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Chimeric Peptides as Implant Functionalization Agents for Titanium Alloy Implants with Antimicrobial Properties

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Abstract

Implant-associated infections can have severe effects on the longevity of implant devices and they also represent a major cause of implant failures. Treating these infections associated with implants by antibiotics is not always an effective strategy due to poor penetration rates of antibiotics into biofilms. Additionally, emerging antibiotic resistance poses serious concerns. There is an urge to develop effective antibacterial surfaces that prevent bacterial adhesion and proliferation. A novel class of bacterial therapeutic agents, known as antimicrobial peptides (AMPs), are receiving increasing attention as an unconventional option to treat septic infection, partly due to their capacity to stimulate innate immune responses and for the difficulty of microorganisms to develop resistance towards them. While host and bacterial cells compete in determining the ultimate fate of the implant, functionalization of implant surfaces with AMPs can shift the balance and prevent implant infections. In the present study, we developed a novel chimeric peptide to functionalize the implant material surface. The chimeric peptide simultaneously presents two functionalities, with one domain binding to a titanium alloy implant surface through a titanium-binding domain while the other domain displays an antimicrobial property. This approach gains strength through control over the bio-material interfaces, a property built upon molecular recognition and self-assembly through a titanium alloy binding domain in the chimeric peptide. The efficiency of chimeric peptide both in-solution and absorbed onto titanium alloy surface was evaluated in vitro against three common human host infectious bacteria, Streptococcus mutans, Staphylococcus epidermidis, and Escherichia coli. In biological interactions such as occur on implants, it is the surface and the interface that dictate the ultimate outcome. Controlling the implant surface by creating an interface composed chimeric peptides may therefore open up new possibilities to modify the implant site and tailor it to a desirable bioactivity.

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References

  1. S. Bauer, P. Schmuki, K. von der Mark, and J. Park, Prog. Mater. Sci. 58, 261 (2013).

    Article  Google Scholar 

  2. D. Puleo and A. Nanci, Biomaterials 20, 2311 (1999).

    Article  Google Scholar 

  3. M. Geetha, A. Singh, R. Asokamani, and A. Gogia, Prog. Mater. Sci. 54, 397 (2009).

    Article  Google Scholar 

  4. L. Le Guéhennec, A. Soueidan, P. Layrolle, and Y. Amouriq, Dent. Mater. 23, 844 (2007).

    Article  Google Scholar 

  5. P.H. Pennekamp, J. Gessmann, O. Diedrich, B. Burian, M.A. Wimmer, V.M. Frauchiger, and C.N. Kraft, J. Orthop. Res. 24, 531 (2006).

    Article  Google Scholar 

  6. J. Costerton, P.S. Stewart, and E. Greenberg, Science 284, 1318 (1999).

    Article  Google Scholar 

  7. R.A. Weinstein and R.O. Darouiche, Clin. Infect. Dis. 33, 1567 (2001).

    Article  Google Scholar 

  8. I. Uçkay, P. Hoffmeyer, D. Lew, and D. Pittet, J. Hosp. Infect. 84, 5 (2013).

    Article  Google Scholar 

  9. V. Antoci Jr, C.S. Adams, J. Parvizi, H.M. Davidson, R.J. Composto, T.A. Freeman, E. Wickstrom, P. Ducheyne, D. Jungkind, and I.M. Shapiro, Biomaterials 29, 4684 (2008).

    Article  Google Scholar 

  10. M. Kazemzadeh-Narbat, J. Kindrachuk, K. Duan, H. Jenssen, R.E. Hancock, and R. Wang, Biomaterials 31, 9519 (2010).

    Article  Google Scholar 

  11. C.R. Rathbone, J.D. Cross, K.V. Brown, C.K. Murray, and J.C. Wenke, J. Orthop. Res. 29, 1070 (2011).

    Article  Google Scholar 

  12. E.M. Hetrick and M.H. Schoenfisch, Chem. Soc. Rev. 35, 780 (2006).

    Article  Google Scholar 

  13. D. Campoccia, L. Montanaro, P. Speziale, and C.R. Arciola, Biomaterials 31, 6363 (2010).

    Article  Google Scholar 

  14. G.M. Harbers, K. Emoto, C. Greef, S.W. Metzger, H.N. Woodward, J.J. Mascali, D.W. Grainger, and M.J. Lochhead, Chem. Mater. 19, 4405 (2007).

    Article  Google Scholar 

  15. A. Shimotoyodome, T. Koudate, H. Kobayashi, J. Nakamura, I. Tokimitsu, T. Hase, T. Inoue, T. Matsukubo, and Y. Takaesu, Antimicrob. Agents Chemother. 51, 3634 (2007).

