Skip to main content
SpringerLink
Log in

Microenvironment Design for Stem Cell Fate Determination

  • Chapter
  • First Online:
Tissue Engineering III: Cell - Surface Interactions for Tissue Culture

Part of the book series: Advances in Biochemical Engineering Biotechnology ((ABE,volume 126))

Abstract

Stem cells are characterized by their dual ability for self-renewal and differentiation, potentially yielding large numbers of cells that can be used in cell therapy and tissue engineering for repairing devastating diseases. Attaining control over stem cell fate decision in culture is a great challenge since these cells integrate a complex array of “niche” signals, which regulate their fate. Given this, the recent findings that synthetic microenvironments can be designed to gain some level of control over stem cell fate are encouraging. This chapter provides an overview of the current state and knowledge of the design of synthetic microenvironments bio-inspired by the adult stem cell niche. We describe the biomaterials used for reconstituting the niche, highlighting the bioengineering principles used in the process. Such synthetic microenvironments constitute powerful tools for elucidating stem cell regulatory mechanisms that should fuel the development of advanced culture systems with accurate regulation of stem cell fate.

Graphical Abstract

Typical fit of model to force-deformation data from compression of a single Saccharomyces cerevisiae cell by micromanipulation

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

References

  1. Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079

    Article  CAS  Google Scholar 

  2. Metallo CM, Mohr JC, Detzel CJ et al (2007) Engineering the stem cell microenvironment. Biotechnol Prog 23:18–23

    Article  CAS  Google Scholar 

  3. Barrilleaux B, Phinney DG, Prockop DJ, O’Connor KC (2006) Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng 12:3007–3019

    Article  CAS  Google Scholar 

  4. Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846

    Article  CAS  Google Scholar 

  5. Jones DL, Wagers AJ (2008) No place like home: anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol 9:11–21

    Article  CAS  Google Scholar 

  6. Nilsson SK, Johnston HM, Whitty GA et al (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–1239

    Article  CAS  Google Scholar 

  7. Yoshihara H, Arai F, Hosokawa K et al (2007) Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1:685–697

    Article  CAS  Google Scholar 

  8. Arai F, Hirao A, Ohmura M et al (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161

    Article  CAS  Google Scholar 

  9. Adams GB, Chabner KT, Alley IR et al (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439:599–603

    Article  CAS  Google Scholar 

  10. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD (2007) Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA 104:5431–5436

    Article  CAS  Google Scholar 

  11. Jang YY, Sharkis SJ (2007) A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110:3056–3063

    Article  CAS  Google Scholar 

  12. Duncan AW, Rattis FM, DiMascio LN et al (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6:314–322

    Article  CAS  Google Scholar 

  13. Di Maggio N, Piccinini E, Jaworski M et al (2011) Toward modeling the bone marrow niche using scaffold-based 3D culture systems. Biomaterials 32:321–329

    Article  CAS  Google Scholar 

  14. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  Google Scholar 

  15. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74

    Article  CAS  Google Scholar 

  16. Zhao LR, Duan WM, Reyes M et al (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20

    Article  Google Scholar 

  17. Miyahara Y, Nagaya N, Kataoka M et al (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465

    Article  CAS  Google Scholar 

  18. Hofstetter CP, Schwarz EJ, Hess D et al (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199–2204

    Article  CAS  Google Scholar 

  19. Maegawa N, Kawamura K, Hirose M et al (2007) Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2). J Tissue Eng Regen Med 1:306–313

    Article  CAS  Google Scholar 

  20. Meinel L, Hofmann S, Karageorgiou V et al. (2004) Engineering cartilage-like tissue using human mesenchymal stem cells and silk protein scaffolds. Biotechnol Bioeng 88:379–391

    Article  CAS  Google Scholar 

  21. Mauck RL, Yuan X, Tuan RS (2006) Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. Osteoarthritis Cartilage 14:179–189

    Article  CAS  Google Scholar 

  22. Martin I, Obradovic B, Treppo S et al (2000) Modulation of the mechanical properties of tissue engineered cartilage. Biorheology 37:141–147

    CAS  Google Scholar 

  23. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272

    Article  CAS  Google Scholar 

  24. Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  CAS  Google Scholar 

  25. Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    Article  CAS  Google Scholar 

  26. Smukler SR, Arntfield ME, Razavi R et al (2011) The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8:281–293

    Article  CAS  Google Scholar 

  27. Shamblott MJ, Axelman J, Wang S et al (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 95:13726–13731

    Article  CAS  Google Scholar 

  28. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  Google Scholar 

  29. Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  Google Scholar 

  30. Yu J, Vodyanik MA, Smuga-Otto K et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Google Scholar 

  31. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  Google Scholar 

  32. Zhao T, Zhang ZN, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215

    Article  CAS  Google Scholar 

  33. Gerecht-Nir S, Cohen S, Ziskind A, Itskovitz-Eldor J (2004) Three-dimensional porous alginate scaffolds provide a conducive environment for generation of well-vascularized embryoid bodies from human embryonic stem cells. Biotechnol Bioeng 88:313–320

