Skip to main content

Recent Advances in 3D Tissue Models

  • Chapter
  • First Online:
Engineered Cell Manipulation for Biomedical Application

Part of the book series: Nanomedicine and Nanotoxicology ((NANOMED))

Abstract

Physiologically relevant tissue models that bridge the gap between 2D tissue culture and animal trials would be highly desirable to study the function of tissues in health and disease as well as for the validation of lead compounds during drug development. The field has made impressive advances in 3D culturing cells and organoids in naturally derived materials. Novel, rationally designed, biomimetic materials have been established, which allow the almost individual variation of matrix parameters, such as stiffness, cell adhesion, degradability, or growth factor binding and controlled release. The combination of innovative materials with novel technological platforms such as printing, microfluidics, and additive or preventive manufacturing provides a great potential to build unprecedented, complex tissue models. Here we review recent advances in the design of materials building blocks which allow the formation of 3D structured microenvironments. We will mainly focus on strategies to locally position cell-instructive molecular cues and discuss needs to generate models which would allow the investigator to controllably manipulate cells in their 3D context with the aim to generate complex but yet scalable tissue models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Friedl P, Brocker EB (2000) The biology of cell locomotion within three-dimensional extracellular matrix. Cell Mol Life Sci 57(1):41–64

    Article  CAS  PubMed  Google Scholar 

  4. Eke I, Cordes N (2011) Radiobiology goes 3D: how ECM and cell morphology impact on cell survival after irradiation. Radiother Oncol 99(3):271–278

    Article  PubMed  Google Scholar 

  5. Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C 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

    Article  CAS  PubMed  Google Scholar 

  6. Lee YJ, Sheu TJ, Keng PC (2005) Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin. Biochem Biophys Res Commun 335(2):286–291

    Article  CAS  PubMed  Google Scholar 

  7. Liu JS, Gartner ZJ (2012) Directing the assembly of spatially organized multicomponent tissues from the bottom up. Trends Cell Biol 22(12):683–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hynds RE, Giangreco A (2013) Concise review: the relevance of human stem cell‐derived organoid models for epithelial translational medicine. Stem Cells 31(3):417–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123(Pt 24):4195–4200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cukierman E, Pankov R, Stevens DR, Yamada KM (2001) Taking cell-matrix adhesions to the third dimension. Science 294(5547):1708–1712

    Article  CAS  PubMed  Google Scholar 

  11. Kelm JM, Fussenegger M (2010) Scaffold-free cell delivery for use in regenerative medicine. Adv Drug Deliv Rev 62(7–8):753–764

    Article  CAS  PubMed  Google Scholar 

  12. Drewitz M, Helbling M, Fried N, Bieri M, Moritz W, Lichtenberg J et al (2011) Towards automated production and drug sensitivity testing using scaffold‐free spherical tumor microtissues. Biotechnol J 6(12):1488–1496

    Article  CAS  PubMed  Google Scholar 

  13. Rimann M, Graf-Hausner U (2012) Synthetic 3D multicellular systems for drug development. Curr Opin Biotechnol 23(5):803–809

    Article  CAS  PubMed  Google Scholar 

  14. Kelm JM, Djonov V, Hoerstrup SP, Guenter CI, Ittner LM, Greve F et al (2006) Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats. Tissue Eng 12(9):2541–2553

    Article  CAS  PubMed  Google Scholar 

  15. Stevens KR, Ungrin MD, Schwartz RE, Ng S, Carvalho B, Christine KS et al (2013) InVERT molding for scalable control of tissue microarchitecture. Nat Commun 4:1847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. L’Heureux N, Paquet S, Labbe R, Germain L, Auger FA (1998) A completely biological tissue-engineered human blood vessel. FASEB J 12(1):47–56

    PubMed  Google Scholar 

  17. McAllister TN, Maruszewski M, Garrido SA, Wystrychowski W, Dusserre N, Marini A et al (2009) Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study. Lancet 373(9673):1440–1446

    Article  PubMed  Google Scholar 

  18. Gauvin R, Ahsan T, Larouche D, Levesque P, Dube J, Auger FA et al (2010) A novel single-step self-assembly approach for the fabrication of tissue-engineered vascular constructs. Tissue Eng Part A 16(5):1737–1747

    Article  CAS  PubMed  Google Scholar 

  19. Bourget JM, Gauvin R, Larouche D, Lavoie A, Labbe R, Auger FA et al (2012) Human fibroblast-derived ECM as a scaffold for vascular tissue engineering. Biomaterials 33(36):9205–9213

    Article  CAS  PubMed  Google Scholar 

  20. Guillemette MD, Gauvin R, Perron C, Labbe R, Germain L, Auger FA (2010) Tissue-engineered vascular adventitia with vasa vasorum improves graft integration and vascularization through inosculation. Tissue Eng Part A 16(8):2617–2626

    Article  CAS  PubMed  Google Scholar 

  21. Elloumi-Hannachi I, Yamato M, Okano T (2010) Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med 267(1):54–70

    Article  CAS  PubMed  Google Scholar 

  22. Guillaume-Gentil O, Semenov OV, Zisch AH, Zimmermann R, Voros J, Ehrbar M (2011) pH-controlled recovery of placenta-derived mesenchymal stem cell sheets. Biomaterials 32(19):4376–4384

