Skip to main content

The Role of Oxidative Stress in the Response of Endothelial Cells to Metals

  • Chapter
  • First Online:
Biologically Responsive Biomaterials for Tissue Engineering

Abstract

The involvement of endothelial cells in inflammation and blood vessel formation (angiogenesis) makes them important for the integration of metal implants. Metal degradation products can, however, influence these processes, possibly leading to ineffective wound healing, prolonged inflammation and eventually aseptic loosening of the implant. Different metal degradation processes have been shown to lead to ROS formation. Oxidative stress, therefore, can mediate the reactions of the human body to the implant. While the response of endothelial cells to oxidative stress has been well studied, the effects of ROS produced as the result of metal degradation have not been addressed as yet. Therefore, in this study the reactions of endothelial cells to the products of cathodic half-reaction of corrosion induced directly on Ti6Al4V alloy by electrochemical polarisation were investigated. Furthermore, models were developed to simulate inflammation- and corrosion-induced oxidative stress applied to endothelial cells grown on Ti6Al4V alloy and on cell culture polystyrene (PS) as a control. Endothelial cells grown on Ti6Al4V alloy were shown to be in a state of oxidative stress, which was further increased upon H2O2 treatment or electrochemical polarisation. The role of oxidative stress in aseptic loosening as well as the possibility to interfere with this process for a better therapeutical outcome are discussed in this chapter.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bauer TW, Schils J (1999) The pathology of total joint arthroplasty II. Mechanisms of implant failure. Skeletal Radiol 28:483–497

    Article  CAS  Google Scholar 

  2. Bikondoa O, Pang CL, Ithinin R, Muryn CA, Onishi H, Thornton G (2006) Direct visualization of defect-mediated dissociation of water on TiO2(110). Nat Mater 5:189–192

    Article  CAS  Google Scholar 

  3. Blumenthal NC, Cosma V, Jaffe W, Stuchin S (1994) A new technique for quantitation of metal particulates and metal reaction products in tissues near implants. J Appl Biomater 5:191–193

    Article  CAS  Google Scholar 

  4. Bockris JOM, Reddy AKN, Gamboa-Aldeco M (1998) Modern electrochemistry. Plenum, New York

    Google Scholar 

  5. Brauchle M, Funk JO, Kind P, Werner S (1996) Ultraviolet B and H2O2 are potent inducers of vascular endothelial growth factor expression in cultured keratinocytes. J Biol Chem 271:21793–21797

    Article  CAS  Google Scholar 

  6. Cai H (2005) Hydrogen peroxide regulation of endothelial function: origins mechanisms and consequences. Cardiovasc Res 68:26–36

    Article  CAS  Google Scholar 

  7. Case CP, Langkamer VG, James C, Palmer MR, Kemp AJ, Heap PF, Solomon L (1994) Widespread dissemination of metal debris from implants. J Bone Joint Surg Br 76:701–712

    CAS  Google Scholar 

  8. Clark T, Johnson D (1997) Activation of titanium electrodes for voltammetric detection of oxygen and hydrogen peroxide in alkaline media. Electroanalysis 9:273–278

    Article  CAS  Google Scholar 

  9. Clechet P, Martelet C, Martin JR, Olier R (1979) Photoelectrochemical behaviour of TiO2 and formation of hydrogen-peroxide. Electrochim Acta 24:457–461

    Article  CAS  Google Scholar 

  10. D’autreaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    Article  Google Scholar 

  11. Davies KJ (1987) Protein damage and degradation by oxygen radicals I general aspects. J Biol Chem 262:9895–9901

    CAS  Google Scholar 

  12. Davies KJ (1999) The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life 48:41–47

    CAS  Google Scholar 

  13. Davies KJ (2000) Oxidative stress antioxidant defenses and damage removal repair and replacement systems. IUBMB Life 50:279–289

    Article  CAS  Google Scholar 

  14. De Bono DP, Yang WD (1995) Exposure to low concentrations of hydrogen peroxide causes delayed endothelial cell death and inhibits proliferation of surviving cells. Atherosclerosis 114:235–245

    Article  Google Scholar 

  15. Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673

    Article  CAS  Google Scholar 

  16. Dickinson DA, Moellering DR, Iles KE, Patel RP, Levonen AL, Wigley A, Darley-Usmar VM, Forman HJ (2003) Cytoprotection against oxidative stress and the regulation of glutathione synthesis. Biol Chem 384:527–537

    Article  CAS  Google Scholar 

  17. Diegelmann RF, Evans MC (2004) Wound healing: an overview of acute fibrotic and delayed healing. Front Biosci 9:283–289