    Article  CAS  Google Scholar 

  34. Gerecht S, Burdick JA, Ferreira LS et al (2007) Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc Natl Acad Sci USA 104:11298–11303

    Article  CAS  Google Scholar 

  35. Watt FM, Hogan BL (2000) Out of Eden: stem cells and their niches. Science 287:1427–1430

    Article  CAS  Google Scholar 

  36. Kang SW, La WG, Kang JM, Park JH, Kim BS (2008) Bone morphogenetic protein-2 enhances bone regeneration mediated by transplantation of osteogenically undifferentiated bone marrow-derived mesenchymal stem cells. Biotechnol Lett 30:1163–1168

    Article  CAS  Google Scholar 

  37. Karamboulas K, Dranse HJ, Underhill TM (2010) Regulation of BMP-dependent chondrogenesis in early limb mesenchyme by TGFbeta signals. J Cell Sci 123:2068–2076

    Article  CAS  Google Scholar 

  38. Nostro MC, Farida SSO, Audrey H et al (2011) Stage-specific signaling through TGFb family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development 138:861–871

    Article  CAS  Google Scholar 

  39. Tuli R, Tuli S, Nandi S et al (2003) Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 278:41227–41236

    Article  CAS  Google Scholar 

  40. Ying QL, Nichols J, Chambers I, Smith A (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115:281–292

    Article  CAS  Google Scholar 

  41. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10:55–63

    Article  CAS  Google Scholar 

  42. Levy O, Ruvinov E, Reem T, Granot Y, Cohen S (2010) Highly efficient osteogenic differentiation of human mesenchymal stem cells by eradication of STAT3 signaling. Int J Biochem Cell Biol 42:1823–1830

    Article  CAS  Google Scholar 

  43. Levy O, Dvir T, Tsur-Gang O, Granot Y, Cohen S (2008) Signal transducer and activator of transcription 3-A key molecular switch for human mesenchymal stem cell proliferation. Int J Biochem Cell Biol 40:2606–2618

    Article  CAS  Google Scholar 

  44. Li W, Ding S (2009) Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci 31:36–45

    Google Scholar 

  45. Zhu S, Wurda k H, Wang J et al (2009) A small molecule primes embryonic stem cells for differentiation. Cell Stem Cell 4:416–426

    Article  CAS  Google Scholar 

  46. Borowiak M, Maehr R, Chen S et al (2009) Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell Stem Cell 4:348–358

    Article  CAS  Google Scholar 

  47. Chen S, Borowiak M, Fox JL et al (2009) A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 5:258–265

    Article  CAS  Google Scholar 

  48. Tun T, Miyoshi H, Aung T et al (2002) Effect of growth factors on ex vivo bone marrow cell expansion using three-dimensional matrix support. Artif Organs 26:333–339

    Article  CAS  Google Scholar 

  49. Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R (2002) Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 99:4391–4396

    Article  CAS  Google Scholar 

  50. Kong HJ, Smith MK, Mooney DJ (2003) Designing alginate hydrogels to maintain viability of immobilized cells. Biomaterials 24:4023–4029

    Article  CAS  Google Scholar 

  51. Dar A, Shachar M, Leor J, Cohen S (2002) Optimization of cardiac cell seeding and distribution in 3D porous alginate scaffolds. Biotechnol Bioeng 80:305–312

    Article  CAS  Google Scholar 

  52. McCloskey KE, Gilroy ME, Nerem RM (2005) Use of embryonic stem cell-derived endothelial cells as a cell source to generate vessel structures in vitro. Tissue Eng 11:497–505

    Article  CAS  Google Scholar 

  53. Chen SS, Fitzgerald W, Zimmerberg J, Kleinman HK, Margolis L (2007) Cell–cell and cell-extracellular matrix interactions regulate embryonic stem cell differentiation. Stem Cells 25:553–561

    Article  CAS  Google Scholar 

  54. Bhang SH, Lee YE, Cho SW et al (2007) Basic fibroblast growth factor promotes bone marrow stromal cell transplantation-mediated neural regeneration in traumatic brain injury. Biochem Biophys Res Commun 359:40–45

    Article  CAS  Google Scholar 

  55. Martino MM, Mochizuki M, Rothenfluh DA et al (2009) Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability. Biomaterials 30:1089–1097

    Article  CAS  Google Scholar 

  56. Rosenthal A, Macdonald A, Voldman J (2007) Cell patterning chip for controlling the stem cell microenvironment. Biomaterials 28:3208–3216