    Article  CAS  PubMed  Google Scholar 

  23. Ide T, Nishida K, Yamato M, Sumide T, Utsumi M, Nozaki T et al (2006) Structural characterization of bioengineered human corneal endothelial cell sheets fabricated on temperature-responsive culture dishes. Biomaterials 27(4):607–614

    Article  CAS  PubMed  Google Scholar 

  24. Murakami D, Yamato M, Nishida K, Ohki T, Takagi R, Yang J et al (2006) The effect of micropores in the surface of temperature-responsive culture inserts on the fabrication of transplantable canine oral mucosal epithelial cell sheets. Biomaterials 27(32):5518–5523

    Article  CAS  PubMed  Google Scholar 

  25. Elloumi Hannachi I, Itoga K, Kumashiro Y, Kobayashi J, Yamato M, Okano T (2009) Fabrication of transferable micropatterned-co-cultured cell sheets with microcontact printing. Biomaterials 30(29):5427–5432

    Article  PubMed  CAS  Google Scholar 

  26. Sekine H, Shimizu T, Sakaguchi K, Dobashi I, Wada M, Yamato M et al (2013) In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun 4:1399

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Langer R, Vacanti JP (1993) Tissue engineering. Science 260(5110):920–926

    Article  CAS  PubMed  Google Scholar 

  28. Couto DS, Hong Z, Mano JF (2009) Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. Acta Biomater 5(1):115–123

    Article  CAS  PubMed  Google Scholar 

  29. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J (2000) Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng 2:9–29

    Article  CAS  PubMed  Google Scholar 

  30. Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101(7):1869–1880

    Article  CAS  PubMed  Google Scholar 

  31. Clevers H, Batlle E (2013) SnapShot: the intestinal crypt. Cell 152(5):1198.e2

    Article  CAS  Google Scholar 

  32. Vidi P-A, Bissell MJ, Lelièvre SA (2013) Three-dimensional culture of human breast epithelial cells: the how and the why. In: Epithelial cell culture protocols. Springer, New York, pp 193–219

    Google Scholar 

  33. Kleinman HK, Martin GR (eds) (2005) Matrigel: basement membrane matrix with biological activity, Seminars in cancer biology. Elsevier, Amsterdam

    Google Scholar 

  34. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE et al (2009) Single Lgr5 stem cells build crypt villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265

    Article  CAS  PubMed  Google Scholar 

  35. Lanza R, Langer R, Vacanti JP (2011) Principles of tissue engineering. Academic, New York

    Google Scholar 

  36. Braziulis E, Diezi M, Biedermann T, Pontiggia L, Schmucki M, Hartmann-Fritsch F et al (2012) Modified plastic compression of collagen hydrogels provides an ideal matrix for clinically applicable skin substitutes. Tissue Eng Part C Methods 18(6):464–474

    Article  CAS  PubMed  Google Scholar 

  37. Sabeh F, Shimizu-Hirota R, Weiss SJ (2009) Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol 185(1):11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Boublik J, Park H, Radisic M, Tognana E, Chen F, Pei M et al (2005) Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric. Tissue Eng 11(7–8):1122–1132

    Article  CAS  PubMed  Google Scholar 

  39. Smidsrød O (1990) Alginate as immobilization matrix for cells. Trends Biotechnol 8:71–78

    Article  PubMed  Google Scholar 

  40. Rowley JA, Madlambayan G, Mooney DJ (1999) Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20(1):45–53

    Article  CAS  PubMed  Google Scholar 

  41. Sun J, Tan H (2013) Alginate-based biomaterials for regenerative medicine applications. Materials 6(4):1285–1309

    Article  CAS  Google Scholar 

  42. Laurent TC, Fraser J (1992) Hyaluronan. FASEB J 6(7):2397–2404

    CAS  PubMed  Google Scholar 

  43. Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28(5):385–397

    Article  CAS  PubMed  Google Scholar 

  44. Allison DD, Grande-Allen KJ (2006) Review. Hyaluronan: a powerful tissue engineering tool. Tissue Eng 12(8):2131–2140

    Article  CAS  PubMed  Google Scholar 

  45. Lesley J, Hyman R, Kincade PW (1993) CD44 and its interaction with extracellular matrix. Adv Immunol 54:271–335

    Article  CAS  PubMed  Google Scholar 

  46. Prestwich GD, Marecak DM, Marecek JF, Vercruysse KP, Ziebell MR (1998) Controlled chemical modification of hyaluronic acid: synthesis, applications, and biodegradation of hydrazide derivatives. J Control Release 53(1):93–103

    Article  CAS  PubMed  Google Scholar 

  47. van Wachem PB, van Luyn MJ, Olde Damink LH, Dijkstra PJ, Feijen J, Nieuwenhuis P (1994) Tissue regenerating capacity of carbodiimide-crosslinked dermal sheep collagen during repair of the abdominal wall. Int J Artif Organs 17(4):230–239