    Article  CAS  Google Scholar 

  18. Disegi JA (2000) Titanium alloys for fracture fixation implants. Injury 31(Suppl 4):14–17

    Article  Google Scholar 

  19. Doorn PF, Campbell PA, Amstutz HC (1996) Metal versus polyethylene wear particles in total hip replacements. A review. Clin Orthop Relat Res (329 Suppl): S206–S216

    Google Scholar 

  20. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    CAS  Google Scholar 

  21. Finkel T (2003) Oxidant signals and oxidative stress. Curr Opin Cell Biol 15:247–254

    Article  CAS  Google Scholar 

  22. Forman HJ, Torres M (2002) Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. Am J Respir Crit Care Med 166:S4–S8

    Article  Google Scholar 

  23. Galli F, Piroddi M, Annetti C, Aisa C, Floridi E, Floridi A (2005) Oxidative stress and reactive oxygen species. Contrib Nephrol 149:240–260

    Article  CAS  Google Scholar 

  24. Gilbert JL, Zarka L, Chang E, Thomas CH (1998) The reduction half cell in biomaterials corrosion: oxygen diffusion profiles near and cell response to polarized titanium surfaces. J Biomed Mater Res 42:321–330

    Article  CAS  Google Scholar 

  25. Gomes A, Fernandes E, Lima JL (2005) Fluorescence probes used for detection of reactive oxygen species. J Biochem Biophys Methods 65:45–80

    Article  CAS  Google Scholar 

  26. Gonzalez-Pacheco FR, Deudero JJ, Castellanos MC, Castilla MA, Alvarez-Arroyo MV, Yague S, Caramelo C (2006) Mechanisms of endothelial response to oxidative aggression: protective role of autologous VEGF and induction of VEGFR2 by H2O2. Am J Physiol Heart Circ Physiol 291:H1395–H1401

    Article  CAS  Google Scholar 

  27. Goodman SB (1994) The effects of micromotion and particulate materials on tissue differentiation. Bone chamber studies in rabbits. Acta Orthop Scand Suppl 258:1–43

    CAS  Google Scholar 

  28. Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453:314–321

    Article  CAS  Google Scholar 

  29. Hallab NJ, Jacobs JJ, Skipor A, Black J, Mikecz K, Galante JO (2000) Systemic metal-protein binding associated with total joint replacement arthroplasty. J Biomed Mater Res 49:353–361

    Article  CAS  Google Scholar 

  30. Harris ED (1992) Regulation of antioxidant enzymes. FASEB J 6:2675–2683

    CAS  Google Scholar 

  31. Harris WH, Schiller AL, Scholler JM, Freiberg RA, Scott R (1976) Extensive localized bone resorption in the femur following total hip replacement. J Bone Joint Surg Am 58:612–618

    CAS  Google Scholar 

  32. Holmgren A (1995) Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide. Structure 3:239–243

    Article  CAS  Google Scholar 

  33. Jacobs JJ, Gilbert JL, Urban RM (1998) Corrosion of metal orthopaedic implants. J Bone Joint Surg Am 80:268–282

    CAS  Google Scholar 

  34. Jacobs JJ, Hallab NJ, Skipor AK, Urban RM (2003) Metal degradation products: a cause for concern in metal-metal bearings? Clin Orthop Relat Res (417):139–147

    Google Scholar 

  35. Jacobs JJ, Silverton C, Hallab NJ, Skipor AK, Patterson L, Black J, Galante JO (1999) Metal release and excretion from cementless titanium alloy total knee replacements. Clin Orthop Relat Res (358):173–180

    Google Scholar 

  36. Jacobs JJ, Skipor AK, Black J, Urban R, Galante JO (1991) Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. J Bone Joint Surg Am 73:1475–1486

    CAS  Google Scholar 

  37. Jacobs JJ, Skipor AK, Patterson LM, Hallab NJ, Paprosky WG, Black J, Galante JO (1998) Metal release in patients who have had a primary total hip arthroplasty. A prospective controlled longitudinal study. J Bone Joint Surg Am 80:1447–1458

    CAS  Google Scholar 

  38. Jefferies H, Coster J, Khalil A, Bot J, Mccauley RD, Hall JC (2003) Glutathione. ANZ J Surg 73:517–522

    Article  Google Scholar 

  39. Kalbacova M, Roessler S, Hempel U, Tsaryk R, Peters K, Scharnweber D, Kirkpatrick JC, Dieter P (2007) The effect of electrochemically simulated titanium cathodic corrosion products on ROS production and metabolic activity of osteoblasts and monocytes/macrophages. Biomaterials 28:3263–3272