    Article  CAS  Google Scholar 

  57. Tielens S, Declercq H, Gorski T et al (2007) Gelatin-based microcarriers as embryonic stem cell delivery system in bone tissue engineering: an in vitro study. Biomacromolecules 8:825–832

    Article  CAS  Google Scholar 

  58. Rohanizadeh R, Swain MV, Mason RS (2008) Gelatin sponges (Gelfoam) as a scaffold for osteoblasts. J Mater Sci Mater Med 19:1173–1182

    Article  CAS  Google Scholar 

  59. Zeng X, Zeng YS, Ma YH et al (2011) Bone marrow mesenchymal stem cells in a three dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis and reduce cavity formation in experimental spinal cord injury. Cell Transplant 20. doi: 10.3727/096368911X566181

  60. Ruhnke M, Ungefroren H, Zehle G et al (2003) Long-term culture and differentiation of rat embryonic stem cell-like cells into neuronal, glial, endothelial, and hepatic lineages. Stem Cells 21:428–436

    Article  Google Scholar 

  61. Radice M, Brun P, Cortivo R et al (2000) Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res 50:101–109

    Article  CAS  Google Scholar 

  62. Lisignoli G, Cristino S, Piacentini A et al (2005) Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold. Biomaterials 26:5677–5686

    Article  CAS  Google Scholar 

  63. Kim J, Kim IS, Cho TH et al (2007) Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 28:1830–1837

    Article  CAS  Google Scholar 

  64. Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F (2004) Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25:3211–3222

    Article  CAS  Google Scholar 

  65. Alsberg E, Anderson KW, Albeiruti A, Franceschi RT, Mooney DJ (2001) Cell-interactive alginate hydrogels for bone tissue engineering. J Dent Res 80:2025–2029

    Article  CAS  Google Scholar 

  66. Alsberg E, Anderson KW, Albeiruti A, Rowley JA, Mooney DJ (2002) Engineering growing tissues. Proc Natl Acad Sci USA 99:12025–12030

    Article  CAS  Google Scholar 

  67. Chang JC, Hsu SH, Chen DC (2009) The promotion of chondrogenesis in adipose-derived adult stem cells by an RGD-chimeric protein in 3D alginate culture. Biomaterials 30:6265–6275

    Article  CAS  Google Scholar 

  68. Connelly JT, Garcia AJ, Levenston ME (2007) Inhibition of in vitro chondrogenesis in RGD-modified three-dimensional alginate gels. Biomaterials 28:1071–1083

    Article  CAS  Google Scholar 

  69. Dvir T, Benishti N, Shachar M, Cohen S (2006) A novel perfusion bioreactor providing a homogenous milieu for tissue regeneration. Tissue Eng 12:2843–2852

    Article  CAS  Google Scholar 

  70. Dvir T, Kedem A, Ruvinov E et al (2009) Prevascularization of cardiac patch on the omentum improves its therapeutic outcome. Proc Natl Acad Sci USA 106:14990–14995

    Article  CAS  Google Scholar 

  71. Dvir-Ginzberg M, Elkayam T, Aflalo ED, Agbaria R, Cohen S (2004) Ultrastructural and functional investigations of adult hepatocyte spheroids during in vitro cultivation. Tissue Eng 10:1806–1817

    Article  CAS  Google Scholar 

  72. Dvir-Ginzberg M, Elkayam T, Cohen S (2008) Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds. FASEB J 22:1440–1449

    Article  CAS  Google Scholar 

  73. Dvir-Ginzberg M, Gamlieli-Bonshtein I, Agbaria R, Cohen S (2003) Liver tissue engineering within alginate scaffolds: effects of cell-seeding density on hepatocyte viability, morphology, and function. Tissue Eng 9:757–766

    Article  CAS  Google Scholar 

  74. Dvir-Ginzberg M, Konson A, Cohen S, Agbaria R (2007) Entrapment of retroviral vector producer cells in three-dimensional alginate scaffolds for potential use in cancer gene therapy. J Biomed Mater Res B Appl Biomater 80:59–66

    Google Scholar 

  75. Elkayam T, Amitay-Shaprut S, Dvir-Ginzberg M, Harel T, Cohen S (2006) Enhancing the drug metabolism activities of C3A–a human hepatocyte cell line–by tissue engineering within alginate scaffolds. Tissue Eng 12:1357–1368

    Article  CAS  Google Scholar 

  76. Freeman I, Cohen S (2009) The influence of the sequential delivery of angiogenic factors from affinity-binding alginate scaffolds on vascularization. Biomaterials 30:2122–2131

    Article  CAS  Google Scholar 

  77. Freeman I, Kedem A, Cohen S (2008) The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. Biomaterials 29:3260–3268

    Article  CAS  Google Scholar 

  78. Glicklis R, Shapiro L, Agbaria R, Merchuk JC, Cohen S (2000) Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol Bioeng 67:344–353