    PubMed  Google Scholar 

  48. Lorentz KM, Kontos S, Frey P, Hubbell JA (2011) Engineered aprotinin for improved stability of fibrin biomaterials. Biomaterials 32(2):430–438

    Article  CAS  PubMed  Google Scholar 

  49. Wissink MJ, Beernink R, Poot AA, Engbers GH, Beugeling T, van Aken WG et al (2000) Improved endothelialization of vascular grafts by local release of growth factor from heparinized collagen matrices. J Control Release 64(1–3):103–114

    Article  CAS  PubMed  Google Scholar 

  50. Pike DB, Cai S, Pomraning KR, Firpo MA, Fisher RJ, Shu XZ et al (2006) Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. Biomaterials 27(30):5242–5251

    Article  CAS  PubMed  Google Scholar 

  51. Sakiyama-Elbert SE, Hubbell JA (2000) Development of fibrin derivatives for controlled release of heparin-binding growth factors. J Control Release 65(3):389–402

    Article  CAS  PubMed  Google Scholar 

  52. Sakiyama SE, Schense JC, Hubbell JA (1999) Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering. FASEB J 13(15):2214–2224

    CAS  PubMed  Google Scholar 

  53. Martino MM, Hubbell JA (2010) The 12th–14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J 24(12):4711–4721

    Article  CAS  PubMed  Google Scholar 

  54. Zisch AH, Schenk U, Schense JC, Sakiyama-Elbert SE, Hubbell JA (2001) Covalently conjugated VEGF–fibrin matrices for endothelialization. J Control Release 72(1–3):101–113

    Article  CAS  PubMed  Google Scholar 

  55. Schmoekel HG, Weber FE, Schense JC, Gratz KW, Schawalder P, Hubbell JA (2005) Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell ingrowth matrices. Biotechnol Bioeng 89(3):253–262

    Article  CAS  PubMed  Google Scholar 

  56. Lorentz KM, Yang L, Frey P, Hubbell JA (2012) Engineered insulin-like growth factor-1 for improved smooth muscle regeneration. Biomaterials 33(2):494–503

    Article  CAS  PubMed  Google Scholar 

  57. Lienemann PS, Lutolf MP, Ehrbar M (2012) Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration. Adv Drug Deliv Rev 64(12):1078–1089

    Article  CAS  PubMed  Google Scholar 

  58. Sakiyama-Elbert SE, Hubbell JA (2000) Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix. J Control Release 69(1):149–158

    Article  CAS  PubMed  Google Scholar 

  59. Johnson PJ, Parker SR, Sakiyama‐Elbert SE (2010) Fibrin‐based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury. J Biomed Mater Res Pt A 92(1):152–163

    Article  CAS  Google Scholar 

  60. Johnson PJ, Tatara A, Shiu A, Sakiyama-Elbert SE (2010) Controlled release of neurotrophin-3 and platelet derived growth factor from fibrin scaffolds containing neural progenitor cells enhances survival and differentiation into neurons in a subacute model of SCI. Cell Transplant 19(1):89

    Article  PubMed  Google Scholar 

  61. Taylor SJ, McDonald JW III, Sakiyama-Elbert SE (2004) Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury. J Control Release 98(2):281–294

    Article  CAS  PubMed  Google Scholar 

  62. Taylor SJ, Rosenzweig ES, McDonald JW III, Sakiyama-Elbert SE (2006) Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. J Control Release 113(3):226–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Taylor SJ, Sakiyama-Elbert SE (2006) Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model. J Control Release 116(2):204–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sakiyama-Elbert SE, Das R, Gelberman RH, Harwood F, Amiel D, Thomopoulos S (2008) Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair. J Hand Surgery 33(9):1548–1557

    Article  Google Scholar 

  65. Thomopoulos S, Zaegel M, Das R, Harwood FL, Silva MJ, Amiel D et al (2007) PDGF‐BB released in tendon repair using a novel delivery system promotes cell proliferation and collagen remodeling. J Orthop Res 25(10):1358–1368

    Article  CAS  PubMed  Google Scholar 

  66. Wissink M, Beernink R, Scharenborg N, Poot A, Engbers G, Beugeling T et al (2000) Endothelial cell seeding of (heparinized) collagen matrices: effects of bFGF pre-loading on proliferation (after low density seeding) and pro-coagulant factors. J Control Release 67(2):141–155

    Article  CAS  PubMed  Google Scholar 

  67. Grieb G, Groger A, Piatkowski A, Markowicz M, Steffens G, Pallua N (2009) Tissue substitutes with improved angiogenic capabilities: an in vitro investigation with endothelial cells and endothelial progenitor cells. Cells Tissues Organs 191(2):96–104

    Article  PubMed  CAS  Google Scholar 

  68. Markowicz M, Heitland A, Steffens G, Pallua N (2005) Effects of modified collagen matrices on human umbilical vein endothelial cells. Int J Artif Organs 28(12):1251

    CAS  PubMed  Google Scholar 

  69. Steffens G, Yao C, Prevel P, Markowicz M, Schenck P, Noah E et al (2004) Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. Tissue Eng 10(9–10):1502–1509

