Micro- and Nanotechnology in Tissue Engineering



This manuscript provides an overview of the recent developments regarding micro and nanotechnologies and their applications in tissue engineering (TE). Micro and nanotechnologies have been increasingly recognized as powerful tools for designing advanced TE strategies, both as production methods and as analysis tools. These technologies can be used to generate scaffolds with enhanced functionality that will not act as mere substrates for cellular adhesion but play the role of an active agent in the process of tissue regeneration. Moreover, these technologies can be used to study and control the phenomena occurring at the cellular microenvironment. Herein, the main technologies developed/under development are described and their diverse potential applications are discussed.


Tissue Engineering Tissue Engineering Application Soft Lithography Microcontact Printing Tissue Engineering Approach 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Daniela Coutinho acknowledges the foundation for science and technology (FCT), for her PhD scholarship (SFRH/BD/37156/2007). This work was carried out under the scope of the EU funded project HIPPOCRATES (NMP3-CT-2003-505758) and was partially supported by European Network of Excellence EXPERTISSUES (NMP3-CT-2004-500283). The authors also thank Albino Martins, Marina Santos, Rogério Pirraco, and Erkan Baran for kindly providing some of the pictures presented.


  1. 1.
    Albert F, Mahmet T. Microengineering of cellular interactions. Annu Rev Biomed Eng. 2000;2:227–56.CrossRefGoogle Scholar
  2. 2.
    Alexander R, Padmavathy R, Arno WT, et al. Designing a hepatocellular microenvironment with protein microarraying and poly(ethylene glycol) photolithography. Langmuir. 2004;20:2999–3005.CrossRefGoogle Scholar
  3. 3.
    Aloy P, Russell RB. Structure-based systems biology: a zoom lens for the cell. FEBS Lett. 2005;579(8):1854–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Alves da Silva ML, Crawford A, Mundy J, et al. Evaluation of extracellular matrix formation in polycaprolactone and starch-compounded polycaprolactone nanofiber meshes when seeded with bovine articular chondrocytes. Tissue Eng Part A. 2008;15(2):377–85.Google Scholar
  5. 5.
    Anderson JR, Chiu DT, Jackman RJ, et al. Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. Anal Chem. 2000;72(14):3158–64.PubMedCrossRefGoogle Scholar
  6. 6.
    Anselme K, Bigerelle M, Noel B, et al. Effect of grooved titanium substratum on human osteoblastic cell growth. J Biomed Mater Res. 2002;60(4):529–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Araújo JV, Martins A, Leonor IB, et al. Surface controlled biomimetic coating of polycaprolactone nanofiber meshes to be used as bone extracellular matrix analogues. J Biomater Sci Polym Edn. 2008;19(10):1261–78.CrossRefGoogle Scholar
  8. 8.
    Bajpai V, He P, Goettler L, et al. Controlled syntheses of conducting polymer micro- and nano-structures for potential applications. Synth Met. 2006;156(5–6):466–9.CrossRefGoogle Scholar
  9. 9.
    Barber RW, Emerson DR. Optimal design of microfluidic networks using biologically inspired principles. Microfluidics Nanofluidics. 2008;4(3):179–91.CrossRefGoogle Scholar
  10. 10.
    Barbucci R, Magnani A. Conformation of human plasma proteins at polymer surfaces: the effectiveness of surface heparinization. Biomaterials. 1994;15(12):955–62.PubMedCrossRefGoogle Scholar
  11. 11.
    Barbucci R, Torricelli P, Fini M, et al. Proliferative and re-defferentiative effects of photo-immobilized micro-patterned hyaluronan surfaces on chondrocyte cells. Biomaterials. 2005;26(36):7596–605.PubMedCrossRefGoogle Scholar
  12. 12.
    Ber S, Torun Köse G, Hasirci V. Bone tissue engineering on patterned collagen films: an in vitro study. Biomaterials. 2005;26(14):1977–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Bernard A, Renault JP, Michel B, et al. Microcontact printing of proteins. Adv Mater. 2000;12(14):1067–70.CrossRefGoogle Scholar
  14. 14.
    Bettinger CJ, Orrick B, Misra A, et al. Microfabrication of poly (glycerol–sebacate) for contact guidance applications. Biomaterials. 2006;27:2558–65.PubMedCrossRefGoogle Scholar
  15. 15.