    Article  CAS  Google Scholar 

  79. Kedem A, Perets A, Gamlieli-Bonshtein I et al (2005) Vascular endothelial growth factor-releasing scaffolds enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng 11:715–722

    Article  CAS  Google Scholar 

  80. Perets A, Baruch Y, Weisbuch F et al (2003) Enhancing the vascularization of three-dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres. J Biomed Mater Res A 65:489–497

    Article  CAS  Google Scholar 

  81. Re’em T, Tsur-Gang O, Cohen S (2010) The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFbeta1-induced chondrogenesis of human mesenchymal stem cells. Biomaterials 31:6746–6755

    Article  CAS  Google Scholar 

  82. Ruvinov E, Leor J, Cohen S (2010) The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hindlimb ischemia model. Biomaterials 31:4573–4582

    Article  CAS  Google Scholar 

  83. Ruvinov E, Leor J, Cohen S (2011) The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. Biomaterials 32:565–578

    Article  CAS  Google Scholar 

  84. Shachar M, Tsur-Gang O, Dvir T, Leor J, Cohen S (2011) The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue engineering. Acta Biomater 7:152–162

    Article  CAS  Google Scholar 

  85. Stevens MM, Qanadilo HF, Langer R, Prasad Shastri V (2004) A rapid-curing alginate gel system: utility in periosteum-derived cartilage tissue engineering. Biomaterials 25:887–894

    Article  CAS  Google Scholar 

  86. Levenberg S, Huang NF, Tsur-Gang O, Ruvinov E, Landa N et al (2009) The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction. Biomaterials 30:189–195

    Article  CAS  Google Scholar 

  87. Barash Y, Dvir T, Tandeitnik P et al (2010) Electric field stimulation integrated into perfusion bioreactor for cardiac tissue engineering. Tissue Eng Part C Methods 16:1417–1426

    Article  CAS  Google Scholar 

  88. Dvir T, Levy O, Shachar M, Granot Y, Cohen S (2007) Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly. Tissue Eng 13:2185–2193

    Article  CAS  Google Scholar 

  89. Wang L, Shelton RM, Cooper PR et al (2003) Evaluation of sodium alginate for bone marrow cell tissue engineering. Biomaterials 24:3475–3481

    Article  CAS  Google Scholar 

  90. Ma HL, Hung SC, Lin SY, Chen YL, Lo WH (2003) Chondrogenesis of human mesenchymal stem cells encapsulated in alginate beads. J Biomed Mater Res A 64:273–281

    Article  CAS  Google Scholar 

  91. Dean SK, Yulyana Y, Williams G, Sidhu KS, Tuch BE (2006) Differentiation of encapsulated embryonic stem cells after transplantation. Transplantation 82:1175–1184

    Article  Google Scholar 

  92. Lee CH, Singla A, Lee Y (2001) Biomedical applications of collagen. Int J Pharm 221:1–22

    Article  CAS  Google Scholar 

  93. Schmidt CE, Baier JM (2000) Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering. Biomaterials 21:2215–2231

    Article  CAS  Google Scholar 

  94. Ifkovits JL, Burdick JA (2007) Review: photopolymerizable and degradable biomaterials for tissue engineering applications. Tissue Eng 13:2369–2385

    Article  CAS  Google Scholar 

  95. Chastain SR, Kundu AK, Dhar S, Calvert JW, Putnam AJ (2006) Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation. J Biomed Mater Res A 78:73–85

    Google Scholar 

  96. Martin I, Shastri VP, Padera RF et al (2001) Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams. J Biomed Mater Res 55:229–235

    Article  CAS  Google Scholar 

  97. Levenberg S, Huang NF, Lavik E et al (2003) Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds. Proc Natl Acad Sci USA 100:12741–12746

    Article  CAS  Google Scholar 

  98. Hwang NS, Kim MS, Sampattavanich S et al (2006) Effects of three-dimensional culture and growth factors on the chondrogenic differentiation of murine embryonic stem cells. Stem Cells 24:284–291

    Article  CAS  Google Scholar 

  99. Kraehenbuehl TP, Zammaretti P, Van der Vlies AJ et al (2008) Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel. Biomaterials 29:2757–2766

    Article  CAS  Google Scholar 

  100. Salinas CN, Cole BB, Kasko AM, Anseth KS (2007) Chondrogenic differentiation potential of human mesenchymal stem cells photoencapsulated within poly(ethylene glycol)-arginine-glycine-aspartic acid-serine thiol-methacrylate mixed-mode networks. Tissue Eng 13:1025–1034

    Article  CAS  Google Scholar 

  101. Salinas CN, Anseth KS (2009) Decorin moieties tethered into PEG networks induce chondrogenesis of human mesenchymal stem cells. J Biomed Mater Res A 90:456–464