    Article  CAS  PubMed  Google Scholar 

  70. Van Wachem P, Plantinga J, Wissink M, Beernink R, Poot A, Engbers G et al (2001) In vivo biocompatibility of carbodiimide‐crosslinked collagen matrices: effects of crosslink density, heparin immobilization, and bFGF loading. J Biomed Mater Res 55(3):368–378

    Article  PubMed  Google Scholar 

  71. Wissink M, Beernink R, Pieper J, Poot A, Engbers G, Beugeling T et al (2001) Binding and release of basic fibroblast growth factor from heparinized collagen matrices. Biomaterials 22(16):2291–2299

    Article  CAS  PubMed  Google Scholar 

  72. Bladergroen BA, Siebum B, Siebers-Vermeulen KG, Van Kuppevelt TH, Poot AA, Feijen J et al (2008) In vivo recruitment of hematopoietic cells using stromal cell–derived factor 1 alpha–loaded heparinized three-dimensional collagen scaffolds. Tissue Eng Part A 15(7):1591–1599

    Article  CAS  Google Scholar 

  73. Martino MM, Tortelli F, Mochizuki M, Traub S, Ben-David D, Kuhn GA et al (2011) Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci Transl Med 3(100):100ra89

    Article  PubMed  CAS  Google Scholar 

  74. Zhao W, Han Q, Lin H, Sun W, Gao Y, Zhao Y et al (2008) Human basic fibroblast growth factor fused with Kringle4 peptide binds to a fibrin scaffold and enhances angiogenesis. Tissue Eng Part A 15(5):991–998

    Article  CAS  Google Scholar 

  75. Zhao W, Han Q, Lin H, Gao Y, Sun W, Zhao Y et al (2008) Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin. J Mol Med 86(10):1127–1138

    Article  CAS  PubMed  Google Scholar 

  76. Yang Y, Zhao Y, Chen B, Han Q, Sun W, Xiao Z et al (2009) Collagen-binding human epidermal growth factor promotes cellularization of collagen scaffolds. Tissue Eng Part A 15(11):3589–3596

    Article  CAS  PubMed  Google Scholar 

  77. Sun W, Lin H, Xie H, Chen B, Zhao W, Han Q et al (2007) Collagen membranes loaded with collagen-binding human PDGF-BB accelerate wound healing in a rabbit dermal ischemic ulcer model. Growth Factors 25(5):309–318

    Article  PubMed  CAS  Google Scholar 

  78. Han Q, Sun W, Lin H, Zhao W, Gao Y, Zhao Y et al (2009) Linear ordered collagen scaffolds loaded with collagen-binding brain-derived neurotrophic factor improve the recovery of spinal cord injury in rats. Tissue Eng Part A 15(10):2927–2935

    Article  CAS  PubMed  Google Scholar 

  79. Bentz H, Schroeder J, Estridge T (1998) Improved local delivery of TGF‐β2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol. J Biomed Mater Res 39(4):539–548

    Article  CAS  PubMed  Google Scholar 

  80. Koch S, Yao C, Grieb G, Prevel P, Noah EM, Steffens GC (2006) Enhancing angiogenesis in collagen matrices by covalent incorporation of VEGF. J Mater Sci Mater Med 17(8):735–741

    Article  CAS  PubMed  Google Scholar 

  81. Shen YH, Shoichet MS, Radisic M (2008) Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. Acta Biomater 4(3):477–489

    Article  CAS  PubMed  Google Scholar 

  82. Geer DJ, Swartz DD, Andreadis ST (2005) Biomimetic delivery of keratinocyte growth factor upon cellular demand for accelerated wound healing in vitro and in vivo. Am J Pathol 167(6):1575–1586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhang G, Nakamura Y, Wang X, Hu Q, Suggs LJ, Zhang J (2007) Controlled release of stromal cell-derived factor-1alpha in situ increases c-kit + cell homing to the infarcted heart. Tissue Eng 13(8):2063–2071

    Article  CAS  PubMed  Google Scholar 

  84. Sakiyama-Elbert SE, Panitch A, Hubbell JA (2001) Development of growth factor fusion proteins for cell-triggered drug delivery. FASEB J 15(7):1300–1302

    CAS  PubMed  Google Scholar 

  85. Ehrbar M, Djonov VG, Schnell C, Tschanz SA, Martiny-Baron G, Schenk U et al (2004) Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res 94(8):1124–1132

    Article  CAS  PubMed  Google Scholar 

  86. Ehrbar M, Metters A, Zammaretti P, Hubbell JA, Zisch AH (2005) Endothelial cell proliferation and progenitor maturation by fibrin-bound VEGF variants with differential susceptibilities to local cellular activity. J Control Release 101(1):93–109

    Article  CAS  PubMed  Google Scholar 

  87. Ehrbar M, Zeisberger SM, Raeber GP, Hubbell JA, Schnell C, Zisch AH (2008) The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis. Biomaterials 29(11):1720–1729

    Article  CAS  PubMed  Google Scholar 

  88. Weber CC, Cai H, Ehrbar M, Kubota H, Martiny-Baron G, Weber W et al (2005) Effects of protein and gene transfer of the angiopoietin-1 fibrinogen-like receptor-binding domain on endothelial and vessel organization. J Biol Chem 280(23):22445–22453