    Article  CAS  Google Scholar 

  40. Kinov P, Leithner A, Radl R, Bodo K, Khoschsorur GA, Schauenstein K, Windhager R (2006) Role of free radicals in aseptic loosening of hip arthroplasty. J Orthop Res 24:55–62

    Article  CAS  Google Scholar 

  41. Konttinen YT, Zhao D, Beklen A, Ma G, Takagi M, Kivela-Rajamaki M, Ashammakhi N, Santavirta S (2005) The microenvironment around total hip replacement prostheses. Clin Orthop Relat Res (430):28–38

    Google Scholar 

  42. Kuwabara K, Ogawa S, Matsumoto M, Koga S, Clauss M, Pinsky DJ, Lyn P, Leavy J, Witte L, Joseph-Silverstein J, Al E (1995) Hypoxia-mediated induction of acidic/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells. Proc Natl Acad Sci U S A 92:4606–4610

    Article  CAS  Google Scholar 

  43. Larsson J, Persson C, Tengvall P, Lundqvist-Gustafsson H (2004) Anti-inflammatory effects of a titanium-peroxy gel: role of oxygen metabolites and apoptosis. J Biomed Mater Res A 68:448–457

    Article  Google Scholar 

  44. Lee MC, Yoshino F, Shoji H, Takahashi S, Todoki K, Shimada S, Kuse-Barouch K (2005) Characterization by electron spin resonance spectroscopy of reactive oxygen species generated by titanium dioxide and hydrogen peroxide. J Dent Res 84:178–182

    Article  CAS  Google Scholar 

  45. Lee SR, Kwon KS, Kim SR, Rhee SG (1998) Reversible inactivation of protein-tyrosine ­phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem 273: 15366–15372

    Article  CAS  Google Scholar 

  46. Lee TM, Chang E, Yang CY (2000) A comparison of the surface characteristics and ion release of Ti6Al4V and heat-treated Ti6Al4V. J Biomed Mater Res 50:499–511

    Article  CAS  Google Scholar 

  47. Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  CAS  Google Scholar 

  48. Li J, Zhang YP, Kirsner RS (2003) Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 60:107–114

    Article  CAS  Google Scholar 

  49. Lin HY, Bumgardner JD (2004) In vitro biocorrosion of Ti-6Al-4V implant alloy by a mouse macrophage cell line. J Biomed Mater Res A 68:717–724

    Article  Google Scholar 

  50. Long M, Rack HJ (1998) Titanium alloys in total joint replacement–a materials science perspective. Biomaterials 19:1621–1639

    Article  CAS  Google Scholar 

  51. Lu SC (2000) Regulation of glutathione synthesis. Curr Top Cell Regul 36:95–116

    Article  CAS  Google Scholar 

  52. Lum H, Roebuck KA (2001) Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280:C719–C741

    CAS  Google Scholar 

  53. Macdonald SJ (2004) Metal-on-metal total hip arthroplasty: the concerns. Clin Orthop Relat Res (429):86–93

    Google Scholar 

  54. Malhotra JD, Miao H, Zhang K, Wolfson A, Pennathur S, Pipe SW, Kaufman RJ (2008) Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci U S A 105:18525–18530

    Article  CAS  Google Scholar 

  55. Mandelin J, Li TF, Liljestrom M, Kroon ME, Hanemaaijer R, Santavirta S, Konttinen YT (2003) Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement. J Bone Joint Surg Br 85:1196–1201

    Article  CAS  Google Scholar 

  56. Marti A (2000) Cobalt-base alloys used in bone surgery. Injury 31(Suppl 4):18–21

    Article  Google Scholar 

  57. Martin P, Leibovich SJ (2005) Inflammatory cells during wound repair: the good, the bad, and the ugly. Trends Cell Biol 15:599–607

    Article  CAS  Google Scholar 

  58. Meilhac O, Zhou M, Santanam N, Parthasarathy S (2000) Lipid peroxides induce expression of catalase in cultured vascular cells. J Lipid Res 41:1205–1213

    CAS  Google Scholar 

  59. Mentus SV (2004) Oxygen reduction on anodically formed titanium dioxide. Electrochim Acta 50:27–32

    Article  CAS  Google Scholar 

  60. Midwood KS, Williams LV, Schwarzbauer JE (2004) Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 36:1031–1037

    Article  CAS  Google Scholar 

  61. Milosev I, Metikos-Hukovic M, Strehblow HH (2000) Passive film on orthopaedic TiAlV alloy formed in physiological solution investigated by X-ray photoelectron spectroscopy. Biomaterials 21:2103–2113