    Google Scholar 

  102. Salinas CN, Anseth KS (2008) The influence of the RGD peptide motif and its contextual presentation in PEG gels on human mesenchymal stem cell viability. J Tissue Eng Regen Med 2:296–304

    Article  CAS  Google Scholar 

  103. Yang F, Williams CG, Wang DA et al (2005) The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells. Biomaterials 26:5991–5998

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  105. Callegari A, Bollini S, Iop L et al (2007) Neovascularization induced by porous collagen scaffold implanted on intact and cryoinjured rat hearts. Biomaterials 28:5449–5461

    Article  CAS  Google Scholar 

  106. Fujimoto KL, Tobita K, Merryman WD et al (2007) An elastic, biodegradable cardiac patch induces contractile smooth muscle and improves cardiac remodeling and function in subacute myocardial infarction. J Am Coll Cardiol 49:2292–2300

    Article  CAS  Google Scholar 

  107. Gaballa MA, Sunkomat JN, Thai H et al (2006) Grafting an acellular 3-dimensional collagen scaffold onto a non-transmural infarcted myocardium induces neo-angiogenesis and reduces cardiac remodeling. J Heart Lung Transplant 25:946–954

    Article  Google Scholar 

  108. Kochupura PV, Azeloglu EU, Kelly DJ et al (2005) Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function. Circulation 112:I-144–I-149

    Google Scholar 

  109. Glicklis R, Merchuk JC, Cohen S (2004) Modeling mass transfer in hepatocyte spheroids via cell viability, spheroid size, and hepatocellular functions. Biotechnol Bioeng 86:672–680

    Article  CAS  Google Scholar 

  110. Kloxin AM, Kloxin CJ, Bowman CN, Anseth KS (2010) Mechanical properties of cellularly responsive hydrogels and their experimental determination. Adv Mater 22:3484–3494

    Article  CAS  Google Scholar 

  111. Benoit DS, Schwartz MP, Durney AR, Anseth KS (2008) Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater 7:816–823

    Article  CAS  Google Scholar 

  112. Gelain F, Bottai D, Vescovi A, Zhang S (2006) Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures. PLoS One 1:e119

    Article  CAS  Google Scholar 

  113. Silva GA, Czeisler C, Niece KL et al (2004) Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 303:1352–1355

    Article  CAS  Google Scholar 

  114. Zhao X, Zhang S (2007) Designer self-assembling peptide materials. Macromol Biosci 7:13–22

    Article  CAS  Google Scholar 

  115. Ki CS, Park SY, Kim HJ et al (2008) Development of 3-D nanofibrous fibroin scaffold with high porosity by electrospinning: implications for bone regeneration. Biotechnol Lett 30:405–410

    Article  CAS  Google Scholar 

  116. Dvir T, Tsur-Gang O, Cohen S (2005) “Designer” scaffolds for tissue engineering and regeneration. Israel J Chem 45:487–494

    Article  CAS  Google Scholar 

  117. Jones FS, Jones PL (2000) The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 218:235–259

    Article  CAS  Google Scholar 

  118. Loeser RF (2002) Integrins and cell signaling in chondrocytes. Biorheology 39:119–124

    CAS  Google Scholar 

  119. Makino H, Sugiyama H, Kashihara N (2000) Apoptosis and extracellular matrix-cell interactions in kidney disease. Kidney Int Suppl 77:S67–75

    Article  CAS  Google Scholar 

  120. Boudreau NJ, Jones PL (1999) Extracellular matrix and integrin signalling: the shape of things to come. Biochem J 339 (Pt 3):481–488

    Article  CAS  Google Scholar 

  121. Lukashev ME, Werb Z (1998) ECM signalling: orchestrating cell behaviour and misbehaviour. Trends in Cell Biol 8:437–441

    Article  CAS  Google Scholar 

  122. Gumbiner BM (1996) Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 84:345–357

    Article  CAS  Google Scholar 

  123. Shin H, Jo S, Mikos AG (2003) Biomimetic materials for tissue engineering. Biomaterials 24:4353–4364

    Article  CAS  Google Scholar 

  124. Engelmayr GC, Jr., Cheng M, Bettinger CJ et al (2008) Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater 7:1003–1010

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  126. Zhao X, Kim J, Cezar CA et al (2011) Active scaffolds for on-demand drug and cell delivery. Proc Natl Acad Sci USA 108:67–72

    Article  CAS  Google Scholar 

  127. Pierschbacher MD, Ruoslahti E (1984) Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc Natl Acad Sci USA 81:5985–5988

    Article  CAS  Google Scholar 

  128. Ruoslahti E, Pierschbacher MD (1986) Arg-Gly-Asp: a versatile cell recognition signal. Cell 44:517–518

    Article  CAS  Google Scholar 

  129. Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RGD and integrins. Science 238:491–497