    Article  CAS  PubMed  Google Scholar 

  89. Zisch AH, Zeisberger SM, Ehrbar M, Djonov V, Weber CC, Ziemiecki A et al (2004) Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: study of angiogenic signaling by ephrin-B2. Biomaterials 25(16):3245–3257

    Article  CAS  PubMed  Google Scholar 

  90. Hall H, Djonov V, Ehrbar M, Hoechli M, Hubbell JA (2004) Heterophilic interactions between cell adhesion molecule L1 and αv β3-integrin induce HUVEC process extension in vitro and angiogenesis in vivo. Angiogenesis 7(3):213–223

    Article  CAS  PubMed  Google Scholar 

  91. Lühmann T, Hänseler P, Grant B, Hall H (2009) The induction of cell alignment by covalently immobilized gradients of the 6th Ig-like domain of cell adhesion molecule L1 in 3D-fibrin matrices. Biomaterials 30(27):4503–4512

    Article  PubMed  CAS  Google Scholar 

  92. Pittier R, Sauthier F, Hubbell JA, Hall H (2005) Neurite extension and in vitro myelination within three‐dimensional modified fibrin matrices. J Neurobiol 63(1):1–14

    Article  CAS  PubMed  Google Scholar 

  93. Arrighi I, Mark S, Alvisi M, von Rechenberg B, Hubbell JA, Schense JC (2009) Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. Biomaterials 30(9):1763–1771

    Article  CAS  PubMed  Google Scholar 

  94. Martino MM, Briquez PS, Guc E, Tortelli F, Kilarski WW, Metzger S et al (2014) Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343(6173):885–888

    Article  CAS  PubMed  Google Scholar 

  95. Largo RA, Ramakrishnan VM, Marschall JS, Ziogas A, Banfi A, Eberli D et al (2014) Long-term biostability and bioactivity of “fibrin linked” VEGF(121) in vitro and in vivo. Biomater Sci-Uk 2(4):581–590

    Article  CAS  Google Scholar 

  96. Ehrbar M, Schoenmakers R, Christen EH, Fussenegger M, Weber W (2008) Drug-sensing hydrogels for the inducible release of biopharmaceuticals. Nat Mater 7(10):800–804

    Article  CAS  PubMed  Google Scholar 

  97. Peppas N (2004) Devices based on intelligent biopolymers for oral protein delivery. Int J Pharm 277(1):11–17

    Article  CAS  PubMed  Google Scholar 

  98. Schmaljohann D (2006) Thermo-and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58(15):1655–1670

    Article  CAS  PubMed  Google Scholar 

  99. Chen G, Hoffman AS (1995) Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373(6509):49–52

    Article  CAS  PubMed  Google Scholar 

  100. Bryant SJ, Nuttelman CR, Anseth KS (2000) Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3 T3 fibroblasts in vitro. J Biomater Sci Polym Ed 11(5):439–457

    Article  CAS  PubMed  Google Scholar 

  101. Fairbanks BD, Schwartz MP, Bowman CN, Anseth KS (2009) Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2, 4, 6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials 30(35):6702–6707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Hu B-H, Su J, Messersmith PB (2009) Hydrogels cross-linked by native chemical ligation. Biomacromolecules 10(8):2194–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Takahashi A, Suzuki Y, Suhara T, Omichi K, Shimizu A, Hasegawa K et al (2013) In situ cross-linkable hydrogel of hyaluronan produced via copper-free click chemistry. Biomacromolecules 14(10):3581–3588

    Article  CAS  PubMed  Google Scholar 

  104. Lutolf MP, Lauer-Fields JL, Schmoekel HG, Metters AT, Weber FE, Fields GB et al (2003) Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc Natl Acad Sci USA 100(9):5413–5418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Deforest CA, Sims EA, Anseth KS (2010) Peptide-functionalized click hydrogels with independently tunable mechanics and chemical functionality for 3D cell CULTURE. Chem Mater 22(16):4783–4790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Jung JP, Moyano JV, Collier JH (2011) Multifactorial optimization of endothelial cell growth using modular synthetic extracellular matrices. Integr Biol (Camb) 3(3):185–196

    Article  CAS  Google Scholar 

  107. Tong X, Yang F (2014) Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties. Biomaterials 35(6):1807–1815

    Article  CAS  PubMed  Google Scholar 

  108. Ehrbar M, Rizzi SC, Schoenmakers RG, Miguel BS, Hubbell JA, Weber FE et al (2007) Biomolecular hydrogels formed and degraded via site-specific enzymatic reactions. Biomacromolecules 8(10):3000–3007

    Article  CAS  PubMed  Google Scholar 

  109. Friedl P, Wolf K (2010) Plasticity of cell migration: a multiscale tuning model. J Cell Biol 188(1):11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ehrbar M, Sala A, Lienemann P, Ranga A, Mosiewicz K, Bittermann A et al (2011) Elucidating the role of matrix stiffness in 3D cell migration and remodeling. Biophys J 100(2):284–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bott K, Upton Z, Schrobback K, Ehrbar M, Hubbell JA, Lutolf MP et al (2010) The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials 31(32):8454–8464