    Bhatia SN, Underhill GH. High-throughput analysis of signals regulating stem cell fate and function. Curr Opin Chem Biol. 2007;11:357–66.PubMedCrossRefGoogle Scholar
  16. 16.
    Biebuyck HA, Larsen NB, Delamarche E, et al. Lithography beyond light: microcontact printing with monolayer resists. Ibm J Res Dev. 1997;41(1–2):159–70.CrossRefGoogle Scholar
  17. 17.
    Biggs MJP, Richards RG, McFarlane S, et al. Adhesion formation of primary human osteoblasts and the functional response of mesenchymal stem cells to 330nm deep microgrooves. J R Soc Interface. 2008;5(27): 1231–42.PubMedCrossRefGoogle Scholar
  18. 18.
    Boland ED, Matthews JA, Pawlowski KJ, et al. Electrospinning collagen and elastin: preliminary vascular tissue engineering. Front Biosci. 2004;9:1422–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Borenstein JT, Terai H, King KR, et al. Microfabrication technology for vascularized tissue engineering. Biomed Microdevices. 2002;4(3):167–75.CrossRefGoogle Scholar
  20. 20.
    Boyan BD, Hummert TW, Dean DD, et al. Role of material surfaces in regulating bone and cartilage cell response. Biomaterials. 1996;17(2):137–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Cannizzaro C, Figallo E, Gerecht S, Burdick JA, Langer R, Elvassore N, et al. Micro-bioreactor array for controlling cellular microenvironments. Lab Chip. 2007; 7:710–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Carraro A, Hsu WM, Kulig KM, et al. In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices. 2008;10(6):795–805.PubMedCrossRefGoogle Scholar
  23. 23.
    Castner DG, Ratner RD. Biomedical surface science: foundations to frontiers. Surf Sci. 2002;500(1–3):28–60.CrossRefGoogle Scholar
  24. 24.
    Chao PG, Tang ZL, Angelini E, et al. Dynamic osmotic loading of chondrocytes using a novel microfluidic device. J Biomech. 2005;38(6):1273–81.PubMedCrossRefGoogle Scholar
  25. 25.
    Charest JL, Eliason MT, Garcia AJ, et al. Combined microscale mechanical topography and chemical patterns on polymer cell culture substrates. Biomaterials. 2006;27(11):2487–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Chaubey A, Ross KJ, Leadbetter RM, et al. Surface patterning: tool to modulate stem cell differentiation in an adipose system. J Biomed Mater Res Part B Appl Biomater. 2008;84B(1):70–8.CrossRefGoogle Scholar
  27. 27.
    Christensen TB, Pedersen CM, Grondhal KG, et al. PCR biocompatibility of lab-on-a-chip and MEMS materials. J Micromech Microeng. 2007;17(8):1527–32.CrossRefGoogle Scholar
  28. 28.
    Chua K-N, Chai C, Lee P-C, et al. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 2006;27(36):6043–51.PubMedCrossRefGoogle Scholar
  29. 29.
    Chua K-N, Lim W-S, Zhang P, et al. Stable immobilization of rat hepatocyte spheroids on galactosylated nanofiber scaffold. Biomaterials. 2005;26:2537–47.PubMedCrossRefGoogle Scholar
  30. 30.
    Cimetta E, Figallo E, Cannizzaro C, et al. Micro-bioreactor arrays for controlling cellular environments: design principles for human embryonic stem cell applications. Methods. 2008;47(2):81–9.Google Scholar
  31. 31.
    Clark P, Connolly P, Curtis AS, et al. Cell guidance by ultrafine topography in vitro. J Cell Sci. 1991;99:73–7.PubMedGoogle Scholar
  32. 32.
    Crozatier C, Le Berre M, Chen Y. Multi-colour micro-contact printing based on microfluidic network inking. Microelectronic Eng. 2006;83(4–9):910–3.CrossRefGoogle Scholar
  33. 33.
    Curtis A, Riehle M. Tissue engineering: the biophysical background. Phys Med Biol. 2001;46(4):R47–65.PubMedCrossRefGoogle Scholar
  34. 34.
    Daxini SC, Nichol JW, Sieminski AL, et al. Micropatterned polymer surfaces improve retention of endothelial cells exposed to flow-induced shear stress. Biorheology. 2006; 43(1):45–55.PubMedGoogle Scholar
  35. 35.