    Article  CAS  Google Scholar 

  130. Hersel U, Dahmen C, Kessler H (2003) RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 24:4385–4415

    Article  CAS  Google Scholar 

  131. Rowley JA, Mooney DJ (2002) Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 60:217–223

    Article  CAS  Google Scholar 

  132. Hwang NS, Varghese S, Zhang Z, Elisseeff J (2006) Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels. Tissue Eng 12:2695–2706

    Article  CAS  Google Scholar 

  133. Alvarez-Barreto JF, Shreve MC, Deangelis PL, Sikavitsas VI (2007) Preparation of a functionally flexible, three-dimensional, biomimetic poly(L-lactic acid) scaffold with improved cell adhesion. Tissue Eng 13:1205–1217

    Article  CAS  Google Scholar 

  134. Sawyer AA, Weeks DM, Kelpke SS, McCracken MS, Bellis SL (2005) The effect of the addition of a polyglutamate motif to RGD on peptide tethering to hydroxyapatite and the promotion of mesenchymal stem cell adhesion. Biomaterials 26:7046–7056

    Article  CAS  Google Scholar 

  135. Nuttelman CR, Tripodi MC, Anseth KS (2005) Synthetic hydrogel niches that promote hMSC viability. Matrix Biol 24:208–218

    Article  CAS  Google Scholar 

  136. Li YJ, Chung EH, Rodriguez RT, Firpo MT, Healy KE (2006) Hydrogels as artificial matrices for human embryonic stem cell self-renewal. J Biomed Mater Res A 79:1–5

    Google Scholar 

  137. Sapir Y, Kryukov O, Cohen S (2011) Integration of multiple cell–matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration. Biomaterials 32:1838–1847

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  139. Raeber GP, Lutolf MP, Hubbell JA (2005) Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. Biophys J 89:1374–1388

    Article  CAS  Google Scholar 

  140. Lutolf MP, Weber FE, Schmoekel HG et al (2003) Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 21:513–518

    Article  CAS  Google Scholar 

  141. Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23:47–55

    Article  CAS  Google Scholar 

  142. Saito A, Suzuki Y, Ogata S, Ohtsuki C, Tanihara M (2003) Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope. Biochim Biophys Acta 1651:60–67

    CAS  Google Scholar 

  143. Saito A, Suzuki Y, Ogata S, Ohtsuki C, Tanihara M (2004) Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide. J Biomed Mater Res A 70:115–121

    Article  CAS  Google Scholar 

  144. Saito A, Suzuki Y, Ogata S, Ohtsuki C, Tanihara M (2005) Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells. J Biomed Mater Res A 72:77–82

    Article  CAS  Google Scholar 

  145. Saito A, Suzuki Y, Kitamura M et al (2006) Repair of 20-mm long rabbit radial bone defects using BMP-derived peptide combined with an alpha-tricalcium phosphate scaffold. J Biomed Mater Res A 77:700–706

    Google Scholar 

  146. Lee JS, Murphy WL (2010) Modular peptides promote human mesenchymal stem cell differentiation on biomaterial surfaces. Acta Biomater 6:21–28

    Article  CAS  Google Scholar 

  147. Choi YJ, Lee JY, Park JH et al (2010) The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis. Biomaterials 31:7226–7238

    Article  CAS  Google Scholar 

  148. Chen Y, Webster TJ (2009) Increased osteoblast functions in the presence of BMP-7 short peptides for nanostructured biomaterial applications. J Biomed Mater Res A 91:296–304

    Google Scholar 

  149. Bergeron E, Senta H, Mailloux A et al (2009) Murine preosteoblast differentiation induced by a peptide derived from bone morphogenetic proteins-9. Tissue Eng Part A 15:3341–3349

    Article  CAS  Google Scholar 

  150. Moore NM, Lin NJ, Gallant ND, Becker ML (2011) Synergistic enhancement of human bone marrow stromal cell proliferation and osteogenic differentiation on BMP-2-derived and RGD peptide concentration gradients. Acta Biomater 7:2091–2100

    Article  CAS  Google Scholar 

  151. Zouani OF, Chollet C, Guillotin B, Durrieu MC (2010) Differentiation of pre-osteoblast cells on poly(ethylene terephthalate) grafted with RGD and/or BMPs mimetic peptides. Biomaterials 31:8245–8253

    Article  CAS  Google Scholar 

  152. Park H, Temenoff JS, Tabata Y, Caplan AI, Mikos AG (2007) Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem cell and growth factor delivery for cartilage tissue engineering. Biomaterials 28:3217–3227

    Article  CAS  Google Scholar 

  153. Ferreira LS, Gerecht S, Fuller J et al (2007) Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. Biomaterials 28:2706–2717

    Article  CAS  Google Scholar 

  154. Carpenedo RL, Bratt-Leal AM, Marklein RA et al (2009) Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules. Biomaterials 30:2507–2515

