 319, 2135 (2013).
37. Lin T.-Y., Ki C.S., and Lin C.-C.: Manipulating hepatocellular carcinoma cell fate in orthogonally cross-linked hydrogels. Biomaterials 35, 6898 (2014).
38. Fischbach C., Kong H.J., Hsiong S.X., Evangelista M.B., Yuen W., and Mooney D.J.: Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement. Proc. Natl. Acad. Sci. U. S. A. 106, 399 (2009).
39. Sieh S., Taubenberger A.V., Rizzi S.C., Sadowski M., Lehman M.L., Rockstroh A., An J., Clements J.A., Nelson C.C., and Hutmacher D.W.: Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment. PLoS ONE 7, e40217 (2012).
40. Xu X., Gurski L.A., Zhang C., Harrington D.A., Farach-Carson M.C., and Jia X.: Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids. Biomaterials 33, 9049 (2012).
41. Loessner D., Stok K.S., Lutolf M.P., Hutmacher D.W., Clements J.A., and Rizzi S.C.: Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials 31, 8494 (2010).
42. Yang Z. and Zhao X.: 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. 5, 303 (2011).
43. Kaemmerer E., Melchels F.P.W., Holzapfel B.M., Meckel T., Hutmacher D.W., and Loessner D.: Gelatine methacrylamide-based hydrogels: an alternative three-dimensional cancer cell culture system. Acta Biomater. 10, 2551 (2014).
44. Holmes D.: The cancer that rises with the Sun. Nature 515, S110 (2014).
45. Glazer A.M., Winkelmann R.R., Farberg A.S., and Rigel D.S.: Analysis of trends in US melanoma incidence and mortality. JAMA Dermatol. 153, 225 (2017).
46. Reed K.B., Brewer J.D., Lohse C.M., Bringe K.E., Pruitt C.N., and Gibson L.E.: Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin. Proc. 87, 328 (2012).
47. Tokuda E.Y., Leight J.L., and Anseth K.S.: Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness. Biomaterials 35, 4310 (2014).
48. Singh S.P., Schwartz M.P., Tokuda E.Y., Luo Y., Rogers R.E., Fujita M., Ahn N.G., and Anseth K.S.: A synthetic modular approach for modeling the role of the 3D microenvironment in tumor progression. Sci. Rep. 5, 1 (2015).
49. Tokuda E.Y., Jones C.E., and Anseth K.S.: PEG-peptide hydrogels reveal differential effects of matrix microenvironmental cues on melanoma drug sensitivity. Integr. Biol. 9, 76 (2017).
50. Kalluri R. and Zeisberg M.: Fibroblasts in cancer. Nat. Rev. Cancer 6, 392 (2006).
51. Leight J.L., Tokuda E.Y., Jones C.E., Lin A.J., and Anseth K.S.: Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition. Proc. Natl. Acad. Sci. U. S. A. 112, 5366 (2015).
52. Sosman J.A., Kim K.B., Schuchter L., Gonzalez R., Pavlick A.C., Weber J.S., McArthur G.A., Hutson T.E., Moschos S.J., Flaherty K.T., Hersey P., Kefford R., Lawrence D., Puzanov I., Lewis K.D., Amaravadi R.K., Chmielowski B., Lawrence H.J., Shyr Y., Ye F., Li J., Nolop K.B., Lee R.J., Joe A.K., and Ribas A.: Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N. Engl. J. Med. 366, 707 (2012).
53. Thakkar J.P., Dolecek T.A., Horbinski C., Ostrom Q.T., Lightner D.D., Barnholtz-Sloan J.S., and Villano J.L.: Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol. Biomark. Prev. 23, 1985 (2014).
54. Omuro A.M.P., Faivre S., and Raymond E.: Lessons learned in the development of targeted therapy for malignant gliomas. Mol. Cancer Ther. 6, 1909 (2007).
55. Ulrich T.A., de Juan Pardo E.M., and Kumar S.: The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. Cancer Res. 69, 4167 (2009).
56. Pathak A. and Kumar S.: Independent regulation of tumor cell migration by matrix stiffness and confinement. Proc. Natl. Acad. Sci. U. S. A. 109, 10334 (2012).
57. Verbridge S.S., Choi N.W., Zheng Y., Brooks D.J., Stroock A.D., and Fischbach C.: Oxygen-controlled three-dimensional cultures to analyze tumor angiogenesis. Tissue Eng. A 16, 2133 (2010).