    Du Y, Lo E, Vidula MK, et al. Method of bottom-up directed assembly of cell-laden microgels. Cell Mol Bioeng. 2008;1(2):157–62.PubMedCrossRefGoogle Scholar
  36. 36.
    Engel E, Michiardi A, Navarro M, et al. Nanotechnology in regenerative medicine: the materials side. Trends Biotechnol. 2007;26(1):39–47.PubMedCrossRefGoogle Scholar
  37. 37.
    Falconnet D, Csucs G, Grandin HM, et al. Surface engineering approaches to micropattern surfaces for cell-based assays. Biomaterials. 2006;27(16):3044–63.PubMedCrossRefGoogle Scholar
  38. 38.
    Felix R, Sommer B, Sprecher C, Leunig M, Ganz R, Hofstetter W. Wear particles and surface topographies are modulators of osteoclastogenesis in vitro. J Biomed Mater Res. 2005;72A(1):67–76.CrossRefGoogle Scholar
  39. 39.
    Flaim CJ, Teng D, Chien S, Bhatia SN. Combinatorial signaling microenvironments for studying stem cell fate. Stem Cells Dev. 2008;17:29–39.PubMedCrossRefGoogle Scholar
  40. 40.
    García AJ. Get a grip: integrins in cell-biomaterial interactions. Biomaterials. 2005;26(36):7525–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Gates BD, Xu Q, Stewart M, et al. New approaches to nanofabrication: molding, printing, and other techniques. Chem Rev. 2005;105(4):1171–96.PubMedCrossRefGoogle Scholar
  42. 42.
    Gomes ME, Reis RL. Tissue engineering: key elements and some trends. Macromol Biosci. 2004;4:737–42.PubMedCrossRefGoogle Scholar
  43. 43.
    Gooding JJ, Mearns F, Yang WR, et al. Self-assembled monolayers into the 21(st) century: recent advances and applications. Electroanalysis. 2003;15(2):81–96.CrossRefGoogle Scholar
  44. 44.
    Hasirci N, Zorlutuna P, Hasirci V. Nanopatterned collagen tubes for vascular tissue engineering. J Tissue Eng Regen Med. 2008;2(6):373–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Hierlemann A, Brand O, Hagleitner C, et al. Microfabrication techniques for chemical/biosensors. Proc IEEE. 2003; 91(6): 839–63.CrossRefGoogle Scholar
  46. 46.
    Huang ZM, Zhang YZ, Kotaki M, et al. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol. 2003;63(15):2223–53.CrossRefGoogle Scholar
  47. 47.
    Ikada Y. Challenges in tissue engineering. J R Soc Interface. 2006;3(10):589–601.PubMedCrossRefGoogle Scholar
  48. 48.
    Jenney CR, Anderson JM. Adsorbed serum proteins responsible for surface dependent human macrophage behavior. J Biomed Mater Res. 2000;49(4):435–47.PubMedCrossRefGoogle Scholar
  49. 49.
    Johnson PC, Mikos AG, Fisher JP, et al. Strategic directions in tissue engineering. Tissue Eng. 2007;13(12): 2827–37.PubMedCrossRefGoogle Scholar
  50. 50.
    Karp JM, Yeh J, Eng G, et al. Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells. Lab Chip. 2007;7:786–94.PubMedCrossRefGoogle Scholar
  51. 51.
    Karp JM, Yeo Y, Geng WL, et al. A photolithographic method to create cellular micropatterns. Biomaterials. 2006;27(27):4755–64.PubMedCrossRefGoogle Scholar
  52. 52.
    Kawata S, Sun HB. Two-photon photopolymerization as a tool for making micro-devices. Appl Surf Sci. 2003;208:153–8.CrossRefGoogle Scholar
  53. 53.
    Kenar H, Kocabas A, Aydinli A, et al. Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement. J Biomed Mater Res Part A. 2008;85A(4):1001–10.CrossRefGoogle Scholar
  54. 54.
    Khademhosseini A, Eng G, Yeh J, et al. Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. J Biomed Mater Res Part A. 2006; 79(3):522–32.CrossRefGoogle Scholar
  55. 55.
    Khademhosseini A, Eng G, Yeh J, et al. Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed Microdevices. 2007;9(2):149–57.PubMedCrossRefGoogle Scholar
  56. 56.
    Khademhosseini A, Ferreira L, Blumling III J, et al. Co-culture of human embryonic stem cells with murine embryonic fibroblasts on microwell-patterned substrates. Biomaterials. 2007;27(36):5968–77.CrossRefGoogle Scholar
  57. 57.