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  156. Fan VH, Tamama K, Au A et al (2007) Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells. Stem Cells 25:1241–1251

    Article  CAS  Google Scholar 

  157. Swindle CS, Tran KT, Johnson TD et al (2001) Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor. J Cell Biol 154:459–468

    Article  CAS  Google Scholar 

  158. Phillippi JA, Miller E, Weiss L et al (2008) Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations. Stem Cell 26:127–134

    Article  CAS  Google Scholar 

  159. Miller ED, Fisher GW, Weiss LE, Walker LM, Campbell PG (2006) Dose-dependent cell growth in response to concentration modulated patterns of FGF-2 printed on fibrin. Biomaterials 27:2213–2221

    Article  CAS  Google Scholar 

  160. Miller ED, Li K, Kanade T et al (2011) Spatially directed guidance of stem cell population migration by immobilized patterns of growth factors. Biomaterials 32:2775–2785

    Article  CAS  Google Scholar 

  161. Bishop JR, Schuksz M, Esko JD (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446:1030–1037

    Article  CAS  Google Scholar 

  162. Chen BL, Arakawa T, Hsu E et al (1994) Strategies to suppress aggregation of recombinant keratinocyte growth factor during liquid formulation development. J Pharm Sci 83:1657–1661

    Article  CAS  Google Scholar 

  163. Shriver Z, Liu D, Sasisekharan R (2002) Emerging views of heparan sulfate glycosaminoglycan structure/activity relationships modulating dynamic biological functions. Trends Cardiovasc Med 12:71–77

    Article  CAS  Google Scholar 

  164. Casu B, Lindahl U (2001) Structure and biological interactions of heparin and heparan sulfate. Adv Carbohydr Chem Biochem 57:159–206

    Article  CAS  Google Scholar 

  165. Wu ZL, Zhang L, Yabe T et al (2003) The involvement of heparan sulfate (HS) in FGF1/HS/FGFR1 signaling complex. J Biol Chem 278:17121–17129

    Article  CAS  Google Scholar 

  166. Pye DA, Vives RR, Turnbulli JE, Hyde P, Gallagher JT (1998) Heparan sulfate oligosaccharides require 6-O-sulfation for promotion of basic fibroblast growth factor mitogenic activity. J Biol Chem 273:22936–22942

    Article  CAS  Google Scholar 

  167. Raman R, Sasisekharan V, Sasisekharan R (2005) Structural insights into biological roles of protein-glycosaminoglycan interactions. Chem Biol 12:267–277

    Article  CAS  Google Scholar 

  168. Forsten-Williams K, Chua CC, Nugent MA (2005) The kinetics of FGF-2 binding to heparan sulfate proteoglycans and MAP kinase signaling. J Theor Biol 233:483–499

    Article  CAS  Google Scholar 

  169. Jakobsson L, Kreuger J, Holmborn K et al (2006) Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis. Dev Cell 10:625–634

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  171. Benoit DS, Collins SD, Anseth KS (2007) Multifunctional hydrogels that promote osteogenic hMSC differentiation through stimulation and sequestering of BMP2. Adv Funct Mater 17:2085–2093

    Article  CAS  Google Scholar 

  172. Willerth SM, Rader A, Sakiyama-Elbert SE (2008) The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds. Stem Cell Res 1:205–218

    Article  CAS  Google Scholar 

  173. Webber MJ, Han X, Murthy SN et al (2010) Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. J Tissue Eng Regen Med 4:600–610

    Article  CAS  Google Scholar 

  174. Oschatz C, Maas C, Lecher B et al (2011) Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 34:258–268

    Article  CAS  Google Scholar 

  175. Kloxin AM, Tibbitt MW, Anseth KS (2010) Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nat Protoc 5:1867–1887

    Article  CAS  Google Scholar 

  176. Guo WH, Frey MT, Burnham NA, Wang YL (2006) Substrate rigidity regulates the formation and maintenance of tissues. Biophys J 90:2213–2220

    Article  CAS  Google Scholar 

  177. Engler AJ, Griffin MA, Sen S et al (2004) Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments. J Cell Biol 166:877–887

    Article  CAS  Google Scholar 

  178. Boontheekul T, Hill EE, Kong HJ, Mooney DJ (2007) Regulating myoblast phenotype through controlled gel stiffness and degradation. Tissue Eng 13:1431–1442

    Article  CAS  Google Scholar 

  179. Collin O, Tracqui P, Stephanou A et al (2006) Spatiotemporal dynamics of actin-rich adhesion microdomains: influence of substrate flexibility. J Cell Sci 119:1914–1925

    Article  CAS  Google Scholar 

  180. Engler AJ, Carag-Krieger C, Johnson CP et al (2008) Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating. J Cell Sci 121:3794–3802

