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Layer-by-Layer Coatings as Infection-Resistant Biomaterials

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Biomaterials in Regenerative Medicine and the Immune System
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Abstract

We discuss the use of layer-by-layer (LbL) films as a powerful platform for engineering multifunctional antibacterial coatings for biomedical devices. These coatings can be designed to incorporate a variety of bioactive antimicrobial molecules, including antibiotics, cationic peptides, biofilm-disrupting and Q-sensing agents, and immunoregulatory cytokines. Here, we focus on active rather than passive delivery of antimicrobials from the coatings achieved through temperature or pH variations, as well as through the application of electric field. Of particular interest are “self-defensive” coatings which are activated in the presence of pathogens by pathogen-specific molecules or by acidification of the immediate environment by pathogenic bacteria. We describe several types of these coatings, which can carry high payloads of antimicrobials but do not release them at normal physiological conditions at pH 7.5 until the arrival of a bacterial trigger. Importantly, these coatings inhibit bacterial colonization while simultaneously promoting a healthy tissue response.

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References

  1. Delcea M, Möhwald H, Skirtach AG. Stimuli-responsive LbL capsules and nanoshells for drug delivery. Adv Drug Delivery Rev. 2011;63:730–47.

    Article  Google Scholar 

  2. Pavlukhina S, Sukhishvili S. Polymer assemblies for controlled delivery of bioactive molecules from surfaces. Adv Drug Delivery Rev. 2011;63(9):822–36.

    Article  Google Scholar 

  3. Ariga K, Lvov YM, Kawakami K, Ji Q, Hill JP. Layer-by-layer self-assembled shells for drug delivery. Adv Drug Delivery Rev. 2011;63:762–71.

    Article  Google Scholar 

  4. Ariga K, Hill JP, Ji Q. Layer-by-layer assembly as a versatile bottom-up nanofabrication technique for exploratory research and realistic application. Phys Chem Chem Phys. 2007;9:2319–40.

    Article  Google Scholar 

  5. Macdonald ML, Rodriguez NM, Shah NJ, Hammond PT. Characterization of tunable FGF-2 releasing polyelectrolyte multilayers. Biomacromolecules. 2010;11(8):2053–9.

    Article  Google Scholar 

  6. Tsai H-A, Wu R-R, Lee IC, Chang H-Y, Shen C-N, Chang Y-C. Selection, enrichment, and maintenance of self-renewal liver stem/progenitor cells utilizing polypeptide polyelectrolyte multilayer films. Biomacromolecules. 2010;11(4):994–1001.

    Article  Google Scholar 

  7. Chassepot A, Gao L, Nguyen I, et al. Chemically detachable polyelectrolyte multilayer platform for cell sheet engineering. Chem Mater. 2011;24(5):930–7.

    Article  Google Scholar 

  8. Gribova V, Auzely-Velty R, Picart C. Polyelectrolyte multilayer assemblies on materials surfaces: from cell adhesion to tissue engineering. Chem Mater. 2011;24(5):854–69.

    Article  Google Scholar 

  9. Dimitrova M, Affolter C, Meyer F, et al. Sustained delivery of siRNAs targeting viral infection by cell-degradable multilayered polyelectrolyte films. Proc Natl Acad Sci. 2008;105(42):16320–5.

    Article  Google Scholar 

  10. Pavlukhina S, Lu Y, Patimetha A, Libera M, Sukhishvili S. Polymer multilayers with pH-triggered release of antibacterial agents. Biomacromolecules. 2010;11(12):3448–56.

    Article  Google Scholar 

  11. Su X, Kim B-S, Kim SR, Hammond PT, Irvine DJ. Layer-by-layer-assembled multilayer films for transcutaneous drug and vaccine delivery. ACS Nano. 2009;3(11):3719–29.

    Article  Google Scholar 

  12. De Geest BG, Sanders NN, Sukhorukov GB, Demeester J, De Smedt SC. Release mechanisms for polyelectrolyte capsules. Chem Soc Rev. 2007;36:636–49.