    Khademhosseini A, Jason Burdick A, Langer R. Fabrication of gradient hydrogels using a microfluidics/photopolymerization process. Langmuir. 2004;20(13):5153–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Khademhosseini A, Langer R, Borenstein J, et al. Microscale technologies for tissue engineering and biology. Proc Nat Acad Sci USA. 2006;103(8):2480–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Khetani SR, Bhatia SN. Microscale culture of human liver cells for drug development. Nat Biotechnol. 2008;26: 120–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Kidoaki S, Kwon IK, Matsuda T. Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. Biomaterials. 2005;26(1):37–46.PubMedCrossRefGoogle Scholar
  61. 61.
    Kjeang E, Djilali N, Sinton D. Planar and three-dimensional microfluidic fuel cell architectures. International Mechanical Engineering Congress and Exposition 2007. Micro Nano Syst. 2008;11(Pt a and Pt B):941–943.Google Scholar
  62. 62.
    Koegler WS, Griffith LG. Osteoblast response to PLGA tissue engineering scaffolds with PEO modified surface chemistries and demonstration of patterned cell response. Biomaterials. 2004;25(14):2819–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Korin N, Bransky A, Dinnar U, et al. A parametric study of human fibroblasts culture in a microchannel bioreactor. Lab Chip. 2007;7(5):611–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Kumar A, Whitesides GM. Features of gold having micrometer to centimiter dimensions can be formed through a combination of stamping with an elastomeric stamp and an alkanethiol ink followed by chemical etching. Appl Phys Lett. 1993;63(14):2002–4.CrossRefGoogle Scholar
  65. 65.
    Kunzler TP, Huwiler C, Drobek T, et al. Systematic study of osteoblast response to nanotopography by means of nanoparticle-density gradients. Biomaterials. 2007;28(33):5000–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Kurpinski K, Chu J, Hashi C, et al. Anisotropic mechanosensing by mesenchymal stem cells. Proc Nat Acad Sci USA. 2006;103(44):16095–100.PubMedCrossRefGoogle Scholar
  67. 67.
    Lange SA, Benes V, Kern DP, et al. Microcontact printing of DNA molecules. Anal Chem. 2004;76(6):1641–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Lanza RP, Langer R, Vacanti J. Principles of tissue engineering. New York: Academic;2000.Google Scholar
  69. 69.
    LeDuc PR, Bellin RM. Nanoscale intracellular organization and functional architecture mediating cellular behavior. Ann Biomed Eng. 2006;34(1):102–13.PubMedCrossRefGoogle Scholar
  70. 70.
    Lee S, Chang W-J, Bashir R, et al. “Bottom-up” approach for implementing nano/microstructure using biological and chemical interactions. Biotechnol Bioprocess Eng. 2007; 12(3):185–99.CrossRefGoogle Scholar
  71. 71.
    Li WJ, Laurencin CT, Caterson EJ, et al. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res. 2002;60(4):613–21.PubMedCrossRefGoogle Scholar
  72. 72.
    Li X, van der Steen G, van Dedem GWK, et al. Improving mixing in microbioreactors. Chem Eng Sci. 2008;63(11): 3036–46.CrossRefGoogle Scholar
  73. 73.
    Liangfang Zhang Frank Gu, Benjamin Teply A, Nina Mann, Andrew Wang, Aleksandar Radovic-Moreno F, Robert Langer, Omid Farokhzad C. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proceedings of the National Academy of Sciences of the United States of America 105(7);2008.Google Scholar
  74. 74.
    Lin X, Helmke BP. Micropatterned structural control suppresses mechanotaxis of endothelial cells. Biophys J. 2008;95(6):3066–78.PubMedCrossRefGoogle Scholar
  75. 75.
    Ma K, Chan CK, Liao S, et al. Electrospun nanofiber scaffolds for rapid and rich capture of bone marrow-derived hematopoietic stem cells. Biomaterials. 2008;29(13):2096–103.PubMedCrossRefGoogle Scholar
  76. 76.
    Malmsten M. Formation of adsorbed protein layers. J Colloid Interface Sci. 1998;207(2):186–99.PubMedCrossRefGoogle Scholar
  77. 77.