    Article  CAS  Google Scholar 

  181. Saez A, Ghibaudo M, Buguin A, Silberzan P, Ladoux B (2007) Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates. Proc Natl Acad Sci USA 104:8281–8286

    Article  CAS  Google Scholar 

  182. Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  184. Ruiz SA, Chen CS (2008) Emergence of patterned stem cell differentiation within multicellular structures. Stem Cells 26:2921–2927

    Article  Google Scholar 

  185. Karp JM, Yeh J, Eng G et al (2007) Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells. Lab Chip 7:786–794

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  187. Huebsch N, Arany PR, Mao AS et al (2010) Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 9:518–526

    Article  CAS  Google Scholar 

  188. Tse JR, Engler AJ () Stiffness gradients mimicking in vivo tissue variation regulate mesenchymal stem cell fate. PLoS One 6:e15978

    Google Scholar 

  189. Schek RM, Taboas JM, Segvich SJ, Hollister SJ, Krebsbach PH (2004) Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds. Tissue Eng 10:1376–1385

    CAS  Google Scholar 

  190. Holland TA, Bodde EW, Baggett LS et al (2005) Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds. J Biomed Mater Res A 75:156–167

    Google Scholar 

  191. Natesan S, Zhang G, Baer DG et al (2011) A bilayer construct controls adipose-derived stem cell differentiation into endothelial cells and pericytes without growth factor stimulation. Tissue Eng Part A 17:941–953

    Article  CAS  Google Scholar 

  192. Guo X, Park H, Liu G et al (2009) In vitro generation of an osteochondral construct using injectable hydrogel composites encapsulating rabbit marrow mesenchymal stem cells. Biomaterials 30:2741–2752

    Article  CAS  Google Scholar 

  193. Dormer NH, Singh M, Wang L, Berkland CJ, Detamore MS (2010) Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals. Ann Biomed Eng 38:2167–2182

    Article  Google Scholar 

  194. Wang X, Wenk E, Zhang X et al (2009) Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering. J Control Release 134:81–90

    Article  CAS  Google Scholar 

  195. Winkler IG, Barbier V, Wadley R et al (2010) Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood 116:375–385

    Article  CAS  Google Scholar 

  196. Meinel L, Karageorgiou V, Fajardo R et al (2004) Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Ann Biomed Eng 32:112–122

    Article  Google Scholar 

  197. Gerecht-Nir S, Cohen S, Itskovitz-Eldor J (2004) Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation. Biotechnol Bioeng 86:493–502

    Article  CAS  Google Scholar 

  198. Braccini A, Wendt D, Jaquiery C et al (2005) Three-dimensional perfusion culture of human bone marrow cells and generation of osteoinductive grafts. Stem Cell 23:1066–1072

    Article  Google Scholar 

  199. Sikavitsas VI, Bancroft GN, Holtorf HL, Jansen JA, Mikos AG (2003) Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Proc Natl Acad Sci USA 100:14683–14688

    Article  CAS  Google Scholar 

  200. van den Dolder J, Bancroft GN, Sikavitsas VI et al (2003) Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh. J Biomed Mater Res A 64:235–241

    Article  CAS  Google Scholar 

  201. Terraciano V, Hwang N, Moroni L et al (2007) Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells 25:2730–2738

    Article  CAS  Google Scholar 

  202. Rodrigues CA, Fernandes TG, Diogo MM, da Silva CL,Cabral JM (2011) Stem cell cultivation in bioreactors. Biotechnol Adv. doi: 10.1016/j.biotechadv.2011.06.009

  203. Ruvinov E, Cohen S (2011) Instructive biomaterials for myocardial regeneration and repair. In: Zilberman M (ed) Active implants and scaffolds for tissue regeneration. Springer, Berlin.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel

    Tali Re’em & Smadar Cohen

Authors
  1. Tali Re’em
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Smadar Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Smadar Cohen .

Editor information

Editors and Affiliations

  1. Department für Biotechnologie, Universität für Bodenkultur, Muthgasse 18, Wien, 1190, Austria

    Cornelia Kasper

  2. , CrossBIT - Center for Biocompatibility, Hannover Medical School, Feodor-Lynen-Str. 31, Hannover, 30625, Germany

    Frank Witte

  3. , Bioprozess- und Biosystemtechnik, Technische Universität Hamburg-Harburg, Denickestrasse 15, Hamburg, 21073, Germany

    Ralf Pörtner

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Re’em, T., Cohen, S. (2011). Microenvironment Design for Stem Cell Fate Determination. In: Kasper, C., Witte, F., Pörtner, R. (eds) Tissue Engineering III: Cell - Surface Interactions for Tissue Culture. Advances in Biochemical Engineering Biotechnology, vol 126. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2011_118

Download citation

Publish with us

Policies and ethics

Search

Navigation