    Article  CAS  Google Scholar 

  62. Mu Y, Kobayashi T, Sumita M, Yamamoto A, Hanawa T (2000) Metal ion release from ­titanium with active oxygen species generated by rat macrophages in vitro. J Biomed Mater Res 49:238–243

    Article  CAS  Google Scholar 

  63. Murphy RC, Johnson KM (2008) Cholesterol reactive oxygen species and the formation of biologically active mediators. J Biol Chem 283:15521–15525

    Article  CAS  Google Scholar 

  64. Ni M, Lee AS (2007) ER chaperones in mammalian development and human diseases. FEBS Lett 581:3641–3651

    Article  CAS  Google Scholar 

  65. Ozmen I, Naziroglu M, Okutan R (2005) Comparative study of antioxidant enzymes in tissues surrounding implant in rabbits. Cell Biochem Funct 24:275–281

    Article  Google Scholar 

  66. Pan J, Liao H, Leygraf C, Thierry D, Li J (1998) Variation of oxide films on titanium induced by osteoblast-like cell culture and the influence of an H2O2 pretreatment. J Biomed Mater Res 40:244–256

    Article  CAS  Google Scholar 

  67. Peters K, Schmidt H, Unger RE, Otto M, Kamp G, Kirkpatrick CJ (2002) Software-supported image quantification of angiogenesis in an in vitro culture system: application to studies of biocompatibility. Biomaterials 23:3413–3419

    Article  CAS  Google Scholar 

  68. Plant SD, Grant DM, Leach L (2005) Behaviour of human endothelial cells on surface modified NiTi alloy. Biomaterials 26:5359–5367

    Article  CAS  Google Scholar 

  69. Pohler OE (2000) Unalloyed titanium for implants in bone surgery. Injury 31(Suppl 4):7–13

    Article  Google Scholar 

  70. Rahman I, Bel A, Mulier B, Lawson MF, Harrison DJ, Macnee W, Smith CA (1996) Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells. Biochem Biophys Res Commun 229:832–837

    Article  CAS  Google Scholar 

  71. Rhee SG, Chang TS, Bae YS, Lee SR, Kang SW (2003) Cellular regulation by hydrogen ­peroxide. J Am Soc Nephrol 14:S211–S215

    Article  CAS  Google Scholar 

  72. Ruef J, Hu ZY, Yin LY, Wu Y, Hanson SR, Kelly AB, Harker LA, Rao GN, Runge MS, Patterson C (1997) Induction of vascular endothelial growth factor in balloon-injured baboon arteries. A novel role for reactive oxygen species in atherosclerosis. Circ Res 81:24–33

    Article  CAS  Google Scholar 

  73. Sabokbar A, Pandey R, Quinn JM, Athanasou NA (1998) Osteoclastic differentiation by mononuclear phagocytes containing biomaterial particles. Arch Orthop Trauma Surg 117:136–140

    Article  CAS  Google Scholar 

  74. Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG (1986) Oxidant injury of cells DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 77:1312–1320

    Article  CAS  Google Scholar 

  75. Schroder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569:29–63

    Article  Google Scholar 

  76. Senderowicz AM (2003) Small-molecule cyclin-dependent kinase modulators. Oncogene 22:6609–6620

    Article  CAS  Google Scholar 

  77. Shiraiwa M, Goto T, Yoshinari M, Koyano K, Tanaka T (2002) A study of the initial attachment and subsequent behavior of rat oral epithelial cells cultured on titanium. J Periodontol 73:852–860

    Article  Google Scholar 

  78. Shono T, Ono M, Izumi H, Jimi SI, Matsushima K, Okamoto T, Kohno K, Kuwano M (1996) Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol 16:4231–4239

    CAS  Google Scholar 

  79. Sinha RK, Morris F, Shah SA, Tuan RS (1994) Surface composition of orthopaedic implant metals regulates cell attachment spreading and cytoskeletal organization of primary human osteoblasts in vitro. Clin Orthop Relat Res (305):258–272

    Google Scholar 

  80. Song FM, Kirk DW, Graydon JW, Cormack DE (2002) CO2 corrosion of bare steel under an aqueous boundary layer with oxygen. J Electrochem Soc 149:479–486

    Article  Google Scholar 

  81. Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JA, Gittes GK, Longaker MT (2000) VEGF expression in an osteoblast-like cell line is regulated by a hypoxia response mechanism. Am J Physiol Cell Physiol 278:C853–C860