    Article  Google Scholar 

  13. Alvarez-Lorenzo C, Concheiro A. Smart materials for drug delivery. RSC. Cambridge; 2013

    Google Scholar 

  14. Costerton JW, Cheng KJ, Geesey GG, Ladd TI, Nickel JC, Dasgupta M. Bacterial biofilms in nature and diseases. Ann Rev Microbiol. 1987;41:435–64.

    Article  Google Scholar 

  15. Otto M. Staphylococcal biofilms. Curr Topics Microbiol Immunol. 2008;322:207–28.

    Google Scholar 

  16. Cataldo MA, Petrosillo N, Cipriani M, Cauda R, Tacconelli E. Prosthetic joint infection: recent developments in diagnosis and management. J Infect. 2010;61(6):443–8.

    Article  Google Scholar 

  17. Banerjee I, Pangule RC, Kane RS. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv Mater. 2011;23(6):690–718.

    Article  Google Scholar 

  18. Saldarriaga Fernández IC, van der Mei HC, Lochhead MJ, Grainger DW, Busscher HJ. The inhibition of the adhesion of clinically isolated bacterial strains on multi-component cross-linked poly(ethylene glycol)-based polymer coatings. Biomaterials. 2007;28(28):4105–12.

    Article  Google Scholar 

  19. Harbers GM, Emoto K, Greef C, et al. Functionalized poly(ethylene glycol)-based bioassay surface chemistry that facilitates bio-immobilization and inhibits nonspecific protein, bacterial, and mammalian cell adhesion. Chem Mater. 2007;19(18):4405–14.

    Article  Google Scholar 

  20. Price JS, Tencer AF, Arm DM, Bohach GA. Controlled release of antibiotics from coated orthopedic implants. J Biomed Mater Res. 1996;30(3):281–6.

    Article  Google Scholar 

  21. Campoccia D, Montanaro L, Arciola CR. A review of the biomaterials technologies for infection-resistant surfaces. Biomaterials. 2013;34(34):8533–54.

    Article  Google Scholar 

  22. Siedenbiedel F, Tiller JC. Antimicrobial polymers in solution and on surfaces: overview and functional principles. Polymers. 2012;4(1):46–71.

    Article  Google Scholar 

  23. Schaer TP, Stewart S, Hsu BB, Klibanov AM. Hydrophobic polycationic coatings that inhibit biofilms and support bone healing during infection. Biomaterials. 2012;33(5):1245–54.

    Article  Google Scholar 

  24. Bush K, Courvalin P, Dantas G, et al. Tackling antibiotic resistance. Nat Rev Microbiol. 2011;9(12):894–6.

    Article  Google Scholar 

  25. Pavlukhina SV, Kaplan JB, Xu L, et al. Noneluting enzymatic antibiofilm coatings. ACS Appl Mater Interfaces. 2012;4(9):4708–16.

    Article  Google Scholar 

  26. Swartjes JJTM, Das T, Sharifi S, et al. A functional DNase I coating to prevent adhesion of bacteria and the formation of biofilm. Adv Funct Mater. 2013;23(22):2843–9.

    Article  Google Scholar 

  27. Li B, Jiang B, Boyce BM, Lindsey BA. Multilayer polypeptide nanoscale coatings incorporating IL-12 for the prevention of biomedical device-associated infections. Biomaterials. 2009;30(13):2552–8.

    Article  Google Scholar 

  28. Li B, Jiang B, Dietz MJ, Smith ES, Clovis NB, Rao KMK. Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open fractures. J Orthop Res. 2010;28(1):48–54.

    Google Scholar 

  29. Fu J, Ji J, Yuan W, Shen J. Construction of anti-adhesive and antibacterial multilayer films via layer-by-layer assembly of heparin and chitosan. Biomaterials. 2005;26(33):6684–92.