    Martins A, Araujo JV, Reis RL, et al. Electrospun nanostructured scaffolds for tissue engineering applications. Nanomedicine. 2007;2(6):929–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Martins A, Cunha J, Macedo F, et al. Improvement of Polycaprolactone Nanofibers Topographies: Testing the Influence in Osteoblastic Proliferation. In Technical Proceedings of the 2006 NSTI Nanotechnology Conference and Trade Show. Lausanne, Switzerland; 2006.Google Scholar
  79. 79.
    Martins A, Reis RL, Neves NM. Electrospinning: processing technique for tissue engineering scaffolding. Int Mater Rev. 2008;53(5):257–74.CrossRefGoogle Scholar
  80. 80.
    Matthews JA, Boland ED, Wnek GE, et al. Electrospinning of collagen type II: a feasibility study. J Bioact Compat Polym. 2003;18(2):125–34.CrossRefGoogle Scholar
  81. 81.
    Matthews JA, Wnek GE, Simpson DG, et al. Electrospinning of collagen nanofibers. Biomacromolecules. 2002;3(2): 232–8.PubMedCrossRefGoogle Scholar
  82. 82.
    McGregor A, Pietak A, Gauthier S, Oleschuk R, Waldman SD. Are micropatterned substrates for directed cell organization an effective method to create ordered 3D tissue constructs? J Tissue Eng Regen Med. 2008;2(7):450–3.PubMedCrossRefGoogle Scholar
  83. 83.
    Mijatovic D, Eijkel JC, Tvan den Berg A. Technologies for nanofluidic systems: top-down vs. bottom-up – a review. Lab Chip. 2005;5:492–500.PubMedCrossRefGoogle Scholar
  84. 84.
    Min BM, Lee G, Kim SH, et al. Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. Biomaterials. 2004;25(7–8):1289–97.PubMedCrossRefGoogle Scholar
  85. 85.
    Mironov V, Prestwich G, Forgacs G. Bioprinting living structures. J Mater Chem. 2007;17(20):2054–60.CrossRefGoogle Scholar
  86. 86.
    Morrison D, Suh KY, Khademhosseini A. Micro and nanopatterning for bacteria- and virus-based biosensing applications. In: Zourob M, Elwary S, Turner Anthony PF, editors. Principles of bacterial detection: biosensors, recognition receptors and microsystems. Springer 2008.Google Scholar
  87. 87.
    Mrksich M, Dike LE, Tien J, et al. Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Exp Cell Res. 1997;235(2): 305–13.PubMedCrossRefGoogle Scholar
  88. 88.
    Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci. 2007;32(8–9):762–98.CrossRefGoogle Scholar
  89. 89.
    Nakanishi K, Sakiyama T, Imamura K. On the adsorption of proteins on solid surfaces, a common but very complicated phenomenon. J Biosci Bioeng. 2001;91(3):233–44.PubMedCrossRefGoogle Scholar
  90. 90.
    Nakanishi J, Takarada T, Yamaguchi K, et al. Recent advances in cell micropatterning techniques for bioanalytical and biomedical sciences. Anal Sci. 2008;24(1):67–72.PubMedCrossRefGoogle Scholar
  91. 91.
    Nalayanda DD, Kalukanimuttam M, Schmidtke DW. Micropatterned surfaces for controlling cell adhesion and rolling under flow. Biomed Microdevices. 2007;9(2):207–14.PubMedCrossRefGoogle Scholar
  92. 92.
    Ostrovidov S, Jiang J, Sakai Y, et al. Membrane-based PDMS microbioreactor for perfused 3D primary rat hepatocyte cultures. Biomed Microdevices. 2004;6(4):279–87.PubMedCrossRefGoogle Scholar
  93. 93.
    Ostuni E, Whitesides GM, Takayama S, Jiang X, Ingber DE. Soft lithography in biology and biochemistry. Annu Rev Biomed Eng. 2001;3:335–73.Google Scholar
  94. 94.
    Petersen EF, Spencer RGS, McFarland EW. Microengineering neocartilage scaffolds. Biotechnol Bioeng. 2002;78(7): 801–4.PubMedCrossRefGoogle Scholar
  95. 95.
    Petronis S, Eckert KL, Gold J, et al. Microstructuring ceramic scaffolds for hepatocyte cell culture. J Mater Sci Mater Med. 2001;12:523–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Pincus MR, Nicholas S. Physiological structure and function of proteins. In: Sperelakis N, editors. Cell physiology source book. 3rd ed. San Diego: Academic; 2001.Google Scholar
  97. 97.