    CAS  Google Scholar 

  82. Sundfeldt M, Carlsson LV, Johansson CB, Thomsen P, Gretzer C (2006) Aseptic loosening not only a question of wear: a review of different theories. Acta Orthop 77:177–197

    Article  Google Scholar 

  83. Taylor GC, Waddington RJ, Moseley R, Williams KR, Embery G (1996) Influence of titanium oxide and titanium peroxy gel on the breakdown of hyaluronan by reactive oxygen species. Biomaterials 17:1313–1319

    Article  CAS  Google Scholar 

  84. Tengvall P, Elwing H, Sjoqvist L, Lundstrom I, Bjursten LM (1989) Interaction between hydrogen peroxide and titanium: a possible role in the biocompatibility of titanium. Biomaterials 10:118–120

    Article  CAS  Google Scholar 

  85. Tengvall P, Lundstrom I, Sjoqvist L, Elwing H, Bjursten LM (1989) Titanium-hydrogen peroxide interaction: model studies of the influence of the inflammatory response on titanium implants. Biomaterials 10:166–175

    Article  CAS  Google Scholar 

  86. Trompezinski S, Pernet I, Mayoux C, Schmitt D, Viac J (2000) Transforming growth factor-beta1 and ultraviolet A1 radiation increase production of vascular endothelial growth factor but not endothelin-1 in human dermal fibroblasts. Br J Dermatol 143:539–545

    Article  CAS  Google Scholar 

  87. Tsaryk R, Kalbacova M, Hempel U, Scharnweber D, Unger RE, Dieter P, Kirkpatrick CJ, Peters K (2007) Response of human endothelial cells to oxidative stress on Ti6Al4V alloy. Biomaterials 28:806–813

    Article  CAS  Google Scholar 

  88. Tsaryk R, Peters K, Unger RE, Scharnweber D, Kirkpatrick CJ (2007) The effects of metal implants on inflammatory and healing processes. Int J Mat Res 98:622–629

    CAS  Google Scholar 

  89. Tucci M, Baker R, Benghuzzi H, Hughes J (2000) Levels of hydrogen peroxide in tissues adjacent to failing implantable devices may play an active role in cytokine production. Biomed Sci Instrum 36:215–220

    CAS  Google Scholar 

  90. Ushio-Fukai M, Alexander RW (2004) Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem 264:85–97

    Article  CAS  Google Scholar 

  91. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  CAS  Google Scholar 

  92. Veal EA, Day AM, Morgan BA (2007) Hydrogen peroxide sensing and signaling. Mol Cell 26:1–14

    Article  CAS  Google Scholar 

  93. Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835–870

    CAS  Google Scholar 

  94. Williams DF (1981) Titanium and titanium alloys. In: Williams DF (ed) Biocompatibility of clinical implant materials. CRC, Boca Raton, FL

    Google Scholar 

  95. Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4:278–286

    Article  CAS  Google Scholar 

  96. Wooley PH, Schwarz EM (2004) Aseptic loosening. Gene Ther 11:402–407

    Article  CAS  Google Scholar 

  97. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492

    CAS  Google Scholar 

  98. Yasuda M, Ohzeki Y, Shimizu S, Naito S, Ohtsuru A, Yamamoto T, Kuroiwa Y (1999) Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells. Life Sci 64:249–258

    Article  CAS  Google Scholar 

  99. Zhang Z, Huang C, Li J, Leonard SS, Lanciotti R, Butterworth L, Shi X (2001) Vanadate-induced cell growth regulation and the role of reactive oxygen species. Arch Biochem Biophys 392:311–320

    Article  CAS  Google Scholar 

  100. Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, Wang F, Guo A, Walczysko P, Gu Y, Sasaki T, Suzuki A, Forrester JV, Bourne HR, Devreotes PN, Mccaig CD, Penninger JM (2006) Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 442:457–460

    Article  CAS  Google Scholar 

  101. Zumdahl S (2007) Chemical principles. Brooks Cole, http://www.amazon.com/Chemical-Principles-Steven-S-Zumdahl/dp/061894690X

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roman Tsaryk .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Tsaryk, R., Peters, K., Unger, R.E., Scharnweber, D., Kirkpatrick, C.J. (2013). The Role of Oxidative Stress in the Response of Endothelial Cells to Metals. In: Antoniac, I. (eds) Biologically Responsive Biomaterials for Tissue Engineering. Springer Series in Biomaterials Science and Engineering, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4328-5_4

Download citation

Publish with us

Policies and ethics