    Article  CAS  PubMed  Google Scholar 

  112. Pierschbacher MD, Ruoslahti E (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309(5963):30–33

    Article  CAS  PubMed  Google Scholar 

  113. Zhu J (2010) Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31(17):4639–4656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kohn J, Langer R, Ratner B, Hoffman A, Schoen F, Lemons J (1996) Biomaterials science: an introduction to materials in medicine. Academic, San Diego, pp 64–73

    Google Scholar 

  115. Patterson J, Hubbell JA (2010) Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31(30):7836–7845

    Article  CAS  PubMed  Google Scholar 

  116. Patterson J, Hubbell JA (2011) SPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels. Biomaterials 32(5):1301–1310

    Article  CAS  PubMed  Google Scholar 

  117. Mehta M, Schmidt-Bleek K, Duda GN, Mooney DJ (2012) Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. Adv Drug Deliv Rev 64(12):1257–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. DeLong SA, Moon JJ, West JL (2005) Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. Biomaterials 26(16):3227–3234

    Article  CAS  PubMed  Google Scholar 

  119. Saik JE, Gould DJ, Keswani AH, Dickinson ME, West JL (2011) Biomimetic hydrogels with immobilized ephrinA1 for therapeutic angiogenesis. Biomacromolecules 12(7):2715–2722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mann BK, Schmedlen RH, West JL (2001) Tethered-TGF- β increases extracellular matrix production of vascular smooth muscle cells. Biomaterials 22(5):439–444

    Article  CAS  PubMed  Google Scholar 

  121. Gobin AS, West JL (2003) Effects of epidermal growth factor on fibroblast migration through biomimetic hydrogels. Biotechnol Prog 19(6):1781–1785

    Article  CAS  PubMed  Google Scholar 

  122. Saik JE, Gould DJ, Watkins EM, Dickinson ME, West JL (2011) Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly (ethylene glycol) hydrogels. Acta Biomater 7(1):133–143

    Article  CAS  PubMed  Google Scholar 

  123. He X, Ma J, Jabbari E (2008) Effect of grafting RGD and BMP-2 protein-derived peptides to a hydrogel substrate on osteogenic differentiation of marrow stromal cells. Langmuir 24(21):12508–12516

    Article  CAS  PubMed  Google Scholar 

  124. Leipzig ND, Xu C, Zahir T, Shoichet MS (2010) Functional immobilization of interferon‐gamma induces neuronal differentiation of neural stem cells. J Biomed Mater Res A 93(2):625–633

    PubMed  Google Scholar 

  125. Zisch AH, Lutolf MP, Ehrbar M, Raeber GP, Rizzi SC, Davies N et al (2003) Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth. FASEB J 17(15):2260–2262

    CAS  PubMed  Google Scholar 

  126. Seliktar D, Zisch A, Lutolf M, Wrana J, Hubbell J (2004) MMP‐2 sensitive, VEGF‐bearing bioactive hydrogels for promotion of vascular healing. J Biomed Mater Res A 68(4):704–716

    Article  CAS  PubMed  Google Scholar 

  127. Ehrbar M, Rizzi SC, Hlushchuk R, Djonov V, Zisch AH, Hubbell JA et al (2007) Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials 28(26):3856–3866

    Article  CAS  PubMed  Google Scholar 

  128. Riley CM, Fuegy PW, Firpo MA, Zheng Shu X, Prestwich GD, Peattie RA (2006) Stimulation of in vivo angiogenesis using dual growth factor-loaded crosslinked glycosaminoglycan hydrogels. Biomaterials 27(35):5935–5943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Zhao J, Zhang N, Prestwich GD, Wen X (2008) Recruitment of endogenous stem cells for tissue repair. Macromol Biosci 8(9):836–842

    Article  CAS  PubMed  Google Scholar 

  130. Hosack LW, Firpo MA, Scott JA, Prestwich GD, Peattie RA (2008) Microvascular maturity elicited in tissue treated with cytokine-loaded hyaluronan-based hydrogels. Biomaterials 29(15):2336–2347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Liu Y, Cai S, Shu XZ, Shelby J, Prestwich GD (2007) Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing. Wound Repair Regen 15(2):245–251

    Article  PubMed  Google Scholar 

  132. Cai S, Liu Y, Zheng Shu X, Prestwich GD (2005) Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor. Biomaterials 26(30):6054–6067

    Article  CAS  PubMed  Google Scholar 

  133. Tae G, Scatena M, Stayton PS, Hoffman AS (2006) PEG-cross-linked heparin is an affinity hydrogel for sustained release of vascular endothelial growth factor. J Biomater Sci Polym Ed 17(1–2):187–197

    Article  CAS  PubMed  Google Scholar 

  134. Freudenberg U, Hermann A, Welzel PB, Stirl K, Schwarz SC, Grimmer M et al (2009) A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases. Biomaterials 30(28):5049–5060

    Article  CAS  PubMed  Google Scholar 

  135. Tsurkan MV, Chwalek K, Prokoph S, Zieris A, Levental KR, Freudenberg U et al (2013) Defined polymer-peptide conjugates to form cell-instructive starPEG-heparin matrices in situ. Adv Mater 25(18):2606–2610