    Pla-Roca M, Fernandez JG, Mills CA, et al. Micro/nanopatterning of proteins via contact printing using high aspect ratio PMMA stamps and nanoimprint apparatus. Langmuir. 2007;23(16):8614–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Powers MJ, Domansky K, Kaazempur-Mofrad MR, et al. A Microfrabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng. 2002;78(3):257–69.PubMedCrossRefGoogle Scholar
  99. 99.
    Powers MJ, Janigian DM, Wack KE, et al. Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng. 2002;8(3): 499–513.PubMedCrossRefGoogle Scholar
  100. 100.
    Py C, Roth D, Levesque I, et al. An integrated shadow-mask based on a stack of inorganic insulators for high-resolution OLEDs using evaporated or spun-on materials. Synth Met. 2001;122(1):225–7.CrossRefGoogle Scholar
  101. 101.
    Quist AP, Pavlovic E, Oscarsson S. Recent advances in microcontact printing. Analyt Bioanalyt Chem. 2004;381: 591–600.CrossRefGoogle Scholar
  102. 102.
    Ratner BD, Bryant SJ. Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng. 2004;6:41–75.PubMedCrossRefGoogle Scholar
  103. 103.
    Robert L, Legeais JM, Robert AM, et al. Corneal collagens. Pathol Biol. 2001;49(4):353–63.PubMedCrossRefGoogle Scholar
  104. 104.
    Roco MC. Nanotechnology: convergence with modern biology and medicine. Curr Opin Biotechnol. 2003;14:337–46.PubMedCrossRefGoogle Scholar
  105. 105.
    Rozkiewicz DI, Kraan Y, Werten MWT, et al. Covalent microcontact printing of proteins for cell patterning. Chem Eur J. 2006;12(24):6290–7.CrossRefGoogle Scholar
  106. 106.
    Ruiz SA, Chen CS. Microcontact printing: a tool to pattern. Soft Matter. 2007;3:168–77.CrossRefGoogle Scholar
  107. 107.
    Ryu W, Fasching RJ, Vyakarnam M, et al. Microfabrication technology of biodegradable polymers for interconnecting microstructures. J Microelectromech Syst. 2006;15(6): 1457–65.CrossRefGoogle Scholar
  108. 108.
    Santos MI, Tuzlakoglu K, Fuchs S, et al. Endothelial cell colonization and angiogenic potential of combined nano- and micro-fibrous scaffolds for bone tissue engineering. Biomaterials. 2008;29(32):4306–13.PubMedCrossRefGoogle Scholar
  109. 109.
    Sarkar S, Lee GY, Wong JY, et al. Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications. Biomaterials. 2006; 27(27):4775–82.PubMedCrossRefGoogle Scholar
  110. 110.
    Schoen FJ, Mitchell RN. Tissues, the extracellular matrix and cell-biomaterial interactions. In: Ratner BDH, Hoffman AS, Schoen FJ, Lemons JE, editors. Biomaterials science an introduction to materials in medicine. New York: Academic; 2004.Google Scholar
  111. 111.
    Scholl M, Sprossler C, Denyer M, et al. Ordered networks of rat hippocampal neurons attached to silicon oxide surfaces. J Neurosci Methods. 2000;104(1):65–75.PubMedCrossRefGoogle Scholar
  112. 112.
    Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Curr Opin Cell Biol. 2008;20(5): 551–6.PubMedCrossRefGoogle Scholar
  113. 113.
    Seal BL, Otero TC, Panitch A. Polymeric biomaterials for tissue and organ regeneration. Mater Sci Eng R Rep. 2001;34(4–5):147–230.CrossRefGoogle Scholar
  114. 114.
    Senaratne W, Andruzzi L, Ober CK. Self-assembled monolayers and polymer brushes in biotechnology: current applications and future perspectives. Biomacromolecules. 2005;6(5):2427–48.PubMedCrossRefGoogle Scholar
  115. 115.
    Siebers MC, ter Brugge PJ, Walboomers XF, et al. Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review. Biomaterials. 2005;26(2): 137–46.PubMedCrossRefGoogle Scholar
  116. 116.
    Singhvi R, Kumar A, Lopez GP, et al. Engineering cell shape and function. Science. 1994;264(5159):696–8.PubMedCrossRefGoogle Scholar
  117. 117.
    Skladal P. Advances in electrochemical immunosensors. Electroanalysis. 1997;9(10):737–45.CrossRefGoogle Scholar
  118. 118.
    Staples M, Daniel K, Cima MJ, et al. Application of micro- and nano-electromechanical devices to drug delivery. Pharm Res. 2006;23(5):847–63.PubMedCrossRefGoogle Scholar
  119. 119.
    Stock UA, Vacanti JP. Tissue engineering: current state and prospects. Annu Rev Med. 2001;52:443–51.PubMedCrossRefGoogle Scholar
  120. 120.
    Suh KY, Kim YS, Lee HH. Capillary force lithography. Adv Mater. 2001;13(18):1386–9.CrossRefGoogle Scholar
  121. 121.
    Suh KY, Lee HH. Capillary force lithography: large-area patterning, self-organization, and anisotropic dewetting. Adv Funct Mater. 2002;12(6–7):405–13.CrossRefGoogle Scholar
  122. 122.
    Suh KY, Lee HH. Formation of complex polymeric microstructures through physical self-organization and capillary dynamics. J Micromech Microeng. 2005;15(2):400–7.CrossRefGoogle Scholar
  123. 123.
    Sundaray B, Subramanian V, Natarajan TS, et al. Electrospinning of continuous aligned polymer fibers. Appl Phys Lett. 2004;84(7):1222–4.CrossRefGoogle Scholar
  124. 124.
    Thibault C, De Berre V, Casimirius S, et al. Direct microcontact printing of oligonucleotides for biochip applications. J Nanobiotechnol. 2005;3(1):7.CrossRefGoogle Scholar
  125. 125.
    Thiébaud P, Lauer L, Knoll W, et al. PDMS device for patterned application of microfluids to neuronal cells arranged by microcontact printing. Biosens Bioelectron. 2002;17 (1–2): 87–93.PubMedCrossRefGoogle Scholar
  126. 126.
    Tsang VL, Chen AA, Cho LM, et al. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J. 2007;21(3):790–801.CrossRefGoogle Scholar
  127. 127.
    Tuzlakoglu K, Bolgen N, Salgado AJ, et al. Nano- and micro-fiber combined scaffolds: a new architecture for bone tissue engineering. J Mater Sci Mater Med. 2005; 16(12):1099–104.PubMedCrossRefGoogle Scholar
  128. 128.
    Uludag H, de Vos P, Tresco PA. Technology of mammalian cell encapsulation. Adv Drug Deliv Rev. 2000;42(1): 29–64.PubMedCrossRefGoogle Scholar
  129. 129.
    Vacanti CA. The history of tissue engineering. J Cell Mol Med. 2006;10(3):569–76.PubMedCrossRefGoogle Scholar
  130. 130.
    Vogt AK, Wrobel G, Meyer W, et al. Synaptic plasticity in micropatterned neuronal networks. Biomaterials. 2005; 26(15):2549–57.PubMedCrossRefGoogle Scholar
  131. 131.
    Vozzi G, Flaim CJ, Bianchi F, et al. Microfabricated PLGA scaffolds: a comparative study for application to tissue engineering. Mater Sci Eng C Biomim Supramol Syst. 2002;20(1–2):43–7.CrossRefGoogle Scholar
  132. 132.
    Wang M, Braun HG, Kratzmüller T, et al. Patterning polymers by micro-fluid-contact printing. Adv Mater. 2001; 13(17):1312–7.CrossRefGoogle Scholar
  133. 133.
    Wang F, Wang H, Wang J, et al. Microfluidic delivery of small molecules into mammalian cells based on hydrodynamic focusing. Biotechnol Bioeng. 2008;100(1):150–8.PubMedCrossRefGoogle Scholar
  134. 134.
    Webster TJ, Ergun C, Doremus RH, et al. Enhanced osteoclast-like cell functions on nanophase ceramics. Biomaterials. 2001;22(11):1327–33.PubMedCrossRefGoogle Scholar
  135. 135.
    Wilbur JL, Kim E, Xin YN, et al. Lithographic molding – a convenient route to structures with submicrometer dimensions. Adv Mater. 1995;7(7):649–52.CrossRefGoogle Scholar
  136. 136.
    Wilbur JL, Kumar A, Kim E, et al. Microfabrication by microcontact printing of self-assembled monolayers. Adv Mater. 1994;6:600–4.CrossRefGoogle Scholar
  137. 137.
    Wozniak MA, Modzelewska K, Kwong L, et al. Focal adhesion regulation of cell behavior. Biochimica et Biophysica Acta (BBA) Mol Cell Res. 2004;1692(2–3):103–119.Google Scholar
  138. 138.
    Wu M-H, Huang S-B, Cui Z, et al. Development of perfusion-based micro 3-D cell culture platform and its application for high throughput drug testing. Sens Actuators B Chem. 2008;129(1):231–40.CrossRefGoogle Scholar
  139. 139.
    Wu MH, Lin JL, Wang J, et al. Development of high throughput optical sensor array for on-line pH monitoring in micro-scale cell culture environment. Biomed Microdevices. 2008;11(1):265–73.CrossRefGoogle Scholar
  140. 140.
    Wu MH, Urban JP, Cui Z, et al. Development of PDMS microbioreactor with well-defined and homogenous culture environment for chondrocyte 3-D culture. Biomed Microdevices. 2006;8(4):331–40.PubMedCrossRefGoogle Scholar
  141. 141.
    Xia Y, Whitesides GM. Soft lithography. Angewandte Chemie Int Ed. 1998;37:550–75.CrossRefGoogle Scholar
  142. 142.
    Xie J, Willerth SM, Li X, et al. The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials. 2008;30:354–62.PubMedCrossRefGoogle Scholar
  143. 143.
    Xu CY, Inai R, Kotaki M, et al. Electrospun nanofiber fabrication as synthetic extracellular matrix and its potential for vascular tissue engineering. Tissue Eng. 2004;10(7–8): 1160–8.PubMedGoogle Scholar
  144. 144.
    Xu CY, Inai R, Kotaki M, et al. Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials. 2004;25:877–86.PubMedCrossRefGoogle Scholar
  145. 145.
    Yang F, Murugan R, Wang S, et al. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials. 2005;26(15):2603–10.PubMedCrossRefGoogle Scholar
  146. 146.
    Yang ST, Zhang X, Wen Y. Microbioreactors for high-throughput cytotoxicity assays. Curr Opin Drug Discov Dev. 2008;11(1):111–27.Google Scholar
  147. 147.
    Yeh J, Ling Y, Karp JM, et al. Micromolding of shape-controlled, harvestable cell-laden hydrogels. Biomaterials. 2006;27(31):5391–8.PubMedCrossRefGoogle Scholar
  148. 148.
    Yu BY, Chou PH, Sun YM, et al. Topological micropatterned membranes and its effect on the morphology and growth of human mesenchymal stem cells (hMSCs). J Memb Sci. 2006;273(1–2):31–7.CrossRefGoogle Scholar
  149. 149.
    Zahor D, Radko A, Vago R, et al. Organization of mesenchymal stem cells is controlled by micropatterned silicon substrates. Mater Sci Eng C Biomim Supramol Syst. 2007;27(1):117–21.CrossRefGoogle Scholar
  150. 150.
    Zhang S. Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol. 2003;21(10):1171–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Zhang S. Building from the bottom up. Mater Today. 2003;6(5):20–7.CrossRefGoogle Scholar
  152. 152.
    Zhang S, Marini DM, Hwang W, et al. Design of nanostructured biological materials through self-assembly of peptides and proteins. Curr Opin Chem Biol. 2002;6(6): 865–71.PubMedCrossRefGoogle Scholar
  153. 153.
    Zhao XM, XiaG YN, Whitesides M. Fabrication of three-dimensional micro-structures: microtransfer molding. Adv Mater. 1996;8(10):837.CrossRefGoogle Scholar
  154. 154.
    Zhu B, Zhang Q, Lu Q, et al. Nanotopographical guidance of C6 glioma cell alignment and oriented growth. Biomaterials. 2004;25(18):4215–23.PubMedCrossRefGoogle Scholar
  155. 155.
    Zinger O, Zhao G, Schwartz Z, et al. Differential regulation of osteoblasts by substrate microstructural features. Biomaterials. 2005;26(14):1837–47.PubMedCrossRefGoogle Scholar
  156. 156.
    Zook JD, Burns DW, Herb WR, et al. Optically excited self-resonant microbeams. In 8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX). Stockholm, Sweden: Elsevier Science Sa Lausanne;1995.Google Scholar

Copyright information

© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, Department of Polymer EngineeringUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineTaipas, GuimarãesPortugal
  2. 2.PT Government Associated LaboratoryIBB – Institute for Biotechnology and BioengineeringBragaPortugal

Personalised recommendations