    Article  Google Scholar 

  30. Etienne O, Picart C, Taddei C, et al. Multilayer polyelectrolyte films functionalized by insertion of defensin: a new approach to protection of implants from bacterial colonization. Antimicrob Agents Chemother. 2004;48(10):3662–9.

    Article  Google Scholar 

  31. Guyomard A, Dé E, Jouenne T, Malandain J-J, Muller G, Glinel K. Incorporation of a hydrophobic antibacterial peptide into amphiphilic polyelectrolyte multilayers: a bioinspired approach to prepare biocidal thin coatings. Adv Funct Mater. 2008;18(5):758–65.

    Article  Google Scholar 

  32. Shi Z, Neoh KG, Zhong SP, Yung LYL, Kang ET, Wang W. In vitro antibacterial and cytotoxicity assay of multilayered polyelectrolyte-functionalized stainless steel. J Biomed Mater Res Part A. 2006;76A(4):826–34.

    Article  Google Scholar 

  33. Lee D, Rubner MF, Cohen RE. Formation of nanoparticle-loaded microcapsules based on hydrogen-bonded multilayers. Chem Mater. 2005;17(5):1099–105.

    Article  Google Scholar 

  34. Nguyen PM, Zacharia NS, Verploegen E, Hammond PT. Extended release antibacterial layer-by-layer films incorporating linear-dendritic block copolymer micelles. Chem Mater. 2007;19(23):5524–30.

    Article  Google Scholar 

  35. Chuang HF, Smith RC, Hammond PT. Polyelectrolyte multilayers for tunable release of antibiotics. Biomacromolecules. 2008;9(6):1660–8.

    Article  Google Scholar 

  36. Lichter JA, Van Vliet KJ, Rubner MF. Design of antibacterial surfaces and interfaces: polyelectrolyte multilayers as a multifunctional platform. Macromolecules. 2009;42(22):8573–86.

    Article  Google Scholar 

  37. Moskowitz JS, Blaisse MR, Samuel RE, et al. The effectiveness of the controlled release of gentamicin from polyelectrolyte multilayers in the treatment of Staphylococcus aureus infection in a rabbit bone model. Biomaterials. 2010;31(23):6019–30.

    Article  Google Scholar 

  38. Wong SY, Moskowitz JS, Veselinovic J, et al. Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents. J Am Chem Soc. 2010:188–96.

    Google Scholar 

  39. Shukla A, Fleming KE, Chuang HF, et al. Controlling the release of peptide antimicrobial agents from surfaces. Biomaterials. 2010;31(8):2348–57.

    Article  Google Scholar 

  40. Wood KC, Chuang HF, Batten RD, Lynn DM, Hammond PT. Controlling interlayer diffusion to achieve sustained, multiagent delivery from layer-by-layer thin films. Proc Natl Acad Sci. U S A. 2006;103(27):10207–12.

    Article  Google Scholar 

  41. Hong J, Shah NJ, Drake AC, et al. Graphene multilayers as gates for multi-week sequential release of proteins from surfaces. ACS Nano. 2011;6(1):81–8.

    Article  Google Scholar 

  42. Cao Y, He W. Synthesis and characterization of glucocorticoid functionalized poly(N-vinyl pyrrolidone): a versatile prodrug for neural interface. Biomacromolecules. 2010;11:1298–307.

    Article  Google Scholar 

  43. Thierry B, Kujawa P, Tkaczyk C, Winnik FM, Bilodeau L, Tabrizian M. Delivery platform for hydrophobic drugs: prodrug approach combined with self-assembled multilayers. J Am Chem Soc. 2005;127:1626–7.

    Article  Google Scholar 

  44. Soike T, Streff AK, Guan C, et al. Engineering a material surface for drug delivery and imaging using layer-by-layer assembly of functionalized nanoparticles. Adv Mater. 2010;22(12):1392–7.