    Article  CAS  PubMed  Google Scholar 

  136. Zhang L, Furst EM, Kiick KL (2006) Manipulation of hydrogel assembly and growth factor delivery via the use of peptide–polysaccharide interactions. J Control Release 114(2):130–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Yamaguchi N, Kiick KL (2005) Polysaccharide-poly (ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels. Biomacromolecules 6(4):1921–1930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Nie T, Baldwin A, Yamaguchi N, Kiick KL (2007) Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems. J Control Release 122(3):287–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Yamaguchi N, Zhang L, Chae B-S, Palla CS, Furst EM, Kiick KL (2007) Growth factor mediated assembly of cell receptor-responsive hydrogels. J Am Chem Soc 129(11):3040–3041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Benoit DS, Anseth KS (2005) Heparin functionalized PEG gels that modulate protein adsorption for hMSC adhesion and differentiation. Acta Biomater 1(4):461–470

    Article  PubMed  Google Scholar 

  141. Pratt AB, Weber FE, Schmoekel HG, Müller R, Hubbell JA (2004) Synthetic extracellular matrices for in situ tissue engineering. Biotechnol Bioeng 86(1):27–36

    Article  CAS  PubMed  Google Scholar 

  142. Lin CC, Anseth KS (2009) Controlling affinity binding with peptide‐functionalized poly (ethylene glycol) hydrogels. Adv Funct Mater 19(14):2325–2331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Lienemann PS, Karlsson M, Sala A, Wischhusen HM, Weber FE, Zimmermann R et al (2013) A versatile approach to engineering biomolecule-presenting cellular microenvironments. Adv Healthc Mater 2(2):292–296

    Article  CAS  PubMed  Google Scholar 

  144. Karlsson M, Lienemann PS, Sprossmann N, Heilmann K, Brummer T, Lutolf MP et al (2013) A generic strategy for pharmacological caging of growth factors for tissue engineering. Chem Commun (Camb) 49(53):5927–5929

    Article  CAS  Google Scholar 

  145. Gubeli RJ, Laird D, Ehrbar M, Ritter BS, Steinberg T, Tomakidi P et al (2013) Pharmacologically tunable polyethylene-glycol-based cell growth substrate. Acta Biomater 9(9):8272–8278

    Article  CAS  PubMed  Google Scholar 

  146. Mosiewicz KA, Kolb L, van der Vlies AJ, Martino MM, Lienemann PS, Hubbell JA et al (2013) In situ cell manipulation through enzymatic hydrogel photopatterning. Nat Mater 12(11):1072–1078

    Article  CAS  PubMed  Google Scholar 

  147. Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA (2013) Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci 110(12):4563–4568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bentz H, Schroeder JA, Estridge TD (1998) Improved local delivery of TGF-beta2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol. J Biomed Mater Res 39(4):539–548

    Article  CAS  PubMed  Google Scholar 

  149. Veronese FM (2001) Peptide and protein PEGylation: a review of problems and solutions. Biomaterials 22(5):405–417

    Article  CAS  PubMed  Google Scholar 

  150. Moriyama K, Minamihata K, Wakabayashi R, Goto M, Kamiya N (2013) Enzymatic preparation of streptavidin-immobilized hydrogel using a phenolated linear poly(ethylene glycol). Biochem Eng J 76:37–42

    Article  CAS  Google Scholar 

  151. Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA (2013) Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci USA 110(12):4563–4568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Shah RN, Shah NA, Del Rosario Lim MM, Hsieh C, Nuber G, Stupp SI (2010) Supramolecular design of self-assembling nanofibers for cartilage regeneration. Proc Natl Acad Sci USA 107(8):3293–3298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Chen AA, Underhill GH, Bhatia SN (2010) Multiplexed, high-throughput analysis of 3D microtissue suspensions. Integr Biol (Camb) 2(10):517–527

    Article  CAS  Google Scholar 

  154. Xu F, Wu CA, Rengarajan V, Finley TD, Keles HO, Sung Y et al (2011) Three-dimensional magnetic assembly of microscale hydrogels. Adv Mater 23(37):4254–4260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Eng G, Lee BW, Parsa H, Chin CD, Schneider J, Linkov G et al (2013) Assembly of complex cell microenvironments using geometrically docked hydrogel shapes. Proc Natl Acad Sci USA 110(12):4551–4556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Leong MF, Toh JK, Du C, Narayanan K, Lu HF, Lim TC et al (2013) Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres. Nat Commun 4:2353

    Article  PubMed  Google Scholar 

  157. Fernandez JG, Khademhosseini A (2010) Micro-masonry: construction of 3D structures by microscale self-assembly. Adv Mater 22(23):2538–2541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM et al (2012) Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater 11(9):768–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Sala A, Hanseler P, Ranga A, Lutolf MP, Voros J, Ehrbar M et al (2011) Engineering 3D cell instructive microenvironments by rational assembly of artificial extracellular matrices and cell patterning. Integr Biol (Camb) 3(11):1102–1111

    Article  Google Scholar 

  160. Milleret V, Simona BR, Lienemann PS, Voros J, Ehrbar M (2014) Electrochemical control of the enzymatic polymerization of PEG hydrogels: formation of spatially controlled biological microenvironments. Adv Healthc Mater 3:508–514