58. Nguyen D.T., Fan Y., Akay Y.M., and Akay M.: Investigating glioblastoma angiogenesis using a 3D in vitro GelMA microwell platform. IEEE Trans. Nanobiosci. 15, 289 (2016).
59. Nguyen D.T., Fan Y., Akay Y.M., and Akay M.: TNP-470 reduces glioblastoma angiogenesis in three dimensional GelMA microwell platform. IEEE Trans. Nanobiosci. 15, 683 (2016).
60. Ananthanarayanan B., Kim Y., and Kumar S.: Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform. Biomaterials 32, 7913 (2011).
61. Rao S.S., DeJesus J., Short A.R., Otero J.J., Sarkar A., and Winter J.O.: Glioblastoma behaviors in three-dimensional collagen-hyaluronan composite hydrogels. ACS Appl. Mater. Interfaces 5, 9276 (2013).
62. Pedron S., Becka E., and Harley B.A.C.: Regulation of glioma cell phenotype in 3D matrices by hyaluronic acid. Biomaterials 34, 7408 (2013).
63. Pedron S., Becka E., and Harley B.A.: Spatially gradated hydrogel platform as a 3D engineered tumor microenvironment. Adv. Mater. 27, 1567 (2015).
64. Pedron S. and Harley B.A.C.: Impact of the biophysical features of a 3D gelatin microenvironment on glioblastoma malignancy. J. Biomater. Res. A 101A, 3404 (2013).
65. Wang C., Tong X., and Yang F.: Bioengineered 3D brain tumor model to elucidate the effects of matrix stiffness on glioblastoma cell behavior using PEG-based hydrogels. Mol. Pharm. 11, 2115 (2014).
66. Wang C., Tong X., Jiang X., and Yang F.: Effect of matrix metalloproteinase-mediated matrix degradation on glioblastoma cell behavior in 3D PEG-based hydrogels. J. Biomed. Mater. Res. A 105A, 770 (2017).
67. Jiguet Jiglaire C., Baeza-Kallee N., Denicolaï E., Barets D., Metellus P., Padovani L., Chinot O., Figarella-Branger D., and Fernandez C.: Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening. Exp. Cell Res. 321, 99 (2014).
68. Siegel R.L., Miller K.D., and Jemal A.: Cancer statistics, 2016. CA. Cancer J. Clin. 66, 7 (2016).
69. Woolston C.: Breast cancer. Nature 527, S101 (2015).
70. Bleyer A. and Welch H.G.: Effect of three decades of screening mammography on breast-cancer incidence. N. Engl. J. Med. 367, 1998 (2012).
71. Pradhan S., Hassani I., Seeto W.J., and Lipke E.A.: PEG-fibrinogen hydrogels for three-dimensional breast cancer cell culture. J. Biomed. Mater. Res. A 105A, 236 (2017).
72. Kenny P.A., Lee G.Y., Myers C.A., Neve R.M., Semeiks J.R., Spellman P.T., Lorenz K., Lee E.H., Barcellos-Hoff M.H., Petersen O.W., Gray J.W., and Bissell M.J.: The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol. Oncol. 1, 84 (2007).
73. Pradhan S., Clary J.M., Seliktar D., and Lipke E.A.: A three-dimensional spheroidal cancer model based on PEG- fibrinogen hydrogel microspheres. Biomaterials 115, 141 (2017).
74. Weiss M.S., Bernabé B.P., Shikanov A., Bluver D.A., Mui M.D., Shin S., Broadbelt L.J., and Shea L.D.: The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells. Biomaterials 33, 3548 (2012).
75. Taubenberger A.V., Bray L.J., Haller B., Shaposhnykov A., Binner M., Freudenberg U., Guck J., and Werner C.: 3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments. Acta Biomater. 36, 73 (2016).
76. Kloxin A.M., Kasko A.M., Salinas C.N., and Anseth K.S.: Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324, 59 (2009).
77. Wang H., Tibbitt M.W., Langer S.J., Leinwand L.A., and Anseth K.S.: Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway. Proc. Natl. Acad. Sci. U.S.A. 110, 19336 (2013).
78. Yang C., Tibbitt M.W., Basta L., and Anseth K.S.: Mechanical memory and dosing influence stem cell fate. Nat. Mater. 13, 645 (2014).