    Article  Google Scholar 

  45. Yuan W, Ji J, Fu J, Shen J. A facile method to construct hybrid multilayered films as a strong and multifunctional antibacterial coating. J Biomed Mater Res Part B. 2008;85B(2):556–63.

    Article  Google Scholar 

  46. Li Z, Lee D, Sheng X, Cohen RE, Rubner MF. Two-level antibacterial coating with both release-killing and contact-killing capabilities. Langmuir. 2006;22(24):9820–3.

    Article  Google Scholar 

  47. Fu J, Ji J, Fan D, Shen J. Construction of antibacterial multilayer films containing nanosilver via layer-by-layer assembly of heparin and chitosan-silver ions complex. J Biomed Mater Res Part A. 2006;79A(3):665–74.

    Article  Google Scholar 

  48. Wong SY, Moskowitz JS, Veselinovic J, et al. Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents. J Am Chem Soc. 2010;132(50):17840–8.

    Article  Google Scholar 

  49. Zhu Z, Sukhishvili SA. Layer-by-layer films of stimuli-responsive block copolymer micelles. J Mater Chem. 2012;22(16):7667–71.

    Article  Google Scholar 

  50. Zhu Z, Gao N, Wang H, Sukhishvili SA. Temperature-triggered on-demand drug release enabled by hydrogen-bonded multilayers of block copolymer micelles. J Control Release. 2013;171(1):73–80.

    Article  Google Scholar 

  51. Boulmedais F, Tang CS, Keller B, Vörös J. Controlled electrodissolution of polyelectrolyte multilayers: a platform technology towards the surface-initiated delivery of drugs. Adv Funct Mater. 2006;16:63–70.

    Article  Google Scholar 

  52. Wood KC, Zacharia NS, Schmidt DJ, Wrightman SN, Andaya BJ, Hammond PT. Electroactive controlled release thin films. Proc Natl Acad Sci U S A. 2008;105:2280–5.

    Article  Google Scholar 

  53. Jiang BB, Li BY. Tunable drug loading and release from polypeptide multilayer nanofilms. Int J Nanomed. 2009;4(1):37–53.

    Google Scholar 

  54. Kellum MG, Harris CA, Mccormick CL, Morgan SE. Stimuli-responsive micelles of amphiphilic AMPS-b-AAL copolymers in layer-by-layer films. J Polym Sci Part A. 2010;49:1104–11.

    Article  Google Scholar 

  55. Kim B-S, Park SW, Hammond PT. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces. ACS Nano. 2008;2(2):386–92.

    Article  Google Scholar 

  56. Cado G, Aslam R, Seon L, et al. Self-defensive biomaterial coating against bacteria and yeasts: polysaccharide multilayer film with embedded antimicrobial peptide. Adv Funct Mater. 2013;23(38):4801–9.

    Google Scholar 

  57. Gensel J, Borke T, Pérez NP, et al. Cavitation engineered 3D sponge networks and their application in active surface construction. Adv Mater. 2012;24(7):985–9.

    Article  Google Scholar 

  58. Zhuk I, Jariwala F, Attygalle AB, Wu Y, Libera MR, Sukhishvili SA. Self-defensive layer-by-layer films with bacteria-triggered antibiotic release. ACS Nano. 2014;8(8):7733–45.

    Article  Google Scholar 

  59. Pavlukhina S, Zhuk I, Mentbayeva A, et al. Small-molecule-hosting nanocomposite films with multiple bacteria-triggered responses. NPG Asia Mater. 2014;6:e121.

    Article  Google Scholar 

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Acknowledgments

The author thanks Thomas Cattabiani (Stevens Institute of Technology) for his helpful comments on the chapter.

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Correspondence to Svetlana A. Sukhishvili .

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Sukhishvili, S. (2015). Layer-by-Layer Coatings as Infection-Resistant Biomaterials. In: Santambrogio, L. (eds) Biomaterials in Regenerative Medicine and the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-18045-8_5

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