Advertisement

Bioactive Hydrogels and Their Applications in Regenerative Medicine

  • Xiaolei Nie
  • Yon Jin Chuah
  • Dongan WangEmail author
Chapter

Abstract

Hydrogel-based scaffolds remain a prevalent choice for regenerative medical treatments because of their capacities of imitating native extracellular matrices. Hydrogel can be classified into either synthetic or natural origins. The natural hydrogels are certainly cell benevolent as they mimic the natural microenvironment of the native tissue environment. On the other hand, the nonlethal synthetic hydrogel is hydrophilic and can be tuneable for customised application. This section presents current established gelation mechanism of the hydrogel. The philosophies can be ordered into physical, chemical and biological cross-linking. Bioactive particles known to enhance the functionalities of the hydrogel can be fused into the hydrogel-based scaffold with the approaches of these strategies. Because of the high calibre of hydrogels, the scaffolds have much capacities and applications in regenerative medicine. One of the brilliant standard hydrogels, polyethylene glycol (PEG), is displayed as a classic case to show the theories presented in the first three sections of this chapter which clarified the fusion of different useful particles (e.g. cell-adhesive molecules, enzymatically degradable molecules and cell recognition bioactive molecules) in the hydrogel-based scaffolds. Overall, this chapter intends to provide some insights in the general strategies for designing hydrogel scaffolds with desired functionalities.