79. Stowers R.S., Allen S.C., Sanchez K., Davis C.L., Ebelt N.D., van Den Berg C., and Suggs L.J.: Extracellular matrix stiffening induces a malignant phenotypic transition in breast epithelial cells. Cell. Mol. Bioeng. 10, 114 (2017).
80. Valdez J., Cook C.D., Chopko C., Wang A.J., Brown A., Kumar M., Stockdale L., Rothenberg D., Renggli K., Gordon E., Lauffenburger D., White F., and Griffith L.: On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks. Biomaterials 130, 90 (2017).
81. Gasparian A., Daneshian L., Ji H., Jabbari E., and Shtutman M.: Purification of high-quality RNA from synthetic polyethylene glycol-based hydrogels. Anal. Biochem. 484, 1 (2015).
82. Douglas A.M., Fragkopoulos A.A., Gaines M.K., Lyon L.A., Fernandez-Nieves A., and Barker T.H.: Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers. Proc. Natl. Acad. Sci. U. S. A. 114, 885 (2017).
83. Bray L.J., Binner M., Holzheu A., Friedrichs J., Freudenberg U., Hutmacher D.W., and Werner C.: Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis. Biomaterials 53, 609 (2015).
84. Huang S., Van Arsdall M., Tedjarati S., McCarty M., Wu W., Langley R., and Fidler I.J.: Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J. Natl. Cancer Inst. 94, 1134 (2002).
85. Lin E.Y., Nguyen A. V., Russell R.G., and Pollard J.W.: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193, 727 (2001).
86. Condeelis J. and Pollard J.W.: Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263 (2006).
87. Wittmann K. and Fischbach C.: Contextual control of adipose-derived stem cell function: implications for engineered tumor models. ACS Biomater. Sci. Eng. 3, 1483 (2017).
88. Heddleston J.M., Li Z., Lathia J.D., Bao S., Hjelmeland A.B., and Rich J.N.: Hypoxia inducible factors in cancer stem cells. Br. J. Cancer 102, 789 (2010).
89. Keith B. and Simon M.C.: Hypoxia-inducible factors, stem cells, and cancer. Cell 129, 465 (2007).
90. Heddleston J.M., Li Z., McLendon R.E., Hjelmeland A.B., and Rich J.N.: The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8, 3274 (2009).
91. Conley S.J., Gheordunescu E., Kakarala P., Newman B., Korkaya H., Heath A.N., Clouthier S.G., and Wicha M.S.: Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Proc. Natl. Acad. Sci. U. S. A. 109, 2784 (2012).
92. Rodenhizer D., Gaude E., Cojocari D., Mahadevan R., Frezza C., Wouters B.G., and McGuigan A.P.: A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients. Nat. Mater. 15, 227 (2016).
93. Park K.M. and Gerecht S.: Hypoxia-inducible hydrogels. Nat. Commun. 5, article number 4075 (2014).
94. Lewis D.M., Park K.M., Tang V., Xu Y., Pak K., Eisinger-Mathason T.S.K., Simon M.C., and Gerecht S.: Intratumoral oxygen gradients mediate sarcoma cell invasion. Proc. Natl. Acad. Sci. U. S. A. 113, 9292 (2016).
95. Hartgerink J.D., Beniash E., and Stupp S.I.: Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials. Proc. Natl. Acad. Sci. U. S. A. 99, 5133 (2002).
96. Collier J.H. and Messersmith P.B.: Self-assembling polymer-peptide conjugates: nanostructural tailoring. Adv. Mater. 16, 907 (2004).
97. Baker B.M., Trappmann B., Wang W.Y., Sakar M.S., Kim I.L., Shenoy V.B., Burdick J.A., and Chen C.S.: Cell-mediated fiber recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments. Nat. Mater. 14, 1262 (2015).
98. Guvendiren M. and Burdick J.A.: Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat. Commun. 3, 792 (2012).
99. Young J.L. and Engler A.J.: Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro. Biomaterials 32, 1002 (2011).
100. Rosales A.M., Mabry K.M., Nehls E.M., and Anseth K.S.: Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels. Biomacromoleules 16, 798 (2015).
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

MRS Communications
  • ISSN: 2159-6859
  • EISSN: 2159-6867
  • URL: /core/journals/mrs-communications
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 58
Total number of PDF views: 124 *
Loading metrics...

Abstract views

Total abstract views: 627 *
Loading metrics...

* Views captured on Cambridge Core between 7th September 2017 - 24th February 2018. This data will be updated every 24 hours.