    Article  Google Scholar 

  16. Y. An, G. Stuart, S. McDowell, S. McDaniel, Q. Kang, and R. Friedman, J. Orthop. Res. 14, 846 (1996).

    Article  Google Scholar 

  17. B. Jose, V. Antoci Jr, A.R. Zeiger, E. Wickstrom, and N.J. Hickok, Chem. Biol. 12, 1041 (2005).

    Article  Google Scholar 

  18. J. Price, A. Tencer, D. Arm, and G. Bohach, J. Biomed. Mater. Res. 30, 281 (1996).

    Article  Google Scholar 

  19. A. Russell, U. Tattawasart, J.-Y. Maillard, and J. Furr, Antimicrob. Agents Chemother. 42, 2151 (1998).

    Google Scholar 

  20. D.A. Wininger and R.J. Fass, Antimicrob. Agents Chemother. 40, 2675 (1996).

    Google Scholar 

  21. L. Harris, L. Mead, E. Müller-Oberländer, and R. Richards, J. Biomed. Mater. Res. A 78, 50 (2006).

    Article  Google Scholar 

  22. I. Banerjee, R.C. Pangule, and R.S. Kane, Adv. Mater. 23, 690 (2011).

    Article  Google Scholar 

  23. L. Zhao, P.K. Chu, Y. Zhang, and Z. Wu, J. Biomed. Mater. Res. B Appl. Biomater. 91, 470 (2009).

    Article  Google Scholar 

  24. B. Gottenbos, H.C. van der Mei, F. Klatter, P. Nieuwenhuis, and H.J. Busscher, Biomaterials 23, 1417 (2002).

    Article  Google Scholar 

  25. M. Mrksich and G.M. Whitesides, Annu. Rev. Biophys. 25, 55 (1996).

    Article  Google Scholar 

  26. M. Mohorčič, I. Jerman, M. Zorko, L. Butinar, B. Orel, R. Jerala, and J. Friedrich, J. Mater. Sci. Mater. Med. 21, 2775 (2010).

    Article  Google Scholar 

  27. J.C. Love, L.A. Estroff, J.K. Kriebel, R.G. Nuzzo, and G.M. Whitesides, Chem. Rev. 105, 1103 (2005).

    Article  Google Scholar 

  28. L.G. Harris and R.G. Richards, Injury 37, S3 (2006).

    Article  Google Scholar 

  29. K.A. Brogden, Nat. Rev. Microbiol. 3, 238 (2005).

    Article  Google Scholar 

  30. A. Giuliani, G. Pirri, and S.F. Nicoletto, Cent. Eur. J. Biol. 2, 1 (2007).

    Article  Google Scholar 

  31. M. Zasloff, Nature 415, 389 (2002).

    Article  Google Scholar 

  32. K. Reddy, R. Yedery, and C. Aranha, Int. J. Antimicrob. Agents 24, 536 (2004).

    Article  Google Scholar 

  33. M. Pasupuleti, A. Schmidtchen, and M. Malmsten, Crit. Rev. Biotechnol. 32, 143 (2012).

    Article  Google Scholar 

  34. H. Jenssen, P. Hamill, and R.E. Hancock, Clin. Microbiol. Rev. 19, 491 (2006).

    Article  Google Scholar 

  35. A.B. Ingham and R.J. Moore, Biotechnol. Appl. Biochem. 47, 1 (2007).

    Article  Google Scholar 

  36. K. Hilpert, M.R. Elliott, R. Volkmer-Engert, P. Henklein, O. Donini, Q. Zhou, D.F. Winkler, and R.E. Hancock, Chem. Biol. 13, 1101 (2006).

    Article  Google Scholar 

  37. C.D. Fjell, H. Jenssen, K. Hilpert, W.A. Cheung, N. Pante, R.E. Hancock, and A. Cherkasov, J. Med. Chem. 52, 2006 (2009).

    Article  Google Scholar 

  38. Z. Jiang, A.I. Vasil, J.D. Hale, R.E. Hancock, M.L. Vasil, and R.S. Hodges, J. Pept. Sci. 90, 369 (2008).

    Article  Google Scholar 

  39. M. Sarikaya, C. Tamerler, A.K.-Y. Jen, K. Schulten, and F. Baneyx, Nat. Mater. 2, 577 (2003).

    Article  Google Scholar 

  40. D. Campoccia, L. Montanaro, and C.R. Arciola, Biomaterials 34, 8533 (2013).

    Article  Google Scholar 

  41. P.H. Kwakman, A.A. te Velde, C.M. Vandenbroucke-Grauls, S.J. Van Deventer, and S.A. Zaat, Antimicrob. Agents Chemother. 50, 3977 (2006).