    Article  CAS  PubMed  Google Scholar 

  161. Chan V, Zorlutuna P, Jeong JH, Kong H, Bashir R (2010) Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. Lab Chip 10(16):2062–2070

    Article  CAS  PubMed  Google Scholar 

  162. Wylie RG, Ahsan S, Aizawa Y, Maxwell KL, Morshead CM, Shoichet MS (2011) Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nat Mater 10(10):799–806

    Article  CAS  PubMed  Google Scholar 

  163. Cosson S, Allazetta S, Lutolf MP (2013) Patterning of cell-instructive hydrogels by hydrodynamic flow focusing. Lab Chip 13(11):2099–2105

    Article  CAS  PubMed  Google Scholar 

  164. Cheung YK, Gillette BM, Zhong M, Ramcharan S, Sia SK (2007) Direct patterning of composite biocompatible microstructures using microfluidics. Lab Chip 7(5):574–579

    Article  CAS  PubMed  Google Scholar 

  165. Lee H, Choi B, Moon H, Choi J, Park K, Jeong B et al (2012) Chondrocyte 3D-culture in RGD-modified crosslinked hydrogel with temperature-controllable modulus. Macromol Res 20(1):106–111

    Article  CAS  Google Scholar 

  166. Davis KA, Burke KA, Mather PT, Henderson JH (2011) Dynamic cell behavior on shape memory polymer substrates. Biomaterials 32(9):2285–2293

    Article  CAS  PubMed  Google Scholar 

  167. Klouda L, Perkins KR, Watson BM, Hacker MC, Bryant SJ, Raphael RM et al (2011) Thermoresponsive, in situ cross-linkable hydrogels based on N-isopropylacrylamide: Fabrication, characterization and mesenchymal stem cell encapsulation. Acta Biomater 7(4):1460–1467

    Article  CAS  PubMed  Google Scholar 

  168. Garbern JC, Hoffman AS, Stayton PS (2010) Injectable pH- and temperature-responsive poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers for delivery of angiogenic growth factors. Biomacromolecules 11(7):1833–1839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Fuhrer R, Athanassiou EK, Luechinger NA, Stark WJ (2009) Crosslinking metal nanoparticles into the polymer backbone of hydrogels enables preparation of soft, magnetic field-driven actuators with muscle-like flexibility. Small 5(3):383–388

    Article  CAS  PubMed  Google Scholar 

  170. Gubeli RJ, Ehrbar M, Fussenegger M, Friedrich C, Weber W (2012) Synthesis and characterization of PEG-based drug-responsive biohybrid hydrogels. Macromol Rapid Commun 33(15):1280–1285

    Article  PubMed  CAS  Google Scholar 

  171. Kim SH, Kiick KL (2010) Cell-mediated delivery and targeted erosion of vascular endothelial growth factor-crosslinked hydrogels. Macromol Rapid Commun 31(14):1231–1240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. King WJ, Mohammed JS, Murphy WL (2009) Modulating growth factor release from hydrogels via a protein conformational change. Soft Matter 5(12):2399–2406

    Article  CAS  Google Scholar 

  173. Khetan S, Burdick JA (2011) Patterning hydrogels in three dimensions towards controlling cellular interactions. Soft Matter 7(3):830–838

    Article  CAS  Google Scholar 

  174. DeForest CA, Anseth KS (2012) Photoreversible patterning of biomolecules within click-based hydrogels. Angew Chem Int Ed Engl 51(8):1816–1819

    Article  CAS  PubMed  Google Scholar 

  175. Kloxin AM, Kasko AM, Salinas CN, Anseth KS (2009) Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324(5923):59–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Khetan S, Katz JS, Burdick JA (2009) Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels. Soft Matter 5(8):1601–1606

    Article  CAS  Google Scholar 

  177. Ellis-Davies GC (2007) Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat Methods 4(8):619–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Griffin DR, Borrajo J, Soon A, Acosta-Velez GF, Oshita V, Darling N et al (2014) Hybrid photopatterned enzymatic reaction (HyPER) for in situ cell manipulation. Chembiochem 15(2):233–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Karlsson M, Rebmann B, Lienemann PS, Sprossmann N, Ehrbar M, Radziwill G et al (2013) Pharmacologically controlled protein switch for ON-OFF regulation of growth factor activity. Sci Rep 3:2716

    Article  PubMed  PubMed Central  Google Scholar 

  180. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6(4):483–495

    Article  CAS  PubMed  Google Scholar 

  181. Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    Article  CAS  PubMed  Google Scholar 

  182. Guvendiren M, Burdick JA (2012) Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat Commun 3:792

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We would like to express our gratitude to Dr. Philipp Lienemann for producing the illustrations and for helpful discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Ehrbar Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Kivelio, A., Ehrbar, M. (2014). Recent Advances in 3D Tissue Models. In: Akashi, M., Akagi, T., Matsusaki, M. (eds) Engineered Cell Manipulation for Biomedical Application. Nanomedicine and Nanotoxicology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55139-3_1

Download citation

Publish with us

Policies and ethics