Keywords

Hydrogel Cross-linking Bioactive factors Polyethylene glycol Cell delivery 

References

  1. 1.
    Augst A, Kong H, Mooney D. Alginate hydrogels as biomaterials. Macromol Biosci 2016;6(8):623–33. Science Citation Index, EBSCOhost, viewed 25 January 2016.Google Scholar
  2. 2.
    Bent A, Foote J, Siegel S, Faerber G, Chao R, Gormley E. Collagen implant for treating stress urinary incontinence in women with urethral hypermobility. J Urol 2016;166(4):1354–57. Science Citation Index, EBSCOhost, viewed 16 March 2016.Google Scholar
  3. 3.
    Bohl K, West J. Nitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation. Biomaterials. 2000;21(22):2273–8. MEDLINE, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  4. 4.
    Brownlee M, Cerami A. A glucose-controlled insulin-delivery system: semisynthetic insulin bound to lectin. Science. 1979;4423:1190. JSTOR Journals, EBSCOhost, viewed 3 February 2016.CrossRefGoogle Scholar
  5. 5.
    Burdick J, Mason M, Hinman A, Thorne K, Anseth K. Research article: delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. J Control Release. 2002;83:53–63. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  6. 6.
    Cai W. Engineering in translational medicine. [Electronic Resource], n.p.: London: Springer London: Imprint: Springer, 2014., NTU Library Catalogue, EBSCOhost, viewed 14 March 2016.Google Scholar
  7. 7.
    Chen C, Mrksich M, Huang S, Whitesides G, Ingber D. Geometric control of cell life and death. Science. 1997;5317:1425. JSTOR Journals, EBSCOhost, viewed 6 February 2016.CrossRefGoogle Scholar
  8. 8.
    Chenite A, Chaput C, Wang D, Combes C, Buschmann M, Hoemann C, Leroux J, Atkinson B, Binette F, Selmani A. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials. 2000;21:2155–61. ScienceDirect, EBSCOhost, viewed 25 January 2016.CrossRefPubMedGoogle Scholar
  9. 9.
    Choi C, Hagvall S, Wu B, Dunn J, Beygui R, Kim C. Cell interaction with three-dimensional sharp-tip nanotopography. 2007;9, eScholarship, EBSCOhost, viewed 6 February 2016.Google Scholar
  10. 10.
    Chun C, Lee S, Kim C, Hong K, Kim S, Yang H, Song S. Doxorubicin – polyphosphazene conjugate hydrogels for locally controlled delivery of cancer therapeutics. Biomaterials. 2009;30:4752–62. ScienceDirect, EBSCOhost, viewed 1 February 2016.CrossRefPubMedGoogle Scholar
  11. 11.
    Cushing M, Anseth K. Hydrogel cell cultures. Science. 2007;5828:1133. JSTOR Journals, EBSCOhost, viewed 4 February 2016.CrossRefGoogle Scholar
  12. 12.
    Dalby M, Gadegaard N, Tare R, Andar A, Riehle M, Herzyk P, Wilkinson C, Oreffo R. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6(12):997–1003. MEDLINE, EBSCOhost, viewed 6 February 2016.CrossRefPubMedGoogle Scholar
  13. 13.
    Discher D, Janmey P, Wang Y. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;5751:1139. Expanded Academic ASAP, EBSCOhost, viewed 5 February 2016.CrossRefGoogle Scholar
  14. 14.
    DeForest C, Anseth K. Advances in bioactive hydrogels to probe and direct cell fate. Ann Rev Chem Biomol Eng. 2012;3:421–44. MEDLINE, EBSCOhost, viewed 4 February 2016.CrossRefGoogle Scholar
  15. 15.
    DeForest C, Tirrell D. A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat Mater. 2015;14(5):523–31. MEDLINE, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  16. 16.
    DeLong S, Gobin A, West J. Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration. J Control Release. 2005;109:139–48. Proceedings of the Twelfth International Symposium on Recent Advances in Drug Delivery Systems, ScienceDirect, EBSCOhost, viewed 14March2016.CrossRefPubMedGoogle Scholar
  17. 17.
    Drury J, Mooney D. Review: hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 2003;24:4337–51. Synthesis of Biomimetic Polymers, ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  18. 18.
    Ehrbar M, Djonov V, Schnell C, Tschanz S, Martiny-Baron G, Schenk U, Wood J, Burri P, Hubbell J, Zisch, A. Cell-demanded liberation of VEGF(121) from fibrin implants induces local and controlled blood vessel growth. Circ Res 2016;94(8):1124–32. Science Citation Index, EBSCOhost, viewed 15 March 2016.Google Scholar
  19. 19.
    Elbert D, Pratt A, Lutolf M, Halstenberg S, Hubbell J. Protein delivery from materials formed by self-selective conjugate addition reactions. J Control Release. 2001;76:11–25. ScienceDirect, EBSCOhost, viewed 25 January2016.CrossRefPubMedGoogle Scholar
  20. 20.
    Engler A, Griffin M, Sen S, Bönnemann C, Sweeney H, Discher D. Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments. J Cell Biol. 2004;6:877. JSTOR Journals, EBSCOhost, viewed 5 February 2016.CrossRefGoogle Scholar
  21. 21.
    Engler A, Sen S, Sweeney H, Discher D. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–89. MEDLINE, EBSCOhost, viewed 5 February 2016.CrossRefPubMedGoogle Scholar
  22. 22.
    Fan W, Tong X, Yan Q, Fu S, Zhao Y. Photodegradable and size-tunable single-chain nanoparticles prepared from a single main-chain coumarin-containing polymer precursor. Chem Commun 2016;50(88):13492–94. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  23. 23.
    Girotti A, Reguera J, Rodríguez-Cabello J, Arias F, Alonso M, Matestera A. Design and bioproduction of a recombinant multi(bio)functional elastin-like protein polymer containing cell adhesion sequences for tissue engineering purposes. J Mater Sci Mater Med. 2004;15(4):479–89. MEDLINE, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  24. 24.
    Haubner R, Schmitt W, Holzemann G, Goodman S, Jonczyk A, Kessler H. Cyclic RGD peptides containing beta-turn mimetics. J Am Chem Soc. 1996;34:7881. Expanded Academic ASAP, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  25. 25.
  26. 26.
  27. 27.
    Huebsch N, Arany P, Mao A, Shvartsman D, Ali O, Bencherif S, Rivera-Feliciano J, Mooney D. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 2016;9(6):518–26. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  28. 28.
    Huynh C, Nguyen M, Lee D. Injectable block copolymer hydrogels: achievements and future challenges for biomedical applications. Macromol 2016;44(17):6629–36. Science Citation Index, EBSCOhost, viewed 25 January 2016.Google Scholar
  29. 29.
    Ishihara K, Kobayashi M, Ishimaru N, Shinohara I. Glucose induced permeation control of insulin through a complex membrane consisting of immobilized glucose oxidase and a poly(amine). Polym J. 1984;16(8):625–31. J-STAGE, EBSCOhost, viewed 3 February 2016.CrossRefGoogle Scholar
  30. 30.
    Kast C, Bernkop-Schnürch A. Thiolated polymers—thiomers: development and in vitro evaluation of chitosan–thioglycolic acid conjugates. Biomaterials. 2001;22:2345–52. ScienceDirect, EBSCOhost, viewed 25 January 2016.CrossRefPubMedGoogle Scholar
  31. 31.
    Kim Y, Park M, Song S. Injectable polyplex hydrogel for localized and long-term delivery of siRNA. Acs Nano 2016;6(7):5757–66. Science Citation Index, EBSCOhost, viewed 27 January 2016.Google Scholar
  32. 32.
    Kitano S, Koyama Y, Kataoka K, Okano T, Sakurai Y. A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety. J Control Release. 1992;19:161–70. ScienceDirect, EBSCOhost, viewed 3 February 2016.CrossRefGoogle Scholar
  33. 33.
    Kobayashi S, Uyama H, Kimura S. Enzymatic polymerization. Chem Rev. 2001;12:3793. Academic OneFile, EBSCOhost, viewed 25 January 2016.CrossRefGoogle Scholar
  34. 34.
    Koo L, Irvine D, Mayes A, Lauffenburger D, Griffith L. Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus. J Cell Sci. 2002;115(Pt 7):1423–33. MEDLINE, EBSCOhost, viewed 5 February 2016.PubMedGoogle Scholar
  35. 35.
    Lee K, Peters M, Mooney D. Controlled drug delivery from polymers by mechanical signals. Adv Mater 2016;13(11):837–+.Science Citation Index, EBSCOhost, viewed 3 February 2016.Google Scholar
  36. 36.
    Lee S, Miller J, Moon J, West J. Proteolytically degradable hydrogels with a fluorogenic substrate for studies of cellular proteolytic activity and migration. Biotechnol Prog 2016;21(6):1736–41. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  37. 37.
    Lee S, Moon J, Miller J, West J. Poly(ethylene glycol) hydrogels conjugated with a collagenase-sensitive fluorogenic substrate to visualize collagenase activity during three-dimensional cell migration. Biomaterials. 2007;28:3163–70. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  38. 38.
    Leslie-Barbick J, Moon J, West J. Covalently-immobilized vascular endothelial growth factor promotes endothelial cell tubulogenesis in poly(ethylene glycol) diacrylate hydrogels. J Biomater Sci Polym Ed. 2009;20(12):1763–79. MEDLINE, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  39. 39.
    Lo C, Wang H, Dembo M, Wang Y. Cell movement is guided by the rigidity of the substrate. Biophys J. 2000;79:144–52. ScienceDirect, EBSCOhost, viewed 5 February 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lüdemann I, Pörtner R, Schaefer C, Schick K, Srámkova K, Reher K, Neumaier M, Franěk F, Märkl H. Improvement of the culture stability of non-anchorage-dependent animal cells grown in serum-free media through immobilization. Cytotechnology. 1995;19(2):111–24. MEDLINE, EBSCOhost, viewed 4February 2016.CrossRefPubMedGoogle Scholar
  41. 41.
    Lutolf M, Lauer-Fields J, Schmoekel H, Metters A, Weber F, Fields G, Hubbell J. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc Natl Acad Sci USA. 2003;9:5413. JSTOR Journals, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  42. 42.
    Lutolf M, Raeber G, Zisch A, Tirelli N, Hubbell J.Cell-responsive synthetic hydrogels. Adv Mater 2016;15(11):888–+. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  43. 43.
    Malkoch M, Vestberg R, Gupta N, Mespouille L, Dubois P, Mason A, Hedrick J, Liao Q, Frank C, Kingsbury K, Hawker C. Synthesis of well-defined hydrogel networks using click chemistry. Chem Commun (Cambridge, England). 2006;26:2774–6. MEDLINE, EBSCOhost, viewed 25 January 2016.CrossRefGoogle Scholar
  44. 44.
    Mann B, Tsai A, Scott-Burden T, West J. Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomaterials. 1999;20:2281–6. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  45. 45.
    Mann B, Schmedlen R, West J. Tethered-TGF-b increases extracellular matrix production of vascular smooth muscle cells. Biomater-Guildford. 2001;22(5):439–44. British Library Document Supply Centre Inside Serials & Conference Proceedings, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  46. 46.
    Miller J, Shen C, Legant W, Baranski J, Blakely B, Chen C. Bioactive hydrogels made from step-growth derived PEG – peptide macromers. Biomaterials. 2010;31:3736–43. ScienceDirect, EBSCOhost, viewed 1 April 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Miyata T, Asami N, Uragami T. A reversibly antigen-responsive hydrogel. Nature. 1999;6738:766. Academic OneFile, EBSCOhost, viewed 26 January 2016.CrossRefGoogle Scholar
  48. 48.
    Murdan S. Electro-responsive drug delivery from hydrogels. J Control Release 2016;92(1–2):1–17. Science Citation Index, EBSCOhost, viewed 3 February 2016.Google Scholar
  49. 49.
    Nguyen M, Alsberg E. Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine. Prog Polymer Sci 2016;39, Topical Issue on Biomaterials, pp. 1235–65, ScienceDirect, EBSCOhost, viewed 25 January 2016.Google Scholar
  50. 50.
    Nguyen K, West J. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials. 2002;23:4307–14. Injectable Polymeric Biomaterials, ScienceDirect, EBSCOhost, viewed 25 January 2016.CrossRefPubMedGoogle Scholar
  51. 51.
    Nishida K, Hayashida Y, Yamamoto K, Maeda N, Nagai S, Kikuchi A, Tano Y, Okano T, Watanabe H, Adachi E, Watanabe K, Yamato M. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med. 2004;12:1187. Expanded Academic ASAP, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  52. 52.
    Nuttelman C, Rice M, Rydholm A, Salinas C, Shah D, Anseth K. Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering. Prog Polymer Sci 2016;33(2):167–79. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  53. 53.
    Palecek S, Loftus J, Ginsberg M, Lauffenburger D, Horwitz A. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature. 1997;6616:537. Expanded Academic ASAP, EBSCOhost, viewed 5 February 2016.CrossRefGoogle Scholar
  54. 54.
    Park M, Chun C, Ahn S, Ki M, Cho C, Song S. Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery. Biomaterials. 2010;31:1349–59. ScienceDirect, EBSCOhost, viewed 27 January 2016.CrossRefPubMedGoogle Scholar
  55. 55.
    Patra S, Roy E, Karfa P, Kumar S, Madhuri R, Sharma P. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment. ACS Appl Mater Interfaces. 2015;7(17):9235. Supplemental Index, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  56. 56.
    Pratt A, Weber F, Schmoekel H, Muller R, Hubbell J. Synthetic extracellular matrices for in situ tissue engineering. Biotechnol Bioeng 2016;86(1):27–36. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  57. 57.
    Ruoslahti E, Pierschbacher M. New perspectives in cell adhesion: RGD and integrins. Science. 1987;4826:491. JSTOR Journals, EBSCOhost, viewed 4 February 2016.CrossRefGoogle Scholar
  58. 58.
    Saha K, Keung A, Irwin E, Li Y, Little L, Schaffer D, Healy K. Substrate modulus directs neural stem cell behavior. Biophys J. 2008;95:4426–38. ScienceDirect, EBSCOhost, viewed 5 February 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Salinas C, Anseth K. The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities. Biomaterials. 2008;29:2370–7. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Seliktar D. Designing cell-compatible hydrogels for biomedical applications. Science (New York, NY). 2012;336(6085):1124–8. MEDLINE, EBSCOhost, viewed 20 January 2016.CrossRefGoogle Scholar
  61. 61.
    Seliktar D, Zisch A, Lutolf M, Wrana J, Hubbell J. MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. J Biomed Mater Research Part A 2016;68A(4);704–16. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  62. 62.
    Sharpe L, Daily A, Horava S, Peppas N. Therapeutic applications of hydrogels in oral drug delivery. Expert Opin Drug Delivery 2016;11(6):901–15. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  63. 63.
    Singla A, Garg A, Aggarwal D. Paclitaxel and its formulations. Int J Pharm. 2002;235:179–92. ScienceDirect, EBSCOhost, viewed 1 February 2016.CrossRefPubMedGoogle Scholar
  64. 64.
    Soontornworajit B, Zhou J, Shaw M, Fan T, Wang Y. Hydrogel functionalization with DNA aptamers for sustained PDGF-BB release. Chem Commun (Cambridge, England). 2010;46(11):1857–9. MEDLINE, EBSCOhost, viewed 2 February 2016.CrossRefGoogle Scholar
  65. 65.
    Sternlicht M, Werb Z. How matrix metalloproteinases regulate cell behavior. Ann Rev Cell Dev Biol. 2001;17(1):463. Academic Search Premier, EBSCOhost, viewed 14March 2016.CrossRefGoogle Scholar
  66. 66.
    Tallawi M, Rosellini E, Barbani N, Cascone M, Rai R, Saint-Pierre G, Boccaccini A. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review. J R Soc Interf R Soc. 2015;12(108):20150254. MEDLINE, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  67. 67.
    Tsang V, Chen A, Cho L, Jadin K, Sah R, DeLong S, West J, Bhatia S. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J 2007;3. AGRIS, EBSCOhost, viewed 14 March 2016.Google Scholar
  68. 68.
    Uzman A. Molecular cell biology (4th edition). Biochem Mol Biol Educ. 2001;29(3):126–8. British Library Document Supply Centre Inside Serials & Conference Proceedings, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  69. 69.
    Weber L, Hayda K, Haskins K, Anseth K. The effects of cell-matrix interactions on encapsulated b-cell function within hydrogels functionalized with matrix-derived adhesive peptides. Biomater-Guildford. 2007;28(19):3004–11. British Library Document Supply Centre Inside Serials & Conference Proceedings, EBSCOhost, viewed 14 March 2016.CrossRefGoogle Scholar
  70. 70.
    Weber L, Anseth K. Hydrogel encapsulation environments functionalized with extracellular matrix interactions increase islet insulin secretion. Matrix Biol. 2008;27:667–73. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    West J, Hubbell J. Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromol 2016;32(1):241–4. Science Citation Index, EBSCOhost, viewed 14 March 2016.Google Scholar
  72. 72.
    Xun W, Wu D, Li Z, Wang H, Huang F, Cheng S, Zhang X, Zhuo R. Peptide-functionalized thermo-sensitive hydrogels for sustained drug delivery. Macromol Biosci. 2009;9(12):1219–26. MEDLINE, EBSCOhost, viewed 2 February 2016.CrossRefPubMedGoogle Scholar
  73. 73.
    Yan B, Boyer J, Habault D, BrandaN, Zhao Y. Near infrared light triggered release of biomacromolecules from hydrogels loaded with upconversion nanoparticles. J Am Chem Soc 2016;134(40):16558–61. Science Citation Index, EBSCOhost, viewed 3 February 2016.Google Scholar
  74. 74.
    Young J, Engler A. Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro. Biomaterials. 2011;32:1002–9. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  75. 75.
    Zhou M, Smith A, Das A, Hodson N, Collins R, Ulijn R, Gough J. Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells. Biomaterials. 2009;30:2523–30. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedGoogle Scholar
  76. 76.
    Zhu J. Review: bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials. 2010;31:4639–56. ScienceDirect, EBSCOhost, viewed 14 March 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Zhu J, Marchant R. Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices. 2011;8(5):607–26. MEDLINE, EBSCOhost, viewed 14 March 2011.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  1. 1.School of Chemical and Biomedical EngineeringNanyang Technological UniversitySingaporeSingapore

Personalised recommendations