    Article  Google Scholar 

  42. O. Etienne, C. Picart, C. Taddei, Y. Haikel, J. Dimarcq, P. Schaaf, J. Voegel, J. Ogier, and C. Egles, Antimicrob. Agents Chemother. 48, 3662 (2004).

    Article  Google Scholar 

  43. P. Appendini and J. Hotchkiss, J. Appl. Polym. Sci. 81, 609 (2001).

    Article  Google Scholar 

  44. Z. Yan, M.L. Snead, and C. Tamerler, Nanomedicine 11, 431 (2015).

    Article  Google Scholar 

  45. S.S. Socransky and A.D. Haffajee, Periodontology 2000 28, 12 (2002).

    Article  Google Scholar 

  46. D. Campoccia, L. Montanaro, and C.R. Arciola, Biomaterials 27, 2331 (2006).

    Article  Google Scholar 

  47. F. Costa, I.F. Carvalho, R.C. Montelaro, P. Gomes, and M.C.L. Martins, Acta Biomater. 7, 1431 (2011).

    Article  Google Scholar 

  48. S.R. Meyers, X. Khoo, X. Huang, E.B. Walsh, M.W. Grinstaff, and D.J. Kenan, Biomaterials 30, 277 (2009).

    Article  Google Scholar 

  49. M. Yoshinari, T. Kato, K. Matsuzaka, T. Hayakawa, and K. Shiba, Biofouling 26, 103 (2010).

    Article  Google Scholar 

  50. H. Yazici, H. Fong, B. Wilson, E. Oren, F. Amos, H. Zhang, J. Evans, M. Snead, M. Sarikaya, and C. Tamerler, Acta Biomater. 9, 5341 (2013).

    Article  Google Scholar 

  51. E.E. Oren, C. Tamerler, D. Sahin, M. Hnilova, U.O.S. Seker, M. Sarikaya, and R. Samudrala, Bioinformatics 23, 2816 (2007).

    Article  Google Scholar 

  52. Z. Lu, K.S. Murray, V. Van Cleave, E.R. LaVallie, M.L. Stahl, and J.M. McCoy, Nat. Biotechnol. 13, 366 (1995).

    Article  Google Scholar 

  53. C. Tamerler, D. Khatayevich, M. Gungormus, T. Kacar, E.E. Oren, M. Hnilova, and M. Sarikaya, J. Pept. Sci. 94, 78 (2010).

    Article  Google Scholar 

  54. C. Tamerler and M. Sarikaya, Acta Biomater. 3, 289 (2007).

    Article  Google Scholar 

  55. U.O.S. Seker, B. Wilson, S. Dincer, I.W. Kim, E.E. Oren, J.S. Evans, C. Tamerler, and M. Sarikaya, Langmuir 23, 7895 (2007).

    Article  Google Scholar 

  56. C.D. Fjell, H. Jenssen, W.A. Cheung, R.E. Hancock, and A. Cherkasov, Chem. Biol. Drug Des. 77, 48 (2011).

    Article  Google Scholar 

  57. S. Chaudhury, S. Lyskov, and J.J. Gray, Bioinformatics 26, 689 (2010).

    Article  Google Scholar 

  58. K.T. Simons, C. Kooperberg, E. Huang, and D. Baker, J. Mol. Biol. 268, 209 (1997).

    Article  Google Scholar 

  59. P. Bradley, K.M. Misura, and D. Baker, Science 309, 1868 (2005).

    Article  Google Scholar 

  60. W. Kabsch and C. Sander, Biopolymers 22, 2577 (1983).

    Article  Google Scholar 

  61. J.W. Grzymala-Busse and W. Rzasa, Fund. Inform. 100, 99 (2010).

    MATH  MathSciNet  Google Scholar 

  62. N.E. Shepherd, H.N. Hoang, G. Abbenante, and D.P. Fairlie, J. Am. Chem. Soc. 131, 15877 (2009).

    Article  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge financial support from National Institute of Health (NIH)—Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Musculoskeletal Tissue Engineering Section 7R21AR062249-03 and University of Kansas New Faculty General Research Fund (NFGRF) as well as National Institute of Dental and Craniofacial Research Grant DE13045.

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Correspondence to Candan Tamerler.

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Yucesoy, D.T., Hnilova, M., Boone, K. et al. Chimeric Peptides as Implant Functionalization Agents for Titanium Alloy Implants with Antimicrobial Properties. JOM 67, 754–766 (2015). https://doi.org/10.1007/s11837-015-1350-7

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  • DOI: https://doi.org/10.1007/s11837-015-